FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Gawrisch, K
Soubias, O
Mihailescu, M
AF Gawrisch, Klaus
Soubias, Olivier
Mihailescu, Mihaela
TI Insights from biophysical studies on the role of polyunsaturated fatty
acids for function of G-protein coupled membrane receptors
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Docosahexaenoic acid; G-protein-coupled membrane receptor; Rhodopsin;
Nuclear Magnetic Resonance; Neutron Scattering
ID MOLECULAR-DYNAMICS SIMULATIONS; ACYL-CHAIN; CRYSTAL-STRUCTURE;
LIPID-BILAYERS; H-2 NMR; PHOSPHOLIPID-BILAYERS; STRUCTURAL-PROPERTIES;
DOCOSAHEXAENOIC ACID; PHYSICAL-PROPERTIES; ARACHIDONIC-ACID
AB The composition of the lipid matrix is critical for function of membrane proteins. Perhaps one of the best studied examples is the function of the G-protein-coupled membrane receptor (GPCR) rhodopsin which is located in membranes with high content of phospholipids with polyunsaturated docosahexaenoic acid chains (DHA, 22:6n-3). Technological advances enabled a more detailed study of structure and dynamics of DHA chains and their interaction with rhodopsin. It was established that polyunsaturated DHA differs from saturated and monounsaturated hydrocarbon chains by far more rapid structural conversions. Furthermore, DHA chains tend to have higher density near the lipid/water inter-face while density of saturated chains is higher in the bilayer center. The interface of rhodopsin has a small number of sites for tighter interaction with DHA. Polyunsaturated phosphatidylethanolamines accumulate preferentially near the protein. Surprisingly, the high conformational freedom of most DHA chains is not measurably reduced upon interaction with rhodopsin. While some observations point at an involvement of continuum elastic properties of membranes in modulation of rhodopsin function, there is growing evidence for a role of weakly specific DHA-rhodopsin interactions. (c) 2008 Elsevier Ltd. All rights reserved.
C1 [Gawrisch, Klaus; Soubias, Olivier] NIAAA, Sect NMR, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Mihailescu, Mihaela] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA.
RP Gawrisch, K (reprint author), NIAAA, Sect NMR, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
EM klausg@mail.nih.gov
FU NIAAA; NIH; National Institute of Standards and Technology; University
of California; National Institute for Research Resources [RR14812]
FX This work was supported by the Intramural Research Program of NIAAA,
NIH. The neutron diffraction studies were conducted on the AND/R
instrument, constructed by the Cold Neutrons for Biology and Technology
(CNBT) partnership, supported by the National Institute of Standards and
Technology, the Regents of the University of California, and by a grant
RR14812 from the National Institute for Research Resources awarded to
the University of California at Irvine.
NR 39
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U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD SEP-NOV
PY 2008
VL 79
IS 3-5
BP 131
EP 134
DI 10.1016/j.plefa.2008.09.002
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 388BL
UT WOS:000261995200016
PM 19004627
ER
PT J
AU Rapoport, SI
AF Rapoport, Stanley I.
TI Brain arachidonic and docosahexaenoic acid cascades are selectively
altered by drugs, diet and disease
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Phospholipid; Brain; Metabolism; PUFA; Phospholipase A2 (PLA(2));
Arachidonic; Docosahexaenoic; Diet; Lithium; Rat; Human; Bipolar
disorder
ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; PHOSPHOLIPASE A(2);
RAT-BRAIN; SIGNAL-TRANSDUCTION; BIPOLAR DISORDER; FRONTAL-CORTEX; ADULT
RATS; N-3; TURNOVER
AB Metabolic cascades involving arachidonic acid (AA) and docosahexaenoic acid (DHA) within brain can be independently targeted by drugs, diet and pathological conditions. Thus, AA turnover and brain expression of AA-selective cytosolic phospholipase A(2) (cPLA(2)), but not DHA turnover or expression of DHA-selective Ca2+-independent iPLA(2), are reduced in rats given agents effective against bipolar disorder mania, whereas experimental excitotoxicity and neuroinflammation selectively increase brain AA metabolism. Furthermore, the brain AA and DHA cascades are altered reciprocally by dietary n-3 polyunsaturated fatty acid (PUFA) deprivation in rats. DHA loss from brain is slowed and iPLA2 expression is decreased, whereas cPLA(2) and COX-2 are upregulated, as are brain concentrations of AA and its elongation product, docosapentaenoic acid (DPA).
Positron emission tomography (PET) has shown that the normal human brain consumes 17.8 and 4.6 mg/day, respectively, of AA and DHA, and that brain AA consumption is increased in Alzheimer disease patients. In the future, PET could help to determine how human brain AA or DHA consumption is influenced by diet, aging or disease. (c) 2008 Published by Elsevier Ltd
C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S128,9 Mem Dr, Bethesda, MD 20892 USA.
EM sir@helix.nih.gov
FU National Institute on Aging; National Institutes of Health, Bethesda, MD
FX The author (S. Rapoport) has no conflicts of interest regarding this
work. This work was fully supported by the Intramural Program of the
National Institute on Aging, National Institutes of Health, Bethesda,
MD.
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U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
EI 1532-2823
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD SEP-NOV
PY 2008
VL 79
IS 3-5
SI SI
BP 153
EP 156
DI 10.1016/j.plefa.2008.09.010
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 388BL
UT WOS:000261995200020
PM 18973997
ER
PT J
AU Mandal, DM
Sartor, O
Halton, SL
Mercante, DE
Bailey-Wilson, JE
Rayford, W
AF Mandal, D. M.
Sartor, O.
Halton, S. L.
Mercante, D. E.
Bailey-Wilson, J. E.
Rayford, W.
TI Recruitment strategies and comparison of prostate cancer-specific
clinical data on African-American and Caucasian males with and without
family history
SO PROSTATE CANCER AND PROSTATIC DISEASES
LA English
DT Article
DE prostate cancer disparity; prostate cancer family history; recruitment
genetic studies
ID PATHOLOGICAL FEATURES; MEN; RISK; WHITE; BLACK; EPIDEMIOLOGY; AAHPC
AB Prostate cancer is the most common cancer in men in the United States. This is a complex disease with high heterogeneity and the exact causes are unknown in population-specific samples. Family history is a primary risk factor irrespective of race. Identifying prostate cancer families with multiple affected cancer cases is challenging. Herein we document recruitment techniques and present prostate cancer clinical factors described in a cohort of African Americans and Caucasians with or without a strong family history. A total of 521 prostate cancer patients ( 241 African Americans and 280 Caucasians) were identified using a novel cooperative methodology involving a combination of treating physicians and tumor registries. Higher prostate-specific antigen (PSA, P = 0.0269) was found in familial cases as compared to sporadic cases in African-American men. In addition, PSA values for familial cases were higher (P = 0.0093) in African-American as compared to Caucasian men. No differences were detected in Gleason score values in either race, regardless of family history. These findings remained the same after adjustment was made for age at diagnosis. In conclusion, methodologies for cohort acquisition, and clinical characteristics, are described for men with and without a family history of prostate cancer using both Caucasian and African-American populations.
C1 [Mandal, D. M.; Halton, S. L.] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA 70112 USA.
[Sartor, O.] Louisiana State Univ, Hlth Sci Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA.
[Mercante, D. E.] Louisiana State Univ, Hlth Sci Ctr, Dept Biostat, New Orleans, LA 70112 USA.
[Bailey-Wilson, J. E.] NHGRI, NIH, Baltimore, MD USA.
[Rayford, W.] Louisiana State Univ, Hlth Sci Ctr, Dept Urol, New Orleans, LA 70112 USA.
RP Mandal, DM (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Genet, 533 Bolivar St,CSRB 6-16, New Orleans, LA 70112 USA.
EM dmanda@Isuhsc.edu
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU Louisiana Board of Regents LEQSF [(2002-05)-RD-A-15]; NCI [1 RO3
CA97778-01]; Cancer Research Foundation of America; Centers for Disease
Control and Prevention [H57/CCH 624034-01]; Louisiana Cancer Research
Consortium; Louisiana State University School of Medicine
FX We thank the study participants. We also thank the collaborating
hospitals and the physicians. We especially thank Josalin Hunter for her
assistance in reviewing medical records and Leah Balhoff for her
technical assistance. This research was funded in part by the Louisiana
Board of Regents (LEQSF (2002-05)-RD-A-15), the NCI (1 RO3 CA97778-01),
the Cancer Research Foundation of America, the Centers for Disease
Control and Prevention (H57/CCH 624034-01), Louisiana Cancer Research
Consortium and the institutional funding from the Louisiana State
University School of Medicine.
NR 28
TC 4
Z9 4
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1365-7852
J9 PROSTATE CANCER P D
JI Prostate Cancer Prostatic Dis.
PD SEP
PY 2008
VL 11
IS 3
BP 274
EP 279
DI 10.1038/pcan.2008.5
PG 6
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 338KB
UT WOS:000258505500011
PM 18268528
ER
PT J
AU Moon, KH
Upreti, VV
Yu, LR
Lee, IJ
Ye, XY
Eddington, ND
Veenstra, TD
Song, BJ
AF Moon, Kwan-Hoon
Upreti, Vijay V.
Yu, Li-Rong
Lee, Insong J.
Ye, Xiaoying
Eddington, Natalie D.
Veenstra, Timothy D.
Song, Byoung-Joon
TI Mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-mediated
mitochondrial dysfunction in rat liver
SO PROTEOMICS
LA English
DT Article
DE liver damage; MDMA; mitochondria; oxidative stress; protein oxidation
ID OXIDATIVE STRESS; PROTEIN OXIDATION; HEPATOMA-CELLS; NITRIC-OXIDE;
MOUSE-LIVER; ECSTASY; MDMA; BRAIN; IDENTIFICATION; APOPTOSIS
AB Despite numerous reports citing the acute hepatotoxicity caused by 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy), the underlying mechanism of organ damage is poorly understood. We hypothesized that key mitochondrial proteins are oxidatively modified and inactivated in MDMA-exposed tissues. The aim of this study was to identify and investigate the mechanism of inactivation of oxidatively modified mitochondrial proteins, prior to the extensive mitochondrial dysfunction and liver damage following MDMA exposure. MDMA-treated rats showed abnormal liver histology with significant elevation in plasma transaminases, nitric oxide synthase, and the level of hydrogen peroxide. Oxidatively modified mitochondrial proteins in control and MDMA-exposed rats were labeled with biotin-N-maleimide (biotin-NM) as a sensitive probe for oxidized proteins, purified with streptavidin-agarose, and resolved using 2-DE. Comparative 2-DE analysis of biotin-NM-labeled proteins revealed markedly increased levels of oxidatively modified proteins following MDMA exposure. Mass spectrometric analysis identified oxidatively modified mitochondrial proteins involved in energy supply, fat metabolism, antioxidant defense, and chaperone activities. Among these, the activities of mitochondrial aldehyde dehydrogenase, 3-ketoacyl-CoA thiolases, and ATP synthase were significantly inhibited following MDMA exposure. Our data show for the first time that MDMA causes the oxidative inactivation of key mitochondrial enzymes which most likely contributes to mitochondrial dysfunction and subsequent liver damage in MDMA-exposed animals.
C1 [Moon, Kwan-Hoon; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
[Upreti, Vijay V.; Lee, Insong J.; Eddington, Natalie D.] Univ Maryland, Pharmacokinet & Biopharmaceut Lab, Dept Pharmaceut Sci, Sch Pharm, Baltimore, MD 21201 USA.
[Yu, Li-Rong; Ye, Xiaoying; Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, NCI Frederick, Frederick, MD USA.
RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bjs@mail.nih.gov
FU Intramural NIH HHS [Z01 AA000036-21, Z99 AA999999]; NCI NIH HHS
[N01-CO-12400, N01CO12400]
NR 50
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U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD SEP
PY 2008
VL 8
IS 18
BP 3906
EP 3918
DI 10.1002/pmic.200800215
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 354GC
UT WOS:000259625900023
PM 18780394
ER
PT J
AU Karlsson, RM
Hefner, KR
Sibley, DR
Holmes, A
AF Karlsson, Rose-Marie
Hefner, Kathryn R.
Sibley, David R.
Holmes, Andrew
TI Comparison of dopamine D1 and D5 receptor knockout mice for cocaine
locomotor sensitization
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE dopamine; cocaine; knockout; mouse; psychostimulant; addiction;
locomotor; reward; open field; conditioned place preference; receptor
ID CONDITIONED PLACE PREFERENCE; INDUCED BEHAVIORAL SENSITIZATION;
ETHANOL-RELATED BEHAVIORS; NUCLEUS-ACCUMBENS; DEFICIENT MICE; MUTANT
MICE; DIFFERENTIALLY ALTERS; ENHANCED INHIBITION; NMDA RECEPTORS;
MOTOR-ACTIVITY
AB Rationale There is compelling support for the contribution of dopamine and the D1R-like (D1R, D5R) receptor subfamily to the behavioral and neural effects of psychostimulant drugs of abuse. The relative roles of D1R and D5R subtypes in mediating these effects are not clear.
Objectives The objectives of this study are to directly compare (C57BL/6J congenic) D1R knockout (KO) and D5R KO mice for baseline locomotor exploration, acute locomotor responses to cocaine, and locomotor sensitization to repeated cocaine administration, and to examine cocaine conditioned place preference (CPP) in D5R KO.
Materials and methods D1R KO, D5R KO, and wild-type (WT) were assessed for baseline open field exploration, locomotor-stimulating effects of 15 mg/kg acute cocaine and sensitized locomotor responses to cocaine after repeated home cage treatment with 20 or 30 mg/kg cocaine. D5R KO and WT were tested for CPP to 15 mg/kg cocaine.
Results D1R KO showed modest basal hyperactivity and increased center exploration relative to WT. Acute locomotor responses to cocaine were consistently absent in D1R KO, but intact in D5R KO. D5R KO showed normal locomotor sensitization to cocaine and normal cocaine CPP. D1R KO failed to show a sensitized locomotor response to 30 mg/kg cocaine. Failure to sensitize in D1R KO was not because of excessive stereotypies. Surprisingly, D1R KO showed a strong trend for sensitization to 20 mg/kg cocaine.
Conclusions D5R KO does not alter acute or sensitized locomotor responses to cocaine or cocaine CPP. D1R KO abolishes acute locomotor response to cocaine, but does not fully prevent locomotor sensitization to cocaine at all doses.
C1 [Karlsson, Rose-Marie; Hefner, Kathryn R.; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA.
[Sibley, David R.] NINDS, Mol Neuropharmacol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, 5625 Fishers Lane,Rm 2N09, Rockville, MD 20852 USA.
EM holmesan@mail.nih.gov
OI Hefner, Kathryn/0000-0002-5208-7860
FU National Institute of Alcohol Abuse and Alcoholism; National Institute
of Neurological Disease and Stroke
FX We are very grateful to David Cabrera for maintenance of the breeding
colonies. Research supported by the Intramural Research Programs of the
National Institute of Alcohol Abuse and Alcoholism and National
Institute of Neurological Disease and Stroke.
NR 66
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U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD SEP
PY 2008
VL 200
IS 1
BP 117
EP 127
DI 10.1007/s00213-008-1165-0
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 338WX
UT WOS:000258541200010
PM 18600316
ER
PT J
AU Goldstein, RZ
Parvaz, MA
Maloney, T
Alia-Klein, N
Woicik, PA
Telang, F
Wang, GJ
Volkow, ND
AF Goldstein, Rita Z.
Parvaz, Muhammad A.
Maloney, Thomas
Alia-Klein, Nelly
Woicik, Patricia A.
Telang, Frank
Wang, Gene-Jack
Volkow, Nora D.
TI Compromised sensitivity to monetary reward in current cocaine users: An
ERP study
SO PSYCHOPHYSIOLOGY
LA English
DT Article
DE cocaine addiction; early withdrawal; current drug abuse; P300; reward
processing; monetary reward; secondary reinforcement; inhibitory control
ID EVENT-RELATED POTENTIALS; BRAIN POTENTIALS; FRONTAL-CORTEX; FAMILY
HISTORY; DRUG-ABUSE; P300; ADDICTION; ACTIVATION; ALCOHOLISM; DEPENDENCE
AB We studied modulation of the P300 by monetary reward expected to be received on a sustained attention task in 18 individuals with current cocaine use disorders (CUD) and 18 control subjects. Results in the controls revealed sensitivity to money as measured with P300 amplitude and speed of behavioral response and their intercorrelations. In contrast, despite generally faster P300 waveforms and higher self-reported interest in the task, individuals with CUD did not display these responses to money versus nonreward; at the behavioral level, this impairment correlated with frequency of recent cocaine use. These preliminary results suggest a compromised sensitivity to a secondary reinforcer in CUD. This deficit, which needs to be replicated in larger samples of people with currently active versus abstaining CUD, may underlie the compromised ability to advantageously modify behavior in response to changing inner motivations and environmental contingencies.
C1 [Goldstein, Rita Z.; Parvaz, Muhammad A.; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Parvaz, Muhammad A.] SUNY Stony Brook, Biomed Engn Program, Stony Brook, NY 11794 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA.
RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, POBox 5000, Upton, NY 11973 USA.
EM rgoldstein@bnl.gov
OI Parvaz, Muhammad/0000-0002-2671-2327
FU NCRR NIH HHS [M01 RR010710, M01 RR010710-070110]; NIAAA NIH HHS
[AA/OD09481-04, R01 AA009481-09]; NIDA NIH HHS [K23 DA015517-05, 1K23
DA15517-01, K23 DA015517, R01 DA023579]
NR 49
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U1 4
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2008
VL 45
IS 5
BP 705
EP 713
DI 10.1111/j.1469-8986.2008.00670.x
PG 9
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 336KD
UT WOS:000258361800004
PM 18513362
ER
PT J
AU Carney, RM
Steinmeyer, B
Freedland, KE
Blumenthal, JA
Stein, PK
Steinhoff, WA
Howells, WB
Berkman, LF
Watkins, LL
Czajkowski, SM
Domitrovich, PP
Burg, MM
Hayano, J
Jaffe, AS
AF Carney, Robert M.
Steinmeyer, Brian
Freedland, Kenneth E.
Blumenthal, James A.
Stein, Phyllis K.
Steinhoff, William A.
Howells, William B.
Berkman, Lisa F.
Watkins, Lana L.
Czajkowski, Susan M.
Domitrovich, Peter P.
Burg, Matthew M.
Hayano, Junichiro
Jaffe, Allan S.
TI Nighttime heart rate and survival in depressed patients post acute
myocardial infarction
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE depression; heart rate; nighttime; acute myocardial infarction;
mortality
ID CORONARY-ARTERY-DISEASE; OBSTRUCTIVE SLEEP-APNEA; AUTONOMIC
NERVOUS-SYSTEM; RATE CIRCADIAN-RHYTHM; MIDDLE-AGED MEN;
RATE-VARIABILITY; MAJOR DEPRESSION; PLASMA NOREPINEPHRINE; RISK-FACTOR;
CARDIOVASCULAR MORTALITY
AB Objectives: To determine if: 1) depressed patients with a recent acute myocardial infarction (AMI) have higher nighttime heart rate (FIR) than nondepressed patients, and 2) elevated nighttime FIR is associated with decreased survival post AMI. Depression is a risk factor for mortality post AMI. It is also associated with sleep disturbances and with elevated FIR, which may be more pronounced at night. Resting and 24-hour FIR have been found to predict mortality in patient and community samples. Methods: Ambulatory electrocardiographic data were obtained from 333 depressed patients and 383 nondepressed patients with recent AMI. They were followed for Lip to 30 months (median 24 months). Results: Depressed patients had higher nighttime FIR (70.7 +/- 0.7 versus 67.7 +/- 0.6 beats per minute (bpm); p=.001), and daytime Flit (76.4 +/- 0.7 versus 74.2 +/- 0.6 bpm; p = .02) than nondepressed patients, even after adjusting for potential confounds. Depression (hazard ratio (Haz R) = 2.19; p = .02) and nighttime HR (Haz R = 1.03; p = .004), but not daytime FIR, predicted survival after adjusting for other major predictors and for each other. The interaction between nighttime FIR and depression on survival approached, but did not achieve, significance (p = .08). Conclusions: Mean day and nighttime FIR values are higher in depressed patients than in nondepressed patients post AMI. Depression and elevated nighttime FIR, but not daytime FIR, are independent predictors Of Survival in these patients. Although depressed patients have a higher nighttime FIR than nondepressed patients, nighttime FIR predicts mortality in both depressed and nondepressed patients.
C1 [Carney, Robert M.; Steinmeyer, Brian; Freedland, Kenneth E.; Blumenthal, James A.; Steinhoff, William A.; Howells, William B.; Watkins, Lana L.] Washington Univ, Sch Med, Dept Psychiat, Behav Med Ctr, St Louis, MO 63110 USA.
[Stein, Phyllis K.; Domitrovich, Peter P.; Burg, Matthew M.; Hayano, Junichiro; Jaffe, Allan S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Berkman, Lisa F.] Washington Univ, Sch Med, Dept Epidemiol, St Louis, MO 63110 USA.
[Blumenthal, James A.; Watkins, Lana L.] Duke Univ, Med Ctr, Durham, NC USA.
[Berkman, Lisa F.] Harvard Univ, Boston, MA 02115 USA.
[Czajkowski, Susan M.] NHLBI, Bethesda, MD 20892 USA.
[Hayano, Junichiro] Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi, Japan.
[Burg, Matthew M.] Yale Univ, Sch Med, New Haven, CT USA.
[Jaffe, Allan S.] Mayo Clin, Rochester, MN USA.
RP Carney, RM (reprint author), Washington Univ, Sch Med, Dept Psychiat, Behav Med Ctr, 660 S Euclid Ave,Box 8211, St Louis, MO 63110 USA.
EM carneyr@bmc.wustl.edu
FU National Heart, Lung, and Blood Institute [2 RO-IHL58946]; National
Institutes of Health, Bethesda, Maryland; Lewis and Jean Sachs
Charitable Lead Trust
FX This research was supported, in part, by Grant 2 RO-IHL58946 from the
National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland, and from the Lewis and Jean Sachs Charitable
Lead Trust.
NR 79
TC 8
Z9 8
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD SEP
PY 2008
VL 70
IS 7
BP 757
EP 763
DI 10.1097/PSY.0b013e3181835ca3
PG 7
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 350LC
UT WOS:000259352900002
PM 18725430
ER
PT J
AU Kalaydjian, A
Merikangas, K
AF Kalaydjian, Amanda
Merikangas, Kathleen
TI Physical and mental comorbidity of headache in a nationally
representative sample of US adults
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE headache; migraine; comorbidity; psychiatric; disability; epidemiology
ID QUALITY-OF-LIFE; POPULATION-BASED SURVEY; PSYCHIATRIC COMORBIDITY;
MIGRAINE; DISORDERS; BURDEN; DISABILITY; IMPACT; DEPRESSION; DISEASE
AB Objective: To investigate the contribution of comorbidity to health utilization and negative health perception in a large-scale population-based study. Comorbidity of headache with physical and mental disorders has been reported frequently in clinical samples. Methods: This concern was addressed using combined 6-year data from the 1999 to 2004 National Health Examination and Nutrition Survey (n = 3 1,126 adults), nationally representative datasets of the US population. Measures of physical disorders were based on standardized interviews of chronic conditions, and mental disorders were assessed by the Composite International Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Results: The 3-month prevalence of severe headaches or migraine in the US general population was 22.73%, with females and young adults having greater rates than males and older adults. Adults with headache had increased odds for a variety of physical disorders (including asthma, rheumatoid arthritis, and stroke) and mental disorders (including depression, generalized anxiety disorder, and panic disorder). Adults with headache were more likely to rate their health as "fair or poor" (17.9% versus 6.1%), to seek health care four or more times in a year (43.3% versus 22.7%), and to endorse physical and mental limitations. Health utilization and negative health perception were more strongly influenced by comorbid mental disorders than physical disorders. Conclusions: The results from this nationally representative sample provide new information on the interrelationships of headache with mental and physical disorders. The greater impact of comorbid mental compared with physical disorders on healthcare utilization and health perception has important implications for the clinical evaluation and treatment of headache in the population.
C1 [Kalaydjian, Amanda] NIMH, Intramural Res Program, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA.
RP Kalaydjian, A (reprint author), NIMH, Intramural Res Program, Sect Dev Genet Epidemiol, 35 Convent Dr,1A-108, Bethesda, MD 20892 USA.
EM KalaydjianA@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002870-03, Z01 MH002870-02, ZIA MH002870-04]
NR 44
TC 44
Z9 44
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD SEP
PY 2008
VL 70
IS 7
BP 773
EP 780
DI 10.1097/PSY.0b013e31817f9e80
PG 8
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 350LC
UT WOS:000259352900004
PM 18725426
ER
PT J
AU Raza, H
Epstein, SA
Pao, M
Rosenstein, DL
AF Raza, Haniya
Epstein, Steven A.
Pao, Maryland
Rosenstein, Donald L.
TI Mania: Psychiatric manifestations of the antiphospholipid syndrome
SO PSYCHOSOMATICS
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTICARDIOLIPIN ANTIBODIES; HUGHES
SYNDROME; ASSOCIATION; DYSFUNCTION; DISEASE; AUTOANTIBODIES;
ANTICOAGULANT; PREVALENCE; PSYCHOSIS
AB Background: Antiphospholipid syndrome (APS) is a prothrombotic condition characterized by recurrent vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies. Central nervous system (CNS) involvement is a prominent feature of APS, and many neurological manifestations have been described in published reports. There are limited data on psychiatric syndromes occurring in association with APS, and there have been no previous reports of mania associated with APS. Method: The authors present the case of a 31-year-old man who experienced an acute manic episode in association with APS. They review the literature on psychiatric manifestations of APS, discuss potential mechanisms of CNS pathogenesis, and consider diagnostic and treatment implications of the co-occurrence of APS and psychiatric symptoms.
C1 [Raza, Haniya] Georgetown Univ Hosp, Dept Psychiat, Washington, DC 20007 USA.
NIMH, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
RP Raza, H (reprint author), Georgetown Univ Hosp, Dept Psychiat, Washington, DC 20007 USA.
EM haniyaraza@yahoo.com
FU Intramural NIH HHS [Z99 MH999999]
NR 30
TC 9
Z9 9
U1 0
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD SEP
PY 2008
VL 49
IS 5
BP 438
EP 441
DI 10.1176/appi.psy.49.5.438
PG 4
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 353TG
UT WOS:000259590500010
PM 18794513
ER
PT J
AU Stillerman, KP
Mattison, DR
Giudice, LC
Woodruff, TJ
AF Stillerman, Karen Perry
Mattison, Donald R.
Giudice, Linda C.
Woodruff, Tracey J.
TI Environmental exposures and adverse pregnancy outcomes: A review of the
science
SO REPRODUCTIVE SCIENCES
LA English
DT Review
DE adverse pregnancy outcomes; environmental contaminants; preterm
delivery; low birth weight; environmental exposures
ID LOW-BIRTH-WEIGHT; INTRAUTERINE GROWTH-RETARDATION; MATERNAL OCCUPATIONAL
EXPOSURE; BOTTLED WATER-CONSUMPTION; DISINFECTION BY-PRODUCTS;
ORGANIC-SOLVENT EXPOSURE; OUTDOOR AIR-POLLUTION;
POLYCHLORINATED-BIPHENYLS; DRINKING-WATER; SPONTANEOUS-ABORTION
AB To better understand the science linking environmental contaminants exposures with adverse pregnancy outcomes, we reviewed the relevant epidemiologic literature. We searched PubMed (primarily 1995-2006) using the key word combinations for select environmental exposures and pregnancy outcomes. Environmental tobacco smoke is a risk factor for reduced birth weight and preterm delivery. Outdoor air pollution is associated with reduced term birth weight and preterm delivery. Suggestive evidence associates pesticides and polychlorinated biphenyls with decreased fetal growth and length of gestation. Stronger evidence, primarily occupational, links certain birth defects with exposure to organic solvents and chlorophenoxy herbicides. Evidence suggests dichlorodiphenyltrichloroethane and bisphenol-A could be associated with pregnancy loss. Exposures in utero can also increase the risk of developmental delays (ie, impaired neurological function), adult chronic illnesses (ie, heart disease, diabetes, cancer), and next generation effects (ie, reduced reproductive capacity). Further research, education, and improved public health policy are needed to reduce potentially adverse exposures.
C1 [Mattison, Donald R.] NICHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
[Giudice, Linda C.; Woodruff, Tracey J.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
RP Woodruff, TJ (reprint author), 3333 Calif St,Suite 265, San Francisco, CA 94118 USA.
EM woodrufft@obgyn.ucsf.edu
RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013
OI Mattison, Donald/0000-0001-5623-0874
FU Marisla Foundation
FX The authors acknowledge Physicians for Social Responsibility and the
Marisla Foundation for their support of this article.
NR 185
TC 131
Z9 142
U1 2
U2 41
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD SEP
PY 2008
VL 15
IS 7
BP 631
EP 650
DI 10.1177/1933719108322436
PG 20
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 353VK
UT WOS:000259596500003
PM 18836129
ER
PT J
AU Fiore, MC
Jaen, CR
Baker, TB
Bailey, WC
Benowitz, NL
Curry, SJ
Dorfman, SF
Froelicher, ES
Goldstein, MG
Healton, CG
Henderson, PN
Heyman, RB
Koh, HK
Kottke, TE
Lando, HA
Mecklenburg, RE
Mermelstein, RJ
Mullen, PD
Orleans, CT
Robinson, L
Stitzer, ML
Tommasello, AC
Villejo, L
Wewers, ME
Murray, EW
Bennett, G
Heishman, S
Husten, C
Morgan, G
Williams, C
Christiansen, BA
Piper, ME
Hasselblad, V
Fraser, D
Theobald, W
Connell, M
Leitzke, C
AF Fiore, Michael C.
Jaen, Carlos Roberto
Baker, Timothy B.
Bailey, William C.
Benowitz, Neal L.
Curry, Susan J.
Dorfman, Sally Faith
Froelicher, Erika S.
Goldstein, Michael G.
Healton, Cheryl G.
Henderson, Patricia Nez
Heyman, Richard B.
Koh, Howard K.
Kottke, Thomas E.
Lando, Harry A.
Mecklenburg, Robert E.
Mermelstein, Robin J.
Mullen, Patricia Dolan
Orleans, C. Tracy
Robinson, Lawrence
Stitzer, Maxine L.
Tommasello, Anthony C.
Villejo, Louise
Wewers, Mary Ellen
Murray, Ernestine W.
Bennett, Glenn
Heishman, Stephen
Husten, Corinne
Morgan, Glen
Williams, Christine
Christiansen, Bruce A.
Piper, Megan E.
Hasselblad, Victor
Fraser, David
Theobald, Wendy
Connell, Michael
Leitzke, Cathlyn
CA 2008 PHS Guideline Update Panel
2008 PHS Guideline Update Liaisons
2008 PHS Guideline Update Staff
TI Treating tobacco use and dependence: 2008 update US Public Health
Service Clinical Practice Guideline executive summary
SO RESPIRATORY CARE
LA English
DT Article; Proceedings Paper
CT 23rd Annual New Horizons Symposium
CY DEC 01-04, 2007
CL Orlando, FL
ID SMOKING-CESSATION; UNITED-STATES; MYOCARDIAL-INFARCTION; QUIT SMOKING;
IMPACT; ADULTS; PROGRAMS; THERAPY; DISEASE; ADVICE
C1 [Morgan, Glen] NCI, Bethesda, MD 20892 USA.
RP Fiore, MC (reprint author), Univ Wisconsin, Ctr Tobacco & Res Intervent, Madison, WI 53711 USA.
EM mcf@ctri.medicine.wisc.edu
NR 36
TC 134
Z9 140
U1 1
U2 24
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
J9 RESP CARE
JI Respir. Care
PD SEP
PY 2008
VL 53
IS 9
BP 1217
EP 1222
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 347PM
UT WOS:000259153500011
ER
PT J
AU Reynolds, HY
AF Reynolds, H. Y.
TI BRONCHOALVEOLAR LAVAGE - OBTAINING BIOLOGIC SPECIMENS FROM THE
RESPIRATORY TRACT SURFACE
SO SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES
LA English
DT Editorial Material
ID BRONCHIAL LAVAGE; INFLAMMATION; SARCOIDOSIS; PERSPECTIVE; LUNG
C1 NHLBI, Div Lung Dis, Bethesda, MD 20892 USA.
RP Reynolds, HY (reprint author), NHLBI, Div Lung Dis, 6701 Rockledge Dr 10180, Bethesda, MD 20892 USA.
EM Reynoldh@nhlbi.nih.gov
NR 19
TC 4
Z9 4
U1 0
U2 0
PU FONDAZIONE PNEUMOLOGIA U I P ONLUS
PI MILANO
PA VIA FRUA 15, MILANO, ITALY
SN 1124-0490
J9 SARCOIDOSIS VASC DIF
JI Sarcoidosis Vasc. Diffus. Lung Dis.
PD SEP
PY 2008
VL 25
IS 1
BP 5
EP 9
PG 5
WC Respiratory System
SC Respiratory System
GA 372EG
UT WOS:000260884200002
PM 19070254
ER
PT J
AU Resnik, DB
Gutierrez-Ford, C
Peddada, S
AF Resnik, David B.
Gutierrez-Ford, Christina
Peddada, Shyamal
TI Perceptions of ethical problems with scientific journal peer review: An
exploratory study
SO SCIENCE AND ENGINEERING ETHICS
LA English
DT Article
DE journal peer review; ethics; bias; reform
ID PUBLICATION; QUALITY; AUTHORS; BLIND
AB This article reports the results of an anonymous survey of researchers at a government research institution concerning their perceptions about ethical problems with journal peer review. Incompetent review was the most common ethical problem reported by the respondents, with 61.8% (SE = 3.3%) claiming to have experienced this at some point during peer review. Bias (50.5%, SE = 3.4%) was the next most common problem. About 22.7% (SE = 2.8%) of respondents said that a reviewer had required them to include unnecessary references to his/her publication(s), 17.7% (SE = 2.6%) said that comments from reviewers had included personal attacks, and 9.6% (SE = 2.0%) stated that reviewers had delayed publication to publish a paper on the same topic. Two of the most serious violations of peer review ethics, breach of confidentiality (6.8%, SE = 1.7%) and using ideas, data, or methods without permission (5%, SE = 1.5%) were perceived less often than the other problems. We recommend that other investigators follow up on our exploratory research with additional studies on the ethics of peer review.
C1 [Resnik, David B.; Gutierrez-Ford, Christina; Peddada, Shyamal] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov; cgford123@gmail.com; Peddada@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012
FU Intramural NIH HHS [Z99 ES999999]
NR 13
TC 20
Z9 22
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1353-3452
J9 SCI ENG ETHICS
JI Sci. Eng. Ethics
PD SEP
PY 2008
VL 14
IS 3
BP 305
EP 310
DI 10.1007/s11948-008-9059-4
PG 6
WC Ethics; Engineering, Multidisciplinary; History & Philosophy Of Science;
Multidisciplinary Sciences; Philosophy
SC Social Sciences - Other Topics; Engineering; History & Philosophy of
Science; Science & Technology - Other Topics; Philosophy
GA 339KZ
UT WOS:000258577800003
PM 18311477
ER
PT J
AU Millum, J
AF Millum, Joseph
TI A Biological Alternative to Moral Explanations
SO SOUTHERN JOURNAL OF PHILOSOPHY
LA English
DT Article
ID NATURAL FACTS; EVOLUTION; TRAGEDY; COMMONS
AB Some moral realists claim that moral facts are a species of natural fact, amenable to scientific investigation. They argue that these moral facts are needed in the best explanations of certain phenomena and that this is evidence that they are real. In this paper I present part of a biological account of the function of morality. The account allows the identification of a plausible natural kind that could play the explanatory role that a moral kind would play in naturalist realist theories. It is therefore a candidate for being the moral kind. I argue, however, that it will underdetermine the morally good, that is, identifying the kind is not sufficient to identify what is good. Hence this is not a natural moral kind. Its explanatory usefulness, however, means that we do not have to postulate any further (moral) facts to provide moral explanations. Hence there is no reason to believe that there are any natural moral kinds.
C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Millum, J (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 CL999999]
NR 42
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0038-4283
J9 SOUTHERN J PHILOS
JI South. J. Philos.
PD FAL
PY 2008
VL 46
IS 3
BP 385
EP 407
PG 23
WC Philosophy
SC Philosophy
GA 359XQ
UT WOS:000260022000004
PM 27065499
ER
PT J
AU Maynard, S
Swistowska, AM
Lee, JW
Liu, Y
Liu, ST
Da Cruz, AB
Rao, M
de Souza-Pinto, NC
Zeng, XM
Bohr, VA
AF Maynard, Scott
Swistowska, Anna Maria
Lee, Jae Wan
Liu, Ying
Liu, Su-Ting
Da Cruz, Alexandre Bettencourt
Rao, Mahendra
de Souza-Pinto, Nadja C.
Zeng, Xianmin
Bohr, Vilhelm A.
TI Human embryonic stem cells have enhanced repair of multiple forms of DNA
damage
SO STEM CELLS
LA English
DT Article
DE human embryonic stem cells; DNA repair; genomic maintenance; comet
assay; microarray
ID NUCLEOTIDE EXCISION-REPAIR; INTERSTRAND CROSS-LINKS; STRAND BREAK
REPAIR; MAMMALIAN-CELLS; COMET ASSAY; MISMATCH REPAIR;
GEL-ELECTROPHORESIS; CELLULAR-RESPONSES; MITOCHONDRIAL-DNA; INDIVIDUAL
CELLS
AB Embryonic stem cells need to maintain genomic integrity so that they can retain the ability to differentiate into multiple cell types without propagating DNA errors. Previous studies have suggested that mechanisms of genome surveillance, including DNA repair, are superior in mouse embryonic stem cells compared with various differentiated murine cells. Using single-cell gel electrophoresis (comet assay) we found that human embryonic stem cells (BG01, I6) have more efficient repair of different types of DNA damage (generated from H2O2, UV-C, ionizing radiation, or psoralen) than human primary fibroblasts (WI-38, hs27) and, with the exception of UV-C damage, HeLa cells. Microarray gene expression analysis showed that mRNA levels of several DNA repair genes are elevated in human embryonic stem cells compared with their differentiated forms (embryoid bodies). These data suggest that genomic maintenance pathways are enhanced in human embryonic stem cells, relative to differentiated human cells.
C1 [Maynard, Scott; Liu, Su-Ting; de Souza-Pinto, Nadja C.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Swistowska, Anna Maria; Da Cruz, Alexandre Bettencourt; Zeng, Xianmin] Buck Inst Age Res, Novato, CA USA.
[Lee, Jae Wan] US Patent & Trademark Off, Crystallog & Recombinant Enzyme Art Unit, Alexandria, VA USA.
[Liu, Ying; Rao, Mahendra] Invitrogen Corp, Carlsbad, CA USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM bohrv@grc.nia.nih.gov
RI Souza-Pinto, Nadja/C-3462-2013;
OI Souza-Pinto, Nadja/0000-0003-4206-964X; Maynard,
Scott/0000-0001-5625-936X
FU Intramural Research Program of the National Institute on Aging, NIH
FX We are indebted to Daniel R. McNeill for HPLC analysis of 8-oxoG levels,
Patrice Cook for technical assistance on the OGG1 activity assays, and
Al May for helpful instruction on many aspects of the comet assays. We
also thank Dr. Jason Aulds and Dr. Tomasz Kulikowicz for the critical
reading of the manuscript and Dr. Christopher Morrell for assistance
with the statistical analysis. This work was supported by the Intramural
Research Program of the National Institute on Aging, NIH.
NR 52
TC 99
Z9 102
U1 2
U2 14
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD SEP
PY 2008
VL 26
IS 9
BP 2266
EP 2274
DI 10.1634/stemcells.2007-1041
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 350PE
UT WOS:000259364800008
PM 18566332
ER
PT J
AU Thanos, PK
Ramalhete, RC
Michaelides, M
Piyis, YK
Wang, GJ
Volkow, ND
AF Thanos, Panayotis K.
Ramalhete, Roberto C.
Michaelides, Michael
Piyis, Ylanni K.
Wang, Gene-Jack
Volkow, Nora D.
TI Leptin receptor deficiency is associated with upregulation of
cannabinoid 1 receptors in limbic brain regions
SO SYNAPSE
LA English
DT Article
DE endocannabinoids; obesity; reward, drug abuse; cannabinoid; beta-imager;
Delta(9)-THC
ID CONDITIONED PLACE PREFERENCE; MESSENGER-RNA EXPRESSION;
ALCOHOL-PREFERRING RATS; CB1 RECEPTORS; FOOD-INTAKE; ANTAGONIST
SR-141716; SIGNAL-TRANSDUCTION; KNOCKOUT MICE; ZUCKER RATS; BETA-IMAGER
AB Leptin receptor dysfunction results in overeating and obesity. Leptin regulates hypothalamic signaling that underlies the motivation to hyperphagia, but the interaction between leptin and cannabinoid signaling is poorly understood. We evaluated the role of cannabinoid I receptors (CB(1)R) in overeating and the effects of food deprivation on CB(1)R in the brain. One-month-old Zucker rats were divided into unrestricted and restricted (fed 70% of unrestricted rats) diet groups and maintained until adulthood (4 months). Levels of relative binding sites of CB(1)R (CB(1)R binding levels) were assessed using [(3)H] SR141716A in vitro autoradiography. These levels were higher (except cerebellum and hypothalamus) at 4 months than at 1 month of age. One month CB(1)R binding levels for most brain regions did not differ between Ob and Lean (Le) rats (except in frontal and cingulate cortices in Le and in the hypothalamus in Ob). Four month Ob rats had higher CB(1)R binding levels than Le in most brain regions and food restriction was associated with higher CB(1)R levels in all brain regions in Ob, but not in Le rats. CB(1)R binding levels increased between adolescence and young adulthood which we believe was influenced by leptin and food availability. The high levels of CB(1)R in Ob rats suggest that leptin's inhibition of food-intake is in part mediated by downregulation of CB(1)R and that leptin interferes with CB(1)R upregulation under food-deprivation conditions. These results are consistent with prior findings showing increased levels of endogenous cannabinoids in the Ob rats corroborating the regulation of cannabinoid signaling by leptin.
C1 [Thanos, Panayotis K.; Ramalhete, Roberto C.; Michaelides, Michael; Piyis, Ylanni K.; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Thanos, Panayotis K.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Thanos, Panayotis K.] SUNY Stony Brook, Neurosci Program, Stony Brook, NY 11794 USA.
RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, 30 Bell Ave, Upton, NY 11973 USA.
EM thanos@bnl.gov
RI Michaelides, Michael/K-4736-2013
OI Michaelides, Michael/0000-0003-0398-4917
FU Intramural NIH HHS [Z01 AA000551-04]; NIAAA NIH HHS [AA 11034, AA 07574,
AA 07611, P50 AA007611, R01 AA011034, T32 AA007574]
NR 38
TC 36
Z9 37
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD SEP
PY 2008
VL 62
IS 9
BP 637
EP 642
DI 10.1002/syn.20531
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 329ZT
UT WOS:000257909800001
PM 18563836
ER
PT J
AU Kitanaka, N
Kitanaka, J
Hall, FS
Tatsuta, T
Morita, Y
Takemura, M
Wang, XB
Uhl, GR
AF Kitanaka, Nobue
Kitanaka, Junichi
Hall, F. Scott
Tatsuta, Tomohiro
Morita, Yoshio
Takemura, Motohiko
Wang, Xiao-Bing
Uhl, George R.
TI Alterations in the levels of heterotrimeric G protein subunits induced
by psychostimulants, opiates, barbiturates, and ethanol: Implications
for drug dependence, tolerance, and withdrawal
SO SYNAPSE
LA English
DT Article
DE amphetamine; cocaine; morphine; gene and protein expression;
intracellular effector; transcription factor
ID VENTRAL TEGMENTAL AREA; RECEPTOR-MEDIATED ACTIVATION; CHRONIC MORPHINE
TREATMENT; RAT LOCUS-COERULEUS; FREELY-MOVING RATS;
MOLECULAR-MECHANISMS; NUCLEUS-ACCUMBENS; GENE-EXPRESSION; MESSENGER-RNA;
IN-VIVO
AB Neuronal adaptations have been found to occur in multiple brain regions after chronic intake of abused drugs, and are therefore thought to underlie drug dependence, tolerance, and withdrawal. Pathophysiological changes in drug responsiveness as well as behavioral sequelae of chronic drug exposure are thought to depend largely upon the altered state of heterotrimeric GTP binding protein (G protein)coupled receptor (GPCR)-G protein interactions. Responsiveness of GPCR-related intracellular signaling systems to drugs of abuse is heterogeneous, depending on the types of intracellular effectors to which the specific G alpha protein subtypes are coupled and GPCR- protein coupling efficiency, factors influenced by the class of drug, expression levels of G protein subunits, and drug treatment regimens. To enhance understanding of the molecular mechanisms that underlie the development of pathophysiological states resulting from chronic intake of abused drugs, this review focuses on alterations in the expression levels of G protein subunits induced by various drugs of abuse. Changes in these mechanisms appear to be specific to particular drugs of abuse, and specific conditions of drug treatment.
C1 [Kitanaka, Nobue; Kitanaka, Junichi; Tatsuta, Tomohiro; Takemura, Motohiko] Hyogo Med Univ, Dept Pharmacol, Nishinomiya, Hyogo 6638501, Japan.
[Tatsuta, Tomohiro; Morita, Yoshio] Hyogo Med Univ, Dept Neuropsychiat, Nishinomiya, Hyogo 6638501, Japan.
[Hall, F. Scott; Wang, Xiao-Bing; Uhl, George R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH DHHS, Baltimore, MD 21224 USA.
RP Kitanaka, J (reprint author), Hyogo Med Univ, Dept Pharmacol, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan.
EM kitanaka-hyg@umin.net
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU Intramural NIH HHS [Z99 DA999999]
NR 88
TC 8
Z9 9
U1 1
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD SEP
PY 2008
VL 62
IS 9
BP 689
EP 699
DI 10.1002/syn.20543
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 329ZT
UT WOS:000257909800007
PM 18566973
ER
PT J
AU Seneca, N
Skinbjerg, M
Zoghbi, SS
Liow, JS
Gladding, RL
Hong, J
Kannan, P
Tuan, E
Sibley, DR
Halldin, C
Pike, VW
Innis, RB
AF Seneca, Nicholas
Skinbjerg, Mette
Zoghbi, Sami S.
Liow, Jeih-San
Gladding, Robert L.
Hong, Jinsoo
Kannan, Pavitra
Tuan, Edward
Sibley, David R.
Halldin, Christer
Pike, Victor W.
Innis, Robert B.
TI Kinetic brain analysis and whole-body imaging in monkey of [C-11]MNPA: A
dopamine agonist radioligand
SO SYNAPSE
LA English
DT Article
DE PET; [C-11]MNPA; dosimetry; DA D-2/3 receptor agonist radioligand;
whole-body biodistribution; kinetic analysis
ID POSITRON-EMISSION-TOMOGRAPHY; HIGH-AFFINITY STATE; ENDOGENOUS DOPAMINE;
RECEPTOR-BINDING; RADIATION-DOSIMETRY; REFERENCE REGION; D-2/3 AGONIST;
PET; ANTAGONIST; BIODISTRIBUTION
AB With a view to future extension of the use of the agonist radioligand [C-11]MNPA ([O-methyl-C-11]2-methoxy-N-propylnorapomorphine) from animals to humans, we performed two positron emission tomography (PET) studies in monkeys. First, we assessed the ability to quantify the brain uptake of [C-11]MNPA with compartmental modeling. Second, we estimated the radiation exposure of [C-11]MNPA to human subjects based on whole-body imaging in monkeys. Brain PET scans were acquired for 90 min and included concurrent measurements of the plasma concentration of unchanged radioligand. Time-activity data from striatum and cerebellum were quantified with two methods, a reference tissue model and distribution volume. Whole-body PET scans were acquired for 120 min using four bed positions from head to mid thigh. Regions of interest were drawn on compressed planar whole-body images to identify organs with the highest radiation exposures. After injection of [C-11]MNPA, the highest concentration of radioactivity in brain was in striatum, with lowest levels in cerebellum. Distribution volume was well identified with a two-tissue compartmental model and was quite stable from 60 to 90 min. Whole-body PET scans showed the organ with the highest radiation burden (mu Sv/MBq) was the urinary bladder wall (26.0), followed by lungs (22.5), gallbladder wall (21.9), and heart wall (16.1). With a 2.4-h voiding interval, the effective dose was 6.4 mu Sv/MBq (23.5 mrem/mCi). In conclusion, brain uptake of [C-11]MNPA reflected the density of D-2/3 receptors, quantified relative to serial arterial measurements, and caused moderate to low radiation exposure.
C1 [Seneca, Nicholas; Skinbjerg, Mette; Zoghbi, Sami S.; Liow, Jeih-San; Gladding, Robert L.; Hong, Jinsoo; Kannan, Pavitra; Tuan, Edward; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Seneca, Nicholas; Skinbjerg, Mette; Halldin, Christer] Karolinska Inst, Sect Psychiat, Dept Clin Neurosci, Stockholm, Sweden.
[Skinbjerg, Mette; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA.
RP Seneca, N (reprint author), NIMH, Mol Imaging Branch, Bldg 31,Room B2-1334,MSC-2035, Bethesda, MD 20892 USA.
EM nicholasseneca@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002795-07]; NIMH NIH HHS [Z01 MH002795]
NR 41
TC 7
Z9 7
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD SEP
PY 2008
VL 62
IS 9
BP 700
EP 709
DI 10.1002/syn.20544
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 329ZT
UT WOS:000257909800008
PM 18566975
ER
PT J
AU Listgarten, J
Brumme, Z
Kadie, C
Walker, B
Carrington, M
Goulder, P
Heckerman, D
AF Listgarten, J.
Brumme, Z.
Kadie, C.
Walker, B.
Carrington, M.
Goulder, P.
Heckerman, D.
TI Statistical resolution of ambiguous HLA typing data
SO TISSUE ANTIGENS
LA English
DT Meeting Abstract
CT 15th International Histocompatibility and Immunogenetics Workshop and
Conference
CY SEP 13-20, 2008
CL Rio de Janeiro, BRAZIL
C1 [Brumme, Z.; Walker, B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA.
[Carrington, M.] NCI, SAIC, Frederick, MD 21701 USA.
[Goulder, P.] Univ Oxford, Dept Paediat, Oxford, England.
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 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD SEP
PY 2008
VL 72
IS 3
BP 248
EP 249
PG 2
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 337OD
UT WOS:000258444500053
ER
PT J
AU Single, R
Martin, M
Meyer, D
Gao, X
Carrington, M
AF Single, R.
Martin, M.
Meyer, D.
Gao, X.
Carrington, M.
TI Methods for assessing gene content diversity of KIR in global population
samples
SO TISSUE ANTIGENS
LA English
DT Meeting Abstract
CT 15th International Histocompatibility and Immunogenetics Workshop and
Conference
CY SEP 13-20, 2008
CL Rio de Janeiro, BRAZIL
C1 [Single, R.] Univ Vermont, Burlington, VT USA.
[Martin, M.; Gao, X.; Carrington, M.] NCI, Frederick, MD 21701 USA.
[Meyer, D.] Univ Sao Paulo, Sao Paulo, Brazil.
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 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD SEP
PY 2008
VL 72
IS 3
BP 297
EP 297
PG 1
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 337OD
UT WOS:000258444500175
ER
PT J
AU Nesti, LJ
Li, WJ
Shanti, RM
Jiang, YJ
Jackson, W
Freedman, BA
Kuklo, TR
Giuliani, JR
Tuan, RS
AF Nesti, Leon J.
Li, Wan-Ju
Shanti, Rabie M.
Jiang, Yi Jen
Jackson, Wesley
Freedman, Brett A.
Kuklo, Timothy R.
Giuliani, Jeffrey R.
Tuan, Rocky S.
TI Intervertebral disc tissue engineering using a novel hyaluronic
acid-nanofibrous scaffold (HANFS) amalgam
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; INVESTIGATIONAL DEVICE EXEMPTION; NUCLEUS
PULPOSUS; IN-VITRO; TRANSPLANTATION THERAPY; SOLUTE TRANSPORT; LUMBAR
FUSION; BACK-PAIN; FOLLOW-UP; DIFFERENTIATION
AB Degeneration of the intervertebral disc (IVD) represents a significant musculoskeletal disease burden. Although spinal fusion has some efficacy in pain management, spine biomechanics is ultimately compromised. In addition, there is inherent limitation of hardware-based IVD replacement prostheses, which underscores the importance of biological approaches to disc repair. In this study, we have seeded multipotent, adult human mesenchymal stem cells (MSCs) into a novel biomaterial amalgam to develop a biphasic construct that consisted of electrospun, biodegradable nanofibrous scaffold (NFS) enveloping a hyaluronic acid (HA) hydrogel center. The seeded MSCs were induced to undergo chondrogenesis in vitro in the presence of transforming growth factor-beta for up to 28 days. The cartilaginous hyaluronic acid nanofibrous scaffold (HANFS) construct architecturally resembled a native IVD, with an outer annulus fibrosus-like region and inner nucleus pulposus-like region. Histological and biochemical analyses, immunohistochemistry, and gene expression profiling revealed the time-dependent development of chondrocytic phenotype of the seeded cells. The cells also maintain the microarchitecture of a native IVD. Taken together, these findings suggest the prototypic potential of MSC-seeded HANFS constructs for the tissue engineering of biological replacements of degenerated IVD.
C1 [Nesti, Leon J.; Li, Wan-Ju; Shanti, Rabie M.; Jiang, Yi Jen; Jackson, Wesley; Tuan, Rocky S.] NIAMSD, NIH, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA.
[Nesti, Leon J.; Freedman, Brett A.; Kuklo, Timothy R.; Giuliani, Jeffrey R.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA.
[Shanti, Rabie M.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
RP Tuan, RS (reprint author), NIAMSD, NIH, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, Bldg 50,Room 1503,MSC 8022, Bethesda, MD 20892 USA.
EM tuanr@mail.nih.gov
FU NIAMS; NIH [ZO1 AR41131]
FX This work was supported by the Intramural Research Program of the NIAMS,
NIH (ZO1 AR41131).
NR 61
TC 96
Z9 105
U1 4
U2 21
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD SEP
PY 2008
VL 14
IS 9
SI SI
BP 1527
EP 1537
DI 10.1089/ten.tea.2008.0215
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 350UG
UT WOS:000259378000010
PM 18707229
ER
PT J
AU Ramaswamy, S
Uluer, MC
Leen, S
Bajaj, P
Fishbein, KW
Spencer, RG
AF Ramaswamy, Sharan
Uluer, Mehmet C.
Leen, Stephanie
Bajaj, Preeti
Fishbein, Kenneth W.
Spencer, Richard G.
TI Noninvasive assessment of glycosaminoglycan production in injectable
tissue-engineered cartilage constructs using magnetic resonance imaging
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID GADOLINIUM-ENHANCED MRI; FIXED-CHARGE-DENSITY; ARTICULAR-CARTILAGE;
HUMAN KNEE; MENISCAL CARTILAGE; MICROSCOPY; OSTEOARTHRITIS;
SPECTROSCOPY; EXPERIENCE; HYDROGEL
AB The glycosaminoglycan (GAG) content of engineered cartilage is a determinant of biochemical and mechanical quality. The ability to measure the degree to which GAG content is maintained or increases in an implant is therefore of importance in cartilage repair procedures. The gadolinium exclusion magnetic resonance imaging (MRI) method for estimating matrix fixed charge density (FCD) is ideally suited to this. One promising approach to cartilage repair is use of seeded injectable hydrogels. Accordingly, we assess the reliability of measuring GAG content in such a system ex vivo using MRI. Samples of the photo-polymerizable hydrogel, poly(ethylene oxide) diacrylate, were seeded with bovine chondrocytes (similar to 2.4 million cells/sample). The FCD of the constructs was determined using MRI after 9, 16, 29, 36, 43, and 50 days of incubation. Values were correlated with the results of biochemical determination of GAG from the same samples. FCD and GAG were found to be statistically significantly correlated (R-2 = 0.91, p<0.01). We conclude that MRI-derived FCD measurements of FCD in injectable hydrogels reflect tissue GAG content and that this methodology therefore has potential for in vivo monitoring of such constructs.
C1 [Ramaswamy, Sharan; Uluer, Mehmet C.; Leen, Stephanie; Bajaj, Preeti; Fishbein, Kenneth W.; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Spencer, RG (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, Gerontol Res Ctr, NIH, Room 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM spencer@helix.nih.gov
OI Fishbein, Kenneth/0000-0002-6353-4603
FU Intramural Research Program of the NIH; National Institute on Aging
FX The research was supported by the Intramural Research Program of the
NIH, National Institute on Aging
NR 33
TC 17
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 1937-3384
J9 TISSUE ENG PT C-METH
JI Tissue Eng. Part C-Methods
PD SEP
PY 2008
VL 14
IS 3
BP 243
EP 249
DI 10.1089/ten.tec.2007.0423
PG 7
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 354AT
UT WOS:000259612000008
PM 18620483
ER
PT J
AU Liu, J
Waalkes, MP
AF Liu, Jie
Waalkes, Michael P.
TI Liver is a target of arsenic carcinogenesis
SO TOXICOLOGICAL SCIENCES
LA English
DT Editorial Material
DE arsenic; liver; carcinogenesis; epidemiology; animal models; mechanisms
ID INDUCED MALIGNANT-TRANSFORMATION; ABERRANT GENE-EXPRESSION; DISEASE
ENDEMIC AREA; DRINKING-WATER; IN-UTERO; DIMETHYLARSINIC ACID; DNA
HYPOMETHYLATION; WELL WATER; RAT-LIVER; POSTNATAL DIETHYLSTILBESTROL
AB Inorganic arsenic is clearly a human carcinogen causing tumors of the skin, lung, urinary bladder, and possibly liver (IARC, 2004). At the time of construction of this monograph, the evidence for arsenic as a hepatocarcinogen in humans was considered controversial and in rodents considered insufficient. However, recent data has accumulated indicating hepatocarcinogenicity of arsenic. This forum reevaluates epidemiology studies, rodent studies together with in vitro models, and focuses on the liver as a target organ of arsenic toxicity and carcinogenesis. Hepatocellular carcinoma and hepatic angiosarcoma, have been frequently associated with environmental or medicinal exposure to arsenicals. Preneoplastic lesions, including hepatomegaly, hepatoportal sclerosis, fibrosis, and cirrhosis often occur after chronic arsenic exposure. Recent work in mice clearly shows that exposure to inorganic arsenic during gestation induces tumors, including hepatocellular adenoma and carcinoma, in offspring when they reach adulthood. In rats, the methylated arsenicals, dimethylarsinic acid promotes diethylnitrosamine-initiated liver tumors, whereas trimethylarsine oxide induces liver adenomas. Chronic exposure of rat liver epithelial cells to low concentrations of inorganic arsenic induces malignant transformation, producing aggressive, undifferentiated epithelial tumors when inoculated into the Nude mice. There are a variety of potential mechanisms for arsenical-induced hepatocarcinogenesis, such as oxidative DNA damage, impaired DNA damage repair, acquired apoptotic tolerance, hyperproliferation, altered DNA methylation, and aberrant estrogen signaling. Some of these mechanisms may be liver specific/selective. Overall, accumulating evidence clearly indicates that the liver could be an important target of arsenic carcinogenesis.
C1 [Liu, Jie; Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA.
RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA.
EM Waalkes@niehs.nih.gov
FU Intramural NIH HHS
NR 71
TC 106
Z9 115
U1 4
U2 24
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD SEP
PY 2008
VL 105
IS 1
BP 24
EP 32
DI 10.1093/toxsci/kfn120
PG 9
WC Toxicology
SC Toxicology
GA 335YN
UT WOS:000258331600003
PM 18566022
ER
PT J
AU Barral, DC
Cavallari, M
McCormick, PJ
Garg, S
Magee, AI
Bonifacino, JS
De Libero, G
Brenner, MB
AF Barral, Duarte C.
Cavallari, Marco
McCormick, Peter J.
Garg, Salil
Magee, Anthony I.
Bonifacino, Juan S.
De Libero, Gennaro
Brenner, Michael B.
TI CD1a and MHC class I follow a similar endocytic recycling pathway
SO TRAFFIC
LA English
DT Article
DE CD1; clathrin; cytoplasmic tail; dynamin; internalization; MHC class I;
recycling; S-acylation
ID ANTIGEN PRESENTATION; CYTOPLASMIC TAIL; T-CELLS; LIPID ANTIGENS;
PROTEINS; MOLECULES; TRAFFICKING; ENDOSOMES; COMPARTMENTS; CLATHRIN
AB CD1 proteins are a family of major histocompatibility complex (MHC) class I-like antigen-presenting molecules that present lipids to T cells. The cytoplasmic tails (CTs) of all human CD1 isoforms, with the exception of CD1a, contain tyrosine-based sorting motifs, responsible for the internalization of proteins by the clathrin-mediated pathway. The role of the CD1a CT, which does not possess any sorting motifs, as well as its mode of internalization are not known. We investigated the internalization and recycling pathways followed by CD1a and the role of its CT. We found that CD1a can be internalized by a clathrin- and dynamin-independent pathway and that it follows a Rab22a- and ADP ribosylation factor (ARF)6-dependent recycling pathway, similar to other cargo internalized independent of clathrin. We also found that the CD1a CT is S-acylated. However, this posttranslational modification does not determine the rate of internalization or recycling of the protein or its localization to detergent-resistant membrane microdomains (DRMs) where we found CD1a to be enriched. We also show that plasma membrane DRMs are essential for efficient CD1a-mediated antigen presentation. These findings place CD1a closer to MHC class I in its trafficking and potential antigen-loading compartments among CD1 isoforms. Furthermore, we identify CD1a as a new marker for the clathrin- and dynamin-independent and DRM-dependent pathway of internalization as well as the Rab22a- and ARF6-dependent recycling pathway.
C1 [Barral, Duarte C.; Garg, Salil; Brenner, Michael B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Cavallari, Marco; De Libero, Gennaro] Univ Basel, Univ Hosp, Dept Res, CH-4031 Basel, Switzerland.
[McCormick, Peter J.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Magee, Anthony I.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Sect Mol Med, London SW7 2AZ, England.
[Bonifacino, Juan S.] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Brenner, MB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 1 Jimmy Fund Way,Smith Bldg, Boston, MA 02115 USA.
EM mbrenner@rics.bwh.harvard.edu
RI Barral, Duarte/E-7548-2013; McCormick, Peter/E-7387-2012;
OI Barral, Duarte/0000-0001-8867-2407; McCormick,
Peter/0000-0002-2225-5181; Bonifacino, Juan S./0000-0002-5673-6370
FU Medical Research Council [G0100471]; NIAMS NIH HHS [T32 AR007530-27, T32
AR007530]; NIGMS NIH HHS [T32 GM007753]
NR 38
TC 43
Z9 43
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD SEP
PY 2008
VL 9
IS 9
BP 1446
EP 1457
DI 10.1111/j.1600-0854.2008.00781.x
PG 12
WC Cell Biology
SC Cell Biology
GA 337OU
UT WOS:000258446200006
PM 18564371
ER
PT J
AU Kleinman, S
Glynn, S
Lee, TH
Tobler, L
Schlumpf, K
Todd, D
Busch, MP
AF Kleinman, S.
Glynn, S.
Lee, T-H
Tobler, L.
Schlumpf, K.
Todd, D.
Busch, M. P.
CA NHLBI Retrovirus Epid Donor Study-
TI A linked donor and recipient study of B19 viral transmission by blood
component transfusion
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Kleinman, S.; Lee, T-H] Univ British Columbia, Vancouver, MD USA.
[Glynn, S.] NHLBI, Bethesda, MD USA.
[Tobler, L.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA.
[Schlumpf, K.; Todd, D.] WESTAT Corp, Rockville, MD 20850 USA.
[Busch, M. P.] Blood Syst Inc, San Francisco, CA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 33A
EP 33A
PG 1
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400093
ER
PT J
AU Bryant, BD
Yau, YY
Arceo, S
Hopkins, J
Daniel-Johnson, J
Bolan, C
Leitman, SF
AF Bryant, B. D.
Yau, Y. Y.
Arceo, S.
Hopkins, J.
Daniel-Johnson, J.
Bolan, C.
Leitman, S. F.
TI Iron replacement therapy in the routine management of blood donors
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Daniel-Johnson, J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
EM SLeitman@cc.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 39A
EP 40A
PG 2
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400111
ER
PT J
AU Bryant, BJ
Yau, YY
Arceo, S
Hopkins, J
Leitman, SF
AF Bryant, B. J.
Yau, Y. Y.
Arceo, S.
Hopkins, J.
Leitman, S. F.
TI Ascertainment of iron deficiency and depletion in donors through
screening questions for pica and restless legs syndrome
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Bryant, B. J.; Yau, Y. Y.; Arceo, S.; Hopkins, J.; Leitman, S. F.] NIH, Bethesda, MD 20892 USA.
EM SLeitman@cc.nih.gov
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 40A
EP 40A
PG 1
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400112
ER
PT J
AU Yau, YY
Leitman, SF
Daniel-Johnson, J
Gladden, D
Bryant, BJ
Bolan, C
AF Yau, Y. Y.
Leitman, Susan F.
Daniel-Johnson, Jennifer
Gladden, DeC
Bryant, Barbara J.
Bolan, C.
TI Pre-donation fingerstick and venous hemoglobin levels vary significantly
according to body position, but accurately predict an adequate red cell
unit hemoglobin content regardless of position
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Bolan, C.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Bryant, Barbara J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
EM cbolan@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 67A
EP 68A
PG 2
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400193
ER
PT J
AU Salles, N
Barreto, A
Netol, CA
Otani, M
Chamone, D
Busch, MP
Sabino, E
AF Salles, N.
Barreto, A.
Netol, C. A.
Otani, M.
Chamone, D.
Busch, Michael P.
Sabino, E.
CA II Int Retrovirus E D Study
TI Performance of dual HIV EIA testing algorithm in Brazil
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Salles, N.; Barreto, A.; Otani, M.; Chamone, D.] Fundacao Pro Sangue Hemocentro Sao Paulo, Sao Paulo, Brazil.
[Netol, C. A.] Fundacao Pro Sangue Bloodcenter Sao Paulo, Sao Paulo, Brazil.
[Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Busch, Michael P.] Blood Syst Inc, San Francisco, CA USA.
[Sabino, E.] Fundacao Pro Sangue, Sao Paulo, Brazil.
[II Int Retrovirus E D Study] NHLBI, Rockville, MD USA.
EM sabinoec@usp.br
RI Sabino, Ester/F-7750-2010
OI Sabino, Ester/0000-0003-2623-5126
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 100A
EP 100A
PG 1
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400293
ER
PT J
AU Kakaiya, R
Triulzi, D
Roback, JD
Fang, J
Tu, Y
Kleinman, S
Busch, MP
Gottschall, JL
Rios, JA
Hillyer, C
Glynn, S
Schreiber, G
AF Kakaiya, R.
Triulzi, D.
Roback, John D.
Fang, J.
Tu, Y.
Kleinman, S.
Busch, Michael P.
Gottschall, Jerome L.
Rios, Jorge A.
Hillyer, C.
Glynn, Simone
Schreiber, George
CA Retrovirus Epidemiology Donor St
TI Characteristics of cytomegalovirus (CMV) antibody positive volunteer
blood donors
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Triulzi, D.] Emory Univ, Inst Transfus Med, Atlanta, GA 30322 USA.
[Roback, John D.] Emory Univ, Sch Med, Atlanta, GA USA.
[Fang, J.] Westat Corp, Rockville, MD USA.
[Tu, Y.] WESTAT Corp, Rockville, MD 20850 USA.
[Kleinman, S.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Busch, Michael P.] Blood Syst Inc, San Francisco, CA USA.
[Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Rios, Jorge A.] Amer Red Cross, Blood ServicesMA, Washington, DC 20006 USA.
[Glynn, Simone] NHLBI, Bethesda, MD 20892 USA.
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 104A
EP 105A
PG 2
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400306
ER
PT J
AU Sabino, E
Carneiro-Proietti, A
Leao, S
Proietti, F
Goncalez, TT
Ferreira, JE
Mendronel, A
Custer, B
Schreiber, G
AF Sabino, E.
Carneiro-Proietti, Anna
Leao, S.
Proietti, F.
Goncalez, Thelma T.
Ferreira, J. E.
Mendronel, A.
Custer, B.
Schreiber, G.
CA II Int Retrovirus Epidemiology Don
TI Prevalence of transfusion transmitted infections in Brazilian blood
donors as determined by a dual EIA strategy
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Sabino, E.] Fdn Pro Sangue, Sao Paulo, Brazil.
[Carneiro-Proietti, Anna] Hemominas Fdn, Belo Horizonte, MG, Brazil.
[Goncalez, Thelma T.; Ferreira, J. E.] Blood Syst Res Inst, San Francisco, CA USA.
[Ferreira, J. E.] Univ Sao Paulo, Sao Paulo, Brazil.
[II Int Retrovirus Epidemiology Don] NHLBI, Rockville, MD USA.
RI Sabino, Ester/F-7750-2010; Ferreira, Joao/L-1287-2016
OI Sabino, Ester/0000-0003-2623-5126;
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 106A
EP 107A
PG 2
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400313
ER
PT J
AU Reed, W
Noga, SJ
Gee, AP
Rooney, C
McKenna, DH
Wagner, J
Donnenberg, A
Whiteside, T
Baker, A
Lindblad, R
Wagner, E
Mondoro, T
AF Reed, W.
Noga, Stephen J.
Gee, Adrian P.
Rooney, C.
McKenna, David H.
Wagner, J.
Donnenberg, A.
Whiteside, T.
Baker, A.
Lindblad, R.
Wagner, Elizabeth
Mondoro, Traci
TI Production assistance for cellular therapies (PACT): Four year
experience from the NHLBI
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Reed, W.] Blood Syst Res Inst, San Francisco, CA USA.
[Noga, Stephen J.] Sinai Hosp, Baltimore, MD 21215 USA.
[Gee, Adrian P.] Baylor Coll Med, Houston, TX 77030 USA.
[Rooney, C.; McKenna, David H.; Wagner, J.; Baker, A.] Univ Minnesota, Minneapolis, MN 55455 USA.
[Whiteside, T.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA.
[Lindblad, R.] EMMES Corp, Rockville, MD USA.
[Wagner, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA.
EM mondorot@nhlbi.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 4
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 129A
EP 130A
PG 2
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118400381
ER
PT J
AU Cameiro-Proietti, AB
Goncalez, TT
Sampaio, D
Sabino, E
Proietti, F
Oliveira, CDL
Kavounis, K
King, M
Ferreira, JE
Murphy, E
AF Cameiro-Proietti, A. B.
Goncalez, T. T.
Sampaio, D.
Sabino, E.
Proietti, F.
Oliveira, C. D. L.
Kavounis, K.
King, M.
Ferreira, J. E.
Murphy, E.
CA II Int Retrovirus Epidemiology Don
TI The epidemiological profile of blood donors in brazil: Progress toward
an all volunteer donor base
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Cameiro-Proietti, A. B.; Oliveira, C. D. L.] Hemominas Fdn, Belo Horizonte, MG, Brazil.
[Goncalez, T. T.] Blood Syst Res Inst, San Francisco, CA USA.
[Sabino, E.] Fdn Pro Sangue, Sao Paulo, Brazil.
[Kavounis, K.] WESTAT Corp, Rockville, MD 20850 USA.
[Ferreira, J. E.] Univ Sao Paulo, Sao Paulo, Brazil.
[II Int Retrovirus Epidemiology Don] NHLBI, Rockville, MD USA.
RI Sabino, Ester/F-7750-2010; Ferreira, Joao/L-1287-2016
OI Sabino, Ester/0000-0003-2623-5126;
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 215A
EP 215A
PG 1
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118401162
ER
PT J
AU Caruccio, L
Stroncek, DF
AF Caruccio, L.
Stroncek, D. F.
TI Use of interactive methods to introduce and teach molecular biology to
blood bank staff
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Caruccio, L.] NIH, Bethesda, MD 20892 USA.
[Stroncek, D. F.] CC, Dept Transfus Med, Bethesda, MD USA.
EM DStroncek@cc.nih.gov
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 246A
EP 247A
PG 2
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118401250
ER
PT J
AU Kakaiya, R
Triulzi, D
Steele, W
Wright, D
Kleinman, S
Busch, MP
Norris, P
Hillyer, C
Goftschall, JL
Rios, JA
Carey, P
Glynn, S
AF Kakaiya, R.
Triulzi, D.
Steele, W.
Wright, D.
Kleinman, S.
Busch, M. P.
Norris, P.
Hillyer, C.
Goftschall, J. L.
Rios, J. A.
Carey, P.
Glynn, S.
CA Retrovirus Epidemiology Donor
TI Prevalence of HLA antibodies in transfused volunteer blood donors
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Steele, W.; Wright, D.] WESTAT Corp, Rockville, MD 20850 USA.
[Kleinman, S.] Univ British Columbia, Vancouver, MD USA.
[Busch, M. P.] Blood Syst Inc, San Francisco, CA USA.
[Busch, M. P.; Norris, P.] Blood Syst Res Inst, San Francisco, CA USA.
[Hillyer, C.] Emory Univ, Sch Med, Atlanta, GA USA.
[Carey, P.] Univ Cincinnati, Hoxworth Blood Ctr, Cincinnati, OH 45221 USA.
[Glynn, S.] NHLBI, Bethesda, MD 20892 USA.
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 251A
EP 251A
PG 1
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118401261
ER
PT J
AU Daniel-Johnson, J
Lee-Stroka, A
Schechterly, C
Pantin, J
Scheinberg, P
Alter, H
Leitman, SF
Quillen, K
AF Daniel-Johnson, J.
Lee-Stroka, A.
Schechterly, C.
Pantin, J.
Scheinberg, P.
Alter, H.
Leitman, S. F.
Quillen, K.
TI Probiotic-associated high-titer anti-B in a group a platelet donor as a
cause of severe hemolytic transfusion reactions
SO TRANSFUSION
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO
CY OCT 04-07, 2008
CL Montreal, CANADA
SP Amer Assoc Blood Banks
C1 [Daniel-Johnson, J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Schechterly, C.] NIH, CC, DTM, Bethesda, MD 20892 USA.
[Pantin, J.] NHLBI, NIH, Bethesda, MD 20892 USA.
EM quillenk@cc.nih.gov
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 2
SU S
BP 260A
EP 260A
PG 1
WC Hematology
SC Hematology
GA 347CO
UT WOS:000259118401286
ER
PT J
AU McCullough, J
Kahn, J
Adamson, J
Anderlini, P
Benjamin, R
Confer, D
Eapen, M
Hirsch, B
Kuter, D
Lazarus, E
Pamphilon, D
Stroncek, D
Sugarman, J
Wilson, R
AF McCullough, Jeffrey
Kahn, Jeffrey
Adamson, John
Anderlini, Paolo
Benjamin, Richard
Confer, Dennis
Eapen, Mary
Hirsch, Betsy
Kuter, David
Lazarus, Ellen
Pamphilon, Derwood
Stroncek, David
Sugarman, Jeremy
Wilson, Robert
TI Hematopoietic growth factors - use in normal blood and stem cell donors:
clinical and ethical issues
SO TRANSFUSION
LA English
DT Editorial Material
ID COLONY-STIMULATING FACTOR; ACUTE MYOCARDIAL-INFARCTION; ENDOTHELIAL
PROGENITOR CELLS; PLACEBO-CONTROLLED TRIAL;
RECOMBINANT-HUMAN-ERYTHROPOIETIN; THROMBOPOIETIN RECEPTOR AGONIST;
IMMUNE THROMBOCYTOPENIC PURPURA; HUMAN MEGAKARYOCYTE GROWTH;
MESSENGER-RNA EXPRESSION; ACUTE MYELOID-LEUKEMIA
C1 [McCullough, Jeffrey] Univ Minnesota, Minneapolis, MN 55455 USA.
Natl Marrow Donor Program, Minneapolis, MN USA.
Blood Ctr Wisconsin, Milwaukee, WI USA.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
Amer Red Cross, Biomed Serv, Washington, DC 20006 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
US FDA, Rockville, MD 20857 USA.
Univ Bristol, Bristol, Avon, England.
Natl Inst Hlth, Bethesda, MD USA.
Johns Hopkins Univ, Baltimore, MD USA.
RP McCullough, J (reprint author), Univ Minnesota, Minneapolis, MN 55455 USA.
EM mccu1001@umn.edu
NR 139
TC 18
Z9 18
U1 0
U2 2
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2008
VL 48
IS 9
BP 2008
EP 2025
DI 10.1111/j.1537-2995.2008.01788.x
PG 18
WC Hematology
SC Hematology
GA 347CN
UT WOS:000259118300033
PM 18564401
ER
PT J
AU Bezprozvanny, I
Mattson, MP
AF Bezprozvanny, Ilya
Mattson, Mark P.
TI Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID AMYLOID-BETA-PEPTIDE; CULTURED HIPPOCAMPAL-NEURONS; KNOCK-IN MICE;
CORTICAL-NEURONS; PRECURSOR PROTEIN; TRANSGENIC MICE; MOUSE MODEL;
MITOCHONDRIAL DYSFUNCTION; NICOTINIC RECEPTORS; RYANODINE RECEPTOR
AB Perturbed neuronal Ca2+ homeostasis is implicated in age-related cognitive impairment and Alzheimer's disease (AD). With advancing age, neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular Ca2+ dynamics. Toxic forms of amyloid beta-peptide (AP) can induce Ca2+ influx into neurons by inducing membrane-associated oxidative stress or by forming an oligomeric pore in the membrane, thereby rendering neurons vulnerable to excitotoxicity and apoptosis. AD-causing mutations in the beta-amyloid precursor protein and presenilins can compromise these normal proteins in the plasma membrane and endoplasmic reticulum, respectively. Emerging knowledge of the actions of Ca2+ upstream and downstream of AP provides opportunities to develop novel preventative and therapeutic interventions for AD.
C1 [Bezprozvanny, Ilya] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Bezprozvanny, I (reprint author), Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
EM ilya.bezprozvanny@utsouthwestern.edu; mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU Alzheimer's Association research [IIRG-06-24703]; NINDS [R01 NS38082,
R01 NS056224]; National Institute on Aging
FX We also thank K.C. Alexander for preparing Figures 1 and 2. I.B. is a
holder of the Carla Cocke Francis Professorship in Alzheimer's Research
and is supported by the McKnight Neuroscience of Brain Disorders Award,
Alzheimer's Association research grant IIRG-06-24703 and NINDS grants
R01 NS38082 and R01 NS056224. M.P.M. is supported by the Intramural
Research Program of the National Institute on Aging.
NR 89
TC 374
Z9 380
U1 7
U2 40
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD SEP
PY 2008
VL 31
IS 9
BP 454
EP 463
DI 10.1016/j.tins.2008.06.005
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 355ZY
UT WOS:000259749700003
PM 18675468
ER
PT J
AU Chang, JH
Yen, JT
Shung, KK
AF Chang, Jin Ho
Yen, Jesse T.
Shung, K. Kirk
TI High-speed digital scan converter for high-frequency ultrasound sector
scanners
SO ULTRASONICS
LA English
DT Article
DE digital scan conversion; linear interpolation; high frame rate;
ultrasound sector scanner; high-frequency ultrasound imaging
ID HIGH-FRAME RATE; CONVERSION; INTERPOLATION; SYSTEM; MICE
AB This paper presents a high-speed digital scan converter (DSC) capable of providing more than 400 images per second, which is necessary to examine the activities of the mouse heart whose rate is 5-10 beats per second. To achieve the desired high-speed performance in cost-effective manner, the DSC developed adopts a linear interpolation algorithm in which two nearest samples to each object pixel of a monitor are selected and only angular interpolation is performed. Through computer simulation with the Field II program, its accuracy was investigated by comparing it to that of bilinear interpolation known as the best algorithm in terms of accuracy and processing speed. The simulation results show that the linear interpolation algorithm is capable of providing an acceptable image quality, which means that the difference of the root mean square error (RMSE) values of the linear and bilinear interpolation algorithms is below 1%, if the sample rate of the envelope samples is at least four times higher than the Nyquist rate for the baseband component of echo signals. The designed DSC was implemented with a single FPGA (Stratix EP1S60F1020C6, Altera Corporation, San Jose, CA) on a DSC board that is a part of a high-speed ultrasound imaging system developed. The temporal and spatial resolutions of the implemented DSC were evaluated by examining its maximum processing time with a time stamp indicating when an image is completely formed and wire phantom testing, respectively. The experimental results show that the implemented DSC is capable of providing images at the rate of 400 images per second with negligible processing error. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Chang, Jin Ho; Yen, Jesse T.; Shung, K. Kirk] Univ So Calif, NIH, Resource Ctr Med Ultrason Transducer Technol, Dept Biomed Engn, Los Angeles, CA 90089 USA.
RP Chang, JH (reprint author), Univ So Calif, NIH, Resource Ctr Med Ultrason Transducer Technol, Dept Biomed Engn, Los Angeles, CA 90089 USA.
EM jhchang@ieee.org
FU NIH [R01-HL079976, P41-EB2182]
FX The support of NIH Grants Nos. R01-HL079976 and P41-EB2182 is gratefully
acknowledged.
NR 19
TC 12
Z9 15
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0041-624X
J9 ULTRASONICS
JI Ultrasonics
PD SEP
PY 2008
VL 48
IS 5
BP 444
EP 452
DI 10.1016/j.ultras.2008.03.001
PG 9
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 342BG
UT WOS:000258759000012
PM 18430449
ER
PT J
AU Sostaric, JZ
AF Sostaric, Joe Z.
TI A comparative sonochemical reaction that is independent of the intensity
of ultrasound and the geometry of the exposure apparatus
SO ULTRASONICS SONOCHEMISTRY
LA English
DT Article
DE interface; surface tension; cavitation; surfactants; intensity;
frequency; geometry
ID OH-RADICAL FORMATION; QUANTITATIVE SONOCHEMISTRY; SURFACTANT SOLUTIONS;
ACOUSTIC-EMISSION; AQUEOUS-SOLUTIONS; CAVITATION NOISE; FREQUENCY;
SONOLUMINESCENCE; DEPENDENCE; ADSORPTION
AB Sonolysis of aqueous solutions of n-alkyl anionic surfactants results in the formation of secondary carbon-centered radicals (-(CH)-C-center dot-). The yield of -(CH)-C-center dot- depends on the bulk surfactant concentration up to a maximum attainable radical yield (the 'plateau yield') where an increasing surfactant concentration (be low the critical micelle concentration) no longer affects the -(CH)-C-center dot- yield. In an earlier study it was found that the ratio of -(CH)-C-center dot- detected following sonolysis of aqueous solutions of sodium pentane sulfonate (SPSo) to that of sodium dodecyl sulfate (SDS) (i.e. CHSPSo/CHSDS) depended on the frequency of sonolysis, but was independent of the ultrasound intensity, at the plateau concentrations [J.Z. Sostaric, P. Riesz, Adsorption of surfactants at the gas/solution interface of cavitation bubbles: an ultrasound intensity-independent frequency effect in sonochemistry, J. Phys. Chem. B 106 (2002) 12537-12548]. In the current study, it was found that the CHSPSo/CHSDs ratio depended only on the ultrasound frequency and did not depend on the geometry of the ultrasound exposure apparatus considered. Published by Elsevier B.V.
C1 [Sostaric, Joe Z.] Natl Canc Inst, Radiat Biol Branch, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Sostaric, JZ (reprint author), Ohio State Univ, Davis Heart & Lung Res Inst, 420 W 12th Ave,TMRF-184, Columbus, OH 43210 USA.
EM sostaric.2@osu.edu
RI Sostaric, Joe/A-6033-2008
FU Intramural NIH HHS [Z01 SC006358-24]
NR 30
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1350-4177
J9 ULTRASON SONOCHEM
JI Ultrason. Sonochem.
PD SEP
PY 2008
VL 15
IS 6
BP 1043
EP 1048
DI 10.1016/j.ultsonch.2008.03.007
PG 6
WC Acoustics; Chemistry, Multidisciplinary
SC Acoustics; Chemistry
GA 324KJ
UT WOS:000257517200021
PM 18472292
ER
PT J
AU Mueller, CM
Caporaso, N
Greene, MH
AF Mueller, Christine M.
Caporaso, Neil
Greene, Mark H.
TI Familial and genetic risk of transitional cell carcinoma of the urinary
tract
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Review
DE urinary bladder neoplasms; transitional cell carcinoma; hereditary
neoplastic syndromes; genetic polymorphism
ID NONPOLYPOSIS COLORECTAL-CANCER; MUIR-TORRE-SYNDROME; 2ND PRIMARY TUMORS;
CDC91L1 PIG-U; BLADDER-CANCER; LYNCH-SYNDROME; COSTELLO-SYNDROME;
HEREDITARY RETINOBLASTOMA; BILATERAL RETINOBLASTOMA; GENITOURINARY
TUMORS
AB Environmental exposures, including tobacco smoke and occupational exposure to aromatic amines, have been implicated in bladder cancer etiology. However. the pathogenesis of urinary bladder transitional cell carcinoma remains incompletely defined. In epidemiologic studies. family history confers a 2-fold increase in bladder cancer risk, but it is uncertain whether this represents evidence of a genetic and/or a shared environmental basis for familial aggregation. Polymorphisms in genes involved in the metabolism of environmental toxins (e.g NAT2) clearly modify individual susceptibility to bladder cancer. A genetic predisposition has also been Suggested by case reports describing multiple-case families, and the development of bladder cancer in association with several well-described Mendelian disorders (e.g., HNPCC, retinoblastoma). Here we update a previously reported family, report a new multiple-case kindred. critically review previously reported bladder cancer families, and the epidemiologic literature related to family history of transitional cell carcinoma of the urinary tract (TCCUT) as a risk factor, as well as provide a brief summary of genetic factors that have been implicated in TCCUT risk. We conclude that familial TCCUT is either very uncommon or significantly Under-reported, perhaps on the assumption that this is an environmental rather than a genetic disorder. The interaction between multiple genetic and environmental factors has made it challenging to identify genetic components responsible for man), common diseases; therefore, a proposed genome-wide association Study (GWAS) for urinary bladder cancer may help to clarify the etiologic role of the candidate genetic pathways reviewed here, as well as characterize gene/environement interactions that contribute to TCCUT carcinogenesis. Published by Elsevier Inc.
C1 [Mueller, Christine M.; Greene, Mark H.] NCI, NIH, Clin Genet Branch, Div Canc Epidemiol & Genet,DHHS, Rockville, MD 20852 USA.
[Caporaso, Neil] NCI, NIH, Genet Epidemiol Branch, Div Canc Epidemiol & Genet,DHHS, Rockville, MD 20852 USA.
RP Mueller, CM (reprint author), NCI, NIH, Clin Genet Branch, Div Canc Epidemiol & Genet,DHHS, Rockville, MD 20852 USA.
EM muellerc@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010144-09]
NR 92
TC 28
Z9 30
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD SEP-OCT
PY 2008
VL 26
IS 5
BP 451
EP 464
DI 10.1016/j.urolonc.2008.02.016
PG 14
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 351IC
UT WOS:000259416900001
PM 18562223
ER
PT J
AU Linehan, WM
AF Linehan, W. Marston
TI Kidney cancer: Opportunity for disease specific targeted therapy
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Editorial Material
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z01 SC006659-25]
NR 1
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD SEP-OCT
PY 2008
VL 26
IS 5
BP 542
EP 542
DI 10.1016/j.urolonc.2008.03.014
PG 1
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 351IC
UT WOS:000259416900017
PM 18774470
ER
PT J
AU McMullen, RJ
Clode, AB
Pandiri, AKR
Malarkey, DE
Michau, TM
Gilger, BC
AF McMullen, Richard J.
Clode, Alison B.
Pandiri, Arun Kumar R.
Malarkey, David E.
Michau, Tammy Miller
Gilger, Brian C.
TI Epibulbar melanoma in a foal
SO VETERINARY OPHTHALMOLOGY
LA English
DT Article
DE congenital; epibulbar; equine; melanoma; neoplasia
ID CANINE LIMBAL MELANOMA; TUMOR-LIKE LESIONS; OCULAR MELANOMA;
CORNEOSCLERAL DEFECT; INTRAOCULAR MELANOMA; HORSE; DOGS;
MEDULLOEPITHELIOMA; REPAIR; CAT
AB A case of epibulbar melanoma in a 6-month-old, gelded, chestnut Hanoverian foal is reported. The location and clinical appearance upon initial presentation led to the tentative diagnosis of staphyloma or a congenital mass of unknown origin. An attempt was made to surgically excise the mass under general anesthesia, but due to its infiltrative nature and intraoperative appearance, most, but not all was removed without compromising the integrity of the globe. Histopathological evaluation revealed a multinodular to packeted, poorly demarcated, unencapsulated, infiltrative exophytic melanocytic neoplasm composed of bundles and nests of plump spindloid to polygonal heavily pigmented epithelioid neoplastic cells interspersed with pigment-laden macrophages within a fine fibrovascular stroma. Upon examination after enucleation, neoplastic cells were found to infiltrate into the lateral cornea, sclera and the choroid. This is a unique case of an epibulbar melanoma with choroidal invasion in a foal. Based on the sudden onset and rapid growth as well as the histological evidence of invasion, well-differentiated features, heavy pigmentation, and no apparent mitoses, this neoplasm was considered to be a low-grade malignant melanoma. At 14 months after excision there is no evidence of recurrence.
C1 [McMullen, Richard J.; Clode, Alison B.; Gilger, Brian C.] N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27695 USA.
[Pandiri, Arun Kumar R.] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC USA.
[Malarkey, David E.] Natl Inst Environm Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA.
RP McMullen, RJ (reprint author), N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27695 USA.
EM brian_gilger@ncsu.edu
FU NIH; National Institute of Environmental Health Sciences
FX The authors wish to thank Ms Monica Mattmuller and Mr Nathan Whitehurst
for their excellent technical assistance with the repeated trimming,
bleaching, and staining of the samples. This report was supported (in
part) by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences.
NR 63
TC 7
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1463-5216
J9 VET OPHTHALMOL
JI Vet. Ophthalmol.
PD SEP-OCT
PY 2008
VL 11
SU 1
BP 44
EP 50
DI 10.1111/j.1463-5224.2008.00637.x
PG 7
WC Veterinary Sciences
SC Veterinary Sciences
GA 339TH
UT WOS:000258599700008
PM 19046269
ER
PT J
AU Klaunig, JE
Davis, MA
AF Klaunig, James E.
Davis, Myrtle A.
TI Remembering Benjamin Franklin trump
SO VETERINARY PATHOLOGY
LA English
DT Biographical-Item
C1 [Klaunig, James E.] Indiana Univ, Indianapolis, IN 46204 USA.
[Davis, Myrtle A.] NCI, Rockville, MD USA.
RP Klaunig, JE (reprint author), Indiana Univ, Indianapolis, IN 46204 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL VET PATHOLOGIST
PI LAWRENCE
PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD SEP
PY 2008
VL 45
IS 5
BP 611
EP 612
PG 2
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 353AL
UT WOS:000259538400001
PM 18725462
ER
PT J
AU Veit, AC
Painter, JT
Miller, RA
Hardisty, JF
Dixon, D
AF Veit, A. C.
Painter, J. T.
Miller, R. A.
Hardisty, J. F.
Dixon, D.
TI Characterization of uterine granular cell tumors in B6C3F1 mice: A
histomorphologic, immunohistochemical, and ultrastructural study
SO VETERINARY PATHOLOGY
LA English
DT Article
DE B6C3F1 mouse; cytoplasmic granules; granular cell tumor;
immunohistochemistry; secondary lysosomes; ultrastructure; uterus
ID FEMALE REPRODUCTIVE-TRACT; MYOBLASTOMA; DOG; RATS; LESIONS; ORIGIN;
TONGUE; DIETHYLSTILBESTROL; HISTOGENESIS; PROTEINS
AB The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic Feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors vat-led in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha Smooth Muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.
C1 [Veit, A. C.; Dixon, D.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
[Veit, A. C.; Painter, J. T.; Miller, R. A.; Hardisty, J. F.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
RP Dixon, D (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH,DHHS, POB 12233,MD C2-09,111 TW Alexander Dr,Bldg 101, Res Triangle Pk, NC 27709 USA.
EM dixon@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX We thank Drs. Ronald Herbert and John Peckham for their critical reviews
of this manuscript, Dr. Henry Wall for guidance with electron microscopy
in-iages, Keith Connelly for database management, and Natasha Clayton,
Norris Flagler, Julie Foley, John Horton, JoAnne Johnson, Tiwanda Marsh,
and Sheetal Trive i for their excellent technical assistance. We thank
Arvesta Corporation, in particular Dr. John Kinzell, Director of
Regulatory Affairs, for providing funding for this Study. This research
was supported, in part, by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences.
NR 58
TC 8
Z9 8
U1 0
U2 0
PU AMER COLL VET PATHOLOGIST
PI LAWRENCE
PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD SEP
PY 2008
VL 45
IS 5
BP 654
EP 662
DI 10.1354/vp.45-5-654
PG 9
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 353AL
UT WOS:000259538400009
PM 18725470
ER
PT J
AU Rambold, HA
Miles, FA
AF Rambold, H. A.
Miles, F. A.
TI Human vergence eye movements to oblique disparity stimuli: Evidence for
an anisotropy favoring horizontal disparities
SO VISION RESEARCH
LA English
DT Article
DE the aperture problem; orientation selectivity; disparity vergence;
disparity processing; sine-wave gratings
ID PRIMARY VISUAL-CORTEX; CORTICAL AREA MST; BINOCULAR DISPARITY;
DEPTH-PERCEPTION; MACAQUE MONKEY; LOCAL STEREOPSIS; APERTURE PROBLEM;
V1; RESPONSES; NEURONS
AB Binocular disparities applied to large-field patterns elicit vergence eye movements at ultra-short latencies. We used the electromagnetic search coil technique to record the horizontal and vertical positions of both eyes while subjects briefly viewed (150 ms) large patterns that were identical at the two eyes except for a difference in position (binocular disparity) that was varied in direction from trial to trial. For accurate alignment with the stimuli, the horizontal and vertical disparity vergence responses (HDVRs, VDVRs) should vary as the sine and cosine, respectively, of the direction of the disparity stimulus vector. In a first experiment, using random-dots patterns (RDs) with a binocular disparity of 0.2, this was indeed the case. In a second experiment, using 1-D sine-wave gratings with a binocular phase difference (disparity) of 1/4-wavelength, it was not the case: HDVRs were maximal when the grating was vertical and showed little decrement until the grating was oriented more than similar to 65 degrees away from vertical, whereas VDVRs were maximal when the grating was horizontal and began to decrement roughly linearly when the grating was oriented away from the horizontal. We attribute these complex directional dependencies with gratings to the aperture problem, and the HDVR data strongly resemble the stereothresholds for 1-D gratings, which are minimal when the gratings are vertical and remain constant for orientations up to similar to 80 degrees away from the vertical when expressed as spatial phase disparities [Morgan, M. J., & Castet, E. (1997). The aperture problem in stereopsis. Vision Research, 37, 2737-2744.]. To explain this constancy of stereothresholds, Morgan and Castet (1997) postulated detectors sensitive to the phase disparity of the gratings seen by the two eyes (rather than their linear separation along some fixed axis, such as the horizontal). However, because (1) our VDVR data with gratings did not show this constancy and (2) the available evidence strongly suggests that there are no major differences in the disparity detectors mediating the initial HDVR and VDVR, we sought an alternative explanation for our data. We show that the dependence of the initial HDVR and VDVR on grating orientation can be successfully modeled by a bias in the number and/or efficacy of the detectors that favors horizontal disparities. 2008 Published by Elsevier Ltd.
C1 [Rambold, H. A.; Miles, F. A.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Rambold, HA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49 Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA.
EM ramboldh@nei.nih.gov
OI Rambold, Holger/0000-0002-8056-9429
FU Intramural Program of the National Eye Institute at the NIH; Alexander
von Humboldt Foundation (Germany)
FX This research was supported by the Intramural Program of the National
Eye Institute at the NIH. H.A.R. was also supported by the Alexander von
Humboldt Foundation (Germany). The authors thank Drs. B.M. Sheliga and
E.J. FitzGibbon for technical and experimental support.
NR 57
TC 6
Z9 6
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD SEP
PY 2008
VL 48
IS 19
BP 2006
EP 2019
DI 10.1016/j.visres.2008.05.009
PG 14
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 341XA
UT WOS:000258747700010
PM 18675438
ER
PT J
AU Wurtz, RH
AF Wurtz, Robert H.
TI Neuronal mechanisms of visual stability
SO VISION RESEARCH
LA English
DT Review
DE stable vision; saccades; corollary discharge; efference copy; visual
masking; transsaccadic memory; proprioception
ID SACCADIC EYE-MOVEMENTS; POSTERIOR PARIETAL CORTEX; LATERAL
GENICULATE-NUCLEUS; MONKEY SUPERIOR COLLICULUS; INDUCED STIMULUS
MOVEMENT; OLD-WORLD MONKEYS; STRIATE CORTEX; RECEPTIVE-FIELDS; COROLLARY
DISCHARGE; RHESUS-MONKEY
AB Human vision is stable and continuous in spite of the incessant interruptions produced by saccadic eye movements. These rapid eye movements serve vision by directing the high resolution fovea rapidly from one part of the visual scene to another. They should detract from vision because they generate two major problems: displacement of the retinal image with each saccade and blurring of the image during the saccade. This review considers the substantial advances in understanding the neuronal mechanisms underlying this visual stability derived primarily from neuronal recording and inactivation studies in the monkey, an excellent model for systems in the human brain. For the first problem, saccadic displacement, two neuronal candidates are salient. First are the neurons in frontal and parietal cortex with shifting receptive fields that provide anticipatory activity with each saccade and are driven by a corollary discharge. These could provide the mechanism for a retinotopic hypothesis of visual stability and possibly for a transsaccadic memory hypothesis, The second neuronal mechanism is provided by neurons whose visual response is modulated by eye position (gain field neurons) or are largely independent of eye position (real position neurons), and these neurons could provide the basis for a spatiotopic hypothesis. For the second problem, saccadic suppression, visual masking and corollary discharge are well established mechanisms, and possible neuronal correlates have been identified for each. Published by Elsevier Ltd.
C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,RM 2A50, Bethesda, MD 20892 USA.
EM bob@lsr.nei.nih.gov
FU Intramural NIH HHS [Z01 EY000109-27]
NR 178
TC 248
Z9 248
U1 9
U2 43
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD SEP
PY 2008
VL 48
IS 20
BP 2070
EP 2089
DI 10.1016/j.visres.2008.03.021
PG 20
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 354DQ
UT WOS:000259619500006
PM 18513781
ER
PT J
AU Williams, MJ
Grimley, DM
AF Williams, Makeda J.
Grimley, Diane M.
TI Depressive symptoms and interpersonal victimization among African
American women attending an urban STD clinic
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID SEXUALLY-TRANSMITTED-DISEASE; RISK BEHAVIOR; SUBSTANCE USE; SELF-ESTEEM;
BLACK-WOMEN; PREVALENCE; HIV; INTERVENTIONS; ASSOCIATIONS; ADOLESCENTS
AB Objectives. This study evaluated the association of depressive symptom levels and interpersonal victimization. The sample was comprised of 455 African American women attending an urban sexually transmitted disease clinic. Interpersonal victimization was defined as whether a woman was forced to have sexual intercourse and whether a woman was ever hit, slap or physically hurt by a boyfriend, girlfriend, or spouse in the past 12 months.
Methods. Using audio computer-assisted self-interviewing (ACASI), women responded to questions regarding interpersonal victimization and depressive symptom levels (e.g., depression, sadness, loneliness and crying in the past week).
Results. Results indicated that women with a history of interpersonal victimization were more likely to experience higher levels of depressive symptoms when compared with women who did not. Statistically significant differences were found for being forced to have sexual intercourse (all P's < 0.0001) and ever being hit, slap or physically hurt by a boyfriend, girlfriend, or spouse in the past 12 months (p's range from 0.012 to 0.0003) with regard to each depressive symptom item.
Conclusion. Behavioral women-focused interventions need to address mental health issues associated with risky sexual behaviors in order to be more efficacious.
C1 [Williams, Makeda J.] NCI, NIH, Bethesda, MD 20892 USA.
[Grimley, Diane M.] Univ Alabama, Birmingham Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL USA.
RP Williams, MJ (reprint author), NCI, NIH, 6130 Execut Blvd,Suite 100, Bethesda, MD 20892 USA.
EM willimak@mail.nih.gov
FU NIAID NIH HHS [U19AI35814-06]
NR 27
TC 5
Z9 5
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD SEP-OCT
PY 2008
VL 18
IS 5
BP 375
EP 380
DI 10.1016/j.whi.2008.06.004
PG 6
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA 350DF
UT WOS:000259332100006
PM 18774455
ER
PT J
AU Schepers, RJ
Mahoney, JL
Gehrke, BJ
Shippenberg, TS
AF Schepers, R. J.
Mahoney, Janet Lynn
Gehrke, Brenda Jean
Shippenberg, Toni Shaun
TI Endogenous kappa-opioid receptor systems inhibit hyperalgesia associated
with localized peripheral inflammation
SO PAIN
LA English
DT Article
DE inflammation; kappa-opioid receptor; rostral ventromedial medulla;
knockout; spinal cord; CFA; norbinaltorphimine; gene deletion; rat;
mouse
ID ADMINISTERED NOR-BINALTORPHIMINE; CHRONIC NEUROPATHIC PAIN; DORSAL-HORN
NEURONS; SPINAL-CORD; KNOCKOUT MICE; NERVE INJURY; MECHANICAL
HYPERALGESIA; DESCENDING MODULATION; NOCICEPTIVE RESPONSES; FOS
EXPRESSION
AB Peripheral inflammation evokes functional and biochemical changes in the periphery and spinal cord which result in central sensitization and hypersensitivity. Inhibitory control systems from the rostral ventromedial medulla (RVM) are also activated. The present study investigates whether endogenous kappa-opioid receptor (KOPr) systems contribute to these neuroadaptations. Inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA) into one hindpaw. Mechanical and thermal thresholds were determined using the Von Frey and radiant heat tests, respectively. KOPr gene deletion in mice or systemic administration of the long-acting KOPr antagonist, norbinaltorphimine (norBNI) significantly exacerbated mechanical and thermal hypersensitivity of the ipsilateral, inflamed paw. Thermal and mechanical thresholds of the non-inflamed, contralateral hindpaw were unaffected by CFA treatment. However, gene deletion as well as norBNI treatment resulted in mechanical, but not thermal hypersensitivity of the non-inflamed paw. Similar results were obtained when norBNI was administered intrathecally or into the RVM in rats. These data demonstrate a previously unrecognized role of endogenous KOPr systems in inhibiting hyperalgesia during inflammation. Furthermore, they demonstrate that decreased KOPr activity in either the spinal cord or RVM not only enhances mechanical and thermal hyperalgesia of the inflamed limb but also leads to an unmasking of mechanical hyperalgesia at a site remote from inflammation. The differential effects of KOPr antagonism on mechanical versus thermal thresholds for the non-inflamed paw support the notion that distinct neuroanatomical or neurochemical mechanisms modulate the processing of thermal versus mechanical stimuli. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
C1 [Schepers, R. J.; Mahoney, Janet Lynn; Gehrke, Brenda Jean; Shippenberg, Toni Shaun] Natl Inst Drug Abuse, Integrat Neurosci Sect, Behav Neurosci Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
[Schepers, R. J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Shippenberg, TS (reprint author), Natl Inst Drug Abuse, Integrat Neurosci Sect, Behav Neurosci Branch, NIH,Intramural Res Program, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM tshippen@mail.nih.gov
FU Intramural NIH HHS [Z01 DA000505-01]
NR 87
TC 19
Z9 19
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD AUG 31
PY 2008
VL 138
IS 2
BP 423
EP 439
DI 10.1016/j.pain.2008.01.023
PG 17
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 356IW
UT WOS:000259772900021
PM 18355964
ER
PT J
AU Nemukhin, AV
Topol, IA
Grigorenko, BL
Savitsky, AP
Collins, JR
AF Nemukhin, A. V.
Topol, I. A.
Grigorenko, B. L.
Savitsky, A. P.
Collins, J. R.
TI Conformation dependence of pK(a)'s of the chromophores from the purple
asFP595 and yellow zFP538 fluorescent proteins
SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM
LA English
DT Article
DE biological chromophores; pK(a); cis-trans isomerization; fluorescent
proteins
ID ABSORPTION-SPECTRA; ANEMONIA-SULCATA; STATE STRUCTURE; PROTONATION;
CHROMOPROTEIN; MECHANISM; VALUES; GFP
AB Two members of the green fluorescent protein family, the purple asFP595 and yellow zFP538 proteins, are perspective fluorescent markers for use in multicolor imaging and resonance energy-transfer applications. We report the results of quantum based Calculations of the Solution pK(a) values for selected protonation sites of the denatured asFP595 and zFP538 chromophores in the trans- and cis-conformations in order to add in the interpretation of photo-physical properties of these proteins. The pK(a) Values Were determined from the theromodynamic cycle based on B3LYP/6-311++G(2df, 2p) calculations of the gas phase free energies of the molecules and the B3LYP/6-311++G(d, p) calculations of solvation energies. The results show that the pK(a)'s of the protonation sites of the chromophore from asFP595 noticeably depend on the isomer conformation (cis- or trans-), while those of zFP538 are Much less sensitive to isomerization. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Nemukhin, A. V.; Grigorenko, B. L.] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia.
[Nemukhin, A. V.] Russian Acad Sci, NM Emanuel Inst Biochem Phys, Moscow 119334, Russia.
[Topol, I. A.; Collins, J. R.] SAIC Frederick Inc, NCI, Adv Technol Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Savitsky, A. P.] Russian Acad Sci, AN Bach Inst Biochem, Moscow 119071, Russia.
RP Nemukhin, AV (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Leninskie Gory 1-3, Moscow 119991, Russia.
EM anem@lcc.chem.msu.ru
RI Savitsky, Alexander/O-9799-2015; Nemukhin, Alexander/P-9662-2015
FU Science and Innovation Federal Russian Agency [02.522.11.2002]; Russian
Academy of Sciences; Russian Foundation for Basic Research
[07-03-00059]; Advanced Biomedical Computing Center; National Cancer
Institute; National Institutes of Health [N01-CO-12400]
FX This work was partly supported by the Science and Innovation Federal
Russian Agency (project # 02.522.11.2002). by the Program for Molecular
and Cell Biology from Russian Academy of Sciences, and by the grant from
the Russian Foundation for Basic Research (project #07-03-00059). We
thank the staff and administration of the Advanced Biomedical Computing
Center for their Support Of this project. This project has been funded
in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract N01-CO-12400.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organization imply
endorsement by the U.S. Government.
NR 25
TC 11
Z9 11
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-1280
J9 J MOL STRUC-THEOCHEM
JI Theochem-J. Mol. Struct.
PD AUG 30
PY 2008
VL 863
IS 1-3
BP 39
EP 43
DI 10.1016/j.theochem.2008.05.014
PG 5
WC Chemistry, Physical
SC Chemistry
GA 342NS
UT WOS:000258791400007
ER
PT J
AU Wang, S
Zhou, YF
Yu, ZX
Hunter, T
Hoyt, RF
Horvath, KA
AF Wang, Suna
Zhou, Yifu
Yu, Zuxi
Hunter, Timothy
Hoyt, Robert F., Jr.
Horvath, Keith A.
TI Determining Gene Expression Elucidates the Benefit with Stem Cell
Treatment of Ischemic Myocardium
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference
CY JUL 28-31, 2008
CL Keystone, CO
C1 [Wang, Suna; Zhou, Yifu; Yu, Zuxi; Hunter, Timothy; Hoyt, Robert F., Jr.; Horvath, Keith A.] NIH, 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 0009-7330
J9 CIRC RES
JI Circ.Res.
PD AUG 29
PY 2008
VL 103
IS 5
MA P137
BP E61
EP E61
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 343HX
UT WOS:000258845200148
ER
PT J
AU Xu, X
Fassett, J
Lu, ZB
Hu, XL
Zhu, GS
French, J
Zhang, P
Jacobson, MA
Schnermann, J
Bache, RJ
Chen, YJ
AF Xu, Xin
Fassett, John
Lu, Zhongbing
Hu, Xinli
Zhu, Guangshuo
French, Joel
Zhang, Ping
Jacobson, Marlene A.
Schnermann, Jurgen
Bache, Robert J.
Chen, Yingjie
TI Adenosine A3 Receptor Deficiency Exerts Unanticipated Protective Effects
on the Pressure Overloaded Left Ventricle
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference
CY JUL 28-31, 2008
CL Keystone, CO
C1 [Xu, Xin; Fassett, John; Lu, Zhongbing; Hu, Xinli; Zhu, Guangshuo; French, Joel; Zhang, Ping; Bache, Robert J.; Chen, Yingjie] Univ Minnesota, Minneapolis, MN USA.
[Jacobson, Marlene A.] Merck Rsch Labs, West Point, PA USA.
[Schnermann, Jurgen] NIDDK, Bethesda, 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 0009-7330
J9 CIRC RES
JI Circ.Res.
PD AUG 29
PY 2008
VL 103
IS 5
MA P30
BP E41
EP E41
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 343HX
UT WOS:000258845200047
ER
PT J
AU Zhang, Y
Liao, MJ
Dufau, ML
AF Zhang, Ying
Liao, Mingjuan
Dufau, Maria L.
TI Unlocking repression of the human luteinizing hormone receptor gene by
trichostatin A-induced cell-specific phosphatase release
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; KINASE-C ZETA; REGULATE TRANSCRIPTION;
SP1 SITES; PROMOTER; ACETYLATION; EXPRESSION; COMPLEX; PHOSPHORYLATION;
RECRUITMENT
AB Our previous studies demonstrated that the histone deacetylase inhibitor, trichostatin A (TSA), induces derepression of the human luteinizing hormone receptor (LHR) gene by de-recruitment of the pRB homologue p107 repressor from the promoter in JAR and MCF-7 cancer cells. TSA initiates a mechanism whereby the phosphatidylinositol 3-kinase/protein kinase zeta (PKC zeta) cascade phosphorylates Sp1 at Ser-641, which is essential for the release of the repression of LHR transcription. The present studies have revealed that dissociation of serine/threonine protein phosphatases PP2A and PP1 from the LHR promoter mediates TSA-induced activation of LHR gene transcription in a cell-specific manner. Changes in chromatin structure induced by TSA cause the release of PP2A in JAR cells or of PP1 in MCF-7 cells, which is associated with Sp1 directly or through histone deacetylase 1/2, respectively, at the promoter. This favors the phosphorylation of Sp1 mediated by the phosphatidylinositol 3-kinase/PKC zeta pathway, which in turn causes the release of the p107 inhibitor from Sp1 and marked transcriptional activation of the LHR. These findings reveal the importance of phosphatases in the control of LHR transcription, where the balance between phosphatidylinositol 3-kinase/PKC zeta and phosphatases could be critical for up- and down-regulation of LHR gene expression in physiological and pathological settings.
C1 [Zhang, Ying; Liao, Mingjuan; Dufau, Maria L.] Eunice Kennedy Shriver NICHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA.
RP Dufau, ML (reprint author), NIH, Bldg 49,Rm 6A-36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA.
EM dufaum@mail.nih.gov
FU National Institutes of Health (Intramural Research Program of the NICHD)
FX This work was supported, in whole or in part, by National Institutes of
Health (Intramural Research Program of the NICHD). 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 31
TC 11
Z9 11
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 29
PY 2008
VL 283
IS 35
BP 24039
EP 24046
DI 10.1074/jbc.M801878200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 340II
UT WOS:000258638900059
PM 18596044
ER
PT J
AU Grossfield, A
Pitman, MC
Feller, SE
Soubias, O
Gawrisch, K
AF Grossfield, Alan
Pitman, Michael C.
Feller, Scott E.
Soubias, Olivier
Gawrisch, Klaus
TI Internal hydration increases during activation of the G-protein-coupled
receptor rhodopsin
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE molecular dynamics; NMR; hydration; GPCR
ID CYSTEINE SUBSTITUTION MUTANTS; METARHODOPSIN II FORMATION; RETINAL
COUNTERION SWITCH; SULFHYDRYL REACTIVITY; MOLECULAR SIMULATIONS;
TERTIARY STRUCTURE; CRYSTAL-STRUCTURE; BOVINE RHODOPSIN; HELICES I;
DYNAMICS
AB Rhodopsin, the membrane protein responsible for dim-light vision, until recently was the only G-protein-coupled receptor (GPCR) with a known crystal structure. As a result, there is enormous interest in studying its structure, dynamics, and function. Here we report the results of three all-atom molecular dynamics simulations, each at least 1.5 mu s, which predict that substantial changes in internal hydration play a functional role in rhodopsin activation. We confirm with H magic angle spinning NMR that the increased hydration is specific to the metarhodopsin-I intermediate. The internal water molecules interact with several conserved residues, suggesting that changes in internal hydration may be important during the activation of other GPCRs. The results serve to illustrate the synergism of long-time-scale molecular dynamics simulations and NMR in enhancing our understanding of GPCR function. (c) 2008 Published by Elsevier Ltd.
C1 [Grossfield, Alan; Pitman, Michael C.] IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA.
[Feller, Scott E.] Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA.
[Soubias, Olivier; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
RP Pitman, MC (reprint author), IBM Corp, Thomas J Watson Res Ctr, 1101 Kitchawan Rd,POB 218, Yorktown Hts, NY 10598 USA.
EM pitman@us.ibm.com
OI Grossfield, Alan/0000-0002-5877-2789
FU Intramural Research Program of NIAAA; NIH [MCB-0543124, PHS 2 PN2
EY016570B]
FX We thank the IBM Watson Research Center and the Computational Biology
Center for use of the BGW Blue Gene supercomputing facility. We extend a
special thanks to the Blue Matter development team (B. Fitch, R.
Germain, A. Rayshubskiy, T. J. C. Ward, M. Eleftheriou, F. Suits, Y.
Zhestkov, R. Zhou, J. Pitera, and W. Swope). K.G. and O.S. were
supported by the Intramural Research Program of NIAAA, NIH. S.E.F.
thanks the NSF and NIH for support through awards MCB-0543124 and PHS 2
PN2 EY016570B, respectively.
NR 49
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U2 16
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 29
PY 2008
VL 381
IS 2
BP 478
EP 486
DI 10.1016/j.jmb.2008.05.036
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 338CV
UT WOS:000258483600021
PM 18585736
ER
PT J
AU Ahmed, F
Tessarollo, L
Thiele, C
Mocchetti, I
AF Ahmed, Farid
Tessarollo, Lino
Thiele, Carol
Mocchetti, Italo
TI Brain-derived neurotrophic factor modulates expression of chemokine
receptors in the brain
SO BRAIN RESEARCH
LA English
DT Article
DE BDNF; HIV dementia; CXCR4; CCR5; gp120; TrkB
ID HUMAN NEUROBLASTOMA-CELLS; CENTRAL-NERVOUS-SYSTEM; NEURONAL APOPTOSIS;
IN-VIVO; GLYCOPROTEIN GP120; HIV DEMENTIA; CXCR4; MICE; CCR5; TRKB
AB Chemokine receptors, and in particular CXCR4 and CCR5 play a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV)(4) associated dementia (HAD). Thus, new insight into the expression of CXCR4 in the central nervous system may help develop therapeutic compounds against HAD. Brain-derived neurotrophic factor (BDNF) is neuroprotective in vitro against two strains of the HIV envelope protein gp120 that binds to CXCR4 or CCR5. Therefore, we examined whether BDNF modulates chemokine receptor expression in vivo. The content of CXCR4 mRNA and proteins was determined in the cerebral cortex and hippocampus of 6-month-old BDNF heterozygous mice and wild type littermates by using polymerase chain reaction and immunohistochemistry, respectively. BDNF heterozygous mice exhibited an increase in CXCR4 mRNA compared to wild type. Histological analyses revealed an up-regulation of CXCR4 immunoreactivity mainly in neurons. Most of these neurons were positive for TrkB, the BDNF receptor with a tyrosine kinase activity. Increases in CXCR4 mRNA levels were observed in 18-month-old BDNF heterozygous mice but not in 7-day-old mice, suggesting that the modulatory role of BDNF occurs only in mature animals. To determine whether BDNF affects also CXCR4 internalization, SH-SY5Y neuroblastoma cells were exposed to BDNF and cell surface CXCR4 levels were measured at various times. BDNF induced CXCR4 internalization within minutes. Lastly, BDNF heterozygous mice showed higher levels of CCR5 and CXCR3 mRNA than wild type in the cerebral cortex, hippocampus and striatum. Our data indicate that BDNF may modulate the availability of chemokine receptors implicated in HIV infection. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Ahmed, Farid; Mocchetti, Italo] Georgetown Univ, Dept Neurosci, Med Ctr, Washington, DC 20057 USA.
[Tessarollo, Lino] NCI, Neural Dev Grp, Frederick, MD 21701 USA.
[Thiele, Carol] NCI, Paediat Oncol Branch, Bethesda, MD 20892 USA.
RP Mocchetti, I (reprint author), Georgetown Univ, Dept Neurosci, Med Ctr, New Res Bldg,3970 Reservoir Rd NW, Washington, DC 20057 USA.
EM moccheti@georgetown.edu
FU HHS [040670]; National Cancer Institute, Center for Cancer Research
FX Supported by HHS grant NS 040670 and by the intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
Special thanks to NIH AIDS Research Reference Reagent Program for the
CXCR4 antibody, Amgen for the gift of BDNF and Dr. D. R. Kaplan for the
TrkB antibody.
NR 52
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U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD AUG 28
PY 2008
VL 1227
BP 1
EP 11
DI 10.1016/j.brainres.2008.05.086
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 352PY
UT WOS:000259510700001
PM 18588860
ER
PT J
AU Huang, J
Chen, KQ
Gong, WH
Zhou, Y
Le, YY
Bian, XW
Wang, JM
AF Huang, Jian
Chen, Keqiang
Gong, Wanghua
Zhou, Ye
Le, Yingying
Bian, Xiuwu
Wang, Ji Ming
TI Receptor "hijacking" by malignant glioma cells: A tactic for tumor
progression
SO CANCER LETTERS
LA English
DT Review
DE glioma; formyl peptide receptor; chemotaxis; angiogenesis
ID GROWTH-FACTOR RECEPTOR; FORMYL PEPTIDE RECEPTOR; N-FORMYLPEPTIDE
RECEPTOR; PROTEIN-COUPLED RECEPTORS; KAPPA-B ACTIVATION; FMET-LEU-PHE;
GENE AMPLIFICATION; GLIOBLASTOMA-MULTIFORME; CHEMOKINE RECEPTOR; VEGF
EXPRESSION
AB Gliomas are the most common and deadly tumors ill the central nervous system (CNS). in the course of studying the role of chemoattractant receptors in tumor growth and metastasis, we discovered that highly malignant human glioblastoma and anaplastic astrocytoma specimens were stained positively for the formylpeptide receptor (FPR), which is normally expressed in myeloid cells and accounts for their chemotaxis and activation induced by bacterial peptides. Screening of human glioma cell lilies revealed that FPR was expressed selectively in glioma cell lilies with a more highly malignant phenotype. FPR expressed in glioblastoma cell lilies mediates cell chemotaxis. proliferation and production of all angiogenic factor. vascular endothelial growth factor (VEGF), in response to agonists released by necrotic tumor cells. Furthermore. FPR in glioblastoma cells activates the receptor for epidermal growth factor (EGFR) by increasing the phosphorylation of a selected tyrosine residue in the intracellular tail of EGFR. Thus, FPR hijacked by human glioblastoma cells exploits the function of EGFR to promote rapid tumor progression. Published by Elsevier Ltd.
C1 [Huang, Jian; Chen, Keqiang; Wang, Ji Ming] NCI, Ctr Canc Res, Canc & Inflammat Program, Mol Immunoregulat Lab, Frederick, MD 21702 USA.
[Gong, Wanghua] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
[Huang, Jian] Third Mil Med Univ, Southwest Hosp, Dept Pathophysiol, Chongqing, Peoples R China.
[Bian, Xiuwu] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing, Peoples R China.
[Zhou, Ye] Fudan Univ, Canc Hosp, Shanghai 200433, Peoples R China.
[Le, Yingying] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China.
RP Wang, JM (reprint author), NCI, Ctr Canc Res, Canc & Inflammat Program, Mol Immunoregulat Lab, Bldg 560,Room 31-76, Frederick, MD 21702 USA.
EM wangji@mail.ncifcrf.gov
RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017
OI Bian, Xiu-wu/0000-0003-4383-0197
FU National Cancer Institutes; National Institutes of Health
[NO1-CO-12400]; NCI; NIH
FX The authors thank Dr. Joost J. Oppenheim for reviewing the manuscript
and Mrs. Cheryl N. Magers and Mrs. Cheryl F. Lamb for secretarial
assistance. The content Of this publication does not necessarily reflect
the views or policies of the Department of Health and Human Services,
nor does mention of trade names, commercial products, or organizations
imply endorsement by the U.S. Government.; This project has been funded
in part with federal funds from the National Cancer Institutes, National
Institutes of Health, under Contract No. NO1-CO-12400. The research was
also supported in part by the Intramural Research Program of the NCI,
NIH.; NCI-Frederick is accredited by AAALAC international and follows
the Public Health Service Policy for the Care and Use of Laboratory
Animals. Animal care was provided in accordance with the procedures
outlined in the 'Guide for Care and Use of Laboratory Animals" (National
Research Council; 1996; National Academy Press; Washington, DC).
NR 61
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U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD AUG 28
PY 2008
VL 267
IS 2
BP 254
EP 261
DI 10.1016/j.canlet.2008.03.014
PG 8
WC Oncology
SC Oncology
GA 354HB
UT WOS:000259628400011
PM 18433988
ER
PT J
AU Yedavalli, VSRK
Zhang, N
Cai, HY
Zhang, P
Starost, MF
Hosmane, RS
Jeang, KT
AF Yedavalli, Venkat S. R. K.
Zhang, Ning
Cai, Hongyi
Zhang, Peng
Starost, Matthew F.
Hosmane, Ramachandra S.
Jeang, Kuan-Teh
TI Ring expanded nucleoside analogues inhibit RNA helicase and
intracellular human immunodeficiency virus type 1 replication
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DEAD-BOX PROTEINS; CONVERTING ENZYME-INHIBITORS; WEST-NILE VIRUS;
PRIMASE INHIBITORS; FAT NUCLEOSIDE; HEPATITIS-C; HIV-1 TAT; IN-VITRO;
METHYLATION; INFECTION
AB series of ring expanded nucleoside (REN) analogues were synthesized and screened for inhibition of cellular RNA helicase activity and human immunodeficiency Virus type 1 (HIV-1) replication. We identified two compounds, 1 and 2, that inhibited the ATP dependent activity of human RNA helicase DDX3. Compounds 1 and 2 also Suppressed HIV-I replication in T cells and monocyte-derived macrophages. Neither compound at therapeutic doses was significantly toxic ill ex vivo cell culture or in vivo in mice. Our finding's provide proof-of-concept that a cellular factor, all RNA helicase. Could be targeted for inhibiting HIV-1 replication.
C1 [Yedavalli, Venkat S. R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
[Zhang, Ning; Cai, Hongyi; Zhang, Peng; Hosmane, Ramachandra S.] Univ Maryland, Dept Chem & Biochem, Baltimore, MD 21250 USA.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hosmane@umbc.edu; kjeang@mail.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU National Institute of Allergy and Infectious Diseases (NIAID) [1 R21
AI071802]; National Institutes of Health, Bethesda, Maryland; Nabi
Biopharmaceuticals, Rockville, Maryland; NIAID; Intramural AIDS Targeted
Antiviral Program (IATAP)
FX The research was supported in part by a grant (no. 1 R21 AI071802) (to
R.S.H.) from the National Institute of Allergy and Infectious Diseases
(NIAID) of the National Institutes of Health, Bethesda, Maryland, and by
an unrestricted grant (to R.S.H.) from Nabi Biopharmaceuticals,
Rockville, Maryland. Work in K.T.J.'s laboratory is supported by NIAID
intramural research funds and by funds from the Intramural AIDS Targeted
Antiviral Program (IATAP) from the office of the Director, NIH.
NR 35
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U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 28
PY 2008
VL 51
IS 16
BP 5043
EP 5051
DI 10.1021/jm800332m
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 340HT
UT WOS:000258637400022
PM 18680273
ER
PT J
AU Balboni, G
Fiorini, S
Baldisserotto, A
Trapella, C
Sasaki, Y
Ambo, A
Marczak, ED
Lazarus, LH
Salvadori, S
AF Balboni, Gianfranco
Fiorini, Stella
Baldisserotto, Anna
Trapella, Claudio
Sasaki, Yusuke
Ambo, Akihiro
Marczak, Ewa D.
Lazarus, Lawrence H.
Salvadori, Severo
TI Further studies on lead compounds containing the opioid pharmacophore
Dmt-Tic
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID G-PROTEIN FUSIONS; RECEPTOR AGONIST; IN-VITRO; DELTA; MU; POTENT;
ANTAGONISTS; ANALOGS; MICE; SELECTIVITY
AB Some reference opioids containing the Dmt-Tic pharmacophore, especially the 6 agonists H-Dmt-Tic-Gly-NH-Ph (1) and H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid (4) (UFP-512) were evaluated for the influence of the substitution of Gly with aspartic acid, its chirality, and the importance of the -NH-Ph and (NH)-H-1-Bid hydrogens in the inductions of delta agonism. The results provide the following conclusions: (i) Asp increases delta selectivity by lowering the mu affinity; (ii) -NH-Ph and (NH)-H-1-Bid nitrogens methylation transforms the delta agonists into delta antagonists; (iii) the substitution of Gly with L-Asp/D-Asp in the delta agonist H-Dmt-Tic-Gly-NH-Ph gave 6 antagonists; the same substitution in the delta agonist H-Dmt-Tic-NH-CH2-Bid yielded more selective agonists, H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid and H-Dmt-Tic-NH-(R)CH(CH2-COOH)-Bid; (iV) L-Asp seems important only in functional bioactivity, not in receptor affinity; (v) H-Dmt-Tic-NH-(S)CH(CH2-COOH)-Bid(N-1-Me) (10) evidenced analgesia similar to 4, which was reversed by naltrindole only in the tail flick. 4 and 10 had opposite behaviours in mice; 4 caused agitation, 10 gave sedation and convulsions.
C1 [Balboni, Gianfranco] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy.
[Balboni, Gianfranco; Fiorini, Stella; Baldisserotto, Anna; Trapella, Claudio; Salvadori, Severo] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy.
[Balboni, Gianfranco; Fiorini, Stella; Baldisserotto, Anna; Trapella, Claudio; Salvadori, Severo] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy.
[Sasaki, Yusuke; Ambo, Akihiro] Tohoku Pharmaceut Univ, Dept Pharmacol, Aoba Ku, Sendai, Miyagi 9818558, Japan.
[Marczak, Ewa D.; Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Med Chem Grp, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
RP Balboni, G (reprint author), Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy.
EM gbalboni@unica.it
RI Trapella, Claudio/I-2128-2012;
OI Trapella, Claudio/0000-0002-6666-143X; BALDISSEROTTO,
Anna/0000-0002-2882-3530; SALVADORI, Severo/0000-0002-8224-2358
FU University of Cagliari; University of Ferrara; Intramural Research
Program of the NIH and NIEHS
FX This study was supported in part by the University of Cagliari (G.B.),
the University of Ferrara (S.S.), and by the Intramural Research Program
of the NIH and NIEHS (L.H.L. and E.D.M.).
NR 49
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U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 28
PY 2008
VL 51
IS 16
BP 5109
EP 5117
DI 10.1021/jm800587e
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 340HT
UT WOS:000258637400029
PM 18680274
ER
PT J
AU Johnston, MI
Fauci, AS
AF Johnston, Margaret I.
Fauci, Anthony S.
TI An HIV vaccine - Challenges and prospects
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Johnston, Margaret I.; Fauci, Anthony S.] NIAID, Vaccine Res Program, Div AIDS, Bethesda, MD 20892 USA.
RP Johnston, MI (reprint author), NIAID, Vaccine Res Program, Div AIDS, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 5
TC 76
Z9 77
U1 0
U2 7
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 28
PY 2008
VL 359
IS 9
BP 888
EP 890
DI 10.1056/NEJMp0806162
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 341IU
UT WOS:000258708300002
PM 18753644
ER
PT J
AU Rouse, DJ
Hirtz, DG
Thom, E
Varner, MW
Spong, CY
Mercer, BM
Iams, JD
Wapner, RJ
Sorokin, Y
Alexander, JM
Harper, M
Thorp, JM
Ramin, SM
Malone, FD
Carpenter, M
Miodovnik, M
Moawad, A
O'Sullivan, MJ
Peaceman, AM
Hankins, GDV
Langer, O
Caritis, SN
Roberts, JM
AF Rouse, Dwight J.
Hirtz, Deborah G.
Thom, Elizabeth
Varner, Michael W.
Spong, Catherine Y.
Mercer, Brian M.
Iams, Jay D.
Wapner, Ronald J.
Sorokin, Yoram
Alexander, James M.
Harper, Margaret
Thorp, John M., Jr.
Ramin, Susan M.
Malone, Fergal D.
Carpenter, Marshall
Miodovnik, Menachem
Moawad, Atef
O'Sullivan, Mary J.
Peaceman, Alan M.
Hankins, Gary D. V.
Langer, Oded
Caritis, Steve N.
Roberts, James M.
CA Eunice Kennedy Shriver NICHD Mater
TI A randomized, controlled trial of magnesium sulfate for the prevention
of cerebral palsy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article; Proceedings Paper
CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine
CY JAN 28-FEB 02, 2008
CL Dallas, TX
SP Soc Maternal Fetal Med
ID CLINICAL-TRIALS; PEDIATRIC MORTALITY; POPULATION; BIRTH; PREVALENCE;
CHILDREN; INFANTS; MORBIDITY
AB Background: Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy.
Methods: In this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.
Results: A total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event.
Conclusions: Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989.).
C1 [Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
[Hirtz, Deborah G.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Thom, Elizabeth] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Spong, Catherine Y.] NICHHD, Bethesda, MD 20892 USA.
[Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Mercer, Brian M.] Univ Tennessee, Memphis, TN USA.
[Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Wapner, Ronald J.] Drexel Univ, Philadelphia, PA 19104 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Alexander, James M.] Univ Texas Dallas, SW Med Ctr, Dallas, TX 75230 USA.
[Harper, Margaret] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Ramin, Susan M.] Univ Texas Houston, Houston, TX USA.
[Malone, Fergal D.] Columbia Univ, New York, NY USA.
[Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
[Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA.
[Moawad, Atef] Univ Chicago, Chicago, IL 60637 USA.
[O'Sullivan, Mary J.] Univ Miami, Miami, FL USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
[Hankins, Gary D. V.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA.
[Langer, Oded] Univ Texas San Antonio, San Antonio, TX USA.
[Caritis, Steve N.; Roberts, James M.] Univ Pittsburgh, Pittsburgh, PA USA.
RP Rouse, DJ (reprint author), OHB 457,619 19th St S, Birmingham, AL 35249 USA.
EM drouse@uab.edu
RI Malone, Fergal/D-6233-2012; Varner, Michael/K-9890-2013;
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973;
Peaceman, Alan/0000-0002-4515-4850
FU NICHD NIH HHS [HD21410, HD21414, HD27860, HD27861, HD27869, HD27915,
HD27917, HD34116, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500,
HD40512, HD40544, HD40545, HD40560, HD53907, U01 HD019897, U01 HD036801,
U10 HD021410, U10 HD027860, U10 HD027869, U10 HD027869-11, U10
HD027869-12, U10 HD027869-13, U10 HD027869-14, U10 HD027869-15, U10
HD027869-16, U10 HD027869-16S1, U10 HD027869-17, U10 HD027869-18, U10
HD027905, U10 HD027915, U10 HD027917, U10 HD034116, U10 HD034122, U10
HD034136, U10 HD034208, U10 HD036801, U10 HD040485, U10 HD040500, U10
HD040500-09, U10 HD040512, U10 HD040544, U10 HD040545, U10 HD040560, UG1
HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1
HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560]
NR 35
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Z9 247
U1 3
U2 9
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 28
PY 2008
VL 359
IS 9
BP 895
EP 905
DI 10.1056/NEJMoa0801187
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 341IU
UT WOS:000258708300004
PM 18753646
ER
PT J
AU Han, JC
Liu, QR
Jones, M
Levinn, RL
Menzie, CM
Jefferson-George, KS
Adler-Wailes, DC
Sanford, EL
Lacbawan, FL
Uhl, GR
Rennert, OM
Yanovski, JA
AF Han, Joan C.
Liu, Qing-Rong
Jones, MaryPat
Levinn, Rebecca L.
Menzie, Carolyn M.
Jefferson-George, Kyra S.
Adler-Wailes, Diane C.
Sanford, Ethan L.
Lacbawan, Felicitas L.
Uhl, George R.
Rennert, Owen M.
Yanovski, Jack A.
TI Brain-derived neurotrophic factor and obesity in the WAGR syndrome
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; HUMAN PLATELETS; ENERGY-BALANCE; FACTOR BDNF;
HYPERPHAGIA; DELETION; MICE; CHILDREN; PATIENT; GENE
AB Background: Brain-derived neurotrophic factor (BDNF) has been found to be important in energy homeostasis in animal models, but little is known about its role in energy balance in humans. Heterozygous, variably sized, contiguous gene deletions causing haploinsufficiency of the WT1 and PAX6 genes on chromosome 11p13, approximately 4 Mb centromeric to BDNF (11p14.1), result in the Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome. Hyperphagia and obesity were observed in a subgroup of patients with the WAGR syndrome. We hypothesized that the subphenotype of obesity in the WAGR syndrome is attributable to deletions that induce haploinsufficiency of BDNF.
Methods: We studied the relationship between genotype and body-mass index (BMI) in 33 patients with the WAGR syndrome who were recruited through the International WAGR Syndrome Association. The extent of each deletion was determined with the use of oligonucleotide comparative genomic hybridization.
Results: Deletions of chromosome 11p in the patients studied ranged from 1.0 to 26.5 Mb; 58% of the patients had heterozygous BDNF deletions. These patients had significantly higher BMI z scores throughout childhood than did patients with intact BDNF (mean [+/-SD] z score at 8 to 10 years of age, 2.08+/-0.45 in patients with heterozygous BDNF deletions vs. 0.88+/-1.28 in patients without BDNF deletions; P=0.03). By 10 years of age, 100% of the patients with heterozygous BDNF deletions (95% confidence interval [CI], 77 to 100) were obese (BMI greater/equal 95th percentile for age and sex) as compared with 20% of persons without BDNF deletions (95% CI, 3 to 56; P<0.001). The critical region for childhood-onset obesity in the WAGR syndrome was located within 80 kb of exon 1 of BDNF. Serum BDNF concentrations were approximately 50% lower among the patients with heterozygous BDNF deletions (P=0.001).
Conclusions: Among persons with the WAGR syndrome, BDNF haploinsufficiency is associated with lower levels of serum BDNF and with childhood-onset obesity; thus, BDNF may be important for energy homeostasis in humans. (ClinicalTrials.gov number, NCT00006073.).
C1 [Han, Joan C.; Levinn, Rebecca L.; Menzie, Carolyn M.; Jefferson-George, Kyra S.; Adler-Wailes, Diane C.; Sanford, Ethan L.; Yanovski, Jack A.] NIH, Unit Growth & Obes, Program Dev Endocrinol & Genet, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin Genom, Bethesda, MD USA.
[Jones, MaryPat] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Lacbawan, Felicitas L.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Qing-Rong; Uhl, George R.] NIDA, Mol Neurobiol Branch, Baltimore, MD USA.
RP Yanovski, JA (reprint author), NIH, Unit Growth & Obes, Program Dev Endocrinol & Genet, Hatfield Clin Res Ctr, 10 Ctr Dr,Rm 1E-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
RI Liu, Qing-Rong/A-3059-2012
OI Liu, Qing-Rong/0000-0001-8477-6452
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the National
Institutes of Health (NIH) [Z01-HD-00641]; NIH Office of Rare Diseases
FX Supported by grants from the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
of the National Institutes of Health (NIH) (Z01-HD-00641) and from the
NIH Office of Rare Diseases. Dr. Uhl reports holding patents for OPRM1
and DAT (SLC6A3), which might play roles in obesity, but having no
patents or other financial interests that are related to brain-derived
neurotrophic factor ( BDNF); and Dr. Yanovski, receiving research
support for an obesity-related clinical trial from Obecure but having no
financial interests that are related to BDNF. Drs. Han and Yanovski are
commissioned officers in the U. S. Public Health Service. No other
potential conflict of interest relevant to this article was reported. We
thank the members of International WAGR Syndrome Association for
assistance in identifying families who were willing to participate in
this study, Dr. Jack W. Tsao for his assistance with evaluation of
nociception in our patients and review of an earlier version of the
manuscript, and Chanelle Wijensinghe for administrative assistance.
NR 42
TC 126
Z9 132
U1 2
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 28
PY 2008
VL 359
IS 9
BP 918
EP 927
DI 10.1056/NEJMoa0801119
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 341IU
UT WOS:000258708300006
PM 18753648
ER
PT J
AU Papaleo, F
Crawley, JN
Song, J
Lipska, BK
Pickel, J
Weinberger, DR
Chen, J
AF Papaleo, Francesco
Crawley, Jacqueline N.
Song, Jian
Lipska, Barbara K.
Pickel, Jim
Weinberger, Daniel R.
Chen, Jingshan
TI Genetic dissection of the role of catechol-O-methyltransferase in
cognition and stress reactivity in mice
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE working memory; attentional set shifting; genes; mice; stress;
calcium/calmodulin-dependent kinase
ID RAT PREFRONTAL CORTEX; KINASE KINASE-BETA; CARD SORT TEST;
WORKING-MEMORY; MESSENGER-RNA; DOPAMINE TRANSPORTER; VAL(158)MET
GENOTYPE; OBJECT-RECOGNITION; FRONTAL-CORTEX; HUMAN BRAIN
AB The COMT (catechol-O-methyltransferase) gene has been linked to a spectrum of human phenotypes, including cognition, anxiety, pain sensitivity and psychosis. Doubts about its clinical impact exist, however, because of the complexity of human COMT polymorphism and clinical variability. We generated transgenic mice overexpressing a human COMT-Val polymorphism (Val-tg), and compared them with mice containing a null COMT mutation. Increased COMT enzyme activity in Val-tg mice resulted in disrupted attentional set-shifting abilities, and impaired working and recognition memory, but blunted stress responses and pain sensitivity. Conversely, COMT disruption improved working memory, but increased stress responses and pain sensitivity. Amphetamine ameliorated recognition memory deficits in COMT-Val-tg mice but disrupted it in wild types, illustrating COMT modulation of the inverted-U relationship between cognition and dopamine. COMT-Val-tg mice showed increased prefrontal cortex (PFC) calcium/calmodulin-dependent protein kinase II (CaMKII) levels, whereas COMT deficiency decreased PFC CaMKII but increased PFC CaMKK beta and CaMKIV levels, suggesting the involvement of PFC CaMK pathways in COMT-regulated cognitive function and adaptive stress responses. Our data indicate a critical role for the COMT gene in an apparent evolutionary trade-off between cognitive and affective functions.
C1 [Papaleo, Francesco; Song, Jian; Lipska, Barbara K.; Weinberger, Daniel R.; Chen, Jingshan] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
[Pickel, Jim] NIMH, Genet Lab, Bethesda, MD 20892 USA.
RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA.
EM weinberd@mail.nih.gov
RI Lipska, Barbara/E-4569-2017;
OI Papaleo, Francesco/0000-0002-6326-0657
FU National Institutes of Health-National Institute of Mental Health
FX This work was supported by the Intramural Program of the National
Institutes of Health-National Institute of Mental Health. We thank P.
Patnaik and C. Bes for technical assistance with behavioral tests and G.
Liu for mice genotyping. We thank Drs. M. Karayiorgou and J. A. Gogos
(Columbia University, New York, NY) for generously donating the COMT-/-
mouse breeders and Dr. A.Contarino for critical reading of this
manuscript. We also thank Dr. J. Wu, and G. Ma, S. Le, S. Melhem, B.
Stepp, H. Choxi, and R. Buerlein for technical assistance.
NR 54
TC 174
Z9 179
U1 0
U2 4
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 AUG 27
PY 2008
VL 28
IS 35
BP 8709
EP 8723
DI 10.1523/JNEUROSCI.2077-08.2008
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 342CS
UT WOS:000258762800009
PM 18753372
ER
PT J
AU Brody, T
Yavatkar, AS
Lin, Y
Ross, J
Kuzin, A
Kundu, M
Fann, Y
Odenwald, WF
AF Brody, Thomas
Yavatkar, Amarendra S.
Lin, Yong
Ross, Jermaine
Kuzin, Alexander
Kundu, Mukta
Fann, Yang
Odenwald, Ward F.
TI Horizontal Gene Transfers Link a Human MRSA Pathogen to Contagious
Bovine Mastitis Bacteria
SO PLOS ONE
LA English
DT Article
AB Background: Acquisition of virulence factors and antibiotic resistance by many clinically important bacteria can be traced to horizontal gene transfer (HGT) between related or evolutionarily distant microflora. Comparative genomic analysis has become an important tool for identifying HGT DNA in emerging pathogens. We have adapted the multi-genome alignment tool EvoPrinter to facilitate discovery of HGT DNA sequences within bacterial genomes and within their mobile genetic elements.
Principal Findings: EvoPrinter analysis of 13 different Staphylococcus aureus genomes revealed that one of the human isolates, the hospital epidemic methicillin-resistant MRSA252 strain, uniquely shares multiple putative HGT DNA sequences with different causative agents of bovine mastitis that are not found in the other human S. aureus isolates. MRSA252 shares over 14 different DNA sequence blocks with the bovine mastitis ET3 S. aureus strain RF122, and many of the HGT DNAs encode virulence factors. EvoPrinter analysis of the MRSA252 chromosome also uncovered virulence-factor encoding HGT events with the genome of Listeria monocytogenes and a Staphylococcus saprophyticus associated plasmid. Both bacteria are also causal agents of contagious bovine mastitis.
Conclusions: EvoPrinter analysis reveals that the human MRSA252 strain uniquely shares multiple DNA sequence blocks with different causative agents of bovine mastitis, suggesting that HGT events may be occurring between these pathogens. These findings have important implications with regard to animal husbandry practices that inadvertently enhance the contact of human and livestock bacterial pathogens.
C1 [Brody, Thomas; Ross, Jermaine; Kuzin, Alexander; Kundu, Mukta; Odenwald, Ward F.] NIH, Neural Cell Fate Determinants Sect, Bethesda, MD 20892 USA.
[Yavatkar, Amarendra S.; Lin, Yong; Fann, Yang] NINDS, NIH, Div Intramural Res Informat Technol Program, Bethesda, MD USA.
RP Brody, T (reprint author), NIH, Neural Cell Fate Determinants Sect, Bldg 10, Bethesda, MD 20892 USA.
EM brodyt@ninds.nih.gov; ward@codon.nih.gov
FU Intramural Research Program of the NIH, NINDS
FX This research was supported by the Intramural Research Program of the
NIH, NINDS.
NR 47
TC 20
Z9 20
U1 1
U2 9
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 AUG 27
PY 2008
VL 3
IS 8
AR e3074
DI 10.1371/journal.pone.0003074
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RM
UT WOS:000264796400014
PM 18728754
ER
PT J
AU Scattoni, ML
Gandhy, SU
Ricceri, L
Crawley, JN
AF Scattoni, Maria Luisa
Gandhy, Shruti U.
Ricceri, Laura
Crawley, Jacqueline N.
TI Unusual Repertoire of Vocalizations in the BTBR T plus tf/J Mouse Model
of Autism
SO PLOS ONE
LA English
DT Article
ID BEHAVIORAL TASKS RELEVANT; ULTRASONIC VOCALIZATIONS; MATERNAL-BEHAVIOR;
INBRED STRAINS; LABORATORY RATS; DEVELOPMENTAL INFLUENCES; COMMUNICATION
CALLS; MENTAL-RETARDATION; SOCIAL-INTERACTION; SPECTRUM DISORDER
AB BTBR T+ tf/J (BTBR) is an inbred mouse strain that displays social abnormalities and repetitive behaviors analogous to the first and third diagnostic symptoms of autism. Here we investigate ultrasonic vocalizations in BTBR, to address the second diagnostic symptom of autism, communication deficits. As compared to the commonly used C57BL/6J (B6) strain, BTBR pups called more loudly and more frequently when separated from their mothers and siblings. Detailed analysis of ten categories of calls revealed an unusual pattern in BTBR as compared to B6. BTBR emitted high levels of harmonics, two-syllable, and composite calls, but minimal numbers of chevron-shaped syllables, upward, downward, and short calls. Because body weights were higher in BTBR than B6 pups, one possible explanation was that larger thoracic size was responsible for the louder calls and different distribution of syllable categories. To test this possibility, we recorded separation calls from FVB/NJ, a strain with body weights similar to BTBR, and 129X1/SvJ, a strain with body weights similar to B6. BTBR remained the outlier on number of calls, displaying low numbers of complex, upward, chevron, short, and frequency steps calls, along with high harmonics and composites. Further, developmental milestones and growth rates were accelerated in BTBR, indicating an unusual neurodevelopmental trajectory. Overall, our findings demonstrate strain-specific patterns of ultrasonic calls that may represent different lexicons, or innate variations in complex vocal repertoires, in genetically distinct strains of mice. Particularly intriguing is the unusual pattern of vocalizations and the more frequent, loud harmonics evident in the BTBR mouse model of autism that may resemble the atypical vocalizations seen in some autistic infants.
C1 [Scattoni, Maria Luisa; Gandhy, Shruti U.; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
[Scattoni, Maria Luisa; Ricceri, Laura] Ist Superiore Sanita, Dept Cell Biol & Neurosci, Behav Neurosci Sect, Rome, Italy.
RP Scattoni, ML (reprint author), NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
EM marialuisa.scattoni@iss.it
FU National Institute of Mental Health Intramural Research Program
[Z01-MH-002498-17, ISS-NIH 0F14]
FX Supported by the National Institute of Mental Health Intramural Research
Program (Z01-MH-002498-17, JNC), and ISS-NIH 0F14 Neurobehavioral
phenotyping of genetically modified mouse models of mental
retardation(LR). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. The views expressed in this article do not necessarily
represent the views of the NIMH, NIH, or the United States Government.
NR 78
TC 183
Z9 186
U1 3
U2 11
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 AUG 27
PY 2008
VL 3
IS 8
AR e3067
DI 10.1371/journal.pone.0003067
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RM
UT WOS:000264796400007
PM 18728777
ER
PT J
AU Feng, HL
Leng, Y
Ma, CH
Zhang, J
Ren, M
Chuang, DM
AF Feng, H. -L.
Leng, Y.
Ma, C. -H.
Zhang, J.
Ren, M.
Chuang, D. -M.
TI Combined lithium and valproate treatment delays disease onset, reduces
neurological deficits and prolongs survival in an amyotrophic lateral
sclerosis mouse model
SO NEUROSCIENCE
LA English
DT Article
DE lithium; valproic acid; GSK-3 beta; ALS; G93A mice; behavioral deficits
ID BIPOLAR DISORDER; HISTONE DEACETYLASE; MOOD STABILIZERS; ALS MODEL;
ACID; PROGRESSION; MICE; DIFFERENTIATION; MECHANISMS; INHIBITORS
AB Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar disorder, and have been shown to have neuroprotective properties in vivo and in vitro. A recent study demonstrated that combined treatment with lithium and VPA elicits synergistic neuroprotective effects against glutamate excitotoxicity in cultured brain neurons, and the synergy involves potentiated inhibition of glycogen synthase kinase-3 (GSK-3) activity through enhanced GSK-3 serine phosphorylation [Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM (2008) Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J Neurosci 28:2576-2588]. We therefore investigated the effects of lithium and VPA cotreatment on the disease symptom onset, survival time and neurological deficits in cooper zinc superoxide dismutase (SOD1) G93A mutant mice, a commonly used mouse model of amyotrophic lateral sclerosis (ALS). The G93A ALS mice received twice daily i.p. injections with LiCl (60 mg/kg), VPA (300 mg/kg) or lithium plus VPA, starting from the 30(th) day after birth and continuing until death. We found that combined treatment with lithium and VPA produced a greater and more consistent effect in delaying the onset of disease symptoms, prolonging the lifespan and decreasing the neurological deficit scores, compared with the results of monotreatment with lithium or VPA. Moreover, lithium in conjunction with VPA was more effective than lithium or VPA alone in enhancing the immunostaining of phospho-GSK-3 beta(Ser9) in brain and lumbar spinal cord sections. To our knowledge, this is the first demonstration of enhanced neuroprotection by a combinatorial approach using mood stabilizers in a mouse ALS model. Our results suggest that clinical trials using lithium and VPA in combination for ALS patients are a rational strategy. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Feng, H. -L.; Ma, C. -H.] Harbin Med Coll, Dept Neurol, Affiliated Hosp 1, Harbin 150001, Peoples R China.
[Leng, Y.; Chuang, D. -M.] NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Zhang, J.] Harbin Med Coll, Dept Neurol, Affiliated Hosp 4, Harbin 150001, Peoples R China.
[Ren, M.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20892 USA.
RP Feng, HL (reprint author), Harbin Med Coll, Dept Neurol, Affiliated Hosp 1, Harbin 150001, Peoples R China.
EM fenghonglin567@sina.com
FU Intramural NIH HHS [Z01 MH002468-20, Z99 MH999999]
NR 23
TC 118
Z9 120
U1 2
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD AUG 26
PY 2008
VL 155
IS 3
BP 567
EP 572
DI 10.1016/j.neuroscience.2008.06.040
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 344RK
UT WOS:000258944800002
PM 18640245
ER
PT J
AU DiGiulio, DB
Romero, R
Amogan, HP
Kusanovic, JP
Bik, EM
Gotsch, F
Kim, CJ
Erez, O
Edwin, S
Relman, DA
AF DiGiulio, Daniel B.
Romero, Roberto
Amogan, Harold P.
Kusanovic, Juan Pedro
Bik, Elisabeth M.
Gotsch, Francesca
Kim, Chong Jai
Erez, Offer
Edwin, Sam
Relman, David A.
TI Microbial Prevalence, Diversity and Abundance in Amniotic Fluid During
Preterm Labor: A Molecular and Culture-Based Investigation
SO PLOS ONE
LA English
DT Article
AB Background: Preterm delivery causes substantial neonatal mortality and morbidity. Unrecognized intra-amniotic infections caused by cultivation-resistant microbes may play a role. Molecular methods can detect, characterize and quantify microbes independently of traditional culture techniques. However, molecular studies that define the diversity and abundance of microbes invading the amniotic cavity, and evaluate their clinical significance within a causal framework, are lacking.
Methods and Findings: In parallel with culture, we used broad-range end-point and real-time PCR assays to amplify, identify and quantify ribosomal DNA (rDNA) of bacteria, fungi and archaea from amniotic fluid of 166 women in preterm labor with intact membranes. We sequenced up to 24 rRNA clones per positive specimen and assigned taxonomic designations to approximately the species level. Microbial prevalence, diversity and abundance were correlated with host inflammation and with gestational and neonatal outcomes. Study subjects who delivered at term served as controls. The combined use of molecular and culture methods revealed a greater prevalence (15% of subjects) and diversity (18 taxa) of microbes in amniotic fluid than did culture alone (9.6% of subjects; 11 taxa). The taxa detected only by PCR included a related group of fastidious bacteria, comprised of Sneathia sanguinegens, Leptotrichia amnionii and an unassigned, uncultivated, and previously-uncharacterized bacterium; one or more members of this group were detected in 25% of positive specimens. A positive PCR was associated with histologic chorioamnionitis (adjusted odds ratio [ OR] 20; 95% CI, 2.4 to 172), and funisitis (adjusted OR 18; 95% CI, 3.1 to 99). The positive predictive value of PCR for preterm delivery was 100 percent. A temporal association between a positive PCR and delivery was supported by a shortened amniocentesis-to-delivery interval (adjusted hazard ratio 4.6; 95% CI, 2.2 to 9.5). A dose-response association was demonstrated between bacterial rDNA abundance and gestational age at delivery (r(2) = 0.42; P, 0.002).
Conclusions: The amniotic cavity of women in preterm labor harbors DNA from a greater diversity of microbes than previously suspected, including as-yet uncultivated, previously-uncharacterized taxa. The strength, temporality and gradient with which these microbial sequence types are associated with preterm delivery support a causal relationship.
C1 [DiGiulio, Daniel B.; Relman, David A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[DiGiulio, Daniel B.; Amogan, Harold P.; Bik, Elisabeth M.; Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Kim, Chong Jai; Erez, Offer; Edwin, Sam] NIH, NICHD, Perinatol Res Branch, Bethesda, MD USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48202 USA.
[Kusanovic, Juan Pedro; Erez, Offer] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA.
[Bik, Elisabeth M.; Relman, David A.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA.
RP DiGiulio, DB (reprint author), Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
EM relman@stanford.edu
FU Intramural Research Program of the National Institute of Child Health
and Human Development; NIH [T32 AI052073-01, DP1OD000964]; DHHS
FX This work was supported, in part, by the Intramural Research Program of
the National Institute of Child Health and Human Development, NIH, DHHS,
and by NIH grant T32 AI052073-01 (Epidemiology of Emerging Infections
and Bioterrorism). DAR is supported by an NIH Directors Pioneer Award
(NIH DP1OD000964). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 54
TC 249
Z9 258
U1 0
U2 19
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 AUG 26
PY 2008
VL 3
IS 8
AR e3056
DI 10.1371/journal.pone.0003056
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RL
UT WOS:000264796300003
PM 18725970
ER
PT J
AU Petiet, AE
Kaufman, MH
Goddeeris, MM
Brandenburg, J
Elmore, SA
Johnson, GA
AF Petiet, Alexandra E.
Kaufman, Matthew H.
Goddeeris, Matthew M.
Brandenburg, Jeffrey
Elmore, Susan A.
Johnson, G. Allan
TI High-resolution magnetic resonance histology of the embryonic and
neonatal mouse: A 4D atlas and morphologic database
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE digital atlas; magnetic resonance microscopy; mouse embryo
ID GRADIENT-ECHO SEQUENCE; MR MICROSCOPY; OUTFLOW TRACT; HEART FIELD; NMR;
MALFORMATIONS; ANATOMY; FETUS
AB Engineered mice play an ever-increasing role in defining connections between genotype and phenotypic expression. The potential of magnetic resonance microscopy (MRM) for morphologic phenotyping in the mouse has previously been demonstrated; however, applications have been limited by long scan times, availability of the technology, and a foundation of normative data. This article describes an integrated environment for high-resolution study of normal, transgenic, and mutant mouse models at embryonic and neonatal stages. Three-dimensional images are shown at an isotropic resolution of 19.5 mu m (voxel volumes of 8 pL), acquired in 3 h at embryonic days 10.5-19.5 (10 stages) and postnatal days 0-32 (6 stages). A web-accessible atlas encompassing this data was developed, and for critical stages of embryonic development (prenatal days 14.5-18.5), > 200 anatomical structures have been identified and labeled. Also, matching optical histology and analysis tools are provided to compare multiple specimens at multiple developmental stages. The utility of the approach is demonstrated in characterizing cardiac septal defects in conditional mutant embryos lacking the Smoothened receptor gene. Finally, a collaborative paradigm is presented that allows sharing of data across the scientific community. This work makes magnetic resonance microscopy of the mouse embryo and neonate broadly available with carefully annotated normative data and an extensive environment for collaborations.
C1 [Petiet, Alexandra E.; Brandenburg, Jeffrey; Johnson, G. Allan] Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Durham, NC 27710 USA.
[Johnson, G. Allan] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Petiet, Alexandra E.; Johnson, G. Allan] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
[Kaufman, Matthew H.] Univ Edinburgh, Dept Biomed Sci, Edinburgh EH8 9XD, Midlothian, Scotland.
[Elmore, Susan A.] NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA.
[Goddeeris, Matthew M.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
RP Johnson, GA (reprint author), Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Box 3302, Durham, NC 27710 USA.
EM gaj@orion.duhs.duke.edu
OI Johnson, G.Allan/0000-0002-7606-5447
FU National Institutes of Health/National Center for Research Resources
[P41 RR005959]; National Cancer Institute [U24 CA092656]; Mouse
Biomedical Informatics Research Network [U24 RR021760]; National
Institutes of Health/National Institute of Environmental Health
Sciences; National Institutes of Health/National Institute of Child
Health and Development [R01 HD042803]
FX We thank Dr. Erik Meyers (Cell Biology and Pediatrics, Duke University)
for providing the Mef2C-AHF-Cre;Smo+/- mutant embryos; Maggie
Lin (Biomedical Engineering, Duke University) for tracing hearts on
VoxStation; Dr. Laurence Hedlund and Boma Fubara for help in preparing
specimens; Gary Cofer and Sally Gewalt for acquisition assistance, and
Sally Zimney for editing assistance. This work was supported by National
Institutes of Health/National Center for Research Resources Grant P41
RR005959, National Cancer Institute Grant U24 CA092656, Mouse Biomedical
Informatics Research Network Grant U24 RR021760, the Intramural Research
Program of the National Institutes of Health/National Institute of
Environmental Health Sciences, and National Institutes of
Health/National Institute of Child Health and Development Grant R01
HD042803 (to M.M.G.).
NR 30
TC 66
Z9 66
U1 0
U2 7
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 AUG 26
PY 2008
VL 105
IS 34
BP 12331
EP 12336
DI 10.1073/pnas.0805747105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700043
PM 18713865
ER
PT J
AU Brown, JL
Snir, M
Noushmehr, H
Kirby, M
Hong, SK
Elkahloun, AG
Feldman, B
AF Brown, Jamie L.
Snir, Mirit
Noushmehr, Houtan
Kirby, Martha
Hong, Sung-Kook
Elkahloun, Abdel G.
Feldman, Benjamin
TI Transcriptional profiling of endogenous germ layer precursor cells
identifies dusp4 as an essential gene in zebrafish endoderm
specification
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE microarray; zgc : 55423; gastrulation; mkp2; sox17
ID FLUORESCENT PROTEIN; FATE MAP; GASTRULATION; COMMITMENT; ACTIVATION;
EXPRESSION; BEHAVIOR; EMBRYO; ORIGIN; GREEN
AB A major goal for developmental biologists is to define the behaviors and molecular contents of differentiating cells. We have devised a strategy for isolating cells from diverse embryonic regions and stages in the zebrafish, using computer-guided laser photoconversion of injected Kaede protein and flow cytometry. This strategy enabled us to perform a genome-wide transcriptome comparison of germ layer precursor cells. Mesendoderm and ectoderm precursors cells isolated by this method differentiated appropriately in transplantation assays. Microarray analysis of these cells reidentified known genes at least as efficiently as previously reported strategies that relied on artificial mesendoderm activation or inhibition. We also identified a large set of uncharacterized mesendoderm-enriched genes as well as ectoderm-enriched genes. Loss-of-function studies revealed that one of these genes, the MAP kinase inhibitor dusp4, is essential for early development. Embryos injected with antisense morpholino oligonucleotides that targeted Dusp4 displayed necrosis of head tissues. Marker analysis during late gastrulation revealed a specific loss of sox17, but not of other endoderm markers, and analysis at later stages revealed a loss of foregut and pancreatic endoderm. This specific loss of sox17 establishes a new class of endoderm specification defect.
C1 [Feldman, Benjamin] NHGRI, Vertebrate Embryol Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Kirby, Martha] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
[Elkahloun, Abdel G.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Hong, Sung-Kook] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Feldman, B (reprint author), NHGRI, Vertebrate Embryol Sect, Med Genet Branch, NIH, Bldg 35,Room 1B205,35 Convent Dr,MSC 3717, Bethesda, MD 20892 USA.
EM bfeldman@mail.nih.gov
RI Noushmehr, Houtan/C-9692-2013;
OI Noushmehr, Houtan/0000-0003-4051-8114; Feldman,
Benjamin/0000-0003-4838-8641
FU National Human Genome Research Institute; National Institutes of Health
FX We thank Darryl Leja for artwork and expert assistance with graphics;
Alexandra Joyner, Paul Liu, David Bodine, Igor Dawid, and Mary LaMarca
for helpful comments on the manuscript; Erich Roessler and Stacie
Anderson for valuable discussions; and Atsushi Miyawaki for sharing the
Kaede-pCS2+ vector. This research was supported by the Intramural
Research Program of the National Human Genome Research Institute,
National Institutes of Health.
NR 33
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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 AUG 26
PY 2008
VL 105
IS 34
BP 12337
EP 12342
DI 10.1073/pnas.0805589105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700044
PM 18719100
ER
PT J
AU Hallson, G
Syrzycka, M
Beck, SA
Kennison, JA
Dorsett, D
Page, SL
Hunter, SM
Keall, R
Warren, WD
Brock, HW
Sinclair, DAR
Honda, BM
AF Hallson, Graham
Syrzycka, Monika
Beck, Samantha A.
Kennison, James A.
Dorsett, Dale
Page, Scott L.
Hunter, Sally M.
Keall, Rebecca
Warren, William D.
Brock, Hugh W.
Sinclair, Donald A. R.
Honda, Barry M.
TI The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hedgehog; heterochromatin; Nipped-B; Polycomb; cohesion
ID SISTER-CHROMATID COHESION; GENE-EXPRESSION; FISSION YEAST; CUT GENE;
NIPPED-B; S-PHASE; POLYCOMB; CHROMOSOME; MELANOGASTER; HETEROCHROMATIN
AB The cohesin complex is a key player in regulating cell division. Cohesin proteins SMC1, SMC3, Rad21, and stromalin (SA), along with associated proteins Nipped-B, Pds5, and Ecol, maintain sister chromatid cohesion before segregation to daughter cells during anaphase. Recent chromatin immunoprecipitation (ChIP) data reveal extensive overlap of Nipped-B and cohesin components with RNA polymerase II binding at active genes in Drosophila. These and other data strongly suggest a role for cohesion in transcription; however, there is no clear evidence for any specific mechanisms by which cohesin and associated proteins regulate transcription. We report here a link between cohesin components and trithorax group (trxG) function, thus implicating these proteins in transcription activation and/or elongation. We show that the Drosophila Rad21 protein is encoded by verthandi (vtd), a member of the trxG gene family that is also involved in regulating the hedgehog (hh) gene. In addition, mutations in the associated protein Nipped-B show similar trxG activity i.e., like vtd, they act as dominant suppressors of Pc and hh(Mrt) without impairing cell division. Our results provide a framework to further investigate how cohesin and associated components might regulate transcription.
C1 [Hallson, Graham; Syrzycka, Monika; Sinclair, Donald A. R.; Honda, Barry M.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
[Beck, Samantha A.; Brock, Hugh W.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
[Kennison, James A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Dorsett, Dale] St Louis Univ, Sch Med, Dept Biochem & Mol Biol, St Louis, MO 63104 USA.
[Page, Scott L.; Hunter, Sally M.; Keall, Rebecca; Warren, William D.] James Cook Univ, Comparat Genom Ctr, Townsville, Qld 4811, Australia.
RP Honda, BM (reprint author), Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
EM honda@sfu.ca
RI Dorsett, Dale/A-8197-2009; Page, Scott/B-4984-2009; Warren,
William/D-4419-2009;
OI Warren, William/0000-0002-3753-1871; Dorsett, Dale/0000-0002-0507-2762
FU National Institutes of Health [R01 GM055683, P01 HD052860]; Intramural
Research Program of the National Institutes of Health National Institute
of Child Health and Human Development ((J.A.K.); Basil O'Connor Starter
Scholar Research Award [5-FY0319]; March of Dimes Birth Defects
Foundation (W.D.W.); Natural Sciences and Engineering Research Council,
Canada
FX We thank Nazanin Ghavam and Neahlanna McLeod for technical assistance,
Alan Baxter for the use of laboratory equipment, and Oren Schuldiner for
sharing data before publication. This work was supported in part by
National Institutes of Health Grants R01 GM055683 and P01 HD052860 (to
D.D.); Intramural Research Program of the National Institutes of Health
National Institute of Child Health and Human Development ((J.A.K.);
Basil O'Connor Starter Scholar Research Award Grant 5-FY0319 and the
March of Dimes Birth Defects Foundation (W.D.W.); and the Natural
Sciences and Engineering Research Council, Canada (H.W.B. and B.M.H.,
and a PGSD award to M.S.).
NR 48
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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 AUG 26
PY 2008
VL 105
IS 34
BP 12405
EP 12410
DI 10.1073/pnas.0801698105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700056
PM 18713858
ER
PT J
AU Motegi, A
Liaw, HJ
Lee, KY
Roest, HP
Maas, A
Wu, X
Moinova, H
Markowitz, SD
Ding, H
Hoeijmakers, JHJ
Myung, K
AF Motegi, Akira
Liaw, Hung-Jiun
Lee, Kyoo-Young
Roest, Henk P.
Maas, Alex
Wu, Xiaoli
Moinova, Helen
Markowitz, Sanford D.
Ding, Hao
Hoeijmakers, Jan H. J.
Myung, Kyungjae
TI Polyubiquitination of proliferating cell nuclear antigen by HLTF and
SHPRH prevents genomic instability from stalled replication forks
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID GROSS CHROMOSOMAL REARRANGEMENTS; POSTREPLICATION REPAIR PATHWAY;
DNA-POLYMERASE-ETA; TRANSLESION SYNTHESIS; SACCHAROMYCES-CEREVISIAE;
HOMOLOGOUS RECOMBINATION; MONOUBIQUITINATED PCNA; GENE CONVERSION;
DAMAGE BYPASS; RAD6 PATHWAY
AB Chronic stalling of DNA replication forks caused by DNA damage can lead to genomic instability. Cells have evolved lesion bypass pathways such as postreplication repair (PRR) to resolve these arrested forks. In yeast, one branch of PRR involves proliferating cell nuclear antigen (PCNA) polyubiquitination mediated by the Rad5-Ubc13-Mms2 complex that allows bypass of DNA lesion by a template-switching mechanism. Previously, we identified human SHPRH as a functional homologue of yeast Rad5 and revealed the existence of RAD5-like pathway in human cells. Here we report the identification of HLTF as a second RAD5 homologue in human cells. HLTF, like SHPRH, shares a unique domain architecture with Rad5 and promotes lysine 63-linked polyubiquitination of PCNA. Similar to yeast Rad5, HLTF is able to interact with UBC13 and PCNA, as well as SHPRH; and the reduction of either SHPRH or HLTF expression enhances spontaneous mutagenesis. Moreover, HItf-deficient mouse embryonic fibroblasts show elevated chromosome breaks and fusions after methyl methane sulfonate treatment. Our results suggest that HLTF and SHPRH are functional homologues of yeast Rad5 that cooperatively mediate PCNA polyubiquitination and maintain genomic stability.
C1 [Motegi, Akira; Liaw, Hung-Jiun; Lee, Kyoo-Young; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Roest, Henk P.; Maas, Alex; Hoeijmakers, Jan H. J.] Erasmus MC, Dept Cell Biol & Genet, Ctr Med Genet, NL-3015 GE Rotterdam, Netherlands.
[Wu, Xiaoli; Ding, Hao] Univ Manitoba, Dept Biochem & Med Genet, Fac Med, Winnipeg, MB R3E OW3, Canada.
[Moinova, Helen; Markowitz, Sanford D.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA.
[Markowitz, Sanford D.] Case Western Reserve Univ, Howard Hughes Med Inst, Cleveland, OH 44106 USA.
RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM kmyung@nhgri.nih.gov
RI Liaw, Hungjiun/G-7034-2014
OI Liaw, Hungjiun/0000-0002-3481-709X
FU Canada Research Chair program and the National Cancer Institute of
Canada (to H.D.); Dutch Cancer Society (to J.H. and H.R.); Japan Society
for the Promotion of Science; intramural research program of the NHGRI;
NIH
FX We thank D. Bodine (National Human Genome Research Institute [NHGRI]),
P. Liu (NHGRI), M. Lichten (National Cancer Institute), P. Meltzer
(NHGRI), and Y. Shiloh (Tel Aviv University, Israel) for helpful
discussions; R. Harris (University of Minnesota), M. Jasin (Memorial
Sloan-Kettering Cancer Center [MSKCC)), K. Nakanishi (MSKCC), and R.
Sood (NHGRI) for cells, plasmids, and antibody; S. Anderson (NHGRI) and
M. Kirby (NHGRI) for FACS analysis; and A. Dutra (NHGRI) and E. Pak
(NHGRI) for metaphase chromosome analysis. We also thank E. Hendrickson
(University of Minnesota), the National Institutes of Health (NIH)
Fellows Editorial Board, and members of the Myung laboratory for
comments on the manuscript and J. Fekecs (NHGRI) for figure preparation.
K.M. especially thanks E. Cho. This work was supported by the Canada
Research Chair program and the National Cancer Institute of Canada (to
H.D.), the Dutch Cancer Society (to J.H. and H.R.), the Japan Society
for the Promotion of Science (to A.M.), and the intramural research
program of the NHGRI, NIH (to K.M.). H.D. is the holder of a Canada
Research Chair, and S.D.M. is an investigator of Howard Hughes Medical
Institute.
NR 36
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U1 1
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PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 26
PY 2008
VL 105
IS 34
BP 12411
EP 12416
DI 10.1073/pnas.0805685105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700057
PM 18719106
ER
PT J
AU van Panhuys, N
Tang, SC
Prout, M
Camberis, M
Scarlett, D
Roberts, J
Hu-Li, J
Paul, WE
Le Gros, G
AF van Panhuys, Nicholas
Tang, Shiau-Choot
Prout, Melanie
Camberis, Mali
Scarlett, Debbie
Roberts, Joanna
Hu-Li, Jane
Paul, William E.
Le Gros, Graham
TI In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2
lymphocyte differentiation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE allergen; cytokine; asthma; Nippostrongylus
ID TIME QUANTITATIVE PCR; T-CELL MEMORY; GENE-EXPRESSION; IGE RESPONSES;
INTERLEUKIN-4; IMMUNITY; INVIVO; MICE; SUPPRESSION; INFECTION
AB The expression of interleukin (IL-4) is viewed as the hallmark of a Th2 lymphocyte, whereas the subsequent action of IL-4 and IL-13, mediated through the STAT6 signaling pathway, is seen as a prerequisite for the full development of Th2 immune responses to parasites and allergens. G4 mice, whose IL-4 gene locus contains the fluorescent reporter eGFP, were used to quantify the number of Th2 cells that develop during Nippostrongylus brasiliensis- or allergen-induced immune responses under conditions where IL-4 or STAT6 was absent. Here, we show that deletion of IL-4 or STAT6 had little impact on the number or timing of appearance of IL-4-producing Th2 cells. These data indicate that in vivo differentiation of naive CD4 T cells to Th2 status often occurs independently of IL-4 and STAT6 and that recently described pathways of Th2 cell differentiation may explain how allergens and parasites selectively induce Th2-mediated immunity.
C1 [Hu-Li, Jane; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[van Panhuys, Nicholas; Tang, Shiau-Choot; Prout, Melanie; Camberis, Mali; Scarlett, Debbie; Roberts, Joanna; Le Gros, Graham] Malaghan Inst Med Res, Wellington, New Zealand.
RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wpaul@niaid.nih.gov; glegros@malaghan.org.nz
RI Le Gros, Graham/C-6725-2011; van Panhuys, Nicholas/E-1812-2011;
OI van Panhuys, Nicholas/0000-0003-2199-852X
FU Research Program funding from the Health Research Council of New
Zealand; Marjorie Barclay Trust; Marsden Fund; AMI Insurance Ltd;
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases/National Institutes of Health [Z01 A1000493.22]
FX We thank J. Zhu for helpful discussions and K. Price for expertise with
cell sorting. This work was supported by Research Program funding from
the Health Research Council of New Zealand, the Marjorie Barclay Trust,
the Marsden Fund, AMI Insurance Ltd, and the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases/National
Institutes of Health through Project Z01 A1000493.22.
NR 36
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U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 26
PY 2008
VL 105
IS 34
BP 12423
EP 12428
DI 10.1073/pnas.0806372105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700059
PM 18719110
ER
PT J
AU Hofer, T
Thomas, JD
Burke, TR
Rader, C
AF Hofer, Thomas
Thomas, Joshua D.
Burke, Terrence R., Jr.
Rader, Christoph
TI An engineered selenocysteine defines a unique class of antibody
derivatives
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antibody engineering; Fc fragment; neonatal Fc receptor; small synthetic
molecules; integrin alpha(4)beta(1)
ID MAMMALIAN-CELLS; FC-RECEPTOR; PROTEINS; EXPRESSION; TRANSPORT; DRUGS;
IGG; THERAPEUTICS; AFFINITY; THERAPY
AB Selenocysteine is cotranslationally inserted into proteins by recoding the stop codon UGA from termination to selenocysteine insertion. The nucleophilic selenol group of selenocysteine endows this rare amino acid with unique chemical reactivity that allows regio-specific covalent conjugation in the presence of the other natural amino acids. Using a mammalian expression system, we generated an IgG1-derived Fc fragment with a C-terminal selenocysteine in yields comparable to conventional monoclonal antibodies and conjugated it to an electrophilic derivative of a peptidomimetic that binds with high affinity and specificity to integrin alpha(4)beta(1). Through this conjugation, both the biological and chemical components are endowed with pharmacological advantages. We demonstrate that whereas the Fc protein increases the circulatory half-life from minutes to days and mediates transcytosis through binding to the neonatal Fc receptor, the peptidomimetic introduces cross-species binding to cell surface integrin alpha(4)beta(1) and blocks its interaction with vascular cell adhesion molecule-1. Compared with conventional monoclonal antibodies, our technology benefits economically from combining a generic biological component with a variable chemical component.
C1 [Hofer, Thomas; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Thomas, Joshua D.; Burke, Terrence R., Jr.] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Rader, C (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM raderc@mail.nih.gov
RI Burke, Terrence/N-2601-2014
FU Intramural Research Program of the Center for Cancer Research; National
Cancer Institute; National Institutes of Health (C.R. and T.R.B.);
National Cancer Institute's Director's Intramural Innovation Award
(C.R.)
FX We thank Dr. Dolph L. Hatfield and Bradley A. Carlson for assisting in
the autoradiography study, Dr. Kristy.J. Brown for carrying out the mass
spectrometry study, Dr. Frank Klotz for supervising the in vivo studies,
and Dr. Dimiter S. Dimitrov for reading the manuscript. This work was
supported by the Intramural Research Program of the Center for Cancer
Research, the National Cancer Institute, the National Institutes of
Health (C.R. and T.R.B.), and by the National Cancer Institute's
Director's Intramural Innovation Award (C.R.).
NR 31
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U1 0
U2 5
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 AUG 26
PY 2008
VL 105
IS 34
BP 12451
EP 12456
DI 10.1073/pnas.0800800105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700064
PM 18719095
ER
PT J
AU Lee, JH
Lee, J
Choi, KY
Hepp, R
Lee, JY
Lim, MK
Chatani-Hinze, M
Roche, PA
Kim, DG
Ahn, YS
Kim, CH
Roche, KW
AF Lee, Jeong Ho
Lee, Jinu
Choi, Kyu Yeong
Hepp, Regine
Lee, Jae-Youn
Lim, Mi Kyung
Chatani-Hinze, Mayumi
Roche, Paul A.
Kim, Dong Goo
Ahn, Young Soo
Kim, Chul Hoon
Roche, Katherine W.
TI Calmodulin dynamically regulates the trafficking of the metabotropic
glutamate receptor mGluR5
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE phosphorylation; protein kinase C; receptor trafficking
ID PROTEIN-KINASE-C; NMDA RECEPTOR; ALPHA-ACTININ; NR1 SUBUNIT;
PHOSPHORYLATION; BINDING; CALCIUM; DOMAIN; INACTIVATION; CA2+/CALMODULIN
AB Metabotropic glutamate receptors (mGluRs) 1-8 are G protein-coupled receptors (GPCRs) that modulate excitatory neurotransmission, neurotransmitter release, and synaptic plasticity. PKC regulates many aspects of mGluR function, including protein-protein interactions, Ca2+ signaling, and receptor desensitization. However, the mechanisms by which PKC regulates mGluR function are poorly understood. We have now identified calmodulin (CaM) as a dynamic regulator of mGluR5 trafficking. We show that the major PKC phosphorylation site on the intracellular C terminus of mGluR5 is serine 901 (S901), and phosphorylation of this residue is up-regulated in response to both receptor and PKC activation. In addition, S901 phosphorylation inhibits mGluR5 binding to CaM, decreasing mGluR5 surface expression. Furthermore, blocking PKC phosphorylation of mGluR5 on S901 dramatically affects mGluR5 signaling by prolonging Ca2+ oscillations. Thus, our data demonstrate that mGluR5 activation triggers phosphorylation of S901, thereby directly linking PKC phosphorylation, CaM binding, receptor trafficking, and downstream signaling.
C1 [Lee, Jeong Ho; Lee, Jae-Youn; Lim, Mi Kyung; Kim, Dong Goo; Ahn, Young Soo; Kim, Chul Hoon] Yonsei Univ, Coll Med, Dept Pharmacol, Brain Res Inst,Brain Korea Project Med Sci 21, Seoul 120752, South Korea.
[Lee, Jinu] Pochon CHA Univ, Coll Med, Dept Pharmacol, Songnam 463836, South Korea.
[Choi, Kyu Yeong; Chatani-Hinze, Mayumi; Roche, Katherine W.] NINDS, NIH, Bethesda, MD 20892 USA.
[Hepp, Regine; Roche, Paul A.] NCI, NIH, Bethesda, MD 20892 USA.
RP Kim, CH (reprint author), Yonsei Univ, Coll Med, Dept Pharmacol, Brain Res Inst,Brain Korea Project Med Sci 21, Seoul 120752, South Korea.
EM kimhoon@yuhs.ac
RI Lee, Jeong Ho/G-7361-2012; rchnds, rchnds/D-7595-2016;
OI Roche, Katherine/0000-0001-7282-6539
FU Korean Government (MOEHRD Basic Research Promotion Fund)
[KRF-2006-331-E00063, R11-2007-040-01006-0]; National Institute of
Neurological Disorders and Stroke; National Cancer Institute; Intramural
Research Programs; National Institutes of Health
FX This work was supported by Korea Research Foundation Grant
KRF-2006-331-E00063 (to C.H.K.), funded by the Korean Government (MOEHRD
Basic Research Promotion Fund); Korea Science and Engineering Foundation
Grant R11-2007-040-01006-0 (to C.H.K.), funded by the Korean Government
(MEST); and the National Institute of Neurological Disorders and Stroke
(K.Y.C., M.C.H., and K.W.R.) and National Cancer Institute (R.H. and
P.A.R.) Intramural Research Programs, National Institutes of Health.
NR 36
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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 AUG 26
PY 2008
VL 105
IS 34
BP 12575
EP 12580
DI 10.1073/pnas.0712033105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700085
PM 18715999
ER
PT J
AU Fernandez, AP
Serrano, J
Tessarollo, L
Cuttitta, F
Martinez, A
AF Fernandez, Ana P.
Serrano, Julia
Tessarollo, Lino
Cuttitta, Frank
Martinez, Alfredo
TI Lack of adrenomedullin in the mouse brain results in behavioral changes,
anxiety, and lower survival under stress conditions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; RECEPTOR-LIKE-RECEPTOR; MICE LACKING;
HYDROPS-FETALIS; GENE-EXPRESSION; CEREBRAL-CORTEX; ADULT-RAT; IN-VITRO;
AGE; ABNORMALITIES
AB The adrenomedullin (AM) gene, adm, is widely expressed in the central nervous system (CNS) and several functions have been suggested for brain AM. Until now, a formal confirmation of these actions using genetic models has been elusive since the systemic adm knockout results in embryo lethality. We have built a conditional knockout mouse model using the Cre/loxP approach. When crossed with transgenic mice expressing the Cre recombinase under the tubulin T alpha-1 promoter, we obtained animals with no AM expression in the CNS but normal levels in other organs. These animals lead normal lives and do not present any gross morphological defect. Specific areas of the brain of animals lacking CNS AM contain hyperpolymerized tubulin, a consequence of AM down-regulation. Behavioral analysis shows that mice with no AM in their brain have impaired motor coordination and are hyperactive and overanxious when compared to their wild-type littermates. Treatment with methylphenidate, haloperidol, and diazepam did not show differences between genotypes. Circulating levels of adrenocorticotropic hormone and corticosterone were similar in knockout and wild-type mice. Animals with no brain AM were less resistant to hypobaric hypoxia than wild-type mice, demonstrating the neuroprotective function of AM in the CNS. In conclusion, AM exerts a beneficial action in the brain by maintaining homeostasis both under normal and stress conditions.
C1 [Fernandez, Ana P.; Serrano, Julia; Martinez, Alfredo] CSIC, Inst Cajal, Dept Cellular Mol & Dev Neurobiol, E-28002 Madrid, Spain.
[Tessarollo, Lino] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
[Cuttitta, Frank] NCI, Angiogenesis Core Facil, NIH, Gaithersburg, MD 20877 USA.
RP Martinez, A (reprint author), CSIC, Inst Cajal, Dept Cellular Mol & Dev Neurobiol, E-28002 Madrid, Spain.
EM amartinez@cajal.csic.es
RI Martinez, Alfredo/A-3077-2013; Cuttitta, Frank/B-4758-2016
OI Martinez, Alfredo/0000-0003-4882-4044;
FU Spanish Ministry of Science and Education [BFU2004-02838,
SAF2007-60010]; Instituto de Salud Carlos III [RD06/0026/1001];
Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer
FX This work was supported by Spanish Ministry of Science and Education
Grants BFU2004-02838 and SAF2007-60010, Instituto de Salud Carlos III
Grant RD06/0026/1001, and the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (L.T. and F.C.).
NR 45
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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 AUG 26
PY 2008
VL 105
IS 34
BP 12581
EP 12586
DI 10.1073/pnas.0803174105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 344DJ
UT WOS:000258905700086
PM 18723674
ER
PT J
AU Jiang, HY
Yi, M
Mu, JB
Zhang, L
Ivens, A
Klimczak, LJ
Huyen, Y
Stephens, RM
Su, XZ
AF Jiang, Hongying
Yi, Ming
Mu, Jianbing
Zhang, Louie
Ivens, Al
Klimczak, Leszek J.
Huyen, Yentram
Stephens, Robert M.
Su, Xin-zhuan
TI Detection of genome-wide polymorphisms in the AT-rich Plasmodium
falciparum genome using a high-density microarray
SO BMC GENOMICS
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COPY NUMBER; ASSOCIATION SCAN;
OLIGONUCLEOTIDE ARRAYS; MEFLOQUINE RESISTANCE; COLORECTAL-CANCER; PFMDR1
GENE; MALARIA; DNA; DISCOVERY
AB Background: Genetic mapping is a powerful method to identify mutations that cause drug resistance and other phenotypic changes in the human malaria parasite Plasmodium falciparum. For efficient mapping of a target gene, it is often necessary to genotype a large number of polymorphic markers. Currently, a community effort is underway to collect single nucleotide polymorphisms (SNP) from the parasite genome. Here we evaluate polymorphism detection accuracy of a high-density 'tiling' microarray with 2.56 million probes by comparing single feature polymorphisms (SFP) calls from the microarray with known SNP among parasite isolates.
Results: We found that probe GC content, SNP position in a probe, probe coverage, and signal ratio cutoff values were important factors for accurate detection of SFP in the parasite genome. We established a set of SFP calling parameters that could predict mSFP (SFP called by multiple overlapping probes) with high accuracy (>= 94%) and identified 121,087 mSFP genome-wide from five parasite isolates including 40,354 unique mSFP (excluding those from multi-gene families) and similar to 18,000 new mSFP, producing a genetic map with an average of one unique mSFP per 570 bp. Genomic copy number variation (CNV) among the parasites was also cataloged and compared.
d Conclusion: A large number of mSFP were discovered from the P. falciparum genome using a high-density microarray, most of which were in clusters of highly polymorphic genes at chromosome ends. Our method for accurate mSFP detection and the mSFP identified will greatly facilitate large-scale studies of genome variation in the P. falciparum parasite and provide useful resources for mapping important parasite traits.
C1 [Jiang, Hongying; Mu, Jianbing; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Yi, Ming; Stephens, Robert M.] NCI, Adv Technol Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
[Zhang, Louie] Drexel Univ, Sch Med, Philadelphia, PA 19104 USA.
[Ivens, Al] Wellcome Trust Sanger Inst, Pathogen Microarrays Grp, Cambridge CB10 1SA, England.
[Klimczak, Leszek J.; Huyen, Yentram] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hojiang@niaid.nih.gov; myi@ncifcrf.gov; jmu@niaid.nih.gov;
lz422@drexel.edu; alicat@sanger.ac.uk; klimczakl@niaid.nih.gov;
huyeny@niaid.nih.gov; bobs@ncifcrf.gov; xsu@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Intramural Research
Program of the Center for Cancer Research, National Cancer Institute,
National Institutes of Health; NCI [N01-CO-12400]; Wellcome Trust
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health; and
in part was funded by NCI 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. AI was supported by the Wellcome Trust. We thank NIAID
intramural editor Brenda Rae Marshall for assistance and Jun Yang and
Brandie Fullmer at the Laboratory of Immunopathogenesis and
Bioinformatics, SAIC-Frederick, Inc. for microarray hybridizations, and
David Bennett at Partek Inc. for advanced data analysis help.
NR 49
TC 42
Z9 44
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 25
PY 2008
VL 9
AR 398
DI 10.1186/1471-2164-9-398
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 357CJ
UT WOS:000259823600001
PM 18724869
ER
PT J
AU Song, SM
Lee, HK
Kam, TI
Tai, ML
Lee, JY
Noh, JY
Shim, SM
Seo, SJ
Kong, YY
Nakagawa, T
Chung, CW
Choi, DY
Oubrahim, H
Jung, YK
AF Song, Sungmin
Lee, Huikyong
Kam, Tae-In
Tai, Mei Ling
Lee, Joo-Yong
Noh, Jee-Yeon
Shim, Sang Mi
Seo, Soo Jung
Kong, Young-Yun
Nakagawa, Toshiyuki
Chung, Chul-Woong
Choi, Deog-Young
Oubrahim, Hammou
Jung, Yong-Keun
TI E2-25K/Hip-2 regulates caspase-12 in ER stress-mediated A beta
neurotoxicity
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; CELL-DEATH; AMYLOID-BETA;
ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; PRION PROTEIN; CROSS-TALK;
PROTEASOME; ACTIVATION; NEURODEGENERATION
AB Amyloid-beta (A beta) neurotoxicity is believed to contribute to the pathogenesis of Alzheimer's disease (AD). Previously we found that E2-25K/Hip-2, an E2 ubiquitin-conjugating enzyme, mediates A beta neurotoxicity. Here, we report that E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system. Levels of endoplasmic reticulum (ER)-resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. A beta in creases expression of E2-25K/Hip-2, which then stabilizes caspase-12 protein by inhibiting proteasome activity. This increase in E2-25K/Hip-2 also induces proteolytic activation of caspase-12 through its ability to induce calpainlike activity. Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2-mediated cell death. Finally, we find that E2-25K/Hip-2-deficient cortical neurons are resistant to A beta toxicity and to the induction of ER stress and caspase-12 expression by A beta. E2-25K/Hip-2 is thus an essential upstream regulator of the expression and activation of caspase-12 in ER stress mediated A beta neurotoxicity.
C1 [Song, Sungmin; Lee, Huikyong; Kam, Tae-In; Tai, Mei Ling; Noh, Jee-Yeon; Shim, Sang Mi; Seo, Soo Jung; Jung, Yong-Keun] Seoul Natl Univ, Sch Biol Sci, Seoul 151747, South Korea.
[Lee, Joo-Yong] Univ Ulsan, Coll Med, Seoul 138736, South Korea.
[Kong, Young-Yun] Pohang Univ Sci & Technol, Pohang 790784, South Korea.
[Nakagawa, Toshiyuki] Gifu Univ, Grad Sch Med, Gifu 5011194, Japan.
[Chung, Chul-Woong; Choi, Deog-Young] LG Life Sci Res Pk, Taejon 305389, South Korea.
[Oubrahim, Hammou] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Jung, YK (reprint author), Seoul Natl Univ, Sch Biol Sci, Seoul 151747, South Korea.
EM ykjung@snu.ac.kr
RI Lee, Joo-Yong/F-4545-2014;
OI Kam, Tae-In/0000-0002-7241-4902
FU Brain Research Center of the 21st Century Frontier Research Program;
Korea Science and Engineering Foundation of the Korean government; Basic
Science program of Korea Research Foundation; Korea Health 21 RD
Project; Ministry of Health and Welfare, Korea [A040147]
FX S. Song and T.-I. Kam were supported in part by the BK21 program. This
work was supported by grants from the Brain Research Center of the 21st
Century Frontier Research Program, by Functional Cellulomics funded by
the Korea Science and Engineering Foundation of the Korean government,
by Basic Science program of Korea Research Foundation (Y. K. Jung), and
by a grant of the Korea Health 21 R&D Project, Ministry of Health and
Welfare, Korea (A040147).
NR 36
TC 40
Z9 45
U1 0
U2 3
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 AUG 25
PY 2008
VL 182
IS 4
BP 675
EP 684
DI 10.1083/jcb.200711066
PG 10
WC Cell Biology
SC Cell Biology
GA 346EA
UT WOS:000259050000009
PM 18710920
ER
PT J
AU Kirkpatrick, B
Currier, R
Nierenberg, K
Reich, A
Backer, LC
Stumpf, R
Fleming, L
Kirkpatrick, G
AF Kirkpatrick, Barbara
Currier, Robert
Nierenberg, Kate
Reich, Andrew
Backer, Lorraine C.
Stumpf, Richard
Fleming, Lora
Kirkpatrick, Gary
TI Florida red tide and human health: A pilot beach conditions reporting
system to minimize human exposure
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE asthma; Florida red tide; harmful algal blooms; ocean observing systems;
beach conditions; Karenia brevis
ID AEROSOLIZED BREVETOXINS; TOXINS BREVETOXINS; ASTHMA; POPULATION; EVENTS
AB With over 50% of the US population living in coastal counties, the ocean and coastal environments have substantial impacts on coastal communities. While many of the impacts are positive, such as tourism and recreation opportunities, there are also negative impacts, such as exposure to harmful algal blooms (HABs) and water borne pathogens. Recent advances in environmental monitoring and weather prediction may allow us to forecast these potential adverse effects and thus mitigate the negative impact from coastal environmental threats.
One example of the need to mitigate adverse environmental impacts occurs on Florida's west coast, which experiences annual blooms, or periods of exuberant growth, of the toxic dinoflagellate, Karenia brevis. K. brevis produces a suite of potent neurotoxins called brevetoxins. Wind and wave action can break up the cells, releasing toxin that can then become part of the marine aerosol or sea spray. Brevetoxins in the aerosol cause respiratory irritation in people who inhale it. In addition, asthmatics who inhale the toxins report increase upper and lower airway symptoms and experience measurable changes in pulmonary function. Real-time reporting of the presence or absence of these toxic aerosols will allow asthmatics and local coastal residents to make informed decisions about their personal exposures, thus adding to their quality of life.
A system to protect public health that combines information collected by an Integrated Ocean Observing System (IOOS) has been designed and implemented in Sarasota and Manatee Counties, Florida. This system is based on real-time reports from lifeguards at the eight public beaches. The lifeguards provide periodic subjective reports of the amount of dead fish on the beach, apparent level of respiratory irritation among beach-goers, water color, wind direction, surf condition, and the beach warning flag they are flying.
A key component in the design of the observing system was an easy reporting pathway for the lifeguards to minimize the amount of time away from their primary duties. Specifically, we provided a Personal Digital Assistant for each of the eight beaches. The portable unit allows the lifeguards to report from their guard tower. The data are transferred via wireless Internet to a website hosted on the Mote Marine Laboratory Sarasota Operations of the Coastal Ocean Observation Laboratories (SO COOL) server. The system has proven to be robust and well received by the public. The system has reported variability from beach to beach and has provided vital information to users to minimize their exposure to toxic marine aerosols. (c) 2008 Elsevier B.V. All rights reserved.
C1 [Kirkpatrick, Barbara; Currier, Robert; Nierenberg, Kate; Kirkpatrick, Gary] Mote Marine Lab, Sarasota, FL 32436 USA.
[Reich, Andrew] Florida Dept Hlth, Tallahassee, FL 32399 USA.
[Backer, Lorraine C.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
[Stumpf, Richard] NOAA, Natl Ocean Serv, Silver Spring, MD 20920 USA.
[Fleming, Lora] Univ Miami, NSF, NIEHS, Oceans & Human Hlth Ctr, Miami, FL 33149 USA.
RP Kirkpatrick, B (reprint author), Mote Marine Lab, Environm Hlth Program, 1600 Ken Thompson Pkwy, Sarasota, FL 33236 USA.
EM bkirkpat@mote.org
FU NIEHS NIH HHS [P01 ES010594, P50 ES012736, P50 ES012736-05, P01
ES010594-08, P01 ES 10594]; PHS HHS [U50/CCU423360-02]
NR 19
TC 10
Z9 11
U1 3
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD AUG 25
PY 2008
VL 402
IS 1
BP 1
EP 8
DI 10.1016/j.scitotenv.2008.03.032
PG 8
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 331KJ
UT WOS:000258010800001
PM 18501955
ER
PT J
AU Cai, Y
Xu, Z
Nagarajan, L
Brandt, SJ
AF Cai, Ying
Xu, Zhixiong
Nagarajan, Lalitha
Brandt, Stephen J.
TI Single-stranded DNA-binding proteins regulate the abundance and function
of the LIM-homeodomain transcription factor LHX2 in pituitary cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE single-stranded DNA-binding proteins; LIM-homeodomain proteins; protein
turnover; gene expression; pituitary cells
ID IN-VIVO; GENE-EXPRESSION; DOMAIN; COMPLEX; PROMOTER; LDB1;
DIFFERENTIATION; DLDB/CHIP; COFACTORS; ORGANIZER
AB A family of single-stranded DNA-binding proteins (or SSBPs) has been shown to augment the function of LIM-homeodomain (LIM-HD) transcription factors in embryogenesis by interaction with LIM domain-binding protein-I (LDB1). No DNA-binding complex has been described, however, containing a LIM-HD protein, LDB1, and SSBP, and the mechanism by which SSBPs affect LIM-HD function had not been elucidated. Through use of electrophoretic mobility shift, antibody supershift, and ChIP analyses, we show that an Lhx2-Ldb1-Ssbp3 complex binds a specific element in the Lhx2 target gene Cga (encoding the alpha subunit of glycoprotein hormones) in the alpha T3-1 pituitary cell line. Using overexpression and knockdown approaches, we demonstrate that SSBP3 inhibits Lhx2 and Ldb1 turnover, stimulates assembly of this DNA-binding complex, promotes its recruitment to the Cga promoter, and enhances Cga transcription. These studies provide novel insights into the regulation of pituitary gene expression and LIM-HD function more generally. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Cai, Ying; Brandt, Stephen J.] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Dept Med, Nashville, TN 37232 USA.
[Xu, Zhixiong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Nagarajan, Lalitha] Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Dept Mol Genet, Houston, TX 77030 USA.
Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Program Genes & Dev, Houston, TX 77030 USA.
[Brandt, Stephen J.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, IN 37232 USA.
[Brandt, Stephen J.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA.
[Brandt, Stephen J.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Brandt, Stephen J.] VA Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA.
RP Brandt, SJ (reprint author), Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Dept Med, Room 777 Preston Res Bldg, Nashville, TN 37232 USA.
EM stephen.brandt@vanderbilt.edu
FU NHLBI NIH HHS [R01 HL049118-13, R01 HL074449, R01 HL49118, R01 HL049118]
NR 26
TC 11
Z9 11
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 22
PY 2008
VL 373
IS 2
BP 303
EP 308
DI 10.1016/j.bbrc.2008.06.027
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 327WH
UT WOS:000257758700023
PM 18565323
ER
PT J
AU Lies, M
Maurizi, MR
AF Lies, Mark
Maurizi, Michael R.
TI Turnover of endogenous SsrA-tagged proteins mediated by ATP-dependent
proteases in Escherichia coli
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID N-END RULE; CLPXP DEGRADATION MACHINE; TRANS-TRANSLATION; 10SA RNA; STOP
CODONS; STABLE RNA; SYNTHESIS INHIBITORS; TAGGING ACTIVITY;
MESSENGER-RNA; PEPTIDE
AB Formation and degradation of SsrA-tagged proteins enable ribosome recycling and elimination of defective products of incomplete translation. We produced an antibody against the SsrA peptide and used it to measure the amounts of SsrA-tagged proteins in Escherichia coli cells without interfering with tagging or altering the context of the tag added at the ends of nascent polypeptides. SsrA-tagged proteins were present in very small amounts unless a component of the ClpXP protease was missing. From the levels of tagged proteins in cells in which degradation is essentially blocked, we calculate that >= 1 in 200 translation products receives an SsrA tag. ClpXP is responsible for >= 90% of the degradation of SsrA-tagged proteins. The degradation rate in wild type cells is >= 1.4 min(-1) and decreases to similar to 0.10 min(-1) in a clpX mutant. The rate of degradation by ClpXP is decreased similar to 3-fold in mutants lacking the adaptor SspB, whereas degradation by ClpAP is increased 3-5-fold. However, ClpAP degrades SsrA-tagged proteins slowly even in the absence of SspB, possibly because of interference from ClpA-specific substrates. Lon protease degrades SsrA-tagged proteins at a rate of similar to 0.05 min(-1) in the presence or absence of SspB. We conclude that ClpXP, together with SspB, is uniquely adapted for degradation of SsrA-tagged proteins and is responsible for the major part of their degradation in vivo.
C1 [Lies, Mark; Maurizi, Michael R.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Rm 2128,37 Convent Dr, Bethesda, MD 20892 USA.
EM mmaurizi@helix.nih.gov
FU National Institutes of Health
FX This work was authored, in whole or in part, by National Institutes of
Health staff.
NR 52
TC 41
Z9 42
U1 2
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 22
PY 2008
VL 283
IS 34
BP 22918
EP 22929
DI 10.1074/jbc.M801692200
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 337SI
UT WOS:000258455400005
PM 18550539
ER
PT J
AU Raman, J
Fritz, TA
Gerken, TA
Jamison, O
Live, D
Liu, M
Tabak, LA
AF Raman, Jayalakshmi
Fritz, Timothy A.
Gerken, Thomas A.
Jamison, Oliver
Live, David
Liu, Mian
Tabak, Lawrence A.
TI The catalytic and lectin domains of UDP-GalNAc: Polypeptide
alpha-N-acetylgalactosaminyltransferase function in concert to direct
glycosylation site selection
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACETYL-D-GALACTOSAMINE; MUCIN TANDEM REPEAT; O-GLYCOSYLATION;
STREPTOMYCES-LIVIDANS; SUBMAXILLARY-GLAND; KINETIC MECHANISM;
XYLAN-BINDING; IN-VIVO; GLYCOPEPTIDE; FAMILY
AB UDP-GalNAc: polypeptide alpha-N-Acetylgalactosaminyltransferases (ppGalNAcTs), a family (EC 2.4.1.41) of enzymes that initiate mucin-type O-glycosylation, are structurally composed of a catalytic domain and a lectin domain. Previous studies have suggested that the lectin domain modulates the glycosylation of glycopeptide substrates and may underlie the strict glycopeptide specificity of some isoforms (ppGalNAcT-7 and -10). Using a set of synthetic peptides and glycopeptides based upon the sequence of the mucin, MUC5AC, we have examined the activity and glycosylation site preference of lectin domain deletion and exchange constructs of the peptide/glycopeptide transferase ppGalNAcT-2 (hT2) and the glycopeptide transferase ppGal-NAcT- 10 (hT10). We demonstrate that the lectin domain of hT2 directs glycosylation site selection for glycopeptide substrates. Pre-steady-state kinetic measurements show that this effect is attributable to two mechanisms, either lectin domain-aided substrate binding or lectin domain-aided product release following glycosylation. We find that glycosylation of peptide substrates by hT10 requires binding of existing GalNAcs on the substrate to either its catalytic or lectin domain, thereby resulting in its apparent strict glycopeptide specificity. These results highlight the existence of two modes of site selection used by these ppGalNAcTs: local sequence recognition by the catalytic domain and the concerted recognition of distal sites of prior glycosylation together with local sequence binding mediated, respectively, by the lectin and catalytic domains. The latter mode may facilitate the glycosylation of serine or threonine residues, which occur in sequence contexts that would not be efficiently glycosylated by the catalytic domain alone. Local sequence recognition by the catalytic domain differs between hT2 and hT10 in that hT10 requires a pre-existing GalNAc residue while hT2 does not.
C1 [Raman, Jayalakshmi; Fritz, Timothy A.; Tabak, Lawrence A.] NIDDK, Sect Biol Chem, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Gerken, Thomas A.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA.
[Gerken, Thomas A.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
[Gerken, Thomas A.; Jamison, Oliver] Case Western Reserve Univ, Sch Med, WA Bernbaum Ctr Cyst Fibrosis Res, Cleveland, OH 44106 USA.
[Live, David; Liu, Mian] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA.
RP Tabak, LA (reprint author), NIDDK, Sect Biol Chem, NIH, US Dept HHS, Bethesda, MD 20892 USA.
EM tabakl@mail.nih.gov
FU National Institutes of Health; NIDDK; [NCI-RO1 CA-78834]; [NIGMS-RO1
GM-066148]
FX This work was supported, in whole or in part, by the National Institutes
of Health, through funds of the intramural program of the NIDDK and
Grants NCI-RO1 CA-78834 (to T.A.G.) and NIGMS-RO1 GM-066148 (to D.L.).
NR 36
TC 39
Z9 40
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 22
PY 2008
VL 283
IS 34
BP 22942
EP 22951
DI 10.1074/jbc.M803387200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 337SI
UT WOS:000258455400007
PM 18562306
ER
PT J
AU Basu, NK
Kole, L
Basu, M
Chakraborty, K
Mitra, PS
Owens, IS
AF Basu, Nikhil K.
Kole, Labanyamoy
Basu, Mousumi
Chakraborty, Kushal
Mitra, Partha S.
Owens, Ida S.
TI The major chemical-detoxifying system of UDP-glucuronosyltransferases
requires regulated phosphorylation supported by protein kinase C
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; CARDIAC MYOCYTES; COS-1
CELLS; GLUCURONIDATION; BILIRUBIN; CURCUMIN; EPSILON; TRANSLOCATION;
INHIBITION
AB Finding rapid, reversible down-regulation of human UDP-glucuronosyltransferases (UGTs) in LS180 cells following curcumin treatment led to the discovery that UGTs require phosphorylation. UGTs, distributed primarily in liver, kidney, and gastrointestinal tract, inactivate aromatic-like metabolites and a vast number of dietary and environmental chemicals, which reduces the risk of toxicities, mutagenesis, and carcinogenesis. Our aim here is to determine relevant kinases and mechanism(s) regulating phosphorylation of constitutive UGTs in LS180 cells and 10 different human UGT cDNA-transfected COS-1 systems. Time- and concentration-dependent inhibition of immunodetectable [(33)P] orthophosphate in UGTs and protein kinase C is an element of(PKC is an element of), following treatment of LS180 cells with curcumin or the PKC inhibitor calphostin-C, suggested UGT phosphorylation is supported by active PKC( s). Immunofluorescent and co-immunoprecipitation studies with UGT-transfected cells showed co-localization of UGT1A7His and PKC is an element of and of UGT1A10His and PKC alpha orPKC delta. Inhibition of UGT activity by PKC is an element of-specific antagonist peptide or by PKC is an element of-targeted destruction with PKC is an element of-specific small interference RNA and activation of curcumin-down-regulated UGTs with typical PKC agonists verified a central PKC role in glucuronidation. Moreover, in vitro phosphorylation of nascent UGT1A7His by PKC is an element of confirms it is a bona fide PKC substrate. Finally, catalase or herbimycin-A inhibition of constitutive or hydrogen peroxide-activated UGTs demonstrated that reactive oxygen species-related oxidants act as second messengers in maintaining constitutive PKC-dependent signaling evidently sustaining UGT phosphorylation and activity. Because cells use signal transduction collectively to detect and respond appropriately to environmental changes, this report, combined with our earlier demonstration that specific phospho-groups in UGT1A7 determined substrate selections, suggests regulated phosphorylation allows adaptations regarding differential phosphate utilization by UGTs to function efficiently.
C1 [Basu, Nikhil K.; Kole, Labanyamoy; Basu, Mousumi; Chakraborty, Kushal; Mitra, Partha S.; Owens, Ida S.] NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Owens, IS (reprint author), NICHD, Heritable Disorders Branch, NIH, 9000 Rockville Pike,Bldg 10, Rm 9D-42, Bethesda, MD 20892 USA.
EM owensi@mail.nih.gov
FU National Institutes of Health NICHD Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health NICHD Intramural Research Program.
NR 52
TC 19
Z9 19
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 22
PY 2008
VL 283
IS 34
BP 23048
EP 23061
DI 10.1074/jbc.M800032200
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 337SI
UT WOS:000258455400018
PM 18556656
ER
PT J
AU Guo, R
Yamashita, M
Zhang, Q
Zhou, Q
Chen, D
Reynolds, DG
Awad, HA
Yanoso, L
Zhao, L
Schwarz, EM
Zhang, YE
Boyce, BF
Xing, LP
AF Guo, Ruolin
Yamashita, Motozo
Zhang, Qian
Zhou, Quan
Chen, Di
Reynolds, David G.
Awad, Hani A.
Yanoso, Laura
Zhao, Lan
Schwarz, Edward M.
Zhang, Ying E.
Boyce, Brendan F.
Xing, Lianping
TI Ubiquitin ligase Smurf1 mediates tumor necrosis factor-induced systemic
bone loss by promoting proteasomal degradation of bone morphogenetic
signaling proteins
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NF-KAPPA-B; MURINE CLONAL OSTEOBLASTS; FACTOR-ALPHA; TNF-ALPHA;
RHEUMATOID-ARTHRITIS; RUNX2 DEGRADATION; DIFFERENTIATION; EXPRESSION;
APOPTOSIS; RECEPTOR
AB Chronic inflammatory disorders, such as rheumatoid arthritis, are often accompanied by systemic bone loss, which is thought to occur through inflammatory cytokine-mediated stimulation of osteoclast resorption and inhibition of osteoblast function. However, the mechanisms involved in osteoblast inhibition remain poorly understood. Here we test the hypothesis that increased Smad ubiquitin regulatory factor 1 (Smurf1)-mediated degradation of the bone morphogenetic protein pathway signaling proteins mediates reduced bone formation in inflammatory disorders. Osteoblasts derived from bone marrow or long bone samples of adult tumor necrosis factor (TNF) transgenic (TNF-Tg) mice were used in this study. TNF decreased the steady-state levels of Smad1 and Runx2 protein similarly to those in long bones of TNF-Tg mice. In the presence of the proteasome inhibitor MG132, TNF increased accumulation of ubiquitinated Smad1 protein. TNF administration over calvarial bones caused decreases in Smad1 and Runx2 protein levels and mRNA expression of osteoblast marker genes in wild-type, but not in Smurf1(-/-) mice. Vertebral bone volume and strength of TNF-Tg/Smurf1(-/-) mice were examined by a combination of micro-CT, bone histomorphometry, and biomechanical testing and compared with those from TNF-Tg littermates. TNF-Tg mice had significantly decreased bone volume and biomechanical properties, which were partially rescued in TNF-Tg/Smurf1(-/-) mice. We conclude that in chronic inflammatory disorders where TNF is increased, TNF induces the expression of ubiquitin ligase Smurf1 and promotes ubiquitination and proteasomal degradation of Smad1 and Runx2, leading to systemic bone loss. Inhibition of ubiquitin-mediated Smad1 and Runx2 degradation in osteoblasts could help to treat inflammation-induced osteoporosis.
C1 [Guo, Ruolin; Zhang, Qian; Zhou, Quan; Zhao, Lan; Boyce, Brendan F.; Xing, Lianping] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA.
[Chen, Di; Reynolds, David G.; Awad, Hani A.; Yanoso, Laura; Schwarz, Edward M.; Boyce, Brendan F.; Xing, Lianping] Univ Rochester, Med Ctr, Ctr Musculoskeletal Res, Rochester, NY 14642 USA.
[Yamashita, Motozo; Zhang, Ying E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Xing, LP (reprint author), Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA.
EM Lianping_xing@urmc.rochester.edu
RI Awad, Hani/G-6976-2014; Zhang, Ying/G-3657-2015
OI Awad, Hani/0000-0003-2197-2610; Zhang, Ying/0000-0003-2753-7601
FU National Institutes of Health [AR48697, AR53586, AR43510]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants AR48697 and AR53586 ( to L. X.) and AR43510 ( to B. F.
B.).
NR 42
TC 74
Z9 77
U1 0
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 22
PY 2008
VL 283
IS 34
BP 23084
EP 23092
DI 10.1074/jbc.M709848200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 337SI
UT WOS:000258455400021
PM 18567580
ER
PT J
AU Sordet, O
Goldman, A
Redon, C
Solier, S
Rao, VA
Pommier, Y
AF Sordet, Olivier
Goldman, Abby
Redon, Christophe
Solier, Stephanie
Rao, V. Ashutosh
Pommier, Yves
TI Topoisomerase I requirement for death receptor-induced apoptotic nuclear
fission
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MEDIATED DNA-DAMAGE; CARCINOMA CELL-LINES; TRAIL/APO2L-INDUCED
APOPTOSIS; MITOCHONDRIAL-FUNCTION; RESISTANCE MECHANISM; CLEAVAGE
COMPLEXES; ANTICANCER AGENTS; OXYGEN RADICALS; CYTOCHROME-C;
CANCER-CELLS
AB Topoisomerase I (Top1) is known to relax DNA supercoiling generated by transcription, replication, and chromatin remodeling. However, it can be trapped on DNA as cleavage complexes (Top1cc) by oxidative and carcinogenic DNA lesions, base damage, and camptothecin treatment. We show here that Top1 is also functionally involved in death receptor-induced programmed cell death. In cells exposed to TRAIL or Fas ligand, Top1cc form at the onset of apoptosis. Those apoptotic Top1cc are prevented by caspase inhibition and Bax inactivation, indicating that both caspases and the mitochondrial death pathway are required for their formation. Accordingly, direct activation of the mitochondrial pathway by BH3 mimetic molecules induces apoptotic Top1cc. We also show that TRAIL-induced apoptotic Top1cc are preferentially formed by caspase-3-cleaved Top1 at sites of oxidative DNA lesions with an average of one apoptotic Top1cc/100 kbp. Examination of Top1 knockdown cells treated with TRAIL revealed similar DNA fragmentation but a marked decrease in apoptotic nuclear fission with reduced formation of nuclear bodies. Thus, we propose that Top1 contributes to the full apoptotic responses induced by TRAIL.
C1 [Sordet, Olivier; Goldman, Abby; Redon, Christophe; Solier, Stephanie; Rao, V. Ashutosh; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
RI Sordet, Olivier/M-3271-2014
FU Intramural NIH HHS
NR 64
TC 10
Z9 10
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 22
PY 2008
VL 283
IS 34
BP 23200
EP 23208
DI 10.1074/jbc.M801146200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 337SI
UT WOS:000258455400033
PM 18556653
ER
PT J
AU Lu, ZP
Sack, MN
AF Lu, Zhongping
Sack, Michael N.
TI ATF-1 is a hypoxia-responsive transcriptional activator of skeletal
muscle mitochondrial-uncoupling protein 3
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INDUCIBLE FACTOR-I; OXIDATIVE STRESS; BINDING-PROTEIN; PROMOTER REGION;
FACTOR CREB; FATTY-ACID; GENE; UCP3; OVEREXPRESSION; EXPRESSION
AB Hypoxia induces oxidative damage in skeletal muscle. Uncoupling protein 3 (UCP3) is the skeletal muscle enriched uncoupling protein and has previously been shown to confer resistance against oxidative stress. We show that hypoxia robustly up-regulates skeletal muscle UCP3 and that the absence of UCP3 in primary skeletal myocytes exacerbates hypoxia-induced reactive oxygen species generation. In this context, we reasoned that the investigation of the regulation of UCP3 may identify novel hypoxia-responsive regulatory pathways that modulate intrinsic anti-oxidant defenses. By screening a transcription factor array of 704 full-length cDNAs in murine C2C12 myoblasts following cotransfection of a murine UCP3 promoter-luciferase construct and myoD we identified numerous candidate regulatory factors that up-regulate UCP3. Active transcription factor-1 (ATF-1) was identified, and as this transcription factor is a known component of a multiprotein hypoxia-induced regulatory complex, we explored its role in hypoxia-mediated UCP3 up-regulation. Site-directed mutagenesis and chromatin immunoprecipitation assays identify a 10-bp region required for ATF-1 induction of UCP3 promoter activity. Hypoxia promotes the phosphorylation of ATF-1, and the knockdown of ATF-1 by shRNA prevents hypoxia-mediated up-regulation of UCP3. Pharmacologic inhibition of p38 MAP kinase prevents both hypoxia-mediated ATF-1 phosphorylation and UCP3 up-regulation. PKA signaling does not modulate hypoxia-induced UCP3 up-regulation and neither does HIF-1 alpha activation by cobalt chloride. In conclusion, ATF-1, via p38 MAP kinase activation, functions as a novel regulatory pathway driving UCP3 expression. These data reinforce the role of ATF-1 as a hypoxia-responsive trans-activator and identifies a novel regulatory program that may modulate cellular responses to oxygen-deficit.
C1 [Lu, Zhongping; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10 CRC,Rm 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
FU Intramural NIH HHS
NR 41
TC 18
Z9 20
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 22
PY 2008
VL 283
IS 34
BP 23410
EP 23418
DI 10.1074/jbc.M801236200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 337SI
UT WOS:000258455400050
PM 18579531
ER
PT J
AU Wang, FL
Grigorieva, EV
Li, JF
Senchenko, VN
Pavlova, TV
Anedchenko, EA
Kudryavtseva, AV
Tsimanis, A
Angeloni, D
Lerman, MI
Kashuba, VI
Klein, G
Zabarovsky, ER
AF Wang, Fuli
Grigorieva, Elvira V.
Li, Jingfeng
Senchenko, Vera N.
Pavlova, Tatiana V.
Anedchenko, Ekaterina A.
Kudryavtseva, Anna V.
Tsimanis, Alexander
Angeloni, Debora
Lerman, Michael I.
Kashuba, Vladimir I.
Klein, George
Zabarovsky, Eugene R.
TI HYAL1 and HYAL2 Inhibit Tumour Growth In Vivo but Not In Vitro
SO PLOS ONE
LA English
DT Article
ID HUMAN-CHROMOSOME 3P21.3; HUMAN EPITHELIAL MALIGNANCIES; JAAGSIEKTE SHEEP
RETROVIRUS; HOMOZYGOUS DELETION REGION; REAL-TIME PCR; SUPPRESSOR GENE;
CELL FUSION; LUNG; INACTIVATION; HYALURONAN
AB Background: We identified two 3p21.3 regions (LUCA and AP20) as most frequently affected in lung, breast and other carcinomas and reported their fine physical and gene maps. It is becoming increasingly clear that each of these two regions contains several TSGs. Until now TSGs which were isolated from AP20 and LUCA regions (e. g. G21/NPRL2, RASSF1A, RASSF1C, SEMA3B, SEMA3F, RBSP3) were shown to inhibit tumour cell growth both in vitro and in vivo.
Methodology/Principal Findings: The effect of expression HYAL1 and HYAL2 was studied by colony formation inhibition, growth curve and cell proliferation tests in vitro and tumour growth assay in vivo. Very modest growth inhibition was detected in vitro in U2020 lung and KRC/Y renal carcinoma cell lines. In the in vivo experiment stably transfected KRC/Y cells expressing HYAL1 or HYAL2 were inoculated into SCID mice (10 and 12 mice respectively). Tumours grew in eight mice inoculated with HYAL1. Ectopic HYAL1 was deleted in all of them. HYAL2 was inoculated into 12 mice and only four tumours were obtained. In 3 of them the gene was deleted. In one tumour it was present but not expressed. As expected for tumour suppressor genes HYAL1 and HYAL2 were down-expressed in 15 fresh lung squamous cell carcinomas (100%) and clear cell RCC tumours (60-67%).
Conclusions/Significance: The results suggest that the expression of either gene has led to inhibition of tumour growth in vivo without noticeable effect on growth in vitro. HYAL1 and HYAL2 thus differ in this aspect from other tumour suppressors like P53 or RASSF1A that inhibit growth both in vitro and in vivo. Targeting the microenvironment of cancer cells is one of the most promising venues of cancer therapeutics. As major hyaluronidases in human cells, HYAL1 and HYAL2 may control intercellular interactions and microenvironment of tumour cells providing excellent targets for cancer treatment.
C1 [Wang, Fuli; Grigorieva, Elvira V.; Li, Jingfeng; Pavlova, Tatiana V.; Kashuba, Vladimir I.; Klein, George; Zabarovsky, Eugene R.] Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden.
[Grigorieva, Elvira V.] SD RAMS, Inst Mol Biol & Biophys, Novosibirsk, Russia.
[Senchenko, Vera N.; Pavlova, Tatiana V.; Anedchenko, Ekaterina A.; Kudryavtseva, Anna V.] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia.
[Tsimanis, Alexander] Bioactivity Ltd, Rehovot, Israel.
[Angeloni, Debora; Lerman, Michael I.] NCI, Ctr Canc Res, Lab Immunobiol, Canc Causing Genes Sect, Frederick, MD USA.
[Angeloni, Debora] CNR, Inst Clin Physiol, Scuola Superiore SantAnna, Pisa, Italy.
[Kashuba, Vladimir I.] Ukrainian Acad Scie, Inst Mol Biol & Genet, Kiev, Ukraine.
RP Wang, FL (reprint author), Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden.
EM eugzab@ki.se
RI Grigorieva, Elvira/A-4937-2010; Senchenko, Vera/C-8992-2014;
Kudryavtseva, Anna/C-9032-2014
OI Grigorieva, Elvira/0000-0003-2457-9179; Senchenko,
Vera/0000-0002-3119-515X; Kudryavtseva, Anna/0000-0002-3722-8207
FU Swedish Cancer Society; Swedish Research Council; Swedish Foundation for
International Cooperation in Research and Higher Education (STINT);
Swedish Institute; Royal Swedish Academy of Sciences; INTAS; Karolinska
Institute; Russian Federal Agency of Science and Innovations
[02.512.11.21.01, 02.512.11.2241]; Russian Foundation for Basic Research
[008-04-01577]; Concern Foundation in Los Angeles [fellowship]; Cancer
Research Institute in New York; Intramural Research Program of the
Center for Cancer Research, National Cancer Institute
FX This work was supported by research grants from the Swedish Cancer
Society, the Swedish Research Council, the Swedish Foundation for
International Cooperation in Research and Higher Education (STINT), the
Swedish Institute, the Royal Swedish Academy of Sciences, INTAS and
Karolinska Institute. VNS, EAA and AVK received grants from the Russian
Federal Agency of Science and Innovations (State Contract no
02.512.11.21.01 and 02.512.11.2241) and the Russian Foundation for Basic
Research (Project no. 008-04-01577). EVG was recipient of fellowship
from the Concern Foundation in Los Angeles and the Cancer Research
Institute in New York. TVP was supported by fellowship from The Swedish
Institute. MIL and DA were supported by the Intramural Research Program
of the 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, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 32
TC 25
Z9 29
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 22
PY 2008
VL 3
IS 8
AR e3031
DI 10.1371/journal.pone.0003031
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 422LH
UT WOS:000264428800002
PM 18725949
ER
PT J
AU Feinerman, O
Veiga, J
Dorfman, JR
Germain, RN
Altan-Bonnet, G
AF Feinerman, Ofer
Veiga, Joel
Dorfman, Jeffrey R.
Germain, Ronald N.
Altan-Bonnet, Gregoire
TI Variability and robustness in T cell activation from regulated
heterogeneity in protein levels
SO SCIENCE
LA English
DT Article
ID STOCHASTIC GENE-EXPRESSION; SINGLE-CELL; LIGAND DISCRIMINATION; NOISE;
RESPONSES; SELECTION; DYNAMICS; MEMORY; NUMBER
AB In T cells, the stochasticity of protein expression could contribute to the useful diversification of biological functions within a clonal population or interfere with accurate antigen discrimination. Combining computer modeling and single- cell measurements, we examined how endogenous variation in the expression levels of signaling proteins might affect antigen responsiveness during T cell activation. We found that the CD8 co- receptor fine- tunes activation thresholds, whereas the soluble hematopoietic phosphatase 1 ( SHP- 1) digitally regulates cell responsiveness. Stochastic variation in the expression of these proteins generates substantial diversity of activation within a clonal population of T cells, but co- regulation of CD8 and SHP- 1 levels ultimately limits this very diversity. These findings reveal how eukaryotic cells can draw on regulated variation in gene expression to achieve phenotypic variability in a controlled manner.
C1 [Feinerman, Ofer; Veiga, Joel; Dorfman, Jeffrey R.; Altan-Bonnet, Gregoire] Mem Sloan Kettering Canc Ctr, ImmunoDynam Grp, Program Computat Biol & Immunol, New York, NY 10065 USA.
[Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, Program Syst Immunol & Infect Dis Modeling,NIH,De, Bethesda, MD 20892 USA.
RP Altan-Bonnet, G (reprint author), Mem Sloan Kettering Canc Ctr, ImmunoDynam Grp, Program Computat Biol & Immunol, 1275 York Ave,Box 460, New York, NY 10065 USA.
EM altanbonnet@cbio.mskcc.org
RI Dorfman, Jeffrey/B-4854-2011
OI Dorfman, Jeffrey/0000-0001-9938-8911
FU Intramural NIH HHS [Z01 AI000403-24]
NR 22
TC 158
Z9 159
U1 1
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 22
PY 2008
VL 321
IS 5892
BP 1081
EP 1084
DI 10.1126/science.1158013
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339RL
UT WOS:000258594900038
PM 18719282
ER
PT J
AU Zezula, J
Singer, L
Przybyl, AK
Hashimoto, A
Dersch, CM
Rothman, RB
Deschamps, J
Lee, YS
Jacobson, AE
Rice, KC
AF Zezula, Josef
Singer, Lisa
Przybyl, Anna K.
Hashimoto, Akihiro
Dersch, Christina M.
Rothman, Richard B.
Deschamps, Jeffrey
Lee, Yong Sok
Jacobson, Arthur E.
Rice, Kenner C.
TI Synthesis and pharmacological effects of the enantiomers of the
N-phenethyl analogues of the ortho and para e- and f-oxide-bridged
phenylmorphans
SO ORGANIC & BIOMOLECULAR CHEMISTRY
LA English
DT Article
ID RECEPTOR-MEDIATED PHENOMENA; PROBES; ISOMERS;
5-(3-HYDROXYPHENYL)-N-PHENYLETHYLMORPHAN;
(-)-5-META-HYDROXYPHENYL-2-METHYLMORPHAN; 5-(META-HYDROXYPHENYL)MORPHAN;
5-PHENYLMORPHANS; DERIVATIVES; ANTAGONISTS; NITRATION
AB The N-phenethyl analogues of (1R*,4aR*,9aS*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-6-ol and 8-ol and (1R*,4aR*,9aR*)-2-phenethyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2.3-c]pyridin-6-ol and 8-ol, the ortho- (43) and para-hydroxy e- (20), and f-oxide-bridged 5-phenylmorphans (53 and 26) were prepared in racemic and enantiomerically pure forms from a common precursor, the quaternary salt 12. Optical resolutions were accomplished by salt formation with suitable enantiomerically pure chiral acids or by preparative HPLC on a chiral support. The N-phenethyl (-)- para-e enantiomer (1S,4aS,9aR-(-)-20) was found to be a p-opioid agonist with morphine-like antinociceptive activity in a mouse assay. In contrast, the N-phenethyl (-)-ortho-f enantiomer (1R,4aR,9aR-(-)-53) had good affinity for the g-opioid receptor (K(i) = 7 nM) and was found to be a p-antagonist both in the [(35)S]GTP-gamma-S assay and in vivo. The molecular structures of these rigid enantiomers were energy minimized with density functional theory at the level B3LYP/6-31G* level, and then overlaid on a known potent p-agonist. This superposition study suggests that the agonist activity of the oxide-bridged 5-phenylmorphans can be attributed to formation of a seven membered ring that is hypothesized to facilitate a proton transfer from the protonated nitrogen to a proton acceptor in the p-opioid receptor.
C1 [Zezula, Josef; Singer, Lisa; Przybyl, Anna K.; Hashimoto, Akihiro; Jacobson, Arthur E.; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Drug Design & Synth Sect, Rockville, MD 20852 USA.
[Zezula, Josef; Singer, Lisa; Przybyl, Anna K.; Hashimoto, Akihiro; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, Natl Inst Hlth, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Dersch, Christina M.; Rothman, Richard B.] Natl Inst Drug Abuse, Natl Inst Hlth, Addict Res Ctr,Chem Biol Res Branch, DHHS,Clin Psychopharmacol Sect, Baltimore, MD 21224 USA.
[Deschamps, Jeffrey] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA.
[Lee, Yong Sok] NIH, Ctr Mol Modelling, Div Computat Biosci, CIT,DHHS, Bethesda, MD 20892 USA.
RP Rice, KC (reprint author), Natl Inst Drug Abuse, Chem Biol Res Branch, Drug Design & Synth Sect, 5625 Fishers Lane,Room 4NO3,MSC 9415, Rockville, MD 20852 USA.
EM kennerr@mail.nih.gov
OI Deschamps, Jeffrey/0000-0001-5845-0010
FU National Institute on Drug Abuse (NIDA); National Institute of Alcohol
Abuse and Alcoholism; National Institute of Diabetes and Digestive and
Kidney Diseases; NIH Intramural Research Program; NIDA [YI-DA6002]
FX The research of the Drug Design and Synthesis Section, CBRB, NIDA &
NIAAA, was supported by the NIH Intramural Research Programs of the
National Institute on Drug Abuse (NIDA), the National Institute of
Alcohol Abuse and Alcoholism, and the National Institute of Diabetes and
Digestive and Kidney Diseases, and NIDA supported the research of the
Clinical Psychopharmacology Section. The quantum chemical study utilized
the high-performance computer capabilities of the Helix Systems at the
NIH (http://helix.nih.gov) and the PC/LINUX clusters at the Center for
Molecular Modeling of the NIH (http://cit.nih.gov), and this research
was supported by the NIH Intramural Research Program through the Center
for Information Technology. We thank Dr John Lloyd (NIDDK) for the mass
spectral data, and we thank NIDA for support of the X-ray
crystallographic studies (NIDA contract YI-DA6002). We also thank the
Drug Evaluation Committee, College on Problems of Drug Dependence
(Biological Coordinator, Dr A. Coop, University of Maryland, College of
Pharmacy, Baltimore, MD) for the data obtained from in vivo assays
carried out at Virginia Commonwealth University (Dr M. Aceto and L.
Harris), and Dr Leen Maat, Delft University of Technology, The
Netherlands, for advice on the nomenclature of some of the compounds.
NR 29
TC 10
Z9 10
U1 0
U2 6
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1477-0520
J9 ORG BIOMOL CHEM
JI Org. Biomol. Chem.
PD AUG 21
PY 2008
VL 6
IS 16
BP 2868
EP 2883
DI 10.1039/b803433h
PG 16
WC Chemistry, Organic
SC Chemistry
GA 342FM
UT WOS:000258770000005
PM 18688479
ER
PT J
AU Yoshimura, Y
Ohta, M
Imahori, T
Imamichi, T
Takahata, H
AF Yoshimura, Yuichi
Ohta, Masatoshi
Imahori, Tatsushi
Imamichi, Tomozumi
Takahata, Hiroki
TI A new entry to carbocyclic nucleosides: Oxidative coupling reaction of
cycloalkenylsilanes with a nucleobase mediated by hypervalent iodine
reagent
SO ORGANIC LETTERS
LA English
DT Article
ID ANTIVIRAL ACTIVITY; DERIVATIVES; ALLYLATION; VIRUS; HIV
AB A novel method for synthesizing carbocyclic nucleosides was developed. The new synthesis includes a direct coupling reaction of cycloalkenylsilanes with a silylated nucleobase catalyzed by a hypervalent iodine reagent. By applying the method, a novel carbocyclic cytidine derivative having bis(hydroxymethyl)cyclohexene as a pseudosugar moiety, designed as a potential anti-HIV agent, was successfully synthesized.
C1 [Yoshimura, Yuichi; Ohta, Masatoshi; Imahori, Tatsushi; Takahata, Hiroki] Tohoku Pharmaceut Univ, Fac Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9818558, Japan.
[Imamichi, Tomozumi] NIAID, Lab Human Retrovirol, Appl & Dev Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Yoshimura, Y (reprint author), Tohoku Pharmaceut Univ, Fac Pharmaceut Sci, Aoba Ku, 4-4-1 Komatsushima, Sendai, Miyagi 9818558, Japan.
EM yoshimura@tohoku-pharm.ac.jp
NR 17
TC 16
Z9 16
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1523-7060
J9 ORG LETT
JI Org. Lett.
PD AUG 21
PY 2008
VL 10
IS 16
BP 3449
EP 3452
DI 10.1021/ol8012155
PG 4
WC Chemistry, Organic
SC Chemistry
GA 335LW
UT WOS:000258293100018
PM 18613695
ER
PT J
AU Beres, SB
Sesso, R
Pinto, SWL
Hoe, NP
Porcella, SF
Deleo, FR
Musser, JM
AF Beres, Stephen B.
Sesso, Ricardo
Pinto, Sergio Wyton L.
Hoe, Nancy P.
Porcella, Stephen F.
Deleo, Frank R.
Musser, James M.
TI Genome Sequence of a Lancefield Group C Streptococcus zooepidemicus
Strain Causing Epidemic Nephritis: New Information about an Old Disease
SO PLOS ONE
LA English
DT Article
ID GROUP-A STREPTOCOCCUS; ACUTE POSTSTREPTOCOCCAL GLOMERULONEPHRITIS; EQUI
SUBSP ZOOEPIDEMICUS; GRAM-NEGATIVE BACTERIA; TOXIC-SHOCK-SYNDROME;
TRANSFER-RNA GENES; ALPHA-ENOLASE; NEPHRITOGENIC STREPTOCOCCI; PLASMIN
RECEPTOR; INVASIVE STRAINS
AB Outbreaks of disease attributable to human error or natural causes can provide unique opportunities to gain new information about host-pathogen interactions and new leads for pathogenesis research. Poststreptococcal glomerulonephritis (PSGN), a sequela of infection with pathogenic streptococci, is a common cause of preventable kidney disease worldwide. Although PSGN usually occurs after infection with group A streptococci, organisms of Lancefield group C and G also can be responsible. Despite decades of study, the molecular pathogenesis of PSGN is poorly understood. As a first step toward gaining new information about PSGN pathogenesis, we sequenced the genome of Streptococcus equi subsp. zooepidemicus strain MGCS10565, a group C organism that caused a very large and unusually severe epidemic of nephritis in Brazil. The genome is a circular chromosome of 2,024,171 bp. The genome shares extensive gene content, including many virulence factors, with genetically related group A streptococci, but unexpectedly lacks prophages. The genome contains many apparently foreign genes interspersed around the chromosome, consistent with the presence of a full array of genes required for natural competence. An inordinately large family of genes encodes secreted extracellular collagen-like proteins with multiple integrin-binding motifs. The absence of a gene related to speB rules out the long-held belief that streptococcal pyrogenic exotoxin B or antibodies reacting with it singularly cause PSGN. Many proteins previously implicated in GAS PSGN, such as streptokinase, are either highly divergent in strain MGCS10565 or are not more closely related between these species than to orthologs present in other streptococci that do not commonly cause PSGN. Our analysis provides a comparative genomics framework for renewed appraisal of molecular events underlying APSGN pathogenesis.
C1 [Beres, Stephen B.; Musser, James M.] Methodist Hosp, Ctr Mol & Translat Human Infect Dis Res, Res Inst, Houston, TX 77030 USA.
[Sesso, Ricardo] Univ Fed Sao Paulo, Escola Paulista Med, Div Nephrol, Sao Paulo, Brazil.
[Pinto, Sergio Wyton L.] Hosp Sao Joao Deus, Div Nephrol, Divinopolis, Brazil.
[Hoe, Nancy P.] NIH, Off Res Serv, Div Occupat Hlth & Safety, Hamilton, MT USA.
[Porcella, Stephen F.; Deleo, Frank R.] NIH, NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, Hamilton, MT USA.
RP Beres, SB (reprint author), Methodist Hosp, Ctr Mol & Translat Human Infect Dis Res, Res Inst, 6535 Fannin, Houston, TX 77030 USA.
EM jmmusser@tmhs.org
RI Sesso, Ricardo /B-4767-2013;
OI Sesso, Ricardo/0000-0002-1062-0073; DeLeo, Frank/0000-0003-3150-2516
FU National Institute of Allergy and Infectious Diseases [UO1-60595]
FX This study was supported in part by grant UO1-60595 from the National
Institute of Allergy and Infectious Diseases (to JMM).
NR 142
TC 65
Z9 300
U1 0
U2 10
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 AUG 21
PY 2008
VL 3
IS 8
AR e3026
DI 10.1371/journal.pone.0003026
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 422KO
UT WOS:000264426800005
PM 18716664
ER
PT J
AU Snow, AL
Oliveira, JB
Zheng, LX
Dale, JK
Fleisher, TA
Lenardo, MJ
AF Snow, Andrew L.
Oliveira, Joao B.
Zheng, Lixin
Dale, Janet K.
Fleisher, Thomas A.
Lenardo, Michael J.
TI Critical role for BIM in T cell receptor restimulation-induced death
SO BIOLOGY DIRECT
LA English
DT Article
ID FAMILY-MEMBER BIM; AUTOIMMUNE-LYMPHOPROLIFERATIVE-SYNDROME; LYMPHOCYTE
APOPTOSIS; BH3-ONLY PROTEIN; IMMUNE-RESPONSE; VIRAL-INFECTION;
REGULATORS BIM; SELF-ANTIGEN; FAS; ACTIVATION
AB Background: Upon repeated or chronic antigen stimulation, activated T cells undergo a T cell receptor (TCR)-triggered propriocidal cell death important for governing the intensity of immune responses. This is thought to be chiefly mediated by an extrinsic signal through the Fas-FasL pathway. However, we observed that TCR restimulation still potently induced apoptosis when this interaction was blocked, or genetically impaired in T cells derived from autoimmune lymphoproliferative syndrome (ALPS) patients, prompting us to examine Fas-independent, intrinsic signals.
Results: Upon TCR restimulation, we specifically noted a marked increase in the expression of BIM, a pro-apoptotic Bcl-2 family protein known to mediate lymphocyte apoptosis induced by cytokine withdrawal. In fact, T cells from an ALPS type IV patient in which BIM expression is suppressed were more resistant to restimulation-induced death. Strikingly, knockdown of BIM expression rescued normal T cells from TCR-induced death to as great an extent as Fas disruption.
Conclusion: Our data implicates BIM as a critical mediator of apoptosis induced by restimulation as well as growth cytokine withdrawal. These findings suggest an important role for BIM in eliminating activated T cells even when IL-2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis.
C1 [Oliveira, Joao B.; Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
[Snow, Andrew L.; Zheng, Lixin; Lenardo, Michael J.] NIAID, Mol Dev Sect, Immunol Lab, Bethesda, MD 20892 USA.
[Dale, Janet K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Oliveira, JB (reprint author), NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
EM snowa@niaid.nih.gov; oliveirajb@lim56.fm.usp.br; lzheng@niaid.nih.gov;
jdale@mail.nih.gov; tfleishe@mail.cc.nih.gov; mlenardo@niaid.nih.gov
OI Oliveira, Joao/0000-0001-9388-8173; Snow, Andrew/0000-0002-8728-6691
FU NIH; National Institute of Allergy and Infectious Diseases; Pharmacology
Research Associate Training (PRAT) Program; National Institute of
General Medical Sciences
FX The authors wish to thank the patients for their participation in NIH
ALPS studies, T. Myers and Q. Su in the NIAID Research Technologies
Branch for help with microarray hybridization and analysis, K. Nagashima
and J. de la Cruz at SAIC-Frederick for electron microscopy analysis,
and members of the Lenardo laboratory for helpful suggestions. This
research was supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases. A. L. S. was
supported by a Pharmacology Research Associate Training (PRAT) Program
Fellowship, National Institute of General Medical Sciences.
NR 47
TC 26
Z9 26
U1 0
U2 1
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 AUG 20
PY 2008
VL 3
AR 34
DI 10.1186/1745-6150-3-34
PG 17
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 345RI
UT WOS:000259013700001
PM 18715501
ER
PT J
AU Brand, F
Klutz, AM
Jacobson, KA
Fredholm, BB
Schulte, G
AF Brand, Frank
Klutz, Athena M.
Jacobson, Kenneth A.
Fredholm, Bertil B.
Schulte, Gunnar
TI Adenosine A(2A) receptor dynamics studied with the novel fluorescent
agonist Alexa488-APEC
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE G protein-coupled receptor; endocytosis; cyclic AMP; CREB; nucleoside;
Rab5; clathrin
ID PROTEIN-COUPLED RECEPTORS; SINGLE LIVING CELLS; HAMSTER OVARY CELLS;
INDUCED DESENSITIZATION; DOPAMINE-D-2 RECEPTORS; MEDIATED ENDOCYTOSIS;
BETA-ARRESTIN; IN-VITRO; PHARMACOLOGY; ACTIVATION
AB G protein-coupled receptors, such as the adenosine A(2A) receptor, are dynamic proteins, which undergo agonist-dependent redistribution from the cell surface to intracellular membranous compartments, such as endosomes. In order to study the kinetics of adenosine A(2A) receptor redistribution in living cells, we synthesized a novel fluorescent agonist, Alexa488-APEC Alexa488-APEC binds to adenosine A(2A) (K-i=149 +/- 27 nM) as well as A(3) receptors (K-i=240 +/- 160 nM) but not to adenosine A, receptors. Further, we characterized the dose-dependent increase in Alexa488-APEC-induced cAMP production as well as cAMP response element binding (CREB) protein phosphorylation, verifying the ligand's functionality at adenosine A(2A) but not AN receptors. In live-cell imaging studies, Alexa488-APEC-induced adenosine A(2A) receptor internalization, which was blocked by the competitive reversible antagonist ZM 241385 and hyperosmolaric sucrose. Further, internalized adenosine A(2A) receptors co-localized with clathrin and Rab5, indicating that agonist stimulation promotes adenosine A(2A) receptor uptake through a clathrin-dependent mechanism to Rab5-positive endosomes. The basic characterization of Alexa488-APEC described here showed that it provides a useful tool for tracing adenosine A(2A) receptors in vitro. (c) 2008 Elsevier B.V. All rights reserved.
C1 [Brand, Frank; Schulte, Gunnar] Karolinska Inst, Dept Physiol & Pharmacol, Sect Receptor Biol & Signaling, S-17177 Stockholm, Sweden.
[Klutz, Athena M.; Jacobson, Kenneth A.] NIDDK, NIH, Bethesda, MD USA.
[Fredholm, Bertil B.] Karolinska Inst, Dept Physiol & Pharmacol, Mol Pharmacol Sect, S-17177 Stockholm, Sweden.
RP Schulte, G (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, Sect Receptor Biol & Signaling, Nanna Svartz Vag 2, S-17177 Stockholm, Sweden.
EM gunnar.schulte@ki.se
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Swedish Brain Research Foundation; Swedish Research Council; Karolinska
Institutet; Alex and Eva Wallstrom Foundation; Tore Nilsons Foundation
for Medical Research; Jeanssons Foundation; Ake Wiberg Foundation; Signe
& Olof Wallenius Foundation; Lakaresallskapet/Socialstyrelsen; NIH,
National Institute of Diabetes and Digestive and Kidney Diseases
FX G.S. was supported by the Swedish Brain Research Foundation, the Swedish
Research Council and Karolinska Institutet. The work was supported in
part by Alex and Eva Wallstrom Foundation, Tore Nilsons Foundation for
Medical Research, Jeanssons Foundation, Ake Wiberg Foundation, Signe &
Olof Wallenius Foundation, Lakaresallskapet/Socialstyrelsen and the
Swedish Research Council. We thank Prof. A. Arner for sharing his
confocal microscope. We thank Janet Holmon for proofreading the
manuscript. This research was supported in part by the Intramural
Research Program of the NIH, National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 46
TC 21
Z9 21
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD AUG 20
PY 2008
VL 590
IS 1-3
BP 36
EP 42
DI 10.1016/j.ejphar.2008.05.036
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 341KF
UT WOS:000258712500005
PM 18603240
ER
PT J
AU Lynn, EG
McLeod, CJ
Gordon, JP
Bao, JJ
Sack, MN
AF Lynn, Edward G.
McLeod, Christopher J.
Gordon, Jeffrey P.
Bao, Jianjun
Sack, Michael N.
TI SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via
regulation of 14-3-3 zeta and BAD in H9c2 cells
SO FEBS LETTERS
LA English
DT Article
DE SIRT2; BAD; 14-3-3 zeta; H9c2 cells; anoxia-reoxygenation
ID HISTONE DEACETYLASE; OXIDATIVE STRESS; APOPTOSIS; RESTRICTION
AB Knockdown or inhibition of SIRT2 enhances biological stress-tolerance. We extend this phenotype showing that SIRT2 knockdown reduces anoxia-reoxygenation injury in H9c2 cells. Gene array analysis following SIRT2 siRNA knockdown identifies 14-3-3 zeta as the most robustly induced gene. SIRT2 knockdown evokes induction of this chaperone, facilitating cytosolic sequestration of BAD with a corresponding reduction in mitochondrial BAD localization. Concurrent siRNA against SIRT2 and 14-3-3 zeta abolishes the SIRT2-depleted cytoprotective phenotype. SIRT2 functions to moderate cellular stress-tolerance, in part, by modulating the levels of 14-3-3 zeta with the concordant control of BAD subcellular localization. Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.
C1 [Lynn, Edward G.; McLeod, Christopher J.; Gordon, Jeffrey P.; Bao, Jianjun; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
OI Lynn, Edward/0000-0002-8011-5558
FU National Institutes of Health
FX We thank Nalini Raghavachari and Xiuli Xu from the NHLBI Genomics Core
for assistance with the gene array experiments and analyses, Dr.
Christian A Combs for assistance with confocal microscopy and J. Philip
McCoy Jr. from the NHLBI Flow Cytometry Core for assistance. This work
was supported by funding from the Division of Intramural Research of the
NHLBI of the National Institutes of Health.
NR 15
TC 34
Z9 35
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD AUG 20
PY 2008
VL 582
IS 19
BP 2857
EP 2862
DI 10.1016/j.febslet.2008.07.016
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 347EK
UT WOS:000259123200007
PM 18640115
ER
PT J
AU Irwin, ML
Smith, AW
McTiernan, A
Ballard-Barbash, R
Cronin, K
Gilliland, FD
Baumgartner, RN
Baumgartner, KB
Bernstein, L
AF Irwin, Melinda L.
Smith, Ashley Wilder
McTiernan, Anne
Ballard-Barbash, Rachel
Cronin, Kathy
Gilliland, Frank D.
Baumgartner, Richard N.
Baumgartner, Kathy B.
Bernstein, Leslie
TI Influence of pre- and postdiagnosis physical activity on mortality in
breast cancer survivors: The health, eating, activity, and lifestyle
study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID EXERCISE ACTIVITY; WEIGHT-GAIN; DIAGNOSIS; WOMEN; RECURRENCE; OBESITY;
RISK
AB Purpose
To investigate the association between pre- and postdiagnosis physical activity ( as well as change in prediagnosis to postdiagnosis physical activity) and mortality among women with breast cancer.
Patients and Methods
This was a prospective observational study of 933 women enrolled onto the Health, Eating, Activity, and Lifestyle Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or September 2004, whichever came first. The primary outcomes measured were total deaths and breast cancer deaths. The primary exposures were physical activity in the year before and 2 years after diagnosis and the pre- to postdiagnosis change in physical activity.
Results
Compared with inactive women, the multivariable hazard ratios (HRs) for total deaths for women expending at least 9 metabolic equivalent hours per week ( approximately 2 to 3 h/wk of brisk walking) were 0.69 ( 95% Cl, 0.45 to 1.06; P = .045) for those active in the year before diagnosis and 0.33 (95% Cl, 0.15 to 0.73; P = .046) for those active 2 years after diagnosis. Compared with women who were inactive both before and after diagnosis, women who increased physical activity after diagnosis had a 45% lower risk of death (HR = 0.55; 95% Cl, 0.22 to 1.38), and women who decreased physical activity after diagnosis had a four-fold greater risk of death (HR = 3.95; 95% Cl, 1.45 to 10.50).
Conclusion
Moderate-intensity physical activity after a diagnosis of breast cancer may improve prognosis.
C1 [Irwin, Melinda L.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Univ So Calif, Los Angeles, CA USA.
City Hope Natl Med Ctr, Div Populat Sci, Duarte, CA 91010 USA.
Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
RP Irwin, ML (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA.
EM melinda.irwin@yale.edu
FU NCI NIH HHS [N01-CN-75036-20, N01-CN-05228, N01-PC-67010, T32 CA09661];
NCRR NIH HHS [M01-RR-00037, M01-RR-0997]
NR 22
TC 205
Z9 210
U1 2
U2 11
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2008
VL 26
IS 24
BP 3958
EP 3964
DI 10.1200/JCO.2007.15.9822
PG 7
WC Oncology
SC Oncology
GA 338RN
UT WOS:000258526200010
PM 18711185
ER
PT J
AU Brown, AP
Wendler, DS
Camphausen, KA
Miller, FG
Citrin, D
AF Brown, Aaron P.
Wendler, David S.
Camphausen, Kevin A.
Miller, Franklin G.
Citrin, Deborah
TI Performing nondiagnostic research biopsies in irradiated tissue: A
review of scientific, clinical, and ethical considerations
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID INVASIVE BLADDER-CANCER; EXTERNAL-BEAM RADIOTHERAPY; COMBINED-MODALITY
PROGRAM; PHASE-II TRIAL; RADIATION-THERAPY; NEEDLE-BIOPSY; ORGAN
PRESERVATION; PROSTATE-CANCER; NEOADJUVANT CHEMORADIOTHERAPY;
NASOPHARYNGEAL CARCINOMA
AB Purpose
Recent development of drugs that target specific pathways in tumors has increased scientific interest in studying drug effects on tumor tissue. As a result, biopsies have become an important part of many early-phase clinical trials. Performing nondiagnostic tumor biopsies raises technical and ethical concerns mostly related to the use of a potentially harmful procedure with no potential benefit to the patient. This issue is complicated by uncertainty about whether performing biopsies in irradiated fields adds significant risk. This article reviews the clinical, scientific, and ethical considerations involved in performing nondiagnostic tumor biopsies in competent adults for research purposes, with a focus on biopsies performed in the setting of therapeutic irradiation.
Methods
Clinical trials that performed biopsies during or within 4 months of the completion of radiotherapy were identified with a literature review.
Results T
wenty-nine studies with 2,160 patients were identified. Sixteen of 29 studies reported adverse events (AEs) but did not report active evaluation for biopsy complications. Ten studies did not mention AEs within the study report. At least three studies actively evaluated patients for biopsy complications. Taking this into consideration, 17 (> 1%) of 2,160 patients were reported to have biopsy complications, although reporting of AEs was suboptimal in most studies.
Conclusion
Limited data suggest that biopsies can be performed in irradiated tissues without clinically significant excess risk. Ongoing and future trials including nondiagnostic research biopsies should record and report AEs related to this procedure to provide additional data on safety and toxicity.
C1 [Citrin, Deborah] NCI, Radiat Oncol Branch, Sect Imaging & Mol Therapeut, Ctr Canc Res, Bethesda, MD 20892 USA.
NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
NIH, Clin Res Training Program, Off Director, Bethesda, MD 20892 USA.
RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, Sect Imaging & Mol Therapeut, Ctr Canc Res, 10 CRC,B2-3500, Bethesda, MD 20892 USA.
EM citrind@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010849-01]
NR 62
TC 19
Z9 19
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2008
VL 26
IS 24
BP 3987
EP 3994
DI 10.1200/JCO.2008.16.9896
PG 8
WC Oncology
SC Oncology
GA 338RN
UT WOS:000258526200014
PM 18711189
ER
PT J
AU Volkow, ND
Wang, GJ
Telang, F
Fowler, JS
Logan, J
Wong, C
Ma, J
Pradhan, K
Tomasi, D
Thanos, PK
Ferre, S
Jayne, M
AF Volkow, Nora D.
Wang, Gene-Jack
Telang, Frank
Fowler, Joanna S.
Logan, Jean
Wong, Christopher
Ma, Jim
Pradhan, Kith
Tomasi, Dardo
Thanos, Peter K.
Ferre, Sergi
Jayne, Millard
TI Sleep deprivation decreases binding of [C-11]raclopride to dopamine
D-2/D-3 receptors in the human brain
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dopamine transporters; striatum; thalamus; visual attention; PET;
circadian rhythms
ID VENTRAL TEGMENTAL AREA; EYE BLINK RATE; WORKING-MEMORY; RAT-BRAIN;
COGNITIVE PERFORMANCE; PARKINSONS-DISEASE; DAYTIME SLEEPINESS; WAKE
REGULATION; TRANSPORTER; STIMULANTS
AB Sleep deprivation can markedly impair human performance contributing to accidents and poor productivity. The mechanisms underlying this impairment are not well understood, but brain dopamine systems have been implicated. Here, we test whether one night of sleep deprivation changes dopamine brain activity. We studied 15 healthy subjects using positron emission tomography and [C-11] raclopride (dopamineD(2)/D-3 receptor radioligand) and [C-11] cocaine (dopamine transporter radioligand). Subjects were tested twice: after one night of rested sleep and after one night of sleep deprivation. The specific binding of [C-11] raclopride in the striatum and thalamus were significantly reduced after sleep deprivation and the magnitude of this reduction correlated with increases in fatigue (tiredness and sleepiness) and with deterioration in cognitive performance (visual attention and working memory). In contrast, sleep deprivation did not affect the specific binding of [C-11] cocaine in the striatum. Because [C-11] raclopride competes with endogenous dopamine for binding to D-2/D-3 receptors, we interpret the decreases in binding to reflect dopamine increases with sleep deprivation. However, we cannot rule out the possibility that decreased [C-11] raclopride binding reflects decreases in receptor levels or affinity. Sleep deprivation did not affect dopamine transporters (target for most wake-promoting medications) and thus dopamine increases are likely to reflect increases in dopamine cell firing and/or release rather than decreases in dopamine reuptake. Because dopamine-enhancing drugs increase wakefulness, we postulate that dopamine increases after sleep deprivation is a mechanism by which the brain maintains arousal as the drive to sleep increases but one that is insufficient to counteract behavioral and cognitive impairment.
C1 [Volkow, Nora D.; Ferre, Sergi] NIDA, Bethesda, MD 20892 USA.
[Volkow, Nora D.; Telang, Frank; Ma, Jim; Thanos, Peter K.; Jayne, Millard] NIAAA, Bethesda, MD 20892 USA.
[Wang, Gene-Jack; Fowler, Joanna S.; Logan, Jean; Wong, Christopher; Pradhan, Kith; Tomasi, Dardo] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
RI Sanguansri, Luz/B-6630-2011; Ferre, Sergi/K-6115-2014; Tomasi,
Dardo/J-2127-2015;
OI Sanguansri, Luz/0000-0003-1908-7604; Ferre, Sergi/0000-0002-1747-1779;
Logan, Jean/0000-0002-6993-9994
FU Intramural NIH HHS [Z01 AA000550-04]
NR 54
TC 74
Z9 74
U1 0
U2 12
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 AUG 20
PY 2008
VL 28
IS 34
BP 8454
EP 8461
DI 10.1523/JNEUROSCI.1443-08.2008
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 339US
UT WOS:000258603400009
PM 18716203
ER
PT J
AU London, RE
Wingad, BD
Mueller, GA
AF London, Robert E.
Wingad, Brett D.
Mueller, Geoffrey A.
TI Dependence of amino acid side chain (13)C shifts on dihedral angle:
Application to conformational analysis
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PROTEIN-STRUCTURE DETERMINATION; CARBON-13 MAGNETIC RESONANCE; COLI
DIHYDROFOLATE-REDUCTASE; DNA-POLYMERASE-LAMBDA; MALATE SYNTHASE-G;
CHEMICAL-SHIFTS; SEQUENCE HOMOLOGY; AB-INITIO; MECHANISTIC IMPLICATIONS;
SECONDARY STRUCTURE
AB Chemical shift data from the BiomagResDataBank and conformational data derived from the protein data bank have been correlated in order to explore the conformational dependence of side chain (13)C resonance shifts. Consistent with predictions based on steric compression, upfield shifts for C gamma resonances of Thr, Val, Ile, Leu, Met, Arg, Lys, Glu, and Gln residues correlate with both the number of heavy atom (nonproton) gamma-substituents and with gauche conformational orientations of gamma-substituents. The (13)C shift/conformation correlations are most apparent for C gamma carbons but also can be observed at positions further from the backbone. Intraresidue steric conflict leads to a correlation between upfield-shifted side chain (13)C resonances and statistically lower probabilities in surveys of protein side chain conformation. Illustrative applications to the DNA pol lambda lyase domain and to dihydrofolate reductase are discussed. In the latter case, (13)C shift analysis indicates that the conformation of the remote residue V119 on the F-PG loop is correlated with the redox state of the bound pyridine nucleotide cofactor, providing one basis for discrimination between substrate and product. It is anticipated that (13)C shift data for protein sidechains can provide a useful basis for the analysis of conformational changes even in large, deuterated proteins. Additionally, the large dependence of the leucine methyl shift difference, delta C delta 1-delta C delta 2, on both chi 1 and chi 2 is sufficient to allow this parameter to be used as a restraint in structure calculations if stereospecific assignment data are available.
C1 [London, Robert E.; Wingad, Brett D.; Mueller, Geoffrey A.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP London, RE (reprint author), NIEHS, Struct Biol Lab, TW Alexander Dr,MD MR-01, Res Triangle Pk, NC 27709 USA.
EM london@niehs.nih.gov
FU Intramural NIH HHS [Z01 ES050111-19]
NR 55
TC 48
Z9 48
U1 2
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 20
PY 2008
VL 130
IS 33
BP 11097
EP 11105
DI 10.1021/ja802729t
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 337DO
UT WOS:000258415900054
PM 18652454
ER
PT J
AU Brown, LM
Devesa, SS
Chow, WH
AF Brown, Linda Morris
Devesa, Susan S.
Chow, Wong-Ho
TI Incidence of adenocarcinoma of the esophagus among white Americans by
sex, stage, and age
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; LUNG-CANCER RATES; GASTRIC CARDIA;
UNITED-STATES; BARRETTS-ESOPHAGUS; RISING INCIDENCE; YOUNG MEN; TRENDS;
RISK; PATTERNS
AB Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explored the temporal patterns of this disease among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program. We identified 22759 patients from January 1, 1975, through December 31, 2004, with esophageal cancer, of whom 9526 were diagnosed with adenocarcinoma of the esophagus. Among white men, increases in the incidence of esophageal cancer were largely attributed to a 463% increase in the incidence of adenocarcinoma over this time period, from 1.01 per 100000 person-years (95% confidence interval [Cl] = 0.90 to 1.13) in 1975-1979 to 5.69 per 100000 person-years (95% Cl = 5.47 to 5.91) in 2000-2004. A similar rapid increase was also apparent among white women, among whom the adenocarcinoma rate increased 335%, from 0.17 (95% Cl = 0.13 to 0.21) to 0.74 per 100000 person-years (95% Cl = 0.67 to 0.81), over the same time period. Adenocarcinoma rates rose among white men and women in all stage and age groups, indicating that these increases are real and not an artifact of surveillance.
C1 [Brown, Linda Morris] RTI Int, Rockville, MD 20852 USA.
[Brown, Linda Morris; Devesa, Susan S.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Brown, LM (reprint author), RTI Int, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA.
EM lindabrown@rti.org
FU National Institutes of Health; National Cancer Institute, Division of
Cancer Epidemiology and Genetics
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
to LMB, SSD, and W-HC.
NR 19
TC 345
Z9 350
U1 0
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD AUG 20
PY 2008
VL 100
IS 16
BP 1184
EP 1187
DI 10.1093/jnci/djn211
PG 4
WC Oncology
SC Oncology
GA 344FZ
UT WOS:000258913600012
PM 18695138
ER
PT J
AU Bumb, A
Brechbiel, MW
Choyke, PL
Fugger, L
Eggeman, A
Prabhakaran, D
Hutchinson, J
Dobson, PJ
AF Bumb, A.
Brechbiel, M. W.
Choyke, P. L.
Fugger, L.
Eggeman, A.
Prabhakaran, D.
Hutchinson, J.
Dobson, P. J.
TI Synthesis and characterization of ultra-small superparamagnetic iron
oxide nanoparticles thinly coated with silica
SO NANOTECHNOLOGY
LA English
DT Article
ID MAGNETITE CATIONIC LIPOSOMES; INTRACELLULAR HYPERTHERMIA; CONTRAST
AGENTS; PARTICLES; SIZE; CANCER; ENCAPSULATION; NANOCRYSTALS; BEHAVIOR;
VIVO
AB Ultra-small superparamagnetic iron oxide nanoparticles were synthesized by co-precipitation of iron chloride salts with ammonia and then encapsulated with thin (similar to 2 nm) layers of silica. The particles have been characterized for size, diffraction pattern, surface charge, and magnetic properties. This rapid and economical synthesis has a number of industrial applications; however, the silica-coated particles have been optimized for use in medical applications such as magnetic resonance contrast agents and biosensors, and in DNA capturing, bioseparation and enzyme immobilization.
C1 [Bumb, A.; Dobson, P. J.] Univ Oxford, Kidlington OX5 1PF, Oxon, England.
[Bumb, A.; Brechbiel, M. W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Choyke, P. L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Fugger, L.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, RC Human Immunol Unit, Oxford OX3 9DS, England.
[Eggeman, A.] Univ Oxford, Dept Mat, Oxford OX1 3PH, England.
[Prabhakaran, D.; Hutchinson, J.] Univ Oxford, Dept Phys, Oxford OX1 3PH, England.
RP Dobson, PJ (reprint author), Univ Oxford, Begbroke Sci Pk,Sandy Lane, Kidlington OX5 1PF, Oxon, England.
EM Ambika.Bumb@eng.ox.ac.uk; Peter.Dobson@begbroke.ox.ac.uk
FU Intramural NIH HHS [Z01 SC006353-25, Z01 SC010051-12]
NR 38
TC 59
Z9 61
U1 1
U2 34
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
J9 NANOTECHNOLOGY
JI Nanotechnology
PD AUG 20
PY 2008
VL 19
IS 33
AR 335601
DI 10.1088/0957-4484/19/33/335601
PG 6
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA 324EP
UT WOS:000257500800011
PM 19701448
ER
PT J
AU Harb, N
Archer, TK
Sato, N
AF Harb, Nicole
Archer, Trevor K.
Sato, Noboru
TI The Rho-Rock-Myosin Signaling Axis Determines Cell-Cell Integrity of
Self-Renewing Pluripotent Stem Cells
SO PLOS ONE
LA English
DT Article
ID HUMAN SOMATIC-CELLS; ES CELLS; HUMAN BLASTOCYSTS; DEFINED FACTORS; MOUSE
EPIBLAST; IN-VITRO; DIFFERENTIATION; GTPASES; JUNCTIONS; KINASE
AB Background: Embryonic stem (ES) cells self-renew as coherent colonies in which cells maintain tight cell-cell contact. Although intercellular communications are essential to establish the basis of cell-specific identity, molecular mechanisms underlying intrinsic cell-cell interactions in ES cells at the signaling level remain underexplored.
Methodology/Principal Findings: Here we show that endogenous Rho signaling is required for the maintenance of cell-cell contacts in ES cells. siRNA-mediated loss of function experiments demonstrated that Rock, a major effector kinase downstream of Rho, played a key role in the formation of cell-cell junctional assemblies through regulation of myosin II by controlling a myosin light chain phosphatase. Chemical engineering of this signaling axis by a Rock-specific inhibitor revealed that cell-cell adhesion was reversibly controllable and dispensable for self-renewal of mouse ES cells as confirmed by chimera assay. Furthermore, a novel culture system combining a single synthetic matrix, defined medium, and the Rock inhibitor fully warranted human ES cell self-renewal independent of animal-derived matrices, tight cell contacts, or fibroblastic niche-forming cells as determined by teratoma formation assay.
Conclusions/Significance: These findings demonstrate an essential role of the Rho-Rock-Myosin signaling axis for the regulation of basic cell-cell communications in both mouse and human ES cells, and would contribute to advance in medically compatible xeno-free environments for human pluripotent stem cells.
C1 [Harb, Nicole; Sato, Noboru] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA.
[Archer, Trevor K.] Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC USA.
RP Harb, N (reprint author), Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA.
EM saton@ucr.edu
FU University of California Riverside; Intramural Research Program of the
National Institute of Environmental Health Sciences, NIH [Z01
ES071006-09]
FX N.S. is supported by University of California Riverside. This research
was supported in part by the Intramural Research Program of the National
Institute of Environmental Health Sciences, NIH project #Z01 ES071006-09
(T.K.A.).
NR 62
TC 97
Z9 101
U1 0
U2 9
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 AUG 20
PY 2008
VL 3
IS 8
AR e3001
DI 10.1371/journal.pone.0003001
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 422IM
UT WOS:000264420900026
PM 18714354
ER
PT J
AU Arai, AE
AF Arai, Andrew E.
TI Using magnetic resonance imaging to characterize recent myocardial
injury - Utility in acute coronary syndrome and other clinical scenarios
SO CIRCULATION
LA English
DT Editorial Material
DE editorials; edema; fatty acids; magnetic resonance imaging; myocardial
contraction; scintigraphy
ID INFARCTION; HEART; RISK; EDEMA; BMIPP; SSFP; AREA
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, NIH, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM araia@nih.gov
FU Intramural NIH HHS [Z01 HL004607-09, ZIA HL006136-01]
NR 17
TC 23
Z9 23
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 AUG 19
PY 2008
VL 118
IS 8
BP 795
EP 796
DI 10.1161/CIRCULATIONAHA.108.797373
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 340AS
UT WOS:000258619000001
PM 18711021
ER
PT J
AU Bandmann, O
Singleton, AB
AF Bandmann, O.
Singleton, A. B.
TI Yet another spinocerebellar ataxia - The saga continues
SO NEUROLOGY
LA English
DT Editorial Material
ID ITPR1; DELETION; TYPE-15; SCA15
C1 [Bandmann, O.] Univ Sheffield, Sch Med, Acad Neurol Unit, Sheffield S10 2RX, S Yorkshire, England.
[Singleton, A. B.] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
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 Singleton, Andrew/C-3010-2009
FU Intramural NIH HHS
NR 10
TC 4
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD AUG 19
PY 2008
VL 71
IS 8
BP 542
EP 543
DI 10.1212/01.wnl.0000323932.90720.55
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 338RO
UT WOS:000258526400001
PM 18711106
ER
PT J
AU Baek, K
Liu, X
Ferron, F
Shu, S
Korn, ED
Dominguez, R
AF Baek, Kyuwon
Liu, Xiong
Ferron, Francois
Shu, Shi
Korn, Edward D.
Dominguez, Roberto
TI Modulation of actin structure and function by phosphorylation of Tyr-53
and profilin binding
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE actin phosphorylation; profilin-actin structure; pY53-actin structure;
Dictyostelium discoideum actin; gelsolin-actin structure
ID TYROSINE PHOSPHORYLATION; F-ACTIN; CONFORMATIONAL-CHANGES; DICTYOSTELIUM
CELLS; CRYSTAL-STRUCTURES; DIVALENT-CATION; BETA-ACTIN; FILAMENT;
COMPLEX; MECHANISM
AB On starvation, Dictyostelium cells aggregate to form multicellular fruiting bodies containing spores that germinate when transferred to nutrient-rich medium. This developmental cycle correlates with the extent of actin phosphorylation at Tyr-53 (pY53-actin), which is low in vegetative cells but high in viable mature spores. Here we describe high-resolution crystal structures of pY53-actin and unphosphorylated actin in complexes with gelsolin segment 1 and profilin. In the structure of pY53-actin, the phosphate group on Tyr-53 makes hydrogen-bonding interactions with residues of the DNase 1-binding loop (D-loop) of actin, resulting in a more stable conformation of the D-loop than in the unphosphorylated structures. A more rigidly folded D-loop may explain some of the previously described properties of pY53-actin, including its increased critical concentration for polymerization, reduced rates of nucleation and pointed end elongation, and weak affinity for DNase I. We show here that phosphorylation of Tyr-53 inhibits subtilisin cleavage of the ID-loop and reduces the rate of nucleotide exchange on actin. The structure of profilin-Dictyostelium-actin is strikingly similar to previously determined structures of profilin-beta-actin and profilin-alpha-actin. By comparing this representative set of profilin-actin structures with other structures of actin, we highlight the effects of profilin on the actin conformation. In the profilin-actin complexes, subdomains 1 and 3 of actin close around profilin, producing a 4.7 degrees rotation of the two major domains of actin relative to each other. As a result, the nucleotide cleft becomes moderately more open in the profilin-actin complex, probably explaining the stimulation of nucleotide exchange on actin by profilin.
C1 [Liu, Xiong; Shu, Shi; Korn, Edward D.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Baek, Kyuwon; Ferron, Francois; Dominguez, Roberto] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM edk@nih.gov; droberto@mail.med.upenn.edu
RI Korn, Edward/F-9929-2012
FU National Institutes of Health [GM073791, RR-01646]; Division of
Intramural Research, National Heart, Lung, and Blood Institute; National
Science Foundation [DMR-0225180]; Industrial Macromolecular
Crystallography Association; Department of Energy [W-31-109-Eng-38]
FX This work was supported by National Institutes of Health Grant GM073791
and the Division of Intramural Research, National Heart, Lung, and Blood
Institute. Data collection at the Cornell High Energy Synchrotron Source
and Macromolecular Diffraction facilities was supported by National
Science Foundation Grant DMR-0225180 and National Institutes of Health
Grant RR-01646. Use of IMCA-CAT beamline 17-BM was supported by the
Industrial Macromolecular Crystallography Association through a contract
with the University of Chicago. The Advanced Photon Source was supported
by Department of Energy Contract W-31-109-Eng-38.
NR 44
TC 24
Z9 29
U1 0
U2 5
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 AUG 19
PY 2008
VL 105
IS 33
BP 11748
EP 11753
DI 10.1073/pnas.0805852105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341OM
UT WOS:000258723800031
PM 18689676
ER
PT J
AU Argueso, JL
Westmoreland, J
Mieczkowski, PA
Gawel, M
Petes, TD
Resnick, MA
AF Argueso, Juan Lucas
Westmoreland, James
Mieczkowski, Piotr A.
Gawel, Malgorzata
Petes, Thomas D.
Resnick, Michael A.
TI Double-strand breaks associated with repetitive DNA can reshape the
genome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ectopic recombination; gamma radiation; genome rearrangements;
nonallelic homologous recombination; retrotransposon
ID YEAST SACCHAROMYCES-CEREVISIAE; TRANSPOSABLE ELEMENTS; STRUCTURAL
VARIATION; TY ELEMENTS; CHROMOSOMAL REARRANGEMENTS; RECIPROCAL
TRANSLOCATIONS; DEINOCOCCUS-RADIODURANS; ECTOPIC RECOMBINATION; INDUCED
REPLICATION; REPAIR
AB Ionizing radiation is an established source of chromosome aberrations (CAs). Although double-strand breaks (DSBs) are implicated in radiation-induced and other CAs, the underlying mechanisms are poorly understood. Here, we show that, although the vast majority of randomly induced DSBs in G(2) diploid yeast cells are repaired efficiently through homologous recombination (HR) between sister chromatids or homologous chromosomes, approximate to 2% of all DSBs give rise to CAs. Complete molecular analysis of the genome revealed that nearly all of the CAs resulted from HR between nonallelic repetitive elements, primarily Ty retrotransposons. Nonhomologous end-joining (NHEJ) accounted for few, if any, of the CAs. We conclude that only those DSBs that fall at the 3-5% of the genome composed of repetitive DNA elements are efficient at generating rearrangements with dispersed small repeats across the genome, whereas DSBs in unique sequences are confined to recombinational repair between the large regions of homology contained in sister chromatids or homologous chromosomes. Because repeat-associated DSBs can efficiently lead to CAs and reshape the genome, they could be a rich source of evolutionary change.
C1 [Argueso, Juan Lucas; Mieczkowski, Piotr A.; Gawel, Malgorzata; Petes, Thomas D.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
[Argueso, Juan Lucas] Univ Estadual Campinas, Inst Biol, Dept Genet & Evolucao, BR-13083970 Campinas, SP, Brazil.
[Westmoreland, James] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Petes, TD (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM tom.petes@duke.edu; resnick@niehs.nih.gov
RI Argueso, Juan Lucas/A-5705-2009;
OI Argueso, Juan Lucas/0000-0002-7157-1519
FU National Institutes of Health [GM52319]; National Institute of
Environmental Health Sciences
FX We thank C. Giroux (Wayne State University, Detroit) and A. Gabriel
(Rutgers University, Piscataway, NJ) for sharing unpublished data and A.
Casper, M. Meselson, A. Gabriel, J. Boeke, D. Gordenin, J. Mason, and M.
Shelby for useful discussions and comments on the manuscript. This work
was supported by National Institutes of Health Grant GM52319 (to T.D.P.)
and by intramural research funds from National Institute of
Environmental Health Sciences.
NR 34
TC 114
Z9 115
U1 1
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 19
PY 2008
VL 105
IS 33
BP 11845
EP 11850
DI 10.1073/pnas.0804529105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341OM
UT WOS:000258723800048
PM 18701715
ER
PT J
AU Lettre, G
Sankaran, VG
Bezerra, MAC
Araujo, AS
Uda, M
Sanna, S
Cao, A
Schlessinger, D
Costa, FF
Hirschhorn, JN
Orkin, SH
AF Lettre, Guillaume
Sankaran, Vijay G.
Bezerra, Marcos Andre C.
Araujo, Aderson S.
Uda, Manuela
Sanna, Serena
Cao, Antonio
Schlessinger, David
Costa, Fernando F.
Hirschhorn, Joel N.
Orkin, Stuart H.
TI DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci
associate with fetal hemoglobin levels and pain crises in sickle cell
disease
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE genetic modifier; single nucleotide polymorphism; globin gene regulation
ID GENOME-WIDE ASSOCIATION; RISK-FACTORS; CHROMOSOME 6Q23; GENE; HEIGHT;
CHOLESTEROL; THALASSEMIA; EXPRESSION; VARIANTS; HUMANS
AB Sickle cell disease (SCD) is a debilitating monogenic blood disorder with a highly variable phenotype characterized by severe pain crises, acute clinical events, and early mortality. Interindividual variation in fetal hemoglobin (HbF) expression is a known and potentially heritable modifier of SCD severity. High HbF levels are correlated with reduced morbidity and mortality. Common single nucleotide polymorphisms (SNPs) at the BCL11A and HBS1L-MYB loci have been implicated previously in HbF level variation in nonanemic European populations. We recently demonstrated an association between a BCL11A SNP and HbF levels in one SCD cohort [Uda M, et al. (2008)Proc Natl Acad Sci USA 105:1620-1625]. Here, we genotyped additional BCL11A SNIPS, HBS1L-MYB SNIPS, and an SNP upstream of (G)gamma-globin (HBG2; the Xmnl polymorphism), in two independent SCD cohorts: the African American Cooperative Study of Sickle Cell Disease (CSSCD) and an SCD cohort from Brazil. We studied the effect of these SNIPS on HbF levels and on a measure of SCD-related morbidity (pain crisis rate). We strongly replicated the association between these SNPs and HbF level variation (in the CSSCD, P values range from 0.04 to 2 x 10(-42)). Together, common SNIPS at the BCL11A, HBS1L-MYB, and beta-globin (HBB) loci account for >20% of the variation in HbF levels in SCD patients. We also have shown that HbF-associated SNPs associate with pain crisis rate in SCD patients. These results provide a clear example of inherited common sequence variants modifying the severity of a monogenic disease.
C1 [Lettre, Guillaume; Hirschhorn, Joel N.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Lettre, Guillaume; Hirschhorn, Joel N.] Harvard Univ, Cambridge, MA 02142 USA.
[Lettre, Guillaume; Hirschhorn, Joel N.] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA.
[Lettre, Guillaume; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Sankaran, Vijay G.; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Sankaran, Vijay G.; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Bezerra, Marcos Andre C.; Araujo, Aderson S.] Fdn Hematol & Hemoterapia Pernambuco, BR-52011000 Recife, PE, Brazil.
[Uda, Manuela; Sanna, Serena; Cao, Antonio] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy.
[Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Costa, Fernando F.] Univ Estadual Campinas, Ctr Hemotherapy & Hematol, BR-13083970 Campinas, SP, Brazil.
RP Lettre, G (reprint author), MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
EM lettre@broad.mit.edu; joselh@broad.mit.edu;
stuart_orkin@dfci.harvard.edu
RI Costa, Fernando/D-1566-2012; Sangue, Inct/I-1919-2013;
OI sanna, serena/0000-0002-3768-1749
FU National Institutes of Health (NIH); Howard Hughes Medical Institute
(S.H.O.); Medical Scientist Training Program
FX We thank all of the patients who participated in this study, and we
thank members of our laboratories for comments. We thank D. Nathan, D.
Altshuler, F. Bunn, and M. Weiss for critical reading of this
manuscript; the CSSCD investigators for allowing us access to data and
DNA samples from the study; and S. Coady for support. Funding for this
project was provided by grants from National Institutes of Health (NIH)
and the Howard Hughes Medical Institute (S.H.O.). V.G.S. was supported
by a Medical Scientist Training Program award from the NIH.
NR 30
TC 227
Z9 238
U1 4
U2 20
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 AUG 19
PY 2008
VL 105
IS 33
BP 11869
EP 11874
DI 10.1073/pnas.0804799105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341OM
UT WOS:000258723800052
PM 18667698
ER
PT J
AU Ghosh, MC
Tong, WH
Zhang, D
Ollivierre-Wilson, H
Singh, A
Krishna, MC
Mitchell, JB
Rouault, TA
AF Ghosh, Manik C.
Tong, Wing-Hang
Zhang, Deliang
Ollivierre-Wilson, Hayden
Singh, Anamika
Krishna, Murali C.
Mitchell, James B.
Rouault, Tracey A.
TI Tempol-mediated activation of latent iron regulatory protein activity
prevents symptoms of neurodegenerative disease in IRP2 knockout mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE anemia; axonopathy; ferritin; iron-sulfur cluster; transferrin receptor
ID TARGETED DELETION; MOLECULAR CONTROL; NITRIC-OXIDE; HOMEOSTASIS;
METABOLISM; NITROXIDE; NEUROPROTECTION; DEFICIENT; CLUSTER; ANEMIA
AB In mammals, two homologous cytosolic regulatory proteins, iron regulatory protein 1 (also known as IRP1 and Aco1) and iron regulatory protein 2 (also known as IRP2 and Ireb2), sense cytosolic iron levels and posttranscriptionally regulate iron metabolism genes, including transferrin receptor 1 (TfR1) and ferritin H and L subunits, by binding to iron-responsive elements (IREs) within target transcripts. Mice that lack IRP2 develop microcytic anemia and neurodegeneration associated with functional cellular iron depletion caused by low TfR1 and high ferritin expression. IRP1 knockout (IRP1(-/-)) animals do not significantly misregulate iron metabolism, partly because IRP1 is an iron-sulfur protein that functions mainly as a cytosolic aconitase in mammalian tissues and IRP2 activity increases to compensate for loss of the IRE binding form of IRP1. The neurodegenerative disease of IRP2(-/-) animals progresses slowly as the animals age. In this study, we fed IRP2(-/-) mice a diet supplemented with a stable nitroxide, Tempol, and showed that the progression of neuromuscular impairment was markedly attenuated. In cell lines derived from IRP2(-/-) animals, and in the cerebellum, brainstem, and forebrain of animals maintained on the Tempol diet, IRP1 was converted from a cytosolic aconitase to an IRE binding protein that stabilized the TfR1 transcript and repressed ferritin synthesis. We suggest that Tempol protected IRP2(-/-) mice by disassembling the cytosolic iron-sulfur cluster of IRP1 and activating IRE binding activity, which stabilized the TfR1 transcript, repressed ferritin synthesis, and partially restored normal cellular iron homeostasis in the brain.
C1 [Rouault, Tracey A.] NICHHD, Program Mol Med, Bethesda, MD 20892 USA.
[Krishna, Murali C.; Mitchell, James B.] Natl Canc Inst, Radiat Biol Branch, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), NICHHD, Program Mol Med, Bethesda, MD 20892 USA.
EM rouault@mail.nih.gov
OI Zhang, Deliang/0000-0001-9478-5344
FU National Institute of Child Health and Human Development; National
Cancer Institute
FX We thank Sharon Cooperman, Kavitha Ramaswamy, and Michael Eckhaus for
their help. This work was supported by the intramural programs of the
National Institute of Child Health and Human Development and the
National Cancer Institute.
NR 36
TC 31
Z9 33
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 AUG 19
PY 2008
VL 105
IS 33
BP 12028
EP 12033
DI 10.1073/pnas.0805361105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 341OM
UT WOS:000258723800079
PM 18685102
ER
PT J
AU Lowy, D
AF Lowy, Doug
TI Human papillomavirus, cervical cancer prevention, and more Foreword
SO VACCINE
LA English
DT Editorial Material
C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Lowy, D (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
EM lowyd@mail.nih.gov
NR 13
TC 5
Z9 5
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 AUG 19
PY 2008
VL 26
SU 10
BP III
EP IV
DI 10.1016/j.vaccine.2008.06.032
PG 2
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 364GA
UT WOS:000260323000001
PM 18847562
ER
PT J
AU Giuliano, AR
Tortolero-Luna, G
Ferrer, E
Burchell, AN
de Sanjose, S
Kjaer, SK
Munoz, N
Schiffman, M
Bosch, FX
AF Giuliano, Anna R.
Tortolero-Luna, Guillermo
Ferrer, Elena
Burchell, Ann N.
de Sanjose, Silvia
Kjaer, Susanne Kruger
Munoz, Nubia
Schiffman, Mark
Bosch, F. Xavier
TI Epidemiology of Human Papillomavirus Infection in Men, Cancers other
than Cervical and Benign Conditions
SO VACCINE
LA English
DT Article
DE Cancer; HPV; Men; Women; Infection; Genital warts; Respiratory
papillomatosis; Anogenital cancer
ID VULVAR INTRAEPITHELIAL NEOPLASIA; SQUAMOUS-CELL CARCINOMA; RECURRENT
RESPIRATORY PAPILLOMATOSIS; OF-THE-LITERATURE; RISK HPV TYPES; GENITAL
WARTS; ANOGENITAL CANCER; NATURAL-HISTORY; CONDYLOMATA ACUMINATA;
LARYNGEAL PAPILLOMAS
AB Human papillomavirus (HPV) infection is commonly found in the genital tract of men and women with or without any clinical lesion. The association of HPV DNA with several different ano-genital cancers other than cervical has been reported for the vulva, vagina, anus and penis. HPV DNA has also been identified in head and neck cancers in the oral cavity, the oropharynx and the larynx in both sexes. In men, 80-85% of anal cancers and close to 50% of penile cancers are associated with HPV infection. In women, HPV DNA is prevalent in 36-40% vulvar cancer cases and close to 90% of vaginal cancers. There is limited data available on the natural history and HPV-related diseases in the genital tract in men, although studies are ongoing. Efficacy of HPV vaccines in the prevention of HFV infection and disease among men also remains unknown. Among HPV DNA positive ano-genital cancer cases, HPV-16 is the most frequently found followed distantly by HPV-18. In benign HPV-related diseases such as genital warts or recurrent respiratory papillomatosis HPV-6 and 11, the two most frequent non-oncogenic types, are the predominant types detected. Oncogenic types are rarely detected. In this article we summarize and review studies describing the natural history of HPV infections among men and its impact on HPV related disease in women. We summarize the evidence linking HPV in the epidemiology and etiology of cancers of the vulva, vagina, anus and oropharynx and present recent estimates of the burden of and HPV type distribution in genital warts and in cases of HPV infection of the airways. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Giuliano, Anna R.] H Lee Moffitt Canc Ctr & Res Inst, Risk Assessment Detect & Intervent Program, Tampa, FL USA.
[Tortolero-Luna, Guillermo] Univ Puerto Rico, Ctr Comprehens Canc, Canc Control & Populat Sci Program, San Juan, PR 00936 USA.
[Ferrer, Elena; de Sanjose, Silvia] ICO, CERP, UNIC, Barcelona, Spain.
[Burchell, Ann N.] McGill Univ, Dept Oncol, Div Canc Epidemiol, Montreal, PQ, Canada.
[Burchell, Ann N.] McGill Univ, Dept Epidemiol & Biostat, Div Canc Epidemiol, Montreal, PQ, Canada.
[Kjaer, Susanne Kruger] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Munoz, Nubia] Inst Nacl Cancerol, Bogota, Colombia.
[Schiffman, Mark] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Giuliano, AR (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Risk Assessment Detect & Intervent Program, Tampa, FL USA.
EM anna.giuliano@moffitt.org
RI de Sanjose Llongueras, Silvia/H-6339-2014; BOSCH JOSE, FRANCESC
XAVIER/J-6339-2012;
OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Kjaer,
Susanne/0000-0002-8347-1398
FU US National Institutes Health; National Cancer Institute; Centers for
Disease Control and Prevention; Arizona Disease Control Research
Commission (ADCRC); Instituto de Salud Carlos III [RCESP C03/09, RTICESP
C03/10, RTIC RD06/0020/0095, CIBERESP]; Agencia de Gestio d'Ajuts
Universitaris i de Recerca [2005SGR 00695]; Canadian Cancer Society;
Merck and Co., Inc; Sanofi Pasteur MSD; Merck Sharp Dohme
FX Anna R. Giuliano's work is supported by grants from the US National
Institutes Health, National Cancer Institute, The Centers for Disease
Control and Prevention, and the Arizona Disease Control Research
Commission (ADCRC) provided partial support for the work presented here.
Digene kindly provided STM collection media free of charge and Roche
kindly provided reagents for HPV detection free of charge to some of the
studies presented. F. Xavier Bosch's, Silvia de Sanjose's and Elena
Ferrer's work was partially supported by Spanish public grants from the
Instituto de Salud Carlos III (grants RCESP C03/09, RTICESP C03/10 and
RTIC RD06/0020/0095 and CIBERESP) and from the Agencia de Gestio d'Ajuts
Universitaris i de Recerca (AGAUR 2005SGR 00695). Ann N. Burchell's work
is supported by the Canadian Cancer Society through a research
studentship award from the National Cancer Institute of Canada.;
Disclosed potential conflicts of interest; ARG: Advisory Board (Merck
and Co., Inc); Research Grants (Merck and Co., Inc); Speakers Bureau
(Merck and Co., Inc).; GT-L: Speakers Bureau (Merck Sharp and Dohme).;
EF: Speakers bureau (GlakoSmithKline).; SS: Research Grants (Merck and
Co. Inc., Sanofi Pasteur MSD).; SKK: Advisory Board (Sanofi Pasteur
MSD); Research Grants (Merck and Co., Inc, Sanofi Pasteur MSD); Steering
Committee (Merck and Co., Inc); Travel Grants (Merck and Co., Inc,
Sanofi-Pasteur MSD).; NM: Advisory Board (Merck and Co., Inc, Sanofi
Pasteur MSD); Speakers Bureau (Sanofi Pasteur MSD); Steering Committee
(Merck and Co., Inc).; FXB: Advisory Board (GlaxoSmithKline, Merck Sharp
& Dohme, Sanofi Pasteur MSD); Speakers Bureau (GlaxoSmithKline);
Research Grants (Merck Sharp & Dohme, Sanofi Pasteur MSD).
NR 87
TC 154
Z9 158
U1 1
U2 11
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 AUG 19
PY 2008
VL 26
SU 10
BP K17
EP K28
DI 10.1016/j.vaccine.2008.06.021
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 364GA
UT WOS:000260323000004
PM 18847554
ER
PT J
AU Schiller, JT
Castellsague, X
Villa, LL
Hildesheim, A
AF Schiller, John T.
Castellsague, Xavier
Villa, Luisa L.
Hildesheim, Allan
TI An update of prophylactic human papillomavirus L1 virus-like particle
vaccine clinical trial results
SO VACCINE
LA English
DT Article
DE HPV Clinical trials; Cervical pre-cancer; HPV immunology; HPV vaccines;
Cervical cancer
ID RANDOMIZED CONTROLLED-TRIAL; CELLULAR IMMUNE-RESPONSES; YOUNG-WOMEN;
QUADRIVALENT VACCINE; SUSTAINED EFFICACY; ANTIBODY-RESPONSE; FOLLOW-UP;
TYPE-16; IMMUNOGENICITY; INFECTION
AB This review focuses on recent publications of clinical trials of two prophylactic human papillomavirus (HPV) vaccines: Gardasil (R) (Merck & Co., Inc., Whitehouse Station, NJ USA), a quadrivalent vaccine containing L1 virus-like particles (VLPs) of types -6, 11, 16, and 18, and Cervarix (TM) (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types -16 and 18. In efficacy trials involving young women, both vaccines produced outstanding efficacy against primary and secondary endpoints associated with the vaccine type HPVs and were highly and consistently immunogenic. Both had excellent safety records and, as expected, the most frequent vaccine-related adverse were mild to moderate injection site sequelae. No evidence of waning protection was observed after four years for endpoints examined ranging from incident infection to cervical intraepithelial neoplasia grade 3 associated with the vaccine type HPVs. Gardasil (R) was also highly efficacious at preventing vaginal/vulvar lesions and genital warts. However, neither vaccine demonstrated therapeutic efficacy against prevalent infections or lesions, regardless of the associated HPV type. Cervarix (TM) has shown limited cross-protection against infection with specific closely related types while preliminary results of limited cross-protection have been presented for Gardasil (R). As expected, more limited efficacy was noted for both vaccines when women with prevalent infection were included or endpoints associated with any HPV type were evaluated. Immunological bridging trials involving adolescent girls and boys were also recently published. For both vaccines, serum VLP antibody levels in girls were non-inferior to those generated in young women and antibody response to Gardasil (R) was also non-inferior in boys. The results of these studies have led to the approval of Gardasil (R) and Cervarix (TM) by national regulatory agencies in a number of countries. Published by Elsevier Ltd.
C1 [Schiller, John T.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
[Castellsague, Xavier] ICO, CERP, UNIC, Barcelona, Spain.
[Villa, Luisa L.] Hosp Alemao Oswaldo Cruz, Ludwig Inst Canc Res, Sao Paulo, Brazil.
[Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, Rockville, MD USA.
RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
EM schillej@dc37a.nci.nih.gov
RI Hildesheim, Allan/B-9760-2015; Castellsague Pique, Xavier/N-5795-2014
OI Hildesheim, Allan/0000-0003-0257-2363; Castellsague Pique,
Xavier/0000-0002-0802-3595
FU GlaxoSmithKline; Merck Sharp Dohme.; Sanofi-Pasteur MSD
FX JTS: (Inventor of US government owned patents licensed to
GlaxoSmithKline and Merck and Co., Inc).; XC: Research Grants
(GlaxoSmithKline, Merck Sharp & Dohme., Sanofi-Pasteur MSD); Speakers
Bureau (GlaxoSmithKline, Sanofi-Pasteur MSD); Steering Committee
(GlaxoSmithKline, Sanofi-Pasteur MSD).; LLV: Advisory Board (Merck Sharp
& Dohme).; AH: Research Grants (GlaxoSmithKline).
NR 37
TC 156
Z9 160
U1 4
U2 31
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 AUG 19
PY 2008
VL 26
SU 10
BP K53
EP K61
DI 10.1016/j.vaccine.2008.06.002
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 364GA
UT WOS:000260323000007
PM 18847557
ER
PT J
AU Bosch, FX
Burchell, AN
Schiffman, M
Giuliano, AR
de Sanjose, S
Bruni, L
Tortolero-Luna, G
Kjaer, SK
Munoz, N
AF Xavier Bosch, F.
Burchell, Ann N.
Schiffman, Mark
Giuliano, Anna R.
de Sanjose, Silvia
Bruni, Laia
Tortolero-Luna, Guillermo
Kjaer, Susanne Kruger
Munoz, Nubia
TI Epidemiology and Natural History of Human Papillomavirus Infections and
Type-Specific Implications in Cervical Neoplasia
SO VACCINE
LA English
DT Article
DE HPV; Cervical neoplasia; Epidemiology; Sexual behavior
ID SEXUALLY-TRANSMITTED INFECTIONS; RISK HUMAN-PAPILLOMAVIRUS; CANCER
WORLDWIDE; WOMEN; PREVALENCE; AGE; METAANALYSIS; BEHAVIOR; PERSISTENCE;
MIGRATION
AB Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50-55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45.
Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies.
In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Xavier Bosch, F.; de Sanjose, Silvia; Bruni, Laia] ICO, CERP, UNIC, Barcelona, Spain.
[Burchell, Ann N.] McGill Univ, Dept Oncol, Div Canc Epidemiol, Montreal, PQ, Canada.
[Burchell, Ann N.] McGill Univ, Dept Epidemiol & Biostat, Div Canc Epidemiol, Montreal, PQ, Canada.
[Schiffman, Mark] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Giuliano, Anna R.] H Lee Moffitt Canc Ctr & Res Inst, Risk Assessment Detect & Intervent Program, Tampa, FL USA.
[Tortolero-Luna, Guillermo] Univ Puerto Rico, Ctr Comprehens Canc, Canc Control & Populat Sci Program, San Juan, PR 00936 USA.
[Kjaer, Susanne Kruger] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Munoz, Nubia] Inst Nacl Cancerol, Bogota, Colombia.
RP Bosch, FX (reprint author), ICO, CERP, UNIC, Barcelona, Spain.
EM x.bosch@iconcologia.net
RI de Sanjose Llongueras, Silvia/H-6339-2014; Bruni, Laia/N-5816-2014;
BOSCH JOSE, FRANCESC XAVIER/J-6339-2012;
OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Kjaer,
Susanne/0000-0002-8347-1398; Bruni, Laia/0000-0003-3943-0326
FU Instituto de Salud Carlos III [RCESP C03/09, RTICESP C03/10, RTIC
RD06/0020/0095, CIBERESP]; Agencia de Gestio d'Ajuts Universitaris i de
Recerca [AGAUR 2005SGR 00695]; Canadian Cancer Society; US National
Institutes Health; National Cancer Institute; Centers for Disease
Control and Prevention; Arizona Disease Control Research Commission
(ADCRC); Merck and Co., Inc; Sanofi Pasteur MSD
FX F. Xavier Bosch's and Silvia de Sanjose's work was partially supported
by Spanish public grants from the Instituto de Salud Carlos III (grants
RCESP C03/09, RTICESP C03/10 and RTIC RD06/0020/0095 and CIBERESP) and
from the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR
2005SGR 00695. Ann N. Burchell's work is supported by the Canadian
Cancer Society through a research studentship award from the National
Cancer Institute of Canada. Anna R. Giuliano's work is supported by
grants from the US National Institutes Health, National Cancer
Institute, The Centers for Disease Control and Prevention, and the
Arizona Disease Control Research Commission (ADCRC) provided partial
support for the work presented here. Digene kindly provided STM
collection media free of charge and Roche kindly provided reagents for
HPV detection free of charge to some of the studies presented.;
Disclosed potential conflicts of interest; FXB: Advisory Board
(GlaxoSmithKline, Merck and Co., Inc., Sanofi Pasteur MSD); Speakers
Bureau (GlaxoSmithKline): Research Grants (Merck and Co., Inc., Sanofi
Pasteur MSD).; ARG: Advisory Board (Merck and Co., Inc.); Research
Grants (Merck and Co., Inc.); Speakers Bureau (Merck and Co., Inc.).;
SS: Research Grants (Merck & Co. Inc., Sanofi-Pasteur MSD).; GTL:
Speakers Bureau (Merck Sharp and Dome).; SKK: Advisory Board
(Sanofi-Pasteur MSD); Research Grants (Merck and Co., Inc.,
Sanofi-Pasteur MSD); Steering Committee (Merck and Co., Inc.); Travel
Grants (Merck and Co., Inc., Sanofi-Pasteur MSD); NM: Advisory Board
(Merck and Co., Inc., Sanofi Pasteur MSD); Speakers Bureau (Sanofi
Pasteur MSD); Steering Committee (Merck and Co., Inc.).
NR 51
TC 359
Z9 386
U1 0
U2 26
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 AUG 19
PY 2008
VL 26
SU 10
BP K1
EP K16
DI 10.1016/j.vaccine.2008.05.064
PG 16
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 364GA
UT WOS:000260323000003
PM 18847553
ER
PT J
AU Franco, EL
Tsu, V
Herrero, R
Lazcano-Ponce, E
Hildesheim, A
Munoz, N
Murillo, R
Sanchez, GI
Andrus, JK
AF Franco, Eduardo L.
Tsu, Vivien
Herrero, Rolando
Lazcano-Ponce, Eduardo
Hildesheim, Allan
Munoz, Nubia
Murillo, Raul
Ines Sanchez, Gloria
Andrus, Jon Kim
TI Integration of Human Papillomavirus Vaccination and Cervical Cancer
Screening in Latin America and the Caribbean
SO VACCINE
LA English
DT Article
DE HPV; Vaccination; Latin America; Caribbean; Cervical cancer; Screening;
HPV DNA testing
ID IN-SITU; CYTOLOGY
AB Despite substantial efforts to control cervical cancer by screening, most Latin American and Caribbean countries continue to experience incidence rates of this disease that are much higher than those of other Western countries. The implementation of universal human papillomavirus (HPV) vaccination for young adolescent women is the best prospect for changing this situation. Even though there are financial challenges to overcome to implement such a policy, there is broad political support in the region for adopting universal HPV vaccination. The costs of implementing this policy could be largely alleviated by changing cervical cancer control practices that rely on inefficient use of resources presently allocated to cytology screening, In view of the strong evidence base concerning cervical cancer prevention technologies in the region and the expected impact of vaccination on the performance of cytology. we propose a reformulation of cervical cancer screening policies to be based on HPV testing using validated methods followed by cytologic triage. This approach would serve as the central component of a system that plays the dual role of providing screening and surveillance as integrated and complementary activities sharing centralized resources and coordination. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Franco, Eduardo L.] McGill Univ, Div Canc Epidemiol, Montreal, PQ, Canada.
[Tsu, Vivien] PATH, Seattle, WA USA.
[Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica.
[Lazcano-Ponce, Eduardo] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico.
[Hildesheim, Allan] Natl Canc Inst, Infect & Immunoepidemiol Branch, Rockville, MD USA.
[Munoz, Nubia; Murillo, Raul] Inst Nacl Cancerol, Bogota, Colombia.
[Munoz, Nubia] Hosp Llobregat, Catalan Inst Oncol, CERP, Barcelona, Spain.
[Ines Sanchez, Gloria] Univ Antioquia, Sch Med, Medellin, Colombia.
[Andrus, Jon Kim] Pan Amer Hlth Org, Immunizat Unit, Washington, DC USA.
RP Franco, EL (reprint author), McGill Univ, Div Canc Epidemiol, Montreal, PQ, Canada.
EM eduardo.franco@mcgill.ca
RI Hildesheim, Allan/B-9760-2015;
OI Hildesheim, Allan/0000-0003-0257-2363; Sanchez, Gloria
Ines/0000-0001-5992-0475; Franco, Eduardo/0000-0002-4409-8084
NR 29
TC 25
Z9 29
U1 0
U2 5
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 AUG 19
PY 2008
VL 26
SU 11
BP L88
EP L95
DI 10.1016/j.vaccine.2008.05.026
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 364FZ
UT WOS:000260322900010
PM 18945406
ER
PT J
AU Herrero, R
Ferreccio, C
Salmeron, J
Almonte, M
Sanchez, GI
Lazcano-Ponce, E
Jeronimo, J
AF Herrero, Rolando
Ferreccio, Catterina
Salmeron, Jorge
Almonte, Maribel
Ines Sanchez, Gloria
Lazcano-Ponce, Eduardo
Jeronimo, Jose
TI New Approaches to Cervical Cancer Screening in Latin America and the
Caribbean
SO VACCINE
LA English
DT Article
DE HPV; HPV testing; Latin America; Caribbean; Cervical cancer; Screening;
Cytology
ID RANDOMIZED CONTROLLED-TRIAL; HUMAN-PAPILLOMAVIRUS DNA; LOW-RESOURCE
SETTINGS; VISUAL INSPECTION; ACETIC-ACID; HIGH-RISK; INTRAEPITHELIAL
NEOPLASIA; CONVENTIONAL CYTOLOGY; DEVELOPING-COUNTRIES; COSTA-RICA
AB Cervical cancer remains an important public health problem in the Latin America and Caribbean region (LAC), with an expected significant increase in disease burden in the next decades as a result of population ageing. Prophylactic human papillomavirus (HPV) vaccine is currently unaffordable in LAC countries, However, even if vaccination was implemented, an additional two decades will be required to observe its impact on HPV related disease and cancer. With some exceptions, cytology-based screening programs have been largely ineffective to control the problem in the region, and there is a need for new approaches to the organization of screening and for use of newly developed techniques. Several research groups in LAC have conducted research on new screening methods, some of which are summarized in this paper. A recommendation to reorganize screening programs is presented considering visual inspection for very low resource areas, improvement of cytology where it is operating successfully and HPV DNA testing followed by visual inspection with acetic acid (VIA) or cytology as soon as this method becomes technically and economically sustainable. This could be facilitated by the incorporation of new, low-cost HPV DNA testing methods and the use of self-collected vaginal specimens for selected groups of the population. An important requisite for screening based on HPV testing will be the quality assurance of the laboratory and the technique by validation and certification measures. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica.
[Ferreccio, Catterina] Pontificia Univ Catolica Chile, Escuela Med, Dept Publ Hlth, Santiago, Chile.
[Salmeron, Jorge] Inst Mexicano Seguro Social, Epidemiol Invest & Hlth Res Unit, Cuernavaca, Morelos, Mexico.
[Almonte, Maribel] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Unit, London WC1, England.
[Almonte, Maribel] Wolfson Inst Prevent Med, Canc Res UK Ctr Epidemiol Math & Stat, London, England.
[Ines Sanchez, Gloria] Univ Antioquia, Sch Med, Infect & Canc Grp, Medellin, Colombia.
[Lazcano-Ponce, Eduardo] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico.
[Jeronimo, Jose] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
RP Herrero, R (reprint author), Fdn INCIENSA, San Jose, Costa Rica.
EM rherrero@amnet.co.cr
RI Almonte, Maribel/O-3286-2016;
OI Sanchez, Gloria Ines/0000-0001-5992-0475
NR 54
TC 23
Z9 23
U1 0
U2 3
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 AUG 19
PY 2008
VL 26
SU 11
BP L49
EP L58
DI 10.1016/j.vaccine.2008.05.025
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 364FZ
UT WOS:000260322900006
PM 18945402
ER
PT J
AU Murillo, R
Almonte, M
Pereira, A
Ferrer, E
Gamboa, OA
Jeronimo, J
Lazcano-Ponce, E
AF Murillo, Raul
Almonte, Maribel
Pereira, Ana
Ferrer, Elena
Gamboa, Oscar A.
Jeronimo, Jose
Lazcano-Ponce, Eduardo
TI Cervical Cancer Screening Programs in Latin America and the Caribbean
SO VACCINE
LA English
DT Article
DE HPV; Cervical cancer; Mass screening; Latin America; Caribbean; Cytology
ID DEVELOPING-COUNTRIES; CYTOLOGY; PREVENTION; MORTALITY; PERU
AB Latin America and the Caribbean (LAC) have a significant burden of cervical cancer. Prophylactic human papillomavirus (HPV) vaccines are an opportunity for primary prevention and new screening methods, such as new HPV DNA testing, are promising alternatives to cytology screening that should be analyzed in the context of regional preventive programs. Cytology-based screening programs have not fulfilled their expectations and coverage does not sufficiently explain the lack of impact on screening in LAC. While improved evaluation of screening programs is necessary to increase the impact of screening on the reduction of incidence and mortality, other programmatic aspects will need to be addressed such as follow-up of positive tests and quality control. The implementation of new technologies might enhance screening performance and reduce mortality in the region. The characteristics, performance and impact of cervical cancer screening programs in LAC are reviewed in this article. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Murillo, Raul; Gamboa, Oscar A.] Inst Nacl Cancerol Colombia, Div Res & Publ Hlth, Bogota, Colombia.
[Almonte, Maribel; Pereira, Ana] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Unit, London WC1, England.
[Almonte, Maribel] Wolfson Inst Prevent Med, Canc Res UK Ctr Epidemiol Math & Stat, London, England.
[Pereira, Ana] Univ Chile, Fac Med, Sch Publ Hlth, Santiago, Chile.
[Ferrer, Elena] Hosp Llobregat, ICO, CERP, UNIC, Barcelona, Spain.
[Jeronimo, Jose] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Jeronimo, Jose] PATH, Seattle, WA USA.
[Lazcano-Ponce, Eduardo] Ctr Populat Hlth Res, Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.
RP Murillo, R (reprint author), Inst Nacl Cancerol Colombia, Div Res & Publ Hlth, Bogota, Colombia.
EM rmurillo@cancer.gov.co
RI Pereira, Ana/H-9476-2013; Almonte, Maribel/O-3286-2016; Pereira,
Ana/I-2396-2013
OI Pereira, Ana/0000-0003-1587-4264; Pereira, Ana/0000-0003-1587-4264
NR 42
TC 79
Z9 90
U1 1
U2 9
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 AUG 19
PY 2008
VL 26
SU 11
BP L37
EP L48
DI 10.1016/j.vaccine.2008.06.013
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 364FZ
UT WOS:000260322900005
PM 18945401
ER
PT J
AU Fleming, JM
Long, EL
Ginsburg, E
Gerscovich, D
Meltzer, PS
Vonderhaar, BK
AF Fleming, J. M.
Long, E. L.
Ginsburg, E.
Gerscovich, D.
Meltzer, P. S.
Vonderhaar, B. K.
TI Interlobular and intralobular mammary stroma: Genotype may not reflect
phenotype
SO BMC CELL BIOLOGY
LA English
DT Article
ID PREINVASIVE BREAST DISEASE; CARCINOMA IN-SITU; GENE-EXPRESSION;
CANCER-CELLS; TENASCIN-C; DIFFERENTIAL EXPRESSION; MAMMOGRAPHIC DENSITY;
TUMOR-DEVELOPMENT; EPITHELIAL-CELLS; MENSTRUAL-CYCLE
AB Background: The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes.
Methods: Fresh normal breast tissue was collected from reduction mammoplasty patients and immediately placed into embedding medium and frozen on dry ice. Tissue sections were subjected to laser capture microscopy to isolate the interlobular from the intralobular fibroblasts. RNA was prepared and subjected to microarray analysis using the Affymetrix Human Genome U133 GeneChip (R). Data was analyzed using the Affy and Limma packages available from Bioconductor. Findings from the microarray analysis were validated by RT-PCR and immunohistochemistry.
Results: No statistically significant difference was detected between the gene expression profiles of the interlobular and intralobular fibroblasts by microarray analysis and RT-PCR. However, for some of the genes tested, the protein expression patterns between the two subtypes of fibroblasts were significantly different.
Conclusion: This study is the first to report the gene expression profiles of the two distinct fibroblast populations within the human mammary gland. While there was no significant difference in the gene expression profiles between the groups, there was an obvious difference in the expression pattern of several proteins tested. This report also highlights the importance of studying gene regulation at both the transcriptional and post-translational level.
C1 [Fleming, J. M.; Ginsburg, E.; Gerscovich, D.; Vonderhaar, B. K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Long, E. L.; Meltzer, P. S.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Vonderhaar, BK (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM flemingjo@mail.nih.gov; llori@mail.nih.gov; eg20e@nih.gov;
dgerscov@health.usf.edu; pmeltzer@mail.nih.gov; bv10w@nih.gov
FU Center for Cancer Research; National Cancer Institute; Breast Cancer
Research Stamp proceeds
FX This research was supported by the Center for Cancer Research, an
Intramural Research Program of the National Cancer Institute, and by
Breast Cancer Research Stamp proceeds awarded through competitive peer
review.
NR 58
TC 14
Z9 14
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2121
J9 BMC CELL BIOL
JI BMC Cell Biol.
PD AUG 18
PY 2008
VL 9
AR 46
DI 10.1186/1471-2121-9-46
PG 11
WC Cell Biology
SC Cell Biology
GA 346UK
UT WOS:000259094900001
PM 18710550
ER
PT J
AU Aggarwal, P
Dobrovolskaia, MA
McNeil, SE
AF Aggarwal, Parag
Dobrovolskaia, Marina A.
McNeil, Scott E.
TI Light microscopy and fluorescence assays as alternatives to traditional
ICP-MS and TEM methods for quantitative analysis of gold nanoparticles
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Aggarwal, Parag; Dobrovolskaia, Marina A.; McNeil, Scott E.] NCI Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
EM aggarwalp@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 295-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301228
ER
PT J
AU Amato, KE
Blake, JC
Burgess, JP
Lodge, JW
Fernando, RA
Collins, BJ
AF Amato, Kelly E.
Blake, James C.
Burgess, Jason P.
Lodge, Jon W.
Fernando, Reshan A.
Collins, Bradley J.
TI ANYL 108-Separation and characterization of the cis- and trans- isomers
of isosafrole
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Amato, Kelly E.; Blake, James C.; Burgess, Jason P.; Lodge, Jon W.; Fernando, Reshan A.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Collins, Bradley J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
EM kea@rti.org
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 108-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301088
ER
PT J
AU Babaoglu, K
Simeonov, A
Ferreira, R
Thomas, CJ
Feng, B
Irwin, JJ
Jadhav, A
Inglese, J
Shoichet, BK
Austin, CP
AF Babaoglu, Kerim
Simeonov, Anton
Ferreira, Rafaela
Thomas, Craig J.
Feng, Brian
Irwin, John J.
Jadhav, Ajit
Inglese, James
Shoichet, Brian K.
Austin, Christopher P.
TI COMP 158-Comprehensive analysis of hits from high-throughput and docking
screens
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Babaoglu, Kerim] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA.
[Simeonov, Anton; Thomas, Craig J.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Irwin, John J.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
EM kerim@blur.compbio.ucsf.edu; craigt@nhgri.nih.gov; jji@cgl.ucsf.edu;
shoichet@cgl.ucsf.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 158-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304168
ER
PT J
AU Bai, YW
AF Bai, Yawen
TI PHYS 247-High-resolution structures of protein folding intermediates and
stepwise folding energy landscape
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Bai, Yawen] NCI, Lab Biochem & Mol Biol, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 247-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307210
ER
PT J
AU Banerjee, A
Sackett, DL
Bane, S
AF Banerjee, Abhijit
Sackett, Dan L.
Bane, Susan
TI BIOL 180-Fluorescent labeling of the carboxy terminus of alpha-tubulin
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Banerjee, Abhijit; Bane, Susan] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
[Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
EM abhijit79banerjee@gmail.com; Dlsackett@aol.com
RI Bane, Susan/C-1414-2013
OI Bane, Susan/0000-0002-4270-6314
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 180-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301594
ER
PT J
AU Barchi, JJ
AF Barchi, Joseph J., Jr.
TI CARB 25-On the road running north-south: Conformationally-biased
nucleosides and nucleic acids
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Barchi, Joseph J., Jr.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA.
EM barchi@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 25-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302511
ER
PT J
AU Barry, CE
AF Barry, Clifton E., III
TI BIOL 7-The mechanism of anaerobic activity of antitubercular
nitroimidazoles
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Barry, Clifton E., III] NIH, TB Res Sect, Bethesda, MD 20892 USA.
EM cbarry@mail.nih.gov
RI Barry, III, Clifton/H-3839-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 7-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301548
ER
PT J
AU Basudhar, D
Wink, DA
Miranda, KM
AF Basudhar, Debashree
Wink, David A.
Miranda, Katrina M.
TI INOR 169-Selective inhibition of COX-2
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Basudhar, Debashree] Univ Arizona, Tucson, AZ 85719 USA.
[Wink, David A.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
[Miranda, Katrina M.] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA.
EM basudhar@email.arizona.edu; kmiranda@email.arizona.edu
RI Miranda, Katrina/B-7823-2009
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 169-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306621
ER
PT J
AU Best, RB
Hummer, G
AF Best, Robert B.
Hummer, Gerhard
TI PHYS 210-Position dependence of protein folding diffusion coefficients
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM rbb24@cam.ac.uk; Gerhard.Hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016
OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 210-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307449
ER
PT J
AU Boswell, CA
Regino, CAS
Baidoo, K
Wong, KJ
Milenic, DE
Kelley, JA
Lai, CC
Brechbiel, MW
AF Boswell, C. Andrew
Regino, Celeste A. S.
Baidoo, Kwamena
Wong, Karen J.
Milenic, Diane E.
Kelley, James A.
Lai, Christopher C.
Brechbiel, Martin W.
TI INOR 383-Synthesis and characterization of a side-bridged
phosphonate/acetate pendant-armed cyclam
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Boswell, C. Andrew] Genentech Inc, San Francisco, CA 94080 USA.
[Regino, Celeste A. S.; Wong, Karen J.] NCI, Mol Imaging Program, CCR, NIH, Bethesda, MD 20892 USA.
[Baidoo, Kwamena; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radiolmmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA.
[Kelley, James A.; Lai, Christopher C.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA.
EM boswell.andy@gene.com; reginoc@mail.nih.gov; kelleyja@mail.nih.gov;
laic@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 383-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306635
ER
PT J
AU Boswell, CA
Regino, CAS
Baidoo, K
Wong, KJ
Bumb, A
Milenic, DE
Kelley, JA
Lai, CC
Brechbiel, MW
AF Boswell, C. Andrew
Regino, Celeste A. S.
Baidoo, Kwamena
Wong, Karen J.
Bumb, Ambika
Milenic, Diane E.
Kelley, James A.
Lai, Christopher C.
Brechbiel, Martin W.
TI NUCL 31-Synthesis and evaluation of a cross-bridged bifunctional
chelator for peptide conjugation and copper radionuclide labeling
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Boswell, C. Andrew] Genentech Inc, San Francisco, CA 94080 USA.
[Regino, Celeste A. S.; Wong, Karen J.] NCI, Mol Imaging Program, CCR, NIH, Bethesda, MD 20892 USA.
[Bumb, Ambika] NCI, Radiat Oncol Branch, NIH, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA.
[Kelley, James A.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA.
[Lai, Christopher C.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, CCR, Bethesda, MD 20892 USA.
EM boswell.andy@gene.com; reginoc@mail.nih.gov; bumba@mail.nih.gov;
kelleyja@mail.nih.gov; laic@helix.nih.gov; martinwb@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 31-NUCL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305765
ER
PT J
AU Brechbiel, MW
Milenic, DE
Garmestani, K
Baidoo, K
Regino, CAS
Wong, KJ
Williams, M
Greene, M
Seidel, J
Choyke, P
AF Brechbiel, Martin W.
Milenic, Diane E.
Garmestani, Kayhan
Baidoo, Kwamena
Regino, Celeste A. S.
Wong, Karen J.
Williams, Mark
Greene, Mike
Seidel, Jurgen
Choyke, Peter
TI INOR 385-Targeting EGFR for imaging and alpha-particle therapy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Brechbiel, Martin W.; Garmestani, Kayhan; Regino, Celeste A. S.] NCI, Radioimmune & Inorgan Chem Sect, CCR, Bethesda, MD 20892 USA.
[Milenic, Diane E.; Baidoo, Kwamena] NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA.
[Wong, Karen J.; Williams, Mark; Greene, Mike; Seidel, Jurgen; Choyke, Peter] NCI, Mol Imaging Program, CCR, NIH, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 385-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306528
ER
PT J
AU Brooks, BR
Woodcock, HL
Hodoscek, M
Zheng, WJ
AF Brooks, Bernard R.
Woodcock, H. Lee, III
Hodoscek, Milan
Zheng, Wenjun
TI COMP 352-Examining reaction free energies using QM/MM methods with chain
of states methods or with vibrational subsystem analysis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Brooks, Bernard R.; Woodcock, H. Lee, III] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
[Hodoscek, Milan] Natl Inst Chem, Ctr Mol Modeling, SI-1000 Ljubljana, Slovenia.
[Zheng, Wenjun] SUNY Buffalo, Dept Phys, Buffalo, NY 14260 USA.
EM brb@nih.gov; hlwood@nih.gov
RI Woodc, Henry/D-9275-2011
NR 3
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 352-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304309
ER
PT J
AU Bumb, A
Regino, CAS
Bernardo, M
Dobson, PJ
Choyke, PL
Brechbiel, MW
AF Bumb, Ambika
Regino, Celeste A. S.
Bernardo, Marcelino
Dobson, Peter J.
Choyke, Peter L.
Brechbiel, Martin W.
TI INOR 345-Superparamagnetic iron oxide-based nanoprobe for dual modality
magnetic resonance and fluorescence imaging
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Bumb, Ambika] NCI, Radiat Oncol Branch, NIH, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA.
[Regino, Celeste A. S.; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Govt Res Lab, Bethesda, MD 20892 USA.
[Bernardo, Marcelino] SAIC Frederick Inc, Imaging Phys, Lab Anim Sci Program, Bethesda, MD 20892 USA.
[Dobson, Peter J.] Univ Oxford, Kidlington OX5 1PF, Oxon, England.
[Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, ROB, DCS,NIH, Bethesda, MD 20892 USA.
EM bumba@mail.nih.gov; reginoc@mail.nih.gov; bernardme@mail.nih.gov;
peter.dobson@begbroke.ox.ac.uk; pchoyke@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 345-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306540
ER
PT J
AU Cho, TJ
Hackley, VA
Zheng, JW
Runyon, JR
AF Cho, Tae Joon
Hackley, Vincent A.
Zheng, Jiwen
Runyon, J. Ray
TI ANYL 149-Fractionation and characterization of gold nanoparticles in
aqueous solution: Asymmetrical flow field-flow fractionation with MALS,
DLS and UV-Vis detection
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Cho, Tae Joon; Hackley, Vincent A.] NIST, Mat Sci & Engn Lab, Gaithersburg, MD 20899 USA.
[Zheng, Jiwen] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA.
[Runyon, J. Ray] Colorado Sch Mines, Dept Chem & Geochem, Golden, CO 80401 USA.
EM taejoon.cho@nist.gov; vince.hackley@nist.gov; zhengji@mail.nih.gov;
jrunyon@mines.edu
NR 0
TC 1
Z9 1
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 149-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301286
ER
PT J
AU Choyke, PL
Kobayashi, H
AF Choyke, Peter L.
Kobayashi, Hisataka
TI ANYL 274-NIR Fluorescent probes in lymphatic imaging
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, NIH, Govt Res Lab, Bethesda, MD 20892 USA.
EM pchoyke@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 274-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301233
ER
PT J
AU Clogston, JD
Zheng, JW
Ramalinga, U
Patri, A
McNeil, SE
AF Clogston, Jeffrey D.
Zheng, Jiwen
Ramalinga, Uma
Patri, Anil
McNeil, Scott E.
TI ANYL 198-Nanoparticle metrology: Reporting the hydrodynamic size by DLS
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Clogston, Jeffrey D.; Zheng, Jiwen; Ramalinga, Uma; McNeil, Scott E.] NCI Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Patri, Anil] Natl Canc Inst Frederick, Nanotechnol Characterizat Lab, SAIC Frederick, Frederick, MD 21702 USA.
EM clogstonj@mail.nih.gov; zhengji@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 198-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301238
ER
PT J
AU Deck, JA
Rice, KC
Jacobson, AE
AF Deck, Jason A.
Rice, Kenner C.
Jacobson, Arthur E.
TI ORGN 554-Synthesis and structure-activity relationship of
5-(3-hydroxy)phenylmorphans: Probes for narcotic receptor mediated
phenomena
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Deck, Jason A.] NIH, Drug Design & Synth Sect, Rockville, MD 20852 USA.
[Rice, Kenner C.; Jacobson, Arthur E.] Natl Inst Drug Abuse, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA.
[Rice, Kenner C.; Jacobson, Arthur E.] NIAAA, NIH, DHHS, Rockville, MD 20852 USA.
EM deckj@nida.nih.gov; kr21f@nih.gov; aej@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 554-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256309614
ER
PT J
AU El Kazzouli, S
Lewin, NE
Blumberg, PM
Marquez, VE
AF El Kazzouli, Said
Lewin, Nancy E.
Blumberg, Peter M.
Marquez, Vicror E.
TI MEDI 445-DAG-lactones containing 6-substituted chromen-4-ones as
alpha-arylidene groups expand the repertoire of diacylglycerol (DAG)
lactones that bind specifically to protein kinase C (PKC) and other
DAG-responsive proteins
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [El Kazzouli, Said; Marquez, Vicror E.] NCI, Med Chem Lab, Natl Inst Healt, Ctr Canc Res, Frederick, MD 21702 USA.
[Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
EM elkazzoulis@ncifcrf.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 445-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305480
ER
PT J
AU El Kazzouli, S
Lewin, NE
Blumberg, PM
Janilek, R
Marquez, VE
AF El Kazzouli, Said
Lewin, Nancy E.
Blumberg, Peter M.
Janilek, Raz
Marquez, Vicror E.
TI MEDI 444-DAG-lactones containing 4-alkylpyridinium cations in the
alpha-arylidene position: Evaluation of their interaction with protein
kinase C (PKC) and membranes
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [El Kazzouli, Said; Marquez, Vicror E.] NCI, Med Chem Lab, NIH, Ctr Canc Res, Frederick, MD 21702 USA.
[Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Janilek, Raz] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel.
EM elkazzoulis@ncifcrf.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 444-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305427
ER
PT J
AU Engel, S
AF Engel, Stanislav
TI COMP 180-A virtual screen for diverse ligands: Discovery of selective G
protein-coupled receptor antagonists
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Engel, Stanislav] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
EM engelst@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 180-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304372
ER
PT J
AU Filippov, IV
Nicklaus, MC
AF Filippov, Igor V.
Nicklaus, Marc C.
TI CINF 53-Optical structure recognition application
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Filippov, Igor V.] NCI, Med Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Nicklaus, Marc C.] NCI, Med Chem Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA.
EM igorf@helix.nih.gov; mnl@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 53-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256303504
ER
PT J
AU Frank, JA
AF Frank, Joseph A.
TI PHYS 280-Zeumatograms to cellular MRI
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Frank, Joseph A.] NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA.
EM jafrank@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 280-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307088
ER
PT J
AU Grindrod, S
Suy, S
Fallen, S
Danner, MT
Dailey, V
Toretsky, J
Kallakury, BVS
Eto, M
Bai, RL
Hamel, E
Brown, ML
AF Grindrod, Scott
Suy, Simeng
Fallen, Shannon
Danner, Malika T.
Dailey, Vernon
Toretsky, Jeffrey
Kallakury, Bhashkar V. S.
Eto, Masumi
Bai, Ruoli
Hamel, Ernest
Brown, Milton L.
TI MEDI 115-Specific myosin light chain phosphatase inhibitors as potential
therapeutic agents for human prostate cancer
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Grindrod, Scott] Georgetown Univ, Drug Discovery Program, Wahsington, DC 22057 USA.
[Suy, Simeng] Georgetown Univ, Drug Discovery Program, Med Ctr, Washington, DC 20057 USA.
[Kallakury, Bhashkar V. S.] Georgetown Univ Hosp, Washington, DC USA.
[Eto, Masumi] Thomas Jefferson Univ, Philadelphia, PA USA.
[Bai, Ruoli; Hamel, Ernest] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA.
EM scg36@georgetown.edu; suys@georgetown.edu; mb544@georgetown.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 115-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305475
ER
PT J
AU Horkay, F
Lin, DC
Horkayne-Szakaly, I
Silval, C
Dimitriadis, EK
Basser, PJ
AF Horkay, Ferenc
Lin, David C.
Horkayne-Szakaly, Iren
Silval, Candida
Dimitriadis, Emilios K.
Basser, Peter J.
TI BIOT 184-Structure and macromolecular organization of cartilage
proteoglycans
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Horkay, Ferenc; Lin, David C.; Horkayne-Szakaly, Iren; Silval, Candida; Basser, Peter J.] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
EM horkay@helix.nih.gov; lindavid@mail.nih.gov; horkayi@mail.nih.gov;
dimitria@helix.nih.gov; pjbasser@helix.nih.gov
RI Basser, Peter/H-5477-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 184-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302034
ER
PT J
AU Hummer, G
Rasaiah, JC
Feng, GG
AF Hummer, Gerhard
Rasaiah, Jayendran C.
Feng, Guogang
TI COMP 290-Free energy of hydration in the protein interior
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Rasaiah, Jayendran C.; Feng, Guogang] Univ Maine, Dept Chem, Orono, ME 04469 USA.
EM Gerhard.Hummer@nih.gov; rasaiah@maine.edu; Guogang_Feng@umit.maine.edu
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 290-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304115
ER
PT J
AU Iyer, MR
Jacobson, AE
Rice, KC
AF Iyer, Malliga R.
Jacobson, Arthur E.
Rice, Kenner C.
TI ORGN 485-Synthesis of benzofuro[2,3-c]pyridinols: Probes for narcotic
receptor mediated phenomena.
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA.
NIAAA, NIH, DHHS, Rockville, MD 20852 USA.
EM iyerma@nida.nih.gov; aej@helix.nih.gov; kr21f@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 485-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256309166
ER
PT J
AU Jackson, MS
Lee, JC
AF Jackson, Mark S.
Lee, Jennifer C.
TI INOR 157-Copper binding to alpha-synuclein, the Parkinson's protein
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Jackson, Mark S.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
EM jacksonms@mail.nih.gov; leej4@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 157-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306153
ER
PT J
AU Jacobson, KA
AF Jacobson, Kenneth A.
TI MEDI 238-Molecular recognition in P2Y nucleotide receptors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 238-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305601
ER
PT J
AU Karpiak, JD
Vilar, S
Costanzi, S
AF Karpiak, Joel D.
Vilar, Santiago
Costanzi, Stefano
TI COMP 200-Computational tools for the prediction of ligand efficacy in
the ss(2)-adrenergic receptor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Karpiak, Joel D.; Vilar, Santiago; Costanzi, Stefano] NIDDK, Lab Biol Modeling, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM karpiakj@niddk.nih.gov; qosanti@yahoo.es; stefanoc@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 200-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304261
ER
PT J
AU Keefer, LK
Valdez, CA
Saavedra, JE
Showalter, BM
Davies, KM
Wilde, TC
Citro, ML
Barchi, JJ
Deschamps, JR
Parrish, DA
El-Gayar, S
Schleicher, U
Bogdan, C
AF Keefer, Larry K.
Valdez, Carlos A.
Saavedra, Joseph E.
Showalter, Brett M.
Davies, Keith M.
Wilde, Thomas C.
Citro, Michael L.
Barchi, Joseph J., Jr.
Deschamps, Jeffrey R.
Parrish, Damon A.
El-Gayar, Stefan
Schleicher, Ulrike
Bogdan, Christian
TI MEDI 452-O2-Glycosylated diazeniumdiolates: Targeting nitric oxide to
macrophages for antileishmanial activity
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Keefer, Larry K.; Valdez, Carlos A.; Showalter, Brett M.; Wilde, Thomas C.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
[Saavedra, Joseph E.; Citro, Michael L.] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
[Davies, Keith M.] George Mason Univ, Dept Chem & Biochem, Fairfax, VA 22030 USA.
[Barchi, Joseph J., Jr.] NCI, Med Chem Lab, Washington, DC 20375 USA.
[Deschamps, Jeffrey R.; Parrish, Damon A.] USN, Res Lab, Washington, DC 20375 USA.
[El-Gayar, Stefan; Schleicher, Ulrike; Bogdan, Christian] Univ Klinikum Erlangen, D-91054 Erlangen, Germany.
EM keefer@ncifcrf.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 452-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305490
ER
PT J
AU Kelley, JA
Agbaria, R
Driscoll, JS
Ford, H
Lai, CC
Marquez, VE
AF Kelley, James A.
Agbaria, Riad
Driscoll, John S.
Ford, Harry, Jr.
Lai, Christopher C.
Marquez, Victor E.
TI CARB 40-Serendipity and challenge in the bioanalysis of modified
nucleosides and their metabolites: The Marquez effect
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Kelley, James A.; Lai, Christopher C.; Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Agbaria, Riad] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel.
EM kelleyj@dc37a.nci.nih.gov; riad@bgumail.bgu.ac.il; laic@helix.nih.gov;
marquezv@dc37a.nci.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 40-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302587
ER
PT J
AU Kiesewetter, DO
Kramer-Marek, G
Ma, Y
Capala, J
AF Kiesewetter, Dale O.
Kramer-Marek, Gabriela
Ma, Ying
Capala, Jacek
TI INOR 665-Radiolabeling of HER2 specific Affibody (R) molecule with F-18
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Kiesewetter, Dale O.; Ma, Ying] NIBIB, PET Radiochem Grp, NIH, Bethesda, MD 20892 USA.
[Kramer-Marek, Gabriela; Capala, Jacek] NCI, Radiat Oncol Branch, NIH, Gaithersburg, MD 20878 USA.
EM dk7k@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 665-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306017
ER
PT J
AU Kimura, T
Lee, JC
Pletneva, EV
Gray, HB
Winkler, JR
AF Kimura, Tetsunari
Lee, Jennifer C.
Pletneva, Ekaterina V.
Gray, Harry B.
Winkler, Jay R.
TI PHYS 248-Folding dynamics of four-helix-bundle proteins
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Kimura, Tetsunari; Gray, Harry B.; Winkler, Jay R.] CALTECH, Beckman Inst, Pasadena, CA 91125 USA.
[Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Pletneva, Ekaterina V.] Dartmouth Coll, Hanover, NH 03755 USA.
EM kimtet@caltech.edu; leej4@nhlbi.nih.gov;
Ekaterina.Pletneva@dartmouth.edu; winklerj@caltech.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 248-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307170
ER
PT J
AU Kirk, KL
AF Kirk, Kenneth L.
TI FLUO 23-Chemistry and biology of ring-fluorinated imidazoles: A review
and update
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
EM kennethk@bdg8.niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 23-FLUO
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304582
ER
PT J
AU Konas, DW
Ilagan, RP
Tiso, M
Hemann, C
Hille, R
Stuehr, DJ
AF Konas, David W.
Ilagan, Robielyn P.
Tiso, Mauro
Hemann, Craig
Hille, Russ
Stuehr, Dennis J.
TI BIOL 29-Activation and regulatory mechanisms of the constitutive nitric
oxide synthase flavoproteins
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Konas, David W.] Montclair State Univ, Dept Chem & Biochem, Montclair, NJ 07043 USA.
[Ilagan, Robielyn P.; Stuehr, Dennis J.] Cleveland Clin Fdn, Dept Pathobiol, Lerner Res Inst, Cleveland, OH 44195 USA.
[Tiso, Mauro] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Hemann, Craig] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
[Hille, Russ] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA.
EM konasd@mail.montclair.edu; stuehrd@ccf.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 29-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301472
ER
PT J
AU Kralj, JG
Player, A
Kawasaki, E
Locascio, LE
AF Kralj, Jason G.
Player, Audrey
Kawasaki, Ernest
Locascio, Laurie E.
TI ANYL 58-Gene expression profiling using linear amplification of cDNA on
microfluidic packed columns
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Kralj, Jason G.; Locascio, Laurie E.] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA.
[Player, Audrey; Kawasaki, Ernest] NCI, NIH, Gaithersburg, MD 20877 USA.
EM locascio@nist.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 58-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301273
ER
PT J
AU Kumar, V
Tomar, S
Pei, C
Parmar, VS
Malhotra, SV
AF Kumar, Vineet
Tomar, Shilpi
Pei, Cao
Parmar, Virinder S.
Malhotra, Sanjay V.
TI ORGN 351-Synthesis of active pharmaceutical ingredients in ionic liquids
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick, Frederick, MD 21702 USA.
[Tomar, Shilpi; Pei, Cao; Parmar, Virinder S.] Univ Delhi, Dept Chem, Delhi 110007, India.
EM kumarvin@mail.nih.gov; virparmar@gmail.com; malhotrasa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 351-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256309366
ER
PT J
AU Kurimura, M
Sulima, A
Hashimoto, A
Przybyl, AK
Ohshima, E
Kodato, S
Deschamps, JR
Dersch, CM
Rothman, RB
Jacobson, AE
Rice, KC
AF Kurimura, Muneaki
Sulima, A.
Hashimoto, Akihiro
Przybyl, Anna K.
Ohshima, Etsuo
Kodato, Shinichi
Deschamps, Jeffrey R.
Dersch, Christina M.
Rothman, Richard B.
Jacobson, Arthur E.
Rice, Kenner C.
TI MEDI 180-Synthesis and opioid binding affinity of the final pair of
N-methyl substituted oxide-bridged phenylmorphans, the ortho-, para-b
isomers, and their N-phenethyl analogs
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Kurimura, Muneaki] Otsuka Pharmaceut Co Ltd, Inst New Drug Discovery 2, Med Chem Grp, Tokushima 77101, Japan.
[Sulima, A.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
[Hashimoto, Akihiro] Achill Pharmaceut Inc, New Haven, CT 06511 USA.
[Przybyl, Anna K.] Adam Mickiewicz Univ Poznan, Fac Chem, PL-60780 Poznan, Poland.
[Ohshima, Etsuo] Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Ctr, Shizuoka, Japan.
[Kodato, Shinichi] Bushu Pharmaceut Ltd, Qual Div, Kawagoe, Saitama, Japan.
[Deschamps, Jeffrey R.] USN, Res Lab, Washington, DC 20375 USA.
[Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, Baltimore, MD 21224 USA.
[Jacobson, Arthur E.; Rice, Kenner C.] Natl Inst Drug Abuse, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA.
[Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, DHHS, Rockville, MD 20852 USA.
EM m_kuri@research.otsuka.co.jp; przybylanna@hotmail.com;
aej@helix.nih.gov; kr21f@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 180-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305305
ER
PT J
AU Lai, BT
Lee, JC
Winkler, JR
Gray, HB
AF Lai, Bert T.
Lee, Jennifer C.
Winkler, Jay R.
Gray, Harry B.
TI PHYS 557-Binding of alpha-synuclein to membrane mimics and calcium ions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Lai, Bert T.; Winkler, Jay R.; Gray, Harry B.] CALTECH, Beckman Inst, Pasadena, CA 91125 USA.
[Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
EM bert@caltech.edu; leej4@nhlbi.nih.gov; winklerj@caltech.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 557-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307171
ER
PT J
AU Leapman, R
Aronova, M
AF Leapman, Richard
Aronova, Maria
TI ANYL 308-Nanoscale elemental imaging of cellular structures by electron
energy loss spectroscopy in the transmission electron microscope
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Leapman, Richard; Aronova, Maria] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
EM leapmanr@mail.nih.gov; aronovaa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 308-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301388
ER
PT J
AU LeClair, CA
Vaque, JP
Turjanski, AG
Gutkind, JS
Thomas, CJ
AF LeClair, Christopher A.
Vaque, Jose P.
Turjanski, Adrian G.
Gutkind, J. Silvio
Thomas, Craig J.
TI MEDI 363-Synthesis of selective and potent ERK inhibitors utilizing a
protein kinase/small-molecule inhibitor complementary pair method
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [LeClair, Christopher A.; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA.
[Vaque, Jose P.; Turjanski, Adrian G.; Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM leclairc@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 363-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305646
ER
PT J
AU Leiston-Belanger, JM
Raviv, Y
Viard, M
Bess, JW
Blumenthal, R
AF Leiston-Belanger, Julie M.
Raviv, Yossef
Viard, Mathias
Bess, Julian W., Jr.
Blumenthal, Robert
TI BIOT 411-Novel vaccine strategy via the orthogonal inactivation of
enveloped viruses using a bifunctional hydrophobic crosslinker and
detergent treatment
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Leiston-Belanger, Julie M.; Blumenthal, Robert] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Raviv, Yossef; Viard, Mathias] NCI, Basic Res Program, SAIC, Frederick, MD 21702 USA.
[Bess, Julian W., Jr.] SAIC NCI Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA.
EM jbelanger@ncifcrf.gov; blumenthalr@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 411-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302061
ER
PT J
AU Leiston-Belanger, JM
Raviv, Y
Viard, M
Bess, JW
Blumenthal, R
AF Leiston-Belanger, Julie M.
Raviv, Yossef
Viard, Mathias
Bess, Julian W., Jr.
Blumenthal, Robert
TI AEI 23-Novel vaccine strategy via the orthogonal inactivation of
enveloped viruses using a bifunctional hydrophobic crosslinker and
detergent treatment
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Leiston-Belanger, Julie M.; Blumenthal, Robert] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
[Raviv, Yossef; Viard, Mathias] NCI, Basic Res Program, SAIC, Frederick, MD 21702 USA.
[Bess, Julian W., Jr.] NCI, SAIC, AIDS Vaccine Program, Frederick, MD 21702 USA.
EM jbelanger@ncifcrf.gov; blumenthalr@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 23-AEI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256300002
ER
PT J
AU Levine, KE
Essader, AS
Perlmutter, JM
Ross, GT
Fernando, RA
Collins, BJ
AF Levine, Keith E.
Essader, Amal S.
Perlmutter, Jason M.
Ross, Glenn T.
Fernando, Reshan A.
Collins, Brad J.
TI ANYL 167-Development and validation of a simple and rapid analytical
method for determination of chromium in feces and urine from rats and
mice exposed to sodium dichromate dihydrate and chromium picolinate
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Collins, Brad J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
[Levine, Keith E.; Essader, Amal S.; Perlmutter, Jason M.; Ross, Glenn T.; Fernando, Reshan A.] RTI Int, Res Triangle Pk, NC 27709 USA.
EM levine@rti.org; asessader@rti.org; jmperlmu@rti.org; gtr@rti.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 167-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301105
ER
PT J
AU Li, F
Jacobson, AE
Rice, KC
AF Li, Feng
Jacobson, Arthur E.
Rice, Kenner C.
TI MEDI 129-Synthesis of pyrazole-type inhibitors of Hsp90 molecular
chaperone
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, NIH,DHHS, Rockville, MD 20852 USA.
NIAAA, NIH, DHHS, Rockville, MD 20852 USA.
EM life@mail.nih.gov; aej@helix.nih.gov; kr21f@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 129-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305644
ER
PT J
AU Ludek, OR
Marquez, VE
AF Ludek, Olaf R.
Marquez, Victor E.
TI CARB 96-Synthesis of conformationally locked nucleosides built on
oxabicyclo[3.1.0]hexane scaffolds
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Ludek, Olaf R.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA.
[Marquez, Victor E.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA.
EM oludek@ncifcrf.gov; marquezv@dc37a.nci.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 96-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302590
ER
PT J
AU Malhotra, SV
Kumar, V
Parchment, RE
Jia, L
Noker, PE
Misra, RN
Narayanan, VL
Tomaszewski, JE
AF Malhotra, Sanjay V.
Kumar, Vineet
Parchment, Ralph E.
Jia, Lee
Noker, Patricia E.
Misra, Raj N.
Narayanan, Ven L.
Tomaszewski, Joseph E.
TI ORGN 303-Ionic liquid "Therapeutic Agents": New paradigm in drug
development
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Malhotra, Sanjay V.; Kumar, Vineet] NCI, Lab Synthet Chem, SAIC Frederick, Frederick, MD 21702 USA.
[Parchment, Ralph E.] NCI, Lab Human Toxicol & Pharmacol, SAIC Frederick, Frederick, MD 21702 USA.
[Jia, Lee; Misra, Raj N.; Narayanan, Ven L.; Tomaszewski, Joseph E.] NCI, Dev Therapeut Program, Bethesda, MD 20852 USA.
[Noker, Patricia E.] So Res Inst, Birmingham, AL 35205 USA.
EM malhotrasa@mail.nih.gov; kumarvin@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 303-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256309264
ER
PT J
AU Manzoni, MR
Boeggeman, E
Ramakrishnan, B
Qasba, PK
AF Manzoni, Maria R.
Boeggeman, Elizabeth
Ramakrishnan, Boopathy
Qasba, Pradman Krishen
TI BIOT 167-Useful applications of synthetic modified-sugar nucleotide
donor substrates
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Boeggeman, Elizabeth; Ramakrishnan, Boopathy] NCI, Struct Glycobiol Sect, Nanobiol Program,SAIC Inc, Ctr Canc Res,NIH, Ft Detrick, MD 21702 USA.
EM mmanzoni@ncifcrf.gov; eeb@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 167-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302110
ER
PT J
AU Marquez, VE
AF Marquez, Victor E.
TI CARB 30-The properties of locked methanocarba nucleosides in
biochemistry, biotechnology and medicinal chemistry
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Marquez, Victor E.] NCI, Med Chem Lab, Frederick, MD 21702 USA.
EM marquezv@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 30-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302514
ER
PT J
AU Marshall, GR
Che, Y
Taylor, CM
Yang, R
Kuster, DJ
AF Marshall, Garland R.
Che, Ye
Taylor, Christina M.
Yang, Robert
Kuster, Daniel J.
TI COMP 98-Diverse reverse-turn and helix mimetics: Applications and
limitations.
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Marshall, Garland R.; Taylor, Christina M.; Yang, Robert; Kuster, Daniel J.] Washington Univ, Ctr Computat Biol, St Louis, MO 63110 USA.
[Marshall, Garland R.; Taylor, Christina M.; Yang, Robert] Washington Univ, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Che, Ye] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Kuster, Daniel J.] Washington Univ, Dept Biomed Engn, St Louis, MO 63110 USA.
EM garlandm@gmail.com; cheye77@gmail.com; christina.m.taylor@gmail.com;
ryyang@artsci.wustl.edu; dkuster@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 98-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304160
ER
PT J
AU Miller, T
Singh, RP
Klauda, JB
Hodosceck, M
Brooks, BR
Woodcock, HL
AF Miller, Tim
Singh, Rishi P.
Klauda, Jeffery B.
Hodosceck, Milan
Brooks, Bernard R.
Woodcock, H. Lee, III
TI COMP 67-CHARMMing: A new web based front-end to the CHARMM
macromolecular modeling package
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Singh, Rishi P.; Klauda, Jeffery B.; Woodcock, H. Lee, III] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
[Hodosceck, Milan] Natl Inst Chem, Ctr Mol Modeling, SI-1000 Ljubljana, Slovenia.
[Brooks, Bernard R.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
EM bm318h@nih.gov; klauda@helix.nih.gov; brb@mail.nih.gov; hlwood@nih.gov
RI Woodc, Henry/D-9275-2011
NR 0
TC 0
Z9 0
U1 2
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 67-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304374
ER
PT J
AU Mitsuya, H
AF Mitsuya, Hiroaki
TI MEDI 210-Development of antiviral therapy of HIV infection: From AZT to
Darunavir
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
EM hmitsuya@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 210-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305550
ER
PT J
AU Mitsuya, H
AF Mitsuya, Hiroaki
TI CARB 29-Anti-HIV drugs: Past, present, and medicinal challenges
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
EM hmitsuya@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 29-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302534
ER
PT J
AU Mittal, J
Hummer, G
AF Mittal, Jeetain
Hummer, Gerhard
TI PHYS 158-Static and dynamic correlations in water near hydrophobic
interfaces
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM jeetain@helix.nih.gov; Gerhard.Hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 158-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307247
ER
PT J
AU Mittal, J
Best, RB
AF Mittal, Jeetain
Best, Robert B.
TI PHYS 209-Universal and nonuniversal features of protein folding
thermodynamics and kinetics under confinement
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Mittal, Jeetain] NIH, Chem Phys Lab, Bethesda, MD 20892 USA.
[Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
EM jeetain@helix.nih.gov; rbb24@cam.ac.uk
RI Best, Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 209-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307248
ER
PT J
AU Mott, BT
Simeonov, A
Maloney, DJ
Jadhav, A
Thomas, CJ
Inglese, J
Ferreira, R
Shoichet, BK
Austin, CP
AF Mott, Bryan T.
Simeonov, Anton
Maloney, David J.
Jadhav, Ajit
Thomas, Craig J.
Inglese, Jim
Ferreira, Rafaela
Shoichet, Brian K.
Austin, Christopher P.
TI MEDI 301-Identification and optimization of potential Cruzain inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Mott, Bryan T.; Simeonov, Anton; Maloney, David J.; Jadhav, Ajit; Thomas, Craig J.; Inglese, Jim; Austin, Christopher P.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Ferreira, Rafaela; Shoichet, Brian K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM mottb@mail.nih.gov; craigt@nhgri.nih.gov; shoichet@cgl.ucsf.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 301-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305366
ER
PT J
AU Nakagawa-Goto, K
Bastow, KF
Hamel, E
Chang, PC
Chen, TH
Morris-Natschke, S
Lee, KH
AF Nakagawa-Goto, Kyoko
Bastow, Kenneth F.
Hamel, Ernest
Chang, Po-Cheng
Chen, Tzu-Hsuan
Morris-Natschke, Susan
Lee, Kuo-Hsiung
TI MEDI 134-Desmosdumotins as promising antitumor agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Nakagawa-Goto, Kyoko; Bastow, Kenneth F.; Chang, Po-Cheng; Chen, Tzu-Hsuan; Morris-Natschke, Susan; Lee, Kuo-Hsiung] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Ft Detrick, MD 21702 USA.
RI GOTO, Kyoko/D-8389-2015
OI GOTO, Kyoko/0000-0002-1642-6538
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 134-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305578
ER
PT J
AU Negussie, AH
Miller, JL
Dreher, MR
Wood, B
AF Negussie, Ayele H.
Miller, Jenna L.
Dreher, Matthew R.
Wood, Bradford
TI MEDI 135-Synthesis and cellular binding of a novel cyclic NGR peptide
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Negussie, Ayele H.; Miller, Jenna L.; Dreher, Matthew R.; Wood, Bradford] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
EM negussiea@cc.nih.gov; millerj@cc.nih.gov; bwood@cc.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 135-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305518
ER
PT J
AU Nussinov, R
Jang, H
Lal, R
Ma, BY
AF Nussinov, Ruth
Jang, Hyunbum
Lal, Ratnesh
Ma, Buyong
TI COMP 297-Modeling amyloid conformations and toxic ion channels
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Nussinov, Ruth; Jang, Hyunbum; Ma, Buyong] NCI, SAIC, Frederick, MD 21702 USA.
[Lal, Ratnesh] Univ Chicago, Sch Med, Chicago, IL 60637 USA.
EM ruthn@ncifcrf.gov; jangh@ncifcrf.gov; rlal@uchicago.edu; mab@ncifcrf.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 297-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304085
ER
PT J
AU Nussinov, R
Tsai, CJ
Sauna, Z
Kimchi-Sarfati, C
Ambudkar, S
Gottesman, M
AF Nussinov, Ruth
Tsai, Chung-Jung
Sauna, Zuben
Kimchi-Sarfati, Chava
Ambudkar, Suresh
Gottesman, Michael
TI BIOT 335-Synonymous mutations and ribosome stalling can lead to altered
folding pathways and distinct minima
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, CCR Nanobiol Program, Frederick, MD 21701 USA.
[Sauna, Zuben; Kimchi-Sarfati, Chava; Ambudkar, Suresh; Gottesman, Michael] NCI, CCR, LCB, Bethesda, MD 20892 USA.
EM ruthn@ncifcrf.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 335-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256302011
ER
PT J
AU Patri, AK
Ramalinga, U
Zheng, JW
Clogston, JD
Dobrovolskaia, MA
Stern, ST
McNeil, SE
AF Patri, Anil K.
Ramalinga, Uma
Zheng, Jiwen
Clogston, Jeffrey D.
Dobrovolskaia, Marina A.
Stern, Stephen T.
McNeil, Scott E.
TI COLL 101-Nanotechnology characterization laboratory: A resource for
translational research in nanomedicine
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Patri, Anil K.; Stern, Stephen T.] SAIC Frederick, NCI Frederick, Adv Technol Program, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA.
[Ramalinga, Uma; Clogston, Jeffrey D.; Dobrovolskaia, Marina A.; McNeil, Scott E.] SAIC Frederick Inc, NCI Frederick, Adv Technol Program, Nanotechnol Characterizat Lab, Frederick, MD 21701 USA.
EM patria@mail.nih.gov; clogstonj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 101-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256303770
ER
PT J
AU Pierson, ME
Andersson, J
Nyberg, S
Soderstrom, J
McCarthy, DJ
Finnema, SJ
Varnas, K
Takano, A
Karlsson, P
Gulyas, B
Powell, ME
Heys, JR
Potts, W
Maier, D
Medd, A
Sobotka-Briner, CD
Seneca, N
Farde, L
Halldin, C
AF Pierson, M. Edward
Andersson, Jan
Nyberg, Svante
Soderstrom, J.
McCarthy, Dennis J.
Finnema, Sjoerd J.
Varnas, Katarina
Takano, Akihiro
Karlsson, Per
Gulyas, Balazs
Powell, Mark E.
Heys, J. Richard
Potts, William
Maier, Donna
Medd, Amy
Sobotka-Briner, Cynthia D.
Seneca, Nicholas
Farde, Lars
Halldin, Christer
TI MEDI 223-AZ10419369 a translational tool for 5-HT1B receptors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Heys, J. Richard] AstraZeneca, CNS Discovery, Wilmington, DE 19850 USA.
[Andersson, Jan; Finnema, Sjoerd J.; Varnas, Katarina; Takano, Akihiro; Karlsson, Per; Gulyas, Balazs; Farde, Lars; Halldin, Christer] Karolinska Univ Hosp, Dept Clin Neurosci, Karolinska Inst, Psychiat Sect, S-17176 Stockholm, Sweden.
[Nyberg, Svante; Soderstrom, J.] AstraZeneca, Clin Neurosci, S-15185 Sodertalje, Sweden.
[Seneca, Nicholas] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
EM edward.pierson@astrazeneca.com
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 223-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305293
ER
PT J
AU Pike, VW
Chun, JH
Simeon, FG
Lu, SY
Lee, YS
AF Pike, Victor W.
Chun, Joong-Hyun
Simeon, Fabrice G.
Lu, Shuiyu
Lee, Yong-Sok
TI INOR 296-[18F]fluoroarenes from [18F]fluoride ion
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Pike, Victor W.; Chun, Joong-Hyun; Simeon, Fabrice G.; Lu, Shuiyu] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Yong-Sok] NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov; simeonf@mail.nih.gov; leeys@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 296-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306661
ER
PT J
AU Pike, VW
Simeon, FG
Zoghbi, SS
Shetty, HU
Brown, AK
Innis, RB
AF Pike, Victor W.
Simeon, Fabrice G.
Zoghbi, Sami S.
Shetty, H. Umesha
Brown, Amira K.
Innis, Robert B.
TI MEDI 227-PET Radioligand discovery and development for mGluR5 receptors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Pike, Victor W.; Simeon, Fabrice G.; Zoghbi, Sami S.; Shetty, H. Umesha; Brown, Amira K.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov; simeonf@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 227-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305378
ER
PT J
AU Preusch, PC
AF Preusch, Peter C.
TI MEDI 283-NIH support for structure-based drug design for GPCR targets
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Preusch, Peter C.] Natl Inst Gen Med Sci, Biophys Branch, Div Cell Biol & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM preuschp@nigms.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 283-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305684
ER
PT J
AU Ramanathan, M
Sarsenova, A
Chen, IH
Barbaree, J
Ramanculov, E
Simonian, AL
AF Ramanathan, Madhumati
Sarsenova, Amur
Chen, I-Hsuan
Barbaree, J.
Ramanculov, Erlan
Simonian, Aleksandr L.
TI ANYL 46-Phage-based array biosensor: Application for Bacillus anthracis
spores detection and their quantification using fluorescence
spectroscopy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Ramanathan, Madhumati; Simonian, Aleksandr L.] Auburn Univ, Mat Res & Educ Ctr, Auburn, AL 36849 USA.
[Sarsenova, Amur; Ramanculov, Erlan] Natl Ctr Biotechnol Republ Kazakhstan, Astana 00001, Kazakhstan.
[Chen, I-Hsuan] Auburn Univ, Dept Biol Sci, Auburn, AL 36849 USA.
EM ramanma@auburn.edu; saramur@rambler.ru; chenh1@auburn.edu;
jbarbare@acesag.auburn.edu; ramanculov@biocenter.auburn.edu;
als@eng.auburn.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 46-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301168
ER
PT J
AU Regino, CAS
Ogawa, M
Longmire, M
Kosaka, N
Choyke, PL
Kobayashi, H
AF Regino, Celeste A. S.
Ogawa, Mikako
Longmire, Michelle
Kosaka, Nobuyuki
Choyke, Peter L.
Kobayashi, Hisataka
TI INOR 440-Fluorescence imaging of peritoneal cancers using
galactosamine-conjugated human serum albumin
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Regino, Celeste A. S.; Ogawa, Mikako; Longmire, Michelle; Kosaka, Nobuyuki; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Govt Res Lab, Bethesda, MD 20892 USA.
[Kobayashi, Hisataka] NCI, Mol Imaging Program, CCR, NIH, Bethesda, MD 20892 USA.
EM reginoc@mail.nih.gov; ogawam@mail.nih.gov; longmiremr@mail.nih.gov;
kosakan@mail.nih.gov; pchoyke@mail.nih.gov; Kobayash@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 440-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256306273
ER
PT J
AU Saneyoshi, H
Vu, BC
Hughes, SH
Boyer, PL
Sarafianos, SG
Marquez, VE
AF Saneyoshi, Hisao
Vu, B. Christie
Hughes, Stephen H.
Boyer, Paul L.
Sarafianos, Stefan G.
Marquez, Victor E.
TI MEDI 332-Probing the interaction of HIV reverse transcriptase with
conformationally locked threosyl nucleoside phosphonates: A
stereochemical approach
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Saneyoshi, Hisao; Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Vu, B. Christie] NCI, HIV Drug Resistance Program, CCR, NIH, Frederick, MD 21702 USA.
[Boyer, Paul L.] NCI, HIV Drug Resistance Program, NCI FCRDC, Frederick, MD 21702 USA.
[Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Life Sci Ctr 471D, Columbia, MO 65212 USA.
EM saneyoshih@ncifcrf.gov; cvu@ncifcrf.gov; hughes@ncifcrf.gov;
marquezv@dc37a.nci.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 332-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305536
ER
PT J
AU Schultz, ZD
Stranick, S
Levin, IW
AF Schultz, Zachary D.
Stranick, Stephan
Levin, Ira W.
TI ANYL 288-Nanoscale Raman spectroscopic imaging: Toward biomedical
applications
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Stranick, Stephan] Natl Inst Stand & Technol, Surface & Microanal Sci Div, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA.
[Levin, Ira W.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM zachary.schultz@nist.gov; stranick@nist.gov; iwl@helix.nih.gov
RI Schultz, Zachary/L-5724-2013
OI Schultz, Zachary/0000-0003-1741-8801
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 288-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301403
ER
PT J
AU Simons, CT
Fushan, A
Manichaikul, A
Drayna, D
McCluskey, TS
Slack, JP
AF Simons, Christopher T.
Fushan, A.
Manichaikul, A.
Drayna, D.
McCluskey, T. S.
Slack, Jay P.
TI AGFD 205-Genetic influences on sensory perception and its implication to
diet
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Simons, Christopher T.; McCluskey, T. S.; Slack, Jay P.] Givaudan Flavors Corp, Cincinnati, OH 45216 USA.
[Fushan, A.; Manichaikul, A.; Drayna, D.] NIDCD, Rockville, MD USA.
EM Christopher.Simons@givaudan.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 205-AGFD
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256300217
ER
PT J
AU Singh, RP
Brooks, BR
Klauda, JB
AF Singh, Rishi P.
Brooks, Bernard R.
Klauda, Jeffery B.
TI COMP 109-Binding and release of cholesterol in the Osh4 protein of yeast
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Singh, Rishi P.; Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
[Klauda, Jeffery B.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA.
EM brb@nih.gov; jbklauda@umd.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 109-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256304093
ER
PT J
AU Skoumbourdis, AP
LeClair, CA
Huang, RL
Southall, N
Leister, W
Inglese, J
Austin, CP
Xia, MH
Thomas, CJ
AF Skoumbourdis, Amanda P.
LeClair, Christopher A.
Huang, Ruili
Southall, Noel
Leister, William
Inglese, James
Austin, Christopher P.
Xia, Menghang
Thomas, Craig J.
TI MEDI 398-Discovery and optimization of a potent and selective new class
of PDE4 inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Skoumbourdis, Amanda P.; LeClair, Christopher A.; Huang, Ruili; Southall, Noel; Leister, William; Xia, Menghang] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 398-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305568
ER
PT J
AU Suarez, J
Ranguelova, K
Magliozzo, RS
AF Suarez, Javier
Ranguelova, Kalina
Magliozzo, Richard S.
TI BIOL 32-Cross-linking of M. tuberculosis catalase-peroxidase
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Suarez, Javier; Magliozzo, Richard S.] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA.
[Suarez, Javier; Magliozzo, Richard S.] CUNY, Grad Ctr, Brooklyn, NY 11210 USA.
[Ranguelova, Kalina] NIEHS, Res Triangle Pk, NC 27709 USA.
EM jsuarez@brooklyn.cuny.edu; ranguelovak@niehs.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 32-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301477
ER
PT J
AU Subramaniam, S
AF Subramaniam, Sriram
TI ANYL 335-Visualizing cells and viruses at molecular resolution with 3-D
electron microscopy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Subramaniam, Sriram] NCI, NIH, Bethesda, MD 20892 USA.
EM subramas@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 335-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301402
ER
PT J
AU Tycko, R
AF Tycko, Robert
TI PHYS 86-Unfolded, partly folded, and misfolded proteins: New insights
from solid state NMR
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 86-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307007
ER
PT J
AU Wolkow, CA
Wilson, MA
AF Wolkow, Catherine A.
Wilson, Mark A.
TI AGFD 117-Opening a can of worms: Using C. elegans to identify
prolongevity and antitumor effects of polyphenols in whole animals
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Wolkow, Catherine A.; Wilson, Mark A.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM wolkowca@grc.nia.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 117-AGFD
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256300267
ER
PT J
AU Wu, H
Wilson, C
Kaur, G
Li, H
Neale, N
Shi, Z
Sulima, A
Teng, B
Vasalatiy, O
Xu, B
Cofiell, S
Frohardt, E
Ruddy, B
Griffiths, GL
AF Wu, H.
Wilson, C.
Kaur, G.
Li, H.
Neale, N.
Shi, Z.
Sulima, A.
Teng, B.
Vasalatiy, O.
Xu, B.
Cofiell, S.
Frohardt, E.
Ruddy, B.
Griffiths, G. L.
TI MEDI 31-Imaging probe development center: A new synthetic chemistry
facility producing imaging probes at the NIH
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Wu, H.; Wilson, C.; Kaur, G.; Li, H.; Neale, N.; Shi, Z.; Sulima, A.; Teng, B.; Vasalatiy, O.; Xu, B.; Cofiell, S.; Frohardt, E.; Ruddy, B.; Griffiths, G. L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
EM wuh3@mail.nih.gov; lih3@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 31-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305410
ER
PT J
AU Wu, H
Makar, MS
Micca, PL
Miura, M
AF Wu, H.
Makar, Michael S.
Micca, Peggy L.
Miura, Michiko
TI MEDI 150-Syntheses of halogenated copper (II) tetracarboranylphenyl
porphyrins for boron neutron - capture therapy and their biological
properties in EMT-6 tumor-bearing mice
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Wu, H.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
[Makar, Michael S.; Micca, Peggy L.; Miura, Michiko] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM wuh3@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 150-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305234
ER
PT J
AU Wu, H
Makar, MS
Micca, PL
Miura, M
AF Wu, H.
Makar, Michael S.
Micca, Peggy L.
Miura, Michiko
TI MEDI 151-Syntheses of monosaccharide-conjugated copper (II)
tetracarboranylphenyl porphyrins for boron neutron - capture therapy and
their biological properties in EMT-6 tumor-bearing mice
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Wu, H.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
[Makar, Michael S.; Micca, Peggy L.; Miura, Michiko] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM wuh3@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 151-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305235
ER
PT J
AU Wylie, BJ
Schwieters, CD
Oldfield, E
Sperling, LL
Schmidt, HLF
Shah, GJ
Franks, WT
Rienstra, CM
AF Wylie, Benjamin J.
Schwieters, Charles D.
Oldfield, Eric
Sperling, Lindsay L.
Schmidt, Heather L. Frencks
Shah, Gautam J.
Franks, W. Trent
Rienstra, Chad M.
TI PHYS 16-Solid-state magic-angle spinning NMR methods for protein
structure refinement using chemical shift tensors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Wylie, Benjamin J.; Oldfield, Eric; Sperling, Lindsay L.; Schmidt, Heather L. Frencks; Shah, Gautam J.; Franks, W. Trent; Rienstra, Chad M.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
[Schwieters, Charles D.] NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
EM bwylie@scs.uiuc.edu; eo@chad.scs.uiuc.edu; frericks@scs.uiuc.edu;
wfranks@scs.uiuc.edu; rienstra@scs.uiuc.edu
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 16-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256307386
ER
PT J
AU Zhang, PJ
Khursigara, C
Wu, XW
Subramaniam, S
AF Zhang, Peijun
Khursigara, Cezar
Wu, Xiongwu
Subramaniam, Sriram
TI ANYL 333-Molecular architecture of bacterial chemotaxis sensory
apparatus by 3-D electron microscopy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Zhang, Peijun] Univ Pittsburgh, Dept Biol Struct, Sch Med, Pittsburgh, PA 15260 USA.
[Khursigara, Cezar] NCI, Cell Biol Lab, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wu, Xiongwu] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM pez7@pitt.edu; WuXW@nhlbi.mh.gov; subramas@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 333-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256301390
ER
PT J
AU Zhang, Y
Rothman, RB
Dersch, CM
Jacobson, AE
Rice, KC
AF Zhang, Yi
Rothman, Richard B.
Dersch, Christina M.
Jacobson, Arthur E.
Rice, Kenner C.
TI MEDI 189-Synthesis and opioid binding affinity of optically pure
Benzofuro[2,3-c]pyridin-6-ols
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Zhang, Yi; Jacobson, Arthur E.; Rice, Kenner C.] Natl Inst Drug Abuse, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA.
[Zhang, Yi; Jacobson, Arthur E.; Rice, Kenner C.] Natl Inst Alcohol Abuse & Alcoholism, NIH, DHHS, Rockville, MD 20852 USA.
[Rothman, Richard B.; Dersch, Christina M.] NIDA IRP, Clin Psychopharmacol Sect, NIH, DHHS, Baltimore, MD 21224 USA.
EM yizhang@intra.nida.nih.gov; aej@helix.nih.gov; kr21f@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 189-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305354
ER
PT J
AU Zhao, XZ
Maddali, K
Vu, BC
Semenova, EA
Marchand, C
Pommier, Y
Hughes, SH
Burke, TR
AF Zhao, Xue Zhi
Maddali, Kasthuraiah
Vu, B. Christie
Semenova, Elena A.
Marchand, Christophe
Pommier, Yves
Hughes, Stephen H.
Burke, Terrence R., Jr.
TI MEDI 342-HIV-1 Integrase inhibitors derived from
2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-ones and
4,5-dihydroxy-1H-isoindole-1,3(2H)-diones
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA.
[Maddali, Kasthuraiah; Semenova, Elena A.; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, CCR, NIH, Frederick, MD 21702 USA.
[Vu, B. Christie; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, CCR, NIH, Frederick, MD 21702 USA.
EM cvu@ncifcrf.gov; Semenovel@mail.nih.gov; pommier@nih.gov
RI Marchand, Christophe/D-8559-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 342-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256305484
ER
PT J
AU Zheng, JW
Clogston, JD
Ramalinga, U
McNeill, SE
Runyon, JR
AF Zheng, Jiwen
Clogston, Jeffrey D.
Ramalinga, Uma
McNeill, Scott E.
Runyon, J. Ray
TI COLL 233-Characterization of nanoparticles in animal tissue using energy
dispersive X-ray spectroscopy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 236th National Meeting of the American-Chemical-Society
CY AUG 17-21, 2008
CL Philadelphia, PA
SP Amer Chem Soc
C1 [Zheng, Jiwen; Clogston, Jeffrey D.; Ramalinga, Uma; McNeill, Scott E.] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA.
[Runyon, J. Ray] Colorado Sch Mines, Dept Chem & Geochem, Golden, CO 80401 USA.
EM zhengji@mail.mh.gov; clogstonj@mail.nih.gov; jrunyon@mines.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 17
PY 2008
VL 236
MA 233-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 499WD
UT WOS:000270256303738
ER
PT J
AU Sun, C
Lee, JSH
Zhang, MQ
AF Sun, Conroy
Lee, Jerry S. H.
Zhang, Miqin
TI Magnetic nanoparticles in MR imaging and drug delivery
SO ADVANCED DRUG DELIVERY REVIEWS
LA English
DT Review
DE magnetic nanoparticle; MRI; contrast agent; drug delivery; targeting;
DNA; siRNA; peptide; ligand; cancer; biodistribution
ID SUPERPARAMAGNETIC IRON-OXIDE; RESONANCE CONTRAST AGENTS; ADVANCED SOLID
TUMORS; BREAST-CANCER CELLS; HUMAN BRAIN-TUMORS; ONE-POT SYNTHESIS;
IN-VIVO; BIOMEDICAL APPLICATIONS; INTRACELLULAR UPTAKE; TARGETED
NANOPARTICLES
AB Magnetic nanoparticles (MNPs) possess unique magnetic properties and the ability to function at the cellular and molecular level of biological interactions making them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. Recent advances in nanotechnology have improved the ability to specifically tailor the features and properties of MNPs for these biomedical applications. To better address specific clinical needs, MNPs with higher magnetic moments, non-fouling surfaces, and increased functionalities are now being developed for applications in the detection, diagnosis, and treatment of malignant tumors, cardiovascular disease, and neurological disease. Through the incorporation of highly specific targeting agents and other functional ligands, such as fluorophores and permeation enhancers, the applicability and efficacy of these MNPs have greatly increased. This review provides a background on applications of MNPs as MR imaging contrast agents and as carriers for drug delivery and an overview of the recent developments in this area of research. (c) 2008 Elsevier B.V. All rights reserved.
C1 [Sun, Conroy; Zhang, Miqin] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
[Lee, Jerry S. H.] NCI, Off Technol & Ind Relat, Bethesda, MD 20892 USA.
RP Zhang, MQ (reprint author), Univ Washington, Dept Mat Sci & Engn, 302L Roberts Hall, Seattle, WA 98195 USA.
EM mzhang@u.washington.edu
RI Lee, Jerry/A-3189-2008; Sun, Conroy/B-5611-2013; Lee, Jerry/K-4553-2014;
Zhang, Miqin/F-5537-2010
OI Lee, Jerry/0000-0003-1515-0952; Sun, Conroy/0000-0001-5193-6907; Zhang,
Miqin/0000-0001-8974-1494
FU NCI NIH HHS [R01 CA119408, R01 CA119408-04, R01 CA134213, R01
CA134213-02, R01CA119408, R01CA134213]; NIBIB NIH HHS [R01 EB006043, R01
EB006043-02, R01EB006043]
NR 199
TC 1079
Z9 1102
U1 111
U2 914
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0169-409X
J9 ADV DRUG DELIVER REV
JI Adv. Drug Deliv. Rev.
PD AUG 17
PY 2008
VL 60
IS 11
BP 1252
EP 1265
DI 10.1016/j.addr.2008.03.018
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 335TO
UT WOS:000258313900004
PM 18558452
ER
PT J
AU Vergarajauregui, S
Puertollano, R
AF Vergarajauregui, Silvia
Puertollano, Rosa
TI Mucolipidosis type IV
SO AUTOPHAGY
LA English
DT Article
DE mucolipin-1; MLIV; p62; lysosome; autophagy
ID NEURODEGENERATIVE DISEASE; FRONTOTEMPORAL DEMENTIA; MULTIVESICULAR
BODIES; HUNTINGTON-DISEASE; AUTOPHAGY; MUTATIONS; GENE; PROTEIN;
IDENTIFICATION; MACROAUTOPHAGY
AB Mucolipidosis IV (MLIV) is a lysosomal storage disorder characterized by severe neurological and ophthalmologic abnormalities. In contrast with most lysosomal storage disorders, which are attributed to the absence of specific lysosomal hydrolases, accumulation of material in MLIV results from defects in membrane transport along the late endocytic pathway. Mutations in MCOLN1 are the cause of MLIV; however, how the lack of MCOLN1 function ultimately leads to neurodegeneration remains largely unknown. We found that MCOLN1 is required for efficient fusion of both late endosomes and autophagosomes with lysosomes. Impaired autophagosome degradation results in accumulation of autophagosomes in MLIV fibroblasts. In addition, we found increased levels and aggregation of p62, suggesting that abnormal accumulation of ubiquitinated protein inclusions may contribute to the neurodegenerative phenotype observed in MLIV patients. These findings corroborate recent evidence indicating that defects in autophagy may be a common feature of many neurodegenerative disorders.
C1 [Vergarajauregui, Silvia; Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Puertollano, R (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM puertolr@mail.nih.gov
FU Intramural Research Program of the NIH; National Heart, Lung, and Blood
Institute (NHLBI)
FX This project was supported by the Intramural Research Program of the
NIH, National Heart, Lung, and Blood Institute (NHLBI).
NR 30
TC 12
Z9 12
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD AUG 16
PY 2008
VL 4
IS 6
BP 832
EP 834
PG 3
WC Cell Biology
SC Cell Biology
GA 339TT
UT WOS:000258600900018
PM 18635948
ER
PT J
AU Parikh, NI
Hwang, SJ
Larson, MG
Hoffmann, U
Levy, D
Meigs, JB
O'Donnell, CJ
Fox, CS
AF Parikh, Nisha I.
Hwang, Shih-Jen
Larson, Martin G.
Hoffmann, Udo
Levy, Daniel
Meigs, James B.
O'Donnell, Christopher J.
Fox, Caroline S.
TI Indexes of kidney function and coronary artery and abdominal aortic
calcium (from the Framingham Offspring Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE;
SERUM CREATININE; COMPUTED-TOMOGRAPHY; MINERAL METABOLISM; RISK-FACTORS;
CALCIFICATION; MICROALBUMINURIA; ATHEROSCLEROSIS
AB It is uncertain whether moderate chronic kidney disease (CKD) or measures of kidney function are associated with subclinical atherosclerosis as represented by coronary artery calcium (CAC) or abdominal aortic calcium (AAC). We used logistic and linear regression analyses to relate CKD (glomerular filtration rate < 60 ml/min/1.73 m(2)), cystatin C (cysC), and microalbuminuria (MA) with CAC and AAC obtained using multidetector computed tomography in Framingham Heart Study Offspring participants (mean age 59 years, 55.3% women). Increased CAC and AAC were defined as >= 90th percentile age- and gender-specific cutpoints based on a healthy referent sample. Major cardiovascular disease risk factors were accounted for in multivariable models. Of 1,179 participants, 1,174 had AAC measurements and 1,147 had CAC measurements, 6.3% had CKD, and 8.3% had MA. CKD was not associated with CAC (multivariable-adjusted odds ratio [OR] for CKD 1.18, 95% confidence interval 0.59 to 2.36, p = 0.63) or AAC (multivariable-adjusted OR for CKD 1.11, 95% confidence interval 0.61 to 2.04, p = 0.73). CysC was associated with CAC in age- and gender-adjusted but not in multivariable models (age- and gender-adjusted OR for log cysC per SD increment and CAC 1.19, 95% confidence interval 1.01 to 1.41, p = 0.04; multivariable-adjusted OR 1.14, 95% confidence interval 0.95 to 1.38, p = 0.15). MA was not associated with CAC (OR 0.81, 95% confidence interval 0.41 to 1.61, p = 0.54). Neither cysC nor MA was significantly associated with AAC in age- and gender- or multivariable-adjusted models. In conclusion, CKD, cysC, and MA are not associated with CAC or AAC when accounting for cardiovascular disease risk factors. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Parikh, Nisha I.; Hwang, Shih-Jen; Larson, Martin G.; Levy, Daniel; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Parikh, Nisha I.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Dept Endocrinol Diabetol & Hypertens, Boston, MA 02115 USA.
[Hoffmann, Udo; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Meigs, James B.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM foxca@nhlbi.nih.gov
OI Larson, Martin/0000-0002-9631-1254
FU National Heart, Lung and Blood Institute, Bethesda, Maryland
[N01-HC-25195]; American Diabetes Association research; Roche
Diagnostics (Indianapolis, Indiana); Career Development Award from the
American Diabetes Association, Alexandria, Virginia; [NIDDK K24
DKO80140]
FX The Framingham Heart Study is supported by Grant N01-HC-25195 from the
National Heart, Lung and Blood Institute, Bethesda, Maryland. This study
was supported by an American Diabetes Association research grant and by
Roche Diagnostics (Indianapolis, Indiana) who donated assay reagents for
measurement of urinary albumin and creatinine. Dr. Meigs was supported
by a Career Development Award from the American Diabetes Association,
Alexandria. Virginia, and by Grant NIDDK K24 DKO80140. Bethesda,
Maryland.
NR 30
TC 6
Z9 7
U1 1
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 AUG 15
PY 2008
VL 102
IS 4
BP 440
EP 443
DI 10.1016/j.amjcard.2008.04.007
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 343IY
UT WOS:000258848000013
PM 18678302
ER
PT J
AU Klebanoff, MA
Cole, SR
AF Klebanoff, Mark A.
Cole, Stephen R.
TI Use of multiple imputation in the epidemiologic literature
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE expectation; imputation; missing data; probability weighting
ID AIR-POLLUTION; CHILD HEALTH; BACK-PAIN; RISK; TRIAL; RATIO
AB The authors attempted to catalog the use of procedures to impute missing data in the epidemiologic literature and to determine the degree to which imputed results differed in practice from unimputed results. The full text of articles published in 2005 and 2006 in four leading epidemiologic journals was searched for the text imput. Sixteen articles utilizing multiple imputation, inverse probability weighting, or the expectation-maximization algorithm to impute missing data were found. The small number of relevant manuscripts and diversity of detail provided precluded systematic analysis of the use of imputation procedures. To form a bridge between current and future practice, the authors suggest details that should be included in articles that utilize these procedures.
C1 [Klebanoff, Mark A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Cole, Stephen R.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP Klebanoff, MA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, 6100 Executive Blvd,Room 7B05F,MSC 7510, Bethesda, MD 20892 USA.
EM mk90h@nih.gov
FU Intramural NIH HHS [, NIH0010045861]; PHS HHS [NIH0010045861]
NR 23
TC 107
Z9 107
U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2008
VL 168
IS 4
BP 355
EP 357
DI 10.1093/aje/kwn071
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 335XU
UT WOS:000258329700001
PM 18591202
ER
PT J
AU Katki, HA
AF Katki, Hormuzd A.
TI Invited commentary: Evidence-based evaluation of p values and Bayes
factors
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE Bayes theorem; empirical research; epidemiologic methods; meta-analysis;
observation; statistics
ID FALSE; EPIDEMIOLOGY; PROBABILITY
AB Despite clear deficiencies of the p value as a summary of statistical evidence, compelling alternatives with strong theoretical justification, such as the Bayes factor and the related likelihood ratio, are rarely presented in epidemiologic publications. Comparison of the historical performance of the p value with that of its competitors in the epidemiologic literature may help epidemiologists evaluate whether Bayes factors or likelihood ratios lead to conclusions more quickly and reliably than a p value, given the same data. Empirical evidence presented by Ioannidis (Am J Epidemiol 2008; 168: 374-83) demonstrates that findings with p values near 0.05 tend not to be confirmed in future studies. Similarly, Bayes factors interpret p values near 0.05 as having, at best, promising evidence against the null hypothesis. However, the different types of Bayes factors require empirical evaluation of their performance in practice. P values remain popular because miniscule p values are unlikely to mislead and p values do not require alternative hypotheses. Publishing p values near 0.05 could be considered a low-threshold screen to allow many (possibly null) results to be published for follow-up consideration. Meta-analyses and studies meant to decisively convince skeptics require a stronger standard (p values much below 0.05) and a Bayes factor to interpret the p value and to facilitate incorporation of background expertise necessary for drawing comprehensive conclusions.
C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Katki, HA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8014,Execut Plaza S,MSC 724, Rockville, MD 20852 USA.
EM katkih@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015
NR 20
TC 21
Z9 21
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2008
VL 168
IS 4
BP 384
EP 388
DI 10.1093/aje/kwn148
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 335XU
UT WOS:000258329700005
ER
PT J
AU Mikolajczyk, RT
Zhang, J
Ford, J
Grewal, J
AF Mikolajczyk, Rafael T.
Zhang, Jun
Ford, Jessie
Grewal, Jagteshwar
TI Effects of interpregnancy interval on blood pressure in consecutive
pregnancies
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE birth intervals; blood pressure; pre-eclampsia; pregnancy
ID COMPLICATED PREGNANCIES; PREECLAMPSIA; RISK; VARIABILITY; POPULATION;
PARTNER; HEALTHY; PARITY; IMPACT; 2ND
AB The lower risk of preeclampsia observed in parous women has prompted a hypothesis that cardiovascular adaptation from a first pregnancy has ongoing benefits which contribute to a reduced risk of preeclampsia in the second pregnancy. However, how the interpregnancy interval affects mean arterial pressure (MAP) as an indicator of cardiovascular adaptation in subsequent pregnancies has not been well studied. The authors examined the effect of interpregnancy interval on MAP in consecutive pregnancies using data from the Collaborative Perinatal Project (1959-1965) and a semiparametric random-effects regression model. Prenatal MAP measurements were available for 533 women with both first and second births. MAP was lower in the second pregnancy (by approximately 2 mmHg) for very short interpregnancy intervals. However, this difference diminished when the interval increased, and it totally disappeared for intervals longer than 2 years. The authors conclude that although MAP is lower in the second pregnancy than in the first pregnancy, the effect persists for only a short time. It is therefore unlikely that mechanisms involving MAP as an indicator of cardiovascular adaptation contribute appreciably to the reduced risk of preeclampsia in subsequent pregnancies. However, it does not rule out the possibility that other mechanisms of cardiovascular adaptation persist longer.
C1 [Mikolajczyk, Rafael T.; Zhang, Jun; Ford, Jessie; Grewal, Jagteshwar] NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA.
RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA.
EM zhangj@mail.nih.gov
OI Mikolajczyk, Rafael/0000-0003-1271-7204; Grewal,
Jagteshwar/0000-0002-0141-4876
FU Intramural NIH HHS
NR 24
TC 5
Z9 6
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2008
VL 168
IS 4
BP 422
EP 426
DI 10.1093/aje/kwn115
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 335XU
UT WOS:000258329700010
PM 18495629
ER
PT J
AU Ness, RB
Zhang, J
Bass, D
Klebanoff, MA
AF Ness, Roberta B.
Zhang, Jun
Bass, Debra
Klebanoff, Mark A.
TI Interactions between smoking and weight in pregnancies complicated by
preeclampsia and small-for-gestational-age birth
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE body weight; infant; small for gestational age; overweight;
pre-eclampsia; pregnancy; smoking
ID INTRAUTERINE GROWTH RESTRICTION; FREE FATTY-ACIDS; CIGARETTE-SMOKING;
UNITED-STATES; RISK-FACTORS; DEVELOP PREECLAMPSIA; WOMEN; POPULATION;
OBESITY; OUTCOMES
AB Cigarette smoking protects against preeclampsia but increases the risk of small-for-gestational-age birth (SGA). Regarding body weight, the converse is true: obesity elevates rates of preeclampsia but reduces rates of SGA. The authors assessed the combined effects of smoking and weight among US women developing preeclampsia or SGA, studying 7,757 healthy, primigravid women with singleton pregnancies in 1959-1965. Smoking (never, light, heavy), stratified by prepregnancy body mass index (BMI (weight (kg)/height (m)(2)); underweight, overweight, obese), was examined in relation to preeclampsia and SGA. Among underweight (BMI < 18.5) and normal-weight (BMI 18.5-24.9) women, smoking decreased the risk of preeclampsia (for heavy smoking, light smoking, nonsmoking, test for trend > = 0.002 for underweight and p = 0.009 for normal weight) after adjustment for age, race, and socioeconomic status. However, among overweight/obese women (BMI >= 25), this trend was not apparent (p = 0.4). Among both underweight and overweight women, smoking significantly increased SGA risk (trend p < 0.001 for underweight and p = 0.02 for overweight/obese). Obesity eliminated the inverse association between smoking and preeclampsia but did not substantially alter the positive association between smoking and SGA. A possible unifying biologic explanation is discussed in this paper.
C1 [Ness, Roberta B.; Bass, Debra] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Zhang, Jun; Klebanoff, Mark A.] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Ness, RB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Room A527 Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA.
EM repro@pitt.edu
FU NCRR NIH HHS [5MO1 RR00056, M01 RR000056, M01 RR000056-430894]; NICHD
NIH HHS [P01 HD030367-04A19001, P01 HD030367, P01 HD030367-059001, P01
HD030367-069001, P01 HD030367-06S19001, P01 HD030367-079001, P01
HD030367-07S19001, P01 HD030367-089001, P01 HD030367-08S19001, P01
HD030367-099001, P01 HD030367-109001, P01 HD030367-119001, P01
HD030367-129001, P01 HD030367-139001, P01 HD30367]
NR 39
TC 32
Z9 33
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2008
VL 168
IS 4
BP 427
EP 433
DI 10.1093/aje/kwn140
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 335XU
UT WOS:000258329700011
PM 18558661
ER
PT J
AU Kurotani, R
Tomita, T
Yang, Q
Carlson, BA
Chen, C
Kimura, S
AF Kurotani, Reiko
Tomita, Takeshi
Yang, Qian
Carlson, Bradley A.
Chen, Chi
Kimura, Shioko
TI Role of secretoglobin 3A2 in lung development
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE secretoglobin 3A2; uteroglobin-related protein 1; NKX2-1; fetal lung
development; growth factor
ID UTEROGLOBIN-RELATED PROTEIN-1; THYROID TRANSCRIPTION FACTOR-1; ALLERGIC
AIRWAY INFLAMMATION; LEPTIN RECEPTOR EXPRESSION; DOWNSTREAM TARGET GENE;
SP-A GENE; DEFICIENT MICE; FACTOR-I; SURFACTANT; MORPHOGENESIS
AB Rationale: Secretoglobin 3A2 (SCGB3A2) was originally identified as a downstream target in lung for the homeodomain transcription factor NKX2-1, whose null mutation resulted in severely hypoplastic lungs. A very low level of SCGB3A2 is expressed in lungs at Embryonic Day (E) 11.5 during mouse development, which markedly increases by E16.5, the time when lung undergoes dramatic morphologic changes, suggesting that SCGB3A2 may be involved in lung development in addition to a known role in lung inflammation.
Objectives: To determine whether SCGB3A2 plays a role in lung development.
Methods: To assess a potential role for SCGB3A2 during early lung development, wild-type and Nkx2-1-null fetal lungs of early developmental stages were subjected to ex vivo organ culture in the presence of SCGB3A2. Nkx2-1-null fetuses were exposed to SCGB3A2 during early organogenesis period through intravenous administration of this protein to Nkx2-1-heterozygous pregnant females carrying these null fetuses. Cultured lungs and fetal lungs were subjected to histologic and immunohistochemical analyses. To assess a role for SCGB3A2 in late lung development, SCGB3A2 was administered to pregnant wild-type females during mid- to late organogenesis stages, and the preterm pups and/or their lungs were evaluated for extent of maturity using breathing motion, gross morphology and histology of lungs, expression of gestational stage-specific genes, and phospholipid profiles.
Measurements and Main Results: SCGB3A2 significantly promoted both early and late stages of lung development.
Conclusions: SCGB3A2 is a novel growth factor in lung.
C1 [Kurotani, Reiko; Tomita, Takeshi; Yang, Qian; Chen, Chi; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Carlson, Bradley A.] NCI, Sect Mol Biol Selenium, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3112B, Bethesda, MD 20892 USA.
EM kimuras@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, Center for
Cancer Research; Japanese Society for the Promotion of Science;
[19890175]
FX Supported by the Intramural Research Program of the National Cancer
Institute, Center for Cancer Research (S.K.), and by a postdoctoral
fellowship from the Japanese Society for the Promotion of Science and
Grant-in-Aid for Young Scientists (Start-up) (No. 19890175) (R.K.).
NR 44
TC 26
Z9 28
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 AUG 15
PY 2008
VL 178
IS 4
BP 389
EP 398
DI 10.1164/rccm.200707-1104OC
PG 10
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 340XP
UT WOS:000258678600012
PM 18535256
ER
PT J
AU Jones, CN
Lee, JY
Zhu, J
Stybayeva, G
Ramanculov, E
Zern, MA
Revzin, A
AF Jones, Caroline N.
Lee, Ji Youn
Zhu, James
Stybayeva, Gulnaz
Ramanculov, Erlan
Zern, Mark A.
Revzin, Alexander
TI Multifunctional protein microarrays for cultivation of cells and
immunodetection of secreted cellular products
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID POLY(ETHYLENE GLYCOL) PHOTOLITHOGRAPHY; GENE-EXPRESSION; ARRAYS;
DIFFERENTIATION; TECHNOLOGY; SANDWICH; PLATFORM; BIOLOGY; GLASS
AB The microarray format is being used extensively for combinatorial screening of cellular interactions with proteins, small molecules, or biomaterials. The utility of microarray-based cell cultivation approaches may be enhanced further by incorporating biosensing elements alongside the cell-adhesive ligands to enable local detection of secreted cellular products. The concept of combining cells and sensing elements in the same microarray is demonstrated in the present paper with hepatocytes serving as a model cellular system. Robotic microarraying was employed to print arrays of 300-mu m-diameter collagen (1) spots alongside the antibody (Ab) spots specific to liver proteins: albumin and alpha 1-antittypsin (alpha 1-AT). Protein microarrays were printed onto poly(ethylene glycol) hydrogel-coated glass slides, thus eliminating nonspecific adsorption of cells or proteins. When incubated with printed microarrays, hepatocytes became localized on collagen (1) domains but did not attach on Ab spots or elsewhere on hydrogel-coated glass substrates. Liver-specific proteins secreted by hepatocytes were captured on Ab domains in the immediate vicinity of the cells, detected with a sandwich immunofluorescent assay and quantified using a microarray scanner. Importantly, hepatic albumin and alpha 1-AT production detected in the microarray was comparable to enzyme-linked immunosorbent assay measurements of these proteins. In the future, the juxtaposition of sensing Ab regions with cell arrays will be particularly useful for the detection of local appearance or loss of phenotype of cells interacting with the printed components of the cellular microenvironment.
C1 [Jones, Caroline N.; Lee, Ji Youn; Zhu, James; Stybayeva, Gulnaz; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Zern, Mark A.] Univ Calif Davis, Transplant Res Inst, Dept Med, Davis, CA 95616 USA.
[Stybayeva, Gulnaz; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan.
RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
EM arevzin@ucdavis.edu
FU NIBIB NIH HHS [EB003827]; NIDDK NIH HHS [DK073901]
NR 33
TC 23
Z9 23
U1 1
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD AUG 15
PY 2008
VL 80
IS 16
BP 6351
EP 6357
DI 10.1021/ac8007626
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 337PN
UT WOS:000258448100028
PM 18642875
ER
PT J
AU Chen, T
Lee, MJ
Kim, YS
Lee, S
Kummar, S
Gutierrez, M
Hewitt, SM
Trepel, JB
Levin, IW
AF Chen, Tsoching
Lee, Min-Jung
Kim, Yeong Sang
Lee, Sunmin
Kummar, Shivaani
Gutierrez, Martin
Hewitt, Stephen M.
Trepel, Jane B.
Levin, Ira W.
TI Pharmacodynamic assessment of histone deacetylase inhibitors: Infrared
vibrational spectroscopic imaging of protein acetylation
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID TARGET ENTROPY MINIMIZATION; FLOW-CYTOMETRY; CANCER-THERAPY; TISSUE;
CELLS; SPECTRA
AB Infrared spectroscopy identifies molecules by detection of vibrational patterns characteristic of molecular bonds. We apply this approach to measure protein acetylation after treatment with histone deacetylase inhibitors. The anticancer activity of histone deacetylase inhibitors (HDACi) is ascribed to the hyperacetylation of both core nucleosomal histones and nonhistone proteins critical to the maintenance of the malignant phenotype (Marks, P. A.; Richon, V. M.; Breslow, R.; Rifkind, R. A. Curr. Opin. Oncol. 2001, 13, 477-483; Mai, A.; Massa, S.; Rotili, D.; Cerbara, I.; Valente, S.; Pezzi, R.; Simeoni, S.; Ragno, R. Med. Res. Rev. 2005, 25, 261-309). After incubation of the peripheral blood mononuclear cells (PBMCs) in vitro with the HDACi SNDX-275, a benzamide drug derivative, vibrational spectral changes in the methyl and methylene stretching mode regions, which reflect concentration-dependent increases in protein acetylation, were detected and quantified. We applied these metrics, based upon spectral differences, to peripheral blood mononuclear cells from patients treated in vivo with this agent. The data demonstrate a new approach to a sensitive assessment of global molecular modifications that is independent of antibodies, requires minimal cell processing, and is easily adapted to high-throughput screening.
C1 [Chen, Tsoching; Levin, Ira W.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Lee, Min-Jung; Kim, Yeong Sang; Lee, Sunmin; Trepel, Jane B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kummar, Shivaani; Gutierrez, Martin; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Levin, IW (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM IraL@intra.niddk.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU Intramural NIH HHS [Z01 DK029065-01]
NR 27
TC 14
Z9 14
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD AUG 15
PY 2008
VL 80
IS 16
BP 6390
EP 6396
DI 10.1021/ac800840y
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 337PN
UT WOS:000258448100033
PM 18651756
ER
PT J
AU Nadareishvili, Z
Michaud, K
Hallenbeck, JM
Wolfe, F
AF Nadareishvili, Zurab
Michaud, Kaleb
Hallenbeck, John M.
Wolfe, Frederick
TI Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in
patients with rheumatoid arthritis: A nested, case-control study
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NECROSIS FACTOR THERAPY;
LOW-DENSITY-LIPOPROTEIN; C-REACTIVE PROTEIN; BODY-MASS INDEX;
RISK-FACTORS; LONG-TERM; MYOCARDIAL-INFARCTION; RADIOGRAPHIC DAMAGE;
DISEASE-ACTIVITY
AB Objective. To determine the risk of stroke in patients with rheumatoid arthritis (RAJ and risk factors associated with stroke.
Methods. We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA.
Results. We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]).
Conclusion. RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.
C1 [Michaud, Kaleb; Wolfe, Frederick] Natl Data Bank Rheumat Dis, Wichita, KS 67214 USA.
[Nadareishvili, Zurab] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA.
[Hallenbeck, John M.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Wolfe, F (reprint author), Natl Data Bank Rheumat Dis, 1035 N Emporia,Suite 288, Wichita, KS 67214 USA.
EM fwolfe@arthritis-research.org
FU Abbott; Amgen; Wyeth-Australia; Merck; Pfizer
FX The National Data Bank for Rheumatic Diseases has conducted safety
registries for Centocor, Sanofi-Aventis, and Bristol-Myers Squibb, and
has received research grants from Abbott, Amgen, Wyeth-Australia. Merck,
and Pfizer.
NR 51
TC 67
Z9 68
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD AUG 15
PY 2008
VL 59
IS 8
BP 1090
EP 1096
DI 10.1002/art.23935
PG 7
WC Rheumatology
SC Rheumatology
GA 343XF
UT WOS:000258888800006
PM 18668583
ER
PT J
AU Rider, LG
Lachenbruch, P
Isenberg, DA
Miller, FW
AF Rider, Lisa G.
Lachenbruch, Peter
Isenberg, David A.
Miller, Frederick W.
TI Applicability of the Paediatric Rheumatology International Trials
Organisation disease activity core set for juvenile dermatomyositis:
comment on the article by Ruperto et al
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Letter
C1 [Rider, Lisa G.; Miller, Frederick W.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Bethesda, MD USA.
[Lachenbruch, Peter] Oregon State Univ, Corvallis, OR 97331 USA.
[Isenberg, David A.] UCL, London, England.
RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Bethesda, MD USA.
OI Isenberg, David/0000-0001-9514-2455; Rider, Lisa/0000-0002-6912-2458;
Miller, Frederick/0000-0003-2831-9593
NR 3
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 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD AUG 15
PY 2008
VL 59
IS 8
BP 1197
EP 1198
DI 10.1002/art.23919
PG 2
WC Rheumatology
SC Rheumatology
GA 343XF
UT WOS:000258888800020
PM 18668578
ER
PT J
AU Samuni, Y
Zheng, CY
Cawley, NX
Cotrim, AP
Loh, YP
Baum, BJ
AF Samuni, Yuval
Zheng, Changyu
Cawley, Niamh X.
Cotrim, Ana P.
Loh, Y. Peng
Baum, Bruce J.
TI Sorting of growth hormone-erythropoietin fusion proteins in rat salivary
glands
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE adenovirus; gene therapeutics; protein secretion; protein sorting;
salivary glands
ID REGULATED SECRETORY PATHWAY; MEDIATED GENE-TRANSFER; TRANS-GOLGI
NETWORK; SUBMANDIBULAR-GLANDS; ENDOCRINE SECRETION; CARBOXYPEPTIDASE-E;
EPITHELIAL-CELLS; PAROTID-GLANDS; IN-VIVO; THERAPEUTICS
AB Neuroendocrine and exocrine cells secrete proteins in either a constitutive manner or via the regulated secretory pathway (RSP), but the specific sorting mechanisms involved are not fully understood. After gene transfer to rat salivary glands, the transgenic model proteins human growth hormone (hGH) and erythropoietin (hEpo) are secreted primarily into saliva (RSP; exocrine) and serum (constitutive: endocrine), respectively. We hypothesized that fusion of hGH at either the C-terminus or the N-terminus of hEpo would re-direct hEpo from the bloodstream into saliva. We constructed and expressed two fusion proteins, hEpo-hGH and hGH-hEpo, using serotype 5-adenoviral vectors, and delivered them to rat submandibular glands in vivo via retroductal cannulation. Both the hEpo-hGH and hGH-hEpo fusion proteins, but not hEpo alone, were secreted primarily into saliva (p < 0.0001 and p = 0.0083, respectively). These in vivo studies demonstrate for the first time that hGH, in an N- as well as C-terminal position, influences the secretion of a constitutive pathway protein. (c) Published by Elsevier Inc.
C1 [Samuni, Yuval; Zheng, Changyu; Cotrim, Ana P.; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA.
[Cawley, Niamh X.; Loh, Y. Peng] NICHHD, Cellular Neurobiol Sect, Bethesda, MD 20892 USA.
RP Samuni, Y (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3B69,MSC-1002,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ysamuni@mail.nih.gov
FU Intramural NIH HHS [NIH0010536820]; PHS HHS [NIH0010536820]
NR 34
TC 5
Z9 5
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 15
PY 2008
VL 373
IS 1
BP 136
EP 139
DI 10.1016/j.bbrc.2008.05.177
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 324XV
UT WOS:000257553600026
PM 18544341
ER
PT J
AU Ochaion, A
Bar-Yehuda, S
Cohen, S
Amital, H
Jacobson, KA
Joshi, BV
Gao, ZG
Barer, F
Patoka, R
Del Valle, L
Perez-Liz, G
Fishman, P
AF Ochaion, A.
Bar-Yehuda, S.
Cohen, S.
Amital, H.
Jacobson, K. A.
Joshi, B. V.
Gao, Z. G.
Barer, F.
Patoka, R.
Del Valle, L.
Perez-Liz, G.
Fishman, P.
TI The A(3) adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and
NF-kappa B signaling pathway in synoviocytes from rheumatoid arthritis
patients and in adjuvant-induced arthritis rats
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE A(3) adenosine receptor; CF502; rheumatoid arthritis; PKB/Akt; NF-kappa
B; TNF-alpha
ID EXPERIMENTAL COLITIS; CANCER CELLS; ACTIVATION; TRANSCRIPTION;
EXPRESSION; REDUCTION; INJURY; CF101
AB The A(3) adenosine receptor (A(3)AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant-and collagen-induced arthritis.
In this study we present a novel A(3)AR agonist, CF502, with high affinity and selectivity at the human A(3)AR. CFS02 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-kappa B) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of adjuvant- induced arthritis (AIA) in a rat experimental model when given orally at a low dose (100 mu g/kg). As is typical of other G-protein coupled receptors, the A(3)AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of protein kinase B/Akt (PKB/Akt), I kappa B kinase (IKK), I kappa B (I kappa B), NF-kappa B and tumor necrosis factor-alpha (TNF-alpha) took place. in addition, the expression levels of glycogen synthase kinase-3 beta (GSK-3 beta), beta-catenin, and poly(ADP-ribose)polymerase (PARP), known to control the level and activity of NF-kappa B, were down-regulated upon treatment with CF502.
Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A3AR agonists; for the treatment of rheumatoid arthritis. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Ochaion, A.; Bar-Yehuda, S.; Cohen, S.; Barer, F.; Patoka, R.; Fishman, P.] Can Fite Biopharma Ltd, IL-49170 Kiryat Matalon, Petah Tikva, Israel.
[Ochaion, A.] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel.
[Amital, H.] Meir Med Ctr, Internal Dept D, Kefar Sava, Israel.
[Jacobson, K. A.; Joshi, B. V.; Gao, Z. G.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Del Valle, L.; Perez-Liz, G.] Temple Univ, Sch Med, Dept Neurosci, Philadelphia, PA 19122 USA.
[Del Valle, L.; Perez-Liz, G.] Temple Univ, Sch Med, Ctr NeuroVirol, Philadelphia, PA 19122 USA.
RP Fishman, P (reprint author), Can Fite Biopharma Ltd, 10 Bareket St,POB 7537, IL-49170 Petah Tiqwa, Israel.
EM pnina@canfite.co.il
RI Jacobson, Kenneth/A-1530-2009; Del Valle, Luis/J-4085-2015
OI Jacobson, Kenneth/0000-0001-8104-1493; Del Valle,
Luis/0000-0003-3894-9206
FU Intramural NIH HHS [Z01 DK031117-20]
NR 33
TC 34
Z9 36
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD AUG 15
PY 2008
VL 76
IS 4
BP 482
EP 494
DI 10.1016/j.bcp.2008.05.032
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 338XM
UT WOS:000258542700005
PM 18602896
ER
PT J
AU Chen, HIH
Hsu, FH
Jiang, Y
Tsai, MH
Yang, PC
Meltzer, PS
Chuang, EY
Chen, YD
AF Chen, Hung-I Harry
Hsu, Fang-Han
Jiang, Yuan
Tsai, Mong-Hsun
Yang, Pan-Chyr
Meltzer, Paul S.
Chuang, Eric Y.
Chen, Yidong
TI A probe-density-based analysis method for array CGH data: simulation,
normalization and centralization
SO BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT Joint Meeting of the 7th European Conference on Computational
Biology/5th Meeting of the Bioinformatics-Italian-Society
CY SEP 22-26, 2008
CL Cagliari, ITALY
SP Bioinformat Italian Soc
ID COMPARATIVE GENOMIC HYBRIDIZATION; LUNG ADENOCARCINOMA; CDNA
MICROARRAYS; ABERRATIONS; CANCER; MODEL; SEGMENTATION; ALGORITHM;
PROFILES
AB Motivation: Genomic instability is one of the fundamental factors in tumorigenesis and tumor progression. Many studies have shown that copy-number abnormalities at the DNA level are important in the pathogenesis of cancer. Array comparative genomic hybridization (aCGH), developed based on expression microarray technology, can reveal the chromosomal aberrations in segmental copies at a high resolution. However, due to the nature of aCGH, many standard expression data processing tools, such as data normalization, often fail to yield satisfactory results.
Results: We demonstrated a novel aCGH normalization algorithm, which provides an accurate aCGH data normalization by utilizing the dependency of neighboring probe measurements in aCGH experiments. To facilitate the study, we have developed a hidden Markov model (HMM) to simulate a series of aCGH experiments with random DNA copy number alterations that are used to validate the performance of our normalization. In addition, we applied the proposed normalization algorithm to an aCGH study of lung cancer cell lines. By using the proposed algorithm, data quality and the reliability of experimental results are significantly improved, and the distinct patterns of DNA copy number alternations are observed among those lung cancer cell lines.
C1 [Chen, Hung-I Harry; Hsu, Fang-Han; Chuang, Eric Y.] Natl Taiwan Univ, Dept Elect Engn, Taipei 106, Taiwan.
[Chen, Hung-I Harry; Hsu, Fang-Han; Tsai, Mong-Hsun; Chuang, Eric Y.] Natl Taiwan Univ, Res Ctr Med Excellence, Taipei 100, Taiwan.
[Jiang, Yuan; Meltzer, Paul S.; Chen, Yidong] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Tsai, Mong-Hsun; Chuang, Eric Y.] Natl Taiwan Univ, Inst Biotechnol, Ctr Syst Biol & Bioinformat, Taipei 106, Taiwan.
[Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Taipei 100, Taiwan.
[Chuang, Eric Y.] Natl Taiwan Univ, Dept Life Sci, Taipei 106, Taiwan.
[Chuang, Eric Y.] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 106, Taiwan.
[Chuang, Eric Y.] Natl Taiwan Univ, Grad Inst Epidemiol, Taipei 106, Taiwan.
RP Chuang, EY (reprint author), Natl Taiwan Univ, Dept Elect Engn, Taipei 106, Taiwan.
EM chuangey@ntu.edu.tw
RI Tsou , YY/H-4160-2011
OI Tsou , YY/0000-0003-3345-4351
FU Intramural NIH HHS
NR 34
TC 20
Z9 21
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 15
PY 2008
VL 24
IS 16
BP 1749
EP 1756
DI 10.1093/bioinformatics/btn321
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 337YN
UT WOS:000258471500039
PM 18603568
ER
PT J
AU Morgulis, A
Coulouris, G
Raytselis, Y
Madden, TL
Agarwala, R
Schaffer, AA
AF Morgulis, Aleksandr
Coulouris, George
Raytselis, Yan
Madden, Thomas L.
Agarwala, Richa
Schaeffer, Alejandro A.
TI Database indexing for production MegaBLAST searches
SO BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT Joint Meeting of the 7th European Conference on Computational
Biology/5th Meeting of the Bioinformatics-Italian-Society
CY SEP 22-26, 2008
CL Cagliari, ITALY
SP Bioinformat Italian Soc
ID SEQUENCE DATABASES; DNA-SEQUENCES; ALGORITHM; MATCHES; BLAST
AB Motivation: The BLAST software package for sequence comparison speeds up homology search by preprocessing a query sequence into a lookup table. Numerous research studies have suggested that preprocessing the database instead would give better performance. However, production usage of sequence comparison methods that preprocess the database has been limited to programs such as BLAT and SSAHA that are designed to find matches when query and database subsequences are highly similar.
Results: We developed a new version of the MegaBLAST module of BLAST that does the initial phase of finding short seeds for matches by searching a database index. We also developed a program makembindexthat preprocesses the database into a data structure for rapid seed searching. We show that the new indexed MegaBLAST is faster than the non-indexed version for most practical uses. We show that indexed MegaBLAST is faster than miBLAST, another implementation of BLAST nucleotide searching with a preprocessed database, for most of the 200 queries we tested. To deploy indexed MegaBLAST as part of NCBIsWeb BLAST service, the storage of databases and the queueing mechanism were modified, so that some machines are now dedicated to serving queries for a specific database. The response time for such Web queries is now faster than it was when each computer handled queries for multiple databases.
C1 [Morgulis, Aleksandr; Coulouris, George; Raytselis, Yan; Madden, Thomas L.; Agarwala, Richa; Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
RP Schaffer, AA (reprint author), NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bldg 38A,Room 6S608,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM schaffer@helix.nih.gov
RI Schaffer, Alejandro/F-2902-2012
FU Intramural NIH HHS
NR 16
TC 171
Z9 177
U1 1
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 15
PY 2008
VL 24
IS 16
BP 1757
EP 1764
DI 10.1093/bioinformatics/btn322
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 337YN
UT WOS:000258471500040
PM 18567917
ER
PT J
AU Rigden, DJ
Galperin, MY
AF Rigden, Daniel J.
Galperin, Michael Y.
TI Sequence analysis of GerM and SpoVS, uncharacterized bacterial
sporulation proteins with widespread phylogenetic distribution
SO BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT Joint Meeting of the 7th European Conference on Computational
Biology/5th Meeting of the Bioinformatics-Italian-Society
CY SEP 22-26, 2008
CL Cagliari, ITALY
SP Bioinformat Italian Soc
ID BACILLUS-SUBTILIS; STRUCTURE PREDICTION; III DOMAINS; DATABASE;
RECOGNITION; CHITINASE; BINDING; SYSTEM; GENE; EXPRESSION
AB Sporulation in low-GC gram-positive bacteria (Firmicutes) is an important survival mechanism that involves up to 150 genes, acting in a highly regulated manner. Many sporulation genes have close homologs in non-sporulating bacteria, including cyanobacteria, proteobacteria and spirochaetes, indicating that their products play a wider biological role. Most of them have been characterized as regulatory proteins or enzymes of peptidoglycan turnover; functions of others remain unknown but they are likely to have a general role in cell division and/or development. We have compiled a list of such widely conserved sporulation and germination proteins with poorly characterized functions, ranked them by the width of their phylogenetic distribution, and performed detailed sequence analysis and, where possible, structural modeling aimed at estimating their potential functions. Here we report the results of sequence analysis of Bacillus subtilis spore germination protein GerM, suggesting that it is a widespread cell development protein, whose function might involve binding to peptidoglycan. GerM consists of two tandem copies of a new domain (designated the GERMN domain) that forms phylum-specific fusions with two other newly described domains, GERMN-associated domains 1 and 2 (GMAD1 and GMAD2). Fold recognition reveals a -propeller fold for GMAD1, while ab initio modeling suggests that GMAD2 adopts a fibronectin type III fold. SpoVS is predicted to adopt the AlbA archaeal chromatin protein fold, which suggests that it is a DNA-binding protein, most likely a novel transcriptional regulator.
C1 [Rigden, Daniel J.] Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England.
[Galperin, Michael Y.] Natl Lib Med, NCBI, NIH, Bethesda, MD 20894 USA.
RP Rigden, DJ (reprint author), Univ Liverpool, Sch Biol Sci, Crown St, Liverpool L69 7ZB, Merseyside, England.
EM drigden@liverpool.ac.uk
RI Galperin, Michael/B-5859-2013;
OI Galperin, Michael/0000-0002-2265-5572; Rigden,
Daniel/0000-0002-7565-8937
FU Intramural NIH HHS [Z99 LM999999]
NR 47
TC 13
Z9 13
U1 2
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 15
PY 2008
VL 24
IS 16
BP 1793
EP 1797
DI 10.1093/bioinformatics/btn314
PG 5
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 337YN
UT WOS:000258471500045
PM 18562273
ER
PT J
AU Mast, BT
Miles, T
Penninx, BW
Yaffe, K
Rosano, C
Satterfield, S
Ayonayon, HN
Harris, T
Simonsick, EM
AF Mast, Benjamin T.
Miles, Toni
Penninx, Brenda W.
Yaffe, Kristine
Rosano, Caterina
Satterfield, Suzanne
Ayonayon, Hilsa N.
Harris, Tamara
Simonsick, Eleanor M.
TI Vascular disease and future risk of depressive symptomatology in older
adults: Findings from the Health, Aging, and Body Composition study
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE cerebrovascular disease; geriatric depression; vascular depression
ID LATE-LIFE DEPRESSION; PRIMARY-CARE PATIENTS; WHITE-MATTER
HYPERINTENSITIES; SCALE CES-D; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR
HEALTH; COGNITIVE IMPAIRMENT; CRITERION VALIDITY; MAJOR DEPRESSION;
COMMUNITY
AB Background: The vascular depression hypothesis suggests that age-related vascular diseases and risk factors contribute to late-life depression. Although neuroimaging studies provide evidence for an association between depression and severity of vascular lesions in the brain, studies of depression and indicators of vascular risk have been less consistent.
Methods: We examined 1796 elders ages 70-79 from the Health, Aging and Body Composition study without depression at baseline and examined the association between prevalent vascular disease and related conditions at baseline and 2-year incidence of elevated depressive symptoms, defined as a score > 8 on the 10-item Center for Epidemiologic Studies Depression (CES-D) scale.
Results: After adjustment for demographic data and physical and cognitive functioning, several vascular conditions remained associated with increased risk of depressive symptomatology including metabolic syndrome and its components (low high-density lipoprotein cholesterol and high fasting glucose), coronary heart disease, a positive Rose questionnaire for angina, and high hemoglobin a1c. Cumulative vascular risk based upon a composite of 10 vascular diseases and risk factors was independently associated with incident elevated depression at 2-year follow-up after controlling for demographic data, physical and cognitive functioning, and selected comorbid medical conditions.
Conclusions: These results provide support for the vascular depression hypothesis in demonstrating an association between vascular conditions and risk factors and subsequent risk of depressive symptomatology. Older adults with vascular conditions and risk factors require close monitoring of depressive symptoms.
C1 [Mast, Benjamin T.; Miles, Toni] Univ Louisville, Louisville, KY 40292 USA.
[Penninx, Brenda W.] VU Univ Med, Amsterdam, Netherlands.
[Yaffe, Kristine; Ayonayon, Hilsa N.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Rosano, Caterina] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Satterfield, Suzanne] Univ Tennessee, Memphis, TN USA.
[Harris, Tamara] NIA, Lab Epidemol Demog & Biometry, Bethesda, MD 20892 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Simonsick, Eleanor M.] Johns Hopkins Sch Med, Baltimore, MD USA.
RP Mast, BT (reprint author), Univ Louisville, 317 Life Sci Bldg, Louisville, KY 40292 USA.
EM b.mast@louisville.edu
OI Miles, Toni/0000-0003-0823-2319; Rosano, Caterina/0000-0002-0909-1506;
Rosano, Caterina/0000-0002-4271-6010
FU Intramural NIH HHS; NHLBI NIH HHS [R01-HL972972]; NIA NIH HHS
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]
NR 61
TC 38
Z9 42
U1 3
U2 5
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 AUG 15
PY 2008
VL 64
IS 4
BP 320
EP 326
DI 10.1016/j.biopsych.2008.01.025
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 336IJ
UT WOS:000258357200009
PM 18367153
ER
PT J
AU Osuch, EA
Willis, MW
Bluhrn, R
Ursano, RJ
Drevets, WC
AF Osuch, Elizabeth A.
Willis, Mark W.
Bluhrn, Robyn
Ursano, Robert J.
Drevets, Wayne C.
CA CSTS Neuroimaging Study Grp
TI Neurophysiological responses to traumatic reminders in the acute
aftermath of serious motor vehicle collisions using [(15)O]-H(2)O
positron emission tomography
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE acute stress disorder; amygdala; fear extinction; perirhinal cortex;
PET; prefrontal cortex; PTSD
ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX;
CEREBRAL-BLOOD-FLOW; SCRIPT-DRIVEN IMAGERY; PERIRHINAL CORTEX;
CONDITIONED FEAR; SYMPTOM PROVOCATION; EMOTION PERCEPTION;
TEMPORAL-LOBE; PET IMAGES
AB Background: Neuroimaging studies report that individuals with posttraumatic stress disorder show abnormal responses in the amygdala and medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) during exposure to traumatic reminders. However, neural responses arising in the early aftermath of a traumatic event have not been studied.
Methods: Twenty-two motor vehicle collision survivors and 12 nontraumatized control subjects participated. Regional cerebral blood flow (rCBF) was measured using [(15)O]-H(2)O positron emission tomography (PET) at rest and as subjects listened to scripts of traumatic and neutral events. Self-report measures rated emotional responses to the scripts; standardized assessments (Impact of Events-Revised) evaluated acute stress symptoms at scanning and at 3-month follow-up. Most subjects improved symptomatically.
Results: At rest, trauma subjects showed hyperperfusion in right mPFC/ACC and hypoperfusion in right amygdala compared with control subjects. In trauma subjects, listening to trauma scripts versus neutral scripts resulted in decreased flow in the right amygdala and left amygdala/perirhinal cortex, and symptom scores correlated negatively with right hippocampal flow changes. Symptom improvement at 3 months correlated negatively with rCBF changes in right perirhinal cortex and hippocampus during the trauma versus neutral script contrast. Subjective disturbance during the trauma versus neutral contrast correlated positively with rCBF changes in right amygdala and left mPFC. Functional connectivity analyses of rCBF changes during trauma versus neutral scripts demonstrated left amygdala coupling with right ACC and bilateral anterior insula, as well as coupling between the amygdala and contralateral hippocampus.
Conclusions: In recently traumatized subjects functional interactions between the amygdala, perirhinal cortex and ACC/mPFC that occur during exposure to traumatic reminders may underlie adaptive/recuperative processes.
C1 [Osuch, Elizabeth A.; Bluhrn, Robyn] Univ Western Ontario, Dept Psychiat, London, ON N6A 4G5, Canada.
[Willis, Mark W.; Ursano, Robert J.] NIMH, Intramural Res Program, Ctr Study Traumat Stress, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] NIMH, Intramural Res Program, Sect Neuroimaging Mood & Anxiety Disorders, Uniformed Serv Univ Hlth Sci, Bethesda, MD 20892 USA.
RP Osuch, EA (reprint author), Univ Western Ontario, Dept Psychiat, 339 Windermere Rd, London, ON N6A 4G5, Canada.
EM elizabeth.osuch@lhsc.on.ca
RI Osuch, Elizabeth/B-5009-2015
OI Osuch, Elizabeth/0000-0001-5946-1862
FU Intramural NIH HHS; NIMH NIH HHS [U01 MH063397, U01 MH063397-01A1, U01
MH063397-01A1S1, U01 MH063397-02, U01 MH063397-03, U01 MH63397-01A1]
NR 76
TC 33
Z9 35
U1 5
U2 5
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 AUG 15
PY 2008
VL 64
IS 4
BP 327
EP 335
DI 10.1016/j.biopsych.2008.03.010
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 336IJ
UT WOS:000258357200010
PM 18423575
ER
PT J
AU Mavencamp, TL
Rhoderick, JF
Bridges, RJ
Esslinger, CS
AF Mavencamp, Terri L.
Rhoderick, Joseph F.
Bridges, Richard J.
Esslinger, C. Sean
TI Synthesis and preliminary pharmacological evaluation of novel
derivatives of L-beta-threo-benzylaspartate as inhibitors of the
neuronal glutamate transporter EAAT3
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE pharmacophore; bound conformation; diastereoselective; lipophilic pocket
ID SUBSTRATE; ASPARTATE; BLOCKERS; BINDING
AB A series of beta-benzylaspartate derivatives were prepared from N-trityl-L-aspartate dimethyl ester and evaluated as inhibitors of neuronal glutamate transporter EAAT3. The result of the structure-activity studies suggests that the position occupied by the aromatic ring of beta-benzylaspartate within the binding site of EAAT3 may be different from that occupied by comparable groups in previously identified inhibitors, such as L-threo-benzyloxy aspartate (TBOA). Further, halogen substitutions at the 3-postition of the aromatic ring of beta-benzylaspartate can increase the potency with which the analogues inhibit EAAT3. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Mavencamp, Terri L.; Rhoderick, Joseph F.; Bridges, Richard J.; Esslinger, C. Sean] Univ Montana, NIH COBRE Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
RP Esslinger, CS (reprint author), Univ Montana, NIH COBRE Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
EM christopher.esslinger@umontana.edu
FU NCRR NIH HHS [P20 RR015583, RR15583]; NINDS NIH HHS [R01 NS030570, R01
NS030570-12, NS30570, NS045704, R01 NS045704, R01 NS045704-04]
NR 19
TC 9
Z9 9
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 15
PY 2008
VL 16
IS 16
BP 7740
EP 7748
DI 10.1016/j.bmc.2008.07.001
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 341PL
UT WOS:000258726300024
PM 18650095
ER
PT J
AU Lee, H
Venable, RM
MacKerell, AD
Pastor, RW
AF Lee, Hwankyu
Venable, Richard M.
MacKerell, Alexander D., Jr.
Pastor, Richard W.
TI Molecular dynamics studies of polyethylene oxide and polyethylene
glycol: Hydrodynamic radius and shape anisotropy
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID POLY(ETHYLENE OXIDE); AQUEOUS-SOLUTIONS; STOCHASTIC SIMULATIONS;
DIFFUSION-COEFFICIENTS; NMR RELAXATION; LIPID-BILAYERS; RANDOM-WALKS;
N-ALKANES; PORE-SIZE; X-RAY
AB A revision (C35r) to the CHARMM ether force field is shown to reproduce experimentally observed conformational populations of dimethoxyethane. Molecular dynamics simulations of 9, 18, 27, and 36-mers of polyethylene oxide (PEO) and 27-mers of polyethylene glycol (PEG) in water based on C35r yield a persistence length lambda = 3.7 angstrom, in quantitative agreement with experimentally obtained values of 3.7 angstrom for PEO and 3.8 angstrom for PEG; agreement with experimental values for hydrodynamic radii of comparably sized PEG is also excellent. The exponent nu relating the radius of gyration and molecular weight (R-g proportional to M-w(nu)) of PEO from the simulations equals 0.515 +/- 0.023, consistent with experimental observations that low molecular weight PEG behaves as an ideal chain. The shape anisotropy of hydrated PEO is 2.59:1.44:1.00. The dimension of the middle length for each of the polymers nearly equals the hydrodynamic radius R-h obtained from diffusion measurements in solution. This explains the correspondence of R-h and R-p, the pore radius of membrane channels: a polymer such as PEG diffuses with its long axis parallel to the membrane channel, and passes through the channel without substantial distortion.
C1 [Lee, Hwankyu; Venable, Richard M.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[MacKerell, Alexander D., Jr.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
RP Pastor, RW (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM pastorr@nhlbi.nih.gov
OI MacKerell, Alex/0000-0001-8287-6804
FU Intramural NIH HHS; NIGMS NIH HHS [GM070855, GM51501, R01 GM051501, R01
GM070855, R29 GM051501]
NR 67
TC 178
Z9 179
U1 6
U2 112
PU BIOPHYSICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 15
PY 2008
VL 95
IS 4
BP 1590
EP 1599
DI 10.1529/biophysj.108.133025
PG 10
WC Biophysics
SC Biophysics
GA 329RX
UT WOS:000257889400005
PM 18456821
ER
PT J
AU Ferguson, ML
Prasad, K
Boukari, H
Sackett, DL
Krueger, S
Lafer, EM
Nossal, R
AF Ferguson, Matthew L.
Prasad, Kondury
Boukari, Hacene
Sackett, Dan L.
Krueger, Susan
Lafer, Eileen M.
Nossal, Ralph
TI Clathrin triskelia show evidence of molecular flexibility
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID ANGLE NEUTRON-SCATTERING; ELECTRON CRYOMICROSCOPY; LIGHT-SCATTERING;
PROTEIN; ENDOCYTOSIS; POLYMERS; RIGIDITY; CAGE
AB The clathrin triskelion, which is a three-legged pinwheel-shaped heteropolymer, is a major component in the protein coats of certain post-Golgi and endocytic vesicles. At low pH, or at physiological pH in the presence of assembly proteins, triskelia will self-assemble to form a closed clathrin cage, or "basket''. Recent static light scattering and dynamic light scattering studies of triskelia in solution showed that an individual triskelion has an intrinsic pucker similar to, but differing from, that inferred from a high resolution cryoEM structure of a triskelion in a clathrin basket. We extend the earlier solution studies by performing small-angle neutron scattering (SANS) experiments on isolated triskelia, allowing us to examine a higher q range than that probed by static light scattering. Results of the SANS measurements are consistent with the light scattering measurements, but show a shoulder in the scattering function at intermediate q values (0.016 angstrom(-1)), just beyond the Guinier regime. This feature can be accounted for by Brownian dynamics simulations based on flexible bead-spring models of a triskelion, which generate time-averaged scattering functions. Calculated scattering profiles are in good agreement with the experimental SANS profiles when the persistence length of the assumed semi. exible triskelion is close to that previously estimated from the analysis of electron micrographs.
C1 [Ferguson, Matthew L.; Boukari, Hacene; Sackett, Dan L.; Nossal, Ralph] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, NIH, Bethesda, MD USA.
[Ferguson, Matthew L.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
[Prasad, Kondury; Lafer, Eileen M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Krueger, Susan] Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA.
RP Nossal, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, NIH, Bethesda, MD USA.
EM nossalr@mail.nih.gov
RI Ferguson, Matthew/C-4140-2014
OI Ferguson, Matthew/0000-0003-0760-757X
FU Intramural NIH HHS; NINDS NIH HHS [R01 NS029051, R56 NS029051, NS29051]
NR 37
TC 12
Z9 12
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 AUG 15
PY 2008
VL 95
IS 4
BP 1945
EP 1955
DI 10.1529/biophysj.107.126342
PG 11
WC Biophysics
SC Biophysics
GA 329RX
UT WOS:000257889400032
PM 18502808
ER
PT J
AU Metcalfe, DD
AF Metcalfe, Dean D.
TI Mast cells and mastocytosis
SO BLOOD
LA English
DT Review
ID SLOW-REACTING SUBSTANCE; C-KIT MUTATION; AGGRESSIVE SYSTEMIC
MASTOCYTOSIS; BLOOD MONONUCLEAR-CELLS; GUINEA PIG LUNG; FC-EPSILON-RI;
GROWTH-FACTOR; IMMUNOGLOBULIN-E; BONE-MARROW; MOLECULAR-CLONING
AB Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34(+) cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors.
C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10-11C207,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA.
EM dmetcalfe@niaid.nih.gov
FU Intramural NIH HHS
NR 109
TC 225
Z9 230
U1 2
U2 11
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 15
PY 2008
VL 112
IS 4
BP 946
EP 956
DI 10.1182/blood-2007-11-078097
PG 11
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300012
PM 18684881
ER
PT J
AU Ji, M
Li, HJ
Suh, HC
Klarmann, KD
Yokota, Y
Keller, JR
AF Ji, Ming
Li, Huajie
Suh, Hyung Chan
Klarmann, Kimberly D.
Yokota, Yoshifumi
Keller, Jonathan R.
TI Id2 intrinsically regulates lymphoid and erythroid development via
interaction with different target proteins
SO BLOOD
LA English
DT Article
ID LOOP-HELIX PROTEINS; COLONY-STIMULATING FACTOR; HEMATOPOIETIC
STEM-CELLS; FACTOR-RECEPTOR PROMOTER; TRANSCRIPTION FACTORS;
DNA-BINDING; PU.1 SPI-1; GATA-1; GENE; EXPRESSION
AB inhibitors of DNA binding (Id) family members are key regulators of cellular differentiation and proliferation. These activities are related to the ability of Id proteins to antagonize E proteins and other transcription factors. As negative regulators of E proteins, Id proteins have been implicated in lymphocyte development. Overexpression of Id1, Id2, or Id3 has similar effects on lymphocyte development. However, which Id protein plays a physiologic role during lymphocyte development is not clear. By analyzing Id2 knock-out mice and retroviral transduced hematopoietic progenitors, we demonstrated that Id2 is an intrinsic negative regulator of B-cell development. Hematopoietic progenitor cells overexpressing Id2 did not reconstitute B-cell development in vivo, which resembled the phenotype of E2A null mice. The B-cell population in bone marrow was significantly expanded in Id2 knock-out mice compared with their wildtype littermates. Knock-down of Id2 by shRNA in hematopoietic progenitor cells promoted B-cell differentiation and induced the expression of B-cell lineage-specific genes. These data identified Id2 as a physiologically relevant regulator of E2A during B lymphopoiesis. Furthermore, we identified a novel Id2 function in erythroid development. Overexpression of Id2 enhanced erythroid development, and decreased level of Id2 impaired normal erythroid development. Id2 regulation of erythroid development is mediated via interacting with transcription factor PU.1 and modulating PU.1 and GATA-1 activities. We conclude that Id2 regulates lymphoid and erythroid development via interaction with different target proteins.
C1 [Ji, Ming; Li, Huajie; Suh, Hyung Chan; Klarmann, Kimberly D.; Keller, Jonathan R.] NCI, Basic Res Program, SAIC Frederick, Canc Res Ctr, Frederick, MD 21702 USA.
[Yokota, Yoshifumi] Fukui Med Univ, Dept Biochem, Fukui, Japan.
RP Keller, JR (reprint author), NCI, Basic Res Program, SAIC Frederick, Canc Res Ctr, Bldg 560,Rm 12-03, Frederick, MD 21702 USA.
EM kellerj@ncifcrf.gov
RI Ji, Ming/C-2795-2011
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12 400]
NR 42
TC 45
Z9 46
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 AUG 15
PY 2008
VL 112
IS 4
BP 1068
EP 1077
DI 10.1182/blood-2008-01-133504
PG 10
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300028
PM 18523151
ER
PT J
AU Helft, J
Jacquet, A
Joncker, NT
Grandjean, I
Dorothee, G
Kissenpfennig, A
Malissen, B
Matzinger, P
Lantz, O
AF Helft, Julie
Jacquet, Alexandra
Joncker, Nathalie T.
Grandjean, Isabelle
Dorothee, Guillaume
Kissenpfennig, Adrien
Malissen, Bernard
Matzinger, Polly
Lantz, Olivier
TI Antigen-specific T-T interactions regulate CD4 T-cell expansion
SO BLOOD
LA English
DT Article
ID MHC CLASS-II; DENDRITIC CELLS; IN-VIVO; CLONAL EXPANSION;
MHC/COSTIMULATORY COMPLEX; PRECURSOR FREQUENCY; PEPTIDE COMPLEXES;
PRESENTASOME APS; MEMORY; NAIVE
AB The regulation of CD4 T-cell numbers during an immune response should take account of the amount of antigen (Ag), the initial frequency of Ag-specific T cells, the mix of naive versus experienced cells, and (ideally) the diversity of the repertoire. Here we describe a novel Mechanism of T-cell regulation that potentially deals with all of these parameters. We found that CD4 T cells establish a negative feedback loop by capturing their cognate major histocompatibility class (MHC)/peptide complexes from Ag-presenting cells and presenting them to Ag-experienced CD4 T cells, thereby inhibiting their recruitment into the response while allowing recruitment of naive T cells. The inhibition is Ag specific, begins at day 2 (long before Ag disappearance), and cannot be overcome by providing new Ag-loaded dendritic cells. In this way, CD4 T-cell proliferation is regulated in a functional relationship to the amount of Ag, while allowing naive T cells to generate repertoire variety.
C1 [Helft, Julie; Jacquet, Alexandra; Joncker, Nathalie T.; Grandjean, Isabelle; Dorothee, Guillaume; Lantz, Olivier] Inst Curie, Immunol Lab, F-75005 Paris, France.
[Helft, Julie; Jacquet, Alexandra; Joncker, Nathalie T.; Grandjean, Isabelle; Dorothee, Guillaume; Lantz, Olivier] Inst Curie, INSERM, U653, F-75005 Paris, France.
[Kissenpfennig, Adrien; Malissen, Bernard] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, Marseille, France.
[Kissenpfennig, Adrien; Malissen, Bernard] INSERM, U631, F-13258 Marseille, France.
[Kissenpfennig, Adrien; Malissen, Bernard] CNRS, UMR6102, Marseille, France.
[Matzinger, Polly] NIAID, Ghost Lab, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Lantz, O (reprint author), Inst Curie, Immunol Lab, 26 Rue Ulm, F-75005 Paris, France.
EM olivier.lantz@curie.net
RI Lantz, Olivier/J-4960-2012; DOROTHEE, Guillaume/O-9760-2016;
OI Lantz, Olivier/0000-0003-3161-7719; Dorothee,
Guillaume/0000-0001-5763-3632; Malissen, Bernard/0000-0003-1340-9342
FU Intramural NIH HHS
NR 51
TC 29
Z9 29
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 AUG 15
PY 2008
VL 112
IS 4
BP 1249
EP 1258
DI 10.1182/blood-2007-09-114389
PG 10
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300050
PM 18539897
ER
PT J
AU Semnani, RT
Venugopal, PG
Leifer, CA
Mostbock, S
Sabzevari, H
Nutman, TB
AF Semnani, Roshanak Tolouei
Venugopal, Priyanka Goel
Leifer, Cynthia A.
Mostboeck, Sven
Sabzevari, Helen
Nutman, Thomas B.
TI Inhibition of TLR3 and TLR4 function and expression in human dendritic
cells by helminth parasites
SO BLOOD
LA English
DT Article
ID NF-KAPPA-B; TOLL-LIKE RECEPTOR-2; TOXOPLASMA-GONDII; CUTTING EDGE;
IMMUNE-RESPONSES; TRYPANOSOMA-CRUZI; GENE-EXPRESSION; BRUGIA-MALAYI;
LYMPHATIC FILARIASIS; TETANUS VACCINATION
AB Patent lymphatic filariasis is characterized by antigen-specific T-cell unresponsiveness with diminished IFN-gamma and IL-2 production and defects in dendritic cell (DC) function. Because Toll-like receptors (TLRs) play an important role in pathogen recognition and TLR expression is diminished on B and T cells of filaria-infected individuals, we examined the effect of live microfilariae (mf) on expression and function of TLRs in human DCs. We show that mf-exposed monocyte-derived human DCs (mhDCs) demonstrate marked diminution of TLR3 and TLR4 mRNA expression compared with mf-unexposed mhDCs that translated into loss of function in response to appropriate TLR ligands. Exposure to mf significantly down-regulated production of IFN-alpha, MIP-1 alpha, IL-12p70, and IL-1 alpha following activation with poly I:C, and of IL-12p40 following activation with poly I:C or LIPS. mRNA expression of MyD88, the adaptor molecule involved in TLR4 signaling, was significantly diminished in mh-DCs after exposure to mf. Moreover, mf interfered with NF-kappa B activation (particularly p65 and p50) following stimulation with poly I:C or LIPS. These data suggest that mf interfere with mhDC function by altering TLR expression and interfering with both MyD88-dependent signaling and a pathway that ultimately diminishes NF-kappa B activity. This down-regulated NF-kappa B activity impairs mhDC-produced cytokines needed for full T-cell activation.
C1 [Semnani, Roshanak Tolouei; Venugopal, Priyanka Goel; Nutman, Thomas B.] NIAID, LPD, Natl Inst Hlth, Natl Canc Inst, Bethesda, MD 20892 USA.
[Leifer, Cynthia A.] Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA.
[Mostboeck, Sven; Sabzevari, Helen] NCI, Tumor Immunol & Biol Lab, Natl Inst Hlth, Bethesda, MD USA.
RP Semnani, RT (reprint author), NIAID, LPD, Natl Inst Hlth, Natl Canc Inst, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM rsemnani@niaid.nih.gov
FU Intramural NIH HHS
NR 49
TC 48
Z9 52
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 15
PY 2008
VL 112
IS 4
BP 1290
EP 1298
DI 10.1182/blood-2008-04-149856
PG 9
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300054
PM 18541719
ER
PT J
AU Paugh, SW
Paugh, BS
Rahmani, M
Kapitonov, D
Almenara, JA
Kordula, T
Milstien, S
Adams, JK
Zipkin, RE
Grant, S
Spiegel, S
AF Paugh, Steven W.
Paugh, Barbara S.
Rahmani, Mohamed
Kapitonov, Dmitri
Almenara, Jorge A.
Kordula, Tomasz
Milstien, Sheldon
Adams, Jeffrey K.
Zipkin, Robert E.
Grant, Steven
Spiegel, Sarah
TI A selective sphingosine kinase 1 inhibitor integrates multiple molecular
therapeutic targets in human leukemia
SO BLOOD
LA English
DT Article
ID PROTEIN-KINASE-C; ACUTE MYELOID-LEUKEMIA; CELL-DEATH; DOWN-REGULATION;
FUNCTIONAL-CHARACTERIZATION; MYELOGENOUS LEUKEMIA; INDUCED APOPTOSIS;
U937 CELLS; 1-PHOSPHATE; CERAMIDE
AB The potent bioactive sphingolipid mediator, sphingosine-1-phosphate (S1P), is produced by 2 sphingosine kinase isoenzymes, SphK1 and SphK2. Expression of SphK1 is up-regulated in cancers, including leukemia, and associated with cancer progression. A screen of sphingosine analogs identified (2R,3S,4E)-N-methyl-5-(4'-pentylphenyl)-2-aminopent-4-ene-1,3- diol, designated SK1-I (BML-258), as a potent, water-soluble, isoenzyme-specific inhibitor of SphK1. In contrast to pan-SphK inhibitors, SK1-I did not inhibit SphK2, PKC, or numerous other protein kinases. SK1-I decreased growth and survival of human leukemia U937 and Jurkat cells, and enhanced apoptosis and cleavage of Bcl-2. Lethality of SK1-I was reversed by caspase inhibitors and by expression of Bcl-2. SK1-I not only decreased S1P levels but concomitantly increased levels of its proapoptotic precursor ceramide. Conversely, S1P protected against SK1-I-incluced apoptosis. SK1-I also induced multiple perturbations in activation of signaling and survival-related proteins, including diminished phosphorylation of ERK1/2 and Akt. Expression of constitutively active Akt protected against SK1-I-incluced apoptosis. Notably, SK1-I potently induced apoptosis in leukemic blasts isolated from patients with acute myelogenous leukemia but was relatively sparing of normal peripheral blood mononuclear leukocytes. Moreover, SK1-I markedly reduced growth of AML xenograft tumors. Our results suggest that specific inhibitors of SphK1 warrant attention as potential additions to the therapeutic armamentarium in leukemia.
C1 [Paugh, Steven W.; Paugh, Barbara S.; Kapitonov, Dmitri; Kordula, Tomasz; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA.
[Rahmani, Mohamed; Almenara, Jorge A.] Virginia Commonwealth Univ, Sch Med, Dept Med, Richmond, VA 23298 USA.
Massey Canc Ctr, Richmond, VA USA.
[Milstien, Sheldon] NIMH, Bethesda, MD 20892 USA.
[Adams, Jeffrey K.; Zipkin, Robert E.] BIOMOL Int, Plymouth Meeting, PA USA.
RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, 1101 E Marshall St, Richmond, VA 23298 USA.
EM sspiegel@vcu.edu
RI Paugh, Steven/A-7739-2008; Paugh, Barbara/B-3625-2009
OI Paugh, Steven/0000-0001-5697-9228;
FU Intramural NIH HHS; NCI NIH HHS [P30 CA016059, P30CA16059, R01 CA061774,
R01CA61774]; NIAID NIH HHS [T32AI007407, T32 AI007407]; NIGMS NIH HHS
[R37 GM043880, R37GM043880]
NR 61
TC 116
Z9 125
U1 1
U2 7
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 AUG 15
PY 2008
VL 112
IS 4
BP 1382
EP 1391
DI 10.1182/blood-2008-02-138958
PG 10
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300065
PM 18511810
ER
PT J
AU Soehnlein, O
Zernecke, A
Eriksson, EE
Rothfuchs, AG
Pham, CT
Herwald, H
BidzhekoV, K
Rottenberg, ME
Weber, C
Lindbom, L
AF Soehnlein, Oliver
Zernecke, Alma
Eriksson, Einar E.
Rothfuchs, Antonio Gigliotti
Pham, Christine T.
Herwald, Heiko
Bidzhekov, Kiril
Rottenberg, Martin E.
Weber, Christian
Lindbom, Lennart
TI Neutrophil secretion products pave the way for inflammatory monocytes
SO BLOOD
LA English
DT Article
ID N-FORMYLPEPTIDE RECEPTOR; FORMYL PEPTIDE RECEPTOR; FACTOR C/EBP-EPSILON;
BINDING PROTEIN; GRANULE DEFICIENCY; IMMUNE-RESPONSES; CATHEPSIN-G;
T-CELLS; SUBSETS; LL-37
AB The leukocyte response in inflammation is characterized by an initial recruitment of polymorphonuclear leukocytes (PMN) preceding a second wave of monocytes to the site of injury or infection. In the mouse, 2 populations of monocytes have been identified, Gr1-CCR2-CX3CR1(hi) resident monocytes and Gr1+CCR2+CX3CR1(lo) inflammatory monocytes. Here, intravital microscopy of the musculus cremasterand a subcutaneous air pouch model were used to investigate a possible link between PMN extravasation and the subsequent emigration of inflammatory monocytes in response to local stimulation with PAR In mice that were made neutropenic by injection of a PMN-depleting antibody, the extravasation of inflammatory monocytes, but not resident monocytes, was markedly reduced compared with mice with intact white blood cell count but was restored by local treatment with secretion of activated PMN. Components of the PMN secretion were found to and further examination revealed PMN-derived LL-37 and heparin-binding protein (HBP/CAP37/azurocidin) as primary mediators of the recruitment of inflammatory monocytes via activation of formyl-peptide receptors. These data show that LL-37 and HBP specifically stimulate mobilization of inflammatory monocytes. This cellular cross-talk functionally results in enhanced cytokine levels and increased bacterial clearance, thus boosting the early immune response.
C1 [Soehnlein, Oliver; Eriksson, Einar E.; Lindbom, Lennart] Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden.
[Zernecke, Alma; Bidzhekov, Kiril; Weber, Christian] Rhein Westfal TH Aachen, IMCAR, Aachen, Germany.
[Rothfuchs, Antonio Gigliotti] NIAID, Parasit Dis Lab, Natl Inst Hlth, Bethesda, MD USA.
[Pham, Christine T.] Washington Univ, Dept Med, St Louis, MO USA.
[Herwald, Heiko] Lund Univ, Dept Clin Sci, Lund, Sweden.
[Rottenberg, Martin E.] Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden.
RP Soehnlein, O (reprint author), Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden.
EM oliver.sohnlein@ki.se
RI Rothfuchs, Antonio/F-5981-2013;
OI Rothfuchs, Antonio/0000-0001-6001-7240; Lindbom,
Lennart/0000-0001-9243-257X; Herwald, Heiko/0000-0002-8111-2842; Weber,
Christian/0000-0003-4610-8714
FU NIAID NIH HHS [R01 AI049261]
NR 57
TC 186
Z9 191
U1 0
U2 13
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 AUG 15
PY 2008
VL 112
IS 4
BP 1461
EP 1471
DI 10.1182/blood-2008-02-139634
PG 11
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300073
PM 18490516
ER
PT J
AU Kautz, L
Meynard, D
Monnier, A
Darnaud, V
Bouvet, R
Wang, RH
Deng, C
Vaulont, S
Mosser, J
Coppin, H
Roth, MP
AF Kautz, Leon
Meynard, Delphine
Monnier, Annabelle
Darnaud, Valerie
Bouvet, Regis
Wang, Rui-Hong
Deng, Chiuxia
Vaulont, Sophie
Mosser, Jean
Coppin, Helene
Roth, Marie-Paule
TI Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6,
Smad7, Id1, and Atoh8 in the mouse liver
SO BLOOD
LA English
DT Article
ID MESSENGER-RNA EXPRESSION; ANTIMICROBIAL PEPTIDE HEPCIDIN; JUVENILE
HEMOCHROMATOSIS; MICROARRAY EXPERIMENTS; SIGNAL-TRANSDUCTION;
DIFFERENTIATION; INFLAMMATION; HEMOJUVELIN; CELLS; IDENTIFICATION
AB Although hepcidin expression was shown to be induced by the BMP/Smad signaling pathway, it is not yet known how iron regulates this pathway and what its exact molecular targets are. We therefore assessed genome-wide liver transcription profiles of mice of 2 genetic backgrounds fed iron-deficient, -balanced, or -enriched diets. Among 1419 transcripts siginificantly modulated by the dietary iron content, 4 were regulated similarly to the hepcidin genes Hamp1 and Hamp2. They are coding for Bmp6, Smad7, Id1, and Atoh8 all related to the Bmp/Smad pathway. As shown by Western blot analysis, variations in Bmp6 expression induced by the diet iron content have for functional consequence similar changes in Smad1/5/8 phosphorylation that leads to formation of heteromeric complexes with Smad4 and their translocation to the nucleus. Gene expression variations induced by secondary iron deficiency or iron overload were compared with those consecutive to Smad4 and Hamp1 deficiency. Iron overload developed by Smad4- and Hamp1-deficient mice also increased Bmp6 transcription. However, as shown by analysis of mice with liver-specific disruption of Smad4, activation of Smad7, Id1, and Atoh8 transcription by iron requires Smad4. This study points out molecules that appear to play a critical role in the control of systemic iron balance.
C1 [Kautz, Leon; Meynard, Delphine; Darnaud, Valerie; Coppin, Helene; Roth, Marie-Paule] Ctr Physiopathol Toulouse Purpan, INSERM, U563, Toulouse, France.
[Kautz, Leon; Meynard, Delphine; Darnaud, Valerie; Coppin, Helene; Roth, Marie-Paule] Univ Toulouse 3, IFR 30, F-31062 Toulouse, France.
[Monnier, Annabelle; Mosser, Jean] Univ Rennes 1, CNRS, UMR6061, Inst Genet & Dev, Rennes, France.
[Monnier, Annabelle] Univ Rennes 1, CNRS, UMR6553, Rennes, France.
[Bouvet, Regis; Mosser, Jean] CHU Rennes, Serv Genom Med, Rennes, France.
[Wang, Rui-Hong; Deng, Chiuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
[Vaulont, Sophie] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France.
[Vaulont, Sophie] INSERM, U567, Paris, France.
[Mosser, Jean] Plate Forme Transcriptome OUEST Genopole, Rennes, France.
RP Roth, MP (reprint author), CHU Purpan, INSERM, U563, BP 3028, F-31024 Toulouse 3, France.
EM marie-paule.roth@inserm.fr
RI meynard, delphine/B-4236-2014; deng, chuxia/N-6713-2016; coppin,
helene/G-4326-2013
NR 43
TC 216
Z9 222
U1 1
U2 11
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 15
PY 2008
VL 112
IS 4
BP 1503
EP 1509
DI 10.1182/blood-2008-03-143354
PG 7
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300077
PM 18539898
ER
PT J
AU Sun, K
Li, MH
Sayers, TJ
Welniak, LA
Murphy, WJ
AF Sun, Kai
Li, Minghui
Sayers, Thomas J.
Welniak, Lisbeth A.
Murphy, William J.
TI Differential effects of donor T-cell cytokines on outcome with
continuous bortezomib administration after allogeneic bone marrow
transplantation
SO BLOOD
LA English
DT Article
ID VERSUS-HOST-DISEASE; NECROSIS-FACTOR-ALPHA; INTERFERON-GAMMA; FAS
LIGAND; LEUKEMIA RESPONSES; TUMOR ACTIVITY; CD4(+); GVHD; INHIBITION;
ALLOANTIGEN
AB Dissociating graft-versus-tumor (GVT) effect from acute graft-versus-host disease (GVHD) still remains a great challenge in allogeneic bone marrow transplantation (allo-BMT). Bortezomib, a proteasome inhibitor, has shown impressive efficacy as a single agent in patients with hematologic malignancies but can result in toxicity when administered late after allogeneic transplantation in murine models of GVHD. In the current study, the effects of T-cell subsets and their associated cytokines on the efficacy of bortezomib in murine allogeneic BMT were investigated. Increased levels of serum tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN-gamma) were observed after allo-BMT and continuous bortezomib administration. Bortezomib-induced GVHD-dependent mortality was preventable by depletion of CD4(+) but not CD8(+) T cells from the donor graft. The improved survival correlated with markedly reduced serum TNF alpha but not IFN gamma levels. Transfer of Tnf(-/-) T cells also protected recipients from bortezomib-induced GVHD-dependent toxicity. Importantly, prolonged administration of bortezomib after transplantation of purified CD8(+) T cells resulted in enhanced GVT response, which was dependent on donor CD8(+) T cell derived IFN gamma. These results indicate that decreased toxicity and increased efficacy of bortezomib in murine allo-BMT can be achieved by removal of CD4(+) T cells from the graft or by inhibiting TNF alpha.
C1 [Sayers, Thomas J.] NCI, Basic Sci Program, SAIC Frederick, Expt Immunol Lab,Canc & Inflammat Program, Frederick, MD 21701 USA.
[Sun, Kai; Li, Minghui; Welniak, Lisbeth A.; Murphy, William J.] Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA.
[Sun, Kai; Li, Minghui; Welniak, Lisbeth A.; Murphy, William J.] Univ Nevada, Sch Med, Dept Immunol, Reno, NV 89557 USA.
RP Murphy, WJ (reprint author), Univ Nevada, Sch Med, Dept Microbiol & Immunol, Mail Stop 199, Reno, NV 89557 USA.
EM wmurphy@medicine.nevada.edu
RI Li, Wayne/F-8303-2011; Li, MH/G-3019-2011; Sayers, Thomas/G-4859-2015
FU Intramural NIH HHS; NCI NIH HHS [R01 CA102282, R01 CA102282-05,
N01CO12400]
NR 38
TC 25
Z9 29
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 AUG 15
PY 2008
VL 112
IS 4
BP 1522
EP 1529
DI 10.1182/blood-2008-03-143461
PG 8
WC Hematology
SC Hematology
GA 336VH
UT WOS:000258392300080
PM 18539902
ER
PT J
AU White, DA
Ballard, ME
Harmon, AC
Holtzman, SG
AF White, David A.
Ballard, Michael E.
Harmon, Alvin C.
Holtzman, Stephen G.
TI Acute delta- and kappa-opioid agonist pretreatment potentiates opioid
antagonist-induced suppression of water consumption
SO BRAIN RESEARCH BULLETIN
LA English
DT Article
DE rats; drinking suppression; antinociception; hot-plate; tail-flick;
acute dependence
ID DIFFERENTIAL ANTAGONISM; MORPHINE-WITHDRAWAL; RECEPTOR SUBTYPES; OPIATE
RECEPTORS; RHESUS-MONKEYS; RATS; DEPENDENCE; MU; NALTREXONE; NALOXONE
AB The primary objective of this study was to determine whether pretreatment with kappa- and delta-opioid agonists potentiates naltrexone-induced suppression of water consumption following 24 h of deprivation. This study also examined the temporal effects of agonist-induced antinociception using the tail-flick and hot-plate tests. Adult male Sprague-Dawley rats were water deprived 20 h and then given an injection (s.c. or i.c.) of an opioid agonist or saline. Drugs included the mu-opioid agonists morphine and DAMGO ([D-Ala2,NMePhe4,Gly-ol5]-enkephalin), the kappa-opioid agonists spiradoline, bremazocine, and U69,593, and the delta-opioid agonists BW 373U86 and DPDPE ([D-Pen2, D-Pen5]-enkephalin). Three hours and forty-five minutes later, animals received a single dose of naltrexone (0.1-30 mg/kg, s.c.) or saline. Fifteen minutes later, animals were allowed free access to water for 30 min. For the tail-flick and hot-plate tests, animals were given a single injection of agonist and tested in both procedures every 30 min for up to 2 h, then hourly up to 6h post-injection. Naltrexone dose-dependently suppressed fluid consumption 24h after deprivation. The effects of naltrexone on drinking were potentiated following pretreatment with at least one dose of the agonists tested except BW 373U86. With the exception of BW 373U86, DAMGO, and DPDPE, all of the opioid agonists produced significant antinociception in the hot-plate test. Only BW 373U86 failed to have an antinociceptive effect in the tail-flick test. By 4h after treatment, drug-induced antinociception had largely waned, suggesting the potentiation of naltrexone-induced drinking suppression was not a result of a direct interaction with the agonists. In conclusion, kappa-opioid and delta-opioid receptors appear to contribute to the manifestation of acute opioid dependence, albeit to a lesser degree than mu-opioid receptors. Published by Elsevier Inc.
C1 [White, David A.; Ballard, Michael E.; Harmon, Alvin C.; Holtzman, Stephen G.] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
RP White, DA (reprint author), Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, Medicat Discovery & Toxicol Branch, 6001 Execut Blvd,Room 4123,MSC 9551, Bethesda, MD 20892 USA.
EM whitedav@nida.nih.gov
RI Ballard, Michael/L-2275-2015
OI Ballard, Michael/0000-0002-2651-6588
FU NIDA NIH HHS [K05 DA000008-30, K05 DA00008, R21 DA011384-02, DA11384]
NR 47
TC 2
Z9 2
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD AUG 15
PY 2008
VL 76
IS 6
BP 597
EP 604
DI 10.1016/j.brainresbull.2008.04.002
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 332BV
UT WOS:000258057600007
PM 18598850
ER
PT J
AU Coleman, RL
Kohn, EC
AF Coleman, Robert L.
Kohn, Elise C.
TI Rationale for combination use of targeted agents in ovarian cancer - Do
we have one?
SO CANCER
LA English
DT Editorial Material
ID RENAL-CELL CARCINOMA; LUNG-CANCER; GEFITINIB ZD1839; PHASE-III;
MUTATIONS; SURVIVAL; IMATINIB; THERAPY; TABLETS; TRIALS
C1 [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Coleman, RL (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, 1155 Herman Pressler Dr, Houston, TX 77030 USA.
EM rcoleman@mdanderson.org
NR 20
TC 1
Z9 1
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD AUG 15
PY 2008
VL 113
IS 4
BP 665
EP 667
DI 10.1002/cncr.23604
PG 3
WC Oncology
SC Oncology
GA 335SV
UT WOS:000258311800001
PM 18623195
ER
PT J
AU Trimble, EL
Harlan, LC
Gius, D
Stevens, J
Schwartz, SM
AF Trimble, Edward L.
Harlan, Linda C.
Gius, David
Stevens, Jennifer
Schwartz, Stephen M.
TI Patterns of care for women with cervical cancer in the United States
SO CANCER
LA English
DT Article
DE cervical cancer; chemoradiation; radiation; chemotherapy; survival
ID CONCURRENT CHEMOTHERAPY; RADIATION-THERAPY; PELVIC RADIATION; CARCINOMA;
CISPLATIN; RADIOTHERAPY; TOMOGRAPHY
AB BACKGROUND. Recommendations for pretreatment evaluation and treatment of cervical cancer have significantly evolved over the last decade because of the results of multiple randomized studies comparing the addition of platin-based chemoradiation as well as the widespread dissemination and use of imaging modalities. This analysis was initiated to determine any systemic changes in management of cervical cancers.
METHODS. Surveillance, Epidemiology, and End Results program data were used to sample newly diagnosed women in 1997, 2000, and 2001 with cancer of the Cervix. A total of 3116 women with no previous diagnosis of cancer were selected, Data were re,abstracted, additional information nor routinely collected was obtained, therapy was verified with the treating physician, and multiple end-points were analyzed.
RESULTS. A marked rise was observed in the percentage receiving chemotherapy (34% to 85%) as well as concurrent chemoradiation (20% to 72%) from 1997 to 2001.
CONCLUSIONS. The significant change in the management and treatment of cervical cancer appears to correspond temporally with the publication of 5 clinical trials, all of which showed a significant improvement in overall survival associated with chemoradiation. This change also corresponded with the NCI Clinical Announcement that was disseminated in 1999 to those oncologists roost likely to treat women with cervical cancer.
C1 [Trimble, Edward L.] NCI, Surg Sect, Bethesda, MD 20892 USA.
[Harlan, Linda C.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Gius, David] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stevens, Jennifer] Informat Management Serv Management, Silver Spring, MD USA.
[Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
RP Trimble, EL (reprint author), NCI, Surg Sect, 6130 Execut Blvd,Suite 7025, Bethesda, MD 20892 USA.
EM tt6m@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 13
TC 21
Z9 22
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD AUG 15
PY 2008
VL 113
IS 4
BP 743
EP 749
DI 10.1002/cncr.23682
PG 7
WC Oncology
SC Oncology
GA 335SV
UT WOS:000258311800013
PM 18618500
ER
PT J
AU Shida, D
Fang, XJ
Kordula, T
Takabe, K
Lepine, S
Alvarez, SE
Milstien, S
Spiegel, S
AF Shida, Dai
Fang, Xianjun
Kordula, Tomasz
Takabe, Kazuaki
Lepine, Sandrine
Alvarez, Sergio E.
Milstien, Sheldon
Spiegel, Sarah
TI Cross-talk between LPA(1) and epidermal growth factor receptors mediates
up-regulation of sphingosine kinase 1 to promote gastric cancer cell
motility and invasion
SO CANCER RESEARCH
LA English
DT Article
ID LYSOPHOSPHATIDIC ACID LPA; KINASE-1 EXPRESSION; COLORECTAL-CANCER;
OVARIAN-CANCER; LINE MCF7; 1-PHOSPHATE; MIGRATION;
SPHINGOSINE-1-PHOSPHATE; PROLIFERATION; CARCINOMA
AB Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lysophospholipid mediators of diverse cellular processes important for cancer progression. S1P is produced by two sphingosine kinases, SphK1 and SphK2. Expression of SphK1 is elevated in many cancers. Here, we report that LPA markedly enhanced SphK1 mRNA and protein in gastric cancer MKN1 cells but had no effect on SphK2. LPA also upregulated SphK1 expression in other human cancer cells that endogenously express the LPA(1) receptor, such as DLD1 colon cancer cells and MDA-MB-231 breast cancer cells, but not in HT29 colon cancer cells or MDA-MB-453 breast cancer cells, which do not express the LPA, receptor. An LPA(1) receptor antagonist or down-regulation of its expression prevented SphK1 and S1P:, receptor up-regulation by LPA. LPA trans-activated the epidermal growth factor receptor (EGFR) in these cells, and the FGFR inhibitor AG1478 attenuated the increased SphK1 and S1P(3) expression induced by LPA. Moreover, down-regulation of SphK1 attenuated LPA-stimulated migration and invasion of MNK1 cells yet had no effect oil expression of neovascularizing factors, such as interleukin (IL)-8, IL-6, urokinase-type plasminogen activator (uPA), or uPA receptor induced by LPA. Finally, down-regulation of S1P(3), but not S1P,, also reduced LPA-stimulated migration and invasion of MKN1 cells. Collectively, our results suggest that SphK1 is a convergence point of multiple cell surface receptors for three different ligands, LPA, EGF, and S1P, which have all been implicated in regulation of motility and invasiveness of cancer cells.
C1 [Shida, Dai; Fang, Xianjun; Kordula, Tomasz; Takabe, Kazuaki; Lepine, Sandrine; Alvarez, Sergio E.; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA.
[Shida, Dai; Fang, Xianjun; Kordula, Tomasz; Takabe, Kazuaki; Lepine, Sandrine; Alvarez, Sergio E.; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA 23298 USA.
[Takabe, Kazuaki] Virginia Commonwealth Univ, Sch Med, Dept Surg, Richmond, VA 23298 USA.
[Milstien, Sheldon] NIMH, Bethesda, MD 20892 USA.
RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA.
EM sspiegel@vcu.edu
FU NIH [CA6177-1, R37GM043880, CA102196]; National Institute of Mental
Health Intramural Research Program [T32GM008695]
FX Received 2/1/2008; revised 5/13/2008; accepted 5/23/2008.; Grant
support: NIH grants CA6177-1 and R37GM043880 (S. Spiegel). CA102196 (X.
Fang). Training Grant T32GM008695 (K. Takabe). and National Institute of
Mental Health Intramural Research Program (S. Milstien). The costs of
publication of this article were defrayed in part by the payment of page
charges. This article must therefore he hereby marked advertisement in
accordance with IS U.S.C. Section 1734 solely to indicate this fact.
NR 50
TC 72
Z9 81
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2008
VL 68
IS 16
BP 6569
EP 6577
DI 10.1158/0008-5472.CAN-08-0411
PG 9
WC Oncology
SC Oncology
GA 338ZP
UT WOS:000258548200013
PM 18701480
ER
PT J
AU Kotliarova, S
Pastorino, S
Kovell, LC
Kotliarov, Y
Song, H
Zhang, W
Bailey, R
Maric, D
Zenklusen, JC
Lee, JW
Fine, HA
AF Kotliarova, Svetlana
Pastorino, Sandra
Kovell, Lara C.
Kotliarov, Yuri
Song, Hua
Zhang, Wei
Bailey, Rolanda
Maric, Dragan
Zenklusen, Jean Claude
Lee, Jeongwu
Fine, Howard A.
TI Glycogen synthase kinase-3 inhibition induces glioma cell death through
c-MYC, nuclear factor-kappa B, and glucose regulation
SO CANCER RESEARCH
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; HUMAN COLON-CANCER; PROTEIN-KINASE; MITOCHONDRIAL
HEXOKINASES; HUMAN GLIOBLASTOMAS; SKELETAL-MUSCLE; GENE-EXPRESSION;
IN-VITRO; APOPTOSIS; ACTIVATION
AB Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, is involved in diverse cellular processes ranging from nutrient and energy homeostasis to proliferation and apoptosis. Its role in glioblastoma multiforme has yet to be elucidated. We identified GSK3 as a regulator of glioblastoma multiforme cell survival using microarray analysis and small-molecule and genetic inhibitors of GSK3 activity. Various molecular and genetic approaches were then used to dissect out the molecular mechanisms responsible for GSK3 inhibition-induced cytotoxicity. We show that multiple small molecular inhibitors of GSK3 activity and genetic down-regulation of GSK3 alpha/beta significantly inhibit glioma cell survival and clonogenicity. The potency of the cytotoxic effects is directly correlated with decreased enzyme activity-activating phosphorylation of GSK3 alpha/beta Y276/Y216 and with increased enzyme activity inhibitory phosphorylation of GSK3 alpha S21. Inhibition of GSK3 activity results in c-MYC activation, leading to the induction of Bax, Bim, DR4/DR5, and tumor necrosis factor-related apoptosis-inducing ligand expression and subsequent cytotoxicity. Additionally, down-regulation of GSK3 activity results in alteration of intracellular glucose metabolism resulting in dissociation of hexokinase It from the outer mitochondrial membrane with subsequent mitochondrial destabilization. Finally, inhibition of GSK3 activity causes a dramatic decrease in intracellular nuclear factor-kappa B activity. Inhibition of GSK3 activity results in c-MYC-dependent glioma cell death through multiple mechanisms, all of which converge on the apoptotic pathways. GSK3 may therefore be an important therapeutic target for gliomas. Future studies will further define the optimal combinations of GSK3 inhibitors and cytotoxic agents for use in gliomas and other cancers.
C1 [Kotliarova, Svetlana; Pastorino, Sandra; Kovell, Lara C.; Kotliarov, Yuri; Song, Hua; Zhang, Wei; Bailey, Rolanda; Zenklusen, Jean Claude; Lee, Jeongwu; Fine, Howard A.] NCI, Neurooncol Branch, Bethesda, MD 20892 USA.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Fine, HA (reprint author), NCI, Neurooncol Branch, Room 225,Bloch Bldg 82,9030 Old Georgetown Rd, Bethesda, MD 20892 USA.
EM hfine@mail.nih.gov
RI Kotliarov, Yuri/B-6938-2017
FU NIH; National Cancer Institute; Center for Cancer Research
FX Received 3/5/2008; revised 5/8/2008; accepted 6/3/2008.; Grant support:
Intramural Research Program of the NIH. National Cancer Institute,
Center for Cancer Research.; The costs of publication of this article
were defrayed in part. by the payment of page charges. This article must
therefore lie hereby marked advertisement in accordance with 19 U.S.C.
Section 1734 solely to indicate this fact.; We thank The Developmental
Therapeutics Program,The National Cancer Institute (Bethesda, MD) and
Dr. Zaharevitz for kindly providing GSK3 inhibitors 705701, 708244. and
709125; Dr. Sears for providing us with an aliquot of anti-phospho S62
c-MYC antibody; Dr. Baba for the generous gilt. of the
anti-glycogen-specific antibody., Dr. Nogueira for sharing her detailed
protocol Mull us on Hexokinase activity, assays (NF-kappaB plasmid was
kindly provided by Drs. Bren arid Paya from Mayo Clinic College of
Medicine); and James W Nagle and Deborah Kauffman From National
Institute of Neurological Disorders and Stroke sequencing facility arid
Dr. Carolyn L. Smith from National Institute of Neurological Disorders
arid Stroke light image facility for their valuable contributions to
this work.
NR 46
TC 119
Z9 121
U1 3
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2008
VL 68
IS 16
BP 6643
EP 6651
DI 10.1158/0008-5472.CAN-08-0850
PG 9
WC Oncology
SC Oncology
GA 338ZP
UT WOS:000258548200021
PM 18701488
ER
PT J
AU Steeg, PS
Horak, CE
Miller, KD
AF Steeg, Patricia S.
Horak, Christine E.
Miller, Kathy D.
TI Clinical-translational approaches to the Nm23-H1 metastasis suppressor
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID NUCLEOSIDE DIPHOSPHATE KINASE; EPSTEIN-BARR-VIRUS; LYSOPHOSPHATIDIC ACID
RECEPTOR; BREAST-CARCINOMA CELLS; ATP-CITRATE LYASE; MEDROXYPROGESTERONE
ACETATE; CANCER-CELLS; TUMOR-METASTASIS; GENE-EXPRESSION; GROWTH-FACTOR
AB Nm23-H1 significantly reduces metastasis without effects on primary tumor size and was the first discovered metastasis suppressor gene. At least three mechanisms are thought to contribute to the metastasis-suppressive effect of Nm23-H1: (a) its histidine kinase activity toward ATP-citrate lyase, aldolase C, and the kinase suppressor of ras, with the last inactivating mitogen-activated protein kinase signaling; (b) binding proteins that titer out "free" Nm23-H1 and inhibit its ability to suppress metastasis; and (c) altered gene expression downstream of Nm23-H1, particularly an inverse association with the lysophosphatidic acid receptor endothelial differentiation gene-28 (EDG2). Most metastasis suppressor genes, including Nm23-H1, affect metastatic colonization, which is the outgrowth of tumor cells in distant locations; therefore, they are of high translational interest. A phase II trial is ongoing to test the hypothesis that a compound, high-dose medroxyprogesterone acetate (MPA), used as an unconventional gluocorticoid, will stimulate breast cancer cells to reexpress Nm23-H1 and limit subsequent metastatic colonization.
C1 [Steeg, Patricia S.; Horak, Christine E.] NCI, Ctr Canc Res, Mol Pharmacol Lab, Womens Canc Sect, Bethesda, MD 20892 USA.
[Miller, Kathy D.] Indiana Univ, Div Hematol Oncol, Indianapolis, IN 46204 USA.
RP Steeg, PS (reprint author), NCI, Ctr Canc Res, Mol Pharmacol Lab, Womens Canc Sect, Room 1122,37 Convent Dr, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
FU GlaxoSmith Kline
FX P.S. Steeg has a commercial research grant from GlaxoSmith Kline.
NR 84
TC 53
Z9 58
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2008
VL 14
IS 16
BP 5006
EP 5012
DI 10.1158/1078-0432.CCR-08-0238
PG 7
WC Oncology
SC Oncology
GA 338QX
UT WOS:000258523800003
PM 18698018
ER
PT J
AU Milenic, DE
Garmestani, K
Brady, ED
Baidoo, KE
Albert, PS
Wong, KJ
Flynn, J
Brechbiel, M
AF Milenic, Diane E.
Garmestani, Kayhan
Brady, Erik D.
Baidoo, Kwamena E.
Albert, Paul S.
Wong, Karen J.
Flynn, Joseph
Brechbiel, MartinW.
TI Multimodality therapy: Potentiation of high linear energy transfer
radiation with paclitaxel for the treatment of disseminated peritoneal
disease
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID COMBINED-MODALITY RADIOIMMUNOTHERAPY; CANCER CELLS; BREAST-CANCER;
MONOCLONAL-ANTIBODY; PANCREATIC-CANCER; PROSTATE-CANCER; INTRAPERITONEAL
RADIOIMMUNOTHERAPY; SPECTROPHOTOMETRIC METHOD; TARGETING HER2;
OVARIAN-CANCER
AB Purpose: Studies herein explore paclitaxel enhancement of the therapeutic efficacy of alpha-particle-targeted radiation therapy.
Experimental Design: Athymic mice bearing 3 day i.p. LS-174T xenografts were treated with 300 or 600 mu g paclitaxel at 24 h before, concurrently, or 24 h after [Bi-213] or [Pb-212]trastuzumab.
Results: Paclitaxel (300 or 600 mu g) followed 24 h later with [Bi-213]trastuzumab (500 mu Ci) provided no therapeutic enhancement. Paclitaxel (300 mu g) administered concurrently with [Bi-213] trastuzumab or [Bi-213] HulgG resulted in median survival of 93 and 37 days, respectively; no difference was observed with 600 mu g paclitaxel. Mice receiving just [Bi-213]trastuzumab or [Bi-213]HulgG or left untreated had a median survival of 31, 21, and 15 days, respectively, 23 days for just either paclitaxel dose alone. Paclitaxel (300 or 600 mu) given 24 h after [Bi-213]trastuzumab increased median survival to 100 and 135 days, respectively. The greatest improvement in median survival (198 days) was obtained with two weekly doses of paclitaxel (600 mu g) followed by [Bi-213]trastuzumab. Studies were also conducted investigating paclitaxel administered 24 h before, concurrently, or 24 h after [Pb-212]trastuzumab (10 mu Ci). The 300 mu g paclitaxel 24 h before radioimmunotherapy (RIT) failed to provide benefit, whereas 600 mu g extended the median survival from 44 to 171 days.
Conclusions: These results suggest that regimens combining chemotherapeutics and high linear energy transfer (LET) RIT may have tremendous potential in the management and treatment of cancer patients. Dose dependency and administration order appear to be critical factors requiring careful investigation.
C1 [Milenic, Diane E.; Garmestani, Kayhan; Brady, Erik D.; Baidoo, Kwamena E.; Brechbiel, MartinW.] NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Milenic, Diane E.; Wong, Karen J.] NCI, NIH, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Albert, Paul S.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Flynn, Joseph] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
RP Milenic, DE (reprint author), NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, 10 Ctr Dr,MSC-1088,Bldg 10,Room 11340, Bethesda, MD 20892 USA.
EM dm71q@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 50
TC 24
Z9 25
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2008
VL 14
IS 16
BP 5108
EP 5115
DI 10.1158/1078-0432.CCR-08-0256
PG 8
WC Oncology
SC Oncology
GA 338QX
UT WOS:000258523800014
PM 18698028
ER
PT J
AU Walker, EB
Haley, D
Petrausch, U
Floyd, K
Miller, W
Sanjuan, N
Alvord, G
Fox, BA
Urba, WJ
AF Walker, Edwin B.
Haley, Daniel
Petrausch, Ulf
Floyd, Kevin
Miller, William
Sanjuan, Nelson
Alvord, Greg
Fox, Bernard A.
Urba, Walter J.
TI Phenotype and functional characterization of long-term gp100-specific
memory CD8(+) T cells in disease-free melanoma patients before and after
boosting immunization
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; IN-VIVO; GP100(209-2M) PEPTIDE; LINEAGE
RELATIONSHIP; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; TUMOR
PROGRESSION; FLOW-CYTOMETRY; SELF-ANTIGENS; CD8+T CELLS
AB Purpose: Effective cancer vaccines must both drive a strong CTL response and sustain long-term memoryTcells capable of rapid recall responses to tumor antigens. We sought to characterize the phenotype and function of gp100 peptide-specific memory CD8(+) T cells in melanoma patients after primary gp100(209-2M) immunization and assess the anamnestic response to boosting immunization. Experimental Design: Eight-color flow cytometry analysis of gp100-specific CD8(+) Tcells was done on peripheral blood mononuclear cells collected shortly after the primary vaccine regimen, 12 to 24 months after primary vaccination, and after boosting immunization. The anamnestic response was assessed by comparing the frequency of circulating gp100-specific T cells before and after boosting. Gp100 peptide-induced in vitro functional avidity and proliferation responses and melanoma-stimulated T-cell CD107 mobilization were compared for cells from all three time points for multiple patients. Results:The frequency of circulating gp100-specific memory CD8(+) Tcells was comparable with cytomegalovirus-specific and FLU-specific T cells in the same patients, and the cells exhibited anamnestic proliferation after boosting. Their phenotypes were not unique, and individual patients exhibited one of two distinct phenotype signatures that were homologous to either cytomegalovirus-specific or FLU-specific memoryTcells. Gp100-specific memoryTcells showed some properties of competent memoryTcells, such as heightened in vitro peptide-stimulated proliferation and increase in central memory (T-CM) differentiation when compared with T-cell responses measured after the primary vaccine regimen. However, they did not acquire enhanced functional avidity usually associated with competent memory T-cell maturation. Conclusions: Although vaccination with class I - restricted melanoma peptides alone can break tolerance to self-tumor antigens, it did not induce fully competent memory CD8(+) Tcells-even in disease-free patients. Data presented suggest other vaccine strategies will be required to induce functionally robust long-term memory T cells.
C1 [Walker, Edwin B.; Haley, Daniel; Petrausch, Ulf; Floyd, Kevin; Miller, William; Sanjuan, Nelson; Fox, Bernard A.; Urba, Walter J.] Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR 97213 USA.
[Alvord, Greg] Frederick Canc Res & Dev Ctr, Data Management Serv, Frederick, MD USA.
RP Walker, EB (reprint author), Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, 4805 NE Glisan St,N Pavil,2nd Floor,2N35, Portland, OR 97213 USA.
EM Edwin.walker@providence.org
FU NCI NIH HHS [R01 CA119123, R01 CA119123-01, R21 CA099265, R21
CA099265-02, RA21-CA099265-02, R21 CA082614-01, R01-CA119123]; PHS HHS
[IR21-CS82614-01]
NR 67
TC 21
Z9 22
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 AUG 15
PY 2008
VL 14
IS 16
BP 5270
EP 5283
DI 10.1158/1078-0432.CCR-08-0022
PG 14
WC Oncology
SC Oncology
GA 338QX
UT WOS:000258523800034
PM 18698047
ER
PT J
AU Lechleider, RJ
Arlen, PM
Tsang, KY
Steinberg, SM
Yokokawa, J
Cereda, V
Camphausen, K
Schlom, J
Dahut, WL
Gulley, JL
AF Lechleider, Robert J.
Arlen, Philip M.
Tsang, Kwong-Yok
Steinberg, Seth M.
Yokokawa, Junko
Cereda, Vittore
Camphausen, Kevin
Schlom, Jeffrey
Dahut, William L.
Gulley, James L.
TI Safety and immunologic response of a viral vaccine to prostate-specific
antigen in combination with radiation therapy when metronomic-dose
interleukin 2 is used as an adjuvant
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID REGULATORY T-CELLS; RADICAL PROSTATECTOMY; IN-VIVO; RECOMBINANT
INTERLEUKIN-2; DEFINITIVE RADIOTHERAPY; EXTERNAL RADIOTHERAPY; ANDROGEN
SUPPRESSION; COMBINED ORCHIECTOMY; PHASE-II; CANCER
AB Purpose: We have previously reported on the safety and immunologic response of a poxvirus-based vaccine encoding prostate-specific antigen (PSA) used in combination with radiation therapy in patients with localized prostate cancer. We hypothesized that a "metronomic" dose of interleukin 2 (IL-2) as a biological adjuvant would cause less toxicity while maintaining immunologic response. Experimental Design: Eighteen patients with localized prostate cancer were treated in a single-arm trial using previously established doses of vaccine and radiation therapy. The vaccine used was a recombinant vaccinia virus engineered to encode PSA admixed with a recombinant vaccinia encoding the costimulatory molecule B7.1, followed by booster vaccinations with a recombinant fowlpox vector expressing PSA. Patients received a total of eight planned vaccination cycles, once every 4 weeks, with granulocyte-macrophage colony-stimulating factor given on days 1 to 4 and interleukin 2 (IL-2) at a dose of 0.6 MIU/M-2 given from days 8 to 21 after each vaccination. Definitive external beam radiation therapy was initiated after the third vaccination cycle. Patients were evaluated for safety and immunologic response. Toxicity and immunologic activity were compared with the previously reported regimen containing a higher dose of IL-2. Results: Seventeen of 18 patients received all eight cycles of vaccine with IL-2. Five of eight HLA-A2(+) patients evaluated had an increase in PSA-specific T cells of >= 3-fold. Toxicities were generally mild, with only seven vaccination cycles of 140 given resulting in grade 3 toxicities possibly attributable to IL-2. Conclusions: Metronomic-dose IL-2 in combination with vaccine and radiation therapy is safe, can induce prostate-specific immune responses, and has immunologic activity similar to low-dose IL-2, with markedly reduced toxicities.
C1 [Lechleider, Robert J.; Arlen, Philip M.; Tsang, Kwong-Yok; Steinberg, Seth M.; Yokokawa, Junko; Cereda, Vittore; Camphausen, Kevin; Schlom, Jeffrey; Gulley, James L.] NCI, NIH, Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, NIH, Ctr Canc Res, Biostat & Data Management Sect,Off Clin Director, Bethesda, MD 20892 USA.
[Dahut, William L.] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
[Lechleider, Robert J.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Oncol Drug Prod, Silver Spring, MD USA.
RP Schlom, J (reprint author), NCI, NIH, Ctr Canc Res, Tumor Immunol & Biol Lab, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Intramural NIH HHS [Z01 BC010425-09]
NR 36
TC 60
Z9 61
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2008
VL 14
IS 16
BP 5284
EP 5291
DI 10.1158/1078-0432.CCR-07-5162
PG 8
WC Oncology
SC Oncology
GA 338QX
UT WOS:000258523800035
PM 18698048
ER
PT J
AU Effros, RB
Fletcher, CV
Gebo, K
Halter, JB
Hazzard, WR
Horne, FM
Huebner, RE
Janoff, EN
Justice, AC
Kuritzkes, D
Nayfield, SG
Plaeger, SF
Schmader, KE
Ashworth, JR
Campanelli, C
Clayton, CP
Rada, B
Woolard, NF
High, KP
AF Effros, Rita B.
Fletcher, Courtney V.
Gebo, Kelly
Halter, Jeffrey B.
Hazzard, William R.
Horne, Frances McFarland
Huebner, Robin E.
Janoff, Edward N.
Justice, Amy C.
Kuritzkes, Daniel
Nayfield, Susan G.
Plaeger, Susan F.
Schmader, Kenneth E.
Ashworth, John R.
Campanelli, Christine
Clayton, Charles P.
Rada, Beth
Woolard, Nancy F.
High, Kevin P.
TI Workshop on HIV infection and aging: What is known and future research
directions
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; MULTICENTER
AIDS COHORT; VARICELLA-ZOSTER-VIRUS; CHRONIC KIDNEY-DISEASE; HEPATITIS-C
VIRUS; CD4 CELL COUNT; LYMPHATIC TISSUE FIBROSIS; IMMUNE RISK PHENOTYPE;
AGE-RELATED-CHANGES
AB Highly active antiretroviral treatment has resulted in dramatically increased life expectancy among patients with HIV infection who are now aging while receiving treatment and are at risk of developing chronic diseases associated with advanced age. Similarities between aging and the courses of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome suggest that HIV infection compresses the aging process, perhaps accelerating comorbidities and frailty. In a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the HIV Medical Association, the National Institute on Aging, and the National Institute on Allergy and Infectious Diseases, researchers in infectious diseases, geriatrics, immunology, and gerontology met to review what is known about HIV infection and aging, to identify research gaps, and to suggest high priority topics for future research. Answers to the questions posed are likely to help prioritize and balance strategies to slow the progression of HIV infection, to address comorbidities and drug toxicity, and to enhance understanding about both HIV infection and aging.
C1 [High, Kevin P.] Wake Forest Univ, Sch Med, Dept Internal Med, Infect Dis Sect, Winston Salem, NC 27157 USA.
[Effros, Rita B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Fletcher, Courtney V.] Univ Nebraska, Hlth Sci Ctr, Omaha, NE 68182 USA.
[Gebo, Kelly] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Huebner, Robin E.; Plaeger, Susan F.] NIAID, Bethesda, MD 20892 USA.
[Nayfield, Susan G.] NIA, Bethesda, MD 20892 USA.
[Halter, Jeffrey B.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Hazzard, William R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Horne, Frances McFarland; Ashworth, John R.; Clayton, Charles P.] Assoc Specialty Prof, Washington, DC USA.
[Janoff, Edward N.] Univ Colorado, Sch Med, Mucolsal & Vaccine Res Program Colorado, Denver, CO 80202 USA.
[Justice, Amy C.] Yale Univ, West Haven, CT USA.
[Kuritzkes, Daniel] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Kuritzkes, Daniel] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rada, Beth] Infect Dis Society Amer, Arlington, VA USA.
[Schmader, Kenneth E.] Duke Univ, Sch Med, Durham, NC 27710 USA.
[Campanelli, Christine] Amer Geriatr Society, New York, NY USA.
RP High, KP (reprint author), Wake Forest Univ, Sch Med, Dept Internal Med, Infect Dis Sect, 100 Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM khigh@wfubmc.edu
RI Gebo, Kelly/B-9223-2009
FU NIAAA NIH HHS [U10 AA013566, U10 AA013566-08]
NR 174
TC 267
Z9 270
U1 4
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 15
PY 2008
VL 47
IS 4
BP 542
EP 553
DI 10.1086/590150
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 327VD
UT WOS:000257755700022
PM 18627268
ER
PT J
AU Yang, M
Hanson, T
Christensen, R
AF Yang, Mingan
Hanson, Timothy
Christensen, Ronald
TI Nonparametric Bayesian estimation of a bivariate density with interval
censored data
SO COMPUTATIONAL STATISTICS & DATA ANALYSIS
LA English
DT Article
ID MULTIPLE IMPUTATION; MAXIMUM-LIKELIHOOD; SURVIVAL-DATA; MODEL
AB Mixture of Polya trees nonparametric estimation of a bivariate density is presented for interval censored data. Real and simulated data are analyzed and compared with nonparametric maximum likelihood (NPMLE) and Bayesian G-spline estimates. An advantage of the mixture of Polya trees approach over the NPMLE is the relative ease with which continuous bivariate density and hazard plots are obtained. (c) 2008 Published by Elsevier B.V.
C1 [Yang, Mingan] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Hanson, Timothy] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Christensen, Ronald] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA.
RP Yang, M (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA.
EM mingany@yahoo.com
RI Hanson, Timothy/A-9127-2016
NR 21
TC 6
Z9 6
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-9473
J9 COMPUT STAT DATA AN
JI Comput. Stat. Data Anal.
PD AUG 15
PY 2008
VL 52
IS 12
BP 5202
EP 5214
DI 10.1016/j.csda.2008.04.022
PG 13
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA 346NR
UT WOS:000259075900013
ER
PT J
AU Wan, LB
Pan, H
Hannenhalli, S
Cheng, Y
Ma, J
Fedoriw, A
Lobanenkov, V
Latham, KE
Schultz, RM
Bartolomei, MS
AF Wan, Le-Ben
Pan, Hua
Hannenhalli, Sridhar
Cheng, Yong
Ma, Jun
Fedoriw, Andrew
Lobanenkov, Victor
Latham, Keith E.
Schultz, Richard M.
Bartolomei, Marisa S.
TI Maternal depletion of CTCF reveals multiple functions during oocyte and
preimplantation embryo development
SO DEVELOPMENT
LA English
DT Article
DE CTCF; mouse; oocyte; preimplantation embryo; meiosis
ID IMPRINTING CONTROL REGION; ENHANCER-BLOCKING ACTIVITY; INSULATOR PROTEIN
CTCF; RNA-POLYMERASE-II; MOUSE DEVELOPMENT; EFFECT GENE; C-MYC;
BINDING-SITES; HUMAN GENOME; H19/IGF2 LOCUS
AB CTCF is a multifunctional nuclear factor involved in epigenetic regulation. Despite recent advances that include the systematic discovery of CTCF-binding sites throughout the mammalian genome, the in vivo roles of CTCF in adult tissues and during embryonic development are largely unknown. Using transgenic RNAi, we depleted maternal stores of CTCF from growing mouse oocytes, and identified hundreds of misregulated genes. Moreover, our analysis suggests that CTCF predominantly activates or derepresses transcription in oocytes. CTCF depletion causes meiotic defects in the egg, and mitotic defects in the embryo that are accompanied by defects in zygotic gene expression, and culminate in apoptosis. Maternal pronuclear transfer and CTCF mRNA microinjection experiments indicate that CTCF is a mammalian maternal effect gene, and that persistent transcriptional defects rather than persistent chromosomal defects perturb early embryonic development. This is the first study detailing a global and essential role for CTCF in mouse oocytes and preimplantation embryos.
C1 [Wan, Le-Ben; Fedoriw, Andrew; Bartolomei, Marisa S.] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
[Pan, Hua; Ma, Jun; Schultz, Richard M.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
[Hannenhalli, Sridhar] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
[Hannenhalli, Sridhar] Univ Penn, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA.
[Cheng, Yong; Latham, Keith E.] Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19104 USA.
[Cheng, Yong; Latham, Keith E.] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19104 USA.
[Lobanenkov, Victor] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Bartolomei, MS (reprint author), Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
EM bartolom@mail.med.upenn.edu
OI Lobanenkov, Victor/0000-0001-6665-3635
FU NCRR NIH HHS [R01 RR018907, RR018907]; NICHD NIH HHS [HD42026, R01
HD042026, R01 HD042026-06A1]; NIGMS NIH HHS [GM078203, GM08216, R21
GM078203, S06 GM008216]
NR 61
TC 53
Z9 57
U1 0
U2 9
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD AUG 15
PY 2008
VL 135
IS 16
BP 2729
EP 2738
DI 10.1242/dev.024539
PG 10
WC Developmental Biology
SC Developmental Biology
GA 330EP
UT WOS:000257922600006
PM 18614575
ER
PT J
AU Liu, J
Qian, SY
Guo, Q
Jiang, J
Waalkes, MP
Mason, RP
Kadiiska, MB
AF Liu, Jie
Qian, Steven Y.
Guo, Qiong
Jiang, Jinjie
Waalkes, Michael P.
Mason, Ronald P.
Kadiiska, Maria B.
TI Cadmium generates reactive oxygen- and carbon-centered radical species
in rats: Insights from in vivo spin-trapping studies
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE cadmium; free radicals; rat; spin-trapping; electron spin resonance
spectroscopy
ID INDUCED LIVER-INJURY; OXIDATIVE STRESS; INDUCED HEPATOTOXICITY;
LIPID-PEROXIDATION; INDUCED APOPTOSIS; CELL-CULTURES; KUPFFER CELLS;
NULL MICE; WILD-TYPE; TOXICITY
AB Cadmium (Cd) is a known industrial and environmental pollutant. In the present work, an in vivo spin-trapping technique was used in conjunction with electron spin resonance (ESR) spectroscopy to investigate free radical generation in rats following administration of cadmium chloride (CdCl(2), 40 mu mol/kg) and the spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN, 1 g/kg). In Cd-treated rats, POBN radical adducts were formed in the liver, were excreted into the bile, and exhibited an ESR spectrum consistent with a carbon-centered radical species probably derived from endogenous lipids. Isotope substitution of dimethyl strlfoxide [(CH(3))(2)SO] with (13)C demonstrated methyl radical formation (POBN/(center dot 13)CH(3)). This adduct indicated the production of hydroxyl radical, which reacted with [((13)CH(3))(2)SO] to form (center dot 13)CH(3), which then reacted with POBN to form POBN/(center dot 13)CH(3). Depletion of hepatic glutathione by diethyl maleate significantly increased free radical production, whereas inactivation of Kupffer cells by gadolinium chloride and chelation of iron by desferal inhibited it. Treatment with the xanthine oxidase inhibitor allopurinol, the catalase inhibitor aminobenzotriazole, or the cytochrome P450 inhibitor 3-amino-1,2,4-triazole had no effect. This is the first study to show Cd generation of reactive oxygen- and carbon-centered radical species by involvement of both iron mediation through iron-catalyzed reactions and activation of Kupffer cells, the resident liver macrophages. Published by Elsevier Inc.
C1 [Jiang, Jinjie; Mason, Ronald P.; Kadiiska, Maria B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Liu, Jie; Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NIH, Res Triangle Pk, NC 27709 USA.
[Qian, Steven Y.] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA.
[Guo, Qiong] La Jolla Labs, Pfizer Global Res & Dev, Dept Vaccine Res, San Diego, CA 92121 USA.
RP Kadiiska, MB (reprint author), NIEHS, NIH, 111 TW Alexander Dr,MD FO-02, Res Triangle Pk, NC 27709 USA.
EM Kadiiska@niehs.nih.gov
FU Intramural NIH HHS [Z01 ES050117-17, NIH0011069698, Z99 ES999999]
NR 46
TC 38
Z9 43
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 15
PY 2008
VL 45
IS 4
BP 475
EP 481
DI 10.1016/j.freeradbiomed.2008.04.041
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 339ZB
UT WOS:000258614700013
PM 18501199
ER
PT J
AU Dong, J
Nanda, JS
Rahman, H
Pruitt, MR
Shin, BS
Wong, CM
Lorsch, JR
Hinnebusch, AG
AF Dong, Jinsheng
Nanda, Jagpreet S.
Rahman, Hafsa
Pruitt, Margaret R.
Shin, Byung-Sik
Wong, Chi-Ming
Lorsch, Jon R.
Hinnebusch, Alan G.
TI Genetic identification of yeast 18S rRNA residues required for efficient
recruitment of initiator tRNA(Met) and AUG selection
SO GENES & DEVELOPMENT
LA English
DT Article
DE GCN4 translational control; rRNA; ribosome; scanning; translation
initiation
ID START CODON SELECTION; GCN4 MESSENGER-RNA; TRANSLATION INITIATION;
SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; 80S RIBOSOME; IN-VIVO;
SUBUNIT; COMPLEX; EIF1A
AB High-resolution structures of bacterial 70S ribosomes have provided atomic details about mRNA and tRNA binding to the decoding center during elongation, but such information is lacking for preinitiation complexes (PICs). We identified residues in yeast 18S rRNA critical in vivo for recruiting methionyl tRNAi(Met) to 40S subunits during initiation by isolating mutations that derepress GCN4 mRNA translation. Several such Gcd(-) mutations alter the A928:U1389 base pair in helix 28 (h28) and allow PICs to scan through the start codons of upstream ORFs that normally repress GCN4 translation. The A928U substitution also impairs TC binding to PICs in a reconstituted system in vitro. Mutation of the bulge G926 in h28 and certain other residues corresponding to direct contacts with the P-site codon or tRNA in bacterial 70S complexes confer Gcd(-) phenotypes that (like A928 substitutions) are suppressed by overexpressing tRNAi Met. Hence, the nonconserved 928: 1389 base pair in h28, plus conserved 18S rRNA residues corresponding to P-site contacts in bacterial ribosomes, are critical for efficient Met-tRNAi(Met) binding and AUG selection in eukaryotes.
C1 [Dong, Jinsheng; Rahman, Hafsa; Pruitt, Margaret R.; Shin, Byung-Sik; Wong, Chi-Ming; Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
[Nanda, Jagpreet S.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
RP Hinnebusch, AG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
EM ahinnebusch@nih.gov
RI Nanda, Jagpreet/F-9833-2011; Wong, Chi-Ming/A-7627-2013;
OI Wong, Chi-Ming/0000-0002-0025-7135; Lorsch, Jon/0000-0002-4521-4999
FU Intramural Research Program of NIH; NIH [GM62128]
FX We thank Masayasu Nomura and Jon Dinman for strains, plasmids, and
advice Venki Ramakrishnan for helpful discussion regarding C934,
Christian Spahn for valuable advice, and Tom Dever for critical
comments. This work was supported by the Intramural Research Program of
NIH and by NIH grant GM62128 to J.R.L.
NR 36
TC 22
Z9 22
U1 0
U2 2
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD AUG 15
PY 2008
VL 22
IS 16
BP 2242
EP 2255
DI 10.1101/gad.1696608
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 338DW
UT WOS:000258486800010
PM 18708582
ER
PT J
AU Burdick, KE
Kamiya, A
Hodgkinson, CA
Lencz, T
DeRosse, P
Ishizuka, K
Elashvili, S
Arai, H
Goldman, D
Sawa, A
Malhotra, AK
AF Burdick, Katherine E.
Kamiya, Atsushi
Hodgkinson, Colin A.
Lencz, Todd
DeRosse, Pamela
Ishizuka, Koko
Elashvili, Sarah
Arai, Hiroyuki
Goldman, David
Sawa, Akira
Malhotra, Anil K.
TI Elucidating the relationship between DISC1, NDEL1and NDE1 and the risk
for schizophrenia: Evidence of epistasis and competitive binding
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID NEURITE OUTGROWTH; NEURONAL MIGRATION; CYTOPLASMIC DYNEIN; GENOTYPE
DATA; NUDEL; DISRUPTED-IN-SCHIZOPHRENIA-1; PROTEIN; LIS1; ASSOCIATION;
POPULATION
AB DISC1 influences susceptibility to psychiatric disease and related phenotypes. Intact functions of DISC1 and its binding partners, NDEL1 and NDE1, are critical to neurodevelopmental processes aberrant in schizophrenia (SZ). Despite evidence of an NDEL1-DISC1 protein interaction, there have been no investigations of theNDEL1 gene or the relationship betweenNDEL1 andDISC1 in SZ. We genotyped sixNDEL1 single-nucleotide polymorphisms (SNPs) in 275 Caucasian SZ patients and 200 controls and tested for association and interaction between the functional SNP Ser704Cys inDISC1 andNDEL1. We also evaluated the relationship betweenNDE1 andDISC1 genotype and SZ. Finally, in a series ofin vitro assays, we determined the binding profiles of NDEL1 and NDE1, in relation toDISC1 Ser704Cys. We observed a single haplotype block withinNDEL1; the majority of variation was captured byNDEL1 rs1391768. We observed a significant interaction between rs1391768 andDISC1 Ser704Cys, with the effect ofNDEL1 on SZ evident only against the background ofDISC1 Ser704 homozygosity. Secondary analyses revealed no direct relationship betweenNDE1 genotype and SZ; however, there was an opposite pattern of risk forNDE1 genotype when conditioned onDISC1 Ser704Cys, withNDE1 rs3784859 imparting a significant effect but only in the context of a Cys-carrying background. In addition, we report opposing binding patterns of NDEL1 and NDE1 to Ser704 versus Cys704, at the same DISC1 binding domain. These data suggest thatNDEL1 significantly influences risk for SZ via an interaction withDISC1. We propose a model where NDEL1 and NDE1 compete for binding with DISC1.
C1 [Burdick, Katherine E.; Lencz, Todd; DeRosse, Pamela; Malhotra, Anil K.] N Shore Long Isl Jewish Hlth System, Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY 11004 USA.
[Burdick, Katherine E.; Lencz, Todd; Malhotra, Anil K.] Albert Einstein Coll Med, Dept Psychiat, New York, NY USA.
[Burdick, Katherine E.; Lencz, Todd; Malhotra, Anil K.] Feinstein Inst Med Res, Manhasset, NY USA.
[Kamiya, Atsushi; Ishizuka, Koko; Elashvili, Sarah; Sawa, Akira] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA.
[Hodgkinson, Colin A.; Goldman, David] NIAAA, Bethesda, MD USA.
[Arai, Hiroyuki] Univ Tokyo, Fac Pharmaceut Sci, Dept Hlth Chem, Grad Sch Pharmaceut Sci, Tokyo 113, Japan.
[Sawa, Akira] Johns Hopkins Univ, Dept Neurosci, Grad Program Cellular & Mol Med, Baltimore, MD USA.
RP Burdick, KE (reprint author), N Shore Long Isl Jewish Hlth System, Zucker Hillside Hosp, Dept Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA.
EM kburdick@lij.edu
RI Burdick, Katherine/G-6124-2012; Goldman, David/F-9772-2010; kamiya,
atsushi/L-8550-2016; Lencz, Todd/J-3418-2014
OI Goldman, David/0000-0002-1724-5405; Lencz, Todd/0000-0001-8586-338X
FU Intramural NIH HHS [Z01 AA000301-09]; NIMH NIH HHS [K23 MH077807, K99
MH086756, K99 MH086756-01, K99 MH086756-02, R00 MH086756, R00
MH086756-03]
NR 47
TC 69
Z9 72
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2008
VL 17
IS 16
BP 2462
EP 2473
DI 10.1093/hmg/ddn146
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 330SL
UT WOS:000257963000006
PM 18469341
ER
PT J
AU Silvera, SAN
Mayne, ST
Risch, H
Gammon, MD
Vaughan, TL
Chow, WH
DubroW, R
Schoenberg, JB
Stanford, JL
West, AB
Rotterdarm, H
Blot, WJ
Fratimeni, JF
AF Silvera, Stephanie A. Navarro
Mayne, Susan T.
Risch, Harvey
Gammon, Marilee D.
Vaughan, Thomas L.
Chow, Wong-Ho
Dubrow, Robert
Schoenberg, Janet B.
Stanford, Janet L.
West, A. Brian
Rotterdarm, Heidrun
Blot, William J.
Fratimeni, Joseph F., Jr.
TI Food group intake and risk of subtypes of esophageal and gastric cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE esophageal neoplasms; gastric neoplasms; food groups; case-control
ID GASTROESOPHAGEAL-REFLUX DISEASE; SQUAMOUS-CELL CARCINOMA; N-NITROSO
COMPOUNDS; NUTRIENT INTAKE; DIETARY INDICATORS; PHARYNGEAL CANCER;
LARYNGEAL-CANCER; STOMACH-CANCER; BODY-MASS; ADENOCARCINOMA
AB Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non-cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multicenter, population-based case-control study in Connecticut, New Jersey and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI=1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73) and noncardia gastric adenocarcinoma (OR = 1.39, 95 % CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and noncardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High-fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high-fat dairy was associated with increased risk of gastric cardia adenocarcinoma. (c) 2008 Wiley-Liss, Inc.
C1 [Silvera, Stephanie A. Navarro] Montclair State Univ, Dept Hlth & Nutr Sci, Montclair, NJ 07043 USA.
[Mayne, Susan T.; Risch, Harvey; Dubrow, Robert] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Gammon, Marilee D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Vaughan, Thomas L.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Vaughan, Thomas L.; Schoenberg, Janet B.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Chow, Wong-Ho; Fratimeni, Joseph F., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[West, A. Brian] NYU, Dept Pathol, New York, NY 10016 USA.
[Rotterdarm, Heidrun] Columbia Univ, Dept Pathol, New York, NY USA.
[Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Stanford, Janet L.] New Jersey Dept Hlth & Senior Serv, Ctr Canc Initiat, Trenton, NJ 08625 USA.
RP Silvera, SAN (reprint author), Montclair State Univ, Dept Hlth & Nutr Sci, 1 Normal Ave, Montclair, NJ 07043 USA.
EM silveras@mail.montelair.edu
NR 58
TC 53
Z9 53
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2008
VL 123
IS 4
BP 852
EP 860
DI 10.1002/ijc.23544
PG 9
WC Oncology
SC Oncology
GA 328SL
UT WOS:000257818000015
ER
PT J
AU Cerhan, JR
Engels, EA
Cozen, W
Davis, S
Severson, RK
Morton, LM
Gridley, G
Hartge, P
Linet, M
AF Cerhan, James R.
Engels, Eric A.
Cozen, Wendy
Davis, Scott
Severson, Richard K.
Morton, Lindsay M.
Gridley, Gloria
Hartge, Patricia
Linet, Martha
TI Blood transfusion, anesthesia, surgery and risk of non-Hodgkin lymphoma
in a population-based case-control study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE anesthesia; blood transfusion; non-Hodgkin lymphoma; surgery
ID TOTAL HIP-REPLACEMENT; FRANCISCO BAY AREA; CANCER-RISK; UNITED-STATES;
TUMOR-GROWTH; APPENDECTOMY; ARTHROPLASTY; METAANALYSIS; LAPAROSCOPY;
LAPAROTOMY
AB The incidence of NHL has increased dramatically since at least the 1950s, and during this timeframe there has been a major increase in the use of blood transfusions, invasive surgical procedures and anesthesia, all of which can impact immune function. We evaluated these factors with NHL risk in a population-based study of 759 cases and 589 frequency-matched controls. Risk factor data were collected during in-person interviews. Unconditional logistic regression was used to estimate ORs and 95% CIs, adjusted for the matching factors. History of transfusion was associated with a 26% higher risk of NHL (95% CI 0.91-1.73), and the elevated risk was specific to transfusions first given 5-29 years before the reference date (OR = 1.69; 95% CI 1.08-2.62) and transfusions given for a medical condition (OR = 2.09; 95% CI 1.03-4.26). The total number of surgeries and dental procedures (OR = 1.53 for 26+ surgeries compared to 0-6; 95% CI 1.02-2.29) and to a lesser extent the total number of exposures to general or local/regional anesthesia (OR = 1.35 for 24+ times compared to 0-6; 95% CI 0.91-2.02) were positively associated with risk of NHL. Inclusion of transfusion and surgery or transfusion and anesthesia in the same model did not attenuate these associations. All results were broadly consistent for both DLBCL and follicular subtypes. Blood transfusions were associated with NHL risk, but appear to be a marker for underlying medical conditions. Multiple surgical procedures and/or repeated administration of anesthesia have not been previously reported to be associated with risk of NHL and these exposures warrant further evaluation. Published 2008 Wiley-Liss, Inc.
C1 [Cerhan, James R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Cerhan, James R.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Engels, Eric A.; Morton, Lindsay M.; Gridley, Gloria; Hartge, Patricia; Linet, Martha] NCI, Bethesda, MD 20892 USA.
[Cozen, Wendy] Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Severson, Richard K.] Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Severson, Richard K.] Karmanos Canc Inst, Detroit, MI USA.
RP Cerhan, JR (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA.
EM cerhan.james@mayo.edu
RI Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X
FU Intramural NIH HHS [ZIA CP010170-13]; NCI NIH HHS [N01 PC065064, N01
PC067008, N01 PC067009, N01 PC067009-025, N01 PC067010, P50 CA097274,
R01 CA092153]
NR 46
TC 12
Z9 13
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2008
VL 123
IS 4
BP 888
EP 894
DI 10.1002/ijc.23561
PG 7
WC Oncology
SC Oncology
GA 328SL
UT WOS:000257818000020
PM 18506687
ER
PT J
AU Sokolnikov, ME
Gilbert, ES
Preston, DL
Ron, E
Shilnikova, NS
Khokhryakov, VV
Vasilenko, EK
Koshurnikova, NA
AF Sokolnikov, Mikhail E.
Gilbert, Ethel S.
Preston, Dale L.
Ron, Elaine
Shilnikova, Natalia S.
Khokhryakov, Victor V.
Vasilenko, Evgeny K.
Koshurnikova, Nina A.
TI Lung, liver and bone cancer mortality in Mayak workers
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE lung cancer; liver cancer; bone cancer; plutonium; ionizing radiation;
nuclear workers
ID ATOMIC-BOMB SURVIVORS; PLUTONIUM EXPOSURE; NUCLEAR-COMPLEX; RISK;
RADIATION; SMOKING; INDUCTION; DOSIMETRY; TUMORS; MODEL
AB Workers at the Mayak nuclear facility in the Russian Federation offer the only adequate human data for evaluating cancer risks from exposure to plutonium. Risks of mortality from cancers of the lung, liver and bone, the organs receiving the largest doses from plutonium, were evaluated in a cohort of 17,740 workers initially hired 1948-1972 using, for the first time, recently improved individual organ dose estimates. Excess relative risk (ERR) models were used to evaluate risks as functions of internal (plutonium) dose, external (primarily gamma) dose, gender, attained age and smoking. By December 31, 2003, 681 lung cancer deaths, 75 liver cancer deaths and 30 bone cancer deaths had occurred. Of these 786 deaths, 239 (30%) were attributed to plutonium exposure. Significant plutonium dose-response relationships (p < 0.001) were observed for all 3 endpoints, with lung and liver cancer risks reasonably described by linear functions. At attained age 60, the ERRs per Gy for lung cancer were 7.1 for males and 15 for females; the averaged-attained age ERRs for liver cancer were 2.6 and 29 for males and females, respectively; those for bone cancer were 0.76 and 3.4. This study is the first to present and compare dose-response analyses for cancers of all 3 organs. The unique Mayak cohort with its high exposures and well characterized doses has allowed quantification of the plutonium dose-response for lung, liver and bone cancer risks based on direct human data. These results will play an important role in plutonium risk assessment. Published 2008 Wiley-Liss, Inc.
C1 [Gilbert, Ethel S.; Ron, Elaine] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Sokolnikov, Mikhail E.; Shilnikova, Natalia S.; Khokhryakov, Victor V.; Koshurnikova, Nina A.] So Urals Biophys Inst, Ozyorsk, Chelyabinsk Reg, Russia.
[Preston, Dale L.] Hirosoft Int Corp, Seattle, WA USA.
[Vasilenko, Evgeny K.] Mayak Prod Assoc, Dept Radiat Safety, Ozyorsk, Chelyabinsk Reg, Russia.
RP Gilbert, ES (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Executive Plaza S,Room 7050, Bethesda, MD 20892 USA.
EM gilberte@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010133-18]; NCI NIH HHS [N01-CP-41003-13]
NR 32
TC 49
Z9 61
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2008
VL 123
IS 4
BP 905
EP 911
DI 10.1002/ijc.23581
PG 7
WC Oncology
SC Oncology
GA 328SL
UT WOS:000257818000023
PM 18528867
ER
PT J
AU Busse, KH
Formentini, E
Alfaro, RM
Kovacs, JA
Penzak, SR
AF Busse, Kristin H.
Formentini, Elizabeth
Alfaro, Raul M.
Kovacs, Joseph A.
Penzak, Scott R.
TI Influence of antiretroviral drugs on the pharmacokinetics of
prednisolone in HIV-infected individuals
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE drug interaction; cytochrome P450; nonnucleoside reverse transcriptase
inhibitor; protease inhibitor; corticosteroid
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IATROGENIC CUSHINGS-SYNDROME;
RITONAVIR-FLUTICASONE INTERACTION; INHALED FLUTICASONE; NASAL
FLUTICASONE; OSTEONECROSIS; CORTICOSTEROIDS; KETOCONAZOLE; METABOLISM;
EFAVIRENZ
AB Background: Corticosteroids are cytochrome P450 3A4 substrates, which have been associated with toxicities in patients receiving cytochrome P450 3A4 inhibitors such as human immunodeficiency virus protease inhibitors. In a study in healthy volunteers, ritonavir significantly increased prednisolone exposure.
Methods: We investigated the influence of antiretroviral (ARV) medications on prednisolone pharmacokinetics in 3 groups of 10 human immunodeficiency virus-infected subjects. One group received lopinavir/ritonavir, and another efavirenz, as part of their ARV regimen; a third group did not receive ARV medications. Each subject received a single 20-mg prednisone dose followed by serial blood sampling for prednisolone. Prednisolone pharmacokinetics were compared among the groups.
Results: Area under the concentration-time curve was significantly lower in efavirenz recipients versus subjects receiving lopinavir/ ritonavir (geometric mean ratio = 0.60, P = 0.01). Average prednisolone area under the concentration-time curve was higher in subjects taking lopinavir/ritonavir versus subjects not on ARVs; however, this difference was not significant (P > 0.05).
Conclusions: These data indicate that prednisolone concentrations may fluctuate widely when human immunodeficiency virus-positive individuals established on efavirenz therapy change to lopinavir/ ritonavir or vice versa.
C1 [Busse, Kristin H.; Alfaro, Raul M.; Penzak, Scott R.] NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA.
[Formentini, Elizabeth; Kovacs, Joseph A.] NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Penzak, SR (reprint author), NIH, Ctr Clin, Dept Pharm, 9000 Rockville Pike,Bldg 10,Room 1N-257, Bethesda, MD 20896 USA.
EM spenzak@cc.nih.gov
FU Intramural NIH HHS [Z01 CL005096-05]
NR 39
TC 10
Z9 10
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2008
VL 48
IS 5
BP 561
EP 566
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 332KP
UT WOS:000258082200007
PM 18645517
ER
PT J
AU Tross, S
Campbell, ANC
Cohen, LR
Calsyn, D
Pavlicova, M
Miele, GM
Hu, MC
Haynes, L
Nugent, N
Gan, W
Hatch-Maillette, M
Mandler, R
McLaughlin, P
El-Bassel, N
Crits-Christoph, P
Nunes, EV
AF Tross, Susan
Campbell, Aimee N. C.
Cohen, Lisa R.
Calsyn, Donald
Pavlicova, Martina
Miele, Gloria M.
Hu, Mei-Chen
Haynes, Louise
Nugent, Nancy
Gan, Weijin
Hatch-Maillette, Mary
Mandler, Raul
McLaughlin, Paul
El-Bassel, Nabila
Crits-Christoph, Paul
Nunes, Edward V.
TI Effectiveness of HIV/STD sexual risk reduction groups for women in
substance abuse treatment programs: Results of NIDA clinical trials
network trial
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article; Proceedings Paper
CT 18th Annual Meeting of the American-Academy-of-Addiction-Psychiatry
CY DEC 01, 2007
CL Coronado, CA
SP Amer Acad Addict Psychiat
DE HIV prevention intervention; drug treatment; skills building; randomized
control trial
ID INJECTING DRUG-USERS; HIV RISK; FOLLOW-UP; BEHAVIOR; INTERVENTIONS;
METAANALYSIS; TRANSMISSION; EFFICACY; IMPACT; SKILLS
AB Context: Because drug-involved women are among the fastest growing groups with AIDS, sexual risk reduction intervention for them is a public health imperative.
Objective: To test effectiveness of HIV/STD safer sex skills building (SSB) groups for women in community drug treatment.
Design: Randomized trial of SSB versus standard HIV/STD Education (HE); assessments at baseline, 3 and 6 months.
Participants: Women recruited from 12 methadone or psychosocial treatment programs in Clinical Trials Network of National Institute on Drug Abuse. Five hundred fifteen women with ! I unprotected vaginal or anal sex occasion (USO) with a male partner in the past 6 months were randomized.
Interventions: In SSB, five 90-minute groups used problem solving and skills rehearsal to increase HIV/STD risk awareness, condom use, and partner negotiation skills. In HE, one 60-minute group covered HIV/STD disease, testing, treatment, and prevention information.
Main Outcome: Number of USOs at follow-up.
Results: A significant difference in mean USOs was obtained between SSB and HE overtime (F = 67.2,P < 0.0001). At 3 months, significant decrements were observed in both conditions. At 6 months, SSB maintained the decrease and HE returned to baseline (P < 0.0377). Women in SSB had 29% fewer USOs than those in HE.
Conclusions: Skills building interventions can produce ongoing sexual risk reduction in women in community drug treatment.
C1 [Tross, Susan] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, Dept Psychiat, New York, NY 10032 USA.
[Tross, Susan; Miele, Gloria M.; Nunes, Edward V.] Columbia Univ, Med Ctr, Substance Res Ctr, Dept Psychiat, New York, NY USA.
[Campbell, Aimee N. C.; Cohen, Lisa R.; El-Bassel, Nabila] Columbia Univ, Sch Social Work, Social Intervent Grp, New York, NY USA.
[Calsyn, Donald; Hatch-Maillette, Mary] Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA.
[Calsyn, Donald; Hatch-Maillette, Mary] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Pavlicova, Martina] Columbia Univ, Med Ctr, Dept Biostat, New York, NY USA.
[Hu, Mei-Chen] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA.
[Haynes, Louise] Lexington Richland Alcohol & Drug Abuse Council, Richland, WA USA.
[Nugent, Nancy] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Gan, Weijin] NYU, Ctr Child Study, Sch Med, New York, NY USA.
[Mandler, Raul] Natl Inst Drug Abuse, Ctr Clin Trials Network, Bethesda, MD USA.
[McLaughlin, Paul] Hartford Dispensary, Hartford, CT USA.
[Crits-Christoph, Paul] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Tross, S (reprint author), New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, Dept Psychiat, 1051 Riverside Dr,Unit 15, New York, NY 10032 USA.
EM st130@columbia.edu
FU NIDA NIH HHS [U10 DA013035-07, U10 DA013035, U10 DA13732, U10 DA13714,
U10 DA13711, U10 DA13045, U10 DA013038, U10 DA013045, U10 DA013711, U10
DA013714, U10 DA013732, U10 DA13043, U10 DA13727, U10 DA13035, U10
DA13038, U10 DA013043, U10 DA013727]
NR 45
TC 54
Z9 54
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2008
VL 48
IS 5
BP 581
EP 589
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 332KP
UT WOS:000258082200011
PM 18645513
ER
PT J
AU Li, Y
Bevilacqua, E
Chiribau, CB
Majumder, M
Wang, CP
Croniger, CM
Snider, MD
Johnson, PF
Hatzoglou, M
AF Li, Yi
Bevilacqua, Elena
Chiribau, Calin-Bogdan
Majumder, Mithu
Wang, Chuanping
Croniger, Colleen M.
Snider, Martin D.
Johnson, Peter F.
Hatzoglou, Maria
TI Differential control of the CCAAT/enhancer-binding protein beta (C/EBP
beta) products liver-enriched transcriptional activating protein (LAP)
and liver- enriched transcriptional inhibitory protein (LIP) and the
regulation of gene expression during the response to endoplasmic
reticulum stress
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ASPARAGINE SYNTHETASE GENE; SITE-MEDIATED TRANSLATION; MESSENGER-RNA
TRANSLATION; AMINO-ACID AVAILABILITY; ER STRESS; MAMMALIAN-CELLS;
ARGININE/LYSINE TRANSPORTER; PROTEASOME INHIBITION; NEGATIVE FEEDBACK;
CODING SEQUENCE
AB The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers a stress response program that protects cells early in the response and can lead to apoptosis during prolonged stress. The basic leucine zipper transcription factor, CCAAT/enhancer-binding protein beta (C/EBP beta), is one of the genes with increased expression during ER stress. Translation of the C/EBP beta mRNA from different initiation codons leads to the synthesis of two transcriptional activators (LAP-1 and -2) and a transcriptional repressor (LIP). The LIP/LAP ratio is a critical factor in C/EBP beta-mediated gene transcription. It is shown here that the LIP/LAP ratio decreased by 5-fold during the early phase of ER stress and increased by 20-fold during the late phase, mostly because of changes in LIP levels. The early decrease in LIP required degradation via the proteasome pathway and phosphorylation of the translation initiation factor, eIF2 alpha. The increased LIP levels during the late phase were due to increased synthesis and increased stability of the protein. It is proposed that regulation of synthesis and degradation rates during ER stress controls the LIP/LAP ratio. The importance of C/EBP beta in the ER-stress response program was demonstrated using C/EBP beta-deficient mouse embryonic fibroblasts. It is shown that C/EBP beta attenuates expression of pro-survival ATF4 target genes in late ER stress and enhances expression of cell death-associated genes downstream of CHOP. The inhibitory effect of LIP on ATF4-induced transcription was demonstrated for the cat-1 amino acid transporter gene. We conclude that regulation of LIP/LAP ratios during ER stress is a novel mechanism for modulating the cellular stress response.
C1 [Li, Yi; Bevilacqua, Elena; Chiribau, Calin-Bogdan; Majumder, Mithu; Wang, Chuanping; Croniger, Colleen M.; Hatzoglou, Maria] Case Western Reserve Univ, Dept Nutr, Sch Med, Cleveland, OH 44106 USA.
[Snider, Martin D.] Case Western Reserve Univ, Dept Biochem, Sch Med, Cleveland, OH 44106 USA.
[Johnson, Peter F.] NCI Frederick, Basic Res Lab, Natl Inst Hlth, Frederick, MD 21702 USA.
RP Hatzoglou, M (reprint author), Case Western Reserve Univ, Dept Nutr, Sch Med, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM mxh8@case.edu
RI Johnson, Peter/A-1940-2012
OI Johnson, Peter/0000-0002-4145-4725
FU Intramural NIH HHS; NIDDK NIH HHS [DK053307, DK060596, DK075040, R01
DK075040, R01 DK075040-03]
NR 80
TC 52
Z9 57
U1 1
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 15
PY 2008
VL 283
IS 33
BP 22443
EP 22456
DI 10.1074/jbc.M801046200
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 335VR
UT WOS:000258321000012
PM 18550528
ER
PT J
AU Pagel-Langenickel, I
Bao, JJ
Joseph, JJ
Schwartz, DR
Mantell, BS
Xu, XL
Raghavachari, N
Sack, MN
AF Pagel-Langenickel, Ines
Bao, Jianjun
Joseph, Joshua J.
Schwartz, Daniel R.
Mantell, Benjamin S.
Xu, Xiuli
Raghavachari, Nalini
Sack, Michael N.
TI PGC-1 alpha integrates insulin signaling, mitochondrial regulation, and
bioenergetic function in skeletal muscle
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TYPE-2 DIABETES-MELLITUS; ADIPOSE-TISSUE; FATTY-ACID;
OXIDATIVE-METABOLISM; GENE-EXPRESSION; IN-VIVO; GLUCOSE; RESISTANCE;
OVEREXPRESSION; ROSIGLITAZONE
AB The pathophysiology underlying mitochondrial dysfunction in insulin-resistant skeletal muscle is incompletely characterized. To further delineate this we investigated the interaction between insulin signaling, mitochondrial regulation, and function in C2C12 myotubes and in skeletal muscle. In myotubes elevated insulin and glucose disrupt insulin signaling, mitochondrial biogenesis, and mitochondrial bioenergetics. The insulin-sensitizing thiazolidinedione pioglitazone restores these perturbations in parallel with induction of the mitochondrial biogenesis regulator PGC-1 alpha. Overexpression of PGC-1 alpha rescues insulin signaling and mitochondrial bioenergetics, and its silencing concordantly disrupts insulin signaling and mitochondrial bioenergetics. In primary skeletal myoblasts pioglitazone also up-regulates PGC-1 alpha expression and restores the insulin-resistant mitochondrial bioenergetic profile. In parallel, pioglitazone upregulates PGC-1 alpha in db/db mouse skeletal muscle. Interestingly, the small interfering RNA knockdown of the insulin receptor in C2C12 myotubes down-regulates PGC-1 alpha and attenuates mitochondrial bioenergetics. Concordantly, mitochondrial bioenergetics are blunted in insulin receptor knock-out mouse-derived skeletal myoblasts. Taken together these data demonstrate that elevated glucose and insulin impairs and pioglitazone restores skeletal myotube insulin signaling, mitochondrial regulation, and bioenergetics. Pioglitazone functions in part via the induction of PGC-1 alpha. Moreover, PGC-1 alpha is identified as a bidirectional regulatory link integrating insulin-signaling and mitochondrial homeostasis in skeletal muscle.
C1 [Pagel-Langenickel, Ines; Bao, Jianjun; Joseph, Joshua J.; Schwartz, Daniel R.; Mantell, Benjamin S.; Sack, Michael N.] NHLBI, Natl Inst Hlth, Translat Med Branch, Bethesda, MD 20892 USA.
[Xu, Xiuli; Raghavachari, Nalini] NHLBI, Natl Inst Hlth, Genom Core, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Natl Inst Hlth, Translat Med Branch, Bldg 10-CRC,Rm 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
FU Intramural NIH HHS
NR 41
TC 54
Z9 55
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 15
PY 2008
VL 283
IS 33
BP 22464
EP 22472
DI 10.1074/jbc.M800842200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 335VR
UT WOS:000258321000014
PM 18579525
ER
PT J
AU Li, M
Gustchina, A
Alexandratos, J
Wlodawer, A
Wunschmann, S
Kepley, CL
Chapman, MD
Pomes, A
AF Li, Mi
Gustchina, Alla
Alexandratos, Jerry
Wlodawer, Alexander
Wunschmann, Sabina
Kepley, Christopher L.
Chapman, Martin D.
Pomes, Anna
TI Crystal structure of a dimerized cockroach allergen Bla g 2 complexed
with a monoclonal antibody
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GRASS-POLLEN ALLERGEN; IGE-BINDING EPITOPES; MAJOR ALLERGEN; BIRCH
POLLEN; PROTEIN; ASTHMA; CRYSTALLOGRAPHY; SENSITIZATION; REFINEMENT;
REACTIVITY
AB The crystal structure of a 1: 1complex between the German cockroach allergen Bla g 2 and the Fab' fragment of a monoclonal antibody 7C11 was solved at 2.8-angstrom resolution. Bla g 2 binds to the antibody through four loops that include residues 60 -70, 83 -86, 98 -100, and 129 -132. Cation-Pi interactions exist between Lys65, Arg-83, and Lys-132 in Bla g 2 and several tyrosines in 7C11. In the complex with Fab ', Bla g 2 forms a dimer, which is stabilized by a quasi-four-helix bundle comprised of an alpha-helix and a helical turn from each allergen monomer, exhibiting a novel dimerization mode for an aspartic protease. A disulfide bridge between C51a and C113, unique to the aspartic protease family, connects the two helical elements within each Bla g 2 monomer, thus facilitating formation of the bundle. Mutation of these cysteines, as well as the residues Asn-52, Gln-110, and Ile-114, involved in hydrophobic interactions within the bundle, resulted in a protein that did not dimerize. The mutant proteins induced less beta hexosaminidase release from mast cells than the wild-type Bla g 2, suggesting a functional role of dimerization in allergenicity. Because 7C11 shares a binding epitope with IgE, the information gained by analysis of the crystal structure of its complex provided guidance for site-directed mutagenesis of the allergen epitope. We have now identified key residues involved in IgE antibody binding; this information will be useful for the design of vaccines for immunotherapy.
C1 [Li, Mi; Gustchina, Alla; Alexandratos, Jerry; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
[Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
[Wunschmann, Sabina; Chapman, Martin D.; Pomes, Anna] INDOOR Biotechnol Inc, Charlottesville, VA 22903 USA.
[Kepley, Christopher L.] Univ Hlth Syst, Sch Med, Richmond, VA 23298 USA.
RP Gustchina, A (reprint author), NCI, Macromol Crystallog Lab, NIH, Bldg 539, Frederick, MD 21702 USA.
EM alla@ncifcrf.gov
OI Pomes, Anna/0000-0002-8729-1829
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [R01
AI077653]
NR 35
TC 49
Z9 50
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 15
PY 2008
VL 283
IS 33
BP 22806
EP 22814
DI 10.1074/jbc.M800937200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 335VR
UT WOS:000258321000048
PM 18519566
ER
PT J
AU Bagorda, A
Parent, CA
AF Bagorda, Anna
Parent, Carole A.
TI Eukaryotic chemotaxis at a glance
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
ID NEUTROPHIL CHEMOTAXIS; RHOA ACTIVITY; LEADING-EDGE; DICTYOSTELIUM;
ACTIVATION; MIGRATION; POLARITY; BACK; MORPHOGENESIS; RECEPTORS
C1 [Bagorda, Anna; Parent, Carole A.] NCI, NIH, Ctr Canc Res, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
RP Parent, CA (reprint author), NCI, NIH, Ctr Canc Res, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
EM parentc@mail.nih.gov
NR 38
TC 71
Z9 72
U1 1
U2 8
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD AUG 15
PY 2008
VL 121
IS 16
BP 2621
EP 2624
DI 10.1242/jcs.018077
PG 4
WC Cell Biology
SC Cell Biology
GA 334TK
UT WOS:000258243900001
PM 18685153
ER
PT J
AU Stein, GS
Davie, JR
Knowlton, JR
Zaidi, SK
AF Stein, Gary S.
Davie, James R.
Knowlton, J. Randy
Zaidi, Sayyed K.
TI Nuclear microenvironments and cancer
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Editorial Material
ID TRANSCRIPTIONAL REGULATION; STRUCTURAL BASIS; CELL-GROWTH; CHROMATIN;
DYNAMICS; RNA; REORGANIZATION; REPLICATION; RECOGNITION; EXPRESSION
AB Nucleic acids and regulatory proteins are architecturally organized in nuclear microenvironments. The compartmentalization of regulatory machinery for gene expression, replication and repair, is obligatory for fidelity of biological control. Perturbations in the organization, assembly and integration of regulatory machinery have been functionally linked to the onset and progression of tumorigenesis. The combined application of cellular, molecular, biochemical and in vivo genetic approaches, together with structural biology, genomics, proteomics and bioinformatics, will likely lead to new approaches in cancer diagnostics and therapy.
C1 [Stein, Gary S.; Zaidi, Sayyed K.] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA.
[Davie, James R.] Manitoba Inst Cell Biol, Winnipeg, MB R3E OV9, Canada.
[Knowlton, J. Randy] NCI, Struct Biol & Mol Applicat, Div Canc Biol, NIH, Bethesda, MD 20892 USA.
RP Stein, GS (reprint author), 55 Lake Ave N, Worcester, MA 01655 USA.
EM gary.stein@umassmed.edu
OI Zaidi, Kaleem/0000-0001-6664-5168
FU NCI NIH HHS [R01 CA139322]
NR 46
TC 5
Z9 6
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD AUG 15
PY 2008
VL 104
IS 6
BP 1949
EP 1952
DI 10.1002/jcb.21846
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 336TJ
UT WOS:000258387200001
PM 18649350
ER
PT J
AU Ye, LL
Liu, XD
Rout, SN
Li, ZL
Yan, YQ
Lu, L
Kamala, T
Nanda, NK
Song, WX
Samal, SK
Zhu, XP
AF Ye, Lilin
Liu, Xindong
Rout, Subrat N.
Li, Zili
Yan, Yongqi
Lu, Li
Kamala, Tirumalai
Nanda, Navreet K.
Song, Wenxia
Samal, Siba K.
Zhu, Xiaoping
TI The MHC class II-associated invariant chain interacts with the neonatal
Fc gamma receptor and modulates its trafficking to endosomal/lysosomal
compartments
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INTESTINAL EPITHELIAL-CELLS; INTRACELLULAR TRAFFICKING; ENDOCYTIC
COMPARTMENTS; FUNCTIONAL EXPRESSION; ENDOPLASMIC-RETICULUM;
ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; CYTOPLASMIC TAIL; BINDING GROOVE;
IGG TRANSPORT
AB The neonatal Fc receptor for IgG (FcRn) transfers maternal IgG to the offspring and protects IgG from degradation. The FcRn resides in an acidic intracellular compartment, allowing it to bind IgG. In this study, we found the association of FcRn and invariant chain (Ii). The interaction was initiated within the endoplasmic reticulum by Ii binding to either the FcRn H chain alone or FcRn H chain-beta(2)-microglobulin complex and appeared to be maintained throughout the endocytic pathway. The CLIP in Ii was not required for FcRn-Ii association. The interaction was also detected in IFN-gamma-treated THP-1, epithelial and endothelial cells, and immature mouse DCs. A truncated FcRn without the cytoplasmic tail was unable to traffic to early endosomes; however, its location in early endosomes was restored by Ii expression. FcRn was also detected in the late endosome/lysosome only in the presence of Ii or on exposure to IFN-gamma. In immature human or mouse DCs, FcRn was barely detected in the late endosome/lysosome in the absence of Ii. Furthermore, the cytoplasmic tail of Ii conferred tailless FcRn to route to both the early endosome and late endosome/lysosome in a hybrid molecule. Because the FcRn is expressed in macrophages and DCs or epithelial and endothelial cells where Ii is induced under inflammation and infection, these results reveal the complexity of FcRn trafficking in which Ii is capable of expanding the boundary of FcRn trafficking. Taken together, the intracellular trafficking of FcRn is regulated by its intrinsic sorting information and/or an interaction with Ii chain.
C1 [Rout, Subrat N.; Yan, Yongqi; Samal, Siba K.; Zhu, Xiaoping] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Ye, Lilin; Liu, Xindong; Li, Zili; Lu, Li; Zhu, Xiaoping] Univ Maryland, Immunol Lab, College Pk, MD 20742 USA.
[Song, Wenxia] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
[Ye, Lilin; Liu, Xindong; Li, Zili; Song, Wenxia; Zhu, Xiaoping] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA.
[Kamala, Tirumalai; Nanda, Navreet K.] NIH, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA.
[Kamala, Tirumalai] NIH, T Cell Tolerance & Memory Sect, Bethesda, MD 20892 USA.
RP Zhu, XP (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA.
EM xzhu1@umd.edu
RI Lu, Li/A-2237-2014; liu, xindong/D-4473-2014; liu, xindong/F-8422-2014
FU Intramural NIH HHS; NIAID NIH HHS [N01-AO-6009, AI59617, AI65892,
AI67965, AI73139, R01 AI059617, R01 AI065892, R01 AI065892-02, R21
AI067965, R21 AI067965-02, R21 AI073139, R21 AI073139-02]
NR 67
TC 34
Z9 35
U1 1
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2008
VL 181
IS 4
BP 2572
EP 2585
PG 14
WC Immunology
SC Immunology
GA 336DU
UT WOS:000258345300037
PM 18684948
ER
PT J
AU Venturi, V
Chin, HY
Price, DA
Douek, DC
Davenport, MP
AF Venturi, Vanessa
Chin, Hui Yee
Price, David A.
Douek, Daniel C.
Davenport, Miles P.
TI The role of production frequency in the sharing of simian
immunodeficiency virus-specific CD8(+) TCRs between macaques
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL REPERTOIRE; COMPLEX CLASS-I; MYELIN BASIC-PROTEIN; HUMAN
CYTOMEGALOVIRUS; BETA-CHAIN; RECEPTOR RECOGNITION; ANTIGEN RECEPTOR;
GENE REARRANGEMENTS; MULTIPLE-SCLEROSIS; PERSISTENT VIRUSES
AB In some epitope-specific responses, T cells bearing identical TCRs occur in many MHC-matched individuals. The sharing of public TCRs is unexpected, given the enormous potential diversity of the TCR repertoire. We have previously studied the sharing of TCR beta-chains in the CD8(+) T cell responses to two influenza epitopes in mice. Analysis of these TCRP repertoires suggests that, even with unbiased V(D)J recombination mechanisms, some TCR beta s can be produced more frequently than others, by a process of convergent recombination. The TCR beta production frequency was shown to be a good predictor of the observed sharing of epitope-specific TCR beta s between mice. However, this study was limited to immune responses in an inbred population. In this study, we investigated TCR beta sharing in CD8(+) T cell responses specific for the immunodominant Mamu-A*01-restricted Tat-SL8/TL8 and Gag-CM9 epitopes of SIV in rhesus macaques. Multiple data sets were used, comprising a total of similar to 6000 TCR beta s sampled from 20 macaques. We observed a spectrum in the number of macaques sharing epitope-specific TCR beta s in this outbred population. This spectrum of TCR beta sharing was negatively correlated with the minimum number of nucleotide additions required to produce the sequences and strongly positively correlated with the number of observed nucleotide sequences encoding the amino acid sequences. We also found that TCR beta sharing was correlated with the number of times, and the variety of different ways, the sequences were produced in silico via random gene recombination. Thus, convergent recombination is a major determinant of the extent of TCR beta sharing.
C1 [Venturi, Vanessa; Chin, Hui Yee; Davenport, Miles P.] Univ New S Wales, Complex Syst Biol Grp, Ctr Vasc Res, Kensington, NSW 2052, Australia.
[Price, David A.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales.
[Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Davenport, MP (reprint author), Univ New S Wales, Complex Syst Biol Grp, Ctr Vasc Res, Kensington, NSW 2052, Australia.
EM m.davenport@unsw.edu.au
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Medical Research Council [, G0501963]
NR 74
TC 20
Z9 20
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2008
VL 181
IS 4
BP 2597
EP 2609
PG 13
WC Immunology
SC Immunology
GA 336DU
UT WOS:000258345300039
PM 18684950
ER
PT J
AU Nagarsekar, A
Greenberg, RS
Shah, NG
Singh, IS
Hasday, JD
AF Nagarsekar, Ashish
Greenberg, Rachel S.
Shah, Nirav G.
Singh, Ishwar S.
Hasday, Jeffrey D.
TI Febrile-range hyperthermia accelerates caspase-dependent apoptosis in
human neutrophils
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; CYTOCHROME-C RELEASE;
NF-KAPPA-B; SIGNALING PATHWAYS; DEATH RECEPTORS; CELL-DEATH; ACTIVATION;
MITOCHONDRIA; PROTEIN
AB Human neutrophilic polymorphonuclear leukocytes (PMNs) are central to innate immunity and are responsible for clearance of pathogens. PMNs undergo a tightly regulated apoptosis program that allows for timely clearance of PMNs without extravasation of toxic intracellular contents. We investigated the rate of spontaneous apoptosis of human peripheral blood PMNs cultured at basal (37 degrees C) and febrile-range (39.5 degrees C) temperatures (FRT). We found that PMN apoptosis is accelerated at FRT, reaching similar to 90% completion by 8 h at 39.5 degrees C vs 18 h at 37 degrees C based on morphologic criteria. Caspase-8 activation peaked within 15 min of PMN exposure to FRT, and subsequent activation of caspase-3 and -9, cleavage of the BH3 (Bcl-2 homology domain 3) only protein Bid, and mitochondrial release of cytochrome c were also greater in FRT-exposed PMNs. Inhibition of caspase-3, -8, and -9 conferred comparable protection from apoptosis in FRT-exposed PMNs. These results demonstrate that exposure to FRT enhances caspase-8 activation and subsequent mitochondrial-dependent and mitochondrial-independent apoptosis pathways. The PMN survival factors G-CSF, GM-CSF, and IL-8 each prolonged PMN survival at 37 degrees C and 39.5 degrees C, but did not reduce the difference in survival at the two temperatures. In a mouse model of intratracheal endotoxin-induced alveolitis, coexposure to FRT (core temperature similar to 39.5 degrees C) doubled the proportion of bronchoalveolar PMNs undergoing apoptosis compared with euthermic mice. This process may play an important role in limiting inflammation and tissue injury during febrile illnesses.
C1 [Singh, Ishwar S.; Hasday, Jeffrey D.] Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA.
[Nagarsekar, Ashish; Shah, Nirav G.; Singh, Ishwar S.; Hasday, Jeffrey D.] Univ Maryland, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA.
[Greenberg, Rachel S.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Singh, Ishwar S.; Hasday, Jeffrey D.] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Shah, Nirav G.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Hasday, JD (reprint author), Baltimore Vet Affairs Med Ctr, Res Serv, Room 3D122,10 N Greene St, Baltimore, MD 21201 USA.
EM jhasday@umaryland.edu
FU NHLBI NIH HHS [HL085256, R01 HL069057, R01 HL085256-02, R01 HL085256,
HL69057, R01 HL069057-05A2]; NIGMS NIH HHS [R01 GM066855, GM066855, R01
GM069431, GM069431]
NR 47
TC 19
Z9 20
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2008
VL 181
IS 4
BP 2636
EP 2643
PG 8
WC Immunology
SC Immunology
GA 336DU
UT WOS:000258345300043
PM 18684954
ER
PT J
AU Baudino, L
Yoshinobu, K
Morito, N
Kikuchi, S
Fossati-Jimack, L
Morley, BJ
Vyse, TJ
Hirose, S
Jorgensen, TN
Tucker, RM
Roark, CL
Kotzin, BL
Evans, LH
Izui, S
AF Baudino, Lucie
Yoshinobu, Kumiko
Morito, Naoki
Kikuchi, Shuichi
Fossati-Jimack, Liliane
Morley, Bernard J.
Vyse, Timothy J.
Hirose, Sachiko
Jorgensen, Trine N.
Tucker, Rebecca M.
Roark, Christina L.
Kotzin, Brian L.
Evans, Leonard H.
Izui, Shozo
TI Dissection of genetic mechanisms governing the expression of serum
retroviral gp70 implicated in murine lupus nephritis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NEW-ZEALAND MICE; CELL-SURFACE ANTIGENS; ACUTE-PHASE RESPONSE;
LEUKEMIA-VIRUS; ENVELOPE GLYCOPROTEIN; IMMUNE-COMPLEXES; NZB MICE;
AUTOANTIBODY PRODUCTION; POLYTROPIC PROVIRUSES; AUTOIMMUNE-DISEASE
AB The endogenous retroviral envelope glycoprotein, gp70, implicated in murine lupus nephritis is secreted by hepatocytes as an acute phase protein, and it has been thought to be a product of an endogenous xenotropic virus, NZB-X1. However, since endogenous polytropic (PT) and modified polytropic (mPT) viruses encode gp70s that are closely related to xenotropic gp70, these viruses can be additional sources of serum gp70. To better understand the genetic basis of the expression of serum gp70, we analyzed the abundance of xenotropic, PT, or mPT gp70 RNAs in livers and the genomic composition of corresponding proviruses in various strains of mice, including two different Sgp (serum gp70 production) congenic mice. Our results demonstrated that the expression of different viral gp70 RNAs was remarkably heterogeneous among various mouse strains and that the level of serum gp70 production was regulated by multiple structural and regulatory genes. Additionally, a significant contribution of PT and mPT gp70s to serum gp70 was revealed by the detection of PT and mPT, but not xenotropic transcripts in 129 mice, and by a closer correlation of serum levels of gp70 with the abundance of PT and mPT gp70 RNAs than with that of xenotropic gp70 RNA in Sgp3 congenic mice. Furthermore, the injection of lipopolysaccharides selectively up-regulated the expression of xenotropic and mPT gp70 RNAs, but not PT gp70 RNA. Our data indicate that the genetic origin of serum gp70 is more heterogeneous than previously thought, and that distinct retroviral gp70s are differentially regulated in physiological vs inflammatory conditions.
C1 [Baudino, Lucie; Yoshinobu, Kumiko; Morito, Naoki; Kikuchi, Shuichi; Izui, Shozo] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland.
[Fossati-Jimack, Liliane; Morley, Bernard J.; Vyse, Timothy J.] Univ London Imperial Coll Sci Technol & Med, Mol Genet & Rheumatol Sect, London, England.
[Hirose, Sachiko] Juntendo Univ, Sch Med, Dept Pathol, Tokyo 113, Japan.
[Jorgensen, Trine N.; Tucker, Rebecca M.; Roark, Christina L.; Kotzin, Brian L.] Natl Jewish Med & Res Ctr, Integrated Dept Immunol, Denver, CO 80206 USA.
[Evans, Leonard H.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Izui, S (reprint author), Ctr Med Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, Switzerland.
EM Shozo.lzui@medecine.unige.ch
FU Intramural NIH HHS [Z01 AI000266-26]
NR 55
TC 15
Z9 15
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2008
VL 181
IS 4
BP 2846
EP 2854
PG 9
WC Immunology
SC Immunology
GA 336DU
UT WOS:000258345300065
PM 18684976
ER
PT J
AU Read, SW
Sereti, I
AF Read, Sarah W.
Sereti, Irini
TI HIV infection and the gut: Scarred for life?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID LYMPHATIC TISSUE FIBROSIS; VIRUS TYPE-1 INFECTION; T-CELL DEPLETION;
ACTIVATION; THERAPY; COUNT
C1 [Read, Sarah W.] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA.
[Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Read, SW (reprint author), NIAID, DAIDS, NIH, 6700B Rockledge Dr,Rm 5111, Bethesda, MD 20892 USA.
EM readsa@niaid.nih.gov
NR 20
TC 2
Z9 2
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2008
VL 198
IS 4
BP 453
EP 455
DI 10.1086/590113
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 329TK
UT WOS:000257893300001
PM 18598195
ER
PT J
AU Estes, J
Baker, JV
Brenchley, JM
Khoruts, A
Barthold, JL
Bantle, A
Reilly, CS
Beilman, GJ
George, ME
Douek, DC
Haase, AT
Schacker, TW
AF Estes, Jacob
Baker, Jason V.
Brenchley, Jason M.
Khoruts, Alex
Barthold, Jacob L.
Bantle, Anne
Reilly, Cavan S.
Beilman, Gregory J.
George, Mark E.
Douek, Daniel C.
Haase, Ashley T.
Schacker, Timothy W.
TI Collagen deposition limits immune reconstitution in the gut
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; T-CELL DEPLETION; IMMUNODEFICIENCY
VIRUS-INFECTION; LYMPHATIC TISSUE FIBROSIS; HERPES-SIMPLEX-VIRUS;
GASTROINTESTINAL-TRACT; TYPE-1 INFECTION; HIV-1 INFECTION;
LYMPHOID-TISSUE; SIV INFECTION
AB Despite suppression of human immunodeficiency virus (HIV) replication by antiretroviral therapy, reconstitution of CD4(+) cells is variable and incomplete, particularly in gut-associated lymphatic tissues (GALT). We have previously shown that immune activation and inflammation in HIV-infected and simian immunodeficiency virus-infected lymph nodes results in collagen deposition and disruption of the lymphatic tissue architecture, and this damage contributes to CD4(+) cell depletion before treatment and affects the extent of immune reconstitution after treatment. In the present study, we compared collagen deposition and the extent of depletion and reconstitution of total CD4(+) cells and subsets in peripheral blood, lymph nodes, and inductive and effector sites in GALT. We show that CD4(+) cell depletion in GALT correlates with the rapidity and greater magnitude of collagen deposition in this compartment, compared with that in peripheral lymph nodes, and that although treatment does not restore CD4(+) cells to effector sites, treatment in the early stages of infection can increase CD4(+) central memory cells in Peyer patches.
C1 [Baker, Jason V.; Khoruts, Alex; Barthold, Jacob L.; Bantle, Anne; Schacker, Timothy W.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Estes, Jacob; Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
[Reilly, Cavan S.] Univ Minnesota, Dept Biostat, Minneapolis, MN 55455 USA.
[Beilman, Gregory J.; George, Mark E.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA.
[Douek, Daniel C.] NIH, Human Immunol Sect, Vaccine Res Ctr, Bethesda, MD USA.
RP Schacker, TW (reprint author), Univ Minnesota, Dept Med, MMC 250,516 Delaware St, Minneapolis, MN 55455 USA.
EM Schacker@umn.edu
OI Beilman, Gregory/0000-0001-5036-3027
FU Intramural NIH HHS [Z99 AI999999]; NCI NIH HHS [P130-CA79458-01]; NCRR
NIH HHS [M01 RR00400, M01 RR000400]; NIAID NIH HHS [R37 AI 28246, R01
AI54232-01A2, 2U01 AI041535, R01 AI054232, R37 AI028246]; NIDCR NIH HHS
[1R01DE12934-01]
NR 31
TC 88
Z9 90
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2008
VL 198
IS 4
BP 456
EP 464
DI 10.1086/590112
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 329TK
UT WOS:000257893300002
PM 18598193
ER
PT J
AU Hoffman, D
AF Hoffman, Dax
TI Firing first: compensatory changes in K(+) channel knockout mice
preserve excitability but not synaptic scaling
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Editorial Material
ID CA1 PYRAMIDAL NEURONS; DENDRITES
C1 NIH, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA.
RP Hoffman, D (reprint author), NIH, Lab Cellular & Synapt Neurophysiol, Rockville Pike 9000A, Bethesda, MD 20892 USA.
EM hoffmand@mail.nih.gov
RI Hoffman, Dax/E-5155-2011
OI Hoffman, Dax/0000-0001-6999-2157
NR 10
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD AUG 15
PY 2008
VL 586
IS 16
BP 3731
EP 3732
DI 10.1113/jphysiol.2008.159335
PG 2
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 339MR
UT WOS:000258582200001
PM 18708490
ER
PT J
AU Jones, TB
Bandettini, PA
Birn, RM
AF Jones, Tyler B.
Bandettini, Peter A.
Birn, Rasmus M.
TI Integration of motion correction and physiological noise regression in
fMRI
SO NEUROIMAGE
LA English
DT Article
ID BOLD HEMODYNAMIC-RESPONSES; FUNCTIONAL CONNECTIVITY; TIME-SERIES;
FLUCTUATIONS; BRAIN; MRI; VARIABILITY; REGIONS; SIGNAL
AB Physiological fluctuations resulting from the heart beat and respiration are a dominant source of noise in fMRI, particularly at high field strengths. Commonly used physiological noise correction techniques, Such as RETROspective Image CORrection (RETROICOR), rely critically on the timing of the image acquisition relative to the heartbeat, but do not account for the effects of subject motion. Such motion affects the fluctuation amplitude, yet volume registration can distort the timing information. In this study, we aimed to systematically determine the optimal order of volume registration, slice-time Correction and RETROICOR in their traditional forms. In addition, we evaluate the sensitivity of RETROICOR to timing errors introduced by the slice acquisition, and we develop a new method of accounting for timing errors introduced by volume registration into physiological correction (motion-modified RETROICOR). Both simulation and resting data indicate that the temporal standard deviation is reduced most by performing Volume registration before RETROICOR and slice-time Correction after RETROCIOR. While simulations indicate that physiological noise correction with regressors constructed on a slice-by-slice basis more accurately modeled physiological noise compared to using the same regressors for the entire volume, the difference between these regression techniques in subject data was minimal. The motion-modified RETROICOR showed marked improvement in simulations with varying amounts Of Subject motion, reducing the temporal standard deviation by up to 36% over the traditional RETROICOR. Though to a lesser degree than in simulation, the motion-modified RETROICOR performed better in nearly every voxel in the brain in both high- and low-resolution Subject data. Published by Elsevier Inc.
C1 [Jones, Tyler B.; Bandettini, Peter A.; Birn, Rasmus M.] NIMH, NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Birn, RM (reprint author), NIMH, NIH, Lab Brain & Cognit, 10 Ctr Dr,Bldg 10,Rm 1D80, Bethesda, MD 20892 USA.
EM rbirn@nih.gov
FU Intramural NIH HHS [ZIA MH002783-08]
NR 26
TC 30
Z9 31
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2008
VL 42
IS 2
BP 582
EP 590
DI 10.1016/j.neuroimage.2008.05.019
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 341DU
UT WOS:000258695200014
PM 18583155
ER
PT J
AU Chang, L
Wang, GJ
Volkow, ND
Ernst, T
Telang, F
Logan, J
Fowler, JS
AF Chang, Linda
Wang, Gene-Jack
Volkow, Nora D.
Ernst, Thomas
Telang, Frank
Logan, Jean
Fowler, Joanna S.
TI Decreased brain dopamine transporters are related to cognitive deficits
in HIV patients with or without cocaine abuse
SO NEUROIMAGE
LA English
DT Article
DE dopamine; HIV; cognition; dementia; PET; transporters
ID AIDS DEMENTIA COMPLEX; PARKINSONS-DISEASE; INFECTION; IMPAIRMENT; AGE;
DEGENERATION; ASSOCIATION; METABOLISM; MORPHOLOGY; SYMPTOMS
AB Objective: Decreased dopamine transporters (DAT) in the basal ganglia were shown in patients with human immunodeficiency virus (HIV) associated dementia. Therefore, we assessed the relationship between striatal DAT and dopamine D2 receptors (D2R) availability and cognitive performance, and whether cocaine abuse, a common co-morbid condition in HIV patients, would be associated with further decreases in DAT and D2 receptors.
Methods: 35 HIV-positive subjects [24 without (HIV) and 11 with a history of cocaine-dependence (HIV+Coc)] and 14 seronegative controls (SN) were evaluated with PET to measure DAT using [C-11]cocaine and D2R using [C-11]raclopride (availability of DAT or D2R estimated with Bmax/Kd), and a battery of neuropsychological tests.
Results: Compared to SN controls, both HIV subject groups had lower DAT in putamen (HIV+Coc: - 16.7%, p = 0.003; HIV: - 12.2%, p = 0.02) and only HIV+Coc showed lower DAT in caudate (- 12.2%, p = 0.04). Lower D2R in both regions of both HIV groups were accounted by the greater nicotine use. Lower DAT, but not D2R, in putamen and caudate were associated with poorer performance oil Multiple neuropsychological tests, corrected for the effects of age. education, intelligence, mood, and nicotine use. Furthermore, a structural equation model (SEM) indicated that lower average dopamine function (both DAT and D2R) were related to poorer overall function oil neuropsychological tests (p = 0.05).
Interpretation: Reduced dopaminergic function may contribute to cognitive dysfunction in HIV patients with or without additional cocaine abuse. These findings suggest that these HIV patients may benefit from treatments that enhance dopamine function OF protection from dopamine cell injury. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Chang, Linda; Ernst, Thomas] Univ Hawaii, Dept Med, John A Burns Sch Med, Queens Med Ctr, Honolulu, HI 96813 USA.
[Wang, Gene-Jack; Telang, Frank; Logan, Jean; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Wang, Gene-Jack; Telang, Frank; Logan, Jean; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA.
[Volkow, Nora D.] NIAAA, Rockville, MD 20852 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Rockville, MD USA.
RP Chang, L (reprint author), Univ Hawaii, Dept Med, John A Burns Sch Med, Queens Med Ctr, Honolulu, HI 96813 USA.
EM LChang@hawaii.edu
OI Logan, Jean/0000-0002-6993-9994
FU U. S. Department of Energy, Office of Biological and Environmental
Research [DE-AC02-76CH00016]; National Institute on Drug Abuse [DA
K24-DA16170, K02-DA16991]
FX This research was carried out at Brookhaven National Laboratory (BNL)
and support by the U. S. Department of Energy, Office of Biological and
Environmental Research (DE-AC02-76CH00016) and the National Institute on
Drug Abuse (DA K24-DA16170: K02-DA16991). We thank David Schlyer and
Michael Schueller for Cyclotron operations; Donald Warner and David
Alexoff for PET operations; Richard Ferried, Colleen Shea, Youwen Xu,
Victor Garza and Payton King for radiotracer preparation and analysis;
Dana Carasig, Lisa Zimmerman and Naomi Pappas for subject recruitment,
Noelwah Netusil, Pauline Carter and Millard Jayne for nursing support,
Chris Wang, Xuena Wang and Caroline Jiang for data management and
analyses. We also thank Dr. Jack Fuhrer (SUNY-Stony Brook Medical
Center) for HIV subject referrals, and we are especially grateful to the
research participants in this study. None of the authors has any
competing interests.
NR 43
TC 60
Z9 60
U1 2
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2008
VL 42
IS 2
BP 869
EP 878
DI 10.1016/j.neuroimage.2008.05.011
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 341DU
UT WOS:000258695200042
PM 18579413
ER
PT J
AU Picchioni, D
Fukunaga, M
Carr, WS
Braun, AR
Balkin, TJ
Duyn, JH
Horovitz, SG
AF Picchioni, Dante
Fukunaga, Masaki
Carr, Walter S.
Braun, Allen R.
Balkin, Thomas J.
Duyn, Jeff H.
Horovitz, Silvina G.
TI fMRI differences between early and late stage-1 sleep
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE fMRI; EEG; stage-1 sleep; sleep scoring; sleep onset
ID FLUCTUATIONS
AB This study sought to test for differences in regional brain activity between stage-1 sleep immediately following wake and immediately preceding stage-2 sleep. Data were collected during daytime fMRI sessions with simultaneous EEG acquisition. A stage-1 interval was defined as follows: >= 30 s of wake, immediately followed by >= 60 s of continuous stage 1, immediately followed by >= 30 s of stage 2. We compared brain activity between the first 30 s of stage 1 (early stage 1), the last 30 s of stage 1 (late stage 1), and isolated wake. A conjunction analysis sorted each voxel into one of a series of mutually exclusive categories that represented the various possible combinations of a significant increase, decrease, or no difference among these three states. The initial dataset consisted of 14 healthy volunteers. A total of 22 sessions in these participants yielded six stage-1 intervals (from four participants) that met criteria for inclusion in the analysis. There were multiple clusters of significant voxels. Examples include changes in default-mode network areas where activity increased compared to wake only in early stage 1 and a bilateral change in the hippocampus where activity increased compared to wake only in late stage 1. These results suggest that activity in anatomically identifiable, volumetric brain regions exhibit differences during stage-1 sleep that would not have been detected with the EEG. These differences may also have specific relevance to understanding the process of sleep onset as well as the neural mechanisms of performance lapses during sleep deprivation. Published by Elsevier Ireland Ltd.
C1 [Picchioni, Dante; Balkin, Thomas J.] Walter Reed Army Inst Res, Div Psychiat & Neurosci, Silver Spring, MD 20910 USA.
[Fukunaga, Masaki; Duyn, Jeff H.; Horovitz, Silvina G.] NINDS, Natl Inst Hlth, Bethesda, MD USA.
[Carr, Walter S.] USN, Med Ctr, Bethesda, MD 20814 USA.
[Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Picchioni, D (reprint author), Walter Reed Army Inst Res, Div Psychiat & Neurosci, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
EM dante.picchioni@amedd.army.mil
RI Duyn, Jozef/F-2483-2010
FU Intramural NIH HHS [Z99 DC999999]
NR 13
TC 22
Z9 22
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD AUG 15
PY 2008
VL 441
IS 1
BP 81
EP 85
DI 10.1016/j.neulet.2008.06.010
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 333TD
UT WOS:000258174400017
PM 18584959
ER
PT J
AU Shamir, L
AF Shamir, Lior
TI Looking for familiar faces
SO SCIENCE
LA English
DT Letter
C1 NIA, Image Informat Unit, Baltimore, MD 21224 USA.
RP Shamir, L (reprint author), NIA, Image Informat Unit, Baltimore, MD 21224 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 15
PY 2008
VL 321
IS 5891
BP 912
EP 912
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 337LD
UT WOS:000258436700013
PM 18703724
ER
PT J
AU Collins, FS
AF Collins, Francis S.
TI Retrospective - Victor A. McKusick (1921-2008)
SO SCIENCE
LA English
DT Biographical-Item
C1 NHGRI, NIH, Bethesda, MD 20892 USA.
RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM 4rancis@mail.nih.gov
NR 0
TC 3
Z9 3
U1 0
U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 15
PY 2008
VL 321
IS 5891
BP 925
EP 925
DI 10.1126/science.1163901
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 337LD
UT WOS:000258436700027
PM 18703732
ER
PT J
AU Brouns, SJJ
Jore, MM
Lundgren, M
Westra, ER
Slijkhuis, RJH
Snijders, APL
Dickman, MJ
Makarova, KS
Koonin, EV
van der Oost, J
AF Brouns, Stan J. J.
Jore, Matthijs M.
Lundgren, Magnus
Westra, Edze R.
Slijkhuis, Rik J. H.
Snijders, Ambrosius P. L.
Dickman, Mark J.
Makarova, Kira S.
Koonin, Eugene V.
van der Oost, John
TI Small CRISPR RNAs guide antiviral defense in prokaryotes
SO SCIENCE
LA English
DT Article
ID PROVIDES ACQUIRED-RESISTANCE; STREPTOCOCCUS-THERMOPHILUS; REPEATS;
IDENTIFICATION; ELEMENTS; DNA; EVOLUTIONARY; SEQUENCE; VIRUSES; SYSTEM
AB Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats ( CRISPRs). Here we show how virus- derived sequences contained in CRISPRs are used by CRISPR- associated ( Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus- derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.
C1 [Brouns, Stan J. J.; Jore, Matthijs M.; Lundgren, Magnus; Westra, Edze R.; Slijkhuis, Rik J. H.; van der Oost, John] Univ Wageningen & Res Ctr, Dept Agrotechnol & Food Sci, Microbiol Lab, NL-6703 HB Wageningen, Netherlands.
[Snijders, Ambrosius P. L.; Dickman, Mark J.] Univ Sheffield, Dept Chem & Proc Engn, Sheffield S1 3JD, S Yorkshire, England.
[Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP van der Oost, J (reprint author), Univ Wageningen & Res Ctr, Dept Agrotechnol & Food Sci, Microbiol Lab, Dreijenpl 10, NL-6703 HB Wageningen, Netherlands.
EM john.vanderoost@wur.nl
OI Snijders, Bram/0000-0002-5416-8592
NR 20
TC 696
Z9 751
U1 25
U2 301
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 15
PY 2008
VL 321
IS 5891
BP 960
EP 964
DI 10.1126/science.1159689
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 337LD
UT WOS:000258436700038
PM 18703739
ER
PT J
AU Peters, NC
Egen, JG
Secundino, N
Debrabant, A
Kimblin, N
Kamhawi, S
Lawyer, P
Fay, MP
Germain, RN
Sacks, D
AF Peters, Nathan C.
Egen, Jackson G.
Secundino, Nagila
Debrabant, Alain
Kimblin, Nicola
Kamhawi, Shaden
Lawyer, Phillip
Fay, Michael P.
Germain, Ronald N.
Sacks, David
TI In vivo imaging reveals an essential role for neutrophils in
leishmaniasis transmitted by sand flies
SO SCIENCE
LA English
DT Article
ID MAJOR INFECTION; MICE; CELLS; MACROPHAGE; APOPTOSIS; SKIN; GRANULOCYTES;
RECRUITMENT; MODULATION; CLEARANCE
AB Infection with the obligate intracellular protozoan Leishmania is thought to be initiated by direct parasitization of macrophages, but the early events following transmission to the skin by vector sand flies have been difficult to examine directly. Using dynamic intravital microscopy and flow cytometry, we observed a rapid and sustained neutrophilic infiltrate at localized sand fly bite sites. Invading neutrophils efficiently captured Leishmania major ( L. m.) parasites early after sand fly transmission or needle inoculation, but phagocytosed L. m. remained viable and infected neutrophils efficiently initiated infection. Furthermore, neutrophil depletion reduced, rather than enhanced, the ability of parasites to establish productive infections. Thus, L. m. appears to have evolved to both evade and exploit the innate host response to sand fly bite in order to establish and promote disease.
C1 [Egen, Jackson G.; Germain, Ronald N.] NIAID, Immunol Lab, Bethesda, MD 20892 USA.
[Peters, Nathan C.; Secundino, Nagila; Kimblin, Nicola; Kamhawi, Shaden; Lawyer, Phillip; Sacks, David] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Debrabant, Alain] US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
RP Egen, JG (reprint author), NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA.
EM jegen@niaid.nih.gov; dsacks@nih.gov
RI Okpebholo, Love/A-8163-2010;
OI Egen, Jackson/0000-0003-2053-0837; Fay, Michael P./0000-0002-8643-9625
FU Intramural NIH HHS [Z01 AI000256-26, Z01 AI000494-21]
NR 26
TC 343
Z9 351
U1 5
U2 28
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 15
PY 2008
VL 321
IS 5891
BP 970
EP 974
DI 10.1126/science.1159194
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 337LD
UT WOS:000258436700041
PM 18703742
ER
PT J
AU Joseph, T
McAuliffe, J
Lu, B
Vogel, L
Swayne, D
Jin, H
Kemble, G
Subbarao, K
AF Joseph, Tomy
McAuliffe, Josephine
Lu, Bin
Vogel, Leatrice
Swayne, David
Jin, Hong
Kemble, George
Subbarao, Kanta
TI A live attenuated cold-adapted influenza A H7N3 virus vaccine provides
protection against homologous and heterologous H7 viruses in mice and
ferrets
SO VIROLOGY
LA English
DT Article
DE avian influenza H7 virus; reverse genetics; live attenuated H7N3 virus
vaccine; immunogenicity; efficacy
ID AVIAN INFLUENZA; BRITISH-COLUMBIA; TEMPERATURE SENSITIVITY;
PATHOGENICITY; CONJUNCTIVITIS; REASSORTANT; GENERATION; CANDIDATE;
INFECTION; CHICKENS
AB The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted AAnn Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials. Published by Elsevier Inc.
C1 [Joseph, Tomy; McAuliffe, Josephine; Vogel, Leatrice; Subbarao, Kanta] NIAID, NIH, Infect Dis Lab, Bethesda, MD 20892 USA.
[Lu, Bin; Jin, Hong; Kemble, George] Medimmune Inc, Mountain View, CA 94043 USA.
[Swayne, David] USDA, SE Poultry Res Lab, Athens, GA 30605 USA.
[Joseph, Tomy] 545 Univ Crescent, Vet Diagnost Serv, Manitoba Agr Food & Rural Initiat, Winnipeg, MB R3T 5S6, Canada.
[McAuliffe, Josephine] Medimmune Inc, Gaithersburg, MD 20878 USA.
RP Subbarao, K (reprint author), Bldg 33 Room 3E13C1,33 N Dr,MSC 3203, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000933-05]; NIAID NIH HHS [K04 AI000155, Z01
AI000155]
NR 32
TC 52
Z9 55
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD AUG 15
PY 2008
VL 378
IS 1
BP 123
EP 132
DI 10.1016/j.virol.2008.05.021
PG 10
WC Virology
SC Virology
GA 335UI
UT WOS:000258316100014
PM 18585748
ER
PT J
AU Anzinger, JJ
Olinger, GG
Spear, GT
AF Anzinger, Joshua J.
Olinger, Gene G.
Spear, Gregory T.
TI Donor variability in HIV binding to peripheral blood mononuclear cells
SO VIROLOGY JOURNAL
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELLS; INFECTION; RECEPTORS;
MACROPHAGES; ENTRY
AB Background: HIV infection of cells varies greatly between individuals, with multiple steps in the replication cycle potentially contributing to the variability. Although entry and post-entry variability of HIV infection levels in cells has been demonstrated, variability in HIV binding has not been examined. In this study, we examined variability of HIV binding to peripheral blood mononuclear cells (PBMC) from different donors.
Results: HIV binding to PBMC varied up to 3.9-fold between individuals and was independent of CD4. Replication of HIV in donor PBMC required CD4 and paralleled virus binding trends of donor PBMC. To assess the stability of virus binding phenotypes over time, HIV was bound to donors with low- and high-binding phenotypes. The binding phenotypes were maintained when tested weekly over a 4-week period for 3 of 4 donors, while one high-binding donor decreased to lower binding on the 4th week. The low- and high-binding phenotypes were also preserved across different HIV strains. Experiments performed to determine if there was an association between HIV binding levels and specific cell subset levels within PBMC showed no correlation, suggesting that HIV binds to multiple cell subsets.
Conclusion: These results show that differences exist in HIV binding to donor PBMC. Our data also show that HIV binding to donor PBMC is CD4-independent and can change over time, suggesting that virus binding variability is due to differences in the expression of changeable cellsurface host factors. Taken together, this study highlights the impact of cell-surface factors in HIV binding to, and infection of, PBMC which likely represents an important step in HIV infection in vivo.
C1 [Anzinger, Joshua J.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA.
[Olinger, Gene G.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Spear, Gregory T.] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA.
RP Anzinger, JJ (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, 10 Ctr Dr,Bldg 10,Room 5N111, Bethesda, MD 20892 USA.
EM anzingerjj@nhlbi.nih.gov; gene.olinger@us.army.mil; gspear@rush.edu
OI Olinger, Gene/0000-0001-7338-0292
FU National Institutes of Health [P01HD40539]
FX This work was supported by National Institutes of Health grant
P01HD40539.
NR 19
TC 3
Z9 3
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD AUG 15
PY 2008
VL 5
AR 95
DI 10.1186/1743-422X-5-95
PG 6
WC Virology
SC Virology
GA 360AG
UT WOS:000260028800001
PM 18706090
ER
PT J
AU Solaja, BA
Opsenica, D
Smith, KS
Milhous, WK
Terzic, N
Opsenica, I
Burnett, JC
Nuss, J
Gussio, R
Bavari, S
AF Solaja, Bogdan A.
Opsenica, Dejan
Smith, Kirsten S.
Milhous, Wilbur K.
Terzic, Natasa
Opsenica, Igor
Burnett, James C.
Nuss, Jon
Gussio, Rick
Bavari, Sina
TI Novel 4-aminoquinolines active against chloroquine-resistant and
sensitive P. falciparum strains that also inhibit botulinum serotype A
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID ANTIMALARIAL ACTIVITY; SIDE-CHAIN; PLASMODIUM-FALCIPARUM; NEUROTOXIN;
DERIVATIVES; METALLOPROTEASE; CANDIDATE; MALARIA
AB We report on the initial result of the coupling of 4-amino7-chloroquinoline with steroidal and adamantane constituents to provide small molecules with excellent in vitro antimalarial activities (IC90 (W2) down to 6.74 nM). The same entities also inhibit the botulinum neurotoxin serotype A light chain metalloprotease at low nlicromolar levels (7-3 1 yM). Interestingly. structural features imparting increased antimalarial activity also provide increased inetalloprotease inhibition, thus allowing for simultaneous compound optimizations against distinct targets.
C1 [Solaja, Bogdan A.; Terzic, Natasa; Opsenica, Igor] Univ Belgrade, Fac Chem, Belgrade 11001, Serbia.
[Opsenica, Dejan; Bavari, Sina] Inst Chem Technol & Met, Belgrade 11000, Serbia.
[Smith, Kirsten S.; Milhous, Wilbur K.] Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Expt Therapeut, Washington, DC 20307 USA.
[Burnett, James C.] SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD USA.
Frederick Inc, Natl Canc Inst, Frederick, MD 21702 USA.
[Gussio, Rick] Natl Canc Inst, Dev Therapeut Program, Frederick, MD 21702 USA.
[Nuss, Jon] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
RP Solaja, BA (reprint author), Univ Belgrade, Fac Chem, Studentski Trg 16,POB 158, Belgrade 11001, Serbia.
EM bsolaja@chem.bg.ac.yu
RI Opsenica, Igor/P-5308-2016;
OI Opsenica, Igor/0000-0003-4942-4042; Solaja, Bogdan/0000-0002-9975-2725
FU NCI NIH HHS [Y3-CM-100505]
NR 26
TC 34
Z9 36
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 14
PY 2008
VL 51
IS 15
BP 4388
EP 4391
DI 10.1021/jm800737y
PG 4
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 335KP
UT WOS:000258289800007
PM 18637666
ER
PT J
AU Andreani, A
Burnelli, S
Granaiola, M
Leoni, A
Locatelli, A
Morigi, R
Rambaldi, M
Varoli, L
Landi, L
Prata, C
Berridge, MV
Grasso, C
Fiebig, HH
Kelter, G
Burger, AM
Kunkel, MW
AF Andreani, Aldo
Burnelli, Silvia
Granaiola, Massimiliano
Leoni, Alberto
Locatelli, Alessandra
Morigi, Rita
Rambaldi, Mirella
Varoli, Lucilla
Landi, Laura
Prata, Cecilia
Berridge, Michael V.
Grasso, Carole
Fiebig, Heinz-Herbert
Kelter, Gerhard
Burger, Angelika M.
Kunkel, Mark W.
TI Antitumor activity of bis-indole derivatives
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POTENTIAL COANTHRACYCLINIC ACTIVITY; MEMBRANE ELECTRON-TRANSPORT;
TUMOR-CELL LINES; CARDIOTONIC ACTIVITY; ANTICANCER DRUG; BREAST-CANCER;
AGENTS; 2-INDOLINONES; INHIBITORS
AB This paper reports the synthesis of compounds formed by two indole systems separated by a heterocycle (pyridine or piperazine). As a primary screening, the new compounds were submitted to the National Cancer Institute for evaluation of antitumor activity in the human cell line screen. The pyridine derivatives were far more active than the piperazine derivatives. For the study of the mechanism of action, the most active compounds were subjected to COMPARE analysis and to further biological tests including proteasome inhibition and inhibition of plasma membrane electron transport. The compound bearing the 5-methoxy2-indolinone moiety was subjected to the first in vivo experiment (hollow fiber assay) and was active. It was therefore selected for the second in vivo experiment (human tumor xenograft in mice). In conclusion we demonstrated that this approach was successful, since some of the compounds described are much more active than the numerous, so far prepared and tested 3-indolylmethylene-2-indolinones.
C1 [Andreani, Aldo; Burnelli, Silvia; Granaiola, Massimiliano; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy.
[Landi, Laura; Prata, Cecilia] Univ Bologna, Dipartimento Biochim G Moruzzi, I-40126 Bologna, Italy.
[Berridge, Michael V.; Grasso, Carole] Malaghan Inst Med Res, Wellington, New Zealand.
[Fiebig, Heinz-Herbert; Kelter, Gerhard] Oncotest GmbH, D-79108 Freiburg, Germany.
[Burger, Angelika M.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA.
[Kunkel, Mark W.] NCI, Dev Therapeut Program, Informat Technol Branch, Div Canc Treatment & Diag, Rockville, MD 20892 USA.
RP Andreani, A (reprint author), Univ Bologna, Dipartimento Sci Farmaceut, Via Belmeloro 6, I-40126 Bologna, Italy.
EM aldo.andreani@unibo.it
RI Berridge, Michael/I-3969-2013;
OI LEONI, ALBERTO/0000-0001-8528-8207
FU NCI NIH HHS [R01 CA127258, R01 CA127258-02]
NR 40
TC 52
Z9 54
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 14
PY 2008
VL 51
IS 15
BP 4563
EP 4570
DI 10.1021/jm800194k
PG 8
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 335KP
UT WOS:000258289800025
PM 18598018
ER
PT J
AU Cinelli, MA
Morrell, A
Dexheimer, TS
Scher, ES
Pommier, Y
Cushman, M
AF Cinelli, Maris A.
Morrell, Andrew
Dexheimer, Thomas S.
Scher, Evan S.
Pommier, Yves
Cushman, Mark
TI Design, synthesis, and biological evaluation of 14-substituted
aromathecins as topoisomerase I inhibitors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PLANT ANTITUMOR AGENTS; LUOTONIN-A; CAMPTOTHECIN ANALOGS; CLEAVAGE
COMPLEXES; DERIVATIVES; CYTOTOXICITY; 22-HYDROXYACUMINATINE; POISON;
DRUGS; RING
AB The aromathecin or "rosettacin", class of topoisomerase I (top1) inhibitors is effectively a "composite" of the natural products camptothecin and luotonin A and the synthetic indenoisoquinolines. The aromathecins have aroused considerable interest following the isolation and total synthesis of 22-hydroxyacuminatine, a rare cytotoxic natural product containing the 12H-5,11a-diazadibenzo[b,h]fluoren-11-one system. We have developed two novel syntheses of this system and prepared a series of 14-substituted aromathecins as novel anti proliferative topoisomerase I poisons. These inhibitors are proposed to act via an intercalation and "poisoning" mechanism identical to camptothecin and the indenoisoquinolines. Many of these compounds possess greater antiproliferative activity and anti-top1 activity than the parent unsubstituted compound (rosettacin) and previously synthesized aromathecins, as well as greater top1 inhibitory activity than 22-hydroxyacuminatine. In addition to potentially aiding solubility and localization to the DNA-enzyme complex, nitrogenous substituents located at the 14-position of the aromathecin system have been proposed to project into the major groove of the top1-DNA complex and hydrogen-bond to major-groove amino acids, thereby stabilizing the ternary complex.
C1 [Cinelli, Maris A.; Morrell, Andrew; Cushman, Mark] Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
[Cinelli, Maris A.; Morrell, Andrew; Cushman, Mark] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA.
[Dexheimer, Thomas S.; Scher, Evan S.; Pommier, Yves] NCI, NIH, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
EM cushman@pharmacy.purdue.edu
FU NCI NIH HHS [T32 CA009634, U01 CA089566, CA09634-12, UO1 CA89566, U01
CA089566-07]
NR 55
TC 46
Z9 46
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 14
PY 2008
VL 51
IS 15
BP 4609
EP 4619
DI 10.1021/jm800259e
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 335KP
UT WOS:000258289800030
PM 18630891
ER
PT J
AU Chinigo, GM
Paige, M
Grindrod, S
Hamel, E
Dakshanamurthy, S
Chruszcz, M
Minor, W
Brown, ML
AF Chinigo, Gary M.
Paige, Mikell
Grindrod, Scott
Hamel, Ernest
Dakshanamurthy, Sivanesan
Chruszcz, Maksymilian
Minor, Wladek
Brown, Milton L.
TI Asymmetric synthesis of 2,3-dihydro-2-arylquinazolin-4-ones: Methodology
and application to a potent fluorescent tubulin inhibitor with
anticancer activity
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID FORCE-FIELD; POLYMERIZATION; DERIVATIVES; ALGORITHM; AGENT; MODEL
AB For several decades the 2,3-dihydroquinazolinone (DHQZ) heterocycle has been known to possess a variety of important biological and medicinal properties. Despite the many interesting facets of these molecules, synthetic access to nonracemic DHQZ analogues has remained elusive. Herein, we disclose a synthetic route that allows access to either enantiomer of a variety of DHQZ derivatives. We illustrate the utility of this chemistry with the asymmetric preparation and biological evaluation of a new chiral fluorescent tubulin binding agent with extremely potent antiproliferative properties against human cancer cells. A computational rationale for the increased potency of the (S)-enantiomer over the (R)-enantiomer is given, based on the crystal structure of alpha,beta-tubulin complexed with colchicine. Taking advantage of the inherent fluorescence of these molecules, confocal images of GMC-5-193 (compound 7) in the cytoplasm of human melanoma cells (MDA-MB-435) cells are presented.
C1 [Paige, Mikell; Grindrod, Scott; Dakshanamurthy, Sivanesan; Brown, Milton L.] Georgetown Univ, Med Ctr, Drug Discovery Program, Dept Oncol, Washington, DC 20057 USA.
[Chinigo, Gary M.; Grindrod, Scott] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA.
[Hamel, Ernest] NCI, NIH, Div Canc Treatment & Diag, Dev Therapeut Program,Toxicol & Pharmacol Branch, Frederick, MD 21702 USA.
[Chruszcz, Maksymilian; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
RP Brown, ML (reprint author), Georgetown Univ, Med Ctr, Drug Discovery Program, Dept Oncol, Washington, DC 20057 USA.
EM mb544@georgetown.edu
RI Chruszcz, Maksymilian/E-6407-2011; Minor, Wladek/F-3096-2014;
OI Chruszcz, Maksymilian/0000-0001-7521-5485; Minor,
Wladek/0000-0001-7075-7090
FU Intramural NIH HHS [Z99 CA999999]
NR 24
TC 92
Z9 93
U1 1
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 14
PY 2008
VL 51
IS 15
BP 4620
EP 4631
DI 10.1021/jm800271c
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 335KP
UT WOS:000258289800031
PM 18610995
ER
PT J
AU Di Santo, R
Costi, R
Roux, A
Miele, G
Crucitti, GC
Iacovo, A
Rosi, F
Lavecchia, A
Marinelli, L
Di Giovanni, C
Novellino, E
Palmisano, L
Andreotti, M
Amici, R
Galluzzo, CM
Nencioni, L
Palamara, AT
Pommier, Y
Marchand, C
AF Di Santo, Roberto
Costi, Roberta
Roux, Alessandra
Miele, Gaetano
Crucitti, Giuliana Cuzzucoli
Iacovo, Alberto
Rosi, Federica
Lavecchia, Antonio
Marinelli, Luciana
Di Giovanni, Carmen
Novellino, Ettore
Palmisano, Lucia
Andreotti, Mauro
Amici, Roberta
Galluzzo, Clementina Maria
Nencioni, Lucia
Palamara, Anna Teresa
Pommier, Yves
Marchand, Christophe
TI Novel quinolinonyl diketo acid derivatives as HIV-1 integrase
inhibitors: Design, synthesis, and biological activities
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IN-VITRO; MECHANISM; CELLS
AB Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.
C1 [Di Santo, Roberto; Costi, Roberta; Roux, Alessandra; Miele, Gaetano; Crucitti, Giuliana Cuzzucoli; Iacovo, Alberto; Rosi, Federica] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, I-00185 Rome, Italy.
[Lavecchia, Antonio; Marinelli, Luciana; Di Giovanni, Carmen; Novellino, Ettore] Univ Naples Federico 2, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy.
[Palmisano, Lucia; Andreotti, Mauro; Amici, Roberta; Galluzzo, Clementina Maria] Ist Super Sanita, Dipartimento Farmaco, I-00161 Rome, Italy.
[Nencioni, Lucia; Palamara, Anna Teresa] Univ Roma La Sapienza, Dipartimento Sci Sanita Pubbl, I-00185 Rome, Italy.
[Pommier, Yves; Marchand, Christophe] NCI, NIH, Ctr Canc Res, Mol Phys Lab, Bethesda, MD 20892 USA.
RP Di Santo, R (reprint author), Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Ist Pasteur Fdn Cenci Bolognetti, P Le A Moro 5, I-00185 Rome, Italy.
EM roberto.disanto@uniroma1.it; marchand@nih.gov
RI palmisano, lucia/G-5577-2011; Marchand, Christophe/D-8559-2016;
andreotti, mauro/K-1436-2016;
OI andreotti, mauro/0000-0001-5168-8624; COSTI,
Roberta/0000-0002-1314-9029; Di Santo, Roberto/0000-0002-4279-7666;
Marinelli, Luciana/0000-0002-4084-8044
NR 19
TC 28
Z9 29
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 14
PY 2008
VL 51
IS 15
BP 4744
EP 4750
DI 10.1021/jm8001422
PG 7
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 335KP
UT WOS:000258289800043
PM 18646746
ER
PT J
AU Gao, YJ
Kuwabara, H
Spivak, CE
Xiao, YX
Kellar, K
Ravert, HT
Kumar, A
Alexander, M
Hilton, J
Wong, DF
Dannals, RF
Horti, AG
AF Gao, Yongjun
Kuwabara, Hiroto
Spivak, Charles E.
Xiao, Yingxian
Kellar, Kenneth
Ravert, Hayden T.
Kumar, Anil
Alexander, Mohab
Hilton, John
Wong, Dean F.
Dannals, Robert F.
Horti, Andrew G.
TI Discovery of (-)-7-methyl-2-exo-[3 '-(6-[(18)F]fluoropyridin-2-yl)-5
'-pyridinyl]-7-azabicyclo[2.2.1]heptane, a radiolabeled antagonist for
cerebral nicotinic acetylcholine receptor ((alpha 4 beta 2-nAChR) with
optimal positron emission tomography Imaging properties
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IN-VIVO TRACER; HUMAN BRAIN; PARKINSONS-DISEASE; GRAPHICAL ANALYSIS;
NONHUMAN PRIMATE; PET; ANALOGS; BINDING; EPIBATIDINE; RADIOLIGAND
AB Several isomers of 7-methyl-2-exo-([(18)F]fluoropyridinyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane have been developed as radioligands with optimized brain kinetics for PET imaging of nAChR. The binding assay demonstrated that all isomers are beta-nAChR selective ligands with K(i) = 0.02-0.3 nM. The experimental lipophilicity values of all isomers were in the. optimal range for the cerebral radioligands (log D(7.4)=0.67-0.99). The isomers with higher binding affinity manifested slow baboon brain kinetics, whereas the isomer with the lowest binding affinity (K(i)=0.3 nM) ((-)-7-methyl-2-exo-[3'-(6-[F]fluoropyridin-2-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane, [(18)F](-)-6c) and greatest lipophilicity (log D(7.4)=0.99) exhibited optimal brain kinetics. [(18)F](-)-6c manifests a unique combination of the optimally rapid brain kinetics, high BP and brain uptake, and favorable metabolic profile. Pharmacological studies showed that (-)-6c is an alpha 4 beta 2-nAChR antagonist with low side effects in mice. This combination of imaging properties suggests that [(18)F]-(-)-6c is a potentially superior replacement for 2-[(18)F]fluoro-A-85380 and 6-[(18)F]fluoro-A-85380, the only available nAChR PET radioligands for humans.
C1 [Gao, Yongjun; Kuwabara, Hiroto; Ravert, Hayden T.; Kumar, Anil; Alexander, Mohab; Hilton, John; Wong, Dean F.; Dannals, Robert F.; Horti, Andrew G.] Johns Hopkins Univ, Sch Med, Dept Radiol, Div Nucl Med, Baltimore, MD 21287 USA.
[Spivak, Charles E.] NIDA, IRP, Cellular Neurobiol Branch, Cellular Neurophysiol Sect, Baltimore, MD 21224 USA.
[Xiao, Yingxian; Kellar, Kenneth] Georgetown Univ, Washington, DC 20007 USA.
RP Horti, AG (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, Div Nucl Med, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM ahorti1@jhmi.edu
RI Kumar, Anil/B-6909-2008
FU NIDA NIH HHS [K24 DA000412, K24 DA000412-09]; NIMH NIH HHS [N01 MH32004,
MH079017]
NR 45
TC 17
Z9 18
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 14
PY 2008
VL 51
IS 15
BP 4751
EP 4764
DI 10.1021/jm800323d
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 335KP
UT WOS:000258289800044
PM 18605717
ER
PT J
AU Hartmann, J
Dragicevic, E
Adelsberger, H
Henning, HA
Sumser, M
Abramowitz, J
Blum, R
Dietrich, A
Freichel, M
Flockerzi, V
Birnbaumer, L
Konnerth, A
AF Hartmann, Jana
Dragicevic, Elena
Adelsberger, Helmuth
Henning, Horst A.
Sumser, Martin
Abramowitz, Joel
Blum, Robert
Dietrich, Alexander
Freichel, Marc
Flockerzi, Veit
Birnbaumer, Lutz
Konnerth, Arthur
TI TRPC3 channels are required for synaptic transmission and motor
coordination
SO NEURON
LA English
DT Article
ID CEREBELLAR PURKINJE-CELLS; METABOTROPIC GLUTAMATE-RECEPTOR; LONG-TERM
DEPRESSION; INWARD CURRENT; NEUROTROPHIC FACTOR; NEURONS; MICE;
ACTIVATION; BRAIN; LOCALIZATION
AB In the mammalian central nervous system, slow synaptic excitation involves the activation of metabotropic glutamate receptors (mGluRs). It has been proposed that C1-type transient receptor potential (TRPC1) channels underlie this synaptic excitation, but our analysis of TRPC1-deficient mice does not support this hypothesis. Here, we show unambiguously that it is TRPC3 that is needed for mGluR-dependent synaptic signaling in mouse cerebellar Purkinje cells. TRPC3 is the most abundantly expressed TRPC subunit in Purkinje cells. In mutant mice lacking TRPC3, both slow synaptic potentials and mGluR-mediated inward currents are completely absent, while the synaptically mediated Ca2+ release signals from intracellular stores are unchanged. Importantly, TRPC3 knockout mice exhibit an impaired walking behavior. Taken together, our results establish TRPC3 as a new type of postsynaptic channel that mediates mGluR-dependent synaptic transmission in cerebellar Purkinje cells and is crucial for motor coordination.
C1 [Hartmann, Jana; Dragicevic, Elena; Adelsberger, Helmuth; Henning, Horst A.; Sumser, Martin; Konnerth, Arthur] Tech Univ Munich, Inst Neurosci, D-80802 Munich, Germany.
[Hartmann, Jana; Dragicevic, Elena; Adelsberger, Helmuth; Henning, Horst A.; Sumser, Martin; Konnerth, Arthur] Tech Univ Munich, Ctr Integrated Prot Sci, D-80802 Munich, Germany.
[Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Transmembrane Signaling Grp, Res Triangle Pk, NC 27709 USA.
[Blum, Robert] Univ Munich, Inst Physiol, D-80336 Munich, Germany.
[Dietrich, Alexander] Univ Marburg, Inst Pharmacol & Toxicol, D-35043 Marburg, Germany.
[Freichel, Marc; Flockerzi, Veit] Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, D-66421 Homburg, Germany.
RP Konnerth, A (reprint author), Tech Univ Munich, Inst Neurosci, D-80802 Munich, Germany.
EM arthur.konnerth@lrz.tum.de
RI Hartmann, Jana/C-1024-2008; Blum, Robert/E-8899-2013; Dietrich,
Alexander/G-8619-2013; Abramowitz, Joel/A-2620-2015; Sumser,
Martin/N-1747-2015;
OI Blum, Robert/0000-0002-5270-3854; Sumser, Martin/0000-0002-1760-8026;
Dietrich, Alexander/0000-0002-1168-8707
FU Deutsche Forschungsgemeinschaft [HA 5388/1-1, IRTG 1373, GRK 333];
Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences [Z01-ES101684]; Schiedel Foundation
FX Supported by the Deutsche Forschungsgemeinschaft (HA 5388/1-1; IRTG
1373, GRK 333), the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (Z01-ES101684), and the
Schiedel Foundation. A.K. is a Carl-von-Linde Senior Fellow of the
Institute for Advanced Study of the TUM.
NR 37
TC 182
Z9 183
U1 1
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD AUG 14
PY 2008
VL 59
IS 3
BP 392
EP 398
DI 10.1016/j.neuron.2008.06.009
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 339GG
UT WOS:000258565500008
PM 18701065
ER
PT J
AU Truog, RD
Miller, FG
AF Truog, Robert D.
Miller, Franklin G.
TI The dead donor rule and organ transplantation
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID BRAIN-DEATH
C1 [Truog, Robert D.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Truog, Robert D.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA.
[Truog, Robert D.] Childrens Hosp, Div Crit Care Med, Boston, MA 02115 USA.
[Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Truog, RD (reprint author), Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
NR 5
TC 89
Z9 91
U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 14
PY 2008
VL 359
IS 7
BP 674
EP 675
DI 10.1056/NEJMp0804474
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 336XE
UT WOS:000258397900003
PM 18703469
ER
PT J
AU Sakthivel, SK
Singh, UP
Singh, S
Taub, DD
Igietseme, JU
Lillard, JW
AF Sakthivel, Senthilkumar K.
Singh, Udai P.
Singh, Shailesh
Taub, Dennis D.
Igietseme, Joseph U.
Lillard, James W., Jr.
TI CCL5 regulation of mucosal chlamydial immunity and infection
SO BMC MICROBIOLOGY
LA English
DT Article
ID GENITAL-TRACT INFECTION; OUTER-MEMBRANE PROTEIN; PROTECTIVE IMMUNITY;
DEFICIENT MICE; IFN-GAMMA; TRANSCUTANEOUS IMMUNIZATION; DIFFERENTIAL
EXPRESSION; TRACHOMATIS INFECTION; DISEASE PROGRESSION; CHEMOKINE
RECEPTORS
AB Background: Following genital chlamydial infection, an early T helper type 1 (Th1)-associated immune response precedes the activation and recruitment of specific Th1 cells bearing distinct chemokine receptors, subsequently leading to the clearance of Chlamydia. We have shown that CCR5, a receptor for CCL5, is crucial for protective chlamydial immunity. Our laboratory and others have also demonstrated that CCL5 deficiencies found in man and animals can increase the susceptibility and progression of infectious diseases by modulating mucosal immunity. These findings suggest the CCR5-CCL5 axis is necessary for optimal chlamydial immunity. We hypothesized CCL5 is required for protective humoral and cellular immunity against Chlamydia.
Results: The present study revealed that CCR5 and CCL5 mRNAs are elevated in the spleen, iliac lymph nodes (ILNs), and genital mucosa following Chlamydia muriduram challenge. Antibody ( Ab)mediated inhibition of CCL5 during genital chlamydial infection suppressed humoral and Th1 > Th2 cellular responses by splenic-, ILN-, and genital mucosa-derived lymphocytes. Antigen (Ag)-specific proliferative responses of CD4(+) T cells from spleen, ILNs, and genital organs also declined after CCL5 inhibition.
Conclusion: The suppression of these responses correlated with delayed clearance of C. muriduram, which indicate chlamydial immunity is mediated by Th1 immune responses driven in part by CCL5. Taken together with other studies, the data show that CCL5 mediates the temporal recruitment and activation of leukocytes to mitigate chlamydial infection through enhancing adaptive mucosal humoral and cellular immunity.
C1 [Igietseme, Joseph U.] CDC, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA.
[Sakthivel, Senthilkumar K.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
[Singh, Udai P.] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC USA.
[Singh, Shailesh; Lillard, James W., Jr.] Univ Louisville, Sch Med, Brown Canc Ctr, Dept Microbiol & Immunol, Louisville, KY 40292 USA.
[Taub, Dennis D.] NIA, Gerontol Res Ctr, Immunol Lab, Baltimore, MD 20892 USA.
[Igietseme, Joseph U.; Lillard, James W., Jr.] Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA.
RP Igietseme, JU (reprint author), CDC, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA.
EM ssakthi@emory.edu; usingh@gw.med.sc.edu; shailesh.singh@louisville.edu;
taubd@grc.nia.nih.gov; jigietseme@cdc.gov; james.lillard@louisville.edu
FU National Institute of Health [RR03034, GM08248, MD000525, AI41231,
AI57808]; Smith & Lucille Gibson Endowment in Medicine; National
Institute on Aging; National Institutes of Health
FX This work was supported in part by National Institute of Health grants
RR03034, GM08248, MD000525, AI41231 and AI57808 and the Smith & Lucille
Gibson Endowment in Medicine. This research was also supported in part
by the Intramural Research Program of the National Institute on Aging,
National Institutes of Health. The content of this manuscript benefited
from many fruitful conversations with colleagues at Morehouse School of
Medicine, Centers for Disease Control & Prevention, and University of
Louisville as well as editing by Andrew Marsh.
NR 50
TC 10
Z9 10
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD AUG 13
PY 2008
VL 8
AR 136
DI 10.1186/1471-2180-8-136
PG 9
WC Microbiology
SC Microbiology
GA 349NC
UT WOS:000259286500001
PM 18700040
ER
PT J
AU Robb, JA
Moore, HM
Compton, CC
AF Robb, James A.
Moore, Helen M.
Compton, Carolyn C.
TI Documenting biospecimen conditions in reports of studies
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Robb, James A.; Moore, Helen M.; Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA.
RP Robb, JA (reprint author), NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA.
EM moorehe@mail.nih.gov
NR 5
TC 3
Z9 3
U1 0
U2 1
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 AUG 13
PY 2008
VL 300
IS 6
BP 650
EP 651
DI 10.1001/jama.300.6.650-c
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 336OM
UT WOS:000258374500014
PM 18698060
ER
PT J
AU Rudebeck, PH
Murray, EA
AF Rudebeck, Peter H.
Murray, Elisabeth A.
TI Amygdala and orbitofrontal cortex lesions differentially influence
choices during object reversal learning
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE reward; prefrontal cortex; learning; macaque; decision; behavior
ID ORBITAL PREFRONTAL CORTEX; RHESUS-MONKEYS; MACAQUE MONKEYS; REWARD;
REINFORCEMENT; DEVALUATION; HIPPOCAMPUS; FAIL; SET
AB In nonhuman primates, interaction between the orbitofrontal cortex (OFC) and the amygdala (AMG) has been seen as critical for learning and subsequently changing associations between stimuli and reinforcement. However, it is still unclear what the precise role of the OFC is in altering these stimulus-reward associations, and recent research has questioned whether the AMG makes an essential contribution at all. To gain a better understanding of the role of these two structures in flexibly associating stimuli with reinforcement, we reanalyzed a set of previously published data from groups of monkeys with either OFC or AMG lesions that had been tested on an object reversal learning task. Based on trial-by-trial analyses of rewarded and unrewarded choices, we report two new findings. First, monkeys with OFC lesions were, compared with both control and AMG groups, unable to use correctly performed trials to optimally guide subsequent choices. Second, monkeys with AMG lesions showed the opposite pattern of behavior. This group benefited more than controls from correctly performed trials that followed an error. Finally, as has been reported by others, after a change in reward contingencies, monkeys with OFC lesions also showed a slightly greater tendency to choose the previously rewarded object. These findings demonstrate that the OFC and AMG make different contributions to object reversal learning not highlighted previously.
C1 [Rudebeck, Peter H.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Rudebeck, PH (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bldg 49,Suite 1B80,49 Convent Dr, Bethesda, MD 20892 USA.
EM rudebeckp@mail.nih.gov
RI Rudebeck, Peter/G-7931-2012;
OI Rudebeck, Peter/0000-0002-1411-7555; Murray,
Elisabeth/0000-0003-1450-1642
FU Intramural Research Program of the National Institute of Mental Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health. We thank A. Izquierdo, R. Suda, and
K. Wright for testing and data collection.
NR 28
TC 67
Z9 68
U1 1
U2 6
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 AUG 13
PY 2008
VL 28
IS 33
BP 8338
EP 8343
DI 10.1523/JNEUROSCI.2272-08.2008
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 337GL
UT WOS:000258423400022
PM 18701696
ER
PT J
AU Langlois, C
Mas, C
Di Lello, P
Jenkins, LMM
Legault, P
Omichinski, JG
AF Langlois, Chantal
Mas, Caroline
Di Lello, Paola
Jenkins, Lisa M. Miller
Legault, Pascale
Omichinski, James G.
TI NMR structure of the complex between the Tfb1 subunit of TFIIH and the
activation domain of VP16: Structural similarities between VP16 and p53
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID HERPES-SIMPLEX-VIRUS; TATA-BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATION;
TRANSACTIVATION DOMAIN; IN-VIVO; AROMATIC INTERACTIONS;
TUMOR-SUPPRESSOR; MULTIPLE REGIONS; MAMMALIAN-CELLS; GENE-EXPRESSION
AB The Herpes Simplex Virion Protein 16 (VP16) activates transcription through a series of protein/protein interactions involving its highly acidic transactivation domain (TAD). The acidic TAD of VP16 (VP16TAD) has been shown to interact with several partner proteins both in vitro and in vivo, and many of these VP16 partners also bind the acidic TAD of the mammalian tumor suppressor protein p53. For example, the TADs of VP16 and p53 (p53TAD) both interact directly with the p62/Tfb1 (human/yeast) subunit of TFIIH, and this interaction correlates with their ability to activate both the initiation and elongation phase of transcription. In this manuscript, we use NMR spectroscopy, isothermal titration calorimetery (ITC) and site-directed mutagenesis studies to characterize the interaction between the VP16TAD and Tfb1. We identify a region within the carboxyl-terminal subdomain of the VP16TAD (VP16C) that has sequence similarity with p53TAD2 and binds Tfb1 with nanomolar affinity. We determine an NMR structure of a Tfb1/VP16C complex, which represents the first high-resolution structure of the VP16TAD in complex with a target protein. The structure demonstrates that like p53TAD2, VP16C forms a 9-residue alpha-helix in complex with Tfb1. Comparison of the VP16/Tfb1 and p53/Tfb1 structures clearly demonstrates how the viral activator VP16C and p53TAD2 shares numerous aspects of binding to Tfb1. Despite the similarities, important differences are observed between the p53TAD2/Tfb1 and VP16C/Tfb1 complexes, and these differences demonstrate how selected activators such as p53 depend on phosphorylation events to selectively regulate transcription.
C1 [Langlois, Chantal; Mas, Caroline; Di Lello, Paola; Legault, Pascale; Omichinski, James G.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.
[Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Omichinski, JG (reprint author), Univ Montreal, Dept Biochim, CP 6128 Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada.
EM jg.omichinski@umontreal.ca
RI di lello, paola/C-8605-2013
NR 79
TC 31
Z9 34
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 13
PY 2008
VL 130
IS 32
BP 10596
EP 10604
DI 10.1021/ja800975h
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 335MD
UT WOS:000258293800044
PM 18630911
ER
PT J
AU Boasso, A
Hardy, AW
Anderson, SA
Dolan, MJ
Shearer, GM
AF Boasso, Adriano
Hardy, Andrew W.
Anderson, Stephanie A.
Dolan, Matthew J.
Shearer, Gene M.
TI HIV-Induced Type I Interferon and Tryptophan Catabolism Drive T Cell
Dysfunction Despite Phenotypic Activation
SO PLOS ONE
LA English
DT Article
AB Infection by the human immunodeficiency virus (HIV) is characterized by functional impairment and chronic activation of T lymphocytes, the causes of which are largely unexplained. We cultured peripheral blood mononuclear cells (PBMC) from HIV-uninfected donors in the presence or absence of HIV. HIV exposure increased expression of the activation markers CD69 and CD38 on CD4 and CD8 T cells. IFN-alpha/beta, produced by HIV-activated plasmacytoid dendritic cells (pDC), was necessary and sufficient for CD69 and CD38 upregulation, as the HIV-induced effect was inhibited by blockade of IFN-alpha/beta receptor and mimicked by recombinant IFN-alpha/beta. T cells from HIV-exposed PBMC showed reduced proliferation after T cell receptor stimulation, partially prevented by 1-methyl tryptophan, a competitive inhibitor of the immunesuppressive enzyme indoleamine (2,3)-dioxygenase (IDO), expressed by HIV-activated pDC. HIV-induced IDO inhibited CD4 T cell proliferation by cell cycle arrest in G1/S, and prevented CD8 T cell from entering the cell cycle by downmodulating the costimulatory receptor CD28. Finally, the expression of CHOP, a marker of the stress response activated by IDO, was upregulated by HIV in T cells in vitro and is increased in T cells from HIV-infected patients. Our data provide an in vitro model for HIV-induced T cell dysregulation and support the hypothesis that activation of pDC concomitantly contribute to phenotypic T cell activation and inhibition of T cell proliferative capacity during HIV infection.
C1 [Boasso, Adriano; Hardy, Andrew W.; Shearer, Gene M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Boasso, Adriano] Imperial Coll, Fac Med, Dept Immunol, London, England.
[Boasso, Adriano] Westminster Med Sch & Hosp, London, England.
[Anderson, Stephanie A.] Henry M Jackson Fdn, Wilford Hall Med Ctr, Infect Dis Clin Res Program IDCRP, Lackland AFB, TX USA.
[Dolan, Matthew J.] Henry M Jackson Fdn, San Antonio Mil Med Ctr SAMMC, Infect Dis Clin Res Program IDCRP, Ft Sam Houston, TX USA.
RP Boasso, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM a.boasso@imperial.ac.uk
OI Boasso, Adriano/0000-0001-9673-6319
FU Intramural research Program of the CCR, NCI; Intramural AIDS Targeted
Antiviral Program (IATAP)
FX This research was supported by the Intramural research Program of the
CCR, NCI and by the Intramural AIDS Targeted Antiviral Program (IATAP).
NR 86
TC 69
Z9 72
U1 0
U2 6
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 AUG 13
PY 2008
VL 3
IS 8
AR e2961
DI 10.1371/journal.pone.0002961
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 422FK
UT WOS:000264412600046
PM 18698365
ER
PT J
AU Jabbi, M
Bastiaansen, J
Keysers, C
AF Jabbi, Mbemba
Bastiaansen, Jojanneke
Keysers, Christian
TI A Common Anterior Insula Representation of Disgust Observation,
Experience and Imagination Shows Divergent Functional Connectivity
Pathways
SO PLOS ONE
LA English
DT Article
ID MIRROR NEURON SYSTEM; OLD-WORLD MONKEY; SOCIAL COGNITION; MOTOR IMAGERY;
EMPATHY; CORTEX; EMOTIONS; HUMANS; BRAIN; RECOGNITION
AB Similar brain regions are involved when we imagine, observe and execute an action. Is the same true for emotions? Here, the same subjects were scanned while they (a) experience, (b) view someone else experiencing and (c) imagine experiencing gustatory emotions (through script-driven imagery). Capitalizing on the fact that disgust is repeatedly inducible within the scanner environment, we scanned the same participants while they (a) view actors taste the content of a cup and look disgusted (b) tasted unpleasant bitter liquids to induce disgust, and (c) read and imagine scenarios involving disgust and their neutral counterparts. To reduce habituation, we inter-mixed trials of positive emotions in all three scanning experiments. We found voxels in the anterior Insula and adjacent frontal operculum to be involved in all three modalities of disgust, suggesting that simulation in the context of social perception and mental imagery of disgust share a common neural substrates. Using effective connectivity, this shared region however was found to be embedded in distinct functional circuits during the three modalities, suggesting why observing, imagining and experiencing an emotion feels so different.
C1 [Jabbi, Mbemba] NIMH, Sect Integrat Neuroimaging, Cognit Brain Disorders Branch, Bethesda, MD 20892 USA.
[Jabbi, Mbemba; Bastiaansen, Jojanneke; Keysers, Christian] Univ Groningen, Univ Med Ctr Groningen, BCN Neuroimaging Ctr, Social Brain Lab, Groningen, Netherlands.
RP Jabbi, M (reprint author), NIMH, Sect Integrat Neuroimaging, Cognit Brain Disorders Branch, Bethesda, MD 20892 USA.
EM jabbim@mail.nih.gov; c.m.keysers@rug.nl
RI Bastiaansen, Jojanneke/F-4849-2013; Keysers, Christian/H-6251-2013;
OI Bastiaansen, Jojanneke/0000-0003-4831-6402; Keysers,
Christian/0000-0002-2845-5467; Lauwereyns, Jan/0000-0003-0551-2550
FU European Marie Curie Excellence; Nederlands Wetenschappelijk Organisatie
NWO; Dutch science foundation; VIDI
FX This work has been funded by the European Marie Curie Excellence and the
Nederlands Wetenschappelijk Organisatie (NWO; Dutch science foundation)
VIDI grants to Christian Keysers. However, the funding bodies have no
further role in any part of this work or the decision to submit the
manuscript to PloS ONE.
NR 61
TC 131
Z9 135
U1 1
U2 9
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 AUG 13
PY 2008
VL 3
IS 8
AR e2939
DI 10.1371/journal.pone.0002939
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 422FK
UT WOS:000264412600025
PM 18698355
ER
PT J
AU Mullen, GED
Ellis, RD
Miura, K
Malkin, E
Nolan, C
Hay, M
Fay, MP
Saul, A
Zhu, DM
Rausch, K
Moretz, S
Zhou, H
Long, CA
Miller, LH
Treanor, J
AF Mullen, Gregory E. D.
Ellis, Ruth D.
Miura, Kazutoyo
Malkin, Elissa
Nolan, Caroline
Hay, Mhorag
Fay, Michael P.
Saul, Allan
Zhu, Daming
Rausch, Kelly
Moretz, Samuel
Zhou, Hong
Long, Carole A.
Miller, Louis H.
Treanor, John
TI Phase 1 Trial of AMA1-C1/Alhydrogel plus CPG 7909: An Asexual
Blood-Stage Vaccine for Plasmodium falciparum Malaria
SO PLOS ONE
LA English
DT Article
AB Background: Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.
Methods: A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 mu g of AMA1-C1/Alhydrogel (R)+564 mu g CPG 7909 (n = 15), 80 mu g of AMA1-C1/Alhydrogel (R) (n = 30), or 80 mu g of AMA1-C1/Alhydrogel+564 mu g CPG 7909 (n = 30).
Results: Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA), and the immune sera of volunteers that received 20 mu g or 80 mu g of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 mg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.
Conclusion/Significance: The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.
Trial Registration: ClinicalTrials.gov NCT00344539
C1 [Mullen, Gregory E. D.; Ellis, Ruth D.; Miura, Kazutoyo; Zhu, Daming; Rausch, Kelly; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA.
[Malkin, Elissa] PATH Malaria Vaccine Initiative, Bethesda, MD USA.
[Nolan, Caroline; Hay, Mhorag; Treanor, John] Univ Rochester, Dept Med, Rochester, NY USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD USA.
[Saul, Allan] Novartis Vaccines Inst Global Hlth Srl NVGH, Siena, Italy.
[Moretz, Samuel; Zhou, Hong; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Mullen, GED (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA.
EM greg.mullen@kcl.ac.uk; ellisru@niaid.nih.gov
RI Saul, Allan/I-6968-2013;
OI Saul, Allan/0000-0003-0665-4091; Fay, Michael P./0000-0002-8643-9625
FU Extramural and Intramural Research Programs of the National Institute of
Allergy and Infectious Diseases, National Institutes of Health, USA; GIA
Reference Center is supported by the PATH Malaria Vaccine Initiative,
USA
FX This research was supported by the Extramural and Intramural Research
Programs of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, USA. The GIA Reference Center is
supported by the PATH Malaria Vaccine Initiative, USA.
NR 35
TC 68
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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 AUG 13
PY 2008
VL 3
IS 8
AR e2940
DI 10.1371/journal.pone.0002940
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 422FK
UT WOS:000264412600026
PM 18698359
ER
PT J
AU Kherlopian, AR
Song, T
Duan, Q
Neimark, MA
Po, MJ
Gohagan, JK
Laine, AF
AF Kherlopian, Armen R.
Song, Ting
Duan, Qi
Neimark, Mathew A.
Po, Ming J.
Gohagan, John K.
Laine, Andrew F.
TI A review of imaging techniques for systems biology
SO BMC SYSTEMS BIOLOGY
LA English
DT Review
ID ATOMIC-FORCE MICROSCOPY; MAGNETIC-RESONANCE-SPECTROSCOPY; RAY
COMPUTED-TOMOGRAPHY; QUANTUM DOTS; IN-VIVO; FLUORESCENCE MICROSCOPY;
MULTIPHOTON MICROSCOPY; STIMULATED-EMISSION; PROSTATE-CANCER;
RNA-POLYMERASE
AB This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography), MRI ( Magnetic Resonance Imaging), PET (Positron Emission Tomography), and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.
C1 [Song, Ting; Duan, Qi; Neimark, Mathew A.; Po, Ming J.; Laine, Andrew F.] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
[Kherlopian, Armen R.] Cornell Univ, Weill Med Coll, Physiol Biophys & Syst Biol Program, New York, NY 10021 USA.
NCI, NIH, Canc Prevent Div, Bethesda, MD 20892 USA.
[Laine, Andrew F.] Columbia Univ, Dept Radiol, New York, NY USA.
RP Laine, AF (reprint author), Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
EM ark2010@med.cornell.edu; ts2060@columbia.edu; qd2002@columbia.edu;
man2003@columbia.edu; mp2591@columbia.edu; gohaganj@mail.nih.gov;
al418@columbia.edu
RI Duan, Qi/J-7916-2016
OI Duan, Qi/0000-0002-2407-6611
NR 109
TC 72
Z9 74
U1 0
U2 31
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD AUG 12
PY 2008
VL 2
AR 74
DI 10.1186/1752-0509-2-74
PG 18
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 350JP
UT WOS:000259349000002
PM 18700030
ER
PT J
AU Pearson, GD
Devereux, R
Loeys, B
Maslen, C
Milewicz, D
Pyeritz, R
Ramirez, F
Rifkin, D
Sakai, L
Svensson, L
Wessels, A
Van Eyk, J
Dietz, HC
AF Pearson, Gail D.
Devereux, Richard
Loeys, Bart
Maslen, Cheryl
Milewicz, Dianna
Pyeritz, Reed
Ramirez, Francesco
Rifkin, Daniel
Sakai, Lynn
Svensson, Lars
Wessels, Andy
Van Eyk, Jennifer
Dietz, Harry C.
TI Report of the National Heart, Lung, and Blood Institute and National
Marfan Foundation working group on research in Marfan syndrome and
related disorders
SO CIRCULATION
LA English
DT Article
DE aortic aneurysm; Marfan syndrome; research
ID THORACIC AORTIC-ANEURYSMS; BETA-BLOCKER THERAPY; VALVE-SPARING
REIMPLANTATION; ARTERIAL-TORTUOSITY-SYNDROME; PATENT DUCTUS-ARTERIOSUS;
MOUSE MODEL; ROOT REPLACEMENT; ASCENDING AORTA; PEDIATRIC-PATIENTS;
VALSALVA CONDUIT
C1 [Pearson, Gail D.] NHLBI, NIH, Div Cardiovasc Dis, Bethesda, MD 20892 USA.
[Devereux, Richard] Weill Cornell Med Ctr, New York, NY USA.
[Loeys, Bart] Univ Ghent, B-9000 Ghent, Belgium.
[Maslen, Cheryl] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Milewicz, Dianna] Univ Texas Houston, Sch Med, Houston, TX USA.
[Pyeritz, Reed] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Ramirez, Francesco] Mt Sinai Sch Med, New York, NY USA.
[Rifkin, Daniel] NYU, Sch Med, New York, NY USA.
[Sakai, Lynn] Shriners Hosp Children, Portland, OR 97201 USA.
[Svensson, Lars] Cleveland Clin, Cleveland, OH 44106 USA.
[Wessels, Andy] Med Univ S Carolina, Charleston, SC 29425 USA.
[Van Eyk, Jennifer] Johns Hopkins Univ, Bayview Prote Ctr, Baltimore, MD USA.
[Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
RP Pearson, GD (reprint author), NHLBI, NIH, Div Cardiovasc Dis, 6701 Rockledge Dr,Room 8104, Bethesda, MD 20892 USA.
EM pearsong@mail.nih.gov
RI Pyeritz, Reed/A-1364-2010;
OI Loeys, Bart/0000-0003-3703-9518
FU NHLBI NIH HHS [RC1 HL100021, RC1 HL100021-01]
NR 71
TC 48
Z9 51
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD AUG 12
PY 2008
VL 118
IS 7
BP 785
EP 791
DI 10.1161/CIRCULATIONAHA.108.783753
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 336IA
UT WOS:000258356300011
PM 18695204
ER
PT J
AU Tsang, WY
Bossard, C
Khanna, H
Peraenen, J
Swaroop, A
Malhotra, V
Dynlacht, BD
AF Tsang, William Y.
Bossard, Carine
Khanna, Hemant
Peraenen, Johan
Swaroop, Anand
Malhotra, Vivek
Dynlacht, Brian David
TI CP110 suppresses primary cilia formation through its interaction with
CEP290, a protein deficient in human ciliary disease
SO DEVELOPMENTAL CELL
LA English
DT Article
ID INTRAFLAGELLAR TRANSPORT; JOUBERT-SYNDROME; CENTROSOMAL PROTEIN;
HUMAN-CELLS; MUTATIONS; BIOGENESIS; COMPLEX; PROGRESSION; CENTRIN; FORMS
AB Primary cilia are nonmotile organelles implicated in signaling and sensory functions. Understanding how primary cilia assemble could shed light on the many human diseases caused by mutations in ciliary proteins. The centrosomal protein CP110 is known to suppress ciliogenesis through an unknown mechanism. Here, we report that CP110 interacts with GEP290-a protein whose deficiency is implicate in human ciliary disease-in a discrete complex separable from other CP110 complexes involved in regulating the centrosome cycle. Ablation of CEP290 prevents ciliogenesis without affecting centrosome function or cell-cycle progression. Interaction with CEP290 is absolutely required for the ability of CP110 to suppress primary cilia formation. Furthermore, CEP290 and CP110 interact with Rab8a, a small GTPase required for cilia assembly. Depletion of CEP290 interferes with localization of Rab8a to centrosomes and cilia. Our results suggest that CEP290 cooperates with Rab8a to promote ciliogenesis and that this function is antagonized by CP110.
C1 [Tsang, William Y.; Dynlacht, Brian David] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Tsang, William Y.; Dynlacht, Brian David] NYU, Sch Med, Inst Canc, New York, NY 10016 USA.
[Bossard, Carine; Malhotra, Vivek] Ctr Genom Regulat, Barcelona 08003, Spain.
[Khanna, Hemant; Swaroop, Anand] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
[Peraenen, Johan] Univ Helsinki, Inst Biotechnol, Program Cellular Biotechnol, Helsinki 00014, Finland.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
RP Dynlacht, BD (reprint author), NYU, Sch Med, Dept Pathol, 522 1st Ave, New York, NY 10016 USA.
EM brian.dynlacht@med.nyu.edu
RI Malhotra, Vivek/O-9811-2014;
OI Malhotra, Vivek/0000-0001-6198-7943; Swaroop, Anand/0000-0002-1975-1141
FU NEI NIH HHS [R01 EY007961, EY007961]
NR 33
TC 110
Z9 112
U1 3
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 12
PY 2008
VL 15
IS 2
BP 187
EP 197
DI 10.1016/j.devcel.2008.07.004
PG 11
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 338YS
UT WOS:000258545900008
PM 18694559
ER
PT J
AU Xu, X
Han, J
Ito, Y
Bringas, P
Deng, CX
Chai, Y
AF Xu, Xun
Han, Jun
Ito, Yoshihiro
Bringas, Pablo, Jr.
Deng, Chuxia
Chai, Yang
TI Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating
TGF-beta/BMP signaling during tooth and palate development
SO DEVELOPMENTAL CELL
LA English
DT Article
ID GROWTH-FACTOR-BETA; CRANIAL NEURAL CREST; CLEFT-PALATE; DIFFERENTIAL
EXPRESSION; KNOCKOUT MICE; ENAMEL KNOT; MORPHOGENESIS; FUSION; RECEPTOR;
TGF-BETA-3
AB Smad4 is a central intracellular effector of TGF-beta signaling. Smad-independent TGF-beta pathways, such as those mediated by p38 MAPK, have been identified in cell culture systems, but their in vivo functional mechanisms remain unclear. In this study, we investigated the role of TGF-beta signaling in tooth and palate development and noted that conditional inactivation of Smad4 in oral epithelium results in much milder phenotypes than those seen with the corresponding receptor mutants, Bmpr1a and Tgfbr2, respectively. Perturbed p38 function in these tissues likewise has no effect by itself; however, when both Smad4 and p38 functions are compromised, dramatic recapitulation of the receptor mutant phenotypes results. Thus, our study demonstrates that p38 and Smad4 are functionally redundant in mediating TGF-beta signaling in diverse contexts during embryonic organogenesis. The ability of epithelium to utilize both pathways illustrates the complicated nature of TGF-beta signaling mechanisms in development and disease.
C1 [Xu, Xun; Han, Jun; Ito, Yoshihiro; Bringas, Pablo, Jr.; Chai, Yang] Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA.
[Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Chai, Y (reprint author), Univ So Calif, Ctr Craniofacial Mol Biol, 2250 Alcazar St,CSA 103, Los Angeles, CA 90033 USA.
EM ychai@usc.edu
RI deng, chuxia/N-6713-2016
FU NlDCR [DE012711]; NIH [DE014078]
FX We thank Sarah Millar for K14-Cre mice and thank Yiping Chen, Robert
Maxson, Irma Thesleff and Andrew McMahon for plasmids. We also thank
Julie Mayo for critical reading of the manuscript. This study was
supported by grants from the NlDCR, NIH (DE012711 and DE014078) to Yang
Chai.
NR 33
TC 90
Z9 93
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 12
PY 2008
VL 15
IS 2
BP 322
EP 329
DI 10.1016/j.devcel.2008.06.004
PG 8
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 338YS
UT WOS:000258545900019
PM 18694570
ER
PT J
AU Blair, RJR
AF Blair, R. J. R.
TI The amygdala and ventromedial prefrontal cortex: functional
contributions and dysfunction in psychopathy
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE amygdala; venromedial perfrontal cortex; psychopathy
ID ANTERIOR CINGULATE CORTEX; CALLOUS-UNEMOTIONAL TRAITS; ORBITOFRONTAL
CORTEX; RESPONSE REVERSAL; DECISION-MAKING; FACIAL EXPRESSIONS;
FRONTAL-CORTEX; NONPSYCHOPATHIC OFFENDERS; PHYSIOLOGICAL-RESPONSES;
NEURAL RESPONSES
AB The current paper examines the functional contributions of the amygdala and ventromedial prefrontal cortex ( vmPFC) and the evidence that the functioning of these systems is compromised in individuals with psychopathy. The amygdala is critical for the formation of stimulus-reinforcement associations, both punishment and reward based, and the processing of emotional expressions. vmPFC is critical for the representation of reinforcement expectancies and, owing to this, decision making. Neuropsychological and neuroimaging data from individuals with psychopathy are examined. It is concluded that these critical functions of the amygdala and vmPFC, and their interaction, are compromised in individuals with the disorder. It is argued that these impairments lead to the development of psychopathy.
C1 NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA.
RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, NIH, 15K N Dr, Bethesda, MD 20892 USA.
EM jamesblair@mail.nih.gov
FU Intramural NIH HHS
NR 101
TC 115
Z9 117
U1 18
U2 52
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD AUG 12
PY 2008
VL 363
IS 1503
BP 2557
EP 2565
DI 10.1098/rstb.2008.0027
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 320PI
UT WOS:000257247000007
PM 18434283
ER
PT J
AU Chen, Q
Espey, MG
Sun, AY
Pooput, C
Kirk, KL
Krishna, MC
Khosh, DS
Drisko, J
Levine, M
AF Chen, Qi
Espey, Michael Graham
Sun, Andrew Y.
Pooput, Chaya
Kirk, Kenneth L.
Krishna, Murali C.
Khosh, Deena Senecla
Drisko, Jeanne
Levine, Mark
TI Pharmacologic doses of ascorbate act as a prooxidant and decrease growth
of aggressive tumor xenografts in mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer; hydrogen peroxide; oxidation; free radical; vitamin C
ID RECOMMENDED DIETARY ALLOWANCE; VITAMIN-C PHARMACOKINETICS; TERMINAL
HUMAN CANCER; HYDROGEN-PEROXIDE; SUPPLEMENTAL ASCORBATE; SUPPORTIVE
TREATMENT; SURVIVAL TIMES; ACID; PROLONGATION; THERAPY
AB Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate administration. Real-time microdialysis sampling in mice bearing gliobiastoma xenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood. Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P < 0.001) tumors established in mice. Similar pharmacologic concentrations were readily achieved in humans given ascorbate intravenously. These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeutic options.
C1 [Chen, Qi; Espey, Michael Graham; Sun, Andrew Y.; Levine, Mark] NIDDKD, Mol & Clin Nutr Sect, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Pooput, Chaya; Kirk, Kenneth L.] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
[Krishna, Murali C.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Khosh, Deena Senecla; Drisko, Jeanne] Univ Kansas, Med Ctr, Program Integrat Med, Kansas City, KS 66160 USA.
RP Espey, MG (reprint author), NIDDKD, Mol & Clin Nutr Sect, Natl Inst Hlth, 10-4D52,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sp@nih.gov; mark.levine@nih.gov
RI leng, xianwei/F-9073-2011; Chen, Qi/D-8278-2015
OI Chen, Qi/0000-0002-7173-8411
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health
FX We thank all those who kindly shared their cell lines with us. This
research was supported in part by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 25
TC 252
Z9 265
U1 3
U2 27
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 AUG 12
PY 2008
VL 105
IS 32
BP 11105
EP 11109
DI 10.1073/pnas.0804226105
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339EK
UT WOS:000258560700016
PM 18678913
ER
PT J
AU Onda, M
Beers, R
Xiang, L
Nagata, S
Wang, QC
Pastan, I
AF Onda, Masanori
Beers, Richard
Xiang, Laiman
Nagata, Satoshi
Wang, Qing-Cheng
Pastan, Ira
TI An immunotoxin with greatly reduced immunogenicity by identification and
removal of B cell epitopes
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antibody engineering; BL22; HA22; immunotherapy; Pseudomonas exotoxin A
ID RECOMBINANT STAPHYLOKINASE VARIANTS; ANTIBODY-BINDING REGIONS; PHASE-I
TRIAL; THERAPEUTIC PROTEINS; ANTITOXIN ANTIBODIES; RFB4(DSFV)-PE38 BL22;
COMPLETE REGRESSION; CYTOTOXIC ACTIVITY; ANTITUMOR-ACTIVITY; FV
FRAGMENTS
AB Recombinant immunotoxins are hybrid proteins composed of an Fv that binds to a tumor antigen fused to a bacterial or plant toxin. Immunotoxin BL22 targets CD22 positive malignancies and is composed of an anti-CD22 Fv fused to a 38-kDa fragment of Pseudomonas exotoxin A (PE38). BL22 has produced many complete remissions in drug-resistant Hairy cell leukemia, where many treatment cycles can be given, because neutralizing antibodies do not form. In marked contrast, only minor responses have been observed in trials with immunotoxins targeting solid tumors, because only a single treatment cycle can be given before antibodies develop. To allow more treatment cycles and increase efficacy, we have produced a less immunogenic immunotoxin by identifying and eliminating most of the B cell epitopes on PE38. This was accomplished by mutation of specific large hydrophilic amino acids (Arg, Gln, Glu, Lys) to Ala, Ser, or Gly. The new immunotoxin (HA22-8X) is significantly less immunogenic in three strains of mice, yet retains full cytotoxic and anti-tumor activities. Elimination of B-cell epitopes is a promising approach to the production of less immunogenic proteins for therapeutic purposes.
C1 [Onda, Masanori; Beers, Richard; Xiang, Laiman; Nagata, Satoshi; Wang, Qing-Cheng; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 35
TC 95
Z9 96
U1 1
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 12
PY 2008
VL 105
IS 32
BP 11311
EP 11316
DI 10.1073/pnas.0804851105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 339EK
UT WOS:000258560700051
PM 18678888
ER
PT J
AU Eichelberger, M
Golding, H
Hess, M
Weir, J
Subbarao, K
Luke, CJ
Friede, M
Wood, D
AF Eichelberger, Maryna
Golding, Hana
Hess, Maureen
Weir, Jerry
Subbarao, Kanta
Luke, Catherine J.
Friede, Martin
Wood, David
TI FDA/NIH/WHO public workshop on immune correlates of protection against
influenza A viruses in support of pandemic vaccine development,
Bethesda, Maryland, US, December 10-11, 2007
SO VACCINE
LA English
DT Editorial Material
DE influenza type A; avian influenza; pandemic; correlated of protection
AB The goals of the workshop were to identify gaps in our knowledge and abilities to address the unique challenges encountered in the development of vaccines intended to protect against pandemic influenza and to facilitate implementation of a global research agenda to improve efficacy assessment of pandemic influenza vaccines. This workshop included discussions on: (i) current knowledge regarding immune correlates of protection against seasonal influenza; (ii) human immune responses to avian influenza infection and vaccines for novel influenza viruses: (iii) limitations of currently available assays to evaluate vaccine immunogenicity; and (iv) potential insights from animal models for correlates of protection against avian influenza.
C1 [Eichelberger, Maryna; Golding, Hana; Hess, Maureen; Weir, Jerry] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA.
[Subbarao, Kanta; Luke, Catherine J.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Friede, Martin; Wood, David] WHO, CH-1211 Geneva, Switzerland.
RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA.
EM hana.golding@fda.hhs.gov
NR 5
TC 72
Z9 73
U1 0
U2 3
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 AUG 12
PY 2008
VL 26
IS 34
BP 4299
EP 4303
DI 10.1016/j.vaccine.2008.06.012
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 342WF
UT WOS:000258813600001
PM 18582523
ER
PT J
AU FitzGerald, LM
Agalliu, I
Johnson, K
Miller, MA
Kwon, EM
Hurtado-Coll, A
Fazli, L
Rajput, AB
Gleave, ME
Cox, ME
Ostrander, EA
Stanford, JL
Huntsman, DG
AF FitzGerald, Liesel M.
Agalliu, Ilir
Johnson, Karynn
Miller, Melinda A.
Kwon, Erika M.
Hurtado-Coll, Antonio
Fazli, Ladan
Rajput, Ashish B.
Gleave, Martin E.
Cox, Michael E.
Ostrander, Elaine A.
Stanford, Janet L.
Huntsman, David G.
TI Association of TMPRSS2-ERG gene fusion with clinical characteristics and
outcomes: results from a population-based study of prostate cancer
SO BMC CANCER
LA English
DT Article
ID IN-SITU HYBRIDIZATION; HETEROGENEITY; FREQUENCY; OVEREXPRESSION;
REARRANGEMENTS; TRANSCRIPTS; EXPRESSION; RISK; FISH
AB Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer.
Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127).
Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03).
Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
C1 [Johnson, Karynn; Hurtado-Coll, Antonio; Fazli, Ladan; Rajput, Ashish B.; Gleave, Martin E.; Cox, Michael E.; Huntsman, David G.] Vancouver Gen Hosp, Prostate Res Ctr, Vancouver, BC V6H 3Z6, Canada.
[FitzGerald, Liesel M.; Agalliu, Ilir; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Agalliu, Ilir] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Miller, Melinda A.; Huntsman, David G.] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada.
[Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA.
[Stanford, Janet L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
RP Huntsman, DG (reprint author), Vancouver Gen Hosp, Prostate Res Ctr, Vancouver, BC V6H 3Z6, Canada.
EM lfitzger@fhcrc.org; iagalliu@aecom.yu.edu; kjohnson5@bccancer.bc.ca;
memiller@bccancer.bc.ca; kwone@mail.nih.gov; Antonio.Hurtadocoll@vch.ca;
lfazli@prostatecentre.com; rajputa@queensu.ca;
gleave@interchange.ubc.ca; mcox@interchange.ubc.ca;
eostrand@mail.nih.gov; jstanfor@fhcrc.org; dhuntsma@bccancer.bc.ca
OI Ostrander, Elaine/0000-0001-6075-9738
FU NIH [RO1 CA56678, RO1 CA114524, P50 CA97186]; Fred Hutchinson Cancer
Research Center; National Human Genome Research Institute
FX We thank all the men who participated in this study for their time,
effort and co-operation and we thank Beatrice Knudson for pathological
support. This work was supported by NIH grants RO1 CA56678, RO1
CA114524, and P50 CA97186; additional support was provided by the Fred
Hutchinson Cancer Research Center and the Intramural Program of the
National Human Genome Research Institute.
NR 37
TC 76
Z9 78
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD AUG 11
PY 2008
VL 8
AR 230
DI 10.1186/1471-2407-8-230
PG 10
WC Oncology
SC Oncology
GA 346MG
UT WOS:000259072000002
PM 18694509
ER
PT J
AU Liu, F
Stephen, AG
Waheed, AA
Aman, MJ
Freed, EO
Fisher, RJ
Burke, TR
AF Liu, Fa
Stephen, Andrew G.
Waheed, Abdul A.
Aman, M. Javad
Freed, Eric O.
Fisher, Robert J.
Burke, Terrence R., Jr.
TI SAR by oxime-containing peptide libraries: Application to Tsg101 ligand
optimization
SO CHEMBIOCHEM
LA English
DT Article
DE aldehydes; combinatorial chemistry; oximes; peptidomimetics; Tsg101
ID PROTEIN-PROTEIN INTERACTIONS; UEV DOMAIN; ANTAGONISTS; DESIGN;
CHEMOTHERAPY; RECOGNITION; INHIBITION; TARGETS; POTENT
AB HIV-1 viral assembly requires a direct interaction between a Pro-Thr-Ala-Pro ("PTAP") motif in the viral protein Gag-p6 and the cellular endosomal sorting factor Tsg101. In an effort to develop competitive inhibitors of this interaction, an SAR study was conducted based on the application of post solid-phase oxime formation involving the sequential insertion of aminooxy-containing residues within a nonamer parent, peptide followed by reaction with libraries of aldehydes. Approximately 15-20-fold enhancement in binding affinity was achieved by this approach.
C1 [Liu, Fa; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, Frederick, MD 21702 USA.
[Stephen, Andrew G.; Fisher, Robert J.] SAIC, Adv Technol Program, Prot Chem Lab, Frederick, MD 21702 USA.
[Waheed, Abdul A.; Freed, Eric O.] NCI, HIV Drug Resistance Program, CCR, Frederick, MD 21702 USA.
[Aman, M. Javad] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), NCI, Med Chem Lab, CCR, Bldg 376 Boyles St, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov
RI Fisher, Robert/B-1431-2009; Burke, Terrence/N-2601-2014
FU Intramural Research Program of the NIH; Center for Cancer Research;
NCI-Frederick; National Cancer Institute; National Institutes of Health
[N01-CO-12400]
FX The Work was supported in part by the Intramural Research Program of the
NIH, Center for Cancer Research, NCI-Frederick, and the National Cancer
Institute, National Institutes of Health, under contract N01-CO-12400.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, neither does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 24
TC 18
Z9 18
U1 0
U2 0
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1439-4227
J9 CHEMBIOCHEM
JI ChemBioChem
PD AUG 11
PY 2008
VL 9
IS 12
BP 2000
EP 2004
DI 10.1002/cbic.200800281
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 339OJ
UT WOS:000258586600022
PM 18655064
ER
PT J
AU Broutin, H
Miller, MA
AF Broutin, H.
Miller, M. A.
TI Early vaccination against measles in developing countries may improve
control of measles but cannot replace doses given at 9-15 months
SO BRITISH MEDICAL JOURNAL
LA English
DT Editorial Material
C1 [Broutin, H.; Miller, M. A.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Broutin, H (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM broutinh@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD AUG 9
PY 2008
VL 337
IS 7665
AR a406
DI 10.1136/bmj.a406
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 339EO
UT WOS:000258561100004
PM 18653638
ER
PT J
AU Byun, HM
Choi, SH
Laird, PW
Trinh, B
Siddiqui, MA
Marquez, VE
Yang, AS
AF Byun, Hyang-Min
Choi, Si Ho
Laird, Peter W.
Trinh, Binh
Siddiqui, Maqbool A.
Marquez, Victor E.
Yang, Allen S.
TI 2 '-deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine: A novel
inhibitor of DNA methyltransferase that requires activation by human
carboxylesterase
SO CANCER LETTERS
LA English
DT Article
DE DNA methylation; decitabine; NPEOC-DAC; carboxylesterase; DNA
methyltransferase
ID 5-AZA-2'-DEOXYCYTIDINE DECITABINE; MYELODYSPLASTIC SYNDROME; CANCER;
METHYLATION; TUMORS; AGENT; 5-FLUOROURACIL; 5-AZACYTIDINE;
5-AZACYTOSINE; MALIGNANCIES
AB 2 '-Deoxy-N4-[2-(4-nitrophenyl)ethoxycarbonyl]-5-azacytidine (NPEOC-DAC), decitabine with a modification of the N4 position of the azacitidine ring can be used to inhibit DNA methyltransferase. This modification protects the azacitidine ring and can be cleaved by carboxylesterase to release decitabine. NPEOC-DAC was 23-fold less potent at low doses (<10 mu M) than decitabine at inhibiting DNA methylation, and was also associated with a 3-day delay in its effect. However, at doses >= 10 mu M NPEOC-DAC was more effective at inhibiting DNA methylation. Theses differences between decitabine and NPEOC-DAC are dependent on the cleavage of the carboxylester bond, and could be potentially exploited pharmacologically. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Byun, Hyang-Min; Choi, Si Ho; Yang, Allen S.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Div Hematol, Los Angeles, CA 90033 USA.
[Laird, Peter W.; Trinh, Binh] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Surg, Los Angeles, CA 90033 USA.
[Laird, Peter W.; Trinh, Binh] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA.
[Siddiqui, Maqbool A.; Marquez, Victor E.] NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21701 USA.
RP Yang, AS (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Div Hematol, 1441 Eastlake Ave,Room 6428, Los Angeles, CA 90033 USA.
EM allenyan@usc.edu
RI Laird, Peter/G-8683-2012
FU Intramural NIH HHS [Z01 BC006176-22]
NR 45
TC 27
Z9 31
U1 2
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD AUG 8
PY 2008
VL 266
IS 2
BP 238
EP 248
DI 10.1016/j.canlet.2008.02.069
PG 11
WC Oncology
SC Oncology
GA 326HI
UT WOS:000257648800014
PM 18499340
ER
PT J
AU Denys, H
Derycke, L
Hendrix, A
Westbroek, W
Gheldof, A
Narine, K
Pauwels, P
Gespach, C
Bracke, M
De Wever, O
AF Denys, Hannelore
Derycke, Lara
Hendrix, An
Westbroek, Wendy
Gheldof, Alexander
Narine, Kishan
Pauwels, Patrick
Gespach, Christian
Bracke, Marc
De Wever, Olivier
TI Differential impact of TGF-beta and EGF on fibroblast differentiation
and invasion reciprocally promotes colon cancer cell invasion
SO CANCER LETTERS
LA English
DT Article
DE bFGF; Rho-GTPases; heterotypic co-cultures; tenascin-C; spheroid; stress
fibers
ID MUSCLE ACTIN EXPRESSION; IN-VITRO; TUMOR MICROENVIRONMENT;
GROWTH-FACTOR; RHO; MIGRATION; ADHESION; BREAST; STROMA; MYOFIBROBLASTS
AB Several studies indicate that cancer-associated fibroblasts play a critical role in cancer cell invasion and metastasis, the hallmarks of malignancy. To better understand the mechanisms underlying such effects, we established a heterotypic model of human fibroblasts (primary colon fibroblasts and immortalized human dermal fibroblasts) in co-culture with human colon cancer cells (HCT-8/E11), using three-dimensional collagen type-1 and Matrigel matrices. We report that TGF-beta is the unique and dominant factor to provide pro-invasive signals to HCT-S/E11 colon cancer cells from TGF-beta-treated human fibroblasts in three-dimensional collagen type I and Matrigel matrices. These effects are not mimicked or reversed by EGF or bFGF, and are associated with the TGF-beta-mediated induction of myofibroblast differentiation and functional markers, such as alpha-SMA, the haptotactic matrix molecule TNC, collagen type 1 maturation enzyme P4H, serine protease FAP, and myofibroblast contractility. Accordingly, TGF-beta induced a strong activation of RhoA and stress fiber formation in fibroblasts, with no impact on Rac1-GTP levels. In contrast, EGF down-regulated Rho-GTP levels in fibroblasts, giving permissive signals for Rac1 activation, fibroblast polarization, and invasion. Taken together, our data imply that TGF-beta and EGF exert invasive growth-promoting actions in human colon tumors through a differential and cumulative impact on the stromal and cancer cell compartments. Our data predict that inhibitors directed at this reciprocal molecular and cellular crosstalk will have therapeutic applications for targeting the invasive growth of human primary tumors and their metastatic spread. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Derycke, Lara; Gheldof, Alexander; Bracke, Marc; De Wever, Olivier] Ghent Univ Hosp, Dept Radiol & Nucl Med, Lab Expt Canc Res, B-9000 Ghent, Belgium.
[Denys, Hannelore; Hendrix, An] Ghent Univ Hosp, Dept Med Oncol, B-9000 Ghent, Belgium.
[Narine, Kishan] Ghent Univ Hosp, Dept Cardiac Surg, B-9000 Ghent, Belgium.
[Pauwels, Patrick] Ghent Univ Hosp, Dept Pathol, B-9000 Ghent, Belgium.
[Westbroek, Wendy] NHGRI, NIH, Bethesda, MD 20892 USA.
[Gespach, Christian] INSERM, U673, Paris, France.
[Gespach, Christian] Univ Paris 06, Fac Med, Lab Mol & Clin Oncol Solid Tumors, F-755071 Paris 12, France.
RP De Wever, O (reprint author), Ghent Univ Hosp, Dept Radiol & Nucl Med, Lab Expt Canc Res, De Pintelaan 185, B-9000 Ghent, Belgium.
EM olivier.dewever@UGent.be
RI de wever, olivier/J-3094-2013
OI de wever, olivier/0000-0002-5453-760X
NR 32
TC 47
Z9 50
U1 3
U2 15
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD AUG 8
PY 2008
VL 266
IS 2
BP 263
EP 274
DI 10.1016/j.canlet.2008.02.068
PG 12
WC Oncology
SC Oncology
GA 326HI
UT WOS:000257648800016
PM 18423981
ER
PT J
AU Luo, RB
Randazzo, PA
AF Luo, Ruibai
Randazzo, Paul A.
TI Kinetic analysis of Arf GAP1 indicates a regulatory role for coatomer
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; ADP-RIBOSYLATION FACTOR; MEMBRANE CURVATURE;
SACCHAROMYCES-CEREVISIAE; COPI VESICLES; N-TERMINUS; ARFGAP1; COMPLEX;
HYDROLYSIS; DOMAIN
AB Arf GAPs are a family of enzymes that catalyze the hydrolysis of GTP bound to Arf. Arf GAP1 is one member of the family that has a critical role in membrane traffic at the Golgi apparatus. Two distinct models for the regulation of Arf GAP1 in membrane traffic have been proposed. In one model, Arf GAP1 functions in a ternary complex with coat proteins and is inhibited by cargo proteins. In another model, Arf GAP1 is recruited to a membrane surface that has defects created by the increased membrane curvature that accompanies transport vesicle formation. Here we have used kinetic and mutational analysis to test predictions of models of regulation of Arf GAP1. We found that Arf GAP1 has a similar affinity for Arf1.GTP as another Arf GAP, ASAP1, but the catalytic rate is approximate to 0.5% that of ASAP1. Coatomer stimulated Arf GAP1 activity; however, different from that predicted from the current model, coatomer affected the K(m) and not the k(cat) values. Effects of most mutations in Arf GAP1 paralleled those in ASAP1. Mutation of an arginine that aligned with an arginine presumed to be catalytic in ASAP1 abrogated activity. Peptide from the cytoplasmic tail of cargo proteins inhibited Arf GAP1; however, the unrelated Arf GAP ASAP1 was also inhibited. The curvature of the lipid bilayer had a small effect on activity of Arf GAP1 under the conditions of our experiments. We conclude that coatomer is an allosteric regulator of Arf GAP1. The relevance of the results to the two models of Arf GAP1-mediated regulation of Arf1 is discussed.
C1 [Luo, Ruibai; Randazzo, Paul A.] NCI, NIH, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), NCI, NIH, Cellular & Mol Biol Lab, Ctr Canc Res, Bldg 37,Rm 2042, Bethesda, MD 20892 USA.
EM randazzo@helix.nih.gov
FU Intramural NIH HHS
NR 50
TC 12
Z9 12
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 8
PY 2008
VL 283
IS 32
BP 21965
EP 21977
DI 10.1074/jbc.M802268200
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 332WV
UT WOS:000258114700016
PM 18541532
ER
PT J
AU Mi, LX
Xiao, Z
Hood, BL
Dakshanamurthy, S
Wang, XT
Govind, S
Conrads, TP
Veenstra, TD
Chung, FL
AF Mi, Lixin
Xiao, Zhen
Hood, Brian L.
Dakshanamurthy, Sivanesan
Wang, Xiantao
Govind, Sudha
Conrads, Thomas P.
Veenstra, Timothy D.
Chung, Fung-Lung
TI Covalent binding to tubulin by isothiocyanates - A mechanism of cell
growth arrest and apoptosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CANCER CHEMOPREVENTIVE AGENT; BETA-PHENYLETHYL ISOTHIOCYANATE;
MITOCHONDRIAL DEATH PATHWAY; PHENETHYL ISOTHIOCYANATE; CYCLE ARREST;
ANTIPROLIFERATIVE ACTIVITY; SULFORAPHANE; INHIBITION; INDUCTION;
POLYMERIZATION
AB Isothiocyanates (ITCs) found in cruciferous vegetables, including benzyl-ITC (BITC), phenethyl-ITC (PEITC), and sulforaphane (SFN), inhibit carcinogenesis in animal models and induce apoptosis and cell cycle arrest in various cell types. The biochemical mechanisms of cell growth inhibition by ITCs are not fully understood. Our recent study showed that ITC binding to intracellular proteins may be an important initiating event for the induction of apoptosis. However, the specific protein target(s) and molecular mechanisms were not identified. In this study, two-dimensional gel electrophoresis of human lung cancer A549 cells treated with radiolabeled PEITC and SFN revealed that tubulin may be a major in vivo binding target for ITC. We examined whether binding to tubulin by ITCs could lead to cell growth arrest. The proliferation of A549 cells was significantly reduced by ITCs, with relative activities of BITC > PEITC > SFN. All three ITCs also induced mitotic arrest and apoptosis with the same order of activity. We found that ITCs disrupted microtubule polymerization in vitro and in vivo with the same order of potency. Mass spectrometry demonstrated that cysteines in tubulin were covalently modified by ITCs. Ellman assay results indicated that the modification levels follow the same order, BITC > PEITC > SFN. Together, these results support the notion that tubulin is a target of ITCs and that ITC-tubulin interaction can lead to downstream growth inhibition. This is the first study directly linking tubulin-ITC adduct formation to cell growth inhibition.
C1 [Mi, Lixin; Dakshanamurthy, Sivanesan; Wang, Xiantao; Govind, Sudha; Chung, Fung-Lung] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Xiao, Zhen; Veenstra, Timothy D.] NCI Frederick, SAIC Frederick Inc, Lab Prote & Analyt Technol, Frederick, MD 21702 USA.
[Hood, Brian L.; Conrads, Thomas P.] Univ Pittsburgh, Sch Med, Inst Canc, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
[Hood, Brian L.; Conrads, Thomas P.] Univ Pittsburgh, Sch Med, Inst Canc, Clin Prote Facil, Pittsburgh, PA 15213 USA.
RP Mi, LX (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd,LL 129,Box 571465, Washington, DC 20057 USA.
EM lm293@georgetown.edu; flc6@georgetown.edu
FU NCI NIH HHS [CA100853]
NR 47
TC 123
Z9 125
U1 4
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 8
PY 2008
VL 283
IS 32
BP 22136
EP 22146
DI 10.1074/jbc.M802330200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 332WV
UT WOS:000258114700033
PM 18524779
ER
PT J
AU Shenoy, SK
Xiao, KH
Venkataramanan, V
Snyder, PM
Freedman, NJ
Weissman, AM
AF Shenoy, Sudha K.
Xiao, Kunhong
Venkataramanan, Vidya
Snyder, Peter M.
Freedman, Neil J.
Weissman, Allan M.
TI Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting,
and degradation of the beta(2)-adrenergic receptor
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; DOWN-REGULATION; BETA-ARRESTIN;
7-TRANSMEMBRANE RECEPTORS; PROMOTED UBIQUITINATION; RNA INTERFERENCE;
PLASMA-MEMBRANE; ENDOCYTOSIS; TRAFFICKING; LIGASE
AB Agonist-stimulated beta(2)-adrenergic receptor (beta(2)AR) ubiquitination is a major factor that governs both lysosomal trafficking and degradation of internalized receptors, but the identity of the E3 ubiquitin ligase regulating this process was unknown. Among the various catalytically inactive E3 ubiquitin ligase mutants that we tested, a dominant negative Nedd4 specifically inhibited isoproterenol-induced ubiquitination and degradation of the beta(2)AR in HEK-293 cells. Moreover, siRNA that downregulates Nedd4 expression inhibited beta(2)AR ubiquitination and lysosomal degradation, whereas siRNA targeting the closely related E3 ligases Nedd4-2 or AIP4 did not. Interestingly, beta(2)AR as well as beta-arrestin2, the endocytic and signaling adaptor for the beta(2)AR, interact robustly with Nedd4 upon agonist stimulation. However, beta(2)AR-Nedd4 interaction is ablated when beta-arrestin2 expression is knocked down by siRNA transfection, implicating an essential E3 ubiquitin ligase adaptor role for beta-arrestin2 in mediating beta(2)AR ubiquitination. Notably, beta-arrestin2 interacts with two different E3 ubiquitin ligases, namely, Mdm2 and Nedd4 to regulate distinct steps in beta(2)AR trafficking. Collectively, our findings indicate that the degradative fate of the beta(2)AR in the lysosomal compartments is dependent upon beta-arrestin2-mediated recruitment of Nedd4 to the activated receptor and Nedd4-catalyzed ubiquitination.
C1 [Shenoy, Sudha K.; Xiao, Kunhong; Venkataramanan, Vidya; Freedman, Neil J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Shenoy, Sudha K.; Freedman, Neil J.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
[Snyder, Peter M.] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52422 USA.
[Snyder, Peter M.] Univ Iowa, Coll Med, Dept Physiol, Iowa City, IA 52422 USA.
[Snyder, Peter M.] Univ Iowa, Coll Med, Dept Biophys, Iowa City, IA 52422 USA.
[Weissman, Allan M.] NCI Frederick, Ctr Canc Res, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA.
RP Shenoy, SK (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
EM sudha@receptor-biol.duke.edu
FU NHLBI NIH HHS [T32 HL007101, HL080525, R01 HL080525, R01 HL080525-03]
NR 64
TC 98
Z9 103
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 8
PY 2008
VL 283
IS 32
BP 22166
EP 22176
DI 10.1074/jbc.M709668200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 332WV
UT WOS:000258114700036
PM 18544533
ER
PT J
AU Fernandez-Capetillo, O
Nussenzweig, A
AF Fernandez-Capetillo, Oscar
Nussenzweig, Andre
TI ATM breaks into heterochromatin
SO MOLECULAR CELL
LA English
DT Editorial Material
ID DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; PATHWAY; REPAIR
AB Heterochromatin is refractory to DNA transactions, including repair. In a recent issue of Molecular Cell, Goodarzi et al. (2008) reveal how the central transducing kinase of the DNA damage response relieves this natural barrier by increasing heterochromatic DNA accessibility.
C1 [Fernandez-Capetillo, Oscar] Spanish Natl Canc Ctr CNIO, Genom Instabil Grp, Madrid 28029, Spain.
[Nussenzweig, Andre] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA.
RP Fernandez-Capetillo, O (reprint author), Spanish Natl Canc Ctr CNIO, Genom Instabil Grp, Madrid 28029, Spain.
EM ofernandez@cnio.es; andre_nussenzweig@nih.gov
RI Fernandez-Capetillo, Oscar/H-3508-2015
OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885
NR 9
TC 5
Z9 5
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 8
PY 2008
VL 31
IS 3
BP 303
EP 304
DI 10.1016/j.molcel.2008.07.004
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 339CU
UT WOS:000258556500001
PM 18691960
ER
PT J
AU Jessop, L
Lichten, M
AF Jessop, Lea
Lichten, Michael
TI Mus81/Mms4 endonuclease and sgs1 helicase collaborate to ensure proper
recombination intermediate metabolism during meiosis
SO MOLECULAR CELL
LA English
DT Article
ID HOLLIDAY JUNCTION RESOLVASE; MEIOTIC CROSSING-OVER;
SACCHAROMYCES-CEREVISIAE; GENOME STABILITY; HETERODUPLEX DNA; JOINT
MOLECULES; KINASE CDC5; YEAST; COMPLEX; REPLICATION
AB Budding yeast lacking the Sgs1 helicase and the Mus81/Mms4 endonuclease are inviable, and indirect studies implicate homologous recombination gone awry as the cause of death. We show that mutants lacking both enzymes have profound defects in meiotic recombination intermediate metabolism and crossover (CO) formation. Recombination intermediates (joint molecules, JMs) accumulate in these cells, many with structures that are infrequent in wild-type cells. These JMs persist, preventing nuclear division. Using an inducible expression system, we restored Mus81 or Sgs1 to sgs1 mus81 cells at a time when JMs are forming. Mus81 expression did not prevent JM formation but did restore JM resolution, CO formation, and nuclear division. In contrast, Sgs1 expression reduced the extent of JM accumulation. These results indicate that Sgs1 and Mus81/Mms4 collaborate to direct meiotic recombination toward interhomolog interactions that promote proper chromosome segregation, and also indicate that Mus81/ Mms4 promotes JM resolution in vivo.
C1 [Jessop, Lea; Lichten, Michael] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Lichten, M (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM lichten@helix.nih.gov
RI Lichten, Michael/C-5795-2013
OI Lichten, Michael/0000-0001-9707-2956
FU Intramural Research Program at the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX We thank Angelika Amon and Gaku Mizuguchi for strains and plasmids;
Shirleen Roeder and Munira Basrai for antisera; Martin Xaver for
assistance with immunocytology; Neil Hunter for communicating data in
advance of publication; and Cyril Buhler, Robert Shroff, and Tamara
Goldfarb for other assistance. We thank members of the Lichten group,
Yikang Rong, and Dhruba Chattoraj for discussions. This research was
supported by the Intramural Research Program at the Center for Cancer
Research, National Cancer Institute, National Institutes of Health.
NR 49
TC 73
Z9 73
U1 2
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 8
PY 2008
VL 31
IS 3
BP 313
EP 323
DI 10.1016/j.molcel.2008.05.021
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 339CU
UT WOS:000258556500005
PM 18691964
ER
PT J
AU Schaffner, N
Witmer, A
Kut, E
Folkers, G
Benninger, DH
Candia, V
AF Schaffner, Nils
Witmer, Amrei
Kut, Elvan
Folkers, Gerd
Benninger, David H.
Candia, Victor
TI Heat pain threshold and tolerance show no left-right perceptual
differences at complementary sites of the human forearm
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE heat pain perception; pain threshold; pain tolerance; human forearm;
homologous skin site; laterality
ID SEX-DIFFERENCES; THERMAL PAIN; HEMISPHERIC LATERALIZATION; CEREBRAL
LATERALITY; MAJOR DEPRESSION; STIMULI; RESPONSES; SENSITIVITY; GENDER;
CORTEX
AB Pain threshold and pain tolerance of heat noxious stimuli were assessed to determine whether they are equivalent when measured at three equidistant sites of both volar forearms. Heat pain threshold and tolerance were measured in 18 healthy volunteers using a standard stimulation device consisting of a thermode. Pain threshold and pain tolerance did not differ within and across forearm sites. Experimenters addressing heat pain threshold and tolerance in healthy volunteers may freely choose and change stimulation sites on both volar forearms, without the risk of confounding site effects on dependent variables. This data completes previous reports on side effects by analyzing the effect of site on the forearm for both heat pain threshold and tolerance. The absence of side and site effects may contribute to setting a more secure basis for assessments of laterality effects of painful stimulation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Schaffner, Nils; Witmer, Amrei; Kut, Elvan; Folkers, Gerd; Candia, Victor] Univ Zurich, Coll Helveticum, CH-8092 Zurich, Switzerland.
[Schaffner, Nils; Witmer, Amrei; Kut, Elvan; Folkers, Gerd; Candia, Victor] ETH, CH-8092 Zurich, Switzerland.
[Benninger, David H.] NINDS, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA.
RP Candia, V (reprint author), Univ Zurich, Coll Helveticum, Schmelzbergstr 25, CH-8092 Zurich, Switzerland.
EM candia@collegium.ethz.ch
RI Benninger, David/A-8157-2015
OI Benninger, David/0000-0002-1049-9533
NR 37
TC 7
Z9 7
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD AUG 8
PY 2008
VL 440
IS 3
BP 309
EP 313
DI 10.1016/j.neulet.2008.05.084
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 331MP
UT WOS:000258016600024
PM 18571850
ER
PT J
AU Horkay, F
Basser, PJ
Hecht, AM
Geissler, E
AF Horkay, Ferenc
Basser, Peter J.
Hecht, Anne-Marie
Geissler, Erik
TI Insensitivity to salt of assembly of a rigid biopolymer aggrecan
SO PHYSICAL REVIEW LETTERS
LA English
DT Article
ID CARTILAGE; GELS
AB Many polyelectrolytes, ranging from sulfonated polystyrene to DNA, exhibit a strong sensitivity of their phase behavior to salt concentration, especially to higher valence salts, which often lead to phase separation. We show that the stiff polyelectrolyte aggrecan exhibits a qualitatively different behavior. Specifically, the scattering properties of aggrecan solutions are exceptionally insensitive to the addition of calcium salt, conferring on aggrecan the role of an ion reservoir mediating calcium metabolism in cartilage and bone, and also providing osmotic resilience to compressive load.
C1 [Horkay, Ferenc; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
[Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble 1, CNRS, Spectrometrie Phys Lab, UMR 5588, F-38402 St Martin Dheres, France.
RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, 13 S Dr, Bethesda, MD 20892 USA.
RI Basser, Peter/H-5477-2011; d2am, beamline/I-6445-2015
FU NICHD; NIH; National Science Foundation [DMR-0454672]
FX This research was supported by the Intramural Research Program of the
NICHD, NIH. We acknowledge the ILL, Grenoble, for access to the IN 15
and to the D22 instruments, and NIST, U. S. Department of Commerce for
access to NG3 as well as the CRG beam line BM2 at the ESRF, Grenoble for
SAXS measurements. This work utilized facilities supported in part by
the National Science Foundation under Agreement No. DMR-0454672. The
authors are grateful to Dr. Jack F. Douglas (NIST) for his helpful
comments.
NR 20
TC 4
Z9 4
U1 0
U2 4
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 0031-9007
J9 PHYS REV LETT
JI Phys. Rev. Lett.
PD AUG 8
PY 2008
VL 101
IS 6
AR 068301
DI 10.1103/PhysRevLett.101.068301
PG 4
WC Physics, Multidisciplinary
SC Physics
GA 338VX
UT WOS:000258538600073
PM 18764510
ER
PT J
AU Kirshenbaum, AS
Swindle, E
Kulka, M
Wu, YL
Metcalfe, DD
AF Kirshenbaum, Arnold S.
Swindle, Emily
Kulka, Marianna
Wu, Yalin
Metcalfe, Dean D.
TI Effect of lipopolysaccharide (LPS) and peptidoglycan (PGN) on human mast
cell numbers, cytokine production, and protease composition
SO BMC IMMUNOLOGY
LA English
DT Article
ID FC-EPSILON-RI; TOLL-LIKE RECEPTOR-2; CUTTING EDGE; EXPRESSION;
ACTIVATION; INTERLEUKIN-6; GENE; MICE; INFLAMMATION; SUPPRESSION
AB Background: Human mast cell (HuMC) maturation occurs in tissues interfacing with the external environment, exposing both mast cell progenitors and mature mast cells, to bacteria and their products. It is unknown, however, whether long- or short-term exposure to bacteria-derived toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS) or peptidoglycan (PGN), influences HuMC biology.
Results: Over 6 wks of culture, LPS had minimal effect on HuMC numbers but increased CD117, tryptase and chymase expression. PGN inhibited HuMC development. For mature mast cells, LPS in the presence of rhSCF (10 ng/ml) increased CD117, tryptase, chymase and carboxypeptidase expression, primarily in CD117(low) HuMC. LPS decreased Fc epsilon RI expression and beta-hexosaminidase release; but had no effect on LTC(4) and PGD(2) production. PGN reduced HuMC numbers; and CD117 and tryptase expression. IL-1 beta and IL-6 (in addition to IL-8 and IL-12) were detected in short-term culture supernatants of LPS treated cells, and reproduced the increases in CD117, tryptase, chymase, and carboxypeptidase expression observed in the presence of LPS. Comparative studies with mouse bone marrow-derived mast cells from wild type, but not TLR4 knockout mice, showed increases in mRNA of mouse mast cell chymases MMCP-1, MMCP-2 and MMCP-4.
Conclusion: PGN inhibits HuMC growth, while LPS exerts its primary effects on mature HuMC by altering cytokine production and protease composition, particularly at low concentrations of SCF. These data demonstrate the ability of bacterial products to alter HuMC mediator production, granular content, and number which may be particularly relevant at mucosal sites where HuMC are exposed to these products.
C1 [Kirshenbaum, Arnold S.; Swindle, Emily; Wu, Yalin; Metcalfe, Dean D.] NIAID, Natl Inst Hlth, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Kulka, Marianna] NRC Canada, Inst Nutrisci & Hlth, Charlottetown, PE C1A 4P3, Canada.
RP Kirshenbaum, AS (reprint author), NIAID, Natl Inst Hlth, Lab Allerg Dis, Bethesda, MD 20892 USA.
EM akirshenba@niaid.nih.gov; emilyswindle@hotmail.com;
marianna.kulka@nrc-cnrc.gc.ca; ywu@niaid.nih.gov;
ddmetcalfe@niaid.nih.gov
FU NIAID Division of Intramural Research; NIH [R01HL068546, R01HL078860]
FX This work was supported by the NIAID Division of Intramural Research. MK
also performed work under NIH grants R01HL068546 and R01HL078860 and the
Ernest S. Bazely Trust.
NR 29
TC 30
Z9 30
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD AUG 7
PY 2008
VL 9
AR 45
DI 10.1186/1471-2172-9-45
PG 13
WC Immunology
SC Immunology
GA 348OP
UT WOS:000259220100001
PM 18687131
ER
PT J
AU Lebiedowska, MK
AF Lebiedowska, Maria K.
TI The kinematic consequences of invariant dynamics in children 6-18 years
of age
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE dynamics; similarity; children; growth; velocity
ID LIMB MOVEMENTS; MUSCLE; JOINT; CONTRACTIONS; LOCOMOTION; STIFFNESS;
VELOCITY; WALKING; ADULTS
AB The effect of limb dynamics on trajectory formation is unclear. The natural frequency of a limb is the major factor in its dynamics. It has previously been shown with ail indirect measurement method that the natural frequency of body segments is invariant during human growth from the age of 6 to 18. The aim of our study was to determine, using a direct measurement method. whether human growth affects: (1) lower limb dynamics (i.e. the natural frequency of the lower leg) and (2) the maximum velocities of the knee during selected motor tasks. In 20 non-disabled children, 6-18 years of age, measurements were taken of the natural frequency of the lower leg (including the foot), and the maximum velocities of knee flexion and extension during Voluntary movement (MVV) and at initial and terminal swing phases of self-paced walking (WAL). The velocities were also estimated using a dynamic model and the results were compared to the measured velocities with a paired t-test. Correlations among the frequencies, velocities, and body height (an indicator of growth) were calculated. The natural frequency of the lower leg (mean +/- standard deviation, omega(0) = 6.58 +/- 0.54 s(-1)), maximum velocities of knee extension and flexion during voluntary movement (MVVe= 10.1 +/- 1.8 rad s(-1) and MVVf = 7.8 +/- 1.3 rad s(-1) respectively), and maximum velocities of knee flexion and extension during the swing phase of walking (WAL(f) = 5.4 +/- 0.6 rad s(-1) and WAL(e) = 6.3 +/- 0.87 rad s(-1), respectively) were each found to be independent of body height. The MVV measured velocities were 22% larger and WAL(f) measured velocities were 25% smaller than the velocities predicted from the dynamic model (p < 0.05). The study found that a segment's dynamic properties, as well as selected kinematics, may be considered invariant with human growth. Published by Elsevier Ltd.
C1 NIH, Phys Disabil Branch, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Lebiedowska, MK (reprint author), NIH, Phys Disabil Branch, Dept Rehabil Med, BLDG 10,CRC RM 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA.
EM lebiedowskam@cc.nih.gov
FU Memorial Medical Center Foundation, Springfield, Ilinois, USA; Southern
Illinois University, Springfield, Illinois, USA
FX This work was supported in part by grants from Memorial Medical Center
Foundation, Springfield, Ilinois, USA, and from Central Research
Committee, Southern Illinois University, Springfield, Illinois, USA. The
author wishes to thank Michelle A. Mattera, M.B.E. for her perceptive
editing of the paper, and the anonymous reviewers, whose insightful
comments improved the paper substantially.
NR 40
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
J9 J BIOMECH
JI J. Biomech.
PD AUG 7
PY 2008
VL 41
IS 11
BP 2458
EP 2464
DI 10.1016/j.jbiomech.2008.05.009
PG 7
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 347GQ
UT WOS:000259129000016
PM 18589427
ER
PT J
AU Agarwal, SK
Simonds, WF
Marx, SJ
AF Agarwal, Sunita K.
Simonds, William F.
Marx, Stephen J.
TI The parafibromin tumor suppressor protein interacts with actin-binding
proteins actinin-2 and actinin-3
SO MOLECULAR CANCER
LA English
DT Article
ID FAMILIAL ISOLATED HYPERPARATHYROIDISM; RNA-POLYMERASE-II; ALPHA-ACTININ;
HEREDITARY HYPERPARATHYROIDISM; PARATHYROID CARCINOMAS;
NUCLEAR-LOCALIZATION; HUMAN PAF1; GENE; HRPT2; MUTATIONS
AB Background: Germline and somatic inactivating mutations in the HRPT2 gene occur in the inherited hyperparathyroidism-jaw tumor syndrome, in some cases of parathyroid cancer and in some cases of familial hyperparathyroidism. HRPT2 encodes parafibromin. To identify parafibromin interacting proteins we used the yeast two-hybrid system for screening a heart cDNA library with parafibromin as the bait.
Results: Fourteen parafibromin interaction positive preys representing 10 independent clones encoding actinin-2 were isolated. Parafibromin interacted with muscle alpha-actinins (actinin-2 and actinin-3), but not with non-muscle alpha-actinins (actinin-1 and actinin-4). The parafibromin-actinin interaction was verified by yeast two-hybrid, GST pull-down, and co-immunoprecipitation. Yeast two-hybrid analysis revealed that the N-terminal region of parafibromin interacted with actinins. In actin sedimentation assays parafibromin did not dissociate skeletal muscle actinins from actin filaments, but interestingly, parafibromin could also bundle/cross-link actin filaments. Parafibromin was predominantly nuclear in undifferentiated proliferating myoblasts (C2C12 cells), but in differentiated C2C12 myotubes parafibromin co- localized with actinins in the cytoplasmic compartment.
Conclusion: These data support a possible contribution of parafibromin outside the nucleus through its interaction with actinins and actin bundling/cross-linking. These data also suggest that actinins (and actin) participate in sequestering parafibromin in the cytoplasmic compartment.
C1 [Agarwal, Sunita K.; Simonds, William F.; Marx, Stephen J.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Agarwal, SK (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM sunitaa@mail.nih.gov; wfs@helix.nih.gov; marxs@mail.nih.gov
RI Agarwal, Sunita/D-1428-2016
OI Agarwal, Sunita/0000-0002-7557-3191
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX authors thank Dr. Neal Epstein for antibodies against actinin-2 and
actinin-3, Dr. Erica Golemis for the yeast strain EGY48, and Dr.
Christian Mosimann for the yeast two-hybrid constructs pCM031 and
pRH95.; This study was supported by the intramural program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 43
TC 16
Z9 16
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD AUG 7
PY 2008
VL 7
AR 65
DI 10.1186/1476-4598-7-65
PG 11
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 344WR
UT WOS:000258958500001
PM 18687124
ER
PT J
AU Jones, PA
Archer, TK
Baylin, SB
Beck, S
Berger, S
Bernstein, BE
Carpten, JD
Clark, SJ
Costello, JF
Doerge, RW
Esteller, M
Feinberg, AP
Gingeras, TR
Greally, JM
Henikoff, S
Herman, JG
Jackson-Grusby, L
Jenuwein, T
Jirtle, RL
Kim, YJ
Laird, PW
Lim, B
Martienssen, R
Polyak, K
Stunnenberg, H
Tlsty, TD
Tycko, B
Ushijima, T
Zhu, JD
Pirrotta, V
Allis, CD
Elgin, SC
Rine, J
Wu, C
AF Jones, Peter A.
Archer, Trevor K.
Baylin, Stephen B.
Beck, Stephan
Berger, Shelley
Bernstein, Bradley E.
Carpten, John D.
Clark, Susan J.
Costello, Joseph F.
Doerge, Rebecca W.
Esteller, Manel
Feinberg, Andrew P.
Gingeras, Thomas R.
Greally, John M.
Henikoff, Steven
Herman, James G.
Jackson-Grusby, Laurie
Jenuwein, Thomas
Jirtle, Randy L.
Kim, Young-Joon
Laird, Peter W.
Lim, Bing
Martienssen, Robert
Polyak, Kornelia
Stunnenberg, Henk
Tlsty, Thea Dorothy
Tycko, Benjamin
Ushijima, Toshikazu
Zhu, Jingde
Pirrotta, Vincenzo
Allis, C. David
Elgin, Sarah C.
Rine, Jasper
Wu, Carl
CA Amer Assoc Canc Res Human Epigenom
European Union Network Excellence
TI Moving AHEAD with an international human epigenome project
SO NATURE
LA English
DT Editorial Material
ID DNA METHYLATION; HUMAN GENOME; ARABIDOPSIS-THALIANA; CELLS;
TRANSCRIPTION; PLURIPOTENT
C1 [Jones, Peter A.; Laird, Peter W.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
[Archer, Trevor K.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Baylin, Stephen B.; Herman, James G.] Johns Hopkins Univ, Baltimore, MD 21231 USA.
[Beck, Stephan] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Berger, Shelley] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
[Bernstein, Bradley E.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Carpten, John D.] TGen, Phoenix, AZ 85004 USA.
[Clark, Susan J.] Garvan Inst Med Res, Sydney, NSW 2010, Australia.
[Costello, Joseph F.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[Doerge, Rebecca W.] Purdue Univ, W Lafayette, IN 47907 USA.
[Esteller, Manel] Spanish Natl Canc Ctr, Madrid, Spain.
[Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Oncol & Mol Biol, Baltimore, MD 21205 USA.
[Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Genet, Baltimore, MD 21205 USA.
[Gingeras, Thomas R.] Affymetrix, Santa Clara, CA 95051 USA.
[Greally, John M.] Albert Einstein Coll Med, Bronx, NY 10461 USA.
[Henikoff, Steven] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Jackson-Grusby, Laurie] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Jenuwein, Thomas] Res Inst Mol Pathol, A-1030 Vienna, Austria.
[Jirtle, Randy L.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Kim, Young-Joon] Yonsei Univ, Seoul 120719, South Korea.
[Lim, Bing] Genome Inst Singapore, Singapore 138672, Singapore.
[Martienssen, Robert] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Polyak, Kornelia] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Stunnenberg, Henk] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands.
[Tlsty, Thea Dorothy] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Tycko, Benjamin] Columbia Univ, New York, NY 10032 USA.
[Ushijima, Toshikazu] Natl Canc Ctr, Tokyo 1040045, Japan.
[Zhu, Jingde] Shanghai Canc Inst, Shanghai 200032, Peoples R China.
[Pirrotta, Vincenzo] Rutgers State Univ, Piscataway, NJ 08854 USA.
[Allis, C. David] Rockefeller Univ, New York, NY 10021 USA.
[Elgin, Sarah C.] Washington Univ, St Louis, MO 63130 USA.
[Rine, Jasper] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Wu, Carl] NCI, Bethesda, MD 20892 USA.
RP Jones, PA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
EM jones_p@ccnt.hsc.usc.edu
RI Clark, Susan/B-2272-2008; Clark, Stewart/A-3462-2012; Stunnenberg,
Hendrik/D-6875-2012; Laird, Peter/G-8683-2012; Esteller,
Manel/L-5956-2014;
OI Greally, John/0000-0001-6069-7960; Clark, Susan/0000-0001-5925-5030;
Esteller, Manel/0000-0003-4490-6093; Gingeras,
Thomas/0000-0001-9106-3573
NR 16
TC 104
Z9 111
U1 2
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 7
PY 2008
VL 454
IS 7205
BP 711
EP 715
DI 10.1038/454711a
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 334NH
UT WOS:000258228000034
ER
PT J
AU Rogozin, IB
Makarova, KS
Pavlov, YI
Koonin, EV
AF Rogozin, Igor B.
Makarova, Kira S.
Pavlov, Youri I.
Koonin, Eugene V.
TI A highly conserved family of inactivated archaeal B family DNA
polymerases
SO BIOLOGY DIRECT
LA English
DT Article
ID CRYSTAL-STRUCTURE; REPLICATION; SEQUENCES; ALIGNMENT; SUBUNIT; ALPHA;
DP1
AB A widespread and highly conserved family of apparently inactivated derivatives of archaeal B-family DNA polymerases is described. Phylogenetic analysis shows that the inactivated forms comprise a distinct clade among archaeal B-family polymerases and that, within this clade, Euryarchaea and Crenarchaea are clearly separated from each other and from a small group of bacterial homologs. These findings are compatible with an ancient duplication of the DNA polymerase gene followed by inactivation and parallel loss in some of the lineages although contribution of horizontal gene transfer cannot be ruled out. The inactivated derivative of the archaeal DNA polymerase could form a complex with the active paralog and play a structural role in DNA replication.
C1 [Rogozin, Igor B.; Makarova, Kira S.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA.
[Pavlov, Youri I.] Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
[Pavlov, Youri I.] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA.
EM rogozin@ncbi.nlm.nih.gov; makarova@ncbi.nlm.nih.gov; ypavlov@unmc.edu;
koonin@ncbi.nlm.nih.gov
FU NIH, National Library of Medicine; NIH [IR01CA129925-01A1]; Nebraska
DHHS [LB506]; Eppley Institute Pilot Project
FX The research of IBR, KSM and EVK is supported by the Department of
Health and Human Services intramural program (NIH, National Library of
Medicine). YIP is supported by the NIH grant IR01CA129925-01A1, Nebraska
DHHS grant LB506 and Eppley Institute Pilot Project grant.
NR 24
TC 21
Z9 22
U1 1
U2 1
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 AUG 6
PY 2008
VL 3
AR 32
DI 10.1186/1745-6150-3-32
PG 5
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 345RH
UT WOS:000259013500001
PM 18684330
ER
PT J
AU Pearson, KJ
Baur, JA
Lewis, KN
Peshkin, L
Price, NL
Labinskyy, N
Swindell, WR
Kamara, D
Minor, RK
Perez, E
Jamieson, HA
Zhang, Y
Dunn, SR
Sharma, K
Pleshko, N
Woollett, LA
Csiszar, A
Ikeno, Y
Le Couteur, D
Elliott, PJ
Becker, KG
Navas, P
Ingram, DK
Wolf, NS
Ungvari, Z
Sinclair, DA
de Cabo, R
AF Pearson, Kevin J.
Baur, Joseph A.
Lewis, Kaitlyn N.
Peshkin, Leonid
Price, Nathan L.
Labinskyy, Nazar
Swindell, William R.
Kamara, Davida
Minor, Robin K.
Perez, Evelyn
Jamieson, Hamish A.
Zhang, Yongcling
Dunn, Stephen R.
Sharma, Kumar
Pleshko, Nancy
Woollett, Laura A.
Csiszar, Anna
Ikeno, Yuji
Le Couteur, David
Elliott, Peter J.
Becker, Kevin G.
Navas, Placido
Ingram, Donald K.
Wolf, Norman S.
Ungvari, Zoltan
Sinclair, David A.
de Cabo, Rafael
TI Resveratrol delays age-related deterioration and mimics transcriptional
aspects of dietary restriction without extending life span
SO CELL METABOLISM
LA English
DT Article
ID OXIDATIVE STRESS RESISTANCE; GENE SET ENRICHMENT; NF-KAPPA-B; CALORIC
RESTRICTION; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER;
CAENORHABDITIS-ELEGANS; INCREASED DOSAGE; MICE; EXPRESSION
AB A small molecule that safely mimics the ability of dietary restriction (DR) to delay, age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene, expression patterns in multiple tissues that parallel those induced by DR and every-othor-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging, including reduced albuminuria, decreased inflammation, and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.
C1 [Pearson, Kevin J.; Lewis, Kaitlyn N.; Price, Nathan L.; Kamara, Davida; Minor, Robin K.; Perez, Evelyn; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Peshkin, Leonid] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Peshkin, Leonid] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Labinskyy, Nazar; Csiszar, Anna; Ungvari, Zoltan] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
[Swindell, William R.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48103 USA.
[Jamieson, Hamish A.; Le Couteur, David] Univ Sydney, Ctr Educ & Res Ageing, Concord, NSW 2139, Australia.
[Jamieson, Hamish A.; Le Couteur, David] Univ Sydney, ANZAC Res Inst, Concord, NSW 2139, Australia.
[Zhang, Yongcling; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
[Dunn, Stephen R.] Thomas Jefferson Univ, Kimmel Canc Ctr, Nucl Acid Microarray Facil, Philadelphia, PA 19107 USA.
[Sharma, Kumar] UCSD, La Jolla, CA 92014 USA.
[Pleshko, Nancy] Hosp Special Surg, New York, NY 10021 USA.
[Woollett, Laura A.] Univ Cincinnati, Med Ctr, Genome Res Ctr, Dept Pathol & Lab Med, Cincinnati, OH 45237 USA.
[Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA.
[Ikeno, Yuji] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78245 USA.
[Ikeno, Yuji] Audie Murphy VA Hosp STVHCS, Res Serv, San Antonio, TX 78245 USA.
[Elliott, Peter J.] Sirtris Pharmaceut Inc, Cambridge, MA 02139 USA.
[Navas, Placido] Univ Pablo Olavide, CSIC, Inst Salud Carlos III, Ctr Andaluz Biol Desarrollo, Seville 41013, Spain.
[Navas, Placido] Univ Pablo Olavide, CSIC, Inst Salud Carlos III, Ctr Invest Biomed & Red Enfermedades Raras, Seville 41013, Spain.
[Ingram, Donald K.] Louisiana State Univ System, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
[Wolf, Norman S.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Baur, Joseph A.; Price, Nathan L.; Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Baur, Joseph A.; Price, Nathan L.; Sinclair, David A.] Harvard Univ, Sch Med, Pau F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA.
RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM david_sinclair@hms.harvard.edu; deCaboRa@grc.nia.nih.gov
RI de Cabo, Rafael/E-7996-2010; Baur, Joseph/D-8163-2011; de Cabo,
Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Baur, Joseph/0000-0001-8262-6549;
Sinclair, David/0000-0002-9936-436X; Becker, Kevin/0000-0002-6794-6656;
, rafael/0000-0003-2830-5693
FU Intramural NIH HHS [Z01 AG000368-03]; NEI NIH HHS [2R01EY011733, R01
EY011733]; NHLBI NIH HHS [HL077256, R01 HL077256]; NIA NIH HHS [AG19719,
AG19972, R01 AG019719, R01 AG019972, R01 AG019972-03, R01 AG028730, R01
AG028730-01A1]; NIAMS NIH HHS [P30 AR046121]; NICHD NIH HHS [HD034089,
R01 HD034089, R56 HD034089]; NIDDK NIH HHS [SP30DK072437]; NIGMS NIH HHS
[R01 GM068072, R01 GM068072-01, R01GM068072]
NR 75
TC 615
Z9 623
U1 10
U2 90
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD AUG 6
PY 2008
VL 8
IS 2
BP 157
EP 168
DI 10.1016/j.cmet.2008.06.011
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 335AH
UT WOS:000258262700008
PM 18599363
ER
PT J
AU Yao, Y
Harrison, CB
Freddolino, PL
Schulten, K
Mayer, ML
AF Yao, Yongneng
Harrison, Chris B.
Freddolino, Peter L.
Schulten, Klaus
Mayer, Mark L.
TI Molecular mechanism of ligand recognition by NR3 subtype glutamate
receptors
SO EMBO JOURNAL
LA English
DT Article
DE crystallography; D-serine; glutamate receptor; glycine; molecular
dynamics; NMDA
ID D-ASPARTATE RECEPTOR; BINDING DOMAIN; NMDA RECEPTORS;
CRYSTAL-STRUCTURES; AMPA RECEPTOR; SUBUNIT NR3A; DYNAMICS SIMULATIONS;
KAINATE; DENSITY; GLYCINE
AB NR3 subtype glutamate receptors have a unique developmental expression profile, but are the least well-characterized members of the NMDA receptor gene family, which have key roles in synaptic plasticity and brain development. Using ligand binding assays, crystallographic analysis, and all atom MD simulations, we investigate mechanisms underlying the binding by NR3A and NR3B of glycine and D-serine, which are candidate neurotransmitters for NMDA receptors containing NR3 subunits. The ligand binding domains of both NR3 subunits adopt a similar extent of domain closure as found in the corresponding NR1 complexes, but have a unique loop 1 structure distinct from that in all other glutamate receptor ion channels. Within their ligand binding pockets, NR3A and NR3B have strikingly different hydrogen bonding networks and solvent structures from those found in NR1, and fail to undergo a conformational rearrangement observed in NR1 upon binding the partial agonist ACPC. MD simulations revealed numerous interdomain contacts, which stabilize the agonist-bound closed-cleft conformation, and a novel twisting motion for the loop 1 helix that is unique in NR3 subunits.
C1 [Yao, Yongneng; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA.
[Harrison, Chris B.; Freddolino, Peter L.] Univ Illinois, Theoret & Computat Biophys Grp, Urbana, IL 61801 USA.
[Harrison, Chris B.; Freddolino, Peter L.; Schulten, Klaus] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA.
[Schulten, Klaus] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bldg 35,Room 3B 1002,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM mlm@helix.nih.gov
RI Freddolino, Peter/C-2288-2008; Schulten, Klaus/D-5561-2009; Mayer,
Mark/H-5500-2013
FU Intramural NIH HHS; NCRR NIH HHS [P41 RR005969, P41 RR05969]; NIGMS NIH
HHS [1 R01 GM067887, R01 GM067887]
NR 50
TC 47
Z9 49
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD AUG 6
PY 2008
VL 27
IS 15
BP 2158
EP 2170
DI 10.1038/emboj.2008.140
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 334JU
UT WOS:000258218900012
PM 18636091
ER
PT J
AU Horemans, N
Szarka, A
De Bock, M
Raeymaekers, T
Potters, G
Levine, M
Banhegyi, G
Guisez, Y
AF Horemans, N.
Szarka, A.
De Bock, M.
Raeymaekers, T.
Potters, G.
Levine, M.
Banhegyi, G.
Guisez, Y.
TI Dehydroascorbate and glucose are taken up into Arabidopsis thaliana cell
cultures by two distinct mechanisms
SO FEBS LETTERS
LA English
DT Article
DE vitamin C; dehydroascorbate transport; glucose transport; plasma
membrane; plant cells
ID SPINACH-CHLOROPLASTS; PLASMA-MEMBRANE; ASCORBIC-ACID; TRANSPORT;
BIOSYNTHESIS; SUSPENSION; HEXOSE; GENES
AB The possible involvement of glucose (Glc) carriers in the uptake of vitamin C in plant cells is still a matter of debate. For the first time, it was shown here that plant cells exclusively take up the oxidised dehydroascorbate (DHA) form. DHA uptake is not affected by 6-bromo-6-deoxy-ascorbate, an ascorbate (ASC) analogue, specifically demonstrating ASC uptake in animal cells. There is no competition between Glc and DHA uptake. Moreover, DHA and Glc carriers respond in the opposite manner to different inhibitors ( cytochalasin B, phloretin and genistein). In conclusion, the plant plasma membrane DHA carrier is distinct from the plant Glc transporters. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
C1 [Horemans, N.; De Bock, M.; Raeymaekers, T.; Guisez, Y.] Univ Antwerp, Dept Biol Plant Physiol, B-2020 Antwerp, Belgium.
[Potters, G.] Univ Antwerp, Dept Biosci Engn, B-2020 Antwerp, Belgium.
[Levine, M.] NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Banhegyi, G.] Hungarian Acad Sci, Pathobiochem Res Grp, Budapest, Hungary.
[Banhegyi, G.] Semmelweis Univ, Budapest, Hungary.
RP Horemans, N (reprint author), Univ Antwerp, Dept Biol Plant Physiol, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
EM nele.horemans@ua.ac.be
RI Szarka, Andras/H-8130-2012; Banhegyi, Gabor/A-1476-2014
FU Intramural NIH HHS [Z01 DK054506-10]
NR 22
TC 9
Z9 10
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD AUG 6
PY 2008
VL 582
IS 18
BP 2714
EP 2718
DI 10.1016/j.febslet.2008.07.001
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 332UK
UT WOS:000258108400007
PM 18619442
ER
PT J
AU Carvalho, FM
Kriegeskorte, N
AF Carvalho, Fabiana Mesquita
Kriegeskorte, Nikolaus
TI The arrow of time: How does the brain represent natural temporal
structure?
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
ID VISUAL-CORTEX; ATTENTION; FMRI
C1 [Carvalho, Fabiana Mesquita] Univ Glasgow, Dept Psychol, Glasgow G12 8QB, Lanark, Scotland.
[Carvalho, Fabiana Mesquita] Univ Sao Paulo, Dept Math & Phys, NeuroImago Lab, Grad Program Psychobiol, BR-14040901 Ribeirao Preto, Brazil.
[Kriegeskorte, Nikolaus] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Carvalho, FM (reprint author), Univ Glasgow, Dept Psychol, 58 Hillhead St, Glasgow G12 8QB, Lanark, Scotland.
EM fabiana@psy.gla.ac.uk
OI Kriegeskorte, Nikolaus/0000-0001-7433-9005
NR 10
TC 0
Z9 0
U1 0
U2 1
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 AUG 6
PY 2008
VL 28
IS 32
BP 7933
EP 7935
DI 10.1523/JNEUROSCI.1781-08.2008
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 334RE
UT WOS:000258238100002
PM 18685018
ER
PT J
AU Hefner, K
Whittle, N
Juhasz, J
Norcross, M
Karlsson, RM
Saksida, LM
Bussey, TJ
Singewald, N
Holmes, A
AF Hefner, Kathryn
Whittle, Nigel
Juhasz, Jaynann
Norcross, Maxine
Karlsson, Rose-Marie
Saksida, Lisa M.
Bussey, Timothy J.
Singewald, Nicolas
Holmes, Andrew
TI Impaired fear extinction learning and cortico-amygdala circuit
abnormalities in a common genetic mouse strain
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE extinction; anxiety; gene; prefrontal cortex; amygdala; intercalated
cell masses
ID MEDIAL PREFRONTAL CORTEX; TRAIT LOCUS ANALYSIS; C-FOS EXPRESSION;
CONDITIONED FEAR; CONTEXTUAL FEAR; D-CYCLOSERINE; POTENTIATED STARTLE;
INBRED MICE; FACILITATES EXTINCTION; BEHAVIORAL-DIFFERENCES
AB Fear extinction is a form of new learning that results in the inhibition of conditioned fear. Trait deficits in fear extinction are a risk factor for anxiety disorders. There are few examples of naturally occurring animal models of impaired extinction. The present study compared fear extinction in a panel of inbred mouse strains. This strain survey revealed an impairment in fear extinction in 129/ SvImJ ( 129S1). The phenotypic specificity of this deficit was evaluated by comparing 129S1 and C57BL/ 6J for one- trial and multitrial fear conditioning, nociception, and extinction of conditioned taste aversion and an appetitive instrumental response. 129S1 were tested for sensitivity to the extinction- facilitating effects of extended training, as well as D- cycloserine and yohimbine treatment. To elucidate the neural basis of impaired 129S1 fear extinction, c- Fos and Zif268 expression was mapped after extinction recall. Results showed that impaired fear extinction in 129S1 was unrelated to altered fear conditioning or nociception, and was dissociable from intact appetitive extinction. Yohimbine treatment facilitated extinction in 129S1, but neither extended extinction training nor D- cycloserine treatment improved 129S1 extinction. After extinction recall, 129S1 showed reduced c- Fos and Zif268 expression in the infralimbic cortex and basolateral amygdala, and elevated c- Fos or Zif268 expression in central nucleus of the amygdala and medial paracapsular intercalated cell mass, relative to C57BL/ 6J. Collectively, these data demonstrate a deficit in fear extinction in 129S1 associated with a failure to properly engage corticolimbic extinction circuitry. This common inbred strain provides a novel model for studying impaired fear extinction in anxiety disorders.
C1 [Hefner, Kathryn; Juhasz, Jaynann; Norcross, Maxine; Karlsson, Rose-Marie; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
[Whittle, Nigel; Singewald, Nicolas] Univ Innsbruck, Dept Pharmacol & Toxicol, Inst Pharm, A-6020 Innsbruck, Austria.
Univ Innsbruck, Ctr Mol Biosci, A-6020 Innsbruck, Austria.
[Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England.
Univ Cambridge, MRC, Cambridge CB2 3EB, England.
Univ Cambridge, Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England.
RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
EM holmesan@mail.nih.gov
RI Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016;
OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041;
Hefner, Kathryn/0000-0002-5208-7860
FU Intramural NIH HHS [Z01 AA000411-04]; Medical Research Council
[G0001354]; NIAAA NIH HHS [Z01 AA000411]
NR 98
TC 135
Z9 137
U1 3
U2 9
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 AUG 6
PY 2008
VL 28
IS 32
BP 8074
EP 8085
DI 10.1523/JNEUROSCI.4904-07.2008
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 334RE
UT WOS:000258238100016
PM 18685032
ER
PT J
AU Tikhonova, IG
Best, RB
Engel, S
Gershengorn, MC
Hummer, G
Costanzi, S
AF Tikhonova, Irina G.
Best, Robert B.
Engel, Stanislav
Gershengorn, Marvin C.
Hummer, Gerhard
Costanzi, Stefano
TI Atomistic insights into rhodopsin activation from a dynamic model
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PROTEIN-COUPLED-RECEPTOR; RETINAL COUNTERION SWITCH; LIGHT-DEPENDENT
CHANGES; METARHODOPSIN-II; MOLECULAR SIMULATIONS; BOVINE RHODOPSIN;
BETA(2)-ADRENERGIC RECEPTOR; CONSTITUTIVE ACTIVATION; CRYSTAL-STRUCTURE;
CYTOPLASMIC END
AB Rhodopsin, the light sensitive receptor responsible for blue-green vision, serves as a prototypical G protein-coupled receptor (GPCR). Upon light absorption, it undergoes a series of conformational changes that lead to the active form, metarhodopsin II (META II), initiating a signaling cascade through binding to the G protein transducin (G(t)). Here, we first develop a structural model of META II by applying experimental distance restraints to the structure of lumi-rhodopsin (LUMI), an earlier intermediate. The restraints are imposed by using a combination of biased molecular dynamics simulations and perturbations to an elastic network model. We characterize the motions of the transmembrane helices in the LUMI-to-META II transition and the rearrangement of interhelical hydrogen bonds. We then simulate rhodopsin activation in a dynamic model to study the path leading from LUMI to our META II model for wild-type rhodopsin and a series of mutants. The simulations show a strong correlation between the transition dynamics and the pharmacological phenotypes of the mutants. These results help identify the molecular mechanisms of activation in both wild type and mutant rhodopsin. While static models can provide insights into the mechanisms of ligand recognition and predict ligand affinity, a dynamic model of activation could be applicable to study the pharmacology of other GPCRs and their ligands, offering a key to predictions of basal activity and ligand efficacy.
C1 [Tikhonova, Irina G.; Costanzi, Stefano] NIDDK, NIH, Lab Biol Modeling, Bethesda, MD 20892 USA.
[Best, Robert B.; Hummer, Gerhard] NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA.
[Engel, Stanislav; Gershengorn, Marvin C.] NIDDK, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA.
RP Costanzi, S (reprint author), NIDDK, NIH, Lab Biol Modeling, Bethesda, MD 20892 USA.
EM stefanoc@mail.nih.gov
RI Hummer, Gerhard/A-2546-2013; Engel, Stanislav/G-2799-2013; Costanzi,
Stefano/G-8990-2013; Best, Robert/H-7588-2016;
OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543;
Costanzi, Stefano/0000-0003-3183-7332
FU Intramural NIH HHS [Z01 DK013025-01]
NR 75
TC 31
Z9 31
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 6
PY 2008
VL 130
IS 31
BP 10141
EP 10149
DI 10.1021/ja0765520
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 332JZ
UT WOS:000258080600034
PM 18620390
ER
PT J
AU Peng, XH
Hong, IS
Li, H
Seiclman, MM
Greenberg, MM
AF Peng, Xiaohua
Hong, In Seok
Li, Hong
Seiclman, Michael M.
Greenberg, Marc M.
TI Interstrand cross-link formation in duplex and triplex DNA by modified
pyrimidines
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID HELIX-FORMING OLIGONUCLEOTIDES; 2'-O-(2-AMINOETHYL) RESIDUES; MODIFIED
NUCLEOTIDE; ALKYLATION; SITES; ACTIVATION; EFFICIENT; STRATEGY; OXYGEN;
PH
AB DNA interstrand cross-links have important biological consequences and are useful biotechnology tools. Phenylselenyl substituted derivatives of thymidine (1) and 5-methyl-2'-deoxycytidine (5) produce interstrand cross-links in duplex DNA when oxidized by NaIO(4). The mechanism involves a [2,3]-sigmatropic rearrangement of the respective selenoxides to the corresponding methide type intermediates, which ultimately produce the interstrand cross-links. Determination of the rate constants for the selenoxide rearrangements indicates that the rate-determining step for cross-linking is after methicle formation. Crosslinking by the thymidine derivative in duplex DNA shows a modest kinetic preference when flanked by pyrimidines as opposed to purines. In contrast, the rate constant for cross-link formation from 5 opposite dG in duplex DNA is strongly dependent upon the flanking sequence and, in general, is at least an order of magnitude slower than that for 1 in an otherwise identical sequence. Introduction of mispairs at the base pairs flanking 5 or substitution of the opposing dG by dI significantly increases the rate constant and yield for cross-linking, indicating that stronger hydrogen bonding between the methide derived from it and dG compared to CIA and the respective electrophile derived from 1 limits reaction by increasing the barrier to rotation into the required syn-conformation. Incorporation of 1 or 5 in triplex forming oligonucleotides (TFOs) that utilize Hoogsteen base pairing also yields interstrand cross-links. The dC derivative produces ICLs approximately 10x faster than the thymidine derivative when incorporated at the 5'-termini of the TFOs and higher yields when incorporated at internal sites. The slower, less efficient ICL formation emanating from 1 is attributed to reaction at N1-dA, which requires local melting of the duplex. In contrast, 5 produces cross-links by reacting with N7-dG. The cross-linking reactions of 1 and 5 illustrate the versatility and utility of these molecules as mechanistic probes and tools for biotechnology.
C1 [Peng, Xiaohua; Hong, In Seok; Greenberg, Marc M.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA.
[Li, Hong; Seiclman, Michael M.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Greenberg, MM (reprint author), Johns Hopkins Univ, Dept Chem, 3400 N Charles St, Baltimore, MD 21218 USA.
EM mgreenberg@jhu.edu
FU Intramural NIH HHS [Z01 AG000738-09]; NIGMS NIH HHS [GM-054996, R01
GM054996]
NR 29
TC 47
Z9 47
U1 1
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 6
PY 2008
VL 130
IS 31
BP 10299
EP 10306
DI 10.1021/ja802177u
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 332JZ
UT WOS:000258080600052
PM 18620398
ER
PT J
AU Gril, B
Palmieri, D
Bronder, JL
Herring, JM
Vega-Valle, E
Feigenbaum, L
Liewehr, DJ
Steinberg, SM
Merino, MJ
Rubin, SD
Steeg, PS
AF Gril, Brunilde
Palmieri, Diane
Bronder, Julie L.
Herring, Jeanne M.
Vega-Valle, Eleazar
Feigenbaum, Lionel
Liewehr, David J.
Steinberg, Seth M.
Merino, Maria J.
Rubin, Stephen D.
Steeg, Patricia S.
TI Effect of lapatinib on the outgrowth of metastatic breast cancer cells
to the brain
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; ADJUVANT CHEMOTHERAPY; KINASE INHIBITOR; CNS
METASTASES; IN-VITRO; RECEPTOR; TRASTUZUMAB; GROWTH; RISK; HER-2/NEU
AB Background The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis.
Methods EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, > 50 mu m(2)) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22-26 mice per treatment group). All statistical tests were two-sided.
Results In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%-53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell-derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell-derived brain metastases from vehicle-treated mice (P < .001).
Conclusions Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer.
C1 [Steeg, Patricia S.] Natl Canc Inst, Womens Canc Sect, Mol Pharmacol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] Natl Canc Res, Biostat & Data Management Sect, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD USA.
[Merino, Maria J.] Natl Canc Inst, Pathol Lab, Natl Inst Hlth, Bethesda, MD USA.
[Rubin, Stephen D.] GlaxoSmithKline Inc, Philadelphia, PA USA.
RP Steeg, PS (reprint author), Natl Canc Inst, Womens Canc Sect, Mol Pharmacol Lab, Natl Inst Hlth, 9000 Rockville Pike,Bldg 37,Room 1122,MSC 4254, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
RI Palmieri, Diane/B-4258-2015;
OI Mason, Julie/0000-0002-5144-175X
FU Intramural NIH HHS [Z01 BC010538-05]
NR 45
TC 146
Z9 148
U1 1
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD AUG 6
PY 2008
VL 100
IS 15
BP 1092
EP 1103
DI 10.1093/jnci/djn216
PG 12
WC Oncology
SC Oncology
GA 335YE
UT WOS:000258330700013
PM 18664652
ER
PT J
AU Geliebter, A
Hashim, SA
Gluck, ME
AF Geliebter, Allan
Hashim, Sami A.
Gluck, Mard E.
TI Appetite-related gut peptides, ghrelin, PYY, and GLP-1 in obese women
with and without binge eating disorder (BED)
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Society-for-the-Study-of-Ingestive-Behavior
CT Conference on Desalination and the Environment
CY JUL 24-28, 2007
CY APR 22-25, 2007
CL Steamboat Springs, CO
CL Halkidiki, GREECE
SP Soc Study Ingest Behav
SP European Desalinat Soc, Ctr Res & Technol Hellas
DE obesity; food intake; eating disorders; treatment; cognitive behavior
therapy; CBT; nutrition
ID RECEPTOR GENE-MUTATIONS; CIRCULATING GHRELIN; GASTRIC CAPACITY;
NONOBESE; MEAL
AB BED is characterized by overeating with a loss of control. The primary aim of the study was to measure plasma concentrations of three key gut peptides influencing hunger (ghrelin) and satiety (PYY, GLP-1) to ascertain potential abnormalities in BED. The participants were 10 obese BED and 9 obese nonBED premenopausal women. They did not differ in age, 30.1 +/- 8.1 SD, BMI, 36.2 +/- 5.9, or % body fat, 43.3+/-5.7. Following a13-h overnight fast, blood was drawn (-15, 0, 5,15, 30, 60,90,120 min) for measurement of total plasma concentrations of ghrelin, PYY and GLP-1, pre and post ingestion of a nutritionally complete liquid meal (1256 kJ) at 9 am (0-5 min). Ratings of hunger and fullness preceded each blood draw. Ghrelin was significantly lower premeal at -15 min (P=.05) and postmeal at 90 min (P=.027) and 120 min (P=.025) in the BED group as compared to the nonBED group. Ghrelin also declined less postprandially in the BED group (P=.019) with a longer time to the nadir value (P=.004). However, fasting and meal-related changes in levels of PYY and GLP-1 did not differ between the groups nor did ratings of hunger and fullness. Following a randomized cognitive behavior and dietary intervention, the ghrelin values in BED normalized. Prior to treatment, the lower fasting ghrelin in BED may be a consequence of down regulation by overeating. The lack of differences in the satiety promoting hormones, PYY and GLP-1, makes them unlikely contributors to the binge eating in BED. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Geliebter, Allan; Hashim, Sami A.] St Lukes Roosevelt Hosp, Dept Med, NY Obes Res Center, New York, NY 10025 USA.
[Geliebter, Allan] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10027 USA.
[Geliebter, Allan] Touro Coll, New York, NY 10010 USA.
[Gluck, Mard E.] NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA.
RP Geliebter, A (reprint author), St Lukes Roosevelt Hosp, Dept Med, NY Obes Res Center, 1111 Amsterdam Ave,Babcock 10A, New York, NY 10025 USA.
EM ag58@columbia.edu
FU NCRR NIH HHS [M01 RR0064529]; NIDDK NIH HHS [R01 DK074046-03, DK074046,
P30DK026687, R01 DK074046, R01 DK074046-01A1, R01 DK074046-01A1S1, R01
DK074046-02, R01 DK074046-02S1, R01 DK074046-02S2, R01 DK074046-04, R01
DK074046-05]
NR 19
TC 22
Z9 23
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD AUG 6
PY 2008
VL 94
IS 5
BP 696
EP 699
DI 10.1016/j.physbeh.2008.04.013
PG 4
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 326FN
UT WOS:000257644000011
PM 18534636
ER
PT J
AU Efroni, S
Carmel, L
Schaefer, CG
Buetow, KH
AF Efroni, Sol
Carmel, Liran
Schaefer, Carl G.
Buetow, Kenneth H.
TI Superposition of Transcriptional Behaviors Determines Gene State
SO PLOS ONE
LA English
DT Article
AB We introduce a novel technique to determine the expression state of a gene from quantitative information measuring its expression. Adopting a productive abstraction from current thinking in molecular biology, we consider two expression states for a gene-Up or Down. We determine this state by using a statistical model that assumes the data behaves as a combination of two biological distributions. Given a cohort of hybridizations, our algorithm predicts, for the single reading, the probability of each gene's being in an Up or a Down state in each hybridization. Using a series of publicly available gene expression data sets, we demonstrate that our algorithm outperforms the prevalent algorithm. We also show that our algorithm can be used in conjunction with expression adjustment techniques to produce a more biologically sound gene-state call. The technique we present here enables a routine update, where the continuously evolving expression level adjustments feed into gene-state calculations. The technique can be applied in almost any multi-sample gene expression experiment, and holds equal promise for protein abundance experiments.
C1 [Efroni, Sol; Schaefer, Carl G.; Buetow, Kenneth H.] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD USA.
[Carmel, Liran] Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD USA.
[Buetow, Kenneth H.] NCI, Lab Populat Genet, NIH, Bethesda, MD USA.
RP Efroni, S (reprint author), NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD USA.
EM buetowk@nih.gov
RI Efroni, Sol/I-6752-2012
OI Efroni, Sol/0000-0001-7927-6349
NR 15
TC 9
Z9 9
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 6
PY 2008
VL 3
IS 8
AR e2901
DI 10.1371/journal.pone.0002901
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 421NW
UT WOS:000264366600057
PM 18682855
ER
PT J
AU Wise, RA
Wang, B
You, ZB
AF Wise, Roy A.
Wang, Bin
You, Zhi-Bing
TI Cocaine Serves as a Peripheral Interoceptive Conditioned Stimulus for
Central Glutamate and Dopamine Release
SO PLOS ONE
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS DOPAMINE; INTRAVENOUS COCAINE;
INTRAADMINISTRATION ASSOCIATIONS; EXTRACELLULAR DOPAMINE; TRANSPORTER
OCCUPANCY; SODIUM-CHANNELS; ONSET CUES; IN-VIVO; RATS
AB Intravenous injections of cocaine HCl are habit-forming because, among their many actions, they elevate extracellular dopamine levels in the terminal fields of the mesocorticolimbic dopamine system. This action, thought to be very important for cocaine's strong addiction liability, is believed to have very short latency and is assumed to reflect rapid brain entry and pharmacokinetics of the drug. However, while intravenous cocaine HCl has almost immediate effects on behavior and extracellular dopamine levels, recent evidence suggests that its central pharmacological effects are not evident until 10 or more seconds after IV injection. Thus the immediate effects of a given intravenous cocaine injection on extracellular dopamine concentration and behavior appear to occur before there is sufficient time for cocaine to act centrally as a dopamine uptake inhibitor. To explore the contribution of peripheral effects of cocaine to the early activation of the dopamine system, we used brain microdialysis to measure the effects of cocaine methiodide (MI)-a cocaine analogue that does not cross the blood brain barrier-on glutamate (excitatory) input to the dopamine cells. IP injections of cocaine MI were ineffective in cocaine-naive animals but stimulated ventral tegmental glutamate release in rats previously trained to lever-press for cocaine HCl. This peripherally triggered glutamate input was sufficient to reinstate cocaine-seeking in previously trained animals that had undergone extinction of the habit. These findings offer an explanation for short-latency behavioral responses and immediate dopamine elevations seen following cocaine injections in cocaine-experienced but not cocaine-naive animals.
C1 [Wise, Roy A.; Wang, Bin; You, Zhi-Bing] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
RP Wise, RA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
EM rwise@intra.nida.nih.gov
RI Wise, Roy/A-6465-2012
FU Intramural Research Program, National Institute on Drug Abuse, National
Institutes of Health, Department of Health and Human Services
FX Funding for this study was provided by the Intramural Research Program,
National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services
NR 48
TC 48
Z9 49
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 6
PY 2008
VL 3
IS 8
AR e2846
DI 10.1371/journal.pone.0002846
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 421NW
UT WOS:000264366600002
PM 18682722
ER
PT J
AU Burgio, KL
Kraus, SR
Menefee, S
Borello-France, D
Corton, M
Johnson, HW
Mallett, V
Norton, P
FitzGerald, MP
Dandreo, KJ
Richter, HE
Rozanski, T
Albo, M
Zyczynski, HM
Lemack, GE
Chai, TC
Khandwala, S
Baker, J
Brubaker, L
Stoddard, AM
Goode, PS
Nielsen-Omeis, B
Nager, CW
Kenton, K
Tennstedt, SL
Kusek, JW
Chang, TD
Nyberg, LM
Steers, W
AF Burgio, Kathryn L.
Kraus, Stephen R.
Menefee, Shawn
Borello-France, Diane
Corton, Marlene
Johnson, Harry W.
Mallett, Veronica
Norton, Peggy
FitzGerald, Mary P.
Dandreo, Kimberly J.
Richter, Holly E.
Rozanski, Thomas
Albo, Michael
Zyczynski, Halina M.
Lemack, Gary E.
Chai, Toby C.
Khandwala, Salil
Baker, Jan
Brubaker, Linda
Stoddard, Anne M.
Goode, Patricia S.
Nielsen-Omeis, Betsy
Nager, Charles W.
Kenton, Kimberly
Tennstedt, Sharon L.
Kusek, John W.
Chang, T. Debuene
Nyberg, Leroy M.
Steers, William
CA Urinary Incontinence Treatment Net
TI Behavioral therapy to enable women with urge incontinence to discontinue
drug treatment
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; URINARY-INCONTINENCE;
OLDER WOMEN; OVERACTIVE BLADDER; CLINICAL-TRIALS; TOLTERODINE; IMPACT
AB Background: Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy.
Objective: To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy.
Design: 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006. Setting: 9 university-affiliated outpatient clinics.
Patients: 307 women with urge-predominant incontinence.
Intervention: 10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months.
Measurements: The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment.
Results: 237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% CI, -12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [CI, -0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P <0.001) at both time points for patient satisfaction and perceived improvement but not health-related quality of life. Adverse events were uncommon (12 events in 6 participants [3 in each group]).
Limitations: Behavioral therapy components (daily bladder diary and recommendations for fluid management) in the group receiving drug therapy alone may have attenuated between-group differences. Assigned treatment was completed by 68% of participants, whereas 8-month outcome status was assessed on 77%.
Conclusion: The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence. Combination therapy has a beneficial effect on patient satisfaction, perceived improvement, and reduction of other bladder symptoms.
C1 [Burgio, Kathryn L.] Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA.
Dept Vet Affairs, Birmingham, AL USA.
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
Univ Calif San Diego, San Diego, CA 92103 USA.
Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA.
Duquesne Univ, Pittsburgh, PA 15219 USA.
SW Texas State Univ, Dallas, TX USA.
Univ Maryland, Baltimore, MD 21201 USA.
Oakwood Hosp, Dearborn, MI USA.
Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
New England Res Inst, Watertown, MA 02172 USA.
NIDDKD, NIH, Bethesda, MD 20892 USA.
Univ Virginia Hlth Syst, Charlottesville, VA USA.
RP Burgio, KL (reprint author), Univ Alabama, Birmingham Vet Affairs Med Ctr, 11G 700 S 19th St, Birmingham, AL 35233 USA.
EM kburgio@aging.uab.edu
FU NIDDK NIH HHS [U01 DK060397, U01 DK058225, U01 DK058231, U01 DK058234,
U01 DK060379, U01 DK58229, U01 DK60380, U01 DK60395, U01 DK60401, U01
DK58234, U01 DK58225, U01 DK060393, U01 DK60379, U01 DK60397, U01
DK58231, U01 DK060380, U01 DK058229, U01 DK060395, U01 DK060401, U01
DK60393]
NR 25
TC 62
Z9 63
U1 1
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD AUG 5
PY 2008
VL 149
IS 3
BP 161
EP 169
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 336CW
UT WOS:000258342900002
PM 18678843
ER
PT J
AU Gonzales, DA
Star, RA
Kern, SJ
Natanson, C
Danner, RL
AF Gonzales, Denise A.
Star, Robert A.
Kern, Steven J.
Natanson, Charles
Danner, Robert L.
TI Is there enough evidence to support use of N-acetylcysteine in
contrast-induced nephropathy?
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID NEPHROTOXICITY; METAANALYSIS
C1 [Gonzales, Denise A.] Presbyterian Hosp, Albuquerque, NM 87110 USA.
[Star, Robert A.; Kern, Steven J.; Natanson, Charles; Danner, Robert L.] NIH, Bethesda, MD 20892 USA.
RP Gonzales, DA (reprint author), Presbyterian Hosp, Albuquerque, NM 87110 USA.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD AUG 5
PY 2008
VL 149
IS 3
BP 213
EP 214
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 336CW
UT WOS:000258342900011
PM 18678852
ER
PT J
AU Moy, SS
Nadler, JJ
Young, NB
Nonneman, RJ
Segall, SK
Andrade, GM
Crawley, JN
Magnuson, TR
AF Moy, Sheryl S.
Nadler, Jessica J.
Young, Nancy B.
Nonneman, Randal J.
Segall, Samantha K.
Andrade, Gabriela M.
Crawley, Jacqueline N.
Magnuson, Terry R.
TI Social approach and repetitive behavior in eleven inbred mouse strains
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE autism; morris water maze; reversal learning; sociability; social
preference; spectrum disorders; stereotypy; T-maze
ID AUTISM SPECTRUM DISORDERS; FMR1 KNOCKOUT MICE; EXECUTIVE FUNCTIONS;
MODEL; GENE; PHENOTYPE; RELEVANT; SOCIABILITY; ENVIRONMENT; CHILDREN
AB Core symptoms of autism include deficits in social interaction, impaired communication, and restricted, repetitive behaviors. The repetitive behavior domain encompasses abnormal motoric stereotypy, an inflexible insistence on sameness, and resistance to change. In recent years, many genetic mouse models of autism and related disorders have been developed, based on candidate genes for disease susceptibility. The present studies are part ofan ongoing initiative to develop appropriate behavioral tasks for the evaluation of mouse models relevant to autism. We have previously reported profiles for sociability, preference for social novelty, and resistance to changes in a learned pattern of behavior, as well as other functional domains, for 10 inbred mouse strains of divergent genetic backgrounds. The present studies extend this multi-component behavioral characterization to several additional strains: C58/J, NOD/LtJ, NZB/B1NJ, PL/J, SJL/J, SWR/J, and the wild-derived PERA/EiJ. C58/J, NOD/LEJ, NZB/B1NJ, SJL/J, and PERA/EiJ demonstrated low sociability, measured by time spent in proximity to an unfamiliar conspecific, with 30-60% of mice from these strains showing social avoidance. In the Morris water maze, NZB/B1NJ had a persistent bias for the quadrant where the hidden platform was located during acquisition, even after 9 days of reversal training. A particularly interesting profile was found for C58/J, which had low social preference, poor performance in the T-maze, and overt motoric stereotypy. Overall, this set of tasks and observational methods provides a strategy for evaluating novel mouse models in behavioral domains relevant to the autism phenotype. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Moy, Sheryl S.; Nadler, Jessica J.; Young, Nancy B.; Nonneman, Randal J.; Andrade, Gabriela M.; Crawley, Jacqueline N.; Magnuson, Terry R.] Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA.
[Moy, Sheryl S.; Crawley, Jacqueline N.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Nadler, Jessica J.; Segall, Samantha K.; Magnuson, Terry R.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
RP Moy, SS (reprint author), Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, CB 7146, Chapel Hill, NC 27599 USA.
EM ssmoy@med.unc.edu
FU Intramural NIH HHS; NICHD NIH HHS [P30 HD003110, P30 HD003110-40, P30
HD03110]; NIMH NIH HHS [U54 MH066418, U54 MH066418-04, U54 MH66418]
NR 50
TC 111
Z9 112
U1 4
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD AUG 5
PY 2008
VL 191
IS 1
BP 118
EP 129
DI 10.1016/j.bbr.2008.03.015
PG 12
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 314CP
UT WOS:000256786700017
PM 18440079
ER
PT J
AU Savas, JN
Makusky, A
Ottosen, S
Baillat, D
Then, F
Krainc, D
Shiekhattar, R
Markey, SP
Tanese, N
AF Savas, Jeffrey N.
Makusky, Anthony
Ottosen, Soren
Baillat, David
Then, Florian
Krainc, Dimitri
Shiekhattar, Ramin
Markey, Sanford P.
Tanese, Naoko
TI Huntington's disease protein contributes to RNA-mediated gene silencing
through association with Argonaute and P bodies
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE microRNA; poly-glutamine; RNA interference; post-transcriptional gene
silencing; neuronal RNA granule
ID MICRORNA-DEPENDENT LOCALIZATION; STRESS GRANULES; PROCESSING BODIES;
PATHOGENESIS; DEGENERATION; INTERACTS; PATHWAYS; CLEAVAGE; REVEALS;
REPEATS
AB Huntington's disease is a dominant autosomal neurodegenerative disorder caused by an expansion of polyglutamines in the huntingtin (Htt) protein, whose cellular function remains controversial. To gain insight into Htt function, we purified epitope-tagged Htt and identified Argonaute as associated proteins. Colocalization studies demonstrated Htt and Agog to be present in P bodies, and depletion of Htt showed compromised RNA-mediated gene silencing. Mouse striatal cells expressing mutant Htt showed fewer P bodies and reduced reporter gene silencing activity compared with wild-type counterparts. These data suggest that the previously reported transcriptional deregulation in HD may be attributed in part to mutant Htt's role in post-transcriptional processes.
C1 [Savas, Jeffrey N.; Ottosen, Soren; Tanese, Naoko] NYU, Inst Canc, Dept Microbiol, New York, NY 10016 USA.
[Savas, Jeffrey N.] NYU, Natl Inst Hlth, Grad Partnership Program Struct Biol, Sch Med, New York, NY 10016 USA.
[Makusky, Anthony; Markey, Sanford P.] NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA.
[Baillat, David; Shiekhattar, Ramin] Ctr Regulacio Genom, Barcelona 08003, Spain.
[Then, Florian; Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat,Med Sch, Charlestown, MA 02129 USA.
RP Tanese, N (reprint author), NYU, Inst Canc, Dept Microbiol, 550 1St Ave, New York, NY 10016 USA.
EM naoko.tanese@med.nyu.edu
OI Tanese, Naoko/0000-0002-1946-3211
FU Intramural NIH HHS; NCRR NIH HHS [S10 RR017970]; NIMH NIH HHS [Z01
MH000274]; NINDS NIH HHS [R01NS050352, R01 NS050352]
NR 42
TC 79
Z9 81
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 AUG 5
PY 2008
VL 105
IS 31
BP 10820
EP 10825
DI 10.1073/pnas.0800658105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 335RT
UT WOS:000258308500037
PM 18669659
ER
PT J
AU Earl, PL
Americo, JL
Wyatt, LS
Espenshade, O
Bassler, J
Gong, K
Lin, S
Peters, E
Rhodes, L
Spano, YE
Silvera, PM
Moss, B
AF Earl, Patricia L.
Americo, Jeffrey L.
Wyatt, Linda S.
Espenshade, Ondraya
Bassler, Jocelyn
Gong, Kathy
Lin, Shuling
Peters, Elizabeth
Rhodes, Lowrey, Jr.
Spano, Yvette Edghill
Silvera, Peter M.
Moss, Bernard
TI Rapid protection in a monkeypox model by a single injection of a
replication-deficient vaccinia virus
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE biodefense; modified vaccinia virus Ankara; poxvirus; smallpox vaccine;
neutralizing antibody
ID SMALLPOX VACCINE; ANKARA MVA; ADVERSE EVENTS; IMMUNOGENICITY; CHALLENGE;
SAFETY; MACAQUES; HOST; ORTHOPOXVIRUS; POSTEXPOSURE
AB The success of the World Health Organization smallpox eradication program three decades ago resulted in termination of routine vaccination and consequent decline in population immunity. Despite concerns regarding the reintroduction of smallpox, there is little enthusiasm for large-scale redeployment of licensed live vaccinia virus vaccines because of medical contraindications and anticipated serious side effects. Therefore, highly attenuated strains such as modified vaccinia virus Ankara (MVA) are under evaluation in humans and animal models. Previous studies showed that priming and boosting with MVA provided protection for > 2 years in a monkeypox virus challenge model. If variola virus were used as a biological weapon, however, the ability of a vaccine to quickly induce immunity would be essential. Here, we demonstrate more rapid immune responses after a single vaccination with MVA compared to the licensed Dryvax vaccine. To determine the kinetics of protection of the two vaccines, macaques were challenged intravenously with monkeypox virus at 4, 6, 10, and 30 days after immunization. At 6 or more days after vaccination with MVA or Dryvax, the monkeys were clinically protected (except for 1 of 16 animals vaccinated with MVA), although viral loads and number of skin lesions were generally higher in the MVA vaccinated group. With only 4 days between immunization and intravenous challenge, however, MVA still protected whereas Dryvax failed. Protection correlated with the more rapid immune response to MVA compared to Dryvax, which may be related to the higher dose of MVA that can be tolerated safely.
C1 [Earl, Patricia L.; Americo, Jeffrey L.; Wyatt, Linda S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Espenshade, Ondraya; Bassler, Jocelyn; Gong, Kathy; Lin, Shuling; Peters, Elizabeth; Rhodes, Lowrey, Jr.; Spano, Yvette Edghill; Silvera, Peter M.] So Res Inst, Frederick, MD 21701 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@niaid.nih.gov
FU Intramural NIH HHS; NIAID NIH HHS [N01AI30063, N01 AI 30063]
NR 40
TC 54
Z9 54
U1 0
U2 0
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 AUG 5
PY 2008
VL 105
IS 31
BP 10889
EP 10894
DI 10.1073/pnas.0804985105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 335RT
UT WOS:000258308500049
PM 18678911
ER
PT J
AU Tang, S
Bertke, AS
Patel, A
Wang, K
Cohen, JI
Krause, PR
AF Tang, Shuang
Bertke, Andrea S.
Patel, Amita
Wang, Kening
Cohen, Jeffrey I.
Krause, Philip R.
TI An acutely and latently expressed herpes simplex virus 2 viral microRNA
inhibits expression of ICP34.5, a viral neurovirulence factor
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HSV; latency-associated transcript; latency; reactivation; human
ID SIMPLEX-VIRUS TYPE-1; PROTEIN-SYNTHESIS; MALIGNANT GLIOMA; INFECTED
NEURONS; HERPES; TRANSCRIPT; GENE; IDENTIFICATION; REACTIVATION;
PROMOTER
AB Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression.
C1 [Tang, Shuang; Bertke, Andrea S.; Patel, Amita; Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA.
[Wang, Kening; Cohen, Jeffrey I.] NIAID, Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA.
RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM philip.krause@fda.hhs.gov
RI Tang, Shuang/F-9115-2014;
OI Tang, Shuang/0000-0002-3084-0903; Krause, Philip/0000-0002-1045-7536
FU Intramural NIH HHS
NR 29
TC 91
Z9 102
U1 3
U2 8
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 AUG 5
PY 2008
VL 105
IS 31
BP 10931
EP 10936
DI 10.1073/pnas.0801845105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 335RT
UT WOS:000258308500056
PM 18678906
ER
PT J
AU Delviks-Frankenberry, KA
Nikolenko, GN
Boyer, PL
Hughes, SH
Coffin, JM
Jere, A
Pathak, VK
AF Delviks-Frankenberry, Krista A.
Nikolenko, Galina N.
Boyer, Paul L.
Hughes, Stephen H.
Coffin, John M.
Jere, Abhay
Pathak, Vinay K.
TI HIV-1 reverse transcriptase connection subdomain mutations reduce
template RNA degradation and enhance AZT excision
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE drug resistance; RNase H; TAMs; NRTI; NNRTI
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DUAL RESISTANCE; H ACTIVITY; ZIDOVUDINE;
NUCLEOSIDE; MECHANISM; INFECTION; FIDELITY; INCREASE; GENERATION
AB We previously proposed that mutations in the connection subdomain (cn) of HIV-1 reverse transcriptase increase AZT resistance by altering the balance between nucleotide excision and template RNA degradation. To test the predictions of this model, we analyzed the effects of previously identified cn mutations in combination with thymidine analog mutations (D67N, K70R, T215Y, and K219Q) on in vitro RNase H activity and AZT monophosphate (AZTMP) excision. We found that cn mutations G335C/D, N348I, A360I/V, V365I, and A376S decreased primary and secondary RNase H cleavages. The patient-derived cns increased ATP- and PPi-mediated AZTMP excision on an RNA template compared with a DNA template. One of 5 cns caused an increase in ATP-mediated AZTMP excision on a DNA template, whereas three cns showed a higher ratio of ATP- to PPi-mediated excision, indicating that some cn mutations also affect excision on a DNA substrate. Overall, the results strongly support the model that cn mutations increase AZT resistance by reducing template RNA degradation, thereby providing additional time for RT to excise AZTMP.
C1 [Delviks-Frankenberry, Krista A.; Nikolenko, Galina N.; Jere, Abhay; Pathak, Vinay K.] Natl Canc Inst, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA.
[Boyer, Paul L.; Hughes, Stephen H.] Natl Canc Inst, HIV Drug Resistance Program, Vector Design & Replicat Sect, Frederick, MD 21702 USA.
[Coffin, John M.] Natl Canc Inst, HIV Drug Resistance Program, Host Virus Interact Unit, Frederick, MD 21702 USA.
[Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Pathak, VK (reprint author), Natl Canc Inst, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA.
EM john.coffin@tufts.edu; vpathak@ncifcrf.gov
RI Delviks-Frankenberry, Krista/M-4822-2013
FU Intramural NIH HHS [Z01 BC010532-05]
NR 29
TC 45
Z9 45
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 5
PY 2008
VL 105
IS 31
BP 10943
EP 10948
DI 10.1073/pnas.0804660105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 335RT
UT WOS:000258308500058
PM 18667707
ER
PT J
AU Gallazzini, M
Ferraris, JD
Burg, MB
AF Gallazzini, Morgan
Ferraris, Joan D.
Burg, Maurice B.
TI GDPD5 is a glycerophosphocholine phosphodiesterase that osmotically
regulates the osmoprotective organic osmolyte GPC
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE high urea; hypertonicity; RNA stability
ID NEUROPATHY TARGET ESTERASE; COLLECTING DUCT CELLS; CHOLINE
PHOSPHODIESTERASE; SACCHAROMYCES-CEREVISIAE; MEMBRANE-PROTEIN;
RENAL-CELLS; MDCK CELLS; HIGH NACL; PHOSPHATIDYLCHOLINE;
GLYCEROPHOSPHORYLCHOLINE
AB Glycerophosphocholine (GPC) is an abundant osmoprotective renal medullary organic osmolyte. We previously found that its synthesis from phosphatidylcholine is catalyzed by tonicity-regulated activity of the phospholipase B, neuropathy target esterase. We also found that its degradation is catalyzed by glycerophosphocholine phosphodiesterase (GPC-PDE) activity and that elevating osmolality from 300 to 500 mosmol/kg by adding NaCl or urea, inhibits GPC-PDE activity, which contributes to the resultant increase of GPC. In the present studies we identify GDPD5 (glycerophosphodiester phosphodiesterase domain containing 5) as a GPC-PDE that is rapidly inhibited by high NaCl or urea. Recombinant GDPD5 colocalizes with neuropathy target esterase in the perinuclear region of HEK293 cells, and immuno-precipitated recombinant GDPD5 degrades GPC in vitro. The in vitro activity is reduced when the cells from which the GDPD5 is immuno-precipitated have been exposed to high NaCl or urea. In addition, high NaCl decreases mRNA abundance of GDPD5 via an increase of its degradation rate, although high urea does not. At 300 mosmol/kg siRNA knockdown of GDPD5 increases GPC in mouse inner medullary collecting duct-3 cells, and over expression of recombinant GDPD5 increases cellular GPC-PDE activity, accompanied by decreased GPC. We conclude that GDPD5 is a GPC-PDE that contributes to osmotic regulation of cellular GPC.
C1 [Gallazzini, Morgan; Ferraris, Joan D.; Burg, Maurice B.] NHLBI, NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20982 USA.
RP Gallazzini, M (reprint author), NHLBI, NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20982 USA.
EM gallazzinim@nhlbi.nih.gov; maurice_burg@nih.gov
RI Gallazzini, Morgan/E-5465-2011
FU Intramural NIH HHS
NR 32
TC 40
Z9 42
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 AUG 5
PY 2008
VL 105
IS 31
BP 11026
EP 11031
DI 10.1073/pnas.0805496105
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 335RT
UT WOS:000258308500072
PM 18667693
ER
PT J
AU Samal, BB
Eiden, LE
AF Samal, Babru B.
Eiden, Lee E.
TI pathFinder: A Static Network Analysis Tool for Pharmacological Analysis
of Signal Transduction Pathways
SO SCIENCE SIGNALING
LA English
DT Article
AB The study of signal transduction is becoming a de facto part of the analysis of gene expression and protein profiling techniques. Many online tools are used to cluster genes in various ways or to assign gene products to signal transduction pathways. Among these, pathFinder is a unique tool that can find signal transduction pathways between first, second, or nth messengers and their targets within the cell. pathFinder can identify qualitatively all possible signal transduction pathway connecting any starting component and target within a database of two-component pathways (directional dyads). One or more intermediate pathway components can be excluded to simulate the use of pharmacological inhibitors or genetic deletion (knockout). Missing elements in a pathway connecting the activator or initiator and target can also be inferred from a null pathway result. The value of this static network analysis tool is illustrated by the predication from pathFinder analysis of a novel cyclic AMP-dependent, protein kinase A-independent signaling pathway in neuroendocrine cells, which has been experimentally confirmed.
C1 [Samal, Babru B.] NIMH, Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[Eiden, Lee E.] NIH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Samal, BB (reprint author), NIMH, Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
EM samalb@mail.nih.edu
OI Eiden, Lee/0000-0001-7524-944X
FU Intramural NIH HHS [Z01 MH002386-21]
NR 15
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD AUG 5
PY 2008
VL 1
IS 31
AR pt4
DI 10.1126/scisignal.131pt4
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA V10WK
UT WOS:000207493900001
PM 18682604
ER
PT J
AU Blaney, JE
Speicher, J
Hanson, CT
Sathe, NS
Whitehead, SS
Murphy, BR
Pletnev, AG
AF Blaney, Joseph E., Jr.
Speicher, James
Hanson, Christopher T.
Sathe, Neeraj S.
Whitehead, Stephen S.
Murphy, Brian R.
Pletnev, Alexander G.
TI Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic
chimeric viruses in mice and rhesus monkeys
SO VACCINE
LA English
DT Article
DE St. Louis encephalitis virus; chimeric virus; vaccine
ID TICK-BORNE ENCEPHALITIS; WEST-NILE-VIRUS; VACCINE CANDIDATES; ATTENUATED
VACCINE; NONHUMAN-PRIMATES; DENGUE TYPE-4; BIOLOGICAL-PROPERTIES;
STRUCTURAL GENES; LIVE; IMMUNOGENICITY
AB To develop a live attenuated virus vaccine against St. Louis encephalitis (SLE) virus, two antigenic chimeric viruses were generated by replacing the membrane precursor and envelope protein genes of dengue virus type 4 (DEN4) with those from SLE with or without a 30 nucleotide deletion in the DEN4 3' untranslated region of the chimeric genome. Chimeric viruses were compared with parental wild-type SLE for level of neurovirulence and neuroinvasiveness in mice and for safety, immunogenicity, and protective efficacy in rhesus monkeys. The resulting viruses, SLE/DEN4 and SLE/DEN4 Delta 30, had greatly reduced neuroinvasiveness in immunodeficient mice but retained neurovirulence in suckling mice. Chimerization of SLE with DEN4 resulted in only moderate restriction in replication in rhesus monkeys, whereas the presence of the Delta 30 mutation led to over-attenuation. Introduction of previously described attenuating paired charge-to-alanine mutations in the DEN4 NS5 protein of SLE/DEN4 reduced neurovirulence in mice and replication in rhesus monkeys. Two modified SLE/DEN4 viruses, SLE/DEN4-436,437 clone 41 and SLE/DEN4-654,655 clone 46, have significantly reduced neurovirulence in mice and conferred protective immunity in monkeys against SLE challenge. These viruses may be considered for use as SLE vaccine candidates and for use as diagnostic reagents with reduced virulence. Published by Elsevier Ltd.
C1 [Blaney, Joseph E., Jr.; Speicher, James; Hanson, Christopher T.; Sathe, Neeraj S.; Whitehead, Stephen S.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,Room 3W10A, Bethesda, MD 20892 USA.
EM apletnev@niaid.nih.gov
FU NIAID Division of Intramural Research
FX We thank Anthony Wlazlo for technical assistance in the generation of
the SLE/DEN4 cDNA clone and Brad Finneyfrock, the staff of Bioclual,
Inc., and Jadon Jackson for assistance with animal studies. These
Studies were supported by funds from the NIAID Division of Intramural
Research.
NR 41
TC 7
Z9 7
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 5
PY 2008
VL 26
IS 33
BP 4150
EP 4159
DI 10.1016/j.vaccine.2008.05.075
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 338QO
UT WOS:000258522800009
PM 18586359
ER
PT J
AU Moir, S
Ho, J
Malaspina, A
Wang, W
DiPoto, AC
O'Shea, MA
Roby, G
Kottilil, S
Arthos, J
Proschan, MA
Chun, TW
Fauci, AS
AF Moir, Susan
Ho, Jason
Malaspina, Angela
Wang, Wei
DiPoto, Angela C.
O'Shea, Marie A.
Roby, Gregg
Kottilil, Shyam
Arthos, James
Proschan, Michael A.
Chun, Tae-Wook
Fauci, Anthony S.
TI Evidence for HIV-associated B cell exhaustion in a dysfunctional memory
B cell compartment in HIV-infected viremic individuals
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHRONIC VIRAL-INFECTION; T-CELLS; DISEASE
PROGRESSION; EXPRESSION; RECEPTORS; PATHOGENESIS; POPULATION;
ACTIVATION; RESPONSES
AB Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20(hi)/CD27(lo)/CD21(lo)) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype ( CD20(hi)/CD27(lo)/CD21(lo)) when compared with B cells with a classical memory (CD27(+)) or naive (CD27(-)/CD21(hi)) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.
C1 [Moir, Susan; Ho, Jason; Malaspina, Angela; Wang, Wei; DiPoto, Angela C.; O'Shea, Marie A.; Roby, Gregg; Kottilil, Shyam; Arthos, James; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Proschan, Michael A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
EM smoir@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank M. D. Cooper and G. Ehrhardt (Emory University School of
Medicine) for helpful discussions. We are grateful to the patients for
their willingness to participate in our study.; This work was supported
by the Intramural Research Program of National Institute of Allergy and
Infectious Diseases, National Institutes of Health.; The authors have no
conflicting financial interests.
NR 32
TC 330
Z9 336
U1 0
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 4
PY 2008
VL 205
IS 8
BP 1797
EP 1805
DI 10.1084/jem.20072683
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 338SH
UT WOS:000258528500010
PM 18625747
ER
PT J
AU Pichler, K
Jeang, KT
AF Pichler, Klemens
Jeang, Kuan-Teh
TI Remembering Ralph Grassmann (1957-2008)
SO RETROVIROLOGY
LA English
DT Editorial Material
ID TAX
AB Friends and colleagues of Ralph Grassmann write their remembrances.
C1 [Jeang, Kuan-Teh] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Pichler, Klemens] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, Erlangen, Germany.
RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Klemens.Pichler@viro.med.uni-erlangen.de; kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008;
OI Pichler, Klemens/0000-0001-6099-8931
NR 4
TC 1
Z9 1
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD AUG 4
PY 2008
VL 5
AR 71
DI 10.1186/1742-4690-5-71
PG 4
WC Virology
SC Virology
GA 344YI
UT WOS:000258962800001
PM 18680572
ER
PT J
AU Eastman, D
Piantadosi, A
Wu, XL
Forthal, DN
Landucci, G
Kimata, JT
Overbaugh, J
AF Eastman, Dawnnica
Piantadosi, Anne
Wu, Xueling
Forthal, Donald N.
Landucci, Gary
Kimata, Jason T.
Overbaugh, Julie
TI Heavily glycosylated, highly fit SIVMne variants continue to diversify
and undergo selection after transmission to a new host and they elicit
early antibody dependent cellular responses but delayed neutralizing
antibody responses
SO VIROLOGY JOURNAL
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; EXTRACELLULAR ENVELOPE GLYCOPROTEIN;
IN-VIVO; LINKED GLYCOSYLATION; INFECTED MACAQUES; TYPE-1 ENVELOPE;
EFFECTOR-CELLS; HIV-INFECTION; MNE VARIANT; PROGRESSION
AB Background: Lentiviruses such as human and simian immunodeficiency viruses (HIV and SIV) undergo continual evolution in the host. Previous studies showed that the late-stage variants of SIV that evolve in one host replicate to significantly higher levels when transmitted to a new host. However, it is unknown whether HIVs or SIVs that have higher replication fitness are more genetically stable upon transmission to a new host. To begin to address this, we analyzed the envelope sequence variation of viruses that evolved in animals infected with variants of SIVMne that had been cloned from an index animal at different stages of infection.
Results: We found that there was more evolution of envelope sequences from animals infected with the late-stage, highly replicating variants than in animals infected with the early-stage, lower replicating variant, despite the fact that the late virus had already diversified considerably from the early virus in the first host, prior to transmission. Many of the changes led to the addition or shift in potential-glycosylation sites-, and surprisingly, these changes emerged in some cases prior to the detection of neutralizing antibody responses, suggesting that other selection mechanisms may be important in driving virus evolution. Interestingly, these changes occurred after the development of antibody whose anti-viral function is dependent on Fc-Fc gamma receptor interactions.
Conclusion: SIV variants that had achieved high replication fitness and escape from neutralizing antibodies in one host continued to evolve upon transmission to a new host. Selection for viral variants with glycosylation and other envelope changes may have been driven by both neutralizing and Fc gamma receptor-ediated antibody activities.
C1 [Eastman, Dawnnica; Piantadosi, Anne; Wu, Xueling; Overbaugh, Julie] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA.
[Eastman, Dawnnica] Univ Washington, Program Mol & Cellular Biol, Seattle, WA 98195 USA.
[Piantadosi, Anne; Overbaugh, Julie] Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA.
[Forthal, Donald N.; Landucci, Gary] Univ Calif Irvine, Div Infect Dis, Irvine, CA USA.
[Kimata, Jason T.] Baylor Coll Med, Houston, TX 77030 USA.
[Wu, Xueling] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Overbaugh, J (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1124 Columbia St, Seattle, WA 98104 USA.
EM dke2002@cornell.edu; apiantad@u.washington.edu; wuxue@niaid.nih.gov;
dnfortha@uci.edu; glanducc@uci.edu; jkimata@bcm.edu; joverbau@fhcrc.org
FU NIH [R01 AI 34251, R01 AI 52039]; Cancer Research Institute; [T32
A107140]; [T32 GM07266]
FX This work was supported by NIH R01 AI 34251 to JO and NIH R01 AI 52039
to DF. AP was supported in part by training grants T32 A107140 and T32
GM07266. XW was supported in part by a postdoctoral fellowship from the
Cancer Research Institute. We thank Mario Pineda for help in optimizing
the neutralization assays and for his insights, and Nancy Haigwood and
members of her lab for helpful discussions.
NR 35
TC 4
Z9 4
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD AUG 4
PY 2008
VL 5
AR 90
DI 10.1186/1743-422X-5-90
PG 15
WC Virology
SC Virology
GA 345QQ
UT WOS:000259011800001
PM 18680596
ER
PT J
AU Mueller, GA
Moon, AF
DeRose, EF
Havener, JM
Ramsden, DA
Pedersen, LC
London, RE
AF Mueller, Geoffrey A.
Moon, Andrea F.
DeRose, Eugene F.
Havener, Jody M.
Ramsden, Dale A.
Pedersen, Lars C.
London, Robert E.
TI A comparison of BRCT domains involved in nonhomologous end-joining:
Introducing the solution structure of the BRCT domain of polymerase
lambda
SO DNA REPAIR
LA English
DT Article
DE family X polymerase; DNA polymerase lambda; TdT; DNA polymerase mu; BRCT
domain; protein-protein interaction; nonhomologous end-joining
ID TRIPLE RESONANCE EXPERIMENTS; SIDE-CHAIN RESONANCES; BASE
EXCISION-REPAIR; STRAND BREAK REPAIR; N-15 NMR RELAXATION; V(D)J
RECOMBINATION; C-13-LABELED PROTEINS; CHEMICAL-EXCHANGE; BACKBONE
DYNAMICS; DNA
AB Three of the four family X polymerases, DNA polymerase X, DNA polymerase L, and TdT, have been associated with repair of double-strand DNA breaks by nonhomologous endjoining. Their involvement in this DNA repair process requires an N-terminal BRCT domain that mediates interaction with other protein factors required for recognition and binding of broken DNA ends. Here we present the NMR solution structure of the BRCT domain of DNA polymerase X, completing the structural portrait for this family of enzymes. Analysis of the overall fold of the polymerase X BRCT domain reveals structural similarity to the BRCT domains of polymerase L and TdT, yet highlights some key sequence and structural differences that may account for important differences in the biological activities of these enzymes and their roles in nonhomologous end-joining. Mutagenesis studies indicate that the conserved Arg57 residue of Pol X plays a more critical role for bindingto the XRCC4-Ligase IV complex than its structural homolog in Pol L, Arg43. In contrast, the hydrophobic Leu60 residue of Pol x contributes less significantly to binding than the structurally homologous Phe46 residue of Pol R. A third leucine residue involved in the binding and activity of Pol [L, is nonconservatively replaced by a glutamine in Pol x (Gln64) and, based on binding and activity data, is apparently unimportant for Pol x interactions with the NHEJ complex. In conclusion, both the structure of the Pol X BRCT domain and its mode of interaction with the other components of the NHEJ complex significantly differ from the two previously studied homologs, Pol L and TdT. Published by Elsevier B.V.
C1 [Mueller, Geoffrey A.; Moon, Andrea F.; DeRose, Eugene F.; Pedersen, Lars C.; London, Robert E.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Havener, Jody M.; Ramsden, Dale A.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
RP Mueller, GA (reprint author), NIEHS, Struct Biol Lab, 111 TW Alexander Dr,MD MR-01, Res Triangle Pk, NC 27709 USA.
EM mueller3@niehs.nih.gov
FU Intramural NIH HHS [Z99 ES999999]; NCI NIH HHS [CA 97096, R01 CA084442,
R01 CA097096]; PHS HHS [HHS27300700046U]
NR 51
TC 18
Z9 18
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG 2
PY 2008
VL 7
IS 8
BP 1340
EP 1351
DI 10.1016/j.dnarep.2008.04.018
PG 12
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 334YY
UT WOS:000258259000015
PM 18585102
ER
PT J
AU Auld, DS
Thorne, N
Nguyen, DT
Inglese, J
AF Auld, Douglas S.
Thorne, Natasha
Nguyen, Dac-Trung
Inglese, James
TI A specific mechanism for nonspecific activation in reporter-gene assays
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID CHEMICAL LIBRARIES; THROUGHPUT; IDENTIFICATION; EXPRESSION; STABILITY
AB The importance of bioluminescence in enabling a broad range of high-throughput screening (HTS) assay formats is evidenced by widespread use in industry and academia. Therefore, understanding the mechanisms by which reporter enzyme activity can be modulated by small molecules is critical to the interpretation of HITS data. In this Perspective, we provide evidence for stabilization of luciferase by inhibitors in cell-based luciferase reporter-gene assays resulting in the counterintuitive phenomenon of signal activation. These data were derived from our analysis of luciferase inhibitor compound structures and their prevalence in the Molecular Libraries Small Molecule Repository using 100 HTS experiments available in PubChem. Accordingly, we found an enrichment of luciferase inhibitors in luciferase reporter-gene activation assays but not in assays using other reporters. In addition, for several luciferase inhibitor chemotypes, we measured reporter stabilization and signal activation in cells that paralleled the inhibition determined using purified luciferase to provide further experimental support for these contrasting effects.
C1 [Auld, Douglas S.; Thorne, Natasha; Nguyen, Dac-Trung; Inglese, James] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Inglese, J (reprint author), NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
EM jinglese@mail.nih.gov
OI Nguyen, Dac-Trung/0000-0003-2591-9948
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research; National Human Genome Research Institute,;
National Institutes of Health
FX This research was supported by the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research and the
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health. We thank N. Southall for
critically reading this manuscript prior to submission and D. Leja for
graphical artwork.
NR 12
TC 62
Z9 63
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD AUG
PY 2008
VL 3
IS 8
BP 463
EP 470
DI 10.1021/cb8000793
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 338JK
UT WOS:000258503800003
PM 18590332
ER
PT J
AU Walsh, JM
Verstraete, AG
Huestis, MA
Morland, J
AF Walsh, J. Michael
Verstraete, Alain G.
Huestis, Marilyn A.
Morland, Jorg
TI Guidelines for research on drugged driving
SO ADDICTION
LA English
DT Article
DE alcohol; driving; DUI; illegal drugs; motor vehicle crash; trauma
AB Aim A major problem in assessing the true public health impact of drug-use on driving and overall traffic safety is that the variables being measured across studies vary significantly. In studies reported in a growing global literature, basic parameters assessed, analytical techniques and drugs tested are simply not comparable due to lack of standardization in the field. These shortcomings severely limit the value of this research to add knowledge to the field. A set of standards to harmonize research findings is sorely needed. This project was initiated by several international organizations to develop guidelines for research on drugged driving. Methods A September 2006 meeting of international experts discussed the harmonization of protocols for future research on drugged driving. The principal objective of the meeting was to develop a consensus report setting guidelines, standards, core data variables and other controls that would form the basis for future international research. A modified Delphi method was utilized to develop draft guidelines. Subsequently, these draft guidelines were posted on the internet for global review, and comments received were integrated into the final document. Results The Guidelines Document is divided into three major sections, each focusing upon different aspects of drugged driving research (e.g. roadside surveys, prevalence studies, hospital studies, fatality and crash investigations, etc.) within the critical issue areas of 'behavior', 'epidemiology' and 'toxicology'. The behavioral section contains 32 specific recommendations; (2) epidemiology 40 recommendations; and (3) toxicology 64 recommendations. Conclusions It is anticipated that these guidelines will improve significantly the overall quality of drugged driving research and facilitate future cross-study comparisons nationally and globally.
C1 [Walsh, J. Michael] Walsh Grp PA, Bethesda, MD 20817 USA.
[Verstraete, Alain G.] Ghent Univ Hosp, Lab Clin Biol Toxicol, B-9000 Ghent, Belgium.
[Huestis, Marilyn A.] Natl Inst Drug Abuse, Chem & Drug Metab Sect, Baltimore, MD USA.
[Morland, Jorg] Norwegian Inst Publ Hlth, Div Forens Toxicol & Drug Abuse, Oslo, Norway.
RP Walsh, JM (reprint author), Walsh Grp PA, 6701 Democracy Blvd,Suite 300, Bethesda, MD 20817 USA.
EM jmwalsh@walshgroup.org
RI Verstraete, Alain/B-4150-2013
OI Verstraete, Alain/0000-0002-0956-3315
FU Intramural NIH HHS [Z01 DA000414-10]
NR 8
TC 72
Z9 72
U1 2
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD AUG
PY 2008
VL 103
IS 8
BP 1258
EP 1268
DI 10.1111/j.1360-0443.2008.02277.x
PG 11
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 326XM
UT WOS:000257692800003
PM 18855814
ER
PT J
AU Bjork, JM
Knutson, B
Hommer, DW
AF Bjork, James M.
Knutson, Brian
Hommer, Daniel W.
TI Incentive-elicited striatal activation in adolescent children of
alcoholics
SO ADDICTION
LA English
DT Article
DE adolescence; alcohol; at-risk children; impulsivity; incentives; nucleus
accumbens; reward; sensation-seeking; striatum; ventral
ID SUBSTANCE USE DISORDERS; BEHAVIORAL DISINHIBITION;
ENVIRONMENTAL-INFLUENCES; SENSATION SEEKING; GENETIC RISK; REWARD;
DEPENDENCE; CIRCUITRY; CONDUCT; FAMILY
AB Aims Deficient recruitment of motivational circuitry by non-drug rewards has been postulated as a pre-morbid risk factor for substance dependence (SD). We tested whether parental alcoholism, which confers risk of SD, is correlated with altered recruitment of ventral striatum (VS) by non-drug rewards in adolescence. Design During functional magnetic resonance imaging, adolescent children of alcoholics (COA; age 12-16 years) with no psychiatric disorders (including substance abuse) and similarly aged children with no risk factors responded to targets to win or avoid losing $0, $0.20, $1, $5 or a variable amount (ranging from $0.20 to $5). Results In general, brain activation by either reward anticipation or outcome notification did not differ between COA and age/gender-matched controls. Cue-elicited reward anticipation activated portions of VS in both COA and controls. In nucleus accumbens (NAcc), signal change increased with anticipated reward magnitude (with intermediate recruitment by variable incentives) but not with loss magnitudes. Reward deliveries activated the NAcc and mesofrontal cortex in both COA and controls. Losses activated anterior insula bilaterally in both groups, with more extensive right anterior insula activation by losses in controls. NAcc signal change during anticipation of maximum rewards (relative to non-reward) correlated positively with both Brief Sensation-Seeking Scale scores and with self-reported excitement in response to maximum reward cues (relative to cues for non-reward). Conclusions Among adolescents with no psychiatric disorders, incentive-elicited VS activation may relate more to individual differences in sensation-seeking personality than to presence of parental alcoholism alone. Future research could focus on adolescents with behavior disorders or additional risk factors.
C1 [Bjork, James M.; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Knutson, Brian] Stanford Univ, Dept Psychol, Palo Alto, CA 94304 USA.
RP Bjork, JM (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr CRC,Room 1-5330, Bethesda, MD 20892 USA.
EM jbjork@mail.nih.gov
OI Bjork, James/0000-0003-0593-3291; Knutson, Brian/0000-0002-7669-426X
FU Intramural NIH HHS
NR 51
TC 70
Z9 72
U1 4
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD AUG
PY 2008
VL 103
IS 8
BP 1308
EP 1319
DI 10.1111/j.1360-0443.2008.02250.x
PG 12
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 326XM
UT WOS:000257692800010
PM 18851716
ER
PT J
AU Boyd, CJ
McCabe, SE
Cranford, JA
Morales, M
Lange, JE
Reed, MB
Ketchie, JM
Scott, MS
AF Boyd, Carol J.
McCabe, Sean Esteban
Cranford, James A.
Morales, Michele
Lange, James E.
Reed, Mark B.
Ketchie, Julie M.
Scott, Marcia S.
TI Heavy episodic drinking and its consequences: The protective effects of
same-sex, residential living-learning communities for undergraduate
women
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE undergraduate women; residential learning communities; heavy episodic
drinking
ID 1ST-YEAR COLLEGE-STUDENTS; BINGE-DRINKING; ALCOHOL INVOLVEMENT; WEB;
CAMPUSES; HEALTH; MAIL
AB Gender and living environment are two of the most consistent factors associated with heavy episodic drinking on college campuses. This study aimed to determine group differences in alcohol misuse and its attendant consequences between undergraduate women living in tour distinct on-campus residential environments. A Web-based survey was self-administered to a stratified random sample of full-time students attending a large Midwestern University, and living in four distinct on-campus residential environments: 1) single-sex (all female) residential learning communities (RLCs), 2) mixed-sex (male and female) RLCs, 3) single-sex (all female) non-RLCs and 4) mixed-sex (male and female) non-RLCs. Respondents living in single-sex and mixed-sex RLCs had significantly lower rates of alcohol use, heavy episodic drinking and related primary alcohol-related consequences when compared to respondents living in non-RLCs; however, women in single-sex RLCs had the lowest rates. RLCs - particularly single-sex learning communities - appear to provide undergraduate women with an environment that supports lower rates of alcohol use and abuse. (c) 2008 Elsevier Ltd. All rights reserved.
C1 [Boyd, Carol J.; McCabe, Sean Esteban] Univ Michigan, Inst Res Women & Gender, Sch Nursing & Womens Studies, Ann Arbor, MI 48109 USA.
[Boyd, Carol J.; McCabe, Sean Esteban; Cranford, James A.; Morales, Michele] Univ Michigan, Subst Abuse Res Ctr, Ann Arbor, MI 48105 USA.
[Lange, James E.; Reed, Mark B.; Ketchie, Julie M.] San Diego State Univ Res Fdn, AOD Initiat Res, San Diego, CA 92120 USA.
[Scott, Marcia S.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
RP Boyd, CJ (reprint author), Univ Michigan, Inst Res Women & Gender, Sch Nursing & Womens Studies, 204 S State St, Ann Arbor, MI 48109 USA.
EM caroboyd@umich.edu
RI Croff, Julie/I-6861-2012;
OI McCabe, Sean/0000-0002-9622-4652
FU NIAAA NIH HHS [AA014738, AA015275, U01 AA014738, U18 AA015275, U18
AA015275-02, U18 AA015275-03]
NR 28
TC 1
Z9 2
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD AUG
PY 2008
VL 33
IS 8
BP 987
EP 993
DI 10.1016/j.addbeh.2008.03.005
PG 7
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 324LN
UT WOS:000257520200002
PM 18485609
ER
PT J
AU Barlow, JB
Domanski, MJ
AF Barlow, Jewel B.
Domanski, Michael J.
TI Lift on stationary and rotating spheres under varying flow and surface
conditions
SO AIAA JOURNAL
LA English
DT Article
AB We examined the coefficient of lift for rotating and nonrotating spheres of varying surface texture under a variety of flight conditions. At Reynolds number less than 500,000 the direction of lift on a nonrotating polished sphere in a uniform flowfield is nonzero and in a direction that varies randomly with Reynolds number. However, once established, the direction and magnitude of lift appears to be stable overtime at a particular Reynolds number. This phenomenon has not been reported previously. Additionally, the texture of a rotating sphere in a uniform flow can modulate direction and magnitude of lift generated by the spin. Although the expected direction of the net force on a spinning sphere is in a direction from the advancing to retreating surface ("Magnus effect"), in certain flight regimes the net force is in the opposite direction ("negative Magnus effect"). In this paper we present the first systematic windtunnel characterization of the How parameters generating a negative Magnus effect on a sphere.
C1 [Barlow, Jewel B.] Univ Maryland, Dept Aerosp Engn, College Pk, MD 20742 USA.
[Domanski, Michael J.] NHLBI, Bethesda, MD 20892 USA.
RP Barlow, JB (reprint author), Univ Maryland, Dept Aerosp Engn, Coll Pk,3181 Martin Hall, College Pk, MD 20742 USA.
NR 12
TC 2
Z9 2
U1 0
U2 4
PU AMER INST AERONAUT ASTRONAUT
PI RESTON
PA 1801 ALEXANDER BELL DRIVE, STE 500, RESTON, VA 22091-4344 USA
SN 0001-1452
J9 AIAA J
JI AIAA J.
PD AUG
PY 2008
VL 46
IS 8
BP 1932
EP 1936
DI 10.2514/1.28129
PG 5
WC Engineering, Aerospace
SC Engineering
GA 335HM
UT WOS:000258281400005
ER
PT J
AU Purohit, V
Bode, JC
Bode, C
Brenner, DA
Choudhry, MA
Hamilton, F
Kang, YJ
Keshavarzian, A
Rao, R
Sartor, RB
Swanson, C
Turner, JR
AF Purohit, Vishnudutt
Bode, J. Christian
Bode, Christiane
Brenner, David A.
Choudhry, Mashkoor A.
Hamilton, Frank
Kang, Y. James
Keshavarzian, Ali
Rao, Radhakrishna
Sartor, R. Balfour
Swanson, Christine
Turner, Jerrold R.
TI Alcohol, intestinal bacterial growth, intestinal permeability to
endotoxin, and medical consequences: Summary of a symposium
SO ALCOHOL
LA English
DT Article
DE alcohol; bacterial growth; intestinal permeability; endotoxin;
acetaldehyde; nitric oxide
ID INDUCED LIVER-INJURY; INFLAMMATORY-BOWEL-DISEASE; HEPATIC STELLATE
CELLS; ACETALDEHYDE-INDUCED INCREASE; EPITHELIAL TIGHT JUNCTIONS; CHAIN
KINASE EXPRESSION; NITRIC-OXIDE SYNTHASE; TOLL-LIKE RECEPTOR-4;
CROHNS-DISEASE; PARACELLULAR PERMEABILITY
AB This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram-negative bacteria in the intestine, which may result in accumulation of endotoxin. In addition, alcohol metabolism by Gram-negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan, which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram-negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, L-glutamine, oats supplementation, or zinc, thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram-negative bacteria and preserving intestinal permeability to endotoxin may attenuate alcoholic liver and other organ injuries. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Purohit, Vishnudutt] NIAAA, Div Metab & Hlth Effects, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Bode, J. Christian; Bode, Christiane] Hohenheim Univ 140, Dept Physiol Nutr, Stuttgart, Germany.
[Brenner, David A.] Univ Calif San Diego Hlth Sci, La Jolla, CA USA.
[Choudhry, Mashkoor A.] Univ Alabama, Surg Res Ctr, Birmingham, AL USA.
[Hamilton, Frank] NIDDK, Div Digest Dis & Nutr, Natl Inst Hlth, Bethesda, MD USA.
[Kang, Y. James] Univ Louisville, Sch Med, Dept Med, Louisville, KY 40292 USA.
[Kang, Y. James] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[Keshavarzian, Ali] Rush Univ, Med Ctr, Div Digest Dis & Nutr, Dept Med, Chicago, IL USA.
[Rao, Radhakrishna] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA.
[Sartor, R. Balfour] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Swanson, Christine] Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD USA.
[Turner, Jerrold R.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
RP Purohit, V (reprint author), Natl Inst Drug Abuse, Div Basic Neurosci & Behav Res, Natl Inst Hlth, 6001 Execut Blvd,Room 4274,MSC 9555, Bethesda, MD 20892 USA.
EM vpurohit@nida.nih.gov
RI Turner, Jerrold/A-6895-2009
OI Turner, Jerrold/0000-0003-0627-9455
FU NHLBI NIH HHS [R01 HL059225, R01 HL059225-07]; NIAAA NIH HHS [R01
AA012307, R01 AA013745, R01 AA013745-05, R01 AA015731, R01 AA015731-02,
R21 AA015979, R21 AA015979-02]; NIDDK NIH HHS [R01 DK068271, P01
DK067887, R01 DK055532, R01 DK055532-11, R01 DK061931, R56 DK094954];
NIMH NIH HHS [R01 MH063760, R01 MH063760-06]; PHS HHS [R01 H063760]
NR 95
TC 128
Z9 139
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
J9 ALCOHOL
JI Alcohol
PD AUG
PY 2008
VL 42
IS 5
BP 349
EP 361
DI 10.1016/j.alcohol.2008.03.131
PG 13
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 331LE
UT WOS:000258012900001
PM 18504085
ER
PT J
AU Palachick, B
Chen, YC
Enoch, AJ
Karlsson, RM
Mishina, M
Holmes, A
AF Palachick, Benjamin
Chen, Yi-Chyan
Enoch, Abigail J.
Karlsson, Rose-Marie
Mishina, Masayoshi
Holmes, Andrew
TI Role of major NMDA or AMPA receptor subunits in MK-801 potentiation of
ethanol intoxication
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE alcohol; glutamate; NMDA; AMPA; mouse; MK-801; ethanol; rotarod;
hypothermia; ataxia; sedation
ID METHYL-D-ASPARTATE; SHORT-SLEEP MICE; INBRED LONG-SLEEP; GABA(A)
PHARMACOLOGICAL MANIPULATIONS; CULTURED HIPPOCAMPAL-NEURONS; ACUTE
FUNCTIONAL TOLERANCE; GLUTAMATE RECEPTORS; LOCOMOTOR-ACTIVITY; RAPID
TOLERANCE; MOUSE STRAINS
AB Background: The glutamate system plays a major role in mediating EtOH's effects on brain and behavior, and is implicated in the pathophysiology of alcohol-related disorders. N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 (dizocilpine) interact with EtOH at the behavioral level, but the molecular basis of this interaction is unclear.
Methods: We first characterized the effects of MK-801 treatment on responses to the ataxic (accelerating rotarod), hypothermic and sedative/hypnotic effects of acute EtOH administration in C57BL/6J and 129/SvImJ inbred mice. Effects of another NMDAR antagonist, phencyclidine, on EtOH-induced sedation/hypnosis were also assessed. Gene knockout of the NMDAR subunit NR2A or L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate GluR1 or pharmacological antagonism of the NMDAR subunit NR2B (via Ro 25-6981) was employed to examine whether inactivating any one of these glutamate signaling molecules modified MK-801's effect on EtOH-related, behaviors.
Results: MK-801 markedly potentiated the ataxic effects of 1.75 g/kg EtOH and the sedative/hypnotic effects of 3.0 g/kg EtOH, but not the hypothermic effects of 3.0 g/kg EtOH, in C57BL/6J and 129/SvImJ mice. Phencyclidine potentiated EtOH-induced sedation/hypnosis in both inbred strains. Neither NR2A nor GluR1 KO significantly altered basal EtOH-induced ataxia, hypothermia, or sedation/hypnosis. Ro 25-6981 modestly increased EtOH-induced sedation/hypnosis. The ability of MK-801 to potentiate EtOH-induced ataxia and sedation/hypnosis was unaffected by GluR1 KO or NR2B antagonism. NR2A KO partially reduced MK-801 + EtOH-induced sedation/hypnosis, but not ataxia or hypothermia.
Conclusions: Data confirm a robust and response-specific potentiating effect of MK-801 on sensitivity to EtOH's intoxicating effects. Inactivation of three major components of glutamate signaling had no or only partial impact on the ability of MK-801 to potentiate behavioral sensitivity to EtOH. Further work to elucidate the mechanisms underlying NMDAR x EtOH interactions could ultimately provide novel insight into the role of NMDARs in alcoholism and its treatment.
C1 [Palachick, Benjamin; Enoch, Abigail J.; Karlsson, Rose-Marie; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
[Chen, Yi-Chyan] Triserv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan.
[Mishina, Masayoshi] Univ Tokyo, Grad Sch Med, Dept Mol Neurobiol & Pharmacol, Tokyo 1138654, Japan.
RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA.
EM holmesan@mail.nih.gov
FU Intramural NIH HHS [Z01 AA000411-04]; NIAAA NIH HHS [Z01 AA000411]
NR 92
TC 22
Z9 25
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG
PY 2008
VL 32
IS 8
BP 1479
EP 1492
DI 10.1111/j.1530-0277.2008.00715.x
PG 14
WC Substance Abuse
SC Substance Abuse
GA 335YM
UT WOS:000258331500016
PM 18565157
ER
PT J
AU Choyke, PL
AF Choyke, Peter L.
TI Radiologic evaluation of hematuria: Guidelines from the American College
of Radiology's appropriateness criteria
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Article
ID ASYMPTOMATIC MICROSCOPIC HEMATURIA; URINARY COLLECTING SYSTEM; ROW CT
UROGRAPHY; INTRAVENOUS UROGRAPHY; ADULTS; MICROHEMATURIA; DIAGNOSIS;
ULTRASONOGRAPHY; STRATEGIES; CARCINOMAS
AB Hematuria, symptomatic and incidental, that involves more than three red blood cells per high-power field on two of three properly collected urinalysis specimens warrants some type of imaging to evaluate the upper tracts. Traditionally, excretory urography or the intravenous pyelogram has been the mainstay of the hematuria work-up, but computed tomography urography has more recently been recognized to have significant advantages. Multidetector computed tomography urography, a cross-sectional technique, is less susceptible to overlying bowel gas and more sensitive for detection of small tumors and calculi. Moreover, intravenous-pyelogram-like images can be obtained by using reconstruction techniques. In specific cases, ultrasound examination and magnetic resonance imaging can also be useful, and are particularly helpful in children and pregnant women. Neither modality has the sensitivity of computed tomography for calculi, but small tumors may be visible on magnetic resonance imaging. This article reviews the appropriateness criteria for the various radiologic imaging tests used in the evaluation of hematuria, as proposed by the American College of Radiology.
C1 NCI, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Bldg 10,Room 1B40, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
NR 30
TC 15
Z9 16
U1 0
U2 1
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
EI 1532-0650
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD AUG 1
PY 2008
VL 78
IS 3
BP 347
EP 352
PG 6
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 334UY
UT WOS:000258247900010
PM 18711950
ER
PT J
AU Kontos, MC
Jamal, S
Tatum, JL
Ornato, JP
Jesse, RL
AF Kontos, Michael C.
Jamal, Sameer
Tatum, James L.
Ornato, Joseph P.
Jesse, Robert L.
TI Predictive power of systolic function and congestive heart failure in
patients with patients admitted for chest pain without ST elevation in
the troponin era
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; VENTRICULAR
EJECTION FRACTION; SEGMENT ELEVATION; INTERNATIONAL TRIAL; GLOBAL
REGISTRY; MORTALITY; OUTCOMES; RISK; STRATIFICATION
AB Background Impaired systolic function and congestive heart failure (CHF) are powerful predictors of adverse outcomes in patients with myocardial infarction (MI). However, there are little data in which both of these variables were assessed in heterogenous patients admitted from the emergency department for exclusion of ischemia.
Methods Consecutive patients admitted for MI exclusion who had ejection fraction (EF) measured were included. Systolic dysfunction was defined as EF < 40%. Congestive heart failure was diagnosed based on clinical or x-ray evidence in the first 24 hours. Multivariate analysis was used to determine predictors of 30-day and 1-year mortality.
Results of the 4,343 consecutive patients admitted, 3,682 (85%) had EF assessed (including 97% of the troponin I [Tnl]-positive patients) and were included. One-year unadjusted mortality was 9.5%, but in the presence of systolic dysfunction or CHF, it increased to 22% and 26%, respectively. The most important multivariate predictors of 30-day and 1-year mortality were similar and included CHF (OR for 1-year mortality 2.5, 95% CI 1.9-3.4), TnI elevations (OR 2.0, 95% CI 1.5-2.6), and severe renal failure (OR 5.2, 95% CI 3.7-7.2). Systolic dysfunction was predictive of 1 year (OR 1.9, 95% CI 1.4-2.5 but not 30-day mortality. Results were similar in the 3,018 patients who were troponin-negative.
Conclusions Congestive heart failure is an independent predictor of both short- and long-term mortality in patients admitted for MI exclusion. In contrast, systolic dysfunction predicts long-term but not short-term mortality. One cannot be used as a surrogate for the other.
C1 [Kontos, Michael C.; Jamal, Sameer; Jesse, Robert L.] Virginia Commonwealth Univ, Med Coll Virginia, Div Cardiol, Dept Internal Med, Richmond, VA 23298 USA.
[Kontos, Michael C.; Ornato, Joseph P.] Virginia Commonwealth Univ, Dept Emergency Med, Richmond, VA 23298 USA.
[Kontos, Michael C.] Virginia Commonwealth Univ, Dept Radiol, Richmond, VA 23298 USA.
[Tatum, James L.] NCI, Dept Canc Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Kontos, MC (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Div Cardiol, Dept Internal Med, Room 285,Gateway Bldg,2nd Floor,POB 980051,1200 E, Richmond, VA 23298 USA.
EM mkontos@mcvh-vcu.edu
NR 32
TC 2
Z9 2
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD AUG
PY 2008
VL 156
IS 2
BP 329
EP 335
DI 10.1016/j.ahj.2008.03.013
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 335ZF
UT WOS:000258333400020
PM 18657664
ER
PT J
AU Lippincott, MF
Carlow, A
Desai, A
Blum, A
Rodrigo, M
Patibandla, S
Zalos, G
Smith, K
Schenke, WH
Csako, G
Waclawiw, MA
Cannon, RO
AF Lippincott, Margaret F.
Carlow, Andrea
Desai, Aditi
Blum, Amon
Rodrigo, Maria
Patibandla, Sushmitha
Zalos, Gloria
Smith, Kevin
Schenke, William H.
Csako, Gyorgy
Waclawiw, Myron A.
Cannon, Richard O., III
TI Relation of endothelial function to cardiovascular risk in women with
sedentary occupations and without known cardiovascular disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; POSTMENOPAUSAL WOMEN; OLDER-ADULTS; EXERCISE;
INCREASES; ESTROGEN; VASODILATION; EXPRESSION; MORTALITY; FITNESS
AB Our purpose was to determine predictors of endothelial function and potential association with cardiovascular risk in women with sedentary occupations, in whom obesity-associated risk factors may contribute to excess morbidity and mortality. Ninety consecutive women (age range 22 to 63 years, 22 overweight (body mass index [BMI] >= 25 to 29.9 kg/m(2)) and 42 obese (BMI >= 30 kg/m(2)), had vital signs, lipids, insulin, glucose, high-sensitivity C-reactive protein, and sex hormones measured. Endothelial function was determined using brachial artery flow-mediated dilation after 5 minutes of forearm ischemia. Treadmill stress testing was performed with gas exchange analysis at peak exercise (peak oxygen consumption [Vo(2)]) to assess cardiorespiratory fitness. Brachial artery reactivity was negatively associated with Framingham risk score (r = -0.3542, p = 0.0007). Univariate predictors of endothelial function included peak Vo2 (r = 0.4483, p <0.0001), age (r = -0.3420, p = 0.0010), BMI (r = -0.3065, p = 0.0035), and high-sensitivity C-reactive protein (r = -0.2220, p = 0.0400). Using multiple linear regression analysis with stepwise modeling, peak Vo(2) (p = 0.0003) was the best independent predictor of brachial artery reactivity, with age as the only other variable reaching statistical significance (p = 0.0436) in this model. In conclusion, endothelial function was significantly associated with cardiovascular risk in women with sedentary occupations, who were commonly overweight or obese. Even in the absence of routine exercise, cardiorespiratory fitness, rather than conventional risk factors or body mass, is the dominant predictor of endothelial function and suggests a modifiable approach to risk. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Lippincott, Margaret F.; Carlow, Andrea; Desai, Aditi; Blum, Amon; Rodrigo, Maria; Patibandla, Sushmitha; Zalos, Gloria; Smith, Kevin; Schenke, William H.; Cannon, Richard O., III] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA.
[Waclawiw, Myron A.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Cannon, RO (reprint author), NHLBI, Translat Med Branch, Bldg 10, Bethesda, MD 20892 USA.
EM cannonr@nih.gov
OI Lippincott, Margaret/0000-0002-3533-1999
FU Intramural NIH HHS [Z01 HL005067-02]
NR 22
TC 11
Z9 11
U1 1
U2 4
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 AUG 1
PY 2008
VL 102
IS 3
BP 348
EP 352
DI 10.1016/j.amjcard.2008.03.069
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 331LD
UT WOS:000258012800019
PM 18638600
ER
PT J
AU Shea, MK
Dallal, GE
Dawson-Hughes, B
Ordovas, JM
O'Donnell, CJ
Gundberg, CM
Peterson, JW
Booth, SL
AF Shea, M. Kyla
Dallal, Gerard E.
Dawson-Hughes, Bess
Ordovas, Jose M.
O'Donnell, Christopher J.
Gundberg, Caren M.
Peterson, James W.
Booth, Sarah L.
TI Vitamin K, circulating cytokines, and bone mineral density in older men
and women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CORONARY-HEART-DISEASE; KAPPA-B LIGAND; POSTMENOPAUSAL WOMEN; RECEPTOR
ACTIVATOR; RHEUMATOID-ARTHRITIS; INFLAMMATORY MARKERS; PHYLLOQUINONE
INTAKE; D SUPPLEMENTATION; CONTROLLED-TRIAL; OSTEOPROTEGERIN
AB Background: Vitamin K modulates cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin in vitro.
Objective: The objective of this study was to assess 1) associations between measures of vitamin K status [plasma phylloquinone and serum percentage of undercarboxylated osteocalcin (%ucOC)] and IL-6, osteoprotegerin, and C-reactive protein (CRP) concentrations and 2) the effect of daily 500 mu g phylloquinone supplementation for 3 y on cytokine concentrations.
Design: Concentrations of IL-6, osteoprotegerin, and CRP and bone mineral density (BMD) were measured at baseline and after 3 y of follow-up in 379 healthy men and women (60-81 y; 58.5% women) participating in a randomized trial that studied the effect of vitamin K supplementation on bone loss.
Results: Cross-sectionally, plasma phylloquinone was inversely associated with IL-6 and CRP, whereas serum %ucOC was inversely associated with IL-6. Osteoprotegerin was associated positively with plasma phylloquinone and inversely with %ucOC. No differences were observed in the 3-y change in IL-6, osteoprotegerin, and CRP concentrations between participants who received phylloquinone supplementation and those who did not. Overall, no association was observed between the 3-y changes in circulating cytokines and BMD.
Conclusions: Poor vitamin K status was associated with high concentrations of cytokines involved in bone turnover, but vitamin K supplementation did not confer a decrease in cytokine concentrations. The healthy status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentrations. This trial was registered with www. clinicaltrials. gov as NCT00183001.
C1 [Shea, M. Kyla; Dallal, Gerard E.; Dawson-Hughes, Bess; Ordovas, Jose M.; Peterson, James W.; Booth, Sarah L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[O'Donnell, Christopher J.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA.
[Gundberg, Caren M.] Yale Univ, Sch Med, Dept Orthopaed, New Haven, CT USA.
RP Booth, SL (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM sarah.booth@tufts.edu
OI Ordovas, Jose/0000-0002-7581-5680
FU US Department of Agriculture, Agricultural Research Service
[58-1950-7-707]; National Institutes of Health [AG14759, HL69272, T32
HL69772-01A1]; American Heart Association [0515605T]
FX Supported by the US Department of Agriculture, Agricultural Research
Service (cooperative agreement 58-1950-7-707), National Institutes of
Health (AG14759, HL69272, and T32 HL69772-01A1), and American Heart
Association (0515605T).
NR 47
TC 35
Z9 35
U1 0
U2 7
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG 1
PY 2008
VL 88
IS 2
BP 356
EP 363
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 346FY
UT WOS:000259055300015
PM 18689371
ER
PT J
AU Bao, Y
Stolzenberg-Solomon, R
Jiao, L
Silverman, DT
Subar, AF
Park, Y
Leitzmann, MF
Hollenbeck, A
Schatzkin, A
Michaud, DS
AF Bao, Ying
Stolzenberg-Solomon, Rachael
Jiao, Li
Silverman, Debra T.
Subar, Amy F.
Park, Yikyung
Leitzmann, Michael F.
Hollenbeck, Albert
Schatzkin, Arthur
Michaud, Dominique S.
TI Added sugar and sugar-sweetened foods and beverages and the risk of
pancreatic cancer in the National Institutes of Health-AARP Diet and
Health Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID GLYCEMIC LOAD; DIABETES-MELLITUS; MALE SMOKERS; COHORT; INDEX;
ASSOCIATION; CONSUMPTION; GLUCOSE; HISTORY; INSULIN
AB Background: Although it has been hypothesized that hyperglycemia, hyperinsulinemia, and insulin resistance are involved in the development of pancreatic cancer, results from epidemiologic studies of added sugar intake are inconclusive.
Objective: Our objective was to investigate whether the consumption of total added sugar and sugar-sweetened foods and beverages is associated with pancreatic cancer risk.
Design: In 1995 and 1996, we prospectively examined 487 922 men and women aged 50-71 y and free of cancer and diabetes. Total added dietary sugar intake (in tsp/d; based on the US Department of Agriculture's Pyramid Servings Database) was assessed with a food-frequency questionnaire. Relative risks (RRs) and 95% CIs were calculated with adjustment for total energy and potential confounding factors.
Results: During an average 7.2 y of follow-up, 1258 incident pancreatic cancer cases were ascertained. The median intakes for the lowest and highest quintiles of total added sugar intake were 12.6 (3 tsp/d) and 96.2 (22.9 tsp/d) g/d, respectively. No overall greater risk of pancreatic cancer was observed in men or women with high intake of total added sugar or sugar-sweetened foods and beverages. For men and women combined, the multivariate RRs of the highest versus lowest intake categories were 0.85 (95% CI: 0.68, 1.06; P for trend = 0.07) for total added sugar, 1.01 (0.82,1.23; P for trend = 0.58) for sweets, 0.98 (0.82,1.18; P for trend = 0.49) for dairy desserts, 1.12 (0.91,1.39; P for trend = 0.35) for sugar added to coffee and tea, and 1.01 (0.77,1.31; P for trend = 0.76) for regular soft drinks.
Conclusion: Our results do not support the hypothesis that consumption of added sugar or of sugar-sweetened foods and beverages is associated with overall risk of pancreatic cancer.
C1 [Bao, Ying; Michaud, Dominique S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stolzenberg-Solomon, Rachael; Jiao, Li; Silverman, Debra T.; Park, Yikyung; Leitzmann, Michael F.; Schatzkin, Arthur; Michaud, Dominique S.] NCI, Div Canc Epidemiol, Rockville, MD USA.
[Stolzenberg-Solomon, Rachael; Jiao, Li; Silverman, Debra T.; Park, Yikyung; Leitzmann, Michael F.; Schatzkin, Arthur; Michaud, Dominique S.] NCI, Div Genet, Rockville, MD USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
[Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London SW7 2AZ, England.
RP Bao, Y (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge 911, Boston, MA 02115 USA.
EM ybao@hsph.harvard.edu
RI Michaud, Dominique/I-5231-2014;
OI Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, National Institutes of Health
FX Supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health.
NR 25
TC 31
Z9 32
U1 1
U2 13
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG 1
PY 2008
VL 88
IS 2
BP 431
EP 440
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 346FY
UT WOS:000259055300024
PM 18689380
ER
PT J
AU Brannon, PM
Yetley, EA
Bailey, RL
Picciano, MF
AF Brannon, Patsy M.
Yetley, Elizabeth A.
Bailey, Regan L.
Picciano, Mary Frances
TI Overview of the conference "Vitamin D and Health in the 21st Century: an
Update"
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; D SUPPLEMENTATION; RESEARCH NEEDS; SUN
EXPOSURE; CALCIUM; 25-HYDROXYVITAMIN-D; SERUM; RISK; CHOLECALCIFEROL;
CANCER
AB We summarize the key findings, strength of the evidence, and research needs identified in the National Institutes of Health conference "Vitamin D and Health in the 21st Century: an Update," which was held in September 2007; a systematic evidence-based review; and a National Institutes of Health roundtable discussion held after the conference by scientists with relevant expertise. The evidence-based review addressed 5 questions on 25-hydroxyvitamin D [25(OH) D] and functional outcomes across the life cycle and response to exposure, bone health outcomes of supplementation, risks and benefits of sun exposure, and adverse outcomes. These questions also framed the conference and roundtable discussions. Researchers have made considerable progress in understanding the relation of 25(OH) D to bone health outcomes in the elderly and in postmenopausal women, but we know less about its impact on other stages of the life cycle and in racial and ethnic groups. Limitations of the existing data include the failure of many studies to control for important confounders [baseline 25(OH) D concentration, skin pigmentation, body mass index, compliance, etc], sparse data on key vulnerable populations (dark-skinned persons, reproducing women, infants, children, and adolescents), problems of accuracy and excessive variability in measuring 25(OH) D, lack of established relation of 25(OH) D with functional outcomes except in the elderly, and limited information on the effects of vitamin D independent of calcium, magnesium, and phosphate. Future research should determine and validate across the life cycle relevant functional outcomes for bone and other health factors as well as adverse outcomes for the biomarker of exposure, 25(OH) D, to enable assessment of the role of vitamin D status in health maintenance and disease prevention.
C1 [Brannon, Patsy M.; Yetley, Elizabeth A.; Bailey, Regan L.; Picciano, Mary Frances] NIH, Off Dietary Supplements, US Dept HHS, Bethesda, MD 20892 USA.
[Brannon, Patsy M.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
RP Picciano, MF (reprint author), NIH, Off Dietary Supplements, US Dept HHS, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA.
EM piccianm@od.nih.gov
NR 27
TC 58
Z9 60
U1 1
U2 10
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG 1
PY 2008
VL 88
IS 2
SU S
BP 483S
EP 490S
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 346GK
UT WOS:000259056600001
PM 18689388
ER
PT J
AU Yetley, EA
AF Yetley, Elizabeth A.
TI Assessing the vitamin D status of the US population
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; DIETARY-SUPPLEMENT USE; FAT-SOLUBLE
VITAMINS; STANDARD REFERENCE MATERIALS; 3RD NATIONAL-HEALTH;
UNITED-STATES; HYPOVITAMINOSIS-D; FORTIFIED MILK; WHITE WOMEN; HUMAN
SERUM
AB This article describes the information currently available in the National Nutrition Monitoring System that is relevant to assessing the vitamin D status of US population groups, the strengths and limitations of this information, and selected results of vitamin D nutritional status assessments. The National Health and Nutrition Examination Survey (NHANES) provides information on vitamin D intakes only from 1988 to 1994. NHANES collected information on supplement use and circulating 25-hydroxyvitamin D [25(OH)D] concentrations from 1988 through current surveys. The National Nutrient Database for Standard Reference started providing limited data on the vitamin D content of foods in 2002 and continues to update these values. The Food Label and Package Survey provides 2006-2007 label information on vitamin D fortification of marketed foods. Despite limitations in the available data and controversies about appropriate criteria for evaluating vitamin D status among population groups, we can make some useful comparisons of vitamin D status among life-stage groups. In general, males have higher vitamin D intakes and 25(OH)D concentrations than do females. Children tend to have higher vitamin D status than adults. The increasing use of multivitamin-mineral dietary supplements in younger to older adults is not associated with a corresponding increase in serum 25(OH)D concentrations. In general, leaner individuals have higher circulating concentrations of 25(OH)D and supplement use than do heavier individuals. Finally, non-Hispanic whites tend to have higher vitamin D status than do non-Hispanic blacks and Mexican Americans.
C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Yetley, EA (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01, Bethesda, MD 20892 USA.
EM beth@yetley.com
NR 50
TC 155
Z9 166
U1 1
U2 14
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG 1
PY 2008
VL 88
IS 2
SU S
BP 558S
EP 564S
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 346GK
UT WOS:000259056600015
PM 18689402
ER
PT J
AU Davis, CD
AF Davis, Cindy D.
TI Vitamin D and cancer: current dilemmas and future research needs
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID D-RECEPTOR POLYMORPHISMS; PROSTATE-CANCER; COLON-CANCER;
ULTRAVIOLET-RADIATION; BREAST-CANCER; RISK; CELLS; CALCIUM; PREVENTION;
EXPOSURE
AB A diversity of scientific literature supports a role for vitamin D in decreasing colorectal cancer incidence, but the available evidence provides only limited support for an inverse association between vitamin D status and the risk of other types of cancer. We need additional studies analyzing the dose-response relation between vitamin D status and cancer risk, the optimal level of 25-hydroxyvitamin D, the length of time required to observe an effect, and the time period of life when exposure is most relevant. Studies of vitamin D receptor polymorphisms have found that not all polymorphisms have the same association with cancer, and the cancer site could further dictate which polymorphisms might be most important; this indicates a need for more research on gene-environment interactions. Several dietary components and the balance between energy intake and expenditure influence vitamin D metabolism. These studies show that scientists need to identify confounders and modifiers of the biological response to vitamin D, including dietary factors, lifestyle factors such as exercise, and race or ethnicity. Transgenic and knockout animals are powerful tools for identifying the molecular targets of bioactive food components. Scientists should therefore make increased use of these models to identify molecular targets for vitamin D. Many research gaps relate to the need to develop predictive, validated, and sensitive biomarkers, including biomarkers that researchers can use to reliably evaluate intake or exposure to vitamin D, assess one or more specific biological effects that are linked to cancer, and effectively predict individual susceptibility as a function of nutrient-nutrient interactions and genetics.
C1 NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3159, Bethesda, MD 20892 USA.
EM davisci@mail.nih.gov
NR 31
TC 66
Z9 71
U1 1
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 AUG 1
PY 2008
VL 88
IS 2
SU S
BP 565S
EP 569S
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 346GK
UT WOS:000259056600016
PM 18689403
ER
PT J
AU Brannon, PM
Yetley, EA
Bailey, RL
Picciano, MF
AF Brannon, Patsy M.
Yetley, Elizabeth A.
Bailey, Regan L.
Picciano, Mary Frances
TI Summary of roundtable discussion on vitamin D research needs
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
AB We summarize the discussions of a roundtable following the conference "Vitamin D and Health in the 21st Century: an Update." The roundtable participants offered additional information on vitamin D research needs from a critical, impartial, and interdisciplinary perspective. Although the group recognized the progress to date, they found that the available evidence on the relation of 25-hydroxyvitamin D, dietary intake, status, functional health, and adverse outcomes has significant limitations because most studies have been short term, have failed to consider important confounders such as baseline vitamin D status and body mass index, and did not study key populations. To meet these data gaps, the roundtable identified several overarching research needs: 1) long-term, high-quality dose-response studies with relevant outcomes, including bone health, other functional outcomes (such as immune function, autoimmune disorders, and chronic disease prevention), and adverse outcomes (such as hypercalcemia and hypercalcuria), especially in understudied population groups such as dark-skinned individuals, infants, adolescents, reproductive-aged women, and pregnant and lactating women; 2) further research to understand the relation of 25-hydroxyvitamin D threshold values to relevant functional outcomes in each life stage and in racial and ethnic groups; 3) further research to understand the metabolic partitioning, fate, and mobilization of key vitamin D metabolites at recommended and greater than recommended intakes to assess the availability of stored vitamin D, relative contributions of endogenously produced and dietary vitamin D, and impact of important confounders (such as body mass index) on vitamin D status; and 4) further research to define the maximal, long-term vitamin D intake to ensure safety for all humans.
C1 [Brannon, Patsy M.; Yetley, Elizabeth A.; Bailey, Regan L.; Picciano, Mary Frances] NIH, Off Dietary Supplements, US Dept HHS, Bethesda, MD 20892 USA.
[Brannon, Patsy M.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
RP Picciano, MF (reprint author), NIH, Off Dietary Supplements, US Dept HHS, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA.
EM piccianm@od.nih.gov
NR 5
TC 21
Z9 21
U1 1
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 AUG 1
PY 2008
VL 88
IS 2
SU S
BP 587S
EP 592S
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 346GK
UT WOS:000259056600020
PM 18689407
ER
PT J
AU Queiroga, EM
Gualco, G
Chioato, L
Harrington, WJ
Araujo, I
Weiss, LM
Bacchi, CE
AF Queiroga, Eduardo M.
Gualco, Gabriela
Chioato, Lucimara
Harrington, William J., Jr.
Araujo, Iguaracyra
Weiss, Lawrence M.
Bacchi, Carlos E.
TI Viral studies in Burkitt lymphoma - Association with Epstein-Barr virus
but not HHV-8
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Burkitt lymphoma; Kaposi sarcoma-associated herpesvirus; human
herpesvirus 8; KSHV/HHV-8; LANA protein; HIV; immunohistochemistry;
polymerase chain reaction; PCR
ID KAPOSIS-SARCOMA; LYMPHOPROLIFERATIVE DISORDERS; CASTLEMAN-DISEASE;
PLASMABLASTIC VARIANT; HODGKIN-LYMPHOMA; HUMAN-HERPESVIRUS-8; BRAZIL;
PCR; GENE; MORPHOLOGY
AB Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma, composed of a monomorphic population of medium-sized B cells with a high proliferation rate and a consistent MYC translocation. Epstein-Barr virus (EBV) has been associated with BL with different frequencies depending on the clinical variant. Kaposi sarcoma-associated herpesvirus, or human herpesvirus 8 (HHV-8), infects a wide range of normal cells, having a well-established role in the pathogenesis of various neoplasms, including Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease (MCD) and MCD-associated plasmablastic lymphoma. In secondary immunodeficiencies, such as HIV-1 infection and organ transplantation, HHV-8 is considered an opportunistic pathogen linked to the development of lymphomas in patients with AIDS and HIV+ patients. We studied the association of EBV and HHV-8 by immunohistochemical analysis, in situ hybridization, and polymerase chain reaction in a large number of well-characterized BLs. EBV was present in 45.0% of all BL cases with higher incidence in the pediatric group; most cases were EBV type A. We found no association of BL with HHV-8 in EBV+ BL or in EBV-cases, including the HIV+ BL group.
C1 [Queiroga, Eduardo M.; Gualco, Gabriela; Chioato, Lucimara; Bacchi, Carlos E.] Pathol Reference Lab, Sao Paulo, Brazil.
[Harrington, William J., Jr.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Harrington, William J., Jr.] AIDS & TB Program, Fogarty Int Ctr, Sylvester Canc Ctr, Miami, FL 33136 USA.
[Araujo, Iguaracyra] Prof Edgard Santos Univ Hosp, Salvador, BA, Brazil.
[Weiss, Lawrence M.] City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA.
RP Bacchi, CE (reprint author), Rua Major Leonidas Cardoso,739 Botucatu, BR-18602010 Sao Paulo, Brazil.
FU NCI NIH HHS [R01 CA121935, 5R01CA082274, 5R01CA112217, R01 CA082274, R01
CA082274-08, R01 CA112217, R01 CA112217-03, R01 CA121935-03, U01
CA121947-016821]
NR 38
TC 9
Z9 10
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD AUG
PY 2008
VL 130
IS 2
BP 186
EP 192
DI 10.1309/2CNAWY6GAR0VQAXX
PG 7
WC Pathology
SC Pathology
GA 328YG
UT WOS:000257833500005
PM 18628086
ER
PT J
AU Hortin, GL
AF Hortin, Glen L.
TI Of immunounreactive urinary albumin and unicorns
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Letter
ID HPLC
C1 Warren Magnuson Clin Ctr, Natl Inst Hlth, Dept Lab Med, Bethesda, MD USA.
RP Hortin, GL (reprint author), Warren Magnuson Clin Ctr, Natl Inst Hlth, Dept Lab Med, Bethesda, MD USA.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD AUG
PY 2008
VL 130
IS 2
BP 314
EP 315
PG 2
WC Pathology
SC Pathology
GA 328YG
UT WOS:000257833500024
PM 18697291
ER
PT J
AU Agalliu, I
Salinas, CA
Hansten, PD
Ostrander, EA
Stanford, JL
AF Agalliu, Ilir
Salinas, Claudia A.
Hansten, Philip D.
Ostrander, Elaine A.
Stanford, Janet L.
TI Statin use and risk of prostate cancer: Results from a population-based
epidemiologic study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; hydroxymethylglutaryl-CoA reductase inhibitors;
obesity; odds ratio; prostatic neoplasms
ID CHOLESTEROL-LOWERING DRUGS; REDUCTASE INHIBITORS; COHORT;
PHARMACOKINETICS; METAANALYSIS; PRAVASTATIN; PATHWAY; SAFETY; HEALTH
AB Epidemiologic studies of statin use in relation to prostate cancer risk have been inconclusive. Recent evidence, however, suggests that longer-term use may reduce risk of more advanced disease. The authors conducted a population-based study of 1,001 incident prostate cancer cases diagnosed in 2002-2005 and 942 age-matched controls from King County, Washington, to evaluate risk associated with statin use. Logistic regression was used to generate odds ratios for ever use, current use, and duration of use. No overall association was found between statin use and prostate cancer risk (odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2 for current use; OR = 1.1, 95% CI: 0.7, 1.8 for > 10 years' use), even for cases with more advanced disease. Risk related to statin use, however, was modified by body mass index (interaction p = 0.04). Obese men (BMI >= 30 kg/m(2)) who used statins had an increased risk (OR = 1.5, 95% CI: 1.0, 2.2) relative to obese nonusers, with a stronger association for longer-term use (OR = 1.8, 95% CI: 1.1, 3.0 for >= 5 years' use). Although statin use was not associated with overall prostate cancer risk, the finding of an increased risk associated with statin use among obese men, particularly use for extended durations, warrants further investigation.
C1 [Agalliu, Ilir; Salinas, Claudia A.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA.
[Agalliu, Ilir] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Salinas, Claudia A.; Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Hansten, Philip D.] Univ Washington, Sch Pharm, Dept Pharm, Seattle, WA 98195 USA.
[Ostrander, Elaine A.] NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA.
EM jstanfor@fhcrc.org
OI Ostrander, Elaine/0000-0001-6075-9738
FU Intramural NIH HHS; NCI NIH HHS [R01-CA092579, N01 CN005230, R01
CA092579]
NR 36
TC 97
Z9 97
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2008
VL 168
IS 3
BP 250
EP 260
DI 10.1093/aje/kwn141
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 328GJ
UT WOS:000257786100002
PM 18556686
ER
PT J
AU Adams, KF
Leitzmann, MF
Albanes, D
Kipnis, V
Moore, SC
Schatzkin, A
Chow, WH
AF Adams, Kenneth F.
Leitzmann, Michael F.
Albanes, Demetrius
Kipnis, Victor
Moore, Steven C.
Schatzkin, Arthur
Chow, Wong-Ho
TI Body size and renal cell cancer incidence in a large US cohort study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE body height; body mass index; body size; carcinoma; renal cell; obesity;
overweight; waist-hip ratio
ID MASS INDEX; RISK-FACTORS; PHYSICAL-ACTIVITY; KIDNEY CANCER;
UNITED-STATES; POSTMENOPAUSAL WOMEN; ENERGY-INTAKE; CARCINOMA; OBESITY;
HYPERTENSION
AB Renal cell cancer (RCC) incidence has increased in the United States over the past three decades. The authors analyzed the association between body mass index (BMI) and invasive RCC in the National Institutes of Health (NIH)-AARP Diet and Health Study, a large, prospective cohort aged 50-71 years at baseline initiated in 1995-1996, with follow-up through December 2003. Detailed analyses were conducted in a subcohort responding to a second questionnaire, including BMI at younger ages (18, 35, and 50 years); weight change across three consecutive age intervals; waist, hip, and waist-to-hip ratio; and height at age 18 years. Incident RCC was diagnosed in 1,022 men and 344 women. RCC was positively and strongly related to BMI at study baseline. Among subjects analyzed in the subcohort, RCC associations were strongest for baseline BMI and BMI recalled at age 50 years and were successively attenuated for BMI recalled at ages 35 and 18 years. Weight gain in early (18-35 years of age) and mid- (35-50 years of age) adulthood was strongly associated with RCC, whereas weight gain after midlife (age 50 years to baseline) was unrelated. Waist-to hip ratio was positively associated with RCC in women and with height at age 18 years in both men and women.
C1 [Adams, Kenneth F.; Leitzmann, Michael F.; Albanes, Demetrius; Moore, Steven C.; Schatzkin, Arthur; Chow, Wong-Ho] Natl Canc Inst, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,Natl Inst Hlth, Rockville, MD USA.
[Kipnis, Victor] Natl Canc Inst, Biometry Res Grp, Canc Prevent Div, Dept Hlth & Human Serv,Natl Inst Hlth, Rockville, MD USA.
RP Adams, KF (reprint author), Hlth Partners Res Fdn, Mail Stop 21111R,8170 33rd Ave S,POB 1524, Minneapolis, MN 55440 USA.
EM kenneth.f.adams@healthpartners.com
RI Albanes, Demetrius/B-9749-2015; Moore, Steven/D-8760-2016
OI Moore, Steven/0000-0002-8169-1661
FU Intramural NIH HHS
NR 42
TC 71
Z9 72
U1 1
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 AUG 1
PY 2008
VL 168
IS 3
BP 268
EP 277
DI 10.1093/aje/kwn122
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 328GJ
UT WOS:000257786100004
PM 18544571
ER
PT J
AU Gordeuk, VR
Reboussin, DM
McLaren, CE
Barton, JC
Acton, RT
McLaren, GD
Harris, EL
Reiss, JA
Adams, PC
Speechley, M
Phatak, PD
Sholinsky, P
Eckfeldt, JH
Chen, WP
Passmore, L
Dawkins, FW
AF Gordeuk, Victor R.
Reboussin, David M.
McLaren, Christine E.
Barton, James C.
Acton, Ronald T.
McLaren, Gordon D.
Harris, Emily L.
Reiss, Jacob A.
Adams, Paul C.
Speechley, Mark
Phatak, Pradyumna D.
Sholinsky, Phyliss
Eckfeldt, John H.
Chen, Wen-Pin
Passmore, Leah
Dawkins, Fitzroy W.
TI Serum ferritin concentrations and body iron stores in a multicenter,
multiethnic primary-care population
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID OVERLOAD SCREENING HEIRS; HEREDITARY HEMOCHROMATOSIS; TRANSFERRIN
SATURATION; DISEASE; PHLEBOTOMY; DIAGNOSIS; THERAPY; BLOOD; LIVER; RISK
AB How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 mu g/L (men), >200 mu g/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 mu g/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 mu g/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but 4 g. In conclusion, serum ferritin >900 mu g/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 mu g/L in male C282Y homozygotes is predictive of moderately increased iron stores.
C1 [Gordeuk, Victor R.; Dawkins, Fitzroy W.] Howard Univ, Dept Med, Washington, DC 20060 USA.
[Gordeuk, Victor R.; Dawkins, Fitzroy W.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20060 USA.
[Reboussin, David M.] Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
[McLaren, Christine E.] Univ Calif Irvine, Div Epidemiol, Dept Epidemiol, Irvine, CA USA.
[Barton, James C.] So Iron Disorders Ctr, Birmingham, AL 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, Birmingham, AL USA.
[Acton, Ronald T.] Univ Alabama, Dept Epidemiol & Int Hlth, Birmingham, AL USA.
[McLaren, Gordon D.] 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.
[Harris, Emily L.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA.
[Adams, Paul C.] London Hlth Sci Ctr, Dept Med, London, ON, Canada.
[Speechley, Mark] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada.
[Phatak, Pradyumna D.] Rochester Gen Hosp, Rochester, NY 14621 USA.
[Sholinsky, Phyliss] DHHS, NIH, NHLBI, Epidemiol & Biometry Program, Bethesda, MD USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Chen, Wen-Pin] Chao Family Comprehens Canc Ctr, Orange, CA USA.
RP Acton, RT (reprint author), Howard Univ, Dept Med, 2041 Georgia Ave NW, Washington, DC 20060 USA.
EM vgordeuk@howard.edu
FU NCI NIH HHS [P30 CA062203]; NCRR NIH HHS [M01 RR010284, M01-RR000827,
M01 RR000032, M01-RR00032, M01 RR000827, M01-RR10284]; NHLBI NIH HHS
[N01HC05191, R01 HL083328, N01-HC-05188, N01HC05190, N01-HC-05186,
N01HC05185, N01HC05189, N01 HC005192, UH1 HL003679, UH1-HL03679-05,
N01-HC-05189, N01HC05188, N01HC05186, R01-HL083328, N01-HC-05191,
N01-HC-05190, N01-HC-05185]
NR 35
TC 22
Z9 22
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD AUG
PY 2008
VL 83
IS 8
BP 618
EP 626
DI 10.1002/ajh.21179
PG 9
WC Hematology
SC Hematology
GA 334WB
UT WOS:000258250900004
PM 18429050
ER
PT J
AU Taylor, JK
Schoenbaurn, M
Katon, WJ
Pincus, HA
Hogan, DM
Unutzer, J
AF Taylor, Jennifer K.
Schoenbaurn, Michael
Katon, Wayne J.
Pincus, Harold A.
Hogan, Diane M.
Unuetzer, Juergen
TI Strategies for identifying and channeling patients for depression care
management
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID CASE-FINDING INSTRUMENTS; COST-EFFECTIVENESS; MAJOR DEPRESSION;
OLDER-ADULTS; VALIDITY; PEOPLE
AB Objective: To determine optimal methods-of - identifying enrollees with possible depression for additional depression screening in the context of a-care management program for chronically ill Medicare recipients.
Study Design: Observational analysis of telephone and mail survey and claims data collected for the Medicare Health Support (MHS) program.
Methods:This study examines data from 14,902, participants with diabetes mellitus and/or congestive heart failure in the MHS program administered by Green Ribbon Health, LLC. Depression screening was performed by administering a 2-item screen (the Patient Health Questionnaire 2[PHQ-2]) by telephone or by mail. Additional information about possible depression was drawn from International Classification of Diseases, Ninth Revision (ICD-9) depression diagnoses on claims and from self-reported use of antidepressant medications. We evaluated positive depression screens using the PHQ-2 administered via telephone versus mail, examined variations in screener-positive findings by care manager, and compared rates of positive screens with antidepressant use and with claims, diagnoses of depression.
Results: Almost 14% of participants received an ICD-9 diagnosis of depression during the year before program enrollment; 71% reported taking antidepressants, and 5.1% screened positive for depression on the PHQ-2. We found substantial, variation in positive depression screens by care manager that could not be explained by case mix, prior depression diagnoses, or current depression treatment. After adjusting for demographic and clinical differences, the PHQ-2-positive screen rates were 6.5% by telephone and 14.1% by mail (P < .001).
Conclusion: A multipronged effort composed of mail screening (using the PHQ-2), self-reported antidepressant use, and claims diagnoses of depression may capture the greatest number of enrollees with possible depression.
C1 [Taylor, Jennifer K.; Hogan, Diane M.] Green Ribbon Hlth LLC, Tampa, FL 33609 USA.
[Schoenbaurn, Michael] NIMH, Mental Hlth Serv, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Katon, Wayne J.; Unuetzer, Juergen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Pincus, Harold A.] Columbia Univ, Dept Psychiat, New York, NY USA.
RP Taylor, JK (reprint author), Green Ribbon Hlth LLC, 5201 W Kennedy Blvd,Ste 205, Tampa, FL 33609 USA.
EM jennifer.taylor@greenribbonhealth.com
FU Green Ribbon Health; LLC
FX We thank the many coworkers who supported our efforts, including the
personal nurses at Green Ribbon Health, LLC and our data manager, Mark
Bingener.
NR 23
TC 9
Z9 9
U1 0
U2 1
PU AMER MED PUBLISHING, M W C COMPANY
PI JAMESBURG
PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD AUG
PY 2008
VL 14
IS 8
BP 497
EP 504
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 337LV
UT WOS:000258438500002
PM 18690765
ER
PT J
AU Wallis, D
Lacbawan, F
Jain, M
Kaloustian, VMD
Steiner, CE
Moeschler, JB
Losken, HW
Kaitila, II
Cantrell, S
Proud, VK
Carey, JC
Day, DW
Lev, D
Teebi, AS
Robinson, LK
Hoyme, HE
Al-Torki, N
Siegel-Bartelt, J
Mulliken, JB
Robin, NH
Saavedra, D
Zackai, EH
Muenke, M
AF Wallis, Decann
Lacbawan, Felicitas
Jain, Mahim
Kaloustian, Vazken M. Der
Steiner, Carlos E.
Moeschler, John B.
Losken, H. Wolfgang
Kaitila, Ilkka I.
Cantrell, Stephen
Proud, Virginia K.
Carey, John C.
Day, Donald W.
Lev, Dorit
Teebi, Ahmad S.
Robinson, Luther K.
Hoyme, H. Eugene
Al-Torki, Nadia
Siegel-Bartelt, Jacqueline
Mulliken, John B.
Robin, Nathaniel H.
Saavedra, Dolores
Zackai, Elaine H.
Muenke, Maximilian
TI Additional EFNB1 mutations in craniofrontonasal syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Letter
ID MORPHOGENESIS; EXPRESSION; PHENOTYPE; EPHRIN-B1
C1 [Wallis, Decann; Lacbawan, Felicitas; Jain, Mahim; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Kaloustian, Vazken M. Der] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Steiner, Carlos E.] Univ Estadual Campinas, Dept Med Genet, Sao Paulo, Brazil.
[Moeschler, John B.] Dartmouth Med Ctr, Lebanon, NH USA.
[Losken, H. Wolfgang] Univ Pittsburgh, Pittsburgh, PA USA.
[Kaitila, Ilkka I.] Univ Helsinki, Haartman Inst, Helsinki, Finland.
[Cantrell, Stephen] Univ Med & Dent New Jersey, New Jersey Dent Sch, Newark, NJ 07103 USA.
[Proud, Virginia K.] Childrens Hosp Kings Daughters, Norfolk, VA USA.
[Carey, John C.] Univ Utah, Med Ctr, Salt Lake City, UT USA.
[Lev, Dorit] Wolfson Med Genet Ctr, Inst Clin Genet, Holon, Israel.
[Teebi, Ahmad S.] Weill Cornell Med Coll, New York, NY USA.
[Robinson, Luther K.] Buffalo Sch Med & Biomed Sci, Buffalo, NY USA.
[Hoyme, H. Eugene] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Al-Torki, Nadia] Kuwait Med Genet Ctr, Sulibihkhat, Kuwait.
[Siegel-Bartelt, Jacqueline] Genet Inst Inc, Pasadena, CA USA.
[Mulliken, John B.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA.
[Robin, Nathaniel H.] Univ Alabama, Birmingham, AL USA.
[Saavedra, Dolores] Hosp Gen Dr Manuel Gea Gonzales, Mexico City, DF, Mexico.
[Zackai, Elaine H.] Childrens Hosp Philadelphia, Div Human & Mol Genet, Philadelphia, PA 19104 USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mmuenke@nhgri.nih.gov
RI Steiner, Carlos/B-9319-2014;
OI Steiner, Carlos/0000-0001-5148-3063; Hoyme, Harold/0000-0002-1979-693X
FU Intramural NIH HHS [Z99 HG999999]
NR 20
TC 15
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 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG 1
PY 2008
VL 146A
IS 15
BP 2008
EP 2012
DI 10.1002/ajmg.a.32388
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 338AI
UT WOS:000258476800018
PM 18627045
ER
PT J
AU Zhang, YQ
Guo, XX
Saitz, R
Levy, D
Sartini, E
Niu, JB
Ellison, RC
AF Zhang, Yuqing
Guo, Xinxin
Saitz, Richard
Levy, Daniel
Sartini, Emily
Niu, Jingbo
Ellison, R. Curtis
TI Secular trends in alcohol consumption over 50 years: The Framingham
study
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE alcohol drinking; alcohol-related disorders; cohort studies; drinking
behavior; epidemiology
ID CORONARY-HEART-DISEASE; DRINKING PATTERNS; NATIONAL-HEALTH; RISK
AB BACKGROUND: Population trends in patterns of alcohol use are important data for policymakers but are generally based on repeated cross-sectional surveys.
METHODS: We used self-reported alcohol consumption data collected repeatedly over 50 years (1948-2003) among 8600 Framingham Heart Study participants to determine patterns of alcohol use and disorders according to sex, age, and birth cohorts.
RESULTS: Among drinkers, there was a decrease across succeeding birth cohorts in average alcohol intake: among individuals between ages 30 and 59 years, age-adjusted mean intake was 30.6, 25.5, and 21.0 g/day for those born in 1900-1919, 1920-1939, and 1940-1959, respectively, in men ( P <.001), and 14.2, 12.3, and 10.4 g/day, respectively, in women (P <.001). In all birth cohorts, proportion of abstinence increased and average consumption among drinkers decreased with age. Furthermore, proportion of moderate use was higher but heavy use was lower in the younger birth cohorts than in the older cohorts. The proportion of alcohol from beer decreased and that from wine increased with age for all cohorts. Among the 2 earlier birth cohorts, the cumulative incidence of an alcohol use disorder from age 40 to 79 years was much higher in men (12.8%) than in women (3.8%); it tended to be slightly higher among subjects born after 1920 than among those born 1900-1919.
CONCLUSIONS: We found a decrease in average intake and more wine consumption over the more than 50 years of follow-up. The cumulative incidence of alcohol use disorders, however, did not show a decrease. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Zhang, Yuqing; Niu, Jingbo] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA.
[Zhang, Yuqing; Guo, Xinxin; Levy, Daniel; Ellison, R. Curtis] Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Saitz, Richard] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med,Clin Addict Res & Educ Unit, Boston, MA 02118 USA.
[Saitz, Richard] Boston Med Ctr, Boston, MA USA.
[Saitz, Richard] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Saitz, Richard] Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA 02215 USA.
[Levy, Daniel; Sartini, Emily] NHLBI Framingham Heart Study, Framingham, MA USA.
RP Zhang, YQ (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, 715 Albany St,Room A203, Boston, MA 02118 USA.
EM yuqing@bu.edu
OI Ellison, Robert Curtis/0000-0002-0582-7467; Niu,
Jingbo/0000-0002-6170-1965; Zhang, Yuqing/0000-0001-7954-1149;
/0000-0002-2535-1427
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health [R01 AA013304]; NHLBI [N01-HC-25195]
FX These analyses were supported by a grant from the National Institute on
Alcohol Abuse and Alcoholism, National Institutes of Health (R01
AA013304). The Framingham Heart Study is funded through NHLBI Contract
N01-HC-25195.
NR 24
TC 28
Z9 28
U1 1
U2 5
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 AUG
PY 2008
VL 121
IS 8
BP 695
EP 701
DI 10.1016/j.amjmed.2008.03.013
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 344WD
UT WOS:000258957100012
PM 18691483
ER
PT J
AU Goldenberg, R
Andrews, W
Caritis, S
Goepfert, A
Ramsey, PS
Rouse, D
Sorokin, Y
Mercer, B
Thom, E
Iams, JD
Thorp, J
Blackwell, S
Leveno, K
Peaceman, A
Carpenter, M
Wapner, R
Spong, C
Saade, G
Davis, L
Varner, M
Van Dorsten, JP
AF Goldenberg, Robert
Andrews, William
Caritis, Steve
Goepfert, Alice
Ramsey, Patrick S.
Rouse, Dwight
Sorokin, Yoram
Mercer, Brian
Thom, Elizabeth
Iams, Jay D.
Thorp, John
Blackwell, Sean
Leveno, Kenneth
Peaceman, Alan
Carpenter, Marshall
Wapner, Ronald
Spong, Catherine
Saade, George
Davis, Lowell
Varner, Michael
Van Dorsten, J. Peter
TI Steering Committee of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development's (NICHD) Maternal-Fetal Medicine
Units Network
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
ID SPONTANEOUS PRETERM BIRTH; PREDICTION
C1 [Goldenberg, Robert; Andrews, William; Caritis, Steve; Goepfert, Alice; Ramsey, Patrick S.; Rouse, Dwight; Sorokin, Yoram; Mercer, Brian; Thom, Elizabeth; Iams, Jay D.; Thorp, John; Blackwell, Sean; Leveno, Kenneth; Peaceman, Alan; Carpenter, Marshall; Wapner, Ronald; Spong, Catherine; Saade, George; Davis, Lowell; Varner, Michael; Van Dorsten, J. Peter] Eunice Kennedy Shriver NICHHD, NIH, Bethesda, MD 20892 USA.
RP Thom, E (reprint author), Eunice Kennedy Shriver NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM E_Thom@biostat.bsc.gwu.edu
RI Varner, Michael/K-9890-2013;
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973;
Peaceman, Alan/0000-0002-4515-4850
NR 8
TC 5
Z9 5
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD AUG
PY 2008
VL 199
IS 2
BP E14
EP E15
DI 10.1016/j.ajog.2008.06.021
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 331RY
UT WOS:000258031500059
PM 18674652
ER
PT J
AU Hemauer, SJ
Yan, R
Patrikeeva, SL
Mattison, DR
Hankins, GDV
Ahmed, MS
Nanovskaya, TN
AF Hemauer, Sarah J.
Yan, Ru
Patrikeeva, Svetlana L.
Mattison, Donald R.
Hankins, Gary D. V.
Ahmed, Mahmoud S.
Nanovskaya, Tatiana N.
TI Transplacental transfer and metabolism of 17-alpha-hydroxyprogesterone
caproate
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine
CY FEB 05-10, 2007
CL San Francisco, CA
SP Soc Maternal Fetal Med
DE dual perfusion; metabolism; preterm delivery;
17-alpha-hydroxyprogesterone caproate
ID HUMAN PLACENTA
AB OBJECTIVE: Determine transplacental transfer and metabolism of 17-alpha-hydroxyprogesterone caproate and its distribution between the tissue and the maternal and fetal circuits of the dually perfused placental lobule.
STUDY DESIGN: 17-alpha-Hydroxyprogesterone caproate (21 ng/mL) and its dual-labeled isotope, 17-alpha-hydroxy-[(3)H] progesterone [(14)C] caproate were added to the maternal circuit. The concentrations of the drug and its metabolite in trophoblast tissue and both circuits were determined by high performance liquid chromatography and liquid scintillation spectrometry.
RESULTS: 17-alpha-Hydroxyprogesterone caproate was transferred from the maternal to fetal circuit. After a 4-hour perfusion period, a metabolite of 17-alpha-hydroxyprogesterone caproate that retained both progesterone and caproate moieties was identified in the tissue and the maternal and fetal circuits. Neither 17-alpha-hydroxyprogesterone caproate nor its metabolite, at the concentrations tested, had adverse effect on determined viability and functional parameters of placental tissue.
CONCLUSION: 17-alpha-Hydroxyprogesterone caproate was metabolized by term placental lobule during its perfusion and both parent compound and its metabolite(s) transferred to the fetal circuit.
C1 [Hemauer, Sarah J.; Yan, Ru; Patrikeeva, Svetlana L.; Hankins, Gary D. V.; Ahmed, Mahmoud S.; Nanovskaya, Tatiana N.] Univ Texas Galveston, Dept Obstet & Gynecol, Med Branch, Galveston, TX 77555 USA.
[Mattison, Donald R.] NICHHD, Obstet Fetal Pharmacol Res Unit, Ctr Res Mothers & Children, Bethesda, MD 20892 USA.
RP Hemauer, SJ (reprint author), Univ Texas Galveston, Dept Obstet & Gynecol, Med Branch, Galveston, TX 77555 USA.
RI Mattison, Donald/C-2015-2009; Yan, Ru/G-3480-2013; Mattison,
Donald/L-4661-2013
OI Yan, Ru/0000-0001-6268-360X; Mattison, Donald/0000-0001-5623-0874
FU NICHD NIH HHS [U10 HD047891, U10-HD047891]
NR 8
TC 2
Z9 2
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 AUG
PY 2008
VL 199
IS 2
AR 169.e1
DI 10.1016/j.ajog.2007.11.065
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 331RY
UT WOS:000258031500031
PM 18674659
ER
PT J
AU Romero, R
Kusanovic, JP
Than, NG
Erez, O
Gotsch, F
Espinoza, J
Edwin, S
Chefetz, I
Gomez, R
Nien, JK
Sammar, M
Pineles, B
Hassan, SS
Meiri, H
Tal, Y
Kuhnreich, I
Papp, Z
Cuckle, HS
AF Romero, Roberto
Kusanovic, Juan Pedro
Than, Nandor Gabor
Erez, Offer
Gotsch, Francesca
Espinoza, Jimmy
Edwin, Samuel
Chefetz, Ilana
Gomez, Ricardo
Nien, Jyh Kae
Sammar, Marei
Pineles, Beth
Hassan, Sonia S.
Meiri, Hamutal
Tal, Yossi
Kuhnreich, Ido
Papp, Zoltan
Cuckle, Howard S.
TI First-trimester maternal serum PP13 in the risk assessment for
preeclampsia
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine
CY FEB 05-10, 2007
CL San Francisco, CA
SP Soc Maternal Fetal Med
DE high-risk pregnancy; maternal serum biochemistry; prenatal care; risk
assessment; screening
ID ENDOTHELIAL GROWTH-FACTOR; UTERINE ARTERY DOPPLER; BED SPIRAL ARTERIES;
EARLY-ONSET PREECLAMPSIA; ELEVATED LIVER-ENZYMES; CIRCULATING ANGIOGENIC
FACTORS; LOW PLATELET COUNT; GESTATIONAL-AGE; PLACENTAL ABRUPTION;
SOLUBLE ENDOGLIN
AB OBJECTIVE: The objective of the study was to determine whether first-trimester maternal serum placental protein 13 (PP13) concentrations can be used in the risk assessment for preeclampsia.
STUDY DESIGN: This case-control study included 50 patients with preeclampsia and 250 patients with normal pregnancies. Samples were collected between 8 and 13 weeks of gestation. Serum PP13 concentrations were measured by immunoassay and expressed as medians and multiples of the median (MoM) for gestational age. Sensitivity and specificity were derived from receiver-operating characteristic curve analysis.
RESULTS: (1) Serum PP13 concentration in the first trimester was significantly lower in patients who developed preterm and early-onset preeclampsia than in those with normal pregnancies; and (2) at 80% specificity, a cutoff of 0.39 MoM had a sensitivity of 100% for early-onset preeclampsia and 85% for preterm preeclampsia.
CONCLUSION: Maternal serum first-trimester PP13 appears to be a reasonable marker for risk assessment for preterm preeclampsia but a weak marker for severe preeclampsia at term, and ineffective for identifying mild preeclampsia at term.
C1 [Romero, Roberto; Kusanovic, Juan Pedro; Than, Nandor Gabor; Erez, Offer; Gotsch, Francesca; Edwin, Samuel; Pineles, Beth; Hassan, Sonia S.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Romero, Roberto; Kusanovic, Juan Pedro; Than, Nandor Gabor; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Edwin, Samuel; Pineles, Beth; Hassan, Sonia S.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Kusanovic, Juan Pedro; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Than, Nandor Gabor; Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary.
[Chefetz, Ilana; Sammar, Marei; Meiri, Hamutal] Diagnost Technol, Yokneam, Israel.
[Gomez, Ricardo; Nien, Jyh Kae] Pontificia Univ Catolica Chile, Sotero Rio Hosp, Ctr Perinatal Diag & Res, Puente Alto, Chile.
[Tal, Yossi; Kuhnreich, Ido] TechnoSTAT, Kfar Sabah, Israel.
[Cuckle, Howard S.] Univ Leeds, Leeds Screening Ctr, Leeds, W Yorkshire, England.
[Cuckle, Howard S.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHHD, Natl Inst Hlth,Dept Hlth & Human Ser,Perinatol Re, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
FU Intramural NIH HHS [Z01 HD002400-16]
NR 103
TC 13
Z9 17
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD AUG
PY 2008
VL 199
IS 2
AR 122.e1
DI 10.1016/j.ajog.2008.01.013
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 331RY
UT WOS:000258031500010
PM 18539259
ER
PT J
AU Macias, E
de Marval, PLM
De Siervi, A
Conti, CJ
Senderowicz, AM
Rodriguez-Puebla, ML
AF Macias, Everardo
de Marval, Paula L. Miliani
De Siervi, Adriana
Conti, Claudio J.
Senderowicz, Adrian M.
Rodriguez-Puebla, Marcelo L.
TI CDK2 activation in mouse epidermis induces keratinocyte proliferation
but does not affect skin tumor development
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CELL-CYCLE CONTROL; BREAST-CANCER; GENE AMPLIFICATION; TRANSGENIC MICE;
TUMORIGENESIS; EXPRESSION; P27(KIP1); PROGRESSION; HYPERPLASIA; KINASE
AB It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21(Cip1) and p27(Kip1). Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5CAk4(D158N) mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4(D158N), but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21(Cip1) in K5Cdk2, but not in K5Cdk4(D158N), epidermis, suggesting that CDK2 overexpression elicits a p21(Cip1) response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis.
C1 [Rodriguez-Puebla, Marcelo L.] N Carolina State Univ, CVM MBS, Dept Mol Biomed Sci, Ctr Comparat Med & Translat Res, Raleigh, NC 27606 USA.
[de Marval, Paula L. Miliani] Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA.
[De Siervi, Adriana; Senderowicz, Adrian M.] Natl Inst Dent & Craniofacial Res, Mol Therapeut Unit, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Conti, Claudio J.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX USA.
[Senderowicz, Adrian M.] Ctr Drug Evaluat, US FDA, Silver Spring, MD USA.
US FDA, Off New Drugs, Off Oncol Drug Prod, Div Drug Oncol Prod, Silver Spring, MD USA.
RP Rodriguez-Puebla, ML (reprint author), N Carolina State Univ, CVM MBS, Dept Mol Biomed Sci, Ctr Comparat Med & Translat Res, 4700 Hillsborough St, Raleigh, NC 27606 USA.
EM marcelo_rodriguez-puebla@ncsu.edu
FU NCI NIH HHS [CA90864, R01 CA090864, CA116328, R01 CA116328]
NR 51
TC 9
Z9 9
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2008
VL 173
IS 2
BP 526
EP 535
DI 10.2353/ajpath.2008.071124
PG 10
WC Pathology
SC Pathology
GA 331LJ
UT WOS:000258013400022
PM 18599613
ER
PT J
AU Smith, PB
Garges, HP
Cotton, CM
Walsh, TJ
Clark, RH
Benjamin, DK
AF Smith, P. Brian
Garges, Harmony P.
Cotton, C. Michael
Walsh, Thomas J.
Clark, Reese H.
Benjamin, Daniel K., Jr.
TI Meningitis in preterm neonates: Importance of cerebrospinal fluid
parameters
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE nosocomial infections; central nervous system; diagnosis; preterm
ID BIRTH-WEIGHT INFANTS; LUMBAR PUNCTURE; BACTERIAL-MENINGITIS; ONSET
SEPSIS; INFECTION; NEWBORN
AB Cerebrospinal fluid parameters are of great importance in diagnosing meningitis, but normal values for preterm neonates are based on small, single-center studies. We sought to determine current values for preterm neonate cerebrospinal fluid parameters and assess the association of cerebrospinal fluid parameters with culture proven meningitis. We performed a cohort study of the first lumbar puncture from 4632 neonates < 34 weeks' gestation performed in the years 1997 to 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical Group. We identified 95 cases of meningitis from the 4632 lumbar punctures. The area under the receiver operating characteristic curves for white blood cell count, glucose, and protein were 0.80, 0.63, and 0.72, respectively, for prediction of culture-proven meningitis. Cerebrospinal fluid parameters used to diagnose meningitis in the absence of dependable cerebrospinal fluid cultures are unreliable. Caution should be employed when Interpreting cerebrospinal fluid parameters in the premature neonate.
C1 [Smith, P. Brian] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[Smith, P. Brian; Benjamin, Daniel K., Jr.] Duke Univ, Clin Res Inst, Durham, NC 27710 USA.
[Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Clark, Reese H.] Pediatrix Obstetrix Ctr Res & Educ, Sunrise, FL USA.
RP Smith, PB (reprint author), Duke Univ, Med Ctr, Dept Pediat, POB 3179, Durham, NC 27710 USA.
EM brian.smith@duke.edu
RI Smith, Phillip/I-5565-2014
FU NIH [T32 (HD-043728-01A2), HD044799-01]; Thrasher Research Fund
FX Dr. Smith received support from NIH T32 (HD-043728-01A2). Dr. Benjamin
received support from HD044799-01 and the Thrasher Research Fund.
NR 23
TC 20
Z9 25
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD AUG
PY 2008
VL 25
IS 7
BP 421
EP 426
DI 10.1055/s-0028-1083839
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 353BX
UT WOS:000259542200006
PM 18726835
ER
PT J
AU Auger, C
Demers, L
Gelinas, I
Jutai, J
Fuhrer, MJ
DeRuyter, F
AF Auger, Claudine
Demers, Louise
Gelinas, Isabelle
Jutai, Jeffrey
Fuhrer, Marcus J.
DeRuyter, Frank
TI Powered mobility for middle-aged and older adults - Systematic review of
outcomes and appraisal of published evidence
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Review
DE wheelchairs; self-help devices; systematic review; aged; middle-aged;
disabled persons; rehabilitation; outcome assessment; health care
ID TECHNOLOGY DEVICE OUTCOMES; QUALITY-OF-LIFE; SPINAL-CORD-INJURY;
ASSISTIVE TECHNOLOGY; WHEELCHAIR USERS; MULTIPLE-SCLEROSIS; PEOPLE;
INDIVIDUALS; PERFORMANCE; SERVICE
AB Objective: To identify the outcomes of power mobility devices for middle-ged and older adult users, and to critically appraise the research evidence.
Design: Systematic review of primary source studies involving adults aged 50 and over using power mobility devices (1996 -2007). Articles were (i) mapped to the Taxonomy of Assistive Technology Device Outcomes, which describes categories of impact of assistive devices from the vantages of effectiveness, social significance, and subjective well-being; and (ii) appraised using the Grading of Recommendations, Assessment, Development, and Evaluation criteria.
Results: This review retained 19 studies and identified 52 different categories of impacts of power mobility devices spanning the three vantages of the taxonomy. The coverage of outcome dimensions was not as extensive for adults age 50 and over as it was for mixed-age groups. Most of the research designs were assigned very low evidence grades. Three studies were low to moderate in quality of evidence, among which one was a randomized trial.
Conclusions: A vast array of potential impacts of powered mobility devices have been described in the last decade. The level of quality of this evidence is improving, but most of these studies were not designed to verify causal relationships, and this is largely responsible for the absence of unequivocal evidence for directly attributing benefits to devices themselves and for quantifying relationships between power mobility device intervention and outcome. To raise the level of evidence about power mobility device interventions in older adults, studies are needed that use prospective designs, better-defined user groups, and well-grounded conceptual frameworks for measuring interventions and outcomes.
C1 [Auger, Claudine; Demers, Louise] Inst Univ Geriatr Montreal, Res Ctr, Montreal, PQ H3W 1W5, Canada.
[Auger, Claudine; Demers, Louise] Univ Montreal, Sch Rehabil, Montreal, PQ, Canada.
[Gelinas, Isabelle] McGill Univ, Sch Phys & Occupat Therapy, Montreal, PQ, Canada.
[Jutai, Jeffrey] Univ Western Ontario, Dept Phys Med & Rehabil, London, ON N6A 3K7, Canada.
[Fuhrer, Marcus J.] NICHHD, NIH, Bethesda, MD 20892 USA.
[DeRuyter, Frank] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Auger, C (reprint author), Inst Univ Geriatr Montreal, Res Ctr, 4565 Queen Mary Rd, Montreal, PQ H3W 1W5, Canada.
RI Auger, Claudine/B-8079-2013;
OI Jutai, Jeffrey/0000-0002-7294-1323
FU PHS HHS [H133A010401, H133A060062]
NR 76
TC 31
Z9 31
U1 1
U2 12
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 AUG
PY 2008
VL 87
IS 8
BP 666
EP 680
DI 10.1097/PHM.0b013e31816de163
PG 15
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 333AK
UT WOS:000258124200008
PM 18401265
ER
PT J
AU Simpson, IA
Dwyer, D
Malide, D
Moley, KH
Travis, A
Vannucci, SJ
AF Simpson, Ian A.
Dwyer, Donard
Malide, Daniela
Moley, Kelle H.
Travis, Alexander
Vannucci, Susan J.
TI The facilitative glucose transporter GLUT3: 20 years of distinction
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
DE neurons; sperm; preimplantation embryo; white blood cells
ID ADULT-RAT BRAIN; CIRCULATING MONONUCLEAR-CELLS; PREIMPLANTATION MOUSE
EMBRYOS; CEREBRAL ENERGY-METABOLISM; INSULIN-RESPONSIVE TISSUES; PRIMARY
CULTURED NEURONS; INDUCIBLE FACTOR-I; PROTEIN-KINASE-B; GROWTH FACTOR-I;
GENE-EXPRESSION
AB Glucose metabolism is vital to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3, which, as implied by its name, was the third glucose transporter to be cloned (Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI. J Biol Chem 263: 15245-15248, 1988) and was originally designated as the neuronal GLUT. The overriding question that drove the early work on GLUT3 was why would neurons need a separate glucose transporter isoform? What is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand? More recently, GLUT3 has been studied in other cell types with quite specific requirements for glucose, including sperm, preimplantation embryos, circulating white blood cells, and an array of carcinoma cell lines. The last are sufficiently varied and numerous to warrant a review of their own and will not be discussed here. However, for each of these cases, the same questions apply. Thus, the objective of this review is to discuss the properties and tissue and cellular localization of GLUT3 as well as the features of expression, function, and regulation that distinguish it from the rest of its family and make it uniquely suited as the mediator of glucose delivery to these specific cells.
C1 [Simpson, Ian A.] Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA.
[Dwyer, Donard] Louisiana State Univ, Hlth Sci Ctr, Dept Psychiat, Shreveport, LA 71105 USA.
[Dwyer, Donard] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol, Shreveport, LA 71105 USA.
[Malide, Daniela] NHLBI, NIH, Bethesda, MD 20892 USA.
[Moley, Kelle H.] Washington Univ, Dept Obstet Gynecol, St Louis, MO USA.
[Travis, Alexander] Cornell Univ, James A Baker Inst Anim Hlth, Ithaca, NY USA.
[Vannucci, Susan J.] Weill Cornell Med Coll, Dept Pediat Newborn Med, New York, NY USA.
RP Simpson, IA (reprint author), Penn State Univ, Coll Med, Dept Neural & Behav Sci, MC H109,C3801,500 Univ Dr, Hershey, PA 17033 USA.
EM ixs10@psu.edu
FU NCRR NIH HHS [RR 00188]; NICHD NIH HHS [HD 040810, HD 045664]; NIDDK NIH
HHS [DK 070351, DK 075130]; NINDS NIH HHS [NS 041405]
NR 135
TC 122
Z9 127
U1 3
U2 25
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD AUG
PY 2008
VL 295
IS 2
BP E242
EP E253
DI 10.1152/ajpendo.90388.2008
PG 12
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 333DS
UT WOS:000258133200004
PM 18577699
ER
PT J
AU Stadler, K
Bonini, MG
Dallas, S
Duma, D
Mason, RP
Kadiiska, MB
AF Stadler, Krisztian
Bonini, Marcelo G.
Dallas, Shannon
Duma, Danielle
Mason, Ronald P.
Kadiiska, Maria B.
TI Direct evidence of iNOS-mediated in vivo free radical production and
protein oxidation in acetone-induced ketosis
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE inducible nitric oxide synthase; acetone; free radicals; electron
paramagnetic resonance
ID LIPID-PEROXIDATION; DIABETIC-PATIENTS; RAT-LIVER; METABOLISM;
HYPERKETONEMIA; ACETOACETATE; METHYLGLYOXAL; ACETALDEHYDE; GLUTATHIONE;
OXIDASE
AB Diabetic patients frequently encounter ketosis that is characterized by the breakdown of lipids with the consequent accumulation of ketone bodies. Several studies have demonstrated that reactive species are likely to induce tissue damage in diabetes, but the role of the ketone bodies in the process has not been fully investigated. In this study, electron paramagnetic resonance (EPR) spectroscopy combined with novel spin-trapping and immunological techniques has been used to investigate in vivo free radical formation in a murine model of acetone-induced ketosis. A six-line EPR spectrum consistent with the alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone radical adduct of a carbon-centered lipid-derived radical was detected in the liver extracts. To investigate the possible enzymatic source of these radicals, inducible nitric oxide synthase (iNOS) and NADPH oxidase knockout mice were used. Free radical production was unchanged in the NADPH oxidase knockout but much decreased in the iNOS knockout mice, suggesting a role for iNOS in free radical production. Longer-term exposure to acetone revealed iNOS overexpression in the liver together with protein radical formation, which was detected by confocal microscopy and a novel immunospin-trapping method. Immunohistochemical analysis revealed enhanced lipid peroxidation and protein oxidation as a consequence of persistent free radical generation after 21 days of acetone treatment in control and NADPH oxidase knockout but not in iNOS knockout mice. Taken together, our data demonstrate that acetone administration, a model of ketosis, can lead to protein oxidation and lipid peroxidation through a free radical-dependent mechanism driven mainly by iNOS overexpression.
C1 [Stadler, Krisztian; Bonini, Marcelo G.; Dallas, Shannon; Mason, Ronald P.; Kadiiska, Maria B.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
[Duma, Danielle] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Stadler, K (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F0-02, Res Triangle Pk, NC 27709 USA.
EM stadlerk@niehs.nih.gov
NR 28
TC 21
Z9 21
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD AUG
PY 2008
VL 295
IS 2
BP E456
EP E462
DI 10.1152/ajpendo.00015.2008
PG 7
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 333DS
UT WOS:000258133200029
PM 18559982
ER
PT J
AU Minneci, PC
Deans, KJ
Shiva, S
Zhi, H
Banks, SM
Kern, S
Natanson, C
Solomon, SB
Gladwin, MT
AF Minneci, Peter C.
Deans, Katherine J.
Shiva, Sruti
Zhi, Huang
Banks, Steven M.
Kern, Steven
Natanson, Charles
Solomon, Steven B.
Gladwin, Mark T.
TI Nitrite reductase activity of hemoglobin as a systemic nitric oxide
generator mechanism to detoxify plasma hemoglobin produced during
hemolysis
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE blood flow; vascular endothelial function; blood substitute; vascular
biology
ID CELL-FREE HEMOGLOBIN; RED-BLOOD-CELLS; ISCHEMIA-REPERFUSION INJURY;
PULMONARY-HYPERTENSION; CARDIOPULMONARY BYPASS; S-NITROSOHEMOGLOBIN;
RELAXING FACTOR; PHYSIOLOGICAL CONDITIONS; XANTHINE OXIDOREDUCTASE;
ERYTHROCYTE CONSUMPTION
AB Hemoglobin (Hb) potently inactivates the nitric oxide (NO) radical via a dioxygenation reaction forming nitrate (NO3-). This inactivation produces endothelial dysfunction during hemolytic conditions and may contribute to the vascular complications of Hb-based blood substitutes. Hb also functions as a nitrite (NO2-) reductase, converting nitrite into NO as it deoxygenates. We hypothesized that during intravascular hemolysis, nitrite infusions would limit the vasoconstrictive properties of plasma Hb. In a canine model of low-and high-intensity hypotonic intravascular hemolysis, we characterized hemodynamic responses to nitrite infusions. Hemolysis increased systemic and pulmonary arterial pressures and systemic vascular resistance. Hemolysis also inhibited NO-dependent pulmonary and systemic vasodilation by the NO donor sodium nitroprusside. Compared with nitroprusside, nitrite demonstrated unique effects by not only inhibiting hemolysis-associated vasoconstriction but also by potentiating vasodilation at plasma Hb concentrations of <25 mu M. We also observed an interaction between plasma Hb levels and nitrite to augment nitroprusside-induced vasodilation of the pulmonary and systemic circulation. This nitrite reductase activity of Hb in vivo was recapitulated in vitro using a mitochondrial NO sensor system. Nitrite infusions may promote NO generation from Hb while maintaining oxygen delivery; this effect could be harnessed to treat hemolytic conditions and to detoxify Hb-based blood substitutes.
C1 [Minneci, Peter C.; Deans, Katherine J.] Childrens Hosp Philadelphia, Childrens Inst Surg Sci, Dept Surg, Philadelphia, PA 19104 USA.
[Minneci, Peter C.] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
[Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Shiva, Sruti; Banks, Steven M.; Kern, Steven; Natanson, Charles; Solomon, Steven B.; Gladwin, Mark T.] Natl Inst Hlth, Ctr Clin, Dept Crit Care Med, Bethesda, MD USA.
RP Gladwin, MT (reprint author), NHLBI, Pulm & Vasc Med Branch, Dept Crit Care Med, Ctr Clin, Bldg 10-CRC,Rm 5-5140,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA.
EM mgladwin@nih.gov
FU Intramural NIH HHS; NHLBI NIH HHS [K22-HL-089041-01]
NR 80
TC 37
Z9 37
U1 0
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD AUG
PY 2008
VL 295
IS 2
BP H743
EP H754
DI 10.1152/ajpheart.00151.2008
PG 12
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 334XE
UT WOS:000258254200034
PM 18552166
ER
PT J
AU Ohayon, J
Finet, G
Gharib, AM
Herzka, DA
Tracqui, P
Heroux, J
Rioufol, G
Kotys, MS
Elagha, A
Pettigrew, RI
AF Ohayon, Jacques
Finet, Gerard
Gharib, Ahmed M.
Herzka, Daniel A.
Tracqui, Philippe
Heroux, Julie
Rioufol, Gilles
Kotys, Melanie S.
Elagha, Abdalla
Pettigrew, Roderic I.
TI Necrotic core thickness and positive arterial remodeling index: emergent
biomechanical factors for evaluating the risk of plaque rupture
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE atherosclerosis; coronary disease; expansive remodeling; wall stress;
biomechanics
ID VULNERABLE ATHEROSCLEROTIC PLAQUES; OPTICAL COHERENCE TOMOGRAPHY; SUDDEN
CORONARY DEATH; INTRAVASCULAR ULTRASOUND; SHEAR-STRESS; CIRCUMFERENTIAL
STRESS; STRUCTURAL-ANALYSIS; CAP THICKNESS; LIPID CORE; FSI MODELS
AB Fibrous cap thickness is often considered as diagnostic of the degree of plaque instability. Necrotic core area (Corearea) and the arterial remodeling index (Remodindex), on the other hand, are difficult to use as clinical morphological indexes: literature data show a wide dispersion of Corearea thresholds above which plaque becomes unstable. Although histopathology shows a strong correlation between Corearea and Remodindex, it remains unclear how these interact and affect peak cap stress (Capstress), a known predictor of rupture. The aim of this study was to investigate the change in plaque vulnerability as a function of necrotic core size and plaque morphology. Capstress value was calculated on 5,500 idealized atherosclerotic vessel models that had the original feature of mimicking the positive arterial remodeling process described by Glagov. Twenty-four nonruptured plaques acquired by intravascular ultrasound on patients were used to test the performance of the associated idealized morphological models. Taking advantage of the extensive simulations, we investigated the effects of anatomical plaque features on Capstress. It was found that: 1) at the early stages of positive remodeling, lesions were more prone to rupture, which could explain the progression and growth of clinically silent plaques and 2) in addition to cap thickness, necrotic core thickness, rather than area, was critical in determining plaque stability. This study demonstrates that plaque instability is to be viewed not as a consequence of fibrous cap thickness alone but rather as a combination of cap thickness, necrotic core thickness, and the arterial remodeling index.
C1 [Ohayon, Jacques; Gharib, Ahmed M.; Herzka, Daniel A.; Heroux, Julie; Kotys, Melanie S.; Elagha, Abdalla; Pettigrew, Roderic I.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Ohayon, Jacques; Tracqui, Philippe] CNRS, Lab Tech Imagerie Modelisat Cognit,DynaCell, Inst Math Grenoble, Unit Mixte Rech 5525,Inst Ingn Informat Sante, Grenoble, France.
[Finet, Gerard; Rioufol, Gilles] Univ Lyon 1, Inst Natl Sante Rech Med, Unit 886, F-69365 Lyon, France.
[Finet, Gerard; Rioufol, Gilles] Hosp Civils Lyon, Dept Hemodynam & Intervent Cardiol, Lyon, France.
[Herzka, Daniel A.] Philips Res N Amer, Clin Sites Res Program, Briarcliff Manor, NY USA.
RP Ohayon, J (reprint author), NHLBI, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ohayonj2@mail.nih.gov
RI Gharib, Ahmed/O-2629-2016;
OI Gharib, Ahmed/0000-0002-2476-481X; Elagha, Abdalla/0000-0003-3136-2293;
Herzka, Daniel/0000-0002-9400-7814
NR 47
TC 103
Z9 105
U1 2
U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD AUG
PY 2008
VL 295
IS 2
BP H717
EP H727
DI 10.1152/ajpheart.00005.2008
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 334XE
UT WOS:000258254200031
PM 18586893
ER
PT J
AU Chen, LY
Woszczek, G
Nagineni, S
Logun, C
Shelhamer, JH
AF Chen, Li-Yuan
Woszczek, Grzegorz
Nagineni, Sahrudaya
Logun, Carolea
Shelhamer, James H.
TI Cytosolic phospholipase A2 alpha activation induced by S1P is mediated
by the S1P3 receptor in lung epithelial cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE eicosanoid; calcium flux; airway inflammation
ID ARACHIDONIC-ACID RELEASE; SPHINGOSINE 1-PHOSPHATE; CERAMIDE 1-PHOSPHATE;
SPHINGOSINE-1-PHOSPHATE RECEPTORS; BARRIER INTEGRITY; CARCINOMA-CELLS;
PROTEIN-KINASE; GROWTH-FACTOR; MAP KINASE; TNF-ALPHA
AB Cytosolic phospholipase A2 alpha(cPLA2 alpha) activation is a regulatory step in the control of arachidonic acid (AA) liberation for eicosanoid formation. Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator involved in the regulation of many important proinflammatory processes and has been found in the airways of asthmatic subjects. We investigated the mechanism of S1P-induced AA release and determined the involvement of cPLA2 alpha in these events in A549 human lung epithelial cells. S1P induced AA release rapidly within 5 min in a dose-and time-dependent manner. S1P-induced AA release was inhibited by the cPLA2 alpha inhibitors methyl arachidonyl fluorophosphonate (MAFP) and pyrrolidine derivative, by small interfering RNA-mediated downregulation of cPLA2 alpha, and by inhibition of S1P-induced calcium flux, suggesting a significant role of cPLA2 alpha in S1P-mediated AA release. Knockdown of the S1P3 receptor, the major S1P receptor expressed on A549 cells, inhibited S1P-induced calcium flux and AA release. The S1P-induced calcium flux and AA release was associated with sphingosine kinase 1 (Sphk1) expression and activity. Furthermore, Rho-associated kinase, downstream of S1P3, was crucial for S1P-induced cPLA2 alpha activation. Our data suggest that S1P acting through S1P3, calcium flux, and Rho kinase activates cPLA2 alpha and releases AA in lung epithelial cells. An understanding of S1P-induced cPLA2 alpha activation mechanisms in epithelial cells may provide potential targets to control inflammatory processes in the lung.
C1 [Shelhamer, James H.] Natl Inst Hlth, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Shelhamer, JH (reprint author), Natl Inst Hlth, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 2C145,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jshelhamer@cc.nih.gov
RI Woszczek, Grzegorz/H-5792-2012
NR 55
TC 20
Z9 20
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD AUG
PY 2008
VL 295
IS 2
BP L326
EP L335
DI 10.1152/ajplung.00393.2007
PG 10
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 331CR
UT WOS:000257990800010
PM 18502815
ER
PT J
AU Hollis, JF
Gullion, CM
Stevens, VJ
Brantley, PJ
Appel, LJ
Ard, JD
Champagne, CM
Dalcin, A
Erlinger, TP
Funk, K
Laferriere, D
Lin, PH
Loria, CM
Samuel-Hodge, C
Vollmer, WM
Svetkey, LP
AF Hollis, Jack F.
Gullion, Christina M.
Stevens, Victor J.
Brantley, Phillip J.
Appel, Lawrence J.
Ard, Jamy D.
Champagne, Catherine M.
Dalcin, Arlene
Erlinger, Thomas P.
Funk, Kristine
Laferriere, Daniel
Lin, Pao-Hwa
Loria, Catherine M.
Samuel-Hodge, Carmen
Vollmer, William M.
Svetkey, Laura P.
CA Weight Loss Maintenance Trial Res
TI Weight loss during the intensive intervention phase of the Weight-Loss
Maintenance trial
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM
MAINTENANCE; BLOOD-PRESSURE; HYPERTENSION PREVENTION; SODIUM REDUCTION;
NONPHARMACOLOGIC INTERVENTIONS; DIABETES-MELLITUS; MILD HYPERTENSION;
PHYSICAL-ACTIVITY
AB Background: To improve methods for long-term weight management, the Weight Loss Maintenance (WLM) trial, a four-center randomized trial, was conducted to compare alternative strategies for maintaining weight loss over a 30-month period. This paper describes methods and results for the initial 6-month weight-loss program (Phase I).
Methods: Eligible adults were aged >= 25, overweight or obese (BMI=25-45 kg/m(2)), and on medications for hypertension and/or dyslipidemia. Anthropomorphic, demographic, and psychosocial measures were collected at baseline and 6 months. Participants (n=1685) attended 20 weekly group sessions to encourage calorie restriction, moderate-intensity physical activity, and the DASH (dietary approaches to stop hypertension) dietary pattern. Weight-loss predictors with missing data were replaced by multiple imputation.
Results: Participants were 44% African American and 67% women; 79% were obese (BMI >= 30), 87% were taking anti-hypertensive medications, and 38% were taking antidyslipidemia medications. Participants attended an average of 72% of 20 group sessions. They self-reported 117 minutes of moderate-intensity physical activity per week, kept 3.7 daily food records per week, and consumed 2.9 servings of fruits and vegetables per day. The Phase-I follow-up rate was 92%. Mean (SD) weight change was -5.8 kg (4.4), and 69% lost at least 4 kg. All race-gender subgroups lost substantial weight: African-American men (-5.4 kg +/- 7.7); African-American women (-4.1 kg +/- 2.9); non-African-American men (-8.5 kg +/- 12.9); and non-African-American women (-5.8 kg +/- 6.1). Behavioral measures (e.g., diet records and physical activity) accounted for most of the weight-loss variation, although the association between behavioral measures and weight loss differed by race and gender groups.
Conclusions: The WLM behavioral intervention successfully achieved clinically significant short-term weight loss in a diverse population of high-risk patients.
C1 [Hollis, Jack F.; Gullion, Christina M.; Stevens, Victor J.; Funk, Kristine; Laferriere, Daniel; Vollmer, William M.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97227 USA.
[Brantley, Phillip J.; Champagne, Catherine M.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Dalcin, Arlene] Univ Alabama, Div Clin Nutr & Dietet, Birmingham, AL USA.
[Erlinger, Thomas P.] Univ Texas Austin, Med Branch, Austin, TX 78712 USA.
[Appel, Lawrence J.; Dalcin, Arlene] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Lin, Pao-Hwa; Svetkey, Laura P.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC USA.
[Samuel-Hodge, Carmen] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
[Samuel-Hodge, Carmen] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA.
[Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
RP Hollis, JF (reprint author), Kaiser Permanente NW, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA.
EM jack.hollis@kpchr.org
RI Kattelmann, Kendra/E-8225-2013
FU NHLBI NIH HHS [U01 HL068955, 5-HL68955, 5-U01 HL68676, 5-U01 HL68734,
5-U01 HL68790, 5-U01 HL68920, U01 HL068676, U01 HL068676-05, U01
HL068734, U01 HL068734-05, U01 HL068790, U01 HL068790-05, U01 HL068920,
U01 HL068920-05, U01 HL068955-05]
NR 67
TC 157
Z9 157
U1 2
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
BP 118
EP 126
DI 10.1016/j.amepre.2008.04.013
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TO
UT WOS:000257893700005
PM 18617080
ER
PT J
AU Fiore, MC
Jaen, CR
Baker, TB
Bailey, WC
Bennett, G
Benowitz, NL
Christiansen, BA
Connell, M
Curry, SJ
Dorfman, SF
Fraser, D
Froelicher, ES
Goldstein, MG
Hasselblad, V
Healton, CG
Heishman, S
Henderson, PN
Heyman, RB
Husten, C
Koh, HK
Kottke, TE
Lando, HA
Leitzke, C
Mecklenburg, RE
Mermelstein, RJ
Morgan, G
Mullen, PD
Murray, EW
Orleans, CT
Piper, ME
Robinson, L
Stitzer, ML
Theobald, W
Tommasello, AC
Villejo, L
Wewers, ME
Williams, C
AF Fiore, Michael C.
Jaen, Carlos Roberto
Baker, Timothy B.
Bailey, William C.
Bennett, Glenn
Benowitz, Neal L.
Christiansen, Bruce A.
Connell, Michael
Curry, Susan J.
Dorfman, Sally Faith
Fraser, David
Froelicher, Erika S.
Goldstein, Michael G.
Hasselblad, Victor
Healton, Cheryl G.
Heishman, Stephen
Henderson, Patricia Nez
Heyman, Richard B.
Husten, Corinne
Koh, Howard K.
Kottke, Thomas E.
Lando, Harry A.
Leitzke, Cathlyn
Mecklenburg, Robert E.
Mermelstein, Robin J.
Morgan, Glen
Mullen, Patricia Dolan
Murray, Ernestine W.
Orleans, C. Tracy
Piper, Megan E.
Robinson, Lawrence
Stitzer, Maxine L.
Theobald, Wendy
Tommasello, Anthony C.
Villejo, Louise
Wewers, Mary Ellen
Williams, Christine
CA Clinical Practice Guideline Treati
TI A Clinical Practice Guideline for Treating Tobacco Use and Dependence:
2008 Update - A US Public Health Service report
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID NICOTINE REPLACEMENT THERAPY; SMOKING-CESSATION INTERVENTION; RANDOMIZED
CONTROLLED-TRIAL; COST-EFFECTIVENESS ANALYSIS; PRIMARY-CARE; TRANSDERMAL
NICOTINE; FORMER SMOKERS; CIGARETTE-SMOKING; SHORT-TERM;
MYOCARDIAL-INFARCTION
AB Objective: To summarize the U.S. Public Health Service guideline Treating Tobacco Use and Dependence: 2008 Update, which provides recommendations for clinical interventions and system changes to promote the treatment of tobacco dependence.
Participants: An independent panel of 24 scientists and clinicians selected by the U.S. Agency for Healthcare Research and Quality on behalf of the U.S. Public Health Service. A consortium of eight governmental and nonprofit organizations sponsored the update.
Evidence: Approximately 8700 English-language, peer-reviewed articles and abstracts, published between 1975 and 2007, were reviewed for data that addressed assessment and treatment of tobacco dependence. This literature served as the basis for more than 35 meta-analyses.
Consensus process: Two panel meetings and numerous conference calls and staff meetings were held to evaluate meta-analyses and relevant literature, to synthesize the results, and to develop recommendations. The updated guideline was then externally reviewed by more than 90 experts, made available for public comment, and revised.
Conclusions: This evidence-based, updated guideline provides specific recommendations regarding brief and intensive tobacco-cessation interventions as well as system-level changes designed to promote the assessment and treatment of tobacco use. Brief clinical approaches for patients willing and unwilling to quit are described.
C1 [Fiore, Michael C.; Baker, Timothy B.; Christiansen, Bruce A.; Connell, Michael; Fraser, David; Leitzke, Cathlyn; Piper, Megan E.; Theobald, Wendy] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Bailey, William C.] Univ Alabama, Birmingham, AL 35294 USA.
[Bennett, Glenn] NHLBI, Bethesda, MD 20892 USA.
[Benowitz, Neal L.; Froelicher, Erika S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Curry, Susan J.; Mermelstein, Robin J.] Univ Illinois, Chicago, IL USA.
[Dorfman, Sally Faith] Ferring Pharmaceut Inc, Parsippany, NJ USA.
[Goldstein, Michael G.] Inst Healthcare Commun, New Haven, CT USA.
[Hasselblad, Victor] Duke Univ, Durham, NC USA.
[Healton, Cheryl G.] Amer Legacy Fdn, Washington, DC USA.
[Heishman, Stephen] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Henderson, Patricia Nez] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA.
[Heyman, Richard B.] Amer Acad Pediat, Cincinnati, OH USA.
[Husten, Corinne] CDC, Atlanta, GA 30333 USA.
[Koh, Howard K.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Kottke, Thomas E.] Univ Minnesota, St Paul, MN 55108 USA.
[Lando, Harry A.] Univ Minnesota, Minneapolis, MN USA.
[Morgan, Glen] NCI, Bethesda, MD 20892 USA.
[Orleans, C. Tracy] Robert Wood Johnson Fdn, Piscataway, NJ USA.
[Robinson, Lawrence] Philadelphia Dept Publ Hlth, Philadelphia, PA USA.
[Stitzer, Maxine L.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA.
[Tommasello, Anthony C.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
[Villejo, Louise] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wewers, Mary Ellen] Ohio State Univ, Columbus, OH 43210 USA.
RP Fiore, MC (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA.
NR 147
TC 226
Z9 237
U1 11
U2 42
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
BP 158
EP 176
DI 10.1016/j.amepre.2008.04.009
PG 19
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TO
UT WOS:000257893700011
ER
PT J
AU Croyle, RT
AF Croyle, Robert T.
TI The National Cancer Institute's transdisciplinary centers initiatives
and the need for building a science of team science
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Croyle, RT (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6138, Bethesda, MD 20892 USA.
EM croyler@mail.nih.gov
NR 32
TC 26
Z9 27
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S90
EP S93
DI 10.1016/j.amepre.2008.05.012
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900002
PM 18619408
ER
PT J
AU Hall, KL
Feng, AX
Moser, RP
Stokols, D
Taylor, BK
AF Hall, Kara L.
Feng, Annie X.
Moser, Richard P.
Stokols, Daniel
Taylor, Brandie K.
TI Moving the science of team science forward - Collaboration and
creativity
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID TRANSDISCIPLINARY; HEALTH
AB Teams of scientists representing diverse disciplines are often brought together for purposes of better understanding and, ultimately, resolving urgent public health and environmental problems. Likewise, the emerging field of the science of team science draws on diverse disciplinary perspectives to better understand and enhance the processes and outcomes of scientific collaboration. In this supplement to the American journal of Preventive Medicine, leading scholars in the nascent field of team science have come together with a common goal of advancing the field with new models, methods, and measures. This summary article highlights key themes reflected in the supplement and identifies several promising directions for future research organized around the following broad challenges: (1) operationalizing cross-disciplinary team science and training more clearly; (2) conceptualizing the multiple dimensions of readiness for team science; (3) ensuring the sustainability of transdisciplinary team science; (4) developing more effective models and strategies for training transdisciplinary scientists; (5) creating and validating improved models, methods, and measures for evaluating team science; and (6) fostering transdisciplinary cross-sector partnerships. A call to action is made to leaders from the research, funding, and practice sectors to embrace strategies of creativity and innovation in a collective effort to move the field forward, which may not only advance the science of team science but, ultimately, public health science and practice.
C1 [Hall, Kara L.; Feng, Annie X.; Moser, Richard P.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Taylor, Brandie K.] NIH, Off Portfolio Anal & Strateg Initiat, Bethesda, MD 20892 USA.
[Stokols, Daniel] Univ Calif Irvine, Sch Social Ecol, Irvine, CA USA.
RP Hall, KL (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4080, Rockville, MD 20850 USA.
EM hallka@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 39
TC 62
Z9 63
U1 3
U2 32
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S243
EP S249
DI 10.1016/j.amepre.2008.05.007
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900020
PM 18619406
ER
PT J
AU Hall, KL
Stokols, D
Moser, RP
Taylor, BK
Thornquist, MD
Nebeling, LC
Ehret, CC
Barnett, MJ
McTiernan, A
Berger, NA
Goran, MI
Jeffery, RW
AF Hall, Kara L.
Stokols, Daniel
Moser, Richard P.
Taylor, Brandie K.
Thornquist, Mark D.
Nebeling, Linda C.
Ehret, Carolyn C.
Barnett, Matthew J.
McTiernan, Anne
Berger, Nathan A.
Goran, Michael I.
Jeffery, Robert W.
TI The collaboration readiness of transdisciplinary research teams and
centers - Findings from the National Cancer Institute's TREC Year-One
evaluation study
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID TRUST
AB Growing interest in promoting cross-disciplinary collaboration among health scientists has prompted several federal agencies, including the NIH, to establish large, multicenter initiatives intended to foster collaborative research and training. In order to assess whether these initiatives are effective in promoting scientific collaboration that ultimately results in public health improvements, it is necessary to develop new strategies for evaluating research processes and products as well as the longer-term societal outcomes associated with these programs. Ideally, evaluative measures should be administered over the entire course of large initiatives, including their near-term and later phases. The present study focuses on the development of new tools for assessing the readiness for collaboration among health scientists at the outset (during the first year) of their participation in the National Cancer Institute's Transdisciplinary Research on Energetics and Cancer (TREC) initiative. Indexes of collaborative readiness, along with additional measures of near-term collaborative processes, were administered as part of the TREC Year-One evaluation survey. Additionally, early progress toward scientific collaboration and integration was assessed, using a protocol for evaluating written research products. Results from the Year-One survey and the ratings of written products provide evidence of cross-disciplinary collaboration among participants during the first year of the initiative, and also reveal opportunities for enhancing collaborative processes and outcomes during subsequent phases of the project. The implications of these findings for future evaluations of team science initiatives are discussed.
C1 [Hall, Kara L.; Moser, Richard P.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20850 USA.
[Taylor, Brandie K.] NIH, Off Portfolio Anal & Strateg Initiat, Bethesda, MD 20892 USA.
[Stokols, Daniel] Univ Calif Irvine, Sch Social Ecol, Irvine, CA USA.
[Thornquist, Mark D.; Ehret, Carolyn C.; Barnett, Matthew J.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98104 USA.
[Berger, Nathan A.] Case Western Reserve Univ, Sch Med, Ctr Sci Hlth & Soc, Cleveland, OH USA.
[Goran, Michael I.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Jeffery, Robert W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Hall, KL (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4080, Bethesda, MD 20850 USA.
EM hallka@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [U54 CA116849, U01
CA-116850-01, U01 CA116850, U54 CA-116847-01, U54 CA-116848-01, U54
CA-116849-01, U54 CA-116867-01, U54 CA116847, U54 CA116848, U54
CA116867]
NR 17
TC 55
Z9 55
U1 3
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S161
EP S172
DI 10.1016/j.amepre.2008.03.035
PG 12
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900010
PM 18619396
ER
PT J
AU Hays, TC
AF Hays, Timothy C.
TI The science of team science - Commentary on measurements of scientific
readiness
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
C1 NIH, Off Portfolio Anal & Strateg Initiat, Bethesda, MD 20892 USA.
RP Hays, TC (reprint author), NIH, Off Portfolio Anal & Strateg Initiat, 1 Ctr Dr,Bldg 1,Room 201, Bethesda, MD 20892 USA.
EM thays@od.nih.gov
NR 9
TC 10
Z9 10
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S193
EP S195
DI 10.1016/j.amepre.2008.05.016
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900013
PM 18619399
ER
PT J
AU Hesse, BW
AF Hesse, Bradford W.
TI Of mice and mentors - Developing cyber-infrastructure to support
transdisciplinary scientific collaboration
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
ID SCIENCE
C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Hesse, BW (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA.
EM hesseb@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
FU Intramural NIH HHS [Z99 CA999999]
NR 39
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 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S235
EP S239
DI 10.1016/j.amepre.2008.05.011
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900018
PM 18619404
ER
PT J
AU Hiatt, RA
Breen, N
AF Hiatt, Robert A.
Breen, Nancy
TI The social determinants of cancer - A challenge for transdisciplinary
science
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID TIME PHYSICAL-ACTIVITY; SMOKE-FREE WORKPLACES; UNITED-STATES;
BREAST-CANCER; SOCIOECONOMIC-STATUS; HEALTH INEQUALITIES; MULTILEVEL
ANALYSIS; CERVICAL-CANCER; ETHNIC DISPARITIES; COLORECTAL-CANCER
AB To make further significant advances in cancer control research, a transdisciplinary science approach is needed that integrates the study of the biological nature of cancer and its clinical applications with the behavioral and social influences on cancer. More-effective interventions to reduce the burden of cancer can be developed and implemented by the adoption of a transdisciplinary research framework that takes into account the social determinants of cancer and seeks to discover interactions among social, environmental, behavioral, and biological factors in cancer etiology. This paper addresses two critical issues in the science of team science: (1) a cross-disciplinary, multilevel framework for organizing future research, and (2) a perspective that could aid in the translation and dissemination of cancer research findings in health care and public health practice. This conceptual framework is designed to encourage transdisciplinary research that will integrate social determinants into cancer research. The authors' goal is to promote a more complete understanding of the causes of cancer that will lead to the improved translation and implementation of the results of research.
C1 [Hiatt, Robert A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Breen, Nancy] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Hiatt, RA (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, Helen Diller Family Comprehens Canc Ctr, 185 Berry St,Suite 5700, San Francisco, CA 94143 USA.
EM rhiatt@cc.ucsf.edu
NR 136
TC 41
Z9 43
U1 4
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S141
EP S150
DI 10.1016/j.amepre.2008.05.006
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900008
PM 18619394
ER
PT J
AU Leischow, SJ
Best, A
Trochim, WM
Clark, PI
Gallagher, RS
Marcus, SE
Matthews, E
AF Leischow, Scott J.
Best, Allan
Trochim, William M.
Clark, Pamela I.
Gallagher, Richard S.
Marcus, Stephen E.
Matthews, Eva
TI Systems thinking to improve the public's health
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
AB Improving population health requires understanding and changing societal structures and functions, but countervailing forces sometimes undermine those changes, thus reflecting the adaptive complexity inherent in public health systems. The purpose of this paper is to propose systems thinking as a conceptual rubric for the practice of team science in public health, and transdisciplinary, translational research as a catalyst for promoting the functional efficiency of science. The paper lays a foundation for the conceptual understanding of systems thinking and transdisciplinary research, and will provide illustrative examples within and beyond public health. A set of recommendations for a systems-centric approach to translational science will be presented.
C1 [Leischow, Scott J.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Matthews, Eva] Univ Arizona, Dept Family & Community Med, Tucson, AZ 85724 USA.
[Best, Allan] Vancouver Coastal Hlth Res Inst, Ctr Clin Epidemiol & Evaluat, Vancouver, BC, Canada.
[Trochim, William M.] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA.
[Gallagher, Richard S.] Gallagher & Associates, Ithaca, NY USA.
[Clark, Pamela I.] Univ Maryland, College Pk, MD 20742 USA.
[Marcus, Stephen E.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Leischow, SJ (reprint author), Univ Arizona, Arizona Canc Ctr, 1515 N Campbell Ave,Room 4943, Tucson, AZ 85724 USA.
EM sleischow@azcc.arizona.edu
FU NCI NIH HHS [R01 CA128638, CA023074]
NR 28
TC 96
Z9 100
U1 1
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S196
EP S203
DI 10.1016/j.amepre.2008.05.014
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900014
PM 18619400
ER
PT J
AU Mabry, PL
Olster, DH
Morgan, GD
Abrams, DB
AF Mabry, Patricia L.
Olster, Deborah H.
Morgan, Glen D.
Abrams, David B.
TI Interdisciplinarity and systems science to improve population health - A
view from the NIH Office of Behavioral and Social Sciences Research
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID UNITED-STATES; PUBLIC-HEALTH; TRANSDISCIPLINARY RESEARCH; CANCER;
STRESS; DISPARITIES; DEPRESSION; PROMOTION; HIV/AIDS; SMOKING
AB Fueled by tire rapid pace of discovery, humankind's ability to understand the ultimate causes of preventable common disease burdens and to identify solutions is now reaching a revolutionary tipping point. Achieving optimal health and well-being for all members of society lies as much in the understanding of the factors identified by the behavioral, social, and public health sciences as by the biological ones. Accumulating advances in mathematical modeling, informatics, imaging, sensor technology, and communication tools have stimulated several converging trends in science: an emerging understanding of epigenomic regulation; dramatic successes in achieving population health-behavior changes; and improved scientific rigor in behavioral, social, and economic sciences. Fostering stronger interdisciplinary partnerships to bring together the behavioral-social-ecologic models of multilevel "causes of the causes" and the molecular, cellular, and, ultimately, physiological bases of health and disease will facilitate breakthroughs to improve the public's health.
The strategic vision of the Office of Behavioral and Social Sciences Research (OBSSR) at the National Institutes of Health (NIH) is rooted in a collaborative approach to addressing the complex and multidimensional issues that challenge the public's health. This paper describes OBSSR's four key programmatic directions (next-generation basic science, interdisciplinary research, systems science, and a problem-based focus for population impact) to illustrate how interdisciplinary and transdisciplinary perspectives can foster the vertical integration of research among biological, behavioral, social, and population levels of analysis over the lifespan and across generations. Interdisciplinary and multilevel approaches are critical both to the OBSSR's mission of integrating behavioral and social sciences more fully into the NIH scientific enterprise and to the overall NIH mission of utilizing science in the pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability.
C1 [Mabry, Patricia L.; Olster, Deborah H.; Abrams, David B.] NIH, Off Behav & Social Sci Res, Off Director, Bethesda, MD 20892 USA.
[Morgan, Glen D.] NCI, Tobacco Control Res Branch, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
RP Mabry, PL (reprint author), NIH, Off Behav & Social Sci Res, Off Director, 31 Ctr Dr,Bldg 31,Room B1-C19, Bethesda, MD 20892 USA.
EM mabryp@od.nih.gov
FU Intramural NIH HHS [Z99 OD999999]
NR 69
TC 109
Z9 110
U1 6
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S211
EP S224
DI 10.1016/j.amepre.2008.05.018
PG 14
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900016
PM 18619402
ER
PT J
AU Masse, LC
Moser, RP
Stokols, D
Taylor, BK
Marcus, SE
Morgan, GD
Hall, KL
Croyle, RT
Trochim, WM
AF Masse, Louise C.
Moser, Richard P.
Stokols, Daniel
Taylor, Brandie K.
Marcus, Stephen E.
Morgan, Glen D.
Hall, Kara L.
Croyle, Robert T.
Trochim, William M.
TI Measuring collaboration and transdisciplinary integration in team
science
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
AB Purpose: As the science of team science evolves, the development of measures that assess important processes related to working in transdisciplinary teams is critical. Therefore, the purpose of this paper is to present the psychometric properties of scales measuring collaborative processes and transdisciplinary integration.
Methods: Two hundred-sixteen researchers and research staff participating in the Transdisciplinary Tobacco Use Research Centers (TTURC) Initiative completed the TTURC researcher survey. Confirmatory-factor analyses were used to verify the hypothesized factor structures. Descriptive data pertinent to these scales and their associations with other constructs were included to further examine the properties of the scales.
Results: Overall, the hypothesized-factor structures, with some minor modifications, were validated. A total of four scales were developed, three to assess collaborative processes (satisfaction with the collaboration, impact of collaboration, trust and respect) and one to assess transdisciplinary integration. All scales were found to have adequate internal consistency (i.e., Cronbach alpha's were all >0.70); were correlated with intermediate markers of collaborations (e.g., the collaboration and transdisciplinary-integration scales were positively associated with the perception of a center's making good progress in creating new methods, new science and models, and new interventions); and showed some ability to detect group differences.
Conclusions: This paper provides valid tools that can be utilized to examine the underlying processes of team science-an important step toward advancing the science of team science.
C1 [Masse, Louise C.] Univ British Columbia, Dept Pediat, Ctr Community Child Hlth Res, Vancouver, BC V6H 3V4, Canada.
[Moser, Richard P.; Marcus, Stephen E.; Morgan, Glen D.; Hall, Kara L.; Croyle, Robert T.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Taylor, Brandie K.] NIH, Off Portfolio Anal & Strateg Initiat, Bethesda, MD 20892 USA.
[Stokols, Daniel] Univ Calif Irvine, Sch Social Ecol, Irvine, CA USA.
[Trochim, William M.] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA.
RP Masse, LC (reprint author), Univ British Columbia, Dept Pediat, Ctr Community Child Hlth Res, L408,4480 Oak St, Vancouver, BC V6H 3V4, Canada.
EM lmasse@cw.bc.ca
NR 27
TC 61
Z9 61
U1 3
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S151
EP S160
DI 10.1016/j.amepre.2008.05.020
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900009
PM 18619395
ER
PT J
AU Stokols, D
Misra, S
Moser, RP
Hall, KL
Taylor, BK
AF Stokols, Daniel
Misra, Shalini
Moser, Richard P.
Hall, Kara L.
Taylor, Brandie K.
TI The ecology of team science - Understanding contextual influences on
transdisciplinary collaboration
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article; Proceedings Paper
CT NCI Conference on the Science of Team Science - Assessing the Value of
Transdiciplinary Resarch
CY OCT 30-31, 2006
CL Bethesda, MD
SP NCI
ID SCIENTIFIC COLLABORATION; PARTICIPATORY RESEARCH; COMMUNITY COALITIONS;
GROUP-PERFORMANCE; PUBLIC-HEALTH; WORK TEAMS; LEADERSHIP; COMMUNICATION;
MANAGEMENT; BEHAVIOR
AB Increased public and private investments in large-scale team science initiatives over the past two decades have underscored the need to better understand how contextual factors influence the effectiveness of transdisciplinary scientific collaboration. Toward that goal, the findings from four distinct areas of research on team performance and collaboration are reviewed: (1) social psychological and management research on the effectiveness of teams in organizational and institutional settings; (2) studies of cyber-infrastructures (i.e., computer-based infrastructures) designed to support transdisciplinary collaboration across remote research sites; (3) investigations of community-based coalitions for health promotion; and (4) studies focusing directly on the antecedents, processes, and outcomes of scientific collaboration within transdisciplinary research centers and training programs. The empirical literature within these four domains reveals several contextual circumstances that either facilitate or hinder team performance and collaboration. A typology of contextual influences on transdisciplinary collaboration is proposed as a basis for deriving practical guidelines for designing, managing, and evaluating successful team science initiatives.
C1 [Stokols, Daniel] Univ Calif Irvine, Dept Planning Policy & Design, Sch Social Ecol, Irvine, CA 92697 USA.
[Moser, Richard P.; Hall, Kara L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Taylor, Brandie K.] NIH, Off Portfolio Anal, Bethesda, MD 20892 USA.
[Taylor, Brandie K.] NIH, Strateg Initiat, Bethesda, MD 20892 USA.
RP Stokols, D (reprint author), Univ Calif Irvine, Dept Planning Policy & Design, Sch Social Ecol, 206-C Social Ecology 1 Bldg, Irvine, CA 92697 USA.
EM dstokols@uci.edu
FU NIDDK NIH HHS [15R13DK69500-03]
NR 127
TC 135
Z9 138
U1 16
U2 65
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S96
EP S115
DI 10.1016/j.amepre.2008.05.003
PG 20
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900004
PM 18619410
ER
PT J
AU Stokols, D
Hall, KL
Taylor, BK
Moser, RP
AF Stokols, Daniel
Hall, Kara L.
Taylor, Brandie K.
Moser, Richard P.
TI The science of team science - Overview of the field and introduction to
the supplement
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
ID TRANSDISCIPLINARY SCIENTIFIC COLLABORATION; INTERDISCIPLINARY RESEARCH;
HEALTH DISPARITIES; SOCIAL-SCIENCES; SPECIAL-ISSUE; LEADERSHIP; SUCCESS;
CANCER; INITIATIVES; CHALLENGES
AB The science of team science encompasses an amalgam of conceptual and methodologic strategies aimed at understanding and enhancing the outcomes of large-scale collaborative research and training programs. This field has emerged rapidly in recent years, largely in response to growing concerns about the cost effectiveness of public- and private-sector investments in team-based science and training initiatives. The distinctive boundaries and substantive concerns of this field, however, have remained difficult to discern. An important challenge for the field is to characterize the science of team science more clearly in terms of its major theoretical, methodologic, and translational concerns. The articles in this supplement address this challenge, especially in the context of designing, implementing, and evaluating cross-disciplinary research initiatives. This introductory article summarizes the major goals and organizing themes of the supplement, draws links between the constituent articles, and identifies new areas of study within the science of team science.
C1 [Stokols, Daniel] Univ Calif Irvine, Dept Planning Policy & Design, Sch Social Ecol, Irvine, CA 92697 USA.
[Hall, Kara L.; Moser, Richard P.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Taylor, Brandie K.] NIH, Off Portfolio Anal, Bethesda, MD 20892 USA.
[Taylor, Brandie K.] NIH, Strateg Initiat, Bethesda, MD 20892 USA.
RP Stokols, D (reprint author), Univ Calif Irvine, Dept Planning Policy & Design, Sch Social Ecol, 206-C Social Ecol 1 Bldg, Irvine, CA 92697 USA.
EM dstokols@uci.cdu
NR 111
TC 201
Z9 205
U1 15
U2 97
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2008
VL 35
IS 2
SU S
BP S77
EP S89
DI 10.1016/j.amepre.2008.05.002
PG 13
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 329TQ
UT WOS:000257893900001
PM 18619407
ER
PT J
AU West, SG
Duan, N
Pequegnat, W
Gaist, P
Jarlais, DCD
Holtgrave, D
Szapocznik, J
Fishbein, M
Rapkin, B
Clatts, M
Mullen, PD
AF West, Stephen G.
Duan, Naihua
Pequegnat, Willo
Gaist, Paul
Jarlais, Don C. Des
Holtgrave, David
Szapocznik, Jose
Fishbein, Martin
Rapkin, Bruce
Clatts, Michael
Mullen, Patricia Dolan
TI Alternatives to the randomized controlled trial
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article; Proceedings Paper
CT Meeting of the
Committee-on-the-Prevention-of-Mental-Disorders-and-Substance-Abuse-amon
g-Children-Youth-and-Young-Adults
CY OCT, 2007
CL Inst Med, Washington, DC
SP Comm Prevent Mental Disorders & Substance Abuse Children Youth & Young Adults
HO Inst Med
ID PROPENSITY SCORE; PROPHYLACTIC TRIALS; CAUSAL INFERENCE; GREATER RISK;
DESIGN; INTERVENTION; REGRESSION
AB Public health researchers are addressing new research questions (e.g., effects of environmental tobacco smoke, Hurricane Katrina) for which the randomized controlled trial (RCT) may not be a feasible option.
Drawing on the potential outcomes framework (Rubin Causal Model) and Campbellian perspectives, we consider alternative research designs that permit relatively strong causal inferences. In randomized encouragement designs, participants are randomly invited to participate in one of the treatment conditions, but are allowed to decide whether to receive treatment.
In quantitative assignment designs, treatment is assigned on the basis of a quantitative measure (e.g., need, merit, risk). In observational studies, treatment assignment is unknown and presumed to be nonrandom. Major threats to the validity of each design and statistical strategies for mitigating those threats are presented.
C1 [West, Stephen G.] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA.
[Duan, Naihua] Columbia Univ, New York, NY USA.
[Duan, Naihua] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Pequegnat, Willo] NIMH, Bethesda, MD 20892 USA.
[Gaist, Paul] NIH, Bethesda, MD 20892 USA.
[Jarlais, Don C. Des] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Holtgrave, David] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Szapocznik, Jose] Univ Miami, Sch Med, Miami, FL USA.
[Fishbein, Martin] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA.
[Rapkin, Bruce] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Clatts, Michael] Natl Dev & Res Inst Inc, New York, NY USA.
[Mullen, Patricia Dolan] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
RP West, SG (reprint author), Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA.
EM sgwest@asu.edu
NR 40
TC 138
Z9 141
U1 1
U2 17
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD AUG
PY 2008
VL 98
IS 8
BP 1359
EP 1366
DI 10.2105/AJPH.2007.124446
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 330KU
UT WOS:000257940800009
PM 18556609
ER
PT J
AU Martinez, A
Pittaluga, S
Rudelius, M
Davies-Hill, T
Sebasigari, D
Fountaine, TJ
Hewitt, S
Jaffe, ES
Raffeld, M
AF Martinez, Antonio
Pittaluga, Stefania
Rudelius, Martina
Davies-Hill, Theresa
Sebasigari, Denise
Fountaine, Thomas J.
Hewitt, Stephen
Jaffe, Elaine S.
Raffeld, Mark
TI Expression of the interferon regulatory factor 8/ICSBP-1 in human
reactive lymphoid tissues and B-cell lymphomas: A novel germinal center
marker
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE IRF8/ICSBP-1; IRF4/MUM1; lymphoma; germinal centers
ID SEQUENCE-BINDING-PROTEIN; CHRONIC LYMPHOCYTIC-LEUKEMIA; TRANSCRIPTION
FACTOR; DENDRITIC CELLS; FACTOR FAMILY; BCL-6; ICSBP; GENE; ACTIVATION;
REPRESSION
AB To assess the role of interferon regulatory factor (IRF) 8 in B-cell development and lymphomagenesis, we studied its expression in reactive lymphoid tissues.. its relationship to other B-cell transcription factors, and its expression in a series of 232 B-cell tumors and 30 cell lines representing a variety of B-cell developmental stages. We found that although IRF8 was detectable in most reactive B-cells, its expression levels differed with developmental stage. Germinal center B cells contained the highest levels of IRF8, with lower levels seen in mantle and marginal zone B cells and none in plasma cells. IRF8 was coexpressed with PAX-5, Pu. 1, and B-cell lymphoma (BCL)-6, and similar to BCL-6, was absent from the small population of IRF4-positive germinal center B cells thought to be committed to postgerminal center developmental programs. Similarly, IRF8 was most strongly expressed in lymphomas of germinal center origin with lower levels present in mantle cell lymphomas, chronic lymphocytic leukemia, and marginal zone lymphomas. and no expression observed in plasmacytic/plasmablastic neoplasms. The reciprocal expression pattern with IRF4 in reactive tissues was generally maintained in lymphomas with some exceptions. These results suggest an important role for IRF8 during germinal center B-cell development and in related lymphomas, and provide a new diagnostic marker helpful in distinguishing B-cell non-Hodgkin lymphoma subtypes.
C1 [Martinez, Antonio; Pittaluga, Stefania; Rudelius, Martina; Davies-Hill, Theresa; Sebasigari, Denise; Fountaine, Thomas J.; Hewitt, Stephen; Jaffe, Elaine S.; Raffeld, Mark] Natl Canc Inst, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA.
[Martinez, Antonio] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer, Hematopathol Sect, Pathol Lab, Barcelona, Spain.
RP Raffeld, M (reprint author), Natl Canc Inst, Pathol Lab, Hematopathol Sect, Bldg 10,Room 2N110,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mraff@box-m.nih.gov
RI Martinez, Antonio/D-8188-2012;
OI Martinez, Antonio/0000-0003-0790-9017; Hewitt,
Stephen/0000-0001-8283-1788
FU Intramural NIH HHS
NR 36
TC 21
Z9 21
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD AUG
PY 2008
VL 32
IS 8
BP 1190
EP 1200
PG 11
WC Pathology; Surgery
SC Pathology; Surgery
GA 332AP
UT WOS:000258054300010
PM 18580679
ER
PT J
AU Xiong, X
Harville, EW
Mattison, DR
Elkind-Hirsch, K
Pridjian, G
Buekens, P
AF Xiong, Xu
Harville, Emily W.
Mattison, Donald R.
Elkind-Hirsch, Karen
Pridjian, Gabriella
Buekens, Pierre
TI Exposure to Hurricane Katrina, post-traumatic stress disorder and birth
outcomes
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE depression; disaster; low birth weight; post-traumatic stress disorder;
pregnancy
ID PREGNANCY OUTCOMES; DISASTER; SUPPORT; SCALE
AB Background. Little is known about the effects of natural disasters on pregnancy outcomes. We studied mental health and birth outcomes among women exposed to Hurricane Katrina. Methods: We collected data prospectively from a cohort of 301 women from New Orleans and Baton Rouge. Pregnant women were interviewed during pregnancy about their experiences during the hurricane, and whether they had experienced symptoms of post-traumatic stress disorder (PTSD) and/or depression. High hurricane exposure was defined as having 3 or more of the 8 severe hurricane experiences, such as feeling that one's life was in danger, walking through floodwaters, or having a loved one die. Results: The frequency of low birth weight was higher in women with high hurricane exposure (14.0%) than women without high hurricane exposure (4.7%), with an adjusted odds ratio (aOR): 3.3; 95% confidence interval (0): 1.13-9.89; P < 0.01. The frequency of preterm birth was higher in women with high hurricane exposure (14.0%) than women without high hurricane exposure (6.3%), with aOR: 2.3; 95% CI: 0.82-6.38; P > 0.05. There were no significant differences in the frequency of low birth weight or preterm birth between women with PTSD or depression and women without PTSD or depression (P > 0.05). Conclusions: Women who had high hurricane exposure were at an increased risk of having low birth weight infants. Rather than a general exposure to disaster, exposure to specific severe disaster events and the intensity of the disaster experience may be better predictors of poor pregnancy outcomes. To prevent poor pregnancy outcomes during and after disasters, future disaster preparedness may need to include the planning of earlier evacuation of pregnant women to minimize their exposure to severe disaster events.
C1 [Xiong, Xu; Harville, Emily W.; Buekens, Pierre] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA.
[Mattison, Donald R.] NICHHD, NIH, Rockville, MD USA.
[Elkind-Hirsch, Karen] Womens Hosp Med Ctr, Womans Hlth Res Inst, Baton Rouge, LA USA.
[Pridjian, Gabriella] Tulane Univ, Sch Med, Dept Obstet & Gynecol, New Orleans, LA 70112 USA.
RP Xiong, X (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,SL-18, New Orleans, LA 70112 USA.
EM xxiong@tulane.edu
RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013
OI Mattison, Donald/0000-0001-5623-0874
FU NIH/NICHD [3U01HD040477-0552]; National Institute of Child Health And
Human Development [K12HD043451]
FX This study was supported by NIH/NICHD 3U01HD040477-0552. Dr. Harville is
a BIRCWH scholar, supported by Grant Number K12HD043451 from the
National Institute of Child Health And Human Development.
NR 17
TC 65
Z9 66
U1 2
U2 9
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 AUG
PY 2008
VL 336
IS 2
BP 111
EP 115
DI 10.1097/MAJ.0b013e318180f21c
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 342KP
UT WOS:000258783300006
PM 18703903
ER
PT J
AU Liu, SF
Mu, JB
Jiang, HY
Su, XZ
AF Liu, Shengfa
Mu, Jianbing
Jiang, Hongying
Su, Xin-zhuan
TI Effects of Plasmodium falciparum mixed infections on in vitro
antimalarial drug tests and genotyping
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID LINKED-IMMUNOSORBENT-ASSAY; RICH PROTEIN-II; MALARIA PARASITES;
CHLOROQUINE RESISTANCE; MICROSATELLITE MARKERS; LACTATE-DEHYDROGENASE;
MULTIDRUG-RESISTANCE; SENSITIVITY; VALIDATION; EFFICACY
AB Studying drug resistance in Plasmodium falciparum requires accurate measurement of parasite response to a drug. Factors such as mixed infection of drug-resistant and -sensitive parasites can influence drug test outcome. Polymorphic DNA sequences are frequently used to detect mixed infections; infections with a single genotype or having a minor allele smaller than a subjectively selected cut-off value are often considered single infection. We studied the effects of mixed parasite populations containing various ratios of parasites resistant and sensitive to chloroquine on outcomes of drug tests and how ratios of parasite mixtures correlated with genotypes using polymerase chain reaction-based methods. Our results show that a mixture with a resistant population as low as 10% could greatly impact a drug test outcome. None of the genotyping methods could reliably detect minor DNA alleles at <= 10%. Mixed infection presents a serious problem for drug tests, and genotyping using microsatellite or other methods may not reliably reflect true ratios of alleles.
C1 [Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
Xiamen Univ, Minist Educ Cell Biol & Tumor Cell Engn, Key Lab, Sch Life Sci, Xiamen, Fujian, Peoples R China.
RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3E24B, Rockville, MD 20852 USA.
EM xsu@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU Intramural NIH HHS [Z99 AI999999, Z01 AI000892-07]
NR 42
TC 36
Z9 37
U1 0
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD AUG
PY 2008
VL 79
IS 2
BP 178
EP 184
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 335RD
UT WOS:000258306800010
PM 18689621
ER
PT J
AU O'Meara, WP
Mwangi, TW
Williams, TN
McKenzie, FE
Snow, RW
Marsh, K
AF O'Meara, Wendy P.
Mwangi, Tabitha W.
Williams, Thomas N.
McKenzie, F. Ellis
Snow, Robert W.
Marsh, Kevin
TI Relationship between exposure, clinical malaria, and age in an area of
changing transmission intensity
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM TRANSMISSION; SEVERE CHILDHOOD MALARIA; KENYAN
COAST; KILIFI DISTRICT; SEVERE DISEASE; DRUG POLICY; CHILDREN;
MORBIDITY; MORTALITY; AFRICA
AB The relationship between malaria transmission intensity and clinical disease is important for predicting the outcome of control measures that reduce transmission. Comparisons of hospital data between areas of differing transmission intensity suggest that the mean age of hospitalized clinical malaria is higher under relatively lower transmission, but the total number of episodes is similar until transmission drops below a threshold, where the risks of hospitalized malaria decline. These observations have rarely been examined longitudinally in a single community where transmission declines over time. We reconstructed 16 years (1991-2006) of pediatric hospital surveillance data and infection prevalence surveys from a circumscribed geographic area on the Kenyan coast. The incidence of clinical malaria remained high, despite sustained reductions in exposure to infection. However, the age group experiencing the clinical attacks of malaria increased steadily as exposure declined and may precede changes in the number of episodes in an area with declining transmission.
C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
Kenya Govt Med Res Ctr, CGMRC, Wellcome Trust Collaborat Programme, Kilifi, Kenya.
KEMRI, Wellcome Trust Collaborat Programme, Nairobi, Kenya.
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, John Radcliffe Hosp, Oxford, England.
RP O'Meara, WP (reprint author), 16 Ctr Dr, Bethesda, MD 20892 USA.
EM prudhomw@mail.nih.gov
FU Intramural NIH HHS [Z99 TW999999]; Wellcome Trust [079080, 079081,
076934/Z/05/Z, 076934]
NR 35
TC 47
Z9 47
U1 2
U2 3
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD AUG
PY 2008
VL 79
IS 2
BP 185
EP 191
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 335RD
UT WOS:000258306800011
PM 18689622
ER
PT J
AU Wu, S
Birnbaumer, M
Guan, ZQ
AF Wu, Shilan
Birnbaumer, Mariel
Guan, Ziqiang
TI Phosphorylation analysis of G protein-coupled receptor by mass
spectrometry: Identification of a phosphorylation site in V2 vasopressin
receptor
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID V2 VASOPRESSIN RECEPTOR; KINASE-C; PHOSPHOPROTEINS; DESENSITIZATION;
CHROMATOGRAPHY; TRAFFICKING; AFFINITY
AB Phosphorylation plays vital roles in the regulation and function of the V2 vasopressin receptor (V2R), a G protein-coupled receptor (GPCR) that is responsible for maintaining water homeostasis in the kidney. Through a combination of immunoaffinity purification, immobilized metal affinity chromatography, and nanoflow liquid chromatography tandem mass spectrometry, we identified a novel phosphorylation site (Ser(255)) in the third intracellular loop of human V2R. We showed that the third intracellular loop could be phosphorylated in vitro by protein kinase A, but not by Akt kinase, although sequence motif analysis predicated otherwise. The analytical procedures and methodologies described in this study should be generally applicable for identifying the endogenous phosphorylation sites in other GPCRs, overcoming the limitations of conventional approaches such as sequence motif analysis and site-directed mutagenesis.
C1 [Wu, Shilan; Birnbaumer, Mariel] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Guan, Ziqiang] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Guan, ZQ (reprint author), NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
EM zguan@biochem.duke.edu
FU Intramural NIH HHS [Z99 ES999999]; NIGMS NIH HHS [U54 GM069338-01,
GM-069338, U54 GM069338, U54 GM069338-019009]
NR 24
TC 5
Z9 5
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD AUG 1
PY 2008
VL 80
IS 15
BP 6034
EP 6037
DI 10.1021/ac8008548
PG 4
WC Chemistry, Analytical
SC Chemistry
GA 332PX
UT WOS:000258096700056
PM 18578504
ER
PT J
AU Carter, MC
Uzzaman, A
Scott, LM
Metcalfe, DD
Quezado, Z
AF Carter, Melody C.
Uzzaman, Ashraf
Scott, Linda M.
Metcalfe, Dean D.
Quezado, Zenaide
TI Pediatric mastocytosis: Routine anesthetic management for a complex
disease
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID SYSTEMIC MASTOCYTOSIS; HISTAMINE-RELEASE; URTICARIA PIGMENTOSA;
MAST-CELL; PATIENT; TUBOCURARINE; CHILD
AB BACKGROUND: Pediatric mastocytosis consists of a spectrum of clinical variants characterized by increased numbers of resident mast cells in various organ systems. Mast cells are instrumental in mediating anaphylaxis and patients with mastocytosis are at risk to develop provoked and unprovoked episodes of anaphylaxis.
METHODS: We examined perianesthetic records of patients with pediatric mastocytosis who were anesthetized for diagnostic and surgical procedures from 1993 to 2006. In addition, we conducted a literature review of the anesthetic experience in pediatric mastocytosis.
RESULTS: Twenty-two patients with pediatric mastocytosis, with a median age of 3.2 yr (range, 6 mo-20 yr) at the time of the procedure, were anesthetized for 29 diagnostic and surgical procedures. All variants of the disease are represented in this series. Most patients had a history of flushing, pruritus, gastro-esophageal reflux diseases, and abdominal pain; one patient had a history of spontaneous anaphylaxis. Routine anesthetic techniques were used and, despite the complexity of the disease, the perioperative courses were uncomplicated and without serious adverse events.
CONCLUSIONS: We reviewed the main features of pediatric mastocytosis, its anesthetic and perioperative implications, and describe a practical approach to the anesthetic management of pediatric patients with the disease. Although many drugs used routinely in anesthesia reportedly caused mast cell degranulation, deviations from routine anesthesia techniques are not necessarily warranted. However, an understanding of the anesthetic implications of the disease and meticulous preparation to treat possible adverse events are advised.
C1 [Carter, Melody C.; Uzzaman, Ashraf; Scott, Linda M.; Metcalfe, Dean D.] NIAID, NIH, LAD, Bethesda, MD 20892 USA.
[Quezado, Zenaide] NIH, Dept Anesthesia & Surg Serv, Ctr Clin, Bethesda, MD USA.
RP Carter, MC (reprint author), NIAID, NIH, LAD, 10 Ctr Dr,MSC 1881,Bldg 10,Room 11C-213, Bethesda, MD 20892 USA.
EM mcarter@niaid.nih.gov; zquezado@nih.gov
RI Quezado, Zenaide/O-4860-2016
OI Quezado, Zenaide/0000-0001-9793-4368
FU Intramural NIH HHS [Z01 AI000249-26, ZIA CL009009-02]
NR 24
TC 33
Z9 33
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD AUG
PY 2008
VL 107
IS 2
BP 422
EP 427
DI 10.1213/ane.0b013e31817e6d7c
PG 6
WC Anesthesiology
SC Anesthesiology
GA 333QV
UT WOS:000258168300015
PM 18633019
ER
PT J
AU Matot, I
Einav, S
Weiniger, CF
Pearl, RG
Abramovitch, R
Joshi, BV
Jacobson, KA
AF Matot, Idit
Einav, Sharon
Weiniger, Carolyn F.
Pearl, Ron G.
Abramovitch, Rinat
Joshi, Balachandra V.
Jacobson, Kenneth A.
TI Lung injury after in vivo reperfusion - Outcome at 27 hours after
reperfusion
SO ANESTHESIOLOGY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the American-Society-of-Anesthesiologists
CY OCT 13-17, 2007
CL San Francisco, CA
SP Amer Soc Anesthesiologists
ID TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASE; ADHESION MOLECULE
EXPRESSION; ISCHEMIA-REPERFUSION; RAT LUNG; FACTOR-ALPHA; ATTENUATES
ISCHEMIA; CELL-DEATH; APOPTOSIS; TRANSPLANTATION
AB Background: Although short-term findings after lung reperfusion have been extensively reported, in vivo animal studies have not described outcome beyond the immediate time period. Therefore, the authors evaluated lung injury 27 h after reperfusion. They also investigated whether attenuation of lung injury with the A(3) adenosine receptor agonist MRS3558 was sustained beyond the immediate time period.
Methods: In intact-chest, spontaneously breathing cats in which the left lower lung lobe was isolated and subjected to 2 h of ischemia and 3 h of reperfusion, MRS3558 was administered before reperfusion. Animals were killed 3 or 27 h after reperfusion.
Results: When compared with 3 h of reperfusion, at 27 h the left lower lobe showed reduced apoptosis and no change in inflammation, but increased edema. increased edema of the nonischemic right lung and hypoxemia were observed at 27 h after left lower lobe reperfusion. Increases in phosphorylated p38 levels were found at 3 h of reperfusion compared with control lung, with further increases at 27 h. The attenuation of injury observed with MRS3558 treatment at 3 h of reperfusion was sustained at 27 h.
Conclusions: Lung edema may worsen hours after the immediate postreperfusion period, even though lung apoptosis and inflammation are reduced or show no change, respectively. This was associated with further increases in phosphorylated p38 levels. The nonischemic lung may also be affected, suggesting a systemic response to reperfusion. In addition, early attenuation of injury is beneficial beyond the immediate period after reperfusion. Treatment aimed at inhibiting p38 activation, such as A(3) receptor activation, should be further studied to explore its potential long-term beneficial effect.
C1 [Matot, Idit] Tel Aviv Sourasky Med Ctr, Dept Anesthesiol & Crit Care Med, IL-64239 Tel Aviv, Israel.
[Einav, Sharon] Shaare Zedek Med Ctr, Gen Intens Care Unit, Jerusalem, Israel.
[Weiniger, Carolyn F.] Hadassah Hebrew Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel.
[Abramovitch, Rinat] Hadassah Hebrew Univ, Med Ctr, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel.
[Pearl, Ron G.] Stanford Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Palo Alto, CA USA.
[Joshi, Balachandra V.; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
RP Matot, I (reprint author), Tel Aviv Sourasky Med Ctr, Dept Anesthesiol & Crit Care Med, 6 Weizman St, IL-64239 Tel Aviv, Israel.
EM iditm@tasmc.health.gov.il
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [Z01 DK031117-20]
NR 46
TC 8
Z9 10
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD AUG
PY 2008
VL 109
IS 2
BP 269
EP 278
PG 10
WC Anesthesiology
SC Anesthesiology
GA 330KK
UT WOS:000257939600015
PM 18648236
ER
PT J
AU Dierker, L
He, JP
Kalaydjian, A
Swendsen, J
Degenhardt, L
Glantz, M
Conway, K
Anthony, J
Chiu, WT
Sampson, NA
Kessler, R
Merikangas, K
AF Dierker, Lisa
He, Jianping
Kalaydjian, Amanda
Swendsen, Joel
Degenhardt, Louisa
Glantz, Meyer
Conway, Kevin
Anthony, James
Chiu, Wai Tat
Sampson, Nancy A.
Kessler, Ronald
Merikangas, Kathleen
TI The importance of timing of transitions for risk of regular smoking and
nicotine dependence
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Article
DE nicotine dependence; smoking; NCS-R; transitions
ID FUTURE SMOKING; UNITED-STATES; ADOLESCENTS; INITIATION; SYMPTOMS
AB Background Estimating the timing and speed among smoking milestones is an important challenge for epidemiology given that further reductions in smoking prevalence may be best achieved by programs that target potentially malleable smoking behavior before the development of nicotine dependence.
Purpose The purpose of the study was to investigate the association between the timing and speed of transition among major smoking milestones (onset, weekly, and daily smoking) and onset and recovery from nicotine dependence.
Methods Analyses are based on data from The National Comorbidity Survey-Replication, a nationally representative face-to-face household survey conducted between February 2001 and April 2003.
Results Of those who had ever smoked (n=5,692), 71.3% had reached weekly smoking levels and 67.5% had reached daily smoking. Four in ten who had ever smoked met criteria for nicotine dependence. A shorter time since the onset of weekly and daily smoking was associated with a transition to both daily smoking and nicotine dependence, respectively. The risk for each smoking transition was highest within the year following the onset of the preceding milestone. Recovery was associated with a longer period of time between smoking initiation and the development of dependence and a later age of smoking onset.
Conclusions These findings shed light on the clinical course of smoking and nicotine dependence. Given the importance of timing of smoking transitions, prevalence may be further reduced through intervention targeted at adolescents and young adults in the months most proximal to smoking initiation.
C1 [Dierker, Lisa] Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA.
[He, Jianping; Kalaydjian, Amanda; Merikangas, Kathleen] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA.
[Swendsen, Joel] Natl Ctr Sci Res, Bordeaux, France.
[Degenhardt, Louisa] Univ New S Wales, Natl Drug & Alcohol Res Ctr, Kensington, NSW 2033, Australia.
[Glantz, Meyer; Conway, Kevin] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent, Bethesda, MD USA.
[Anthony, James] Michigan State Univ, Sch Med, E Lansing, MI 48824 USA.
[Chiu, Wai Tat; Sampson, Nancy A.; Kessler, Ronald] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
RP Dierker, L (reprint author), Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA.
EM ldierker@wesleyan.edu
RI Degenhardt, Louisa/D-4515-2012;
OI Degenhardt, Louisa/0000-0002-8513-2218; Conway,
Kevin/0000-0002-7638-339X
FU Intramural NIH HHS [Z01 MH002804-05, Z01 MH002806-05, Z01 MH002849-03];
NIDA NIH HHS [K01 DA015454, K01 DA015454-01, K01 DA15454]; NIMH NIH HHS
[U01 MH060220, U01 MH060220-01, U01-MH60220]
NR 20
TC 18
Z9 19
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD AUG
PY 2008
VL 36
IS 1
BP 87
EP 92
DI 10.1007/s12160-008-9051-x
PG 6
WC Psychology, Multidisciplinary
SC Psychology
GA 355NK
UT WOS:000259715400010
PM 18704617
ER
PT J
AU Hendee, WR
Cleary, K
Ehman, RL
Fullerton, GD
Grundfest, WS
Haller, J
Kelley, C
Meyer, AE
Murphy, RF
Phillips, W
Torchilin, VP
AF Hendee, William R.
Cleary, Kevin
Ehman, Richard L.
Fullerton, Gary D.
Grundfest, Warren S.
Haller, John
Kelley, Christine
Meyer, Anne E.
Murphy, Robert F.
Phillips, William
Torchilin, Vladimir P.
TI Bioengineering and imaging research opportunities workshop V: A summary
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE tissue engineering; functional, molecular and structural imaging;
imaging of engineered tissues; targeted cell, gene and drug delivery;
single-cell measurements; emerging imaging technologies
ID MAGNETIC-RESONANCE ELASTOGRAPHY; CANCER-THERAPY; WHITE PAPER;
MICROSCOPY; RECOMMENDATIONS; VISUALIZATION; SYSTEMS
AB The fifth Bioengineering and Imaging Research Opportunities Workshop (BIROW V) was held on January 18-19, 2008. As with previous BIROW meetings, the purpose of BIROW V was to identify and characterize research and engineering opportunities in biomedical engineering and imaging. The topic of this BIROW meeting was Imaging and Characterizing Structure and Function in Native and Engineered Tissues. Under this topic, four areas were explored in depth: (1) Heterogeneous single-cell measurements and their integration into tissue and organism models; (2) Functional, molecular, and structural imaging of engineered tissue in vitro and in vivo; (3) New technologies for characterizing cells and tissues in situ; (4) Imaging for targeted cell, gene, and drug delivery.
C1 [Hendee, William R.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Cleary, Kevin] Georgetown Univ, Washington, DC 20007 USA.
[Ehman, Richard L.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA.
[Fullerton, Gary D.; Phillips, William] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, Div Res, San Antonio, TX 78229 USA.
[Grundfest, Warren S.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Haller, John] NIBIB, NIH, Bethesda, MD 20892 USA.
[Kelley, Christine] NIBIB, Div Discovery Sci & Technol, NIH, DHHS, Bethesda, MD 20892 USA.
[Meyer, Anne E.] SUNY Buffalo, Buffalo, NY 14214 USA.
[Murphy, Robert F.] Carnegie Mellon Univ, Dept Biomed Engn, Pittsburgh, PA 15213 USA.
[Torchilin, Vladimir P.] NE Univ, Dept Pharm & Sci, Boston, MA 02115 USA.
RP Hendee, WR (reprint author), Med Coll Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM whendee@mcw.edu
RI Phillips, William/E-8427-2010
OI Phillips, William/0000-0001-8248-7817
NR 26
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD AUG
PY 2008
VL 36
IS 8
BP 1315
EP 1321
DI 10.1007/s10439-008-9529-5
PG 7
WC Engineering, Biomedical
SC Engineering
GA 332DH
UT WOS:000258061700001
PM 18612827
ER
PT J
AU Troncoso, JC
Zonderman, AB
Resnick, SM
Crain, B
Pletnikova, O
O'Brien, RJ
AF Troncoso, Juan C.
Zonderman, Alan B.
Resnick, Susan M.
Crain, Barbara
Pletnikova, Olga
O'Brien, Richard J.
TI Effect of infarcts on dementia in the Baltimore Longitudinal Study of
Aging
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; OLDER PERSONS; CEREBRAL
INFARCTIONS; COGNITIVE FUNCTION; CLINICAL-CRITERIA; BRAIN INFARCTS;
BASAL GANGLIA; POPULATION; PATHOLOGY
AB Objective: To define the magnitude and mechanism of the effect of brain infarcts on the odds of dementia in a prospective study.
Methods: We examined the effects of brain infarcts and Alzheimer's disease (AD) pathology on the risk for dementia in 179 subjects from the Baltimore Longitudinal Study of Aging Autopsy Program. All subjects had longitudinal clinical and cognitive evaluations, and underwent postmortem examination of the brain.
Results: Brain infarcts were common in our cohort, and both symptomatic and asymptomatic infarcts conferred a significant increase in the odds of dementia. Risk factors for stroke in the absence of an infarct did not increase the odds of dementia, which was quantitatively related to the number but not the size of hemispheral infarcts; deep subcortical infarcts conferred no increased risk for dementia. The contribution of microscopic infarcts to dementia was significant and equivalent to that of macroscopic infarcts. In Subjects with intermediate AD pathology scores, a single macroscopic hemispheral infarct was sufficient to cause dementia. A logistic regression model of the effect of infarcts and AD pathology on dementia indicated that AD pathology alone accounts for 50% of the dementia seen in this cohort, and that hemispheral infarcts alone or in conjunction with AD pathology account for 35%.
Interpretation: Cerebrovascular disease is a significant and potentially preventable cause of dementia in the Baltimore Longitudinal Study of Aging. Burden and location of infarcts are significantly associated with cognitive decline.
C1 [O'Brien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Neurol & Med, Baltimore, MD 21224 USA.
[Troncoso, Juan C.; Crain, Barbara; Pletnikova, Olga] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Troncoso, Juan C.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Zonderman, Alan B.; Resnick, Susan M.] NIA, Natl Inst Hlth, Intramural Res Program, Lab Personal & Cognit, Bethesda, MD 20892 USA.
RP O'Brien, RJ (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol & Med, Mason F Lord Ctr Tower,Suite 5100,5200 Eastern Av, Baltimore, MD 21224 USA.
EM robrien@jhmi.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU NIH [P50 AG05146]; Intramural Research Program, National Institute on
Aging; Burroughs Wellcome Fund [1005227]
FX This work was supported by NIH (National Institute on Aging), P50
AG05146 (R.J.O, J.C.T.); Intramural Research Program, National Institute
on Aging (A.B.Z., S.M.R.) and the Burroughs Wellcome Fund for
Translational Research (1005227, R.J.O.).
NR 39
TC 107
Z9 112
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD AUG
PY 2008
VL 64
IS 2
BP 168
EP 176
DI 10.1002/ana.21413
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 344JC
UT WOS:000258921800008
PM 18496870
ER
PT J
AU Zhang, Q
Wu, J
Nguyen, A
Wang, BD
He, P
Laurent, GS
Rennert, OM
Su, YA
AF Zhang, Qiuyang
Wu, Jun
Nguyen, AnhThu
Wang, Bi-Dar
He, Ping
Laurent, Georges St.
Rennert, Owen M.
Su, Yan A.
TI Molecular mechanism underlying differential apoptosis between human
melanoma cell lines UACC903 and UACC903(+6) revealed by
mitochondria-focused cDNA microarrays
SO APOPTOSIS
LA English
DT Article
DE melanoma; apoptosis; pathways; FAS; FASLG; BAK1
ID HUMAN-MALIGNANT MELANOMA; DNA-DAMAGE; EXONUCLEASE ACTIVITY;
GENE-EXPRESSION; CONNEXIN GENES; IN-SITU; TUMORIGENICITY; CHROMOSOME-6;
IDENTIFICATION; SUPPRESSION
AB Human malignant melanoma cell line UACC903 is resistant to apoptosis while chromosome 6-mediated suppressed cell line UACC903(+6) is sensitive. Here, we describe identification of differential molecular pathways underlying this difference. Using our recently developed mitochondria-focused cDNA microarrays, we identified 154 differentially expressed genes including proapoptotic (BAK1 [6p21.3], BCAP31, BNIP1, CASP3, CASP6, FAS, FDX1, FDXR, TNFSF10 and VDAC1) and antiapoptotic (BCL2L1, CLN3 and MCL1) genes. Expression of these pro- and anti-apoptotic genes was higher in UACC903(+6) than in UACC903 before UV treatment and was altered after UV treatment. qRT-PCR and Western blots validated microarray results. Our bioinformatic analysis mapped these genes to differential molecular pathways that predict resistance and sensitivity of UACC903 and UACC903(+6) to apoptosis respectively. The pathways were functionally confirmed by the FAS ligand-induced cell death and by siRNA knockdown of BAK1 protein. These results demonstrated the differential molecular pathways underlying survival and apoptosis of UACC903 and UACC903(+6) cell lines.
C1 [Zhang, Qiuyang; Wu, Jun; Nguyen, AnhThu; Wang, Bi-Dar; Laurent, Georges St.; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
[Zhang, Qiuyang; Wu, Jun; Nguyen, AnhThu; Wang, Bi-Dar; Laurent, Georges St.; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA.
[He, Ping] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hemostasis, Bethesda, MD 20892 USA.
[Laurent, Georges St.] Univ Antioquia, Immunovirol Biogenesis Grp, Medellin, Colombia.
[Rennert, Owen M.] NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA.
RP Su, YA (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Ross Hall,Room 555,2300 I St NW, Washington, DC 20037 USA.
EM bcmyas@gwumc.edu
FU PHS HHS [06-925]
NR 45
TC 9
Z9 10
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
J9 APOPTOSIS
JI Apoptosis
PD AUG
PY 2008
VL 13
IS 8
BP 993
EP 1004
DI 10.1007/s10495-008-0231-8
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 325KL
UT WOS:000257587700004
PM 18563568
ER
PT J
AU Irie, F
Masaki, KH
Petrovitch, H
Abbott, RD
Ross, GW
Taaffe, DR
Launer, LJ
White, LR
AF Irie, Fumiko
Masaki, Kamal H.
Petrovitch, Helen
Abbott, Robert D.
Ross, G. Webster
Taaffe, Dennis R.
Launer, Lenore J.
White, Lon R.
TI Apolipoprotein E epsilon 4 allele genotype and the effect of depressive
symptoms on the risk of dementia in men
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID ISCHEMIC CEREBROVASCULAR-DISEASE; MILD COGNITIVE IMPAIRMENT;
JAPANESE-AMERICAN MEN; WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; MAJOR
DEPRESSION; VASCULAR-DISEASE; APOE GENOTYPE; OLDEST-OLD; DECLINE
AB Context: The apolipoprotein E e4 ( APOE e4) allele is a genetic risk factor for Alzheimer disease. Recently, depression has also become recognized as a risk factor for dementia. However, the possible effect of the APOE genotype on the association between depression and dementia is unexamined.
Objective: To examine the independent and combined effects of depression and APOE e4 on the risk of dementia and its subtypes.
Design: The Honolulu- Asia Aging Study, a populationbased prospective cohort study of Japanese American men.
Settings and Participants: Depressive symptoms and presence of theAPOEe4 allele were assessed between March 1991 and October 1993 in 1932 cognitively healthy men aged 71 to 90 years. Incident cases of dementia were diagnosed during approximately 6 years of follow- up based on neurologic assessment at 2 repeated examinations ( April 1994- April 1996 and October 1997- February 1999).
Main Outcome Measures: Overall dementia, Alzheimer disease, and vascular dementia.
Results: The interaction of depression and APOE e4 was statistically significant in the analytical models. Compared with men with neither APOE e4 nor depression, the risk of dementia in nondepressed men with APOE e4 was not significant ( hazard ratio, 1.1; 95% confidence interval [ CI], 0.6- 1.8); however, depressed men without APOE e4 had a 1.6- fold greater risk ( 95% CI, 0.8- 3.0), whereas depressed men with APOE e4 had a 7.1- fold greater risk ( 95% CI, 3.0- 16.7) of dementia. For subtypes, we found similar increased risks of Alzheimer disease.
Conclusions: The APOE e4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE e4 allele had a markedly increased risk of dementia, one might be especially watchful for early signs of dementia in the older person with depression who is also positive for the APOE e4 allele. Because this cohort includes only men, further investigation in women is required.
C1 [Irie, Fumiko; Masaki, Kamal H.; Petrovitch, Helen; Abbott, Robert D.; Ross, G. Webster; White, Lon R.] Univ Hawaii, Pacific Hlth Res Inst, Honolulu, HI 96822 USA.
[Masaki, Kamal H.; Petrovitch, Helen; Ross, G. Webster; White, Lon R.] Univ Hawaii, Dept Geriatr Med, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Masaki, Kamal H.; Petrovitch, Helen; White, Lon R.] Kuakini Med Ctr, Honolulu, HI USA.
[Ross, G. Webster] Honolulu Dept Vet Affairs, Honolulu, HI USA.
[Irie, Fumiko] Univ Queensland, Ctr Natl Res Disabil & Rehabil Med, Mayne Med Sch, Brisbane, Qld, Australia.
[Taaffe, Dennis R.] Univ Queensland, Sch Human Movement Studies, Brisbane, Qld, Australia.
[Abbott, Robert D.] Univ Virginia, Sch Med, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA.
[Abbott, Robert D.] Shiga Univ Med Sci, Dept Hlth Sci, Shiga, Japan.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Irie, F (reprint author), Univ Queensland, Ctr Natl Res Disabil & Rehabil Med, Mayne Med Sch, Level 3,Herston Rd, Herston, Qld 4006, Australia.
EM f.irie@uq.edu.au
FU Intramural NIH HHS [ZIA AG006000-03]; NCRR NIH HHS [P41 RR013642]; NHLBI
NIH HHS [N01 HC005102]; NIA NIH HHS [N01-AG-4-2149]
NR 52
TC 41
Z9 43
U1 3
U2 5
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 AUG
PY 2008
VL 65
IS 8
BP 906
EP 912
DI 10.1001/archpsyc.65.8.906
PG 7
WC Psychiatry
SC Psychiatry
GA 334MH
UT WOS:000258225400006
PM 18678795
ER
PT J
AU Barr, CS
Dvoskin, RL
Yuan, QP
Lipsky, RH
Gupte, M
Hu, X
Zhou, Z
Schwandt, ML
Lindell, SG
Mckee, M
Becker, ML
Kling, MA
Gold, PW
Higley, D
Heilig, M
Suomi, SJ
Goldman, D
AF Barr, Christina S.
Dvoskin, Rachel L.
Yuan, Qiaoping
Lipsky, Robert H.
Gupte, Manisha
Hu, Xian
Zhou, Zhifeng
Schwandt, Melanie L.
Lindell, Stephen G.
McKee, Megan
Becker, Michelle L.
Kling, Mitchel A.
Gold, Phillip W.
Higley, Dee
Heilig, Markus
Suomi, Stephen J.
Goldman, David
TI CRH haplotype as a factor influencing cerebrospinal fluid levels of
corticotropin-releasing hormone, hypothalamic-pituitary-adrenal axis
activity, temperament, and alcohol consumption in rhesus macaques
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID NONHUMAN PRIMATE MODEL; MESSENGER-RNA LEVELS; GLUCOCORTICOID-RECEPTOR;
GENE-EXPRESSION; PROMOTER POLYMORPHISMS; TRANSCRIPTION FACTORS; FEARFUL
TEMPERAMENT; NATURAL-SELECTION; NEURONAL-ACTIVITY; PREFERRING RATS
AB Context: Both highly stress- reactive and novelty- seeking individuals are susceptible to alcohol use disorders. Variation in stress reactivity, exploration, and response to novelty have been attributed to differences in corticotropinreleasing hormone ( CRH) system function. As such, CRH gene variation may influence risk for alcohol use and dependence.
Objective: To determine whether CRH variation influences relevant intermediate phenotypes, behavior, and alcohol consumption in rhesus macaques.
Design: We sequenced the rhesus macaque CRH locus ( rhCRH) and performed cladistic clustering of haplotypes. In silico analysis, gel shift, and in vitro reporter assays were performed to identify functional variants. Cerebrospinal fluid ( CSF) and blood samples were obtained, and levels of CRH and corticotropin ( ACTH) were measured by radioimmunoassay. Behavioral data were collected from macaques during infancy. Among adolescent/ adult animals, we recorded responses to an unfamiliar conspecific and measured levels of ethanol consumption. Setting: National Institutes of Health Animal Center.
Main Outcome Measures: Animals were genotyped for a single- nucleotide polymorphism disrupting a glucocorticoid response element, rhCRH - 2232 C > G, and the effects of this allele on CSF levels of CRH, plasma levels of ACTH, behavior, and ethanol consumption were assessed by analysis of variance.
Results: We show that - 2232C > G alters DNA X protein interactions and confers decreased sensitivity of the CRH promoter to glucocorticoids in vitro. Consistent with the known effects of glucocorticoids on CRH expression in the brain, carriers of the G allele had lower CSF levels of CRH but higher levels of ACTH. Infants carrying the G allele were more exploratory and bold, and among adolescent and adult male macaques, the G allele was associated with exploratory/ bold responding to an unfamiliar male. Adults with the C/ G genotype also exhibited increased alcohol consumption in the social group, a model for high- risk alcohol- seeking behavior.
Conclusion: Haplotypes that differ in terms of corticosteroid sensitivity have been identified in humans. Our data may suggest that functionally similar CRH variants could influence risk for externalizing disorders in human subjects.
C1 [Barr, Christina S.; Dvoskin, Rachel L.; Gupte, Manisha; Schwandt, Melanie L.; Lindell, Stephen G.; McKee, Megan; Becker, Michelle L.; Heilig, Markus] Natl Inst Alcohol Abuse, Lab Clin & Translat Studies, Natl Inst Hlth, Bethesda, MD USA.
[Yuan, Qiaoping; Lipsky, Robert H.; Hu, Xian; Zhou, Zhifeng; Goldman, David] Natl Inst Alcohol Abuse, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD USA.
[Kling, Mitchel A.; Gold, Phillip W.] NIMH, NIH, Bethesda, MD 20892 USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, Natl Inst Hlth, Poolesville, MD USA.
[Higley, Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
RP Barr, CS (reprint author), NIAAA, Clin Studies Lab, Primate Sect, Div Intramural Clin & Biol Res, TR 112,POB 529, Poolesville, MD 20837 USA.
EM cbarr@mail.nih.gov
RI Kling, Mitchel/F-4152-2010; Goldman, David/F-9772-2010; Schwandt,
Melanie/L-9866-2016;
OI Kling, Mitchel/0000-0002-2232-1409; Goldman, David/0000-0002-1724-5405;
Heilig, Markus/0000-0003-2706-2482; Lipsky, Robert/0000-0001-7753-1473
FU Intramural NIH HHS [Z01 AA000214-06, Z01 AA000305-04, Z01 AA000306-02,
Z99 AA999999]
NR 60
TC 41
Z9 41
U1 0
U2 3
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 AUG
PY 2008
VL 65
IS 8
BP 934
EP 944
DI 10.1001/archpsyc.65.8.934
PG 11
WC Psychiatry
SC Psychiatry
GA 334MH
UT WOS:000258225400009
PM 18678798
ER
PT J
AU Krishnan, C
Kaplin, AI
Brodsky, RA
Drachman, DB
Jones, RJ
Pham, DL
Richert, ND
Pardo, CA
Yousem, DM
Hammond, E
Quigg, M
Trecker, C
McArthur, JC
Nath, A
Greenberg, BM
Calabresi, PA
Kerr, DA
AF Krishnan, Chitra
Kaplin, Adam I.
Brodsky, Robert A.
Drachman, Daniel B.
Jones, Richard J.
Pham, Dzung L.
Richert, Nancy D.
Pardo, Carlos A.
Yousem, David M.
Hammond, Edward
Quigg, Megan
Trecker, Carrilin
McArthur, Justin C.
Nath, Avindra
Greenberg, Benjamin M.
Calabresi, Peter A.
Kerr, Douglas A.
TI Reduction of disease activity and disability with high-dose
cyclophosphamide in patients with aggressive multiple sclerosis
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; CLINICAL-TRIAL; AUTOIMMUNE-DISEASE;
PERIPHERAL-BLOOD; THERAPY; SEGMENTATION; COMBINATION; TOLERANCE
AB Objective: To explore the safety and effectiveness of high-dose cyclophosphamide (HiCy) without bone marrow transplantation in patients with aggressive multiple sclerosis (MS).
Design: A 2-year open-label trial of patients with aggressive relapsing-remitting multiple sclerosis (RRMS) given an immunoablative regimen of HiCy ( 50 mg/kg/d for 4 consecutive days) with no subsequent immunomodulatory therapy unless disease activity reappeared that required rescue therapy.
Setting: The Johns Hopkins University Multiple Sclerosis Center, Baltimore, Maryland.
Patients: A total of 21 patients with RRMS were screened for eligibility and 9 patients were enrolled in the trial. Patients were required to have 2 or more gadolinium-enhancing lesions on each of 2 pretreatment magnetic resonance imaging scans, at least 1 clinical exacerbation in the 12 months prior to HiCy treatment, or a sustained increase of 1.0 point or higher on the Expanded Disability Status Scale (EDSS) in the preceding year.
Main Outcome Measures: The primary outcome of the study was the safety and tolerability of HiCy in patients with RRMS. Secondary outcome measures included a change in gadolinium-enhancing lesions on magnetic resonance images and a change in disability measures (EDSS and Multiple Sclerosis Functional Composite).
Results: Nine patients were treated and followed up for a mean period of 23 months. Eight patients had failed conventional therapy and 1 was treatment naive. The median age at time of entry was 29 years (range, 20-47 years). All patients developed transient total or near-total pancytopenia as expected, followed by hematopoietic recovery in 10 to 17 days, stimulated by granulocyte colony-stimulating factor. There were no deaths or unexpected serious adverse events. There was a statistically significant reduction in disability (EDSS) at follow-up (mean [SD] decrease, 2.11[1.97]; 39.4%; P = .02). The mean(SD) number of gadolinium-enhancing lesions on the 2 pretreatment scans were 6.5(2.1) and 1.2(2.3) at follow-up (81.4% reduction; P = .01). Two patients required rescue treatment with other immunomodulatory therapies during the study owing to MS exacerbations.
Conclusion: Treatment with HiCy was safe and well tolerated in our patients with MS. Patients experienced a pronounced reduction in disease activity and disability after HiCy treatment. This immunoablative regimen of cyclophosphamide for patients with aggressive MS is worthy of further study and may be an alternative to bone marrow transplantation.
C1 [Krishnan, Chitra; Kaplin, Adam I.; Drachman, Daniel B.; Pardo, Carlos A.; Quigg, Megan; McArthur, Justin C.; Nath, Avindra; Greenberg, Benjamin M.; Calabresi, Peter A.; Kerr, Douglas A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA.
[Kaplin, Adam I.; Hammond, Edward; Trecker, Carrilin] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Pham, Dzung L.; Yousem, David M.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA.
[McArthur, Justin C.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA.
[McArthur, Justin C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA.
[Brodsky, Robert A.] Johns Hopkins Univ, Dept Med, Div Hematol, Baltimore, MD 21287 USA.
[Brodsky, Robert A.; Jones, Richard J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
[Richert, Nancy D.] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Bethesda, MD USA.
RP Kerr, DA (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, 600 N Wolfe St,Path 627 C, Baltimore, MD 21287 USA.
EM dkerr@jhmi.edu
OI Greenberg, Benjamin/0000-0002-2091-8201
NR 35
TC 7
Z9 7
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD AUG
PY 2008
VL 65
IS 8
BP E1
EP E8
DI 10.1001/archneurol.65.8.noc80042
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 336PM
UT WOS:000258377100026
ER
PT J
AU Vitale, S
Ellwein, L
Cotch, MF
Ferris, FL
Sperduto, R
AF Vitale, Susan
Ellwein, Leon
Cotch, Mary Frances
Ferris, Frederick L., III
Sperduto, Robert
TI Prevalence of refractive error in the United States, 1999-2004
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID ANGELES LATINO EYE; BLUE MOUNTAINS EYE; QUALITY-OF-LIFE; BEAVER DAM EYE;
VISUAL IMPAIRMENT; ADULT-POPULATION; MYOPIA; AGE; AUSTRALIA; BLINDNESS
AB Objective: To describe the prevalence of refractive error in the United States.
Methods: The 1999-2004 National Health and Nutrition Examination Survey (NHANES) used an autorefractor to obtain refractive error data on a nationally representative sample of the US noninstitutionalized, civilian population 12 years and older. Using data from the eye with a greater absolute spherical equivalent (SphEq) value, we defined clinically important refractive error as follows: hyperopia, SphEq value of 3.0 diopters (D) or greater; myopia, SphEq value of -1.0 D or less; and astigmatism, cylinder of 1.0 D or greater in either eye.
Results: Of 14 213 participants 20 years or older who completed the NHANES, refractive error data were obtained for 12 010 (84.5%). The age-standardized prevalences of hyperopia, myopia, and astigmatism were 3.6% (95% confidence interval [CI], 3.2%-4.0%), 33.1% (95% CI, 31.5%-34.7%), and 36.2% (95% CI, 34.9%-37.5%), respectively. Myopia was more prevalent in women (39.9%) than in men (32.6%) (P < .001) among 20- to 39-year-old participants. Persons 60 years or older were less likely to have myopia and more likely to have hyperopia and/or astigmatism than younger persons. Myopia was more common in non-Hispanic whites (35.2%) than in non-Hispanic blacks (28.6%) or Mexican Americans (25.1%) (P < .001 for both).
Conclusion: Estimates based on the 1999-2004 NHANES vision examination data indicate that clinically important refractive error affects half of the US population 20 years or older.
C1 [Vitale, Susan; Cotch, Mary Frances; Ferris, Frederick L., III; Sperduto, Robert] NEI, NIH, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA.
RP Vitale, S (reprint author), 5635 Fishers Ln,Ste 1100, Bethesda, MD 20892 USA.
EM sev@nei.nih.gov
OI Cotch, Mary Frances/0000-0002-2046-4350
FU Intramural NIH HHS [Z01 EY000402-07, Z99 EY999999, Z01 EY000402-06, ZIA
EY000402-08, ZIA EY000402-09, ZIA EY000402-10]; NEI NIH HHS [Z01
EY000402]
NR 41
TC 187
Z9 194
U1 3
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD AUG
PY 2008
VL 126
IS 8
BP 1111
EP 1119
DI 10.1001/archopht.126.8.1111
PG 9
WC Ophthalmology
SC Ophthalmology
GA 336PQ
UT WOS:000258377500012
PM 18695106
ER
PT J
AU Hintz, SR
Kendrick, DE
Vohr, BR
Poole, WK
Higgins, RD
AF Hintz, Susan R.
Kendrick, Douglas E.
Vohr, Betty R.
Poole, W. Kenneth
Higgins, Rosemary D.
CA NICHD Neonatal Res Network
TI Community supports after surviving extremely low-birth-weight, extremely
preterm birth - Special outpatient services in early childhood
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID HEALTH-CARE NEEDS; GROSS MOTOR FUNCTION; WEEKS GESTATION;
NEURODEVELOPMENTAL OUTCOMES; REGIONAL COHORT; CHILDREN BORN; MEDICAL
HOME; INFANTS BORN; RESOURCE USE; AGE
AB Objective: To determine special outpatient services ( SOS) use, need, associated factors, and neurodevelopmental and functional outcomes among extremely preterm infants at 18 to 22 months' corrected age.
Design: Retrospective analysis. Setting: National Institute of Child Health and Human Development (NICHD) Neonatal Research Network.
Participants: Infants younger than 28 weeks' gestational age who had been born weighing less than 1000 g at an NICHD Neonatal Research Network center from January 1, 1997, to December 31, 2000, and who were receiving follow-up at 18 to 22 months' corrected age.
Interventions: Questionnaires were administered at the 18- to 22-month follow-up visit regarding SOS use since hospital discharge and the current need for SOS ( social work, visiting nurse, medical specialty, early intervention, speech and language services, occupational therapy and physical therapy, and neurodevelopmental and behavioral services).
Main Outcome Measures: The use of and need for SOS were analyzed by gestational age. Logistic regression analysis identified factors independently associated with the use of more than 5 services and with the need for any services.
Results: Of 2315 infants, 54.7% used more than 3 SOS by 18 to 22 months, and 19.1% used 6 to 7 SOS. The need for any SOS was reported by approximately 37%. The following variables that were commonly associated with adverse neurodevelopmental outcomes were also associated with the use of more than 5 SOS: sepsis, birth weight, postnatal corticosteroid use, bronchopulmonary dysplasia, and cystic periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage. Male sex was associated with the need for any SOS. Although high SOS use was more likely among children with adverse neurodevelopmental outcomes, a reported need for SOS was common even among those with mild developmental impairment (39.7%) and mild cerebral palsy (42.2%).
Conclusions: High SOS use is common, has identifiable neonatal risk factors, and is associated with neurodevelopmental impairment. Extremely preterm survivors have substantial need for community supports regardless of their impairment level. Efforts to improve comprehensive delivery of family-centered community-based services are urgently needed.
C1 [Hintz, Susan R.] Stanford Univ, Div Neonatal & Dev Med, Dept Pediat, Sch Med, Palo Alto, CA 94304 USA.
[Kendrick, Douglas E.; Poole, W. Kenneth] RTI Int, Res Triangle Pk, NC USA.
[Vohr, Betty R.] Brown Univ, Sch Med, Neonatal Followup Clin, Women & Infants Hosp, Providence, RI 02912 USA.
[Vohr, Betty R.] Brown Univ, Sch Med, Dept Pediat, Providence, RI 02912 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Rockville, MD USA.
RP Hintz, SR (reprint author), Stanford Univ, Div Neonatal & Dev Med, Dept Pediat, Sch Med, 750 Welch Rd,Ste 315, Palo Alto, CA 94304 USA.
EM srhintz@stanford.edu
FU NCATS NIH HHS [UL1 TR000454]; NCRR NIH HHS [M01 RR08084, M01 RR008084,
M01 RR00750, M01 RR0039-43, M01 RR00125, M01 RR000750, M01 RR00044, M01
RR000070, M01 RR00070, M01 RR000997, M01 RR00997, M01 RR000039, M01
RR00039, M01 RR000125, M01 RR000044]; NICHD NIH HHS [U10 HD40498, U10 HD
21373, U10 HD021373, U10 HD027856, U10 HD027904, U10 HD034216, U10
HD040521, U10 HD27856, U10 HD27904, U10 HD34216, U10 HD40521, U10
HD27853, U10 HD40689, U10 HD40461, U10 HD27880, U10 HD27871, U10
HD27851, U10 HD21415, U10 HD21385, U10 HD040689, U10 HD040498, U10
HD040461, U10 HD027880-16, U10 HD027880, U10 HD027871, U10 HD027853, U10
HD027851, U10 HD021385, U01 HD36790, U01 HD036790, U10 HD27881]
NR 32
TC 26
Z9 27
U1 0
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD AUG
PY 2008
VL 162
IS 8
BP 748
EP 755
DI 10.1001/archpedi.162.8.748
PG 8
WC Pediatrics
SC Pediatrics
GA 334MF
UT WOS:000258225200006
PM 18678807
ER
PT J
AU Matthijnssens, J
Ciarlet, M
Rahman, M
Attoui, H
Banyai, K
Estes, MK
Gentsch, JR
Iturriza-Gomara, M
Kirkwood, CD
Martella, V
Mertens, PPC
Nakagomi, O
Patton, JT
Ruggeri, FM
Saif, LJ
Santos, N
Steyer, A
Taniguchi, K
Desselberger, U
Van Ranst, M
AF Matthijnssens, Jelle
Ciarlet, Max
Rahman, Mustafizur
Attoui, Houssam
Banyai, Krisztian
Estes, Mary K.
Gentsch, Jon R.
Iturriza-Gomara, Miren
Kirkwood, Carl D.
Martella, Vito
Mertens, Peter P. C.
Nakagomi, Osamu
Patton, John T.
Ruggeri, Franco M.
Saif, Linda J.
Santos, Norma
Steyer, Andrej
Taniguchi, Koki
Desselberger, Ulrich
Van Ranst, Marc
TI Recommendations for the classification of group A rotaviruses using all
11 genomic RNA segments
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID MOLECULAR CHARACTERIZATION; INTERSPECIES TRANSMISSION; INTRAGENIC
RECOMBINATION; MAMMALIAN ROTAVIRUSES; GENETIC-HETEROGENEITY;
NONSTRUCTURAL PROTEIN; SEQUENCE-ANALYSIS; STRAINS; NSP4; DISEASE
AB Recently, a classification system was proposed for rotaviruses in which all the 11 genomic RNA segments are used (Matthijnssens et al. in J Virol 82:3204-3219, 2008). Based on nucleotide identity cut-off percentages, different genotypes were defined for each genome segment. A nomenclature for the comparison of complete rotavirus genomes was considered in which the notations Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx are used for the VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 encoding genes, respectively. This classification system is an extension of the previously applied genotype-based system which made use of the rotavirus gene segments encoding VP4, VP7, VP6, and NSP4. In order to assign rotavirus strains to one of the established genotypes or a new genotype, a standard procedure is proposed in this report. As more human and animal rotavirus genomes will be completely sequenced, new genotypes for each of the 11 gene segments may be identified. A Rotavirus Classification Working Group (RCWG) including specialists in molecular virology, infectious diseases, epidemiology, and public health was formed, which can assist in the appropriate delineation of new genotypes, thus avoiding duplications and helping minimize errors. Scientists discovering a potentially new rotavirus genotype for any of the 11 gene segments are invited to send the novel sequence to the RCWG, where the sequence will be analyzed, and a new nomenclature will be advised as appropriate. The RCWG will update the list of classified strains regularly and make this accessible on a website. Close collaboration with the Study Group Reoviridae of the International Committee on the Taxonomy of Viruses will be maintained.
C1 [Matthijnssens, Jelle; Rahman, Mustafizur; Van Ranst, Marc] Univ Leuven, Rega Inst Med Res, Lab Clin & Epidemiol Virol, Dept Microbiol & Immunol, Louvain, Belgium.
[Ciarlet, Max] Merck & Co Inc, Vaccine & Biol Clin Res, N Wales, PA 19454 USA.
[Rahman, Mustafizur] ICDDR B Mohakhali, Virol Lab, Dhaka 1212, Bangladesh.
[Banyai, Krisztian] Hungarian Acad Sci, Vet Med Res Inst, H-1143 Budapest, Hungary.
[Estes, Mary K.] Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA.
[Estes, Mary K.] Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA.
[Estes, Mary K.] Baylor Coll Med, Dept Med GI, Houston, TX 77030 USA.
[Gentsch, Jon R.] CDC, Natl Ctr Immunizat & Resp Dis, Div Viral Dis, Atlanta, GA 30333 USA.
[Iturriza-Gomara, Miren] Hlth Protect Agcy, Enter Virus Unit, Virus Reference Dept, Ctr Infect, London, England.
[Martella, Vito] Univ Bari, Dept Publ Hlth & Anim Sci, Bari, Italy.
[Nakagomi, Osamu] Nagasaki Univ, Dept Mol Microbiol & Immunol, Nagasaki 8528523, Japan.
[Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ruggeri, Franco M.] Ist Super Sanita, Dipartimento Sanita Alimentare & Anim, I-00161 Rome, Italy.
[Saif, Linda J.] Ohio State Univ, Food Anim Hlth Res Program, Ohio Agr Res & Dev Ctr, Columbus, OH 43210 USA.
RP Matthijnssens, J (reprint author), Univ Leuven, Rega Inst Med Res, Lab Clin & Epidemiol Virol, Dept Microbiol & Immunol, Louvain, Belgium.
EM jelle.matthijnssens@uz.kuleuven.be
RI rahman, mustafizur/E-6918-2010; Iturriza Gomara, Miren/B-4351-2013;
Ruggeri, Franco/B-5707-2013; Patton, John/P-1390-2014; Matthijnssens,
Jelle/A-6770-2015; Santos, Norma/H-6986-2015; Matthijnssens,
Jelle/B-8634-2016; Martella, Vito/K-3146-2016;
OI Iturriza Gomara, Miren/0000-0001-5816-6423; Santos,
Norma/0000-0002-5123-9172; Martella, Vito/0000-0002-5740-6947; Van
Ranst, Marc/0000-0002-1674-4157; Steyer, Andrej/0000-0001-6819-2406;
Mertens, Peter/0000-0002-3438-3738; Banyai,
Krisztian/0000-0002-6270-1772
FU Biotechnology and Biological Sciences Research Council
[BBS/E/I/00001144]; Intramural NIH HHS [Z01 AI000754-12]; NIAID NIH HHS
[R01 AI080656]
NR 43
TC 328
Z9 337
U1 1
U2 13
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
J9 ARCH VIROL
JI Arch. Virol.
PD AUG
PY 2008
VL 153
IS 8
BP 1621
EP 1629
DI 10.1007/s00705-008-0155-1
PG 9
WC Virology
SC Virology
GA 327EY
UT WOS:000257713600029
PM 18604469
ER
PT J
AU Herrera-Galeano, JE
Becker, DM
Wilson, AF
Yanek, LR
Bray, P
Vaidya, D
Faraday, N
Becker, LC
AF Herrera-Galeano, J. Enrique
Becker, Diane M.
Wilson, Alexander F.
Yanek, Lisa R.
Bray, Paul
Vaidya, Dhananjay
Faraday, Nauder
Becker, Lewis C.
TI A novel variant in the platelet endothelial aggregation receptor-1 gene
is associated with increased platelet aggregability
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE platelets; genetics; aspirin; family study
ID CORONARY-ARTERY-DISEASE; ASPIRIN RESISTANCE; GLUCOCORTICOID-RECEPTOR;
CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ACTIVATION; RISK;
CYCLOOXYGENASE-1; POLYMORPHISM; INHIBITION
AB Objective - Platelet endothelial aggregation receptor-1 (PEAR1) is a recently identified platelet transmembrane protein that becomes activated by platelet contact. We looked for novel genetic variants in PEAR1 and studied their association with agonist-induced native platelet aggregation and with the inhibitory effect of aspirin on platelets.
Methods and Results - We genotyped PEAR1 for 10 single nucleotide polymorphisms (SNPs), selected for optimal gene coverage at a density of 4 kb, in 1486 apparently healthy individuals from two generations of families with premature CAD. Subjects had a mean age of 45 years; 62% were white and 38% black. Platelet aggregation to collagen, epinephrine, and ADP was measured in platelet rich plasma, at baseline and after 2 weeks of aspirin (ASA, 81 mg/d), and genotype-phenotype associations were examined separately by ethnicity using multivariable generalized linear models adjusted for covariates. The C allele of SNP rs2768759 [A/C], located in the promoter region of the gene, was common in whites and uncommon in blacks (allele frequency 70.2% versus 17.7%). The C allele was generally associated in both ethnic groups with increased aggregation of native platelets to each agonist. After ASA, the associations were stronger and more consistent and remained significant when post-ASA aggregation was adjusted for baseline aggregation, consistent with a relationship between the C allele and reduced platelet responsiveness to ASA. The PEAR1 SNP explained up to 6.9% of the locus specific genetic variance in blacks and up to 2.5% of the genetic variance in whites after ASA.
Conclusion - PEAR1 appears to play an important role in agonist-induced platelet aggregation and in the response to ASA in both whites and blacks.
C1 [Herrera-Galeano, J. Enrique; Becker, Diane M.; Yanek, Lisa R.; Vaidya, Dhananjay; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Herrera-Galeano, J. Enrique; Becker, Diane M.; Yanek, Lisa R.; Vaidya, Dhananjay; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD USA.
[Faraday, Nauder] Johns Hopkins Univ, Sch Med, Dept Crit Care Med, Baltimore, MD USA.
[Wilson, Alexander F.] NIH, Inherited Dis Res Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA.
[Bray, Paul] Thomas Jefferson Univ Hosp, Dept Med, Philadelphia, PA 19107 USA.
RP Becker, LC (reprint author), Johns Hopkins Univ Hosp, Halsted 500,600 N Wolfe St, Baltimore, MD 21287 USA.
EM lbecker@mail.jhmi.edu
RI Wilson, Alexander/C-2320-2009;
OI Vaidya, Dhananjay/0000-0002-7164-1601
FU NCRR NIH HHS [M01 RR000052, M01-RR00052, P41 RR003655, RR03655]; NHLBI
NIH HHS [HL072518, U01 HL072518, U01 HL072518-06]
NR 28
TC 45
Z9 47
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD AUG 1
PY 2008
VL 28
IS 8
BP 1484
EP 1490
DI 10.1161/ATVBAHA.108.168971
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 329PH
UT WOS:000257880100013
PM 18511696
ER
PT J
AU Goldbach-Mansky, R
Shroff, SD
Wilson, M
Snyder, C
Plehn, S
Barham, B
Pham, TH
Pucino, F
Wesley, RA
Papadopoulos, JH
Weinstein, SP
Mellis, SJ
Kastner, DL
AF Goldbach-Mansky, Raphaela
Shroff, Sharukh D.
Wilson, Mildred
Snyder, Christopher
Plehn, Sara
Barham, Beverly
Pham, Tuyet-Hang
Pucino, Frank
Wesley, Robert A.
Papadopoulos, Joanne H.
Weinstein, Steven P.
Mellis, Scott J.
Kastner, Daniel L.
TI A pilot study to evaluate the safety and efficacy of the long-acting
interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) in patients with
familial cold autoinflammatory syndrome
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID CIAS1 MUTATIONS; MEDITERRANEAN FEVER; INFLAMMASOME; ACTIVATION;
CASPASE-1; DISEASE; MEMBER; GENE; ANTAGONIST; EXPRESSION
AB Objective. Familial cold autoinflammatory syndrome (FCAS) is caused by mutations in the CIAS1 gene, leading to excessive secretion of interleukin-1 beta (IL-1 beta), which is associated with cold-induced fevers, joint pain, and systemic inflammation. This pilot study was conducted to assess the safety and efficacy of rilonacept (IL-1 Trap), a long-acting IL-1 receptor fusion protein, in patients with FCAS.
Methods. Five patients with FCAS were studied in an open-label trial. All patients received an initial loading dose of 300 mg of rilonacept by subcutaneous injection, were evaluated 6 and 10 days later for clinical efficacy, and remained off treatment until a clinical flare occurred. At the time of flare, patients were again treated with 300 mg of rilonacept and then given maintenance doses of 100 mg/week. Patients whose FCAS was not completely controlled were allowed a dosage increase to 160 mg/week and then further to 320 mg/week during an intrapatient dosage-escalation phase. Safety, disease activity measures (daily diary reports of rash, joint pain and/or swelling, and fevers), health quality measures (Short Form 36 health survey questionnaire), and serum markers of inflammation (erythrocyte sedimentation rate [ESR], high-sensitivity C-reactive protein [hsCRP], serum amyloid A [SAA], and IL-6) were determined at 3, 6, 9, 12, and 24 months after initiation of rilonacept and were compared with baseline values.
Results. In all patients, clinical symptoms typically induced by cold (rash, fever, and joint pain/swelling) improved within days of rilonacept administration. Markers of inflammation (ESR, hsCRP, and SAA) showed statistically significant reductions (P < 0.01, P < 0.001, and P < 0.001, respectively) at doses of.100 mg. Dosage escalation to 160 mg and 320 mg resulted in subjectively better control of the rash and joint pain. Furthermore, levels of the acute-phase reactants ESR, hsCRP, and SAA were lower at the higher doses; the difference was statistically significant only for the ESR. All patients continued taking the study drug. The drug was well-tolerated. Weight gain in 2 patients was noted. No study drug-related serious adverse events were seen.
Conclusion. In this study, we present 2-year safety and efficacy data on rilonacept treatment in 5 patients with FCAS. The dramatic improvement in clinical and laboratory measures of inflammation, the sustained response, and the good tolerability suggest that this drug may be a promising therapeutic option in patients with FCAS, and the data led to the design of a phase III study in this patient population.
C1 [Goldbach-Mansky, Raphaela; Shroff, Sharukh D.; Wilson, Mildred; Snyder, Christopher; Plehn, Sara; Barham, Beverly; Pham, Tuyet-Hang; Kastner, Daniel L.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Pucino, Frank; Wesley, Robert A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Papadopoulos, Joanne H.; Weinstein, Steven P.; Mellis, Scott J.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
RP Goldbach-Mansky, R (reprint author), NIAMSD, NIH, Bldg 10,Room 6N-216A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM goldbacr@mail.nih.gov
FU Regeneron Pharmaceuticals, Inc; National Institute of Arthritis and
Musculoskeletal and Skin Diseases; NIH
FX Supported by Regeneron Pharmaceuticals, Inc. and by the intramural
program of the National Institute of Arthritis and Musculoskeletal and
Skin Diseases, NIH.
NR 29
TC 118
Z9 124
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD AUG
PY 2008
VL 58
IS 8
BP 2432
EP 2442
DI 10.1002/art.23620
PG 11
WC Rheumatology
SC Rheumatology
GA 346FZ
UT WOS:000259055400028
PM 18668591
ER
PT J
AU Lea, WA
Jadhav, A
Rai, G
Sayed, AA
Cass, CL
Inglese, J
Williams, DL
Austin, CP
Simeonov, A
AF Lea, Wendy A.
Jadhav, Ajit
Rai, Ganesha
Sayed, Ahmed A.
Cass, Cynthia L.
Inglese, James
Williams, David L.
Austin, Christopher P.
Simeonov, Anton
TI A 1,536-well-based kinetic HTS assay for inhibitors of Schistosoma
mansoni thioredoxin glutathione reductase
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article
ID THROUGHPUT SCREENING ASSAYS; PRAZIQUANTEL; IDENTIFICATION
AB Schistosomiasis is a major neglected tropical disease that currently affects over 200 million people and leads to over 200,000 annual deaths. Schistosoma mansoni parasites survive in humans in part because of a set of antioxidant enzymes that continuously degrade reactive oxygen species produced by the host. A principal component of this defense system has been recently identified as thioredoxin glutathione reductase (TGR), a parasite-specific enzyme that combines the functions of two human counterparts, glutathione reductase and thioredoxin reductase, and as such this enzyme presents an attractive new target for anti-schistosomiasis drug development. Herein, we present the development of a highly miniaturized and robust screening assay for TGR. The 5-mu l final volume assay is based on the Ellman reagent [5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)] and utilizes a high-speed absorbance kinetic read to minimize the effect of dust, absorbance interference, and meniscus variation. This assay is further applicable to the testing of other redox enzymes that utilize DTNB as a model substrate.
C1 [Lea, Wendy A.; Jadhav, Ajit; Rai, Ganesha; Inglese, James; Austin, Christopher P.; Simeonov, Anton] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Sayed, Ahmed A.; Cass, Cynthia L.; Williams, David L.] Illinois State Univ, Dept Biol Sci, Normal, IL 61761 USA.
RP Simeonov, A (reprint author), NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov
FU National Institutes of Health Roadmap for Medical Research; Intramural
Research Program of the National Human Genome Research Institute,
National Institutes of Health; National Institutes of Health/National
Institute of Mental Health [1R03MH076449]; National institutes of
Health/National Institute of Allergy and Infectious Diseases
[5R01AI065622]
FX This research was supported by the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research and the
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health, and in part by National
Institutes of Health/National Institute of Mental Health grant
1R03MH076449 and National institutes of Health/National Institute of
Allergy and Infectious Diseases grant 5R01AI065622 (to D.L.W.).
NR 24
TC 12
Z9 12
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD AUG
PY 2008
VL 6
IS 4
BP 551
EP 555
DI 10.1089/adt.2008.149
PG 5
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 354LZ
UT WOS:000259642400006
PM 18665782
ER
PT J
AU Ebbesson, SOE
Roman, MJ
Devereux, RB
Kaufman, D
Fabsitz, RR
MacCluer, JW
Dyke, B
Laston, S
Wenger, CR
Comuzzie, AG
Romenesko, T
Ebbesson, LOE
Nobmann, ED
Howard, BV
AF Ebbesson, Sven O. E.
Roman, Mary J.
Devereux, Richard B.
Kaufman, David
Fabsitz, Richard R.
MacCluer, Jean W.
Dyke, Bennett
Laston, Sandra
Wenger, Charlotte R.
Comuzzie, Anthony G.
Romenesko, Terry
Ebbesson, Lars O. E.
Nobmann, Elizabeth D.
Howard, Barbara V.
TI Consumption of omega-3 fatty acids is not associated with a reduction in
carotid atherosclerosis: The Genetics of Coronary Artery Disease in
Alaska Natives study
SO ATHEROSCLEROSIS
LA English
DT Article
DE atherosclerosis; GOCADAN; omega-3 fatty acids; saturated fatty acids;
palmitate
ID N-3 FATTY-ACIDS; HEART-DISEASE; FISH OIL; TRIAL; PREVENTION; PLASMA;
DEATH; RISK; CHOLESTEROL; MEDICINE
AB Objective: This study was designed to evaluate the relation between omega-3 fatty acid (FA) Consumption and atherosclerosis.
Background: The hypothesis that omega-3 FAs protect against atherosclerosis has not been tested with objective measures of atherosclerosis.
Methods: A population-based sample of 1131 Alaskan Eskimos of age >= 18 underwent ultrasound assessment of carotid atherosclerosis. Those of age >35 (N=686) were included in the analysis. Diet was assessed by a food frequency questionnaire. Intimal-medial thickness (IMT) of the far wall of the distal common carotid arteries and plaque score (number of segments containing plaque) were assessed.
Results; Mean Consumption of total omega-3 FAs was 4.76 g/day in those without and 5.07 g/day in those with plaque. In models adjusting for relevant risk factors. presence and extent of plaque were unrelated to intake of C20-22 omega-3 FAs or total omega-3 FAs. In contrast, the odds of plaque rose significantly with quartiles of palmitic (p=0.02) and stearic acid intake (p=0.04). The extent of plaque (or plaque score) was also associated with a higher percentage intake of palmitic acid (p=0.01). IMT was negatively associated with grams of C20-22 omega-3 FAs (p=0.05). total omega-3 (p=0.05), palmitate (p=0.03), and stearate (p=0.03) consumed.
Conclusions: Dietary intake of omega-3 FAs in a moderate-to-high range does not appear to be associated with reduced plaque, but is negatively associated with IMT. The presence and extent of carotid atherosclerosis among Eskimos is higher with increasing consumption of saturated FAs. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
C1 [Ebbesson, Sven O. E.; Romenesko, Terry] Norton Sound Hlth Corp, Nome, AK 99762 USA.
[Ebbesson, Sven O. E.] Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA.
[Roman, Mary J.; Devereux, Richard B.] Weill Cornel Med Coll, New York, NY USA.
[Kaufman, David; Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD USA.
[Fabsitz, Richard R.] NHLBI, Bethesda, MD 20892 USA.
[MacCluer, Jean W.; Dyke, Bennett; Laston, Sandra; Wenger, Charlotte R.; Comuzzie, Anthony G.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA.
[Ebbesson, Lars O. E.] Univ Bergen, Dept Biol, Bergen, Norway.
[Nobmann, Elizabeth D.] IDM Consulting, Anchorage, AK USA.
RP Ebbesson, SOE (reprint author), Norton Sound Hlth Corp, POB 966, Nome, AK 99762 USA.
EM ffsoe@uaf.edu
RI Ebbesson, Lars/F-9385-2011
FU National Institutes of Health [ROI-HL64244, U01 HL082458, M10RR0047-34]
FX This study was funded by grants ROI-HL64244, U01 HL082458, and
M10RR0047-34 (GCRC) from the National Institutes of Health, Bethesda,
MD. The authors are grateful to the Norton Sound Health Corporation
(NSHC) and the participants of villages participating in this study. We
thank Rachel Schaperow, MedStar Research Institute, Hyattsville, MD. for
editing the manuscript.
NR 50
TC 26
Z9 27
U1 2
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 AUG
PY 2008
VL 199
IS 2
BP 346
EP 353
DI 10.1016/j.atherosclerosis.2007.10.020
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 342LQ
UT WOS:000258786000016
PM 18054937
ER
PT J
AU Tolmachev, V
Xu, H
Wallberg, H
Ahlgren, S
Nertman, M
Sjoberg, A
Sandstrom, M
Abrahmsen, L
Brechbiel, MW
Orlova, A
AF Tolmachev, Vladimir
Xu, Heng
Wallberg, Helena
Ahlgren, Sara
Nertman, Magnus
Sjoberg, Anna
Sandstrom, Mattias
Abrahmsen, Lars
Brechbiel, Martin W.
Orlova, Anna
TI Evaluation of a maleimido derivative of CHX-A '' DTPA for site-specific
labeling of Affibody molecules
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID HER2-EXPRESSING MALIGNANT-TUMORS; DISSEMINATED PERITONEAL DISEASE;
RECEPTOR RADIONUCLIDE THERAPY; GROWTH-FACTOR RECEPTOR; IN-VIVO
EVALUATION; HER2 EXPRESSION; ALPHA-PARTICLE; CORRESPONDING METASTASES;
MONOCLONAL-ANTIBODIES; ANTI-HER2 AFFIBODY
AB Affibody molecules are a new class of small targeting proteins based on a common three-helix bundle structure. Affibody molecules binding a desired target may be selected using phage-display technology. An Affibody molecule Z(HER2:342) binding with subnanomolar affinity to the tumor antigen HER2 has recently been developed for radionuclide imaging in vivo. Introduction of a single cysteine into the cysteine-free Affibody scaffold provides a unique thiol group for site-specific labeling of recombinant Affibody molecules. The recently developed maleimido-CHX-A" DTPA was site-specifically conjugated at the C-terminal cysteine Of Z(HER2:2395)-C, a variant of Z(HER2:342), providing a homogeneous conjugate with a dissociation constant of 56 pM. The yield of labeling with In-111 was >99% after 10 min at room temperature. In vitro cell tests demonstrated specific binding of In-111-CHX-A" DTPA-Z(2395)-C to HER2-expressing cell-line SKOV-3 and good cellular retention of radioactivity, In normal mice, the conjugate demonstrated rapid clearance from all nonspecific organs except kidney. In mice bearing SKOV-3 xenografts, the tumor uptake of In-111-CHX-A" DTPA-Z(2395)-C was 17.3 +/- 4.8% IA/g and the tumor-to-blood ratio 86 +/- 46 (4 h postinjection). HER2-expressing xenografts were clearly visualized 1 h postinjection. In conclusion, coupling of maleimido-CHX-A" DTPA to cysteine-containing Affibody molecules provides a well-defined uniform conjugate, which can be rapidly labeled at room temperature and provides high-contrast imaging of molecular targets in vivo.
C1 [Tolmachev, Vladimir; Orlova, Anna] Uppsala Univ, Rudbeck Lab, Div Biomed Radiat Sci, S-75181 Uppsala, Sweden.
[Tolmachev, Vladimir; Wallberg, Helena; Nertman, Magnus; Sjoberg, Anna; Abrahmsen, Lars; Orlova, Anna] Affibody AB, Bromma, Sweden.
[Tolmachev, Vladimir; Ahlgren, Sara] Uppsala Univ, Div Nucl Med, Dept Med Sci, S-75181 Uppsala, Sweden.
[Xu, Heng; Brechbiel, Martin W.] NCI, Radiat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Sandstrom, Mattias] Univ Uppsala Hosp, Hosp Phys, Dept Oncol, Uppsala, Sweden.
RP Orlova, A (reprint author), Uppsala Univ, Rudbeck Lab, Div Biomed Radiat Sci, S-75181 Uppsala, Sweden.
EM anna.orlova@bms.uu.se
RI Tolmachev, Vladimir/I-3076-2012
FU NIH; National Cancer Institute; Center for Cancer Research; Swedish
Cancer Society (Cancerfonden)
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research and by
grant from Swedish Cancer Society (Cancerfonden).
NR 48
TC 24
Z9 24
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2008
VL 19
IS 8
BP 1579
EP 1587
DI 10.1021/bc800110y
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 339TQ
UT WOS:000258600600011
PM 18620447
ER
PT J
AU Kim, Y
Klutz, AM
Jacobson, KA
AF Kim, Yoonkyung
Klutz, Athena M.
Jacobson, Kenneth A.
TI Systematic investigation of polyamidoamine dendrimers surface-modified
with poly(ethylene glycol) for drug delivery applications: Synthesis,
characterization, and evaluation of cytotoxicity
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID NONVIRAL GENE DELIVERY; PAMAM DENDRIMERS; POLY(AMIDOAMINE) DENDRIMERS;
IN-VITRO; BIOMEDICAL APPLICATIONS; MOLECULAR RECOGNITION; UNIMOLECULAR
MICELLE; POLYMER THERAPEUTICS; DENDRITIC POLYMERS; BLOCK-COPOLYMERS
AB Surface modification of amine-terminated polyamidoamine (PAMAM) dendrimers by poly(ethylene glycol) (PEG) groups generally enhances water-solubility and biocompatibility for drug delivery applications. In order to provide guidelines for designing appropriate dendritic scaffolds, a series of G3 PAMAM-PEG dendrimer conjugates was synthesized by varying the number of PEG attachments and chain length (shorter PEG(550) and PEG(750) and longer PEG(2000)). Each conjugate was purified by size exclusion chromatography (SEC) and the molecular weight (MW) was determined by H-1 NMR integration and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). NOESY experiments performed in D2O on selected structures suggested no penetration of PEG chains to the central PAMAM domain, regardless of chain length and degree of substitution. CHO cell cultures exposed to PAMAM-PEG derivatives (<= 1 mu M) showed a relatively high cell viability. Generally, increasing the degree of PEG substitution reduced cytotoxicity. Moreover, compared to G3 PAMAM dendrimers that were N-acetylated to varying degrees, a lower degree of surface substitution with PEG was needed for a similar cell viability. Interestingly, when longer PEG2000 was fully incorporated on the surface, cell viability was reduced at higher concentrations (32 mu M), suggesting increased toxicity potentially by forming intermolecular aggregates. A similar observation was made for anionic carboxylate G5.5 PAMAM dendrimer at the same dendrimer concentration. Our findings suggest that a lower degree of peripheral substitution with shorter PEG chains may suffice for these PAMAM-PEG conjugates to serve as efficient universal scaffolds for drug delivery, particularly valuable in relation to targeting or other ligand-receptor interactions.
C1 [Kim, Yoonkyung; Klutz, Athena M.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Kim, Y (reprint author), Korea Inst Sci & Technol, Biomed Res Ctr, 39-1 Hawolgok Dong, Seoul 136791, South Korea.
EM kim_yoonkyung@yahoo.com; kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH; NIDDK; Can-Fite Biopharma
FX This research was supported in part by the Intramural Research Program
of the NIH, NIDDK. We thank Dr. Haijun Yao at the Mass Spectrometry
Laboratory of the University of Illinois, for numerous attempts to
obtain MALDI spectra of our PAMAM dendrimer derivatives. We are grateful
to Rick Dreyfuss at ORS, NIH, who helped us to obtain the images for the
cytotoxicity results. Y.K. thanks the Can-Fite Biopharma for financial
support.
NR 84
TC 105
Z9 109
U1 2
U2 57
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2008
VL 19
IS 8
BP 1660
EP 1672
DI 10.1021/bc700483s
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 339TQ
UT WOS:000258600600020
PM 18610944
ER
PT J
AU Longmire, MR
Ogawa, M
Hama, Y
Kosaka, N
Regino, CAS
Choyke, PL
Kobayashi, H
AF Longmire, Michelle R.
Ogawa, Mikako
Hama, Yukihiro
Kosaka, Nobuyuki
Regino, Celeste A. S.
Choyke, Peter L.
Kobayashi, Hisataka
TI Determination of optimal rhodamine fluorophore for in vivo optical
imaging
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID FLUORESCENT PROTEINS; SERUM ALBUMIN; CANCER; METASTASES; PROBES;
EXPRESSION; TISSUE
AB Optical imaging has the potential to improve the efficacy of surgical and endoscopic approaches to cancer treatment; however, the optimal type of fluorescent probe has not yet been established. It is well-known that rhodamine-core-derived fluorophores offer a combination of desirable properties such as good photostability, high extinction coefficient, and high fluorescence quantum yield. However, despite the ubiquitous use of rhodamine fluorophores for in vivo optical imaging, it remains to be determined if unique chemical properties among individual rhodamine core family members affect fluorophore parameters critical to in vivo optical imaging applications. These parameters include preserved fluorescence intensity in low pH environments, similar to that of the endolysosome; efficient fluorescence signal despite conformational changes to targeting proteins as may occur in harsh subcellular environments; persistence of fluorescence after cellular internalization; and sufficient signal-to-background ratios to permit the identification of fluorophore-targeted tumors. In the present study, we conjugated 4 common rhodamine-core based fluorescent dyes to a clinically feasible and quickly internalizing D-galactose receptor targeting reagent, galactosamine serum albumin (GmSA), and conducted a series of in vitro and in vivo experiments using a metastatic ovarian cancer mouse model to determine if differences in optical imaging properties exist among rhodamine fluorophores and if so, which rhodamine core possesses optimal characteristics for in vivo imaging applications. Herein, we demonstrate that the rhodamine-fluorophore, TAMRA, is the most robust of the 4 common rhodamine fluorophores for in vivo optical imaging of ovarian cancer metastases to the peritoneum.
C1 [Longmire, Michelle R.; Ogawa, Mikako; Hama, Yukihiro; Kosaka, Nobuyuki; Regino, Celeste A. S.; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
FU NIH,; National Cancer Institute; Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 18
TC 42
Z9 42
U1 1
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD AUG
PY 2008
VL 19
IS 8
BP 1735
EP 1742
DI 10.1021/bc800140c
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 339TQ
UT WOS:000258600600028
PM 18610943
ER
PT J
AU Simons, SS
AF Simons, S. Stoney, Jr.
TI What goes on behind closed doors: physiological versus pharmacological
steroid hormone actions
SO BIOESSAYS
LA English
DT Review
ID LIGAND-BINDING DOMAIN; GLUCOCORTICOID-RECEPTOR TRANSACTIVATION; PARTIAL
AGONIST ACTIVITY; PROSTATE-CANCER CELLS; REGULATED GENE-EXPRESSION;
DOSE-RESPONSE CURVE; ANDROGEN RECEPTOR; NUCLEAR RECEPTOR;
ESTROGEN-RECEPTOR; PROGESTERONE-RECEPTOR
AB Steroid-hormone-activated receptor proteins are among the best-understood class of factors for altering gene transcription in cells. Steroid receptors are of major importance in maintaining normal human physiology by responding to circulating concentrations of steroid in the nM range. Nonetheless, most studies of steroid receptor action have been conducted using the supra-physiological conditions of saturating concentrations (>= 100 nM) of potent synthetic steroid agonists. Here we summarize the recent developments arising from experiments using two clinically relevant conditions: subsaturating concentrations of agonist (to mimic the circulating concentrations in mammals) and saturating concentrations of antagonists (which are employed in endocrine therapies to block the actions of endogenous steroids). These studies have revealed new facets of steroid hormone action that could not be uncovered by conventional experiments with saturating concentrations of agonist steroids, such as a plethora of factors/conditions for the differential control of gene expression by physiological levels of steroid, a rational approach for examining the gene-specific variations in partial agonist activity of antisteroids, and a dissociation of steroid potency and efficacy that implies the existence of separate, and possibly novel, mechanistic steps and cofactors.
C1 NIDDK CEB, Steroid Hormones Sect, NIH, Bethesda, MD 20892 USA.
RP Simons, SS (reprint author), NIDDK CEB, Steroid Hormones Sect, NIH, Bldg 10,Room 8N-307B, Bethesda, MD 20892 USA.
EM steroids@helix.nih.gov
FU Intramural NIH HHS [Z01 DK047041-01, Z01 DK047040-01, Z01 DK057800-16,
Z01 DK047039-01, Z01 DK047042-01]
NR 114
TC 44
Z9 45
U1 0
U2 6
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0265-9247
J9 BIOESSAYS
JI Bioessays
PD AUG
PY 2008
VL 30
IS 8
BP 744
EP 756
DI 10.1002/bies.20792
PG 13
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 334YG
UT WOS:000258257100007
PM 18623071
ER
PT J
AU Economidou, D
Hansson, AC
Weiss, F
Terasmaa, A
Sommer, WH
Cippitelli, A
Fedeli, A
Martin-Fardon, R
Massi, M
Ciccocioppo, R
Heilig, M
AF Economidou, Daina
Hansson, Anita C.
Weiss, Friedbert
Terasmaa, Anton
Sommer, Wolfgang H.
Cippitelli, Andrea
Fedeli, Amalia
Martin-Fardon, Remi
Massi, Maurizio
Ciccocioppo, Roberto
Heilig, Markus
TI Dysregulation of nociceptin/orphanin FQ activity in the amygdala is
linked to excessive alcohol drinking in the rat
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE addiction; alcohol preferring rats; alcoholism; central amygdala;
nociceptin/orphanin FQ; NOP receptors
ID CORTICOTROPIN-RELEASING-FACTOR; PREFERRING RATS; POSTOPERATIVE PAIN;
EXTENDED AMYGDALA; SEEKING BEHAVIOR; CONTROLLED TRIAL; CENTRAL NUCLEUS;
DEPENDENT RATS; BED NUCLEUS; ORPHANIN-FQ
AB Background: Alcoholism is a complex behavioral disorder in which interactions between stressful life events and heritable susceptibility factors contribute to the initiation and progression of disease. Neural substrates of these interactions remain largely unknown. Here, we examined the role of the nociceptin/orphanin FQ (N/OFQ) system, with an animal model in which genetic selection for high alcohol preference has led to co-segregation of elevated behavioral sensitivity to stress (Marchigian Sardinian alcohol-preferring [msP]).
Methods: The msP and Wistar rats trained to self-administer alcohol received central injections of N/OFQ. In situ hybridization and receptor binding assays were also performed to evaluate N/OFQ receptor (NOP) function in naive msP and Wistar rats.
Results: Intracerebroventricular (ICV) injection of N/OFQ significantly inhibited alcohol self-ad ministration in msP but not in nonselected Wistar rats. The NOP receptor messenger RNA expression and binding was upregulated across most brain regions in msP compared with Wistar rats. However, in msP rats [(35)S]GTP gamma S binding revealed a selective impairment of NOP receptor signaling in the central amygdala (CeA). Ethanol self-administration in msP rats was suppressed after N/OFQ microinjection into the CeA but not into the bed nucleus of the stria terminalis or the basolateral amygdala.
Conclusions: These findings indicate that dysregulation of N/OFQ-NOP receptor signaling in the CeA contributes to excessive alcohol intake in msP rats and that this phenotype can be rescued by local administration of pharmacological doses of exogenous N/OFQ. Data are interpreted on the basis of the anti-corticotropin releasing factor (CRF) actions of N/OFQ and the significance of the CRF system in promoting excessive alcohol drinking in msP rats.
C1 [Economidou, Daina; Cippitelli, Andrea; Fedeli, Amalia; Massi, Maurizio; Ciccocioppo, Roberto] Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, MC, Italy.
[Hansson, Anita C.; Terasmaa, Anton; Sommer, Wolfgang H.; Cippitelli, Andrea; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
[Weiss, Friedbert; Martin-Fardon, Remi] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA USA.
RP Ciccocioppo, R (reprint author), Univ Camerino, Dept Expt Med & Publ Hlth, Via Madonna Carceri, I-62032 Camerino, MC, Italy.
EM roberto.ciccocioppo@unicam.it
RI Terasmaa, Anton/I-3312-2015;
OI Sommer, Wolfgang/0000-0002-5903-6521; Terasmaa,
Anton/0000-0002-5139-1764; Heilig, Markus/0000-0003-2706-2482
FU NIAAA NIH HHS [R01 AA014351, AA014351, R01 AA014351-04]
NR 47
TC 55
Z9 55
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 AUG 1
PY 2008
VL 64
IS 3
BP 211
EP 218
DI 10.1016/j.biopsych.2008.02.004
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 326EI
UT WOS:000257640700006
PM 18367152
ER
PT J
AU Bertolino, A
Di Giorgio, A
Blasi, G
Sambataro, F
Caforio, G
Sinibaldi, L
Latorre, V
Rampino, A
Taurisano, P
Fazio, L
Romano, R
Douzgou, S
Popolizio, T
Kolachana, B
Nardini, M
Weinberger, DR
Dallapiccola, B
AF Bertolino, Alessandro
Di Giorgio, Annabella
Blasi, Giuseppe
Sambataro, Fabio
Caforio, Grazia
Sinibaldi, Lorenzo
Latorre, Valeria
Rampino, Antonio
Taurisano, Paolo
Fazio, Leonardo
Romano, Raffaella
Douzgou, Sofia
Popolizio, Teresa
Kolachana, Bhaskar
Nardini, Marcello
Weinberger, Daniel R.
Dallapiccola, Bruno
TI Epistasis between dopamine regulating genes identifies a nonlinear
response of the human hippocampus during memory tasks
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE dopamine; encoding; hippocampus; prefrontal cortex; working memory
ID CATECHOL-O-METHYLTRANSFERASE; MEDIAL TEMPORAL-LOBE; LONG-TERM-MEMORY;
DEFICIT HYPERACTIVITY DISORDER; VAL(108/158) MET GENOTYPE; EVENT-RELATED
FMRI; WORKING-MEMORY; PREFRONTAL CORTEX; HUMAN BRAIN; VAL(158)MET
GENOTYPE
AB Background: Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted U-curve. Dopamine is also an important factor in regulation of hippocampal mediated memory processing. Here, we investigated the effect of genetic variation of dopamine inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) on hippocampal activity in healthy humans during different memory conditions.
Methods: Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in 82 subjects matched for a series of demographic and genetic variables, we studied the effect of the COMT valine (Val)(158)methionine (Met) and the DAT 3' variable number tandem repeat (VNTR) polymorphisms on function of the hippocampus during encoding of recognition memory and during working memory.
Results: Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier alleles modulated activity in the hippocampus in the exact opposite direction of DAT 10/10-repeat alleles based on COMT Val(158)Met genotype during different memory conditions. Similar results were evident in ventrolateral and dorsolateral prefrontal cortex.
Conclusions: These findings suggest that genetically determined dopamine signaling during memory processing maps to a nonlinear relationship also in the hippocampus. Our data also demonstrate in human brain epistasis of two genes implicated in dopamine signaling on brain activity during different memory conditions.
C1 [Bertolino, Alessandro; Di Giorgio, Annabella; Blasi, Giuseppe; Sambataro, Fabio; Caforio, Grazia; Latorre, Valeria; Rampino, Antonio; Taurisano, Paolo; Fazio, Leonardo; Romano, Raffaella; Nardini, Marcello] Univ Bari, Dept Neurol & Psychiat Sci, Sect Mental Disorders, Psychiat Neurosci Grp, I-70124 Bari, Italy.
[Bertolino, Alessandro; Popolizio, Teresa] IRCCS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, FG, Italy.
[Sambataro, Fabio; Kolachana, Bhaskar; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Sinibaldi, Lorenzo; Douzgou, Sofia; Dallapiccola, Bruno] IRCCS Casa Sollievo Sofferenza, Mendel Sect, Rome, Italy.
[Sinibaldi, Lorenzo; Douzgou, Sofia; Dallapiccola, Bruno] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy.
RP Bertolino, A (reprint author), Univ Bari, Dipartimento Sci Neurol & Psichiat, Piazza Giulio Cesare 9, I-70124 Bari, Italy.
EM a.bertolino@psichiat.uniba.it
RI Dallapiccola, Bruno/K-8692-2016; Picchioni, Marco/E-3300-2010;
Sambataro, Fabio/E-3426-2010; Fazio, Leonardo/J-4570-2012; Bertolino,
Alessandro/O-6352-2016; Rampino, Antonio/Q-4465-2016; Di Giorgio,
Annabella /D-7353-2017
OI Dallapiccola, Bruno/0000-0002-5031-1013; Picchioni,
Marco/0000-0001-6681-147X; Sambataro, Fabio/0000-0003-2102-416X; Fazio,
Leonardo/0000-0003-4000-974X; Bertolino, Alessandro/0000-0002-1251-1380;
Rampino, Antonio/0000-0002-9654-3266; Di Giorgio, Annabella
/0000-0001-7876-3495
NR 75
TC 54
Z9 55
U1 3
U2 9
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 AUG 1
PY 2008
VL 64
IS 3
BP 226
EP 234
DI 10.1016/j.biopsych.2008.02.001
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 326EI
UT WOS:000257640700008
PM 18374902
ER
PT J
AU Chen, Z
Yan, B
Van Waes, C
AF Chen, Zhong
Yan, Bin
Van Waes, Carter
TI Role of the NF-kappa B transcriptome and proteome as biomarkers in human
head and neck squamous cell carcinomas
SO BIOMARKERS IN MEDICINE
LA English
DT Review
DE head and neck cancer; NF-kappa B; proteome; signal pathways;
transcriptome
ID GROWTH-FACTOR RECEPTOR; HISTONE DEACETYLASE INHIBITORS; PROINFLAMMATORY
CYTOKINE EXPRESSION; HOST ENVIRONMENT PROMOTES; LYMPH-NODE METASTASIS;
LUNG-CANCER CELLS; GENE-EXPRESSION; TUMOR-GROWTH; CONSTITUTIVE
ACTIVATION; PROTEASOME INHIBITORS
AB NF-kappa B is a family of signal-activated transcription factors comprising hetero- or homodimers from five different subunits, NF-kappa B1, NF-kappa B2, RELA, cREL and RELB. NF-kappa Bs are normally transiently activated in response to infection or injury, but in cancers are aberrantly activated, regulating a transcriptome of hundreds of genes and corresponding proteome that promote pathogenesis and therapeutic resistance. In head and neck squamous cell carcinomas, an important role of NF-kappa B in the regulation of the altered transcriptome and proteome has been established, providing a catalog of activating and target genes and proteins that may be useful as biomarkers of alterations in this pathway for this and other cancers. An emerging appreciation that NF-kappa B and other signal pathways form an altered regulatory network highlights the need to use biomarkers and combine targeted agents for personalized therapy of cancer.
C1 [Chen, Zhong; Yan, Bin; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20814 USA.
RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD 20814 USA.
EM vanwaesc@nidcd.nih.gov
FU NIDCD [Z01-DC-00016, -00074]
FX C Van Waes and the NIH have Materials Cooperative Research and
Development and Clinical Trials Agreements with Millennium
Pharmaceuticals for investigation of borte-zomib and IKK inhibitors,
with Topo Tatget/CuraGen for belinostat and with Astra Zeneca for
investigation of gefitinib. C Van Waes is supported by NIDCD Intramural
project Z01-DC-00016 and -00074. The authors have no other relevant
affiliations or financial involvement with any organization or entity
with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those
disclosed. No writing assistance was utilized in the production of this
manuscript.
NR 110
TC 13
Z9 15
U1 1
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1752-0363
J9 BIOMARK MED
JI Biomark. Med.
PD AUG
PY 2008
VL 2
IS 4
BP 409
EP 426
DI 10.2217/17520363.2.4.409
PG 18
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 357FS
UT WOS:000259832300012
PM 19444329
ER
PT J
AU Pfeiffer, RM
Bura, E
AF Pfeiffer, Ruth M.
Bura, Efstathia
TI A model free approach to combining biomarkers
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE AUC; dimension reduction; NHANES III; SAVE; SIR; singular value
decomposition
ID SLICED INVERSE REGRESSION; DIMENSION REDUCTION; LINEAR-COMBINATIONS;
MARKERS; CURVE; ROC
AB For most diseases, single biomarkers do not have adequate sensitivity or specificity for practical purposes. We present an approach to combine several biomarkers into a composite marker score without assuming a model for the distribution of the predictors. Using sufficient dimension reduction techniques, we replace the original markers with a lower-dimensional version, obtained through linear transformations of markers that contain sufficient information for regression of the predictors on the outcome. We combine the linear transformations using their asymptotic properties into a scalar diagnostic score via the likelihood ratio statistic. The performance of this score is assessed by the area under the receiver-operator characteristics curve (ROC), a popular summary measure of the discriminatory ability of a single continuous diagnostic marker for binary disease outcomes. An asymptotic chi-squared test for assessing individual biomarker contribution to the diagnostic score is also derived.
C1 [Pfeiffer, Ruth M.] NCI, Biostat Branch, Bethesda, MD 20892 USA.
[Bura, Efstathia] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
RP Pfeiffer, RM (reprint author), NCI, Biostat Branch, 6120 Execut Blvd,EPS-8030, Bethesda, MD 20892 USA.
EM pfeiffer@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
NR 23
TC 12
Z9 12
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0323-3847
EI 1521-4036
J9 BIOMETRICAL J
JI Biom. J.
PD AUG
PY 2008
VL 50
IS 4
BP 558
EP 570
DI 10.1002/bimj.200710428
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 340GO
UT WOS:000258634300007
PM 18663762
ER
PT J
AU Troendle, JR
AF Troendle, James R.
TI Testing for group effect in a 2xk heteroscedastic ANOVA model
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE empirical likelihood; likelihood ratio test; power; simulation
ID FACTORIAL-DESIGNS; 2-WAY ANOVA; STATISTICS; ROBUST
AB It is natural to want to relax the assumption of homoscedasticity and Gaussian error in ANOVA models. For a two-way ANOVA model with 2 x k cells, one can derive tests of main effect for the factor with two levels (referred to as group) without assuming homoscedasticity or Gaussian error. Empirical likelihood can be used to derive testing procedures. An approximate empirical likelihood ratio test (AELRT) is derived for the test of group main effect. To approximate the distributions of the test statistics under the null hypothesis, simulation from the approximate empirical maximum likelihood estimate (AEMLE) restricted by the null hypothesis is used. The homoscedastic ANOVA F-test and a Box-type approximation to the distribution of the heteroscedastic ANOVA F-test are compared to the AELRT in level and power. The AELRT procedure is shown by simulation to have appropriate type I error control (although possibly conservative) when the distribution of the test statistics are approximated by simulation from the constrained AEMLE. The methodology is motivated and illustrated by an analysis of folate levels in the blood among two alcohol intake groups while accounting for gender.
C1 NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA.
RP Troendle, JR (reprint author), NICHHD, Biometry & Math Stat Branch, Bld 6100, Bethesda, MD 20892 USA.
EM jt3t@nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 12
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0323-3847
J9 BIOMETRICAL J
JI Biom. J.
PD AUG
PY 2008
VL 50
IS 4
BP 571
EP 583
DI 10.1002/bimj.200710437
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 340GO
UT WOS:000258634300008
PM 18663763
ER
PT J
AU Li, Y
Tiwari, RC
Zou, ZH
AF Li, Yi
Tiwari, Ram C.
Zou, Zhaohui
TI An age-stratified Poisson model for comparing trends in cancer rates
across overlapping regions
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE age-adjusted incidence/mortality rates; age-stratified Poisson
regression; annual percent change (APC); hypothesis testing;
surveillance; trends
AB The annual percent change (APC) has been used as a measure to describe the trend in the age-adjusted cancer incidence or mortality rate over relatively short time intervals. The yearly data on these age-adjusted rates are available from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. The traditional methods to estimate the APC is to fit a linear regression of logarithm of age-adjusted rates on time using the least squares method or the weighted least squares method, and use the estimate of the slope parameter to define the APC as the percent change in the rates between two consecutive years. For comparing the APC for two regions, one uses a t-test which assumes that the two datasets on the logarithm of the age-adjusted rates are independent and normally distributed with a common variance. Two modifications of this test, when there is an overlap between the two regions or between the time intervals for the two datasets have been recently developed. The first modification relaxes the assumption of the independence of the two datasets but still assumes the common variance. The second modification relaxes the assumption of the common variance also, but assumes that the variances of the age-adjusted rates are obtained using Poisson distributions for the mortality or incidence counts. In this paper, a unified approach to the problem of estimating the APC is undertaken by modeling the counts to follow an age-stratified Poisson regression model, and by deriving a corrected Z-test for testing the equality of two APCs. A simulation study is carried out to assess the performance of the test and an application of the test to compare the trends, for a selected number of cancer sites, for two overlapping regions and with varied degree of overlapping time intervals is presented.
C1 [Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA.
[Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Tiwari, Ram C.] NCI, Stat Res & Applicat Branch, Rockvile, MD 20878 USA.
[Zou, Zhaohui] Informat Management Serv Inc, Silver Spring, MD 20904 USA.
RP Li, Y (reprint author), Harvard Univ, Dept Biostat, 44 Binney St,LW211, Boston, MA 02115 USA.
EM yili@jimmy.harvard.edu
FU NCI NIH HHS [R01 CA095747, R01 CA095747-05A2]
NR 9
TC 7
Z9 7
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0323-3847
J9 BIOMETRICAL J
JI Biom. J.
PD AUG
PY 2008
VL 50
IS 4
BP 608
EP 619
DI 10.1002/bimj.200710430
PG 12
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 340GO
UT WOS:000258634300011
PM 18615411
ER
PT J
AU Kim, H
Cardellina, JH
Akee, R
Champoux, JJ
Stivers, JT
AF Kim, Hyeongnam
Cardellina, John H., II
Akee, Rhone
Champoux, James J.
Stivers, James T.
TI Arylstibonic acids: Novel inhibitors and activators of human
topoisomerase IB
SO BIOORGANIC CHEMISTRY
LA English
DT Article
DE Topoisomerase IB; Arylstibonic acid inhibitors and activators
ID DNA TOPOISOMERASE; CAMPTOTHECIN; MECHANISM; RESISTANCE
AB Human topoisomerase IB (hTopo) forms a covalent phosphotyrosyl linkage with the DNA backbone, and controls genomic DNA topology by relaxing DNA supercoils during the Processes of DNA replication, transcription, chromosome condensation and decondensation. The essential role of hTopo in these processes has made it a preeminent anticancer drug target. We have screened a small library of arylstibonic acids for their effects on plasmid supercoil relaxation catalyzed by hTopo. Despite the similar Structures of the library compounds, some compounds were found to be effective competitive inhibitors, and others, nonessential activators. Some arylstibonic acids show selectivity in their action against hTopo and the related enzyme from poxvirus (vTopo). Structure-activity relationships and structural modeling suggest that competitive inhibition may result from positioning of the negatively charged stibonic acid and carboxylate groups of the inhibitors into DNA phosphate binding pockets on hTopo. The hTopo activators act by a surprising allosteric mechanism without interfering with DNA binding or binding of the widely used hTopo poison camptothecin. Arylstibonic acid competitive inhibitors may become useful small molecules for elucidating the cellular functions of hTopo. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Kim, Hyeongnam; Stivers, James T.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
[Cardellina, John H., II] NCI, Screening Technol Branch, Frederick, MD 21702 USA.
[Akee, Rhone] SAIC Frederick Inc, Nat Prod Support Grp, Frederick, MD 21702 USA.
[Champoux, James J.] Univ Washington, Dept Microbiol, Sch Med, Seattle, WA 98195 USA.
RP Stivers, JT (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, 725 N Wolfe St, Baltimore, MD 21205 USA.
EM jstivers@jhmi.edu
FU NIH [GM56834, GM49156, N01-CO-12400]; National Cancer Institute;
Department of Health and Human Services
FX We thank the Developmental Therapeutics Program at the National Cancer
Institute for the small molecule libraries. This work was supported by
NIH Grants GM56834 to J.T.S. and GM49156 to J.J.C. and in whole or in
part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract N01-CO-12400, and in part by the
Developmental Therapeutics Program in the Division of Cancer Treatment
and Diagnosis of the National Cancer Institute. The content of the
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products or organizations imply endorsement by the US
Government.
NR 19
TC 6
Z9 7
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0045-2068
J9 BIOORG CHEM
JI Bioorganic Chem.
PD AUG-DEC
PY 2008
VL 36
IS 4-6
BP 190
EP 197
DI 10.1016/j.bioorg.2008.04.001
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 386TP
UT WOS:000261905800004
PM 18508107
ER
PT J
AU Hruschka, S
Rosen, TC
Yoshida, S
Kirk, KL
Frohlich, R
Wibbeling, B
Haufe, G
AF Hruschka, Svenja
Rosen, Thomas C.
Yoshida, Shinichi
Kirk, Kenneth L.
Froehlich, Roland
Wibbeling, Birgit
Haufe, Guenter
TI Fluorinated phenylcyclopropylamines. Part 5: Effects of
electron-withdrawing or -donating aryl substituents on the inhibition of
monoamine oxidases A and B by 2-aryl-2-fluoro-cyclopropylamines
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE monoamine oxidase; tranylcypromine; fluorinated phenylcyclopropylamine;
irreversible inhibition; stereochemistry
ID SENSITIVE AMINE OXIDASE; MICROBIAL TYRAMINE OXIDASE; HISTONE DEMETHYLASE
LSD1; ACTIVE-SITE; BENZYLAMINE ANALOGS; INACTIVATOR ADDUCT;
CRYSTAL-STRUCTURES; VINYL FLUORIDES; AROMATIC CAGE; MECHANISM
AB A series of racemic, diastereoisomeric aryl cyclopropylamines substituted with fluorine in the 2-position and electron-donating and electron-withdrawing groups on the aromatic ring have been prepared. These represent analogues of the classic MAO inhibitor tranylcypromine (trans-2-phenylcyclopropylamine, 1). Their activities as inhibitors of recombinant human liver monoamine oxidases A (MAO A) and B (MAO B) were determined. The trans-compounds were low micromolar inhibitors of both MAO A and MAO B with moderate MAO A selectivity while the less active cis-analogues were MAO B selective. In the trans-series, electron-withdrawing para-substituents increased the potency of MAO A inhibition while electron-donating groups such as methyl or methoxy had no influence on this activity. In contrast, aromatic ring substitution in the trans-series had essentially no effect on the inhibition of MAO B. The corresponding cis-compounds were shown to be 10-100 times less active against MAO A, while trans-and cis-compounds were quite similar in terms of inhibition of MAO B. The best MAO A/ MAO B selectivity (7: 1) in the trans-series was found for trans-2-fluoro-2-(para-trifluoromethylphenyl) cyclopropylamine (7d), while a 1: 27 selectivity was found for cis-2-fluoro-2-(para-fluorophenyl) cyclopropylamine (10c). These results are discussed in connection with the pK(a) and logD values, the mechanism of action of tranylcypromines, and the geometry of the active site of the enzymes. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Hruschka, Svenja; Rosen, Thomas C.; Froehlich, Roland; Wibbeling, Birgit; Haufe, Guenter] Univ Munster, Inst Organ Chem, D-48149 Munster, Germany.
[Hruschka, Svenja; Rosen, Thomas C.; Froehlich, Roland; Wibbeling, Birgit; Haufe, Guenter] Univ Munster, Int NRW Grad Sch Chem, D-48149 Munster, Germany.
[Yoshida, Shinichi] Tottori Inst Ind Technol, Tottori 6891112, Japan.
[Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Haufe, G (reprint author), Univ Munster, Inst Organ Chem, Corrensstr 40, D-48149 Munster, Germany.
EM haufe@uni-muenster.de
FU DFG; the International NRW Graduate School of Chemistry; Intramural
Research Funds of NIDDK; NIH; the research grant of Tottoti Prefectural
Government, Japan
FX This work was partially supported by the DFG as a contribution from the
Sonderforschungsbereich 424, the International NRW Graduate School of
Chemistry, the Intramural Research Funds of NIDDK, NIH, and the research
grant of Tottoti Prefectural Government, Japan. We thank Professor Dale
E. Edmondson, Emory University, Atlanta, Georgia, USA, for the kind
donation of recombinant human mitochondrial MAO A and B, Professor Klaus
Muller, F. Hoffmann La Roche Ltd, Basel, Switzerland and Dr. Thomas
Kramer, Bayer Schering Pharma for measurements of pKa, and
logD values, and Prof. Norbert Straeter, University of Leipzig for his
help concerning the structure of the binding pocket of MAO A.
NR 76
TC 14
Z9 14
U1 2
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 1
PY 2008
VL 16
IS 15
BP 7148
EP 7166
DI 10.1016/j.bmc.2008.06.048
PG 19
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 341XR
UT WOS:000258749500008
PM 18640844
ER
PT J
AU Ivanov, AA
Jacobson, KA
AF Ivanov, Andrei A.
Jacobson, Kenneth A.
TI Molecular modeling of a PAMAM-CGS21680 dendrimer bound to an A(2A)
adenosine receptor homodimer
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE nucleoside; G protein-coupled receptor; dimerization; homology modeling;
purines; polymerbound drug; functionalized congener
ID PROTEIN-COUPLED RECEPTORS; BIVALENT LIGANDS; AGONISTS; PHARMACOLOGY;
A(1)
AB The theoretical possibility of bivalent binding of a dendrimer, covalently appended with multiple copies of a small ligand, to a homodimer of a G protein-coupled receptor was investigated with a molecular modeling approach. A molecular model was constructed of a third generation (G3) poly(amidoamine) (PAMAM) dendrimer condensed with multiple copies of the potent A(2A) adenosine receptor agonist CGS21680. The dendrimer was bound to an A(2A) adenosine receptor homodimer. Two units of the nucleoside CGS21680 could occupy the A(2A) receptor homodimer simultaneously. The binding mode of CGS21680 moieties linked to the PAMAM dendrimer and docked to the A(2A) receptor was found to be similar to the binding mode of a monomeric CGS21680 ligand. Published by Elsevier Ltd.
C1 [Ivanov, Andrei A.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [Z01 DK031115-24, Z01 DK031117-20, Z01 DK031126-01]
NR 22
TC 25
Z9 27
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 AUG 1
PY 2008
VL 18
IS 15
BP 4312
EP 4315
DI 10.1016/j.bmcl.2008.06.087
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 331AZ
UT WOS:000257986400011
PM 18639453
ER
PT J
AU Nablo, BJ
Halverson, KM
Robertson, JWF
Nguyen, TL
Panchal, RG
Gussio, R
Bavari, S
Krasilnikov, OV
Kasianowicz, JJ
AF Nablo, Brian J.
Halverson, Kelly M.
Robertson, Joseph W. F.
Nguyen, Tam L.
Panchal, Rekha G.
Gussio, Rick
Bavari, Sina
Krasilnikov, Oleg V.
Kasianowicz, John J.
TI Sizing the Bacillus anthracis PA(63) channel with nonelectrolyte
poly(ethylene glycols)
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SYMMETRICAL TETRAALKYLAMMONIUM IONS; PHOSPHOLIPID-BILAYER MEMBRANES;
TOXIN PROTECTIVE ANTIGEN; PLANAR LIPID-BILAYERS; PROTEIN TRANSLOCATION;
CRYSTAL-STRUCTURE; ANION CHANNEL; PORE RADIUS; CONDUCTIVITY; CONDUCTANCE
AB Nonelectrolyte polymers of poly(ethylene glycol) (PEG) were used to estimate the diameter of the ion channel formed by the Bacillus anthracis protective antigen 63 (PA(63)). Based on the ability of different molecular weight PEGs to partition into the pore and reduce channel conductance, the pore appears to be narrower than the one formed by Staphylococcus aureus a-hemolysin. Numerical integration of the PEG sample mass spectra and the channel conductance data were used to refine the estimate of the pore's PEG molecular mass cutoff (similar to 1400 g/mol). The results suggest that the limiting diameter of the PA(63) pore is < 2 nm, which is consistent with an all-atom model of the PA(63) channel and previous experiments using large ions.
C1 [Nablo, Brian J.; Robertson, Joseph W. F.; Kasianowicz, John J.] NIST, Div Semicond Elect, Elect & Elect Lab, Gaithersburg, MD 20899 USA.
[Halverson, Kelly M.] USA, Ctr Environm Hlth Res, Frederick, MD USA.
[Nguyen, Tam L.; Panchal, Rekha G.; Gussio, Rick] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick, Frederick, MD 21701 USA.
[Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD USA.
[Krasilnikov, Oleg V.] Univ Fed Pernambuco, Lab Membrane Biophys, Dept Biophys & Radiobiol, Recife, PE, Brazil.
RP Kasianowicz, JJ (reprint author), NIST, Div Semicond Elect, Elect & Elect Engn Lab, Gaithersburg, MD 20899 USA.
EM john.kasianowicz@nist.gov
FU NCI NIH HHS [N01-CO-12400, N01CO12400]
NR 53
TC 23
Z9 23
U1 1
U2 5
PU BIOPHYSICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 1
PY 2008
VL 95
IS 3
BP 1157
EP 1164
DI 10.1529/biophysj.107.121715
PG 8
WC Biophysics
SC Biophysics
GA 327HC
UT WOS:000257719200017
PM 18645196
ER
PT J
AU Bennett, MP
Mitchell, DC
AF Bennett, Michael P.
Mitchell, Drake C.
TI Regulation of membrane proteins by dietary lipids: Effects of
cholesterol and docosahexaenoic acid acyl chain-containing phospholipids
on rhodopsin stability and function
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID DIFFERENTIAL SCANNING CALORIMETRY; IRREVERSIBLE THERMAL-DENATURATION;
OUTER SEGMENT MEMBRANES; DISK MEMBRANES; COUPLED RECEPTOR;
PHOTORECEPTOR-MEMBRANES; RECOMBINANT MEMBRANES; CONCANAVALIN-A;
EQUILIBRIUM; MODULATION
AB Purified bovine rhodopsin was reconstituted into vesicles consisting of 1-stearoyl-2-oleoyl phosphatidylcholine or 1-stearoyl-2-docosahexaenoyl phosphatidylcholine with and without 30 mol % cholesterol. Rhodopsin stability was examined using differential scanning calorimetry (DSC). The thermal unfolding transition temperature (T-m) of rhodopsin was scan rate-dependent, demonstrating the presence of a rate-limited component of denaturation. The activation energy of this kinetically controlled process (E-a) was determined from DSC thermograms by four separate methods. Both T-m and Ea varied with bilayer composition. Cholesterol increased the T-m both the presence and absence of docosahexaenoic acid acyl chains (DHA). In contrast, cholesterol lowered Ea in the absence of DHA, but raised Ea in the presence of 20 mol % DHA-containing phospholipid. The relative acyl chain packing order was determined from measurements of diphenylhexatriene fluorescence anisotropy decay. The Tm for thermal unfolding was inversely related to acyl chain packing order. Rhodopsin kinetic stability (E-a) was reduced in highly ordered or disordered membranes. Maximal kinetic stability was found within the range of acyl chain order found in native bovine rod outer segment disk membranes. The results demonstrate that membrane composition has distinct effects on the thermal versus kinetic stabilities of membrane proteins, and suggests that a balance between membrane constituents with opposite effects on acyl chain packing, such as DHA and cholesterol, may be required for maximum protein stability.
C1 [Bennett, Michael P.; Mitchell, Drake C.] NIAAA, Lab Membrane Biochem & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Mitchell, DC (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Natl Inst Hlth, Room 3N-07,5625 Fishers Lane, Bethesda, MD 20892 USA.
EM dmitch@mail.nih.gov
NR 64
TC 23
Z9 23
U1 1
U2 7
PU BIOPHYSICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 1
PY 2008
VL 95
IS 3
BP 1206
EP 1216
DI 10.1529/biophysj.107.122788
PG 11
WC Biophysics
SC Biophysics
GA 327HC
UT WOS:000257719200022
PM 18424497
ER
PT J
AU Han, Q
Cai, T
Tagle, DA
Robinson, H
Li, JY
AF Han, Qian
Cai, Tao
Tagle, Danilo A.
Robinson, Howard
Li, Jianyong
TI Substrate specificity and structure of human aminoadipate
aminotransferase/kynurenine aminotransferase II
SO BIOSCIENCE REPORTS
LA English
DT Article
DE aminoadipic acid; crystal structure; kynurenic acid (KYNA); kynurenine;
kynurenine aminotransferase (KAT); neurodegenerative disease
ID ALPHA-KETOADIPIC ACIDURIA; MITOCHONDRIAL ASPARTATE-AMINOTRANSFERASE;
GLUTAMINE TRANSAMINASE-K; EXCITATORY AMINO-ACIDS; KYNURENINE
AMINOTRANSFERASE; RAT-BRAIN; HUNTINGTONS-DISEASE; CRYSTAL-STRUCTURE;
ESCHERICHIA-COLI; LYSINE METABOLISM
AB KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to a-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an enclotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested alpha-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with alpha-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15-33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.
C1 [Han, Qian; Li, Jianyong] Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA.
[Cai, Tao] NIDCR, OIIB, NIH, Bethesda, MD 20892 USA.
[Tagle, Danilo A.] NINDS, Ctr Neurosci, NIH, Bethesda, MD 20892 USA.
[Robinson, Howard] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
RP Han, Q (reprint author), Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA.
EM qianhan@vt.edu
RI Han, Qian/J-8696-2014
OI Han, Qian/0000-0001-6245-5252
FU Intramural NIH HHS [Z99 DE999999]; NIBIB NIH HHS [P30 EB009998]
NR 95
TC 38
Z9 39
U1 4
U2 5
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0144-8463
J9 BIOSCIENCE REP
JI Biosci. Rep.
PD AUG
PY 2008
VL 28
IS 4
BP 205
EP 215
DI 10.1042/BSR20080085
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 364VZ
UT WOS:000260364900004
PM 18620547
ER
PT J
AU Laffont, S
Seillet, C
Ortaldo, J
Coudert, JD
Guery, JC
AF Laffont, Sophie
Seillet, Cyril
Ortaldo, John
Coudert, Jerome D.
Guery, Jean-Charles
TI Natural killer cells recruited into lymph nodes inhibit alloreactive
T-cell activation through perforin-mediated killing of donor allogeneic
dendritic cells
SO BLOOD
LA English
DT Article
ID NK CELLS; IN-VIVO; ORGAN ALLOGRAFTS; GRAFT-REJECTION; BONE-MARROW;
RECOGNITION; RECEPTORS; TOLERANCE; CYTOTOXICITY; EXPRESSION
AB Natural killer (NK)-cell alloreactivity is exploited in bone marrow transplantation to improve clinical outcome. Likewise, in solid organ transplantation, it has been recently shown that recipient NK cells may limit alloreactive T-cell responses through their capacity to prevent the persistence of graft-derived allogeneic dendritic cells (DCs). In a model of CD4+ T cell-mediated allogeneic skin graft rejection, we show that the absence of host NK-cell alloreactivity was characterized by enhanced expansion of alloreactive effector T lymphocytes, including Th2 cells, and massive eosinophilic infiltrates in the rejected tissues. In CD8+ T celldeficient C57BL/6 (H-2b) recipients injected with allogeneic BALB/c (H-2d) DCs, we demonstrated that NK cells expressing the H-2Dd-specific Ly49D activating receptor were implicated in the regulation of alloreactive CD4+ T-cell responses. Moreover, we showed that Ly49D+ CD127NK cells were recruited within DC drain- ing lymph nodes and rapidly eliminated allogeneic H-2d DCs through the perforin pathway. In normal mice, we further demonstrated that NK cells by quickly eliminating allogeneic DCs strongly inhibited alloreactive CD8+ T-cell responses. Thus, NK cells act as early regulators of alloreactive T-cell priming in allotransplantation through their capacity to kill allogeneic DCs in draining lymph nodes.
C1 [Laffont, Sophie; Seillet, Cyril; Coudert, Jerome D.; Guery, Jean-Charles] Ctr Physiopathol Toulouse Purpan, INSERM, U563, Toulouse, France.
[Laffont, Sophie; Seillet, Cyril; Coudert, Jerome D.; Guery, Jean-Charles] Univ Toulouse 3, F-31062 Toulouse, France.
[Ortaldo, John] NCI, Ctr Canc Res, Expt Immunol Lab, Frederick, MD 21701 USA.
RP Guery, JC (reprint author), CHU Purpan, INSERM, U563, Pl Dr Baylac,BP 3028, F-31024 Toulouse 3, France.
EM Jean-Charles.Guery@inserm.fr
RI Coudert, Jerome David/B-2628-2008; GUERY, Jean-Charles/G-1452-2013;
Laffont, Sophie/K-2683-2014
OI Coudert, Jerome David/0000-0001-6081-8494; GUERY,
Jean-Charles/0000-0003-4499-3270;
NR 40
TC 60
Z9 64
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 1
PY 2008
VL 112
IS 3
BP 661
EP 671
DI 10.1182/blood-2007-10-120089
PG 11
WC Hematology
SC Hematology
GA 334YO
UT WOS:000258257900033
PM 18505782
ER
PT J
AU Bergsagel, FL
Kuehl, WM
AF Bergsagel, F. Leif
Kuehl, W. Michael
TI WSU-WM and BCWM.1 should not be assumed to represent Waldenstrom
macroglobulinemia cell lines
SO BLOOD
LA English
DT Letter
ID MULTIPLE-MYELOMA CELLS; IN-VITRO; SURVIVAL; MODEL; MICE
C1 [Bergsagel, F. Leif] Mayo Clin, Scottsdale, AZ 85259 USA.
[Kuehl, W. Michael] Natl Canc Inst, Bethesda, MD 20814 USA.
RP Bergsagel, FL (reprint author), Mayo Clin, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA.
EM bergsagel.leif@mayo.edu; wmk@helix.nih.gov
NR 17
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 1
PY 2008
VL 112
IS 3
BP 917
EP 917
PG 1
WC Hematology
SC Hematology
GA 334YO
UT WOS:000258257900070
ER
PT J
AU Brody, T
Rasband, W
Baler, K
Kuzin, A
Kundu, M
Odenwald, WF
AF Brody, Thomas
Rasband, Wayne
Baler, Kevin
Kuzin, Alexander
Kundu, Mukta
Odenwald, Ward F.
TI Sequence conservation and combinatorial complexity of Drosophila neural
precursor cell enhancers
SO BMC GENOMICS
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; OF-SPLIT COMPLEX; TARGET GENES; TRANSCRIPTIONAL
ACTIVATOR; PRONEURAL PROTEINS; DOWNSTREAM TARGETS; ORGAN DEVELOPMENT;
DNA RECOGNITION; BINDING-SITES; HOX GENES
AB Background: The presence of highly conserved sequences within cis-regulatory regions can serve as a valuable starting point for elucidating the basis of enhancer function. This study focuses on regulation of gene expression during the early events of Drosophila neural development. We describe the use of EvoPrinter and cis-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among coregulating enhancers.
Results: Analysis of in vivo characterized enhancers that drive neural precursor gene expression has revealed that they contain clusters of highly conserved sequence blocks (CSBs) made up of shorter shared sequence elements which are present in different combinations and orientations within the different co-regulating enhancers; these elements contain either known consensus transcription factor binding sites or consist of novel sequences that have not been functionally characterized. The CSBs of co-regulated enhancers share a large number of sequence elements, suggesting that a diverse repertoire of transcription factors may interact in a highly combinatorial fashion to coordinately regulate gene expression. We have used information gained from our comparative analysis to discover an enhancer that directs expression of the nervy gene in neural precursor cells of the CNS and PNS.
Conclusion: The combined use EvoPrinter and cis-Decoder has yielded important insights into the combinatorial appearance of fundamental sequence elements required for neural enhancer function. Each of the 30 enhancers examined conformed to a pattern of highly conserved blocks of sequences containing shared constituent elements. These data establish a basis for further analysis and understanding of neural enhancer function.
C1 [Brody, Thomas; Kuzin, Alexander; Kundu, Mukta; Odenwald, Ward F.] NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA.
[Rasband, Wayne; Baler, Kevin] NIMH, Off Sci Director, IRP, NIH, Bethesda, MD 20892 USA.
RP Odenwald, WF (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM brodyt@ninds.nih.gov; wsr@nih.gov; kb263@cornell.edu;
kuzina@mail.nih.gov; muktakundu@mail.nih.gov; ward@codon.nih.gov
FU NIH; NINDS
FX The authors would like to thank Jermaine Ross and Antonios Ekatomatis
for their technical assistance and Judith Brody for editorial expertise.
This research was supported by the Intramural Research Program of the
NIH, NINDS.
NR 64
TC 8
Z9 8
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 1
PY 2008
VL 9
AR 371
DI 10.1186/1471-2164-9-371
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 347JW
UT WOS:000259137500003
PM 18673565
ER
PT J
AU Levine, JE
Barrett, AJ
Zhang, MJ
Arora, M
Pulsipher, MA
Bunin, N
Fort, J
Loberiza, F
Porter, D
Giralt, S
Drobyski, W
Wang, D
Pavletic, S
Ringden, O
Horowitz, MM
Collins, R
AF Levine, J. E.
Barrett, A. J.
Zhang, M-J
Arora, M.
Pulsipher, M. A.
Bunin, N.
Fort, J.
Loberiza, F.
Porter, D.
Giralt, S.
Drobyski, W.
Wang, D.
Pavletic, S.
Ringden, O.
Horowitz, M. M.
Collins, R., Jr.
TI Donor leukocyte infusions to treat hematologic malignancy relapse
following allo-SCT in a pediatric population
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE DLI; GVHD; relapse
ID BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL
TRANSPLANTATION; TRIAL
AB Donor leukocyte infusions (DLI) can reverse relapse of hematologic malignancy following allogeneic hematopoietic stem cell transplant (HSCT) in some cases. Little is known regarding the effectiveness of DLI in children who relapse after HSCT. We report outcomes of 49 children who received DLI for relapse after allogeneic transplant. Prognosis was particularly poor (0/14 responses) for patients relapsing within 6 months from transplant. DLI rarely induced remission when given as sole therapy for marrow relapse. One-year disease-free survival was 30% (6/20) in patients who received DLI as consolidation following chemotherapy. The development of GVHD grades 1-2 was associated with superior 3-year survival than patients who developed GVHD grades 3-4 (P < 0.002). To determine the benefit of DLI, 45 children who received DLI for relapse (four children without matches were excluded) were compared to 1229 children with similar characteristics whose relapse was not treated with DLI. There was no difference in survival (P = 0.30) once adjustments were made to account for the time from relapse to DLI. Although a few children achieved durable remissions when DLI was used as part of a post-relapse treatment strategy, DLI was unsuccessful in the majority of cases. Strategies may be better directed at preempting post transplant relapse.
C1 [Levine, J. E.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Levine, J. E.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Barrett, A. J.] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Zhang, M-J; Arora, M.; Loberiza, F.; Wang, D.; Horowitz, M. M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Pulsipher, M. A.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Bunin, N.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Fort, J.] Miami Childrens Hosp, Dept Hematol Oncol, Miami, FL USA.
[Porter, D.] Univ Penn, Bone Marrow & Stem Cell Transplant Program, Philadelphia, PA 19104 USA.
[Giralt, S.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Drobyski, W.] Med Coll Wisconsin, Bone Marrow Transplant Program, Milwaukee, WI 53226 USA.
[Pavletic, S.] Natl Canc Inst, Natl Inst Hlth, Bethesda, MD USA.
[Ringden, O.] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
[Ringden, O.] Karolinska Inst, Stockholm, Sweden.
[Collins, R., Jr.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Hematopoiet Cell Transplantat Program, Dallas, TX 75390 USA.
RP Levine, JE (reprint author), Univ Michigan Hlth System, Canc Ctr 5303, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM jelevine@med.umich.edu
OI Levine, John/0000-0002-9133-0800
NR 14
TC 34
Z9 34
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD AUG
PY 2008
VL 42
IS 3
BP 201
EP 205
DI 10.1038/bmt.2008.135
PG 5
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 337CO
UT WOS:000258413300008
PM 18490913
ER
PT J
AU Towle, VL
Yoon, HA
Castelle, M
Edgar, JC
Biassou, NM
Frim, DM
Spire, JP
Kohrman, MH
AF Towle, Vernon L.
Yoon, Hyun-Ah
Castelle, Michael
Edgar, J. Christopher
Biassou, Nadia M.
Frim, David M.
Spire, Jean-Paul
Kohrman, Michael H.
TI ECoG gamma activity during a language task: differentiating expressive
and receptive speech areas
SO BRAIN
LA English
DT Article
DE language mapping; cortical mapping; direct cortical stimulation;
functional mapping; epilepsy surgery; electrocorticography; ECoG power
ID BAND OSCILLATING-POTENTIALS; HUMAN SENSORIMOTOR CORTEX; HUMAN
AUDITORY-CORTEX; LATERAL TEMPORAL-LOBE; ELECTRICAL-STIMULATION;
EVOKED-POTENTIALS; SUBDURAL ELECTRODES; NEURONAL-ACTIVITY;
VISUAL-CORTEX; EEG COHERENCE
AB Electrocorticographic (ECoG) spectral patterns obtained during language tasks from 12 epilepsy patients (age: 1244 years) were analysed in order to identify and characterize cortical language areas. ECoG from 63 subdural electrodes (500 Hz/channel) chronically implanted over frontal, parietal and temporal lobes were examined. Two language tasks were performed. During the first language task, patients listened to a series of 50 words preceded by warning tones, and were asked to repeat each word. During a second memory task, subjects heard the 50 words from the first task randomly mixed with 50 new words and were asked to repeat the word only if it was a new word. Increases in ECoG gamma power (70100 Hz) were observed in response to hearing tones (primary auditory cortex), hearing words (posterior temporal and parietal cortex) and repeating words (lateral frontal and anterior parietal cortex). These findings were compared to direct electrical stimulation and separate analysis of ECoG gamma changes during spontaneous inter-personal conversations. The results indicate that high-frequency ECoG reliably differentiates cortical areas associated with receptive and expressive speech processes for individual patients. Compared to listening to words, greater frontal lobe and decreased temporal lobe gamma activity was observed while speaking. The data support the concept of distributed functionally specific language modules interacting to serve receptive and expressive speech, with frontal lobe corollary discharges suppressing low-level receptive cortical language areas in the temporal lobe during speaking.
C1 [Towle, Vernon L.; Yoon, Hyun-Ah; Castelle, Michael; Spire, Jean-Paul] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA.
[Towle, Vernon L.; Frim, David M.; Spire, Jean-Paul] Univ Chicago, Dept Surg, Chicago, IL 60637 USA.
[Towle, Vernon L.; Kohrman, Michael H.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Towle, Vernon L.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Edgar, J. Christopher] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA.
[Edgar, J. Christopher] Ctr Funct Brain Imaging, Albuquerque, NM USA.
[Biassou, Nadia M.] NIH, Dept Imaging Sci, Div Neuroradiol, Bethesda, MD 20892 USA.
RP Towle, VL (reprint author), Univ Chicago, Dept Neurol, MC 2030,5841 S Maryland Ave, Chicago, IL 60637 USA.
EM towle@uchicago.edu
FU NINDS NIH HHS [5 R01 NS40514, R01 NS040514]
NR 85
TC 90
Z9 92
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD AUG
PY 2008
VL 131
BP 2013
EP 2027
DI 10.1093/brain/awn147
PN 8
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 335XW
UT WOS:000258329900011
PM 18669510
ER
PT J
AU Sanchez-Pernaute, R
Lee, H
Patterson, M
Reske-Nielsen, C
Yoshizaki, T
Sonntag, KC
Studer, L
Isacson, O
AF Sanchez-Pernaute, Rosario
Lee, Hyojin
Patterson, Michaela
Reske-Nielsen, Casper
Yoshizaki, Takahito
Sonntag, Kai C.
Studer, Lorenz
Isacson, Ole
TI Parthenogenetic dopamine neurons from primate embryonic stem cells
restore function in experimental Parkinsons disease
SO BRAIN
LA English
DT Article
DE stem cells; transplantation; midbrain; Parkinson's disease;
parthenogenesis
ID SUBSTANTIA-NIGRA; NUCLEAR TRANSFER; RAT MODEL; DIRECTED DIFFERENTIATION;
INDUCED DYSKINESIA; NEURAL PRECURSORS; ANIMAL-MODEL; ES CELLS;
TRANSPLANTATION; MICE
AB The identity and functional potential of dopamine neurons derived in vitro from embryonic stem cells are critical for the development of a stem cell-based replacement therapy for Parkinsons disease. Using a parthenogenetic primate embryonic stem cell line, we have generated dopamine neurons that display persistent expression of midbrain regional and cell-specific transcription factors, which establish their proper identity and allow for their survival. We show here that transplantation of parthenogenetic dopamine neurons restores motor function in hemi-parkinsonian, 6-hydroxy-dopamine-lesioned rats. Exposure to Wnt5a and fibroblast growth factors (FGF) 20 and 2 at the final stage of in vitro differentiation enhanced the survival of dopamine neurons and, correspondingly, the extent of motor recovery of transplanted animals. Importantly for future development of clinical applications, dopamine neurons were post-mitotic at the time of transplantation and there was no tumour formation. These data provide proof for the concept that parthenogenetic stem cells are a suitable source of functional neurons for therapeutic applications.
C1 [Sanchez-Pernaute, Rosario; Yoshizaki, Takahito; Sonntag, Kai C.; Isacson, Ole] Harvard Univ, Udall Parkinsons Dis Res Ctr Excellence, McLean Hosp, Belmont, MA 02478 USA.
[Sanchez-Pernaute, Rosario; Patterson, Michaela; Reske-Nielsen, Casper; Yoshizaki, Takahito; Sonntag, Kai C.; Isacson, Ole] Neuroregenerat Labs, McLean Hosp, Belmont, MA 02478 USA.
[Lee, Hyojin; Studer, Lorenz] Mem Sloan Kettering Canc Ctr, Div Neurosurg & Dev Biol, Lab Stem Cell & Tumor Biol, New York, NY 10021 USA.
RP Sanchez-Pernaute, R (reprint author), Fdn Inbiomed, Neuronal Stem Cells Lab, Paseo Mikeletegi 61, San Sebastian 20009, Spain.
EM rosario_pernaute@hms.harvard.edu
FU NINDS NIH HHS [P50 NS039793, R01 NS052671, R01 NS-052671, P50 NS-39793]
NR 61
TC 53
Z9 56
U1 2
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD AUG
PY 2008
VL 131
BP 2127
EP 2139
DI 10.1093/brain/awn144
PN 8
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 335XW
UT WOS:000258329900019
PM 18669499
ER
PT J
AU Martin, LA
Ashwood, P
Braunschweig, D
Cabanlit, M
Van de Water, J
Amaral, DG
AF Martin, Loren A.
Ashwood, Paul
Braunschweig, Daniel
Cabanlit, Maricel
Van de Water, Judy
Amaral, David G.
TI Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from
mothers of children with autism
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE repetitive; primate; macaque; macaca mulatta; activity; Asperger
syndrome
ID ARTHROGRYPOSIS MULTIPLEX CONGENITA; NEONATAL AMYGDALA LESIONS; MATERNAL
MYASTHENIA; ANTIBODIES; AUTOANTIBODIES; BEHAVIOR; DISORDERS; ATTENTION;
DISEASE; ANTIGEN
AB Autism together with Asperger syndrome and pervasive developmental disorder not otherwise specified form a spectrum of conditions (autism spectrum disorders or ASD) that is characterized by disturbances in social behavior, impaired communication and the presence of stereotyped behaviors or circumscribed interests. Recent estimates indicate a prevalence of ASD of 1 per 150 (Kuehn, 2007). The cause(s) of most cases of ASD are unknown but there is an emerging consensus that ASD have multiple etiologies. One proposed cause of ASD is exposure of the fetal brain to maternal autoantibodies during pregnancy [Dalton, P., Deacon, R., Blamire, A., Pike, M., McKinlay, I., Stein, J., Styles, P., Vincent, A., 2003. Maternal neuronal antibodies associated with autism and a language disorder. Ann. Neurol. 53, 533-537]. To provide evidence for this hypothesis, four rhesus monkeys were exposed prenatally to human IgG collected from mothers of multiple children diagnosed with ASD. Four control rhesus monkeys were exposed to human IgG collected from mothers of multiple typically developing children. Five additional monkeys were untreated controls. Monkeys were observed in a variety of behavioral paradigms involving unique social situations. Behaviors were scored by trained observers and overall activity was monitored with actimeters. Rhesus monkeys gestationally exposed to IgG class antibodies from mothers of children with ASD consistently demonstrated increased whole-body stereotypies across multiple testing paradigms. These monkeys were also hyperactive compared to controls. Treatment with IgG purified from mothers of typically developing children did not induce stereotypical or hyperactive behaviors. These findings support the potential for an autoimmune etiology in a subgroup of patients with neurodevelopmental disorders. This research raises the prospect of prenatal evaluation for neurodevelopmental risk factors and the potential for preventative therapeutics. (c) 2008 Elsevier Inc. All rights reserved.
C1 [Martin, Loren A.; Ashwood, Paul; Amaral, David G.] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA.
[Martin, Loren A.; Amaral, David G.] Univ Calif Davis, Calif Natl Primate Res Ctr, Ctr Neurosci, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA.
[Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Sacramento, CA 95817 USA.
[Ashwood, Paul; Van de Water, Judy; Amaral, David G.] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Sacramento, CA 95817 USA.
[Braunschweig, Daniel; Cabanlit, Maricel; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Sacramento, CA 95817 USA.
RP Amaral, DG (reprint author), Univ Calif Davis, MIND Inst, 2825 50th St, Sacramento, CA 95817 USA.
EM dgamaral@ucdavis.edu
FU NIEHS NIH HHS [1P01 ES11269-01, P01 ES011269]; NIMH NIH HHS [MH41479,
R01 MH041479, R01 MH057502, R01 MH057502-03, R37 MH041479, R37 MH057502]
NR 50
TC 112
Z9 117
U1 4
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD AUG
PY 2008
VL 22
IS 6
BP 806
EP 816
DI 10.1016/j.bbi.2007.12.007
PG 11
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 325RL
UT WOS:000257605900003
PM 18262386
ER
PT J
AU Fuxe, K
Marcellino, D
Rivera, A
Diaz-Cabiale, Z
Filip, M
Gago, B
Roberts, DCS
Langel, U
Genedani, S
Ferraro, L
de la Calle, A
Narvaez, J
Tanganelli, S
Woods, A
Agnati, LF
AF Fuxe, K.
Marcellino, D.
Rivera, A.
Diaz-Cabiale, Z.
Filip, M.
Gago, B.
Roberts, D. C. S.
Langel, U.
Genedani, S.
Ferraro, L.
de la Calle, A.
Narvaez, J.
Tanganelli, S.
Woods, A.
Agnati, L. F.
TI Receptor-receptor interactions within receptor mosaics. Impact on
neuropsychopharmacology
SO BRAIN RESEARCH REVIEWS
LA English
DT Review
DE heteromerization; striatum; dopamine receptor; CB1 receptor; adenosine
receptor; mGluR5; 5-HT1A receptor; galanin receptor; Parkinson's
disease; schizophrenia; drug addiction; depression; treatment strategy
ID CENTRAL-NERVOUS-SYSTEM; ADENOSINE A(2A) RECEPTORS; DOPAMINE D-3
RECEPTOR; CB1 CANNABINOID RECEPTOR; CENTRAL CARDIOVASCULAR CONTROL;
LEVODOPA-INDUCED DYSKINESIA; COCAINE-SEEKING BEHAVIOR; VENTRAL LIMBIC
CORTEX; RAT NUCLEUS-ACCUMBENS; MEDIUM SPINY NEURONS
AB Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D-2 receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D-2 RM, located in the dorsal striatopallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D-2 interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D-2/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D-2 signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D-2-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably representing a compensatory up-regulation to counteract the cocaine-induced increases in dopamine D-2 and D-3 signaling. Therefore, A(2A) agonists, through antagonizing D-2 and D-3 signaling within A(2A)/D-2 and A(2)/D-3 RM heteromers in the nucleus accumbens, may be found useful as a treatment for cocaine dependence. Furthermore, antagonistic cannabinoid CB1/D-2 interactions requiring A(2A) receptors have also been discovered and possibly operate in CB1/D-2/A(2A) RM located principally on striatal glutamate terminals but also on some ventral striato-pallidal GABA neurons, thereby opening up a new mechanism for the integration of endocannabinoid, DA and adenosine mediated signals. Thus, A(2A), mGluR5 and/or CB1 receptors can form integrative units with D-2 receptors within RM displaying different compositions, topography and localization. Also galaninR/5-HT1A RM probably participates in the transmission of the ascending 5-hydroxytryptamine neurons, where galanin receptors antagonize 5-HT1A recognition and signaling. Subtype specific galanin receptor antagonists may therefore represent novel antidepressant drugs. These results suggest the importance of a complete understanding of the function of these RM with regard to disease.
Ultimately receptor-recepor interactions within RM that modify dopaminergic and serotonergic signaling may give new strategies for treatment of a wide range of diseases associated with altered dopaminergic and serotonergic signaling. (C) 2007 Elsevier B.V. All rights reserved.
C1 [Fuxe, K.; Marcellino, D.] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
[Rivera, A.; Gago, B.; de la Calle, A.] Univ Malaga, Sch Sci, Dept Cell Biol, E-29071 Malaga, Spain.
[Diaz-Cabiale, Z.; Narvaez, J.] Univ Malaga, Sch Sci, Dept Physiol, E-29071 Malaga, Spain.
[Filip, M.] Polish Acad Sci, Inst Pharmacol, Dept Pharmacol, PL-31343 Krakow, Poland.
[Roberts, D. C. S.] Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA.
[Langel, U.] Stockholm Univ, Dept Neurochem, S-10691 Stockholm, Sweden.
[Ferraro, L.; Tanganelli, S.] Univ Ferrara, Pharmacol Sect, Dept Clin & Expt Med, I-44100 Ferrara, Italy.
[Woods, A.] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224 USA.
[Genedani, S.; Agnati, L. F.] IRCCS San Camillo Lido, Venice, Italy.
[Genedani, S.; Agnati, L. F.] Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy.
RP Fuxe, K (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
EM Kjell.Fuxe@neuro.ki.se
RI Rivera, Alicia/L-2098-2014; Ferraro, Luca/F-9915-2015; Tanganelli,
Sergio/I-7704-2015; Genedani, Susanna/K-4370-2016;
OI Rivera, Alicia/0000-0002-7282-0441; Ferraro, Luca/0000-0003-2390-6414;
Tanganelli, Sergio/0000-0001-7576-3510; Genedani,
Susanna/0000-0003-1526-153X; Diaz-Cabiale, Zaida/0000-0002-1582-2088; de
la Calle Martin, Adelaida/0000-0002-3089-0329; Marcellino,
Daniel/0000-0002-4618-7267; Fuxe, Kjell/0000-0001-8491-4288; Narvaez,
Jose A./0000-0002-3575-6903; Roberts, David/0000-0001-7040-0155; Diaz
Cabiale, Maria Zaida/0000-0003-4613-9430
FU Swedish Research Council [K2006-04X-00715]; Marianne and Marcus and Knut
and Alice Wallenberg Foundations; European Commission
[QLG3-CT-2001-01056]
FX This work has been supported by grants from the Swedish Research Council
(K2006-04X-00715), the Marianne and Marcus and Knut and Alice Wallenberg
Foundations and also by a grant from the European Commission
(QLG3-CT-2001-01056).
NR 283
TC 114
Z9 118
U1 1
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0173
EI 1872-6321
J9 BRAIN RES REV
JI Brain Res. Rev.
PD AUG
PY 2008
VL 58
IS 2
BP 415
EP 452
DI 10.1016/j.brainresrev.2007.11.007
PG 38
WC Neurosciences
SC Neurosciences & Neurology
GA 356IJ
UT WOS:000259771600016
PM 18222544
ER
PT J
AU Agnati, LF
Leo, G
Genedani, S
Andreoli, N
Marcellino, D
Woods, A
Piron, L
Guidolin, D
Fuxe, K
AF Agnati, L. F.
Leo, G.
Genedani, S.
Andreoli, N.
Marcellino, D.
Woods, A.
Piron, L.
Guidolin, D.
Fuxe, K.
TI Structural plasticity in G-protein coupled receptors as demonstrated by
the allosteric actions of homocysteine and computer-assisted analysis of
disordered domains
SO BRAIN RESEARCH REVIEWS
LA English
DT Review
DE homocysteine; D2 receptors; intrinsically disordered proteins; receptor
mosaics; Parkinson's disease
ID ADENOSINE A(2A) RECEPTORS; CENTRAL NERVOUS-SYSTEM; INTRINSIC DISORDER;
DOPAMINE-D-2 RECEPTORS; PARKINSONS-DISEASE; OLIGOMERIZATION; MODULATION;
PREDICTION; MECHANISMS; PROTEOMICS
AB Structural plasticity of G-protein coupled receptors (GPCRs) is of basic importance for their interactions with ligands, in particular with other proteins such as receptors or receptor-modifying proteins that can lead to different functions for the same GPCR. In the present paper, structural plasticity of GPCRs has been investigated discussing allosteric modulatory actions of Homocysteine (Hcy) on D2 receptors together with data obtained by computer-assisted analysis of the presence of disordered domains in GPCRs. Previous evidence for a modulatory action of Hcy on D2 receptors has been further extended by means of experiments on the effects of Hcy local intrastriatal injection on rotational behaviour. Altogether the present data allow considering under a new angle the well known proposal of A2A antagonists as new therapeutic agents in Parkinson's disease (PD). Furthermore, they point out to not only the importance of drugs capable of reducing Hcy brain levels, but also to the potential therapeutic impact of drugs capable of regionally blocking (for PD) or enhancing (for some schizophrenic syndromes) Hcy allosteric action on D2 receptors.
As far as the investigations on GPCR plastic domains, extracellular, intracellular and transmembrane domains of 14 GPCRs have been considered and propensity of each of these domains for a structured or unstructured conformation has been evaluated by means of ad hoc computer programs. It has been shown that the N- and C-terminals as well as intracellular loop 3 have a high propensity towards an unstructured conformation, hence they are potentially very plastic domains, which can undergo easily to interactions with other ligands, particularly with other protein domains. This aspect is obviously of the greatest importance not only for the function of single GPCRs, but also for their interactions either with other receptors (receptor-receptor interactions) or, more generally, for formation of clusters of membrane associated proteins, hence of "protein mosaics", where the GPCRs could represent the input unit of the supra-molecular device. (C) 2007 Elsevier B.V. All rights reserved.
C1 [Agnati, L. F.; Leo, G.; Andreoli, N.] Univ Modena, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy.
[Genedani, S.] Univ Modena, Dept Biomed Sci, Pharmacol Sect, I-41100 Modena, Italy.
[Marcellino, D.; Fuxe, K.] Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, S-17177 Stockholm, Sweden.
[Woods, A.] Natl Inst Drug Abuse, Behav Neurosci Branch, NIH, DHHS, Baltimore, MD 20817 USA.
[Agnati, L. F.; Piron, L.] Osped San Camillo, IRCCS, Venice, Italy.
[Guidolin, D.] Univ Padua, Dept Anat & Physiol, Padua, Italy.
RP Agnati, LF (reprint author), Univ Modena, Dept Biomed Sci, Physiol Sect, Via Campi 287, I-41100 Modena, Italy.
EM luigiagnati@tin.it
RI Genedani, Susanna/K-4370-2016;
OI Genedani, Susanna/0000-0003-1526-153X; Marcellino,
Daniel/0000-0002-4618-7267; Fuxe, Kjell/0000-0001-8491-4288; Guidolin,
Diego/0000-0003-2133-3552
FU IRCCS; PRIN; Knut and Alice Wallenberg Foundation; Swedish Research
Council
FX Dr. Diego Guidolin has carried out the entire computer-assisted analysis
of disordered sequences in GPCRs and greatly contributed to the
theoretical frame of the paper.; The work has been supported by an IRCCS
grant and by a PRIN grant and by a grant from the Knut and Alice
Wallenberg Foundation and the Swedish Research Council.
NR 60
TC 26
Z9 26
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0173
J9 BRAIN RES REV
JI Brain Res. Rev.
PD AUG
PY 2008
VL 58
IS 2
BP 459
EP 474
DI 10.1016/j.brainresrev.2007.10.003
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 356IJ
UT WOS:000259771600018
PM 18022243
ER
PT J
AU Franco, R
Casado, V
Cortes, A
Perez-Capote, K
Mallol, J
Canela, E
Ferre, S
Lluis, C
AF Franco, Rafael
Casado, Vicent
Cortes, Antonio
Perez-Capote, Kamil
Mallol, Josefa
Canela, Enric
Ferre, Sergi
Lluis, Carme
TI Novel pharmacological targets based on receptor heteromers
SO BRAIN RESEARCH REVIEWS
LA English
DT Review
DE adenosine; cannabinoid; dopamine; opioid; fitting data; receptor dimer;
receptor oligomer; allosteric regulation; cooperativity; drug target
ID PROTEIN-COUPLED RECEPTORS; BIOLUMINESCENCE ENERGY-TRANSFER; ADENOSINE
A(2A) RECEPTORS; ALLOSTERIC MODULATION; QUANTITATIVE ASSESSMENT;
DOPAMINE-D-2 RECEPTORS; OPIOID RECEPTORS; AGONIST BINDING;
HETERODIMERIZATION; DIMERIZATION
AB Studies performed in the last 10 years have provided solid evidence indicating that G-protein-coupled receptors are expressed on the plasma membrane as homo and heterodimers. The first consequence of this fact is that homo and heterodimers are the true targets of natural (hormones, neurotransmitters) and synthetic drugs. Furthermore a given receptor in a heteromer may display a different functional and/or pharmacological profile than the same receptor characterized as monomer or as homodimer. Recent evidence indicates that receptor heteromers are sensors that lead to a fine-tuning in neurotransmission or hormone regulation; mainly this is achieved by a modification of the signaling pathways activated via a given receptor when it is forming a given heteromer. Quite often antagonists display variable affinities when a given receptor is expressed with different heteromeric partners. This fact should be taken into account in the development of new drugs. Finally it should be pointed out that radioligand binding data has to be analyzed by a model that considers receptors as dimers and not as monomers. This model provides a novel approach to characterize drugs interacting with the orthosteric center (agonists/antagonists) or with allosteric centers (allosteric regulators). (C) 2008 Elsevier B.V. All rights reserved.
C1 [Franco, Rafael; Casado, Vicent; Cortes, Antonio; Perez-Capote, Kamil; Mallol, Josefa; Canela, Enric; Lluis, Carme] Univ Barcelona, Dept Bioquim & Biol Mol, Inst Invest Biomed Ausgust Pi & Sunyer IDIBAPS, E-08028 Barcelona, Catalonia, Spain.
[Franco, Rafael; Casado, Vicent; Cortes, Antonio; Perez-Capote, Kamil; Mallol, Josefa; Canela, Enric; Lluis, Carme] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08028 Barcelona, Spain.
[Ferre, Sergi] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224 USA.
RP Franco, R (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Inst Invest Biomed Ausgust Pi & Sunyer IDIBAPS, Av Diagonal 645, E-08028 Barcelona, Catalonia, Spain.
EM rfranco@ub.edu
RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco,
Rafael/C-3694-2015; Casado, Vicent/K-1660-2014;
OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779;
Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825
FU Spanish Ministerio de Ciencia y Tecnologia [SAF2006-00170,
SAF2005-00170]; Fundacio La Marato de TV3 [060110]; Intramural Funds of
the NIDA, NIH
FX This research was supported by grants SAF2006-00170 SAF2005-00170 from
the Spanish Ministerio de Ciencia y Tecnologia, grant 060110 from
Fundacio La Marato de TV3 and from Intramural Funds of the NIDA, NIH.
NR 55
TC 15
Z9 15
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0173
J9 BRAIN RES REV
JI Brain Res. Rev.
PD AUG
PY 2008
VL 58
IS 2
BP 475
EP 482
DI 10.1016/j.brainresrev.2008.06.002
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 356IJ
UT WOS:000259771600019
PM 18620000
ER
PT J
AU Kim, KB
Eton, O
Davis, DW
Frazier, ML
McConkey, DJ
Diwan, AH
Papadopoulos, NE
Bedikian, AY
Camacho, LH
Ross, MI
Cormier, JN
Gershenwald, JE
Lee, JE
Mansfield, PF
Billings, LA
Ng, CS
Charnsangavej, C
Bar-Eli, M
Johnson, MM
Murgo, AJ
Prieto, VG
AF Kim, K. B.
Eton, O.
Davis, D. W.
Frazier, M. L.
McConkey, D. J.
Diwan, A. H.
Papadopoulos, N. E.
Bedikian, A. Y.
Camacho, L. H.
Ross, M. I.
Cormier, J. N.
Gershenwald, J. E.
Lee, J. E.
Mansfield, P. F.
Billings, L. A.
Ng, C. S.
Charnsangavej, C.
Bar-Eli, M.
Johnson, M. M.
Murgo, A. J.
Prieto, V. G.
TI Phase II trial of imatinib mesylate in patients with metastatic melanoma
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE phase II; imatinib; metastatic melanoma; protein tyrosine kinases;
antiangiogenesis
ID GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR;
GROWTH-FACTOR; CLINICAL-EFFICACY; IN-VIVO; C-KIT; RECEPTOR; EXPRESSION;
ST1571; MUTATIONS
AB Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK ( c-kit,platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.
C1 [Kim, K. B.; Eton, O.; Papadopoulos, N. E.; Bedikian, A. Y.; Camacho, L. H.; Billings, L. A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 430, Houston, TX 77030 USA.
[Davis, D. W.] ApoCell Inc, Houston, TX USA.
[Frazier, M. L.; Diwan, A. H.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[McConkey, D. J.; Bar-Eli, M.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Ross, M. I.; Cormier, J. N.; Gershenwald, J. E.; Lee, J. E.; Mansfield, P. F.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Ng, C. S.; Charnsangavej, C.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA.
[Johnson, M. M.] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA.
[Murgo, A. J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Eton, O (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 430, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM Omar.Eton@mpi.com
OI Eton, Omar/0000-0002-9141-553X
FU National Cancer Institute [N01 CM-17003, CA16672]; Core Grant [CA16672]
FX This study was supported by National Cancer Institute Grants N01
CM-17003 and CA16672, and Core Grant no. CA16672.
NR 24
TC 108
Z9 114
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG
PY 2008
VL 99
IS 5
BP 734
EP 740
DI 10.1038/sj.bjc.6604482
PG 7
WC Oncology
SC Oncology
GA 341NB
UT WOS:000258720100010
PM 18728664
ER
PT J
AU Cantwell, MM
Forman, MR
Middleton, RJ
Murray, LJ
AF Cantwell, M. M.
Forman, M. R.
Middleton, R. J.
Murray, L. J.
TI Association of early life factors and brain tumour risk in a cohort
study
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE brain tumour; childhood; early life factors
ID CENTRAL-NERVOUS-SYSTEM; BIRTH CHARACTERISTICS; CHILDHOOD; EPIDEMIOLOGY;
CHILDREN
AB Using population-based linked birth and cancer registry data, we investigated whether the risk of brain tumour in childhood (n = 155) was associated with perinatal risk factors. This population-based cohort showed that being born into a larger family or to a mother with a history of miscarriage may increase childhood brain tumour risk.
C1 [Cantwell, M. M.; Murray, L. J.] Queens Univ Belfast, Ctr Clin & Populat Sci, Royal Grp Hosp, Belfast BT12 6BJ, Antrim, North Ireland.
[Cantwell, M. M.] NCI, Canc Prevent Fellowship Program, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Forman, M. R.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Middleton, R. J.] Queens Univ Belfast, No Ireland Canc Registry, Ctr Clin & Populat Sci, Belfast BT12 6BJ, Antrim, North Ireland.
RP Cantwell, MM (reprint author), Queens Univ Belfast, Ctr Clin & Populat Sci, Royal Grp Hosp, Mulhouse Bldg,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM m.cantwell@qub.ac.uk
NR 11
TC 6
Z9 6
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG
PY 2008
VL 99
IS 5
BP 796
EP 799
DI 10.1038/sj.bjc.6604615
PG 4
WC Oncology
SC Oncology
GA 341NB
UT WOS:000258720100018
PM 18728669
ER
PT J
AU Hsing, AW
Sakoda, LC
Rashid, A
Chen, J
Shen, MC
Han, TQ
Wang, BS
Gao, YT
AF Hsing, A. W.
Sakoda, L. C.
Rashid, A.
Chen, J.
Shen, M. C.
Han, T. Q.
Wang, B. S.
Gao, Y. T.
TI Body size and the risk of biliary tract cancer: a population-based study
in China
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE biliary tract cancer; gallstones; obesity; body mass index; waist-to-hip
ratio; China
ID GALLBLADDER CANCER; PHYSICAL-ACTIVITY; MASS INDEX; OBESITY; GALLSTONES;
SHANGHAI; WEIGHT; STONES; WOMEN; MEN
AB Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case-control study of biliary tract cancer in Shanghai, China, odds ratios ( ORs) and 95% confidence intervals ( CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index ( BMI) at various ages and waist-to-hip ratio ( WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer ( 368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood ( ages 20-29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (>= 25.0) was associated with a 1.6-fold risk of gall bladder cancer ( 95% CI 1.2-2.1, P for trend <0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI ( >= 25) and a high WHR ( >0.90) having the highest risk of gall bladder cancer ( OR = 12.6, 95% CI 4.8-33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai.
C1 [Hsing, A. W.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Sakoda, L. C.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rashid, A.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Chen, J.] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Shen, M. C.] Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China.
[Han, T. Q.] Ruijin Hosp, Dept Surg, Shanghai, Peoples R China.
[Wang, B. S.] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China.
[Gao, Y. T.] Shanghai Canc Inst, Shanghai, Peoples R China.
RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Natl Inst Hlth, 6120 Execut Blvd,EPS 5024, Bethesda, MD 20892 USA.
EM hsinga@mail.nih.gov
FU Shelley Niwa of Westat Inc; NCI, NIH; National Cancer Institute,
National Institutes of Health [N01-CO-12400]
FX We thank the collaborating surgeons and pathologists in Shanghai for
assistance in patient recruitment and pathology review; Jiarong Chen and
Lu Sun of the National Shanghai Institute for coordinating data
collection; and Shelley Niwa of Westat Inc. for support with study and
data management. This research was supported by the Intramural Research
Program of the NCI, NIH. This project has been funded in whole or in
part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract N01-CO-12400. 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 24
TC 26
Z9 27
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG
PY 2008
VL 99
IS 5
BP 811
EP 815
DI 10.1038/sj.bjc.6604616
PG 5
WC Oncology
SC Oncology
GA 341NB
UT WOS:000258720100021
PM 18728671
ER
PT J
AU Jensen, BM
Akin, C
Gilfillan, AM
AF Jensen, B. M.
Akin, C.
Gilfillan, A. M.
TI Pharmacological targeting of the KIT growth factor receptor: a
therapeutic consideration for mast cell disorders
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE mast cells; KIT; mastocytosis; anaphylaxis; allergy; tyrosine kinase
inhibitors
ID TYROSINE KINASE INHIBITOR; PROTOONCOGENE C-KIT; CONSTITUTIVELY
ACTIVATING MUTATIONS; AGGRESSIVE SYSTEMIC MASTOCYTOSIS; ELEVATED SERUM
TRYPTASE; BEARING WILD-TYPE; PHASE-II TRIAL; STEM-CELL; IMATINIB
MESYLATE; HEMATOPOIETIC-CELLS
AB KIT is a member of the tyrosine kinase family of growth factor receptors which is expressed on a variety of haematopoietic cells including mast cells. Stem cell factor (SCF)-dependent activation of KIT is critical for mast cell homeostasis and function. However, when KIT is inappropriately activated, accumulation of mast cells in tissues results in mastocytosis. Such dysregulated KIT activation is a manifestation of specific activating point mutations within KIT, with the human D816V mutation considered as a hallmark of human systemic mastocytosis. A number of other activating mutations in KIT have recently been identified and these mutations may also contribute to aberrant mast cell growth. In addition to its role in mast cell growth, differentiation and survival, localized concentration gradients of SCF may control the targeting of mast cells to specific tissues and, once resident within these tissues, mast cell activation by antigen may also be amplified by SCF. Thus, KIT inhibitors may have potential application in multiple conditions linked to mast cells including systemic mastocytosis, anaphylaxis, and asthma. In this review, we discuss the role of KIT in the context of mast cells in these disease states and how recent advances in the development of inhibitors of KIT activity and function may offer novel therapies for the treatment of these disorders.
C1 [Gilfillan, A. M.] NIAID, LAD, NIH, Bethesda, MD 20892 USA.
[Jensen, B. M.] Natl Univ Hosp, RefLab, Copenhagen, Denmark.
[Akin, C.] Univ Michigan, Dept Internal Med, Div Allergy & Immunol, Ann Arbor, MI 48109 USA.
RP Gilfillan, AM (reprint author), NIAID, LAD, NIH, Bldg 10,Room 11C206, Bethesda, MD 20892 USA.
EM agilfillan@niaid.nih.gov
OI Akin, Cem/0000-0001-6301-4520
FU Intramural NIH HHS
NR 130
TC 41
Z9 42
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD AUG
PY 2008
VL 154
IS 8
BP 1572
EP 1582
DI 10.1038/bjp.2008.204
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 336JA
UT WOS:000258358900003
PM 18500355
ER
PT J
AU Tilburt, JC
Kaptchuk, TJ
AF Tilburt, Jon C.
Kaptchuk, Ted J.
TI Herbal medicine research and global health: an ethical analysis
SO BULLETIN OF THE WORLD HEALTH ORGANIZATION
LA English
DT Article
ID TRADITIONAL CHINESE MEDICINE; CONTROLLED-TRIAL
AB Governments, international agencies and corporations are increasingly investing in traditional herbal medicine research. Yet little literature addresses ethical challenges in this research. In this paper, we apply concepts in a comprehensive ethical framework for clinical research to international traditional herbal medicine research. We examine in detail three key, underappreciated dimensions of the ethical framework in which particularly difficult questions arise for international herbal medicine research: social value, scientific validity and favourable risk-benefit ratio, Significant challenges exist in determining shared concepts of social value, scientific validity and favourable risk-benefit ratio across international research collaborations. However, we argue that collaborative partnership, including democratic deliberation, offers the context and process by which many of the ethical challenges in international herbal medicine research can, and should be, resolved. By "cross-training" investigators, and investing in safety-monitoring infrastructure, the issues identified by this comprehensive framework can promote ethically sound international herbal medicine research that contributes to global health.
C1 [Tilburt, Jon C.] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA.
[Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Inst, Boston, MA USA.
RP Tilburt, JC (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM jontilburt@yahoo.com
NR 35
TC 34
Z9 35
U1 0
U2 4
PU WORLD HEALTH ORGANIZATION
PI GENEVA 27
PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND
SN 0042-9686
J9 B WORLD HEALTH ORGAN
JI Bull. World Health Organ.
PD AUG
PY 2008
VL 86
IS 8
BP 594
EP 599
DI 10.2471/BLT.07.042820
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 334YN
UT WOS:000258257800010
PM 18797616
ER
PT J
AU Kump, LI
Moeller, KL
Reed, GF
Kurup, SK
Nussenblatt, RB
Levy-Clarke, GA
AF Kump, Leila I.
Moeller, Kristy L.
Reed, George F.
Kurup, Shree K.
Nussenblatt, Robert B.
Levy-Clarke, Grace A.
TI Behcet's disease: comparing 3 decades of treatment response at the
National Eye Institute
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article; Proceedings Paper
CT World Ophthalmology Congress
CY FEB 19-24, 2006
CL Sao Paulo, BRAZIL
DE Behcet's disease; ocular inflammation; uveitis; autoimmune diesease
ID VISUAL PROGNOSIS; INVOLVEMENT; MANIFESTATIONS
AB Background: The goal of the present study was to analyze differences in response to the treatment of ocular Behcet's disease (BD) in the 1960s, 1980s, and 1990s.
Methods: Medical records of 120 patients with uveitis due to BD followed at the National Eye Institute, National Institutes of Health, from 1962 to 2004, were reviewed.
Results: The patients were categorized into 3 groups according to the time of follow-up: the first group was followed from 1962 until 1972, the second group from 1983 until 1992, and the third group from 1992 through 2004. Snellen visual acuity was converted to logMAR values. The range of values for inflammation was 0.5 (trace), I (mild), 2 (moderate), and 3 (severe). There were 45 patients (89 affected eyes) in the 1960s group, 26 patients (52 eyes) in the 1980s group, and 49 patients (94 eyes) in the most recent group. Statistical analysis showed that the mean logMAR score decreased with each decade. Mean visual acuity in the 1990s group was significantly better than in the previous decades (p < 0.001 for the 1960s group and p = 0.019 for the 1980s). The mean inflammation score was significantly higher in the 1960s than in the subsequent decades (p < 0.001 both for the 1980s and for the 1990s).
C1 [Kump, Leila I.; Moeller, Kristy L.; Reed, George F.; Kurup, Shree K.; Nussenblatt, Robert B.; Levy-Clarke, Grace A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Levy-Clarke, GA (reprint author), NEI, NIH, Bldg 10,Room 10S220B,10 Ctr Dr, Bethesda, MD 20892 USA.
EM clarkeg@nei.nih.gov
FU Intramural NIH HHS [Z01 EY000356-07]
NR 22
TC 16
Z9 16
U1 0
U2 1
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD AUG
PY 2008
VL 43
IS 4
BP 468
EP 472
DI 10.3129/i08-080
PG 5
WC Ophthalmology
SC Ophthalmology
GA 343LB
UT WOS:000258854000014
PM 18711463
ER
PT J
AU Rouhani, P
Fletcher, CDM
Devesa, SS
Toro, JR
AF Rouhani, Panta
Fletcher, Christopher D. M.
Devesa, Susan S.
Toro, Jorge R.
TI Cutaneous soft tissue sarcoma incidence patterns in the US - An analysis
of 12,114 cases
SO CANCER
LA English
DT Article
DE cutaneous soft tissue sarcoma; angiosarcoma; dermatofibrosarcoma
protuberans; Kaposi sarcoma; leiomyosarcoma; malignant fibrous
histiocytoma
ID MALIGNANT FIBROUS HISTIOCYTOMA; BREAST-CONSERVING SURGERY; 20-YEAR
FOLLOW-UP; DERMATOFIBROSARCOMA PROTUBERANS; KAPOSIS-SARCOMA;
UNITED-STATES; ATYPICAL FIBROXANTHOMA; ANGIOSARCOMA; CANCER;
EPIDEMIOLOGY
AB BACKGROUND. Cutaneous soft tissue sarcomas (CSTS) are a heterogeneous group of mesenchymal neoplasms. To the authors' knowledge, no prior large, population-based study has focused on CSTS.
METHODS. Surveillance, Epidemiology, and End Results (SEER) Program incidence and relative survival rates of CSTS were analyzed according to race, sex, and histologic type using the 2002 criteria of the World Health Organization classification.
RESULTS. Among residents of the 13 SEER registries, 12,114 CSTS were diagnosed from 1992 through 2004. Overall age-adjusted CSTS incidence rates were highest among blacks (30.8 per 1,000,000 person-years) followed by whites (25 per 1,000,000 person-years), and American Indians/Alaska Natives (11.2 per 1,000,000 person-years) and were lowest among Asian/Pacific Islanders (7.7 per 1,000,000 person-years). Kaposi sarcoma (KS) accounted for 71.1% of cases, and the rates were similarly ranked. Dermatofibrosarcoma protuberans (DFSP) rates also were highest among blacks, whereas leiomyosarcoma (LS) and angiosarcoma (AS) rates were highest among whites. The rate ratio of men to women was 25.5 for KS, 4.7 for malignant fibrous histiocytoma (MFH), 3.7 for LS, 2.0 for AS, and 0.9 for DFSR The 5-year relative survival rates were 99% for patients with DFSP, 89% for patients with MFH, 92% for patients with LS, and 45% for patients with AS. KS rates among men in the original 9 SEER registries increased more than 30-fold during the 1980s before they peaked around 1991 and subsequently declined rapidly because of human immunodeficiency virus-associated KS and highly active antiretroviral therapy. This KS pattern was evident not only among those ages 20 to 59 years but also among those ages 60 to 69 years. From 1978 through 2004, LS and AS rates among whites increased exponentially.
CONCLUSIONS. CSTS rates varied markedly over time and by race, sex, and histologic type, supporting the notion that these histologic variants of CSTS are etiologically distinct.
C1 [Rouhani, Panta; Toro, Jorge R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Room 7012, Bethesda, MD 20892 USA.
EM toroj@mail.nih.gov
OI Rouhani Schaffer, Panta/0000-0002-8282-3240
NR 60
TC 80
Z9 82
U1 0
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD AUG 1
PY 2008
VL 113
IS 3
BP 616
EP 627
DI 10.1002/cncr.23571
PG 12
WC Oncology
SC Oncology
GA 328VG
UT WOS:000257825700022
PM 18618615
ER
PT J
AU Miles, RJ
Price, DK
Figg, WD
AF Miles, Robert J.
Price, Douglas K.
Figg, William D.
TI Temporal-mediated FGFR1 independence - Implications for targeting
candidate molecules in prostate cancer
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE FGFR1; chemical inducer of dimerization; JOCK-1; adenocarcinoma;
temporal; therapeutic targeting; prostate cancer
ID ACTIVATION
C1 [Miles, Robert J.; Price, Douglas K.; Figg, William D.] NCI, Canc Res Ctr, Med Oncol Branch, Mol Pharmacol Sect,NIH, Bethesda, MD 20892 USA.
RP Miles, RJ (reprint author), NCI, Canc Res Ctr, Med Oncol Branch, Mol Pharmacol Sect,NIH, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC 1910, Bethesda, MD 20892 USA.
EM rjosephmiles@hotmail.com
RI Figg Sr, William/M-2411-2016
NR 5
TC 0
Z9 0
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD AUG
PY 2008
VL 7
IS 8
BP 1180
EP 1181
PG 2
WC Oncology
SC Oncology
GA 342HI
UT WOS:000258774800004
PM 18719360
ER
PT J
AU Kelly, MP
Lee, FT
Tahtis, K
Power, BE
Smyth, FE
Brechbiel, MW
Hudson, PJ
Scott, AM
AF Kelly, Marcus P.
Lee, F. -T.
Tahtis, Kiki
Power, Barbara E.
Smyth, Fiona E.
Brechbiel, Martin W.
Hudson, Peter J.
Scott, Andrew M.
TI Tumor targeting by a multivalent single-chain Fv (scFv) anti-Lewis Y
antibody construct
SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
LA English
DT Article
DE scFv multimeric construct; hu3S193; biodistribution; Lewis Y antigen
ID HUMAN COLON-CARCINOMA; MONOCLONAL-ANTIBODIES; ENGINEERED ANTIBODIES;
F(AB)(2) FRAGMENTS; VARIABLE DOMAINS; BIODISTRIBUTION; PHARMACOKINETICS;
DIABODY; DESIGN; MODEL
AB The use of single-chain variable fragment (scFv) constructs has been investigated in cancer radioimmunotherapy (RIT) and radioimmunodetection, as these molecules permit rapid tumor penetration and clearance from the serum relative to whole IgG. Multimerization of scFv constructs has demonstrated improvements in functional affinity (i.e., avidity) and maximal tumor uptake. In this paper, we report the first biodistribution and pharmacokinetics studies of a noncovalent, direct-linked scFv (V-L-0-V-H) trimeric/tetrameric "multimer" of the anti-Lewis Y monoclonal antibody, hu3S193. The in vitro binding and in vivo biodistribution of the hu3S193 multimer was characterized alongside the hu3S193 F(ab')(2) following radiolabeling with the Indium-111 (In-111) radioisotope. lmmunoreactivities of the radiolabeled multimer and F(ab')(2) were 73% and 53.2%, and binding affinities (K-a) were 1.58 x 10(7) M-1 and 4.31 x 10(6) M-1 for the multimer and F(ab')(2), respectively. Maximal tumor uptake in Le(y)-positive MCF-7 breast cancer xenografted BALB/c nude mice was 12.6 +/- 2.5 percent injected dose/per grain (%ID/g) at 6 hours postinjection for the multimer and 15.7 +/- 2.1 %ID/g at 24 hours postinjection for the F(ab')(2). However, limited in vitro stability and high renal localization of radiolabeled constructs were observed, which, despite the observed tumor targeting of the hu3S193 multimer, most likely preclude its use in RIT and imaging modalities.
C1 [Scott, Andrew M.] Austin Hosp, Melbourne Ctr Clin Sci, Ludwig Inst Canc Res, Tumour Targeting Program, Heidelberg, Vic 3084, Australia.
[Power, Barbara E.; Hudson, Peter J.] CSIRO Mol & Hlth Technol, Parkville, Vic, Australia.
[Brechbiel, Martin W.] Natl Canc Inst, NIH, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD USA.
RP Scott, AM (reprint author), Austin Hosp, Melbourne Ctr Clin Sci, Ludwig Inst Canc Res, Tumour Targeting Program, 145-163 Studley Rd, Heidelberg, Vic 3084, Australia.
EM andrew.scott@ludwig.edu.au
OI Power, Barbara/0000-0002-4182-3375
FU NHMRC Program [290816]; NIH; National Cancer Institute; Center for
Cancer Research; Melbourne Research Scholarship, University of Melbourne
(Melbourne, Australia)
FX The authors wish to thank Usha Krishnan for protein purification of the
hu3S193 multimer and also Angela Rigopoulos, Dongmao Wang, and Sanja
Coso for their assistance in the biodistribution study, Anthony
Papenfuss for pharmacokinetic calculations, and the staff from the
Department of Nuclear Medicine, Austin Hospital, for their assistance in
the gamma-camera imaging of the animals. This research was funded by the
NH&MRC Program Grant 290816 and, in part, by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research. MPK was supported by a Melbourne Research Scholarship,
University of Melbourne (Melbourne, Australia).
NR 49
TC 17
Z9 18
U1 2
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1084-9785
EI 1557-8852
J9 CANCER BIOTHER RADIO
JI Cancer Biother. Radiopharm.
PD AUG
PY 2008
VL 23
IS 4
BP 411
EP 423
DI 10.1089/cbr.2007.0450
PG 13
WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
GA 347US
UT WOS:000259167300003
PM 18771345
ER
PT J
AU Lee, FT
Yuen, A
Osborn, A
Wang, D
Rigopoulos, A
Smyth, FE
Brechbiel, MW
Scott, AM
AF Lee, Fook T.
Yuen, A.
Osborn, A.
Wang, D.
Rigopoulos, A.
Smyth, F. E.
Brechbiel, M. W.
Scott, A. M.
TI Combined modality Lu-177-CHX-A ''-DTPA huA33 radioimmunotherapy of
colorectal cancer xenografts
SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
LA English
DT Meeting Abstract
CT 12th Conference on Cancer Therapy with Antibodies and Immunoconjugates
CY OCT 16-18, 2008
CL Parsippany, NJ
C1 [Lee, Fook T.; Yuen, A.; Osborn, A.; Wang, D.; Rigopoulos, A.; Smyth, F. E.; Scott, A. M.] Ludwig Inst Canc Res, Tumour Targeting Program, Melbourne, Vic 3050, Australia.
[Brechbiel, M. W.] NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1084-9785
J9 CANCER BIOTHER RADIO
JI Cancer Biother. Radiopharm.
PD AUG
PY 2008
VL 23
IS 4
MA 16
BP 518
EP 518
PG 1
WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
GA 347US
UT WOS:000259167300028
ER
PT J
AU Meany, HJ
Fox, E
McCully, C
Tucker, C
Balis, FM
AF Meany, Holly J.
Fox, Elizabeth
McCully, Cynthia
Tucker, Chris
Balis, Frank M.
TI The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its
active metabolite (OSI-420) after intravenous administration of
erlotinib in non-human primates
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE erlotinib; pharmacokinetics; cerebrospinal fluid; non-human primate
ID GROWTH-FACTOR RECEPTOR; CELL-CYCLE ARREST; TYROSINE KINASE;
RHESUS-MONKEY; INHIBITOR; CANCER; PHARMACODYNAMICS; APOPTOSIS; OSI-774;
GLIOMA
AB Purpose Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model.
Methods Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma).
Results Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was < 5% relative to total plasma concentration, but CSF drug exposure was similar to 30% of plasma free drug exposure, which was calculated from published plasma protein binding values. The IV administration of erlotinib was well tolerated.
Conclusions Erlotinib and its active metabolite OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.
C1 [Meany, Holly J.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Fox, Elizabeth; McCully, Cynthia; Balis, Frank M.] Natl Canc Inst, Pediatr Oncol Branch, Bethesda, MD 20892 USA.
[Tucker, Chris] OSI Pharmaceut, Boulder, CO USA.
RP Meany, HJ (reprint author), Childrens Natl Med Ctr, Washington, DC 20010 USA.
EM hmeany@cnmc.org
NR 25
TC 16
Z9 16
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
EI 1432-0843
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD AUG
PY 2008
VL 62
IS 3
BP 387
EP 392
DI 10.1007/s00280-007-0616-3
PG 6
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 314PJ
UT WOS:000256821000003
PM 17932674
ER
PT J
AU Warren, KE
McCully, C
Dvinge, H
Tjornelund, J
Sehested, M
Lichenstein, HS
Balis, FM
AF Warren, Katherine E.
McCully, Cindy
Dvinge, Henrik
Tjornelund, Jette
Sehested, Maxwell
Lichenstein, Henri S.
Balis, Frank M.
TI Plasma and cerebrospinal fluid pharmacokinetics of the histone
deacetylase inhibitor, belinostat (PXD101), in non-human primates
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE cerebrospinal fluid; pharmacokinetics; histone deacetylase; PXD101;
belinostat
ID SUBEROYLANILIDE HYDROXAMIC ACID; DIFFERENTIATION; EXPRESSION; CANCER;
MODEL
AB Purpose Histone deacetylases (HDAC) are involved in the regulation of gene transcription. Aberrant HDAC activity has been associated with tumorigenesis, and, therefore, HDACs are potential targets for the treatment of cancers, including tumors of the central nervous system (CNS). Belinostat is a novel, potent, pan-HDAC inhibitor with antiproliferative activity on a wide variety of tumor cell lines. We studied the cerebrospinal fluid (CSF) penetration of intravenous (IV) belinostat in a non-human primate model as a surrogate for blood:brain barrier penetration.
Design Five adult rhesus monkeys received increasing doses of belinostat (10-60 mg/kg) as a 30-min IV infusion. Serial blood and CSF samples were collected over 48 h. Plasma and CSF concentrations of belinostat were quantified with an LC/MS/MS assay. Pharmacokinetic parameters were calculated using non-compartmental methods, and CSF penetration is expressed as the ratio of the area under the concentration-time curve (AUC) in CSF to the AUC in plasma.
Results Belinostat was cleared rapidly from plasma with a half-life of 1.0 h, a mean residence time of 0.47 h, and a clearance of 425 ml/min/m(2). CSF penetration of belinostat was limited. CSF drug exposure was < 1% of plasma drug exposure and < 10% of free (non-protein bound) plasma drug exposure.
Conclusion IV belinostat is rapidly cleared from plasma and has limited penetration into the CSF.
C1 [Warren, Katherine E.; McCully, Cindy; Balis, Frank M.] Natl Canc Inst, Bethesda, MD 20892 USA.
[Dvinge, Henrik; Tjornelund, Jette; Sehested, Maxwell] Topotarget A S, Copenhagen, Denmark.
[Lichenstein, Henri S.] Curagen Corp, Branford, CT USA.
RP Warren, KE (reprint author), Natl Canc Inst, Bldg 10 CRC,Rm 1-3930,10 Ctr Dr, Bethesda, MD 20892 USA.
EM warrenk@mail.nih.gov
NR 18
TC 13
Z9 13
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD AUG
PY 2008
VL 62
IS 3
BP 433
EP 437
DI 10.1007/s00280-007-0622-5
PG 5
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 314PJ
UT WOS:000256821000009
PM 17960383
ER
PT J
AU Beumer, JH
Eiseman, JL
Parise, RA
Florian, JA
Joseph, E
D'Argenio, DZ
Parker, RS
Kay, B
Covey, JM
Egorin, MJ
AF Beumer, Jan H.
Eiseman, Julie L.
Parise, Robert A.
Florian, Jeffry A., Jr.
Joseph, Erin
D'Argenio, David Z.
Parker, Robert S.
Kay, Brittany
Covey, Joseph M.
Egorin, Merrill J.
TI Plasma pharmacokinetics and oral bioavailability of
3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE tetrahydrouridine; bioavailability; dose-linearity; metabolism; mouse;
cytidine deaminase
ID CYTOSINE-ARABINOSIDE; TETRAHYDROURIDINE NSC-112907;
CLINICAL-PHARMACOLOGY; LEUKEMIC-CELLS;
1-BETA-D-ARABINOFURANOSYLCYTOSINE; METABOLISM; DISPOSITION; TUMORS; DNA;
5-AZA-2'-DEOXYCYTIDINE
AB Cytidine analogues such as cytosine arabinoside, gemcitabine, decitabine, 5-azacytidine, 5-fluoro-2'-deoxycytidine and 5-chloro-2'-deoxycytidine undergo rapid catabolism by cytidine deaminase (CD). 3,4,5,6-tetrahydrouridine (THU) is a potent CD inhibitor that has been applied preclinically and clinically as a modulator of cytidine analogue metabolism. However, THU pharmacokinetics has not been fully characterized, which has impaired the optimal preclinical evaluation and clinical use of THU. Therefore, we characterized the THU pharmacokinetics and bioavailability in mice. Mice were dosed with THU iv (100 mg/kg) or po (30, 100, or 300 mg/kg). Plasma and urine THU concentrations were quantitated with a validated LC-MS/MS assay. Plasma pharmacokinetic parameters were calculated compartmentally and non-compartmentally. THU, at 100 mg/kg iv had a 73 min terminal half-life and produced plasma THU concentrations > 1 mu g/ml, the concentration shown to effectively block deamination, for 4 h. Clearance was 9.1 ml/min/kg, and the distribution volume was 0.95 l/kg. Renal excretion accounted for 36-55% of the THU dose. A three-compartment model fit the iv THU data best. THU, at 100 mg/kg po, produced a concentration versus time profile with a plateau of approximately 10 mu g/ml from 0.5-3 h, followed by a decline with an 85 min half-life. The oral bioavailability of THU was approximately 20%. The 20% oral bioavailability of THU is sufficient to produce and sustain, for several hours, plasma concentrations that inhibit CD. This suggests the feasibility of using THU to decrease elimination and first-pass metabolism of cytidine analogues by CD. THU pharmacokinetics are now being evaluated in humans.
C1 [Beumer, Jan H.] Univ Pittsburgh, Inst Canc, Hillman Res Pavil, Pittsburgh, PA 15213 USA.
[Beumer, Jan H.; Eiseman, Julie L.; Parise, Robert A.; Joseph, Erin; Parker, Robert S.; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA.
[Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA.
[Eiseman, Julie L.; Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA.
[Florian, Jeffry A., Jr.; Parker, Robert S.] Univ Pittsburgh, Sch Engn, Dept Chem & Petr Engn, Pittsburgh, PA 15218 USA.
[D'Argenio, David Z.; Kay, Brittany] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Covey, Joseph M.] Natl Canc Inst, Div Canc Treatment & Diag, Dev Therapeut Program, Toxicol & Pharmacol Branch, Rockville, MD 20852 USA.
[Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Dept Med, Pittsburgh, PA 15213 USA.
RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Hillman Res Pavil, Room G27D,5117 Ctr Ave, Pittsburgh, PA 15213 USA.
EM beumerjh@upmc.edu
OI Beumer, Jan/0000-0002-8978-9401
FU NCI NIH HHS [N01 CM052202, P30 CA047904, P30 CA047904-21, N01CM52202];
NIBIB NIH HHS [P41 EB001978, P41 EB001978-24, P41 EB001978-245377, P41
EB001978-245383]
NR 44
TC 11
Z9 11
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD AUG
PY 2008
VL 62
IS 3
BP 457
EP 464
DI 10.1007/s00280-007-0625-2
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 314PJ
UT WOS:000256821000012
PM 18008070
ER
PT J
AU Adler, V
Bowne, W
Kamran, I
Michl, J
Friedman, FK
Chin, E
Zenilman, M
Pincus, MR
AF Adler, Victor
Bowne, Wilbur
Kamran, Ikram
Michl, Josef
Friedman, Fred K.
Chin, Edwin
Zenilman, Michael
Pincus, Matthew R.
TI Two peptides derived from ras-p21 induce either phenotypic reversion or
tumor cell necrosis of ras-transformed human cancer cells
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE ras-p21 protein; cell transformation; ras peptides; cancer cell lines;
phenotypic reversion; tumor cell necrosis
ID N-TERMINAL KINASE; DUAL-SPECIFICITY KINASES; ONCOGENIC RAS-P21; OOCYTE
MATURATION; CHEMOTHERAPEUTIC-AGENTS; XENOPUS-OOCYTES; JUN PROTEINS;
WILD-TYPE; ACTIVATION; JNK
AB Purpose We investigated the effects of two peptides from the ras-p21 protein, corresponding to residues 35-47 (PNC-7) and 96-110 (PNC-2), on two ras-transformed human cancer cell lines, HT1080 fibrosarcoma and MIAPaCa-2 pancreatic cancer cell lines. In prior studies, we found that both peptides block oncogenic, but not insulin-activated wild-type, ras-p21-induced oocyte maturation. When linked to a transporter penetratin peptide, these peptides induce reversion of ras-transformed rat pancreatic cancer cells (TUC-3) to the untransformed phenotype.
Methods These peptides and a control peptide, linked to a penetratin peptide, were incubated with each cell lines. Cell counts were obtained over several weeks. The cause of cell death was determined by measuring caspase as an indicator of apoptosis and lactate dehydrogenase (LDH) as marker of necrosis. Since both peptides block the phosphorylation of jun-N-terminal kinase (JNK) in oocytes, we blotted cell lysates of the two cancer cell lines for the levels of phosphorylated JNK to determine if the peptides reduced these levels.
Results We find that both peptides, but not control peptides linked to the penetratin sequence, induce phenotypic reversion of the HT-1080 cell line but cause tumor cell necrosis of the MIA-PaCa-2 cell line. On the other hand, neither peptide has any effect on the viability of an untransformed pancreatic acinar cell line, BMRPA1. We find that, while total JNK levels remain constant during peptide treatment, phosphorylated JNK levels decrease dramatically, consistent with the mechanisms of action of these peptides.
Conclusions We conclude that these peptides block tumor but not normal cell growth likely by blocking oncogenic ras-p21-induced phosphorylation of JNK, an essential step on the oncogenic ras-p21-protein pathway. These peptides are therefore promising as possible anti-tumor agents.
C1 [Adler, Victor; Chin, Edwin; Pincus, Matthew R.] New York Harbor VA Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA.
[Bowne, Wilbur; Kamran, Ikram; Zenilman, Michael] Suny Downstate Med Ctr, Dept Surg, Brooklyn, NY 11203 USA.
[Bowne, Wilbur] New York Harbor VA Med Ctr, Dept Surg, Brooklyn, NY 11209 USA.
[Michl, Josef; Pincus, Matthew R.] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA.
[Michl, Josef] Suny Downstate Med Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA.
[Michl, Josef] Suny Downstate Med Ctr, Dept Microbiol & Immunol, Brooklyn, NY 11203 USA.
[Friedman, Fred K.] Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Pincus, MR (reprint author), New York Harbor VA Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA.
EM matthew.pincus2@med.va.gov
RI Friedman, Fred/D-4208-2016
NR 24
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD AUG
PY 2008
VL 62
IS 3
BP 491
EP 498
DI 10.1007/s00280-007-0630-5
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 314PJ
UT WOS:000256821000016
PM 18066549
ER
PT J
AU Ostrander, EA
Udler, MS
AF Ostrander, Elaine A.
Udler, Miriam S.
TI The role of the BRCA2 gene in susceptibility to prostate cancer
revisited
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Review
ID WIDE LINKAGE SCAN; HIGH-RISK PEDIGREES; BREAST-CANCER; GERMLINE
MUTATIONS; OVARIAN-CANCER; INTERNATIONAL CONSORTIUM; BREAST/OVARIAN
CANCER; CHROMOSOME 22Q12.3; CARRIER FREQUENCY; COMMON MUTATIONS
AB Prostate cancer is a genetically complex disease with multiple predisposing factors affecting presentation, progression, and outcome. Epidemiologic studies have long shown an aggregation of breast and prostate cancer in some families. More recently, studies have reported an apparent excess of prostate cancer cases among BRCA2 mutation-carrying families. Additionally, population-based screens of early-onset prostate cancer patients have suggested that the prevalence of deleterious BRCA2 mutations in this group is 1% to 2%, imparting a significantly increased risk of the disease compared with noncarrier cases. However, studies of high-risk prostate cancer families suggest that BRCA2 plays at most a minimal role in these individuals, highlighting the potential genetic heterogeneity of the disease. In this commentary, we review the current literature and hypotheses surrounding the relationship between BRCA2 mutations and susceptibility to prostate cancer and speculate on the potential for involvement of additional genes.
C1 [Ostrander, Elaine A.; Udler, Miriam S.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Udler, Miriam S.] Univ Cambridge, CR UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Room 52451,Bldg 50, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Ostrander, Elaine/0000-0001-6075-9738
FU NIH Oxford/Cambridge Graduate Partnerships Program
FX We thank the many men and their families who have contributed so much to
the studies cited. M.S. Udler thanks Douglas Easton for his support and
the NIH Oxford/Cambridge Graduate Partnerships Program. We also thank
the Intramural Program of the National Human Genome Research Institute.
NR 83
TC 16
Z9 16
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 AUG
PY 2008
VL 17
IS 8
BP 1843
EP 1848
DI 10.1158/1055-9965.EPI-08-0556
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800001
PM 18708369
ER
PT J
AU Rabkin, CS
Janz, S
AF Rabkin, Charles S.
Janz, Siegfried
TI Mechanisms and consequences of chromosomal translocation
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Editorial Material
AB A 2006 National Cancer Institute workshop on chromosomal translocations brought together laboratory, clinical, and population scientists to cross-fertilize and catalyze research on this important disease process. The deliberations revealed significant contrasts between two types of translocations that result in either deregulated expression of oncogenes or formation of novel fusion genes. The classic oncogene-activating translocation, MYC-IGH, has been elucidated in terms of molecular structure and functional consequences yet has little epidemiologic characterization. In comparison, the archetypal fusion-gene translocation, BCR-ABL, has well-described clinical manifestations but is less defined with regard to mechanism of generation. Interdisciplinary collaboration on chromosomal translocations should yield additional insights regarding their biological significance and potential as targets for intervention.
C1 [Rabkin, Charles S.] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Janz, Siegfried] Univ Iowa, Dept Pathol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
RP Rabkin, CS (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-7082, Bethesda, MD 20892 USA.
EM rabkinc@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010142-09]
NR 1
TC 1
Z9 2
U1 1
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 AUG
PY 2008
VL 17
IS 8
BP 1849
EP 1851
DI 10.1158/1055-9965.EPI-07-2902
PG 3
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800002
PM 18708370
ER
PT J
AU Falk, RT
Gentzschein, E
Stanczyk, FZ
Brinton, LA
Garcia-Closas, M
Ioffe, OB
Sherman, ME
AF Falk, Roni T.
Gentzschein, Elisabet
Stanczyk, Frank Z.
Brinton, Louise A.
Garcia-Closas, Montserrat
Ioffe, Olga B.
Sherman, Mark E.
TI Measurement of sex steroid hormones in breast adipocytes: Methods and
implications
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CHAIN-REACTION AMPLIFICATION; MESSENGER-RIBONUCLEIC-ACID; AROMATASE
ACTIVITIES; ADIPOSE-TISSUE; ESTRONE SULFATE; CANCER; WOMEN; ESTROGENS;
ESTRADIOL; CELLS
AB Background: The lack of validated methods for measuring sex steroid hormones in breast tissue has limited our knowledge of their role in the development of breast cancer. We explored the feasibility of measuring hormones in breast adipocytes for epidemiologic and clinical studies by refining an existing assay procedure and assessing the reliability of hormone measurements using the modified assay. This report presents the reproducibility of measurements of androstenedione (A), testosterone (T), estrone (E-1), and estradiol (E-2), using breast adipose tissue samples obtained from women undergoing surgical resection for a variety of pathologic conditions.
Methods: Breast adipose tissues were obtained from 20 women. Measurements of the steroid hormones were carried out by harvesting oil from adipocytes following enzymatic digestion of the adipose tissue, extracting and chromatographing the steroids, and quantifying them by RIA. The study was conducted in three phases: first, samples from five women were used to assess the assay procedure; following this, tissues from an additional five women were assayed repeatedly to determine reproducibility of the hormone measurements. Finally, using samples from 10 women undergoing surgical resection of a breast tumor, we evaluated hormone concentrations in samples distal and proximal to the tumor. The assay coefficient of variation and intraclass correlation coefficient were used to assess hormone reproducibility.
Results: The within-batch coefficients of variation ranged from 5% to 17%, and between-batch estimates were between 2% and 10%, suggesting that E-1, E-2, A, and T can be reliably measured in breast adipocytes. Among samples obtained from women undergoing surgical resection of a breast tumor, hormone levels did not differ between adipose tissue fragments that were distal or proximal to the tumor, with the possible exception of E, in which levels were 10% higher in distal fragments.
Conclusion: These data support the feasibility of measuring steroid hormone concentrations in breast adipocytes in epidemiologic studies. Future investigations that include the measurement of hormones in the breast microenvironment may have value in understanding breast carcinogenesis, developing prevention strategies, and assessing hormonal treatments.
C1 [Falk, Roni T.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Bethesda, MD 20892 USA.
[Gentzschein, Elisabet; Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Gentzschein, Elisabet; Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Ioffe, Olga B.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
RP Falk, RT (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, 6120 Execut Blvd S,Suite 500, Bethesda, MD 20892 USA.
EM falkr@mail.nih.gov
RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562
FU Intramural NIH HHS [Z99 CA999999]
NR 27
TC 15
Z9 16
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2008
VL 17
IS 8
BP 1891
EP 1895
DI 10.1158/1055-9965.EPI-08-0119
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800009
PM 18708377
ER
PT J
AU Lee, YCA
Boffetta, P
SturgiS, EM
Wei, Q
Zhang, ZF
Muscat, J
Lazarus, P
Matos, E
Hayes, RB
Winn, DM
Zaridze, D
Wiinsch, V
Eluf-Neto, J
Koifman, S
Mates, D
Curado, MP
Menezes, A
Fernandez, L
Daudt, AW
Szeszenia-Dabrowska, N
Fabianova, E
Rudnai, P
Ferro, G
Berthiller, J
Brennan, P
Hashibe, M
AF Lee, Yuan-Chin Amy
Boffetta, Paolo
Sturgis, Erich M.
Wei, Qingyi
Zhang, Zuo-Feng
Muscat, Joshua
Lazarus, Philip
Matos, Elena
Hayes, Richard B.
Winn, Deborah M.
Zaridze, David
Wiinsch-Filho, Victor
Eluf-Neto, Jose
Koifman, Sergio
Mates, Dana
Curado, Maria Paula
Menezes, Ana
Fernandez, Leticia
Daudt, Alexander W.
Szeszenia-Dabrowska, Neonila
Fabianova, Eleonora
Rudnai, Peter
Ferro, Gilles
Berthiller, Julien
Brennan, Paul
Hashibe, Mia
TI Involuntary smoking and head and neck cancer risk: Pooled analysis in
the International Head and Neck Cancer Epidemiology Consortium
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ENVIRONMENTAL TOBACCO-SMOKE; SQUAMOUS-CELL CARCINOMA; LUNG-CANCER;
EXPOSURE; NITROSAMINES; HEALTH
AB Although active tobacco smoking has been identified as a major risk factor for head and neck cancer, involuntary smoking has not been adequately evaluated because of the relatively low statistical power in previous studies. We took advantage of data pooled in the International Head and Neck Cancer Epidemiology Consortium to evaluate the role of involuntary smoking in head and neck carcinogenesis. Involuntary smoking exposure data were pooled across six case-control studies in Central Europe, Latin America, and the United States. Adjusted odds ratios (OR) and 95% confidence interval (95% CI) were estimated for 542 cases and 2,197 controls who reported never using tobacco, and the heterogeneity among the study-specific ORs was assessed. In addition, stratified analyses were done by subsite. No effect of ever involuntary smoking exposure either at home or at work was observed for head and neck cancer overall. However, long duration of involuntary smoking exposure at home and at work was associated with an increased risk (OR for >15 years at home, 1.60; 95% CI, 1.12-2.28; P-trend <0-01; OR for >15 years at work, 1.55; 95% CI, 1.04-2.30; P-trend = 0.13). The effect of duration of involuntary smoking exposure at home was stronger for pharyngeal and laryngeal cancers than for other subsites. An association between involuntary smoking exposure and the risk of head and neck cancer, particularly pharyngeal and laryngeal cancers, was observed for long duration of exposure. These results are consistent with those for active smoking and suggest that elimination of involuntary smoking exposure might reduce head and neck cancer risk among never smokers.
C1 [Hashibe, Mia] IARC, Lifestyle Environm & Canc Grp, F-69008 Lyon, France.
[Sturgis, Erich M.; Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA USA.
[Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina.
[Hayes, Richard B.; Winn, Deborah M.] NCI, Bethesda, MD 20892 USA.
[Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia.
[Wiinsch-Filho, Victor; Eluf-Neto, Jose] Univ Sao Paulo, Sao Paulo, Brazil.
[Koifman, Sergio] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
[Curado, Maria Paula] Hosp Araujo Jorge, Goiania, Go, Brazil.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba.
[Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Lodz, Poland.
[Fabianova, Eleonora] Specialized State Hlth Inst, Banska Bystrica, Slovakia.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
RP Hashibe, M (reprint author), IARC, Lifestyle Environm & Canc Grp, 150 Cours Albert Thomas, F-69008 Lyon, France.
EM hashibe@iarc.fr
RI Zaridze, David/K-5605-2013; Epidemiologicas, Centro de pesquisas
/D-4561-2013; Menezes, Ana/G-7266-2012; Szeszenia-Dabrowska,
Neonila/F-7190-2010; Eluf-Neto, Jose/B-2522-2009; Curado, Maria
Paula/M-6200-2013;
OI Hayes, Richard/0000-0002-0918-661X; Eluf-Neto, Jose/0000-0001-7504-2115;
Curado, Maria Paula/0000-0001-8172-2483; mates, dana/0000-0002-6219-9807
FU NIH; National Cancer Institute [R03CA113157]; Central Europe study World
Cancer Research Fund and European Commission's I Program
[IC15-CT98-0332]; National Cancer Institute and National Institute of
Dental and Craniofacial Research intramural programs; Latin America
study : Fondo para la Investigacion Cientifi ca y Tecnologica
(Argentina); Institut Municipal d'Invesigacio Medica (Barcelona); Amparo
a Pesquisa no Estado de Sao Paulo [01/01768-2]; European Commission
[IC18-CT97-0222]; NIH [P01CA068384, K07CA104231, P50CA90388, R01DA11386,
R03CA77954, T32CA09142, U01CA96134, R21ES011667, R01ES11740,
R01CA100264]; Alper Research Program tor Environmental Genomics of the
University of California-Los Angeles Jonsson Comprehensive Cancer Center
FX IARC special training award tor a postdoctoral fellowship (Y-C.A. Lee);
NIH, National Cancer Institute grant R03CA113157. Central Europe study
World Cancer Research Fund and European Commission's I Program contract
IC15-CT98-0332; Puerto Rico study: National Cancer Institute and
National Institute of Dental and Craniofacial Research intramural
programs; Latin America study : Fondo para la Investigacion Cientifi ca
y Tecnologica (Argentina), Institut Municipal d'Invesigacio Medica
(Barcelona), fundacao de Amparo a Pesquisa no Estado de Sao Paulo grant
01/01768-2, and European Commission grant IC18-CT97-0222; Tampa study:
NIH grants P01CA068384 and K07CA104231; Los Angeles study: NIH grants
P50CA90388, R01DA11386, R03CA77954, T32CA09142, U01CA96134, and
R21ES011667 as well as the Alper Research Program tor Environmental
Genomics of the University of California-Los Angeles Jonsson
Comprehensive Cancer Center; and Houston study: NIH grants R01ES11740
and R01CA100264.
NR 26
TC 39
Z9 43
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2008
VL 17
IS 8
BP 1974
EP 1981
DI 10.1158/1055-9965.EPI-08-0047
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800020
PM 18708387
ER
PT J
AU Bhatti, P
Doody, MM
Alexander, BH
Yuenger, J
Simon, SL
Weinstock, RM
Rosenstein, M
Stovall, M
Abendfl, M
Preston, DL
Pharoah, P
Struewing, JP
Sigurdson, AJ
AF Bhatti, Parveen
Doody, Michele M.
Alexander, Bruce H.
Yuenger, Jeff
Simon, Steven L.
Weinstock, Robert M.
Rosenstein, Marvin
Stovall, Marilyn
Abendfl, Michael
Preston, Dale L.
Pharoah, Paul
Struewing, Jeffery P.
Sigurdson, Alice J.
TI Breast cancer risk polymorphisms and interaction with ionizing radiation
among US Radiologic Technologists
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID H19 GENE; EXPOSURE
AB Genome-wide association studies are discovering relationships between single-nucleotide polymorphisms and breast cancer, but the functions of these single-nucleotide polymorphisms are unknown and environmental exposures are likely to be important. We assessed whether breast cancer risk single-nucleotide polymorphisms interacted with ionizing radiation, a known breast carcinogen, among 859 cases and 1,083 controls nested in the U.S. Radiologic Technologists cohort. Among 11 Breast Cancer Association Consortium risk single-nucleotide polymorphisms, we found that the genotype-associated breast cancer risk varied significantly by radiation dose for rs2107425 in the H19 gene (P(interaction) = 0.001). H19 is a maternally expressed imprinted mRNA that is closely involved in regulating the IGF2 gene and could exert its influence by this or by some other radiation-related pathway.
C1 [Bhatti, Parveen; Doody, Michele M.; Simon, Steven L.; Abendfl, Michael; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
[Yuenger, Jeff] Lab Translat Genom, Core Genotyping Facil, Gaithersburg, MD USA.
[Weinstock, Robert M.; Rosenstein, Marvin] Univ Texas MD Anderson Canc Ctr, Res Triangle Inst, Houston, TX 77030 USA.
[Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Abendfl, Michael] Bundeswehr Inst Radiobiol, Munich, Germany.
[Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA.
[Pharoah, Paul] Strangeways Res Lab, Canc Res UK, Cambridge CB1 4RN, England.
[Struewing, Jeffery P.] NCI, Lab Populat Genet, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Bhatti, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S 7049,Mail Stop Co, Bethesda, MD 20892 USA.
EM bhattip@mail.NIH.gov
RI Struewing, Jeffery/I-7502-2013
OI Struewing, Jeffery/0000-0002-4848-3334
FU National Cancer Institute, NIH
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH.
NR 19
TC 8
Z9 9
U1 1
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 AUG
PY 2008
VL 17
IS 8
BP 2007
EP 2011
DI 10.1158/1055-9965.EPI-08-0300
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800025
PM 18708391
ER
PT J
AU Kote-Jarai, Z
Easton, DF
Stanford, JL
Ostrander, EA
Schleutker, J
Ingles, SA
Schaid, D
Thibodeau, S
Dork, T
Neal, D
Cox, A
Maier, C
Vogel, W
Guy, M
Muir, K
Lophatananon, A
Kedda, MA
Spurdle, A
Steginga, S
John, EM
Giles, G
Hopper, J
Chappuis, PO
Hutter, P
Foulkes, WD
Hamel, N
Salinas, CA
Koopmeiners, JS
Karyadi, DM
Johanneson, B
Wahlfors, T
Tammela, TL
Stern, MC
Corral, R
McDonnell, SK
Schurmann, P
Meyer, A
Kuefer, R
Leongamornlert, DA
Tymrakiewicz, M
Liu, JF
O'Mara, T
Gardiner, RA
Aitken, J
Joshi, AD
Severi, G
English, DR
Southey, M
Edwards, SM
Al Olama, AA
Eeles, RA
AF Kote-Jarai, Zsofia
Easton, Douglas F.
Stanford, Janet L.
Ostrander, Elaine A.
Schleutker, Johanna
Ingles, Sue A.
Schaid, Daniel
Thibodeau, Stephen
Doerk, Thilo
Neal, David
Cox, Angela
Maier, Christiane
Vogel, Walter
Guy, Michelle
Muir, Kenneth
Lophatananon, Artitaya
Kedda, Mary-Anne
Spurdle, Amanda
Steginga, Suzanne
John, Esther M.
Giles, Graham
Hopper, John
Chappuis, Pierre O.
Hutter, Pierre
Foulkes, William D.
Hamel, Nancy
Salinas, Claudia A.
Koopmeiners, Joseph S.
Karyadi, Danielle M.
Johanneson, Bo
Wahlfors, Tiina
Tammela, Teuvo L.
Stern, Mariana C.
Corral, Roman
McDonnell, Shannon K.
Schuermann, Peter
Meyer, Andreas
Kuefer, Rainer
Leongamornlert, Daniel A.
Tymrakiewicz, Malgorzata
Liu, Jo-fen
O'Mara, Tracy
Gardiner, R. A. (Frank)
Aitken, Joanne
Joshi, Amit D.
Severi, Gianluca
English, Dallas R.
Southey, Melissa
Edwards, Stephen M.
Al Olama, Ali Amin
Eeles, Rosalind A.
CA PRACTICAL Consortium
TI Multiple novel prostate cancer predisposition loci confirmed by an
international study: The PRACTICAL consortium
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; RISK; INHERITANCE; ANDROGEN;
BINDING; VARIANT; GENE
AB A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10(-17)). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (950% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction.
C1 [Eeles, Rosalind A.] Inst Canc Res, Translat Canc Genet Team, Sect Canc Genet, Sutton SM2 5NG, Surrey, England.
[Easton, Douglas F.] Strangeways Res Lab, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 4RN, England.
[Neal, David] Cambridge Res Inst, Cambridge, England.
[Stanford, Janet L.; Salinas, Claudia A.; Koopmeiners, Joseph S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Stanford, Janet L.; Salinas, Claudia A.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Koopmeiners, Joseph S.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA.
[Ostrander, Elaine A.; Karyadi, Danielle M.; Johanneson, Bo] NHGRI, NIH, Bethesda, MD 20892 USA.
[Schleutker, Johanna; Wahlfors, Tiina] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland.
[Schleutker, Johanna; Wahlfors, Tiina] Tampere Univ Hosp, Tampere, Finland.
[Tammela, Teuvo L.] Univ Tampere, Dept Urol, Temple Univ Hosp & Med Sch, FIN-33101 Tampere, Finland.
[Ingles, Sue A.; Stern, Mariana C.; Corral, Roman; Joshi, Amit D.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Schaid, Daniel; Thibodeau, Stephen; McDonnell, Shannon K.] Mayo Clin, Rochester, MN USA.
[Doerk, Thilo] Hannover Med Sch, Dept Gynecol & Obstet, D-3000 Hannover, Germany.
[Schuermann, Peter] Hannover Med Sch, Gynaecol Res Unit, D-3000 Hannover, Germany.
[Meyer, Andreas] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany.
[Cox, Angela] Univ Sheffield, Sch Med, Inst Canc Studies, Sheffield, S Yorkshire, England.
[Maier, Christiane; Vogel, Walter] Univ Ulm Klinikum, Inst Humangenet, Ulm, Germany.
[Kuefer, Rainer] Univ Ulm Klinikum, Klinikum Urol & Kinderurol, Ulm, Germany.
[Muir, Kenneth; Lophatananon, Artitaya] Univ Nottingham, Nottingham NG7 2RD, England.
[Lophatananon, Artitaya; Liu, Jo-fen] Chulabhorn Canc Res Ctr, Bangkok, Thailand.
[Kedda, Mary-Anne; O'Mara, Tracy] Queensland Univ Technol, Sch Publ Hlth, Brisbane, Qld 4001, Australia.
[Kedda, Mary-Anne; O'Mara, Tracy] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Spurdle, Amanda] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Steginga, Suzanne; Aitken, Joanne] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld, Australia.
[Gardiner, R. A. (Frank)] Univ Queensland, Dept Surg, Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia.
[Aitken, Joanne] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia.
[John, Esther M.] No Calif Canc Ctr, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Giles, Graham; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Giles, Graham; Hopper, John; English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia.
[Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia.
[Chappuis, Pierre O.] Univ Hosp Geneva, Div Med Genet, Geneva, Switzerland.
[Chappuis, Pierre O.] Univ Hosp Geneva, Div Oncol, Geneva, Switzerland.
[Hutter, Pierre] Inst Cent Hop Valaisans, Div Med Genet, Sion, Switzerland.
[Foulkes, William D.; Hamel, Nancy] McGill Univ, Program Canc Genet, Montreal, PQ, Canada.
[Hamel, Nancy] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada.
RP Eeles, RA (reprint author), Inst Canc Res, Translat Canc Genet Team, Sect Canc Genet, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England.
EM Rosalind.Eeles@icr.ac.uk
RI Aitken, Joanne/C-5289-2009; Chambers, Suzanne/C-5508-2009; Gardiner,
Robert/G-2096-2010; Spurdle, Amanda/A-4978-2011; Chambers,
Suzanne/H-5957-2012; Dork, Thilo/J-8620-2012; O'Mara, Tracy/M-7508-2016;
OI Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099;
English, Dallas/0000-0001-7828-8188; Ostrander,
Elaine/0000-0001-6075-9738; Neal, David/0000-0002-6033-5086;
Leongamornlert, Daniel/0000-0002-3486-3168; foulkes,
william/0000-0001-7427-4651; Spurdle, Amanda/0000-0003-1337-7897;
O'Mara, Tracy/0000-0002-5436-3232; Eeles, Rosalind/0000-0002-3698-6241
FU Cancer Research UK [C5047/A3354, C522/A8649]; The Institute of Cancer
Research; The Everyman Campaign; The Prostate Cancer Research
Foundation; Prostate Research Campaign UK; The National Cancer Research
Network UK; The National Cancer Research Institute UK; National Health
and Medical Research Council, Australia [209057, 251533, 450104,
390130]; VicHealth; The Cancer Council Victoria; The Cancer Council
Queensland; The Whitten Foundation; Tattersall's; National Human Genome
Research Institute; Health Technology Assessment Programme [96/20/06,
96/20/99]; Department of Health, England; Medical Research Council of
England [G0500966, ID 75466]; The National Cancer Research Institute,
UK; U.S. Department of Defense [W81XWH-04-1-0280]; National Cancer
Institute [CA56678, CA92579, CA97186]; Fred Hutchinson Cancer Research
Center; U.S. Department of Defense, U.S Army [DAMD17-00-1-0033];
Canadian Genetic Diseases Network; Institut Central des Hopitaux
Valaisans, Sion, Switzerland; U.S. National Cancer Institute
[R01CA72818, R01CAS4979]; California Cancer Research [99-00524V-102-58,
99-00527V-10182]; Academy of Finland [118413,]; The Finnish Career
Organisitions; Sigrid Juselius Foundation; Reino Lahtikari Foundation;
The Medical Research Fund of Tampere University Hospital;
Hannelore-Munke; The Fred Hutchinson Cancer Research Center, Mayo;
Melbourne Collaborative Cohort Study, Montreal, Tampere, U.K; NIH
[CA089600-04]
FX Cancer Research UK grant C5047/A3354. We would also like to thank the
following for funding support: The Institute of Cancer Research and The
Everyman Campaign, The Prostate Cancer Research Foundation, Prostate
Research Campaign UK, The National Cancer Research Network UK, The
National Cancer Research Institute UK, grants from the National Health
and Medical Research Council, Australia (209057, 251533, 450104,
390130), VicHealth, The Cancer Council Victoria, The Cancer Council
Queensland, The Whitten Foundation, and Tattersall's. E.A. Ostrander,
D.M. Karvadi, and B. Johanneson acknowledge the intramural Program of
the National Human Genome Research Institute for their support. The
ProtecT study is ongoing and is funded by the Health Technology
Assessment Programme (projects 96/20/06 and 96/20/99). The ProtecT trial
and its linked ProMPT and CAP (Comparison Arm for ProtecT) Studies are
supported by Department of Health, England; Cancer Research UK grant
C522/A8649, Medical Research Council of England grant G0500966, ID 75466
and The National Cancer Research Institute, UK. DNA extraction in
ProtecT was supported by U.S. Department of Defense award
W81XWH-04-1-0280. The Fred Hutchinson Cancer Research Center work was
supported by grants CA56678, CA92579, and CA97186 from the National
Cancer Institute, NIH, with additional support from the Fred Hutchinson
Cancer Research Center. Ongoing work in Montreal has been funded in turn
by the U.S. Department of Defense (U.S. Army Grant DAMD17-00-1-0033;
Principal Investigator W.D. Foulkes), the Canadian Genetic Diseases
Network, and the NIH The study, in Switzerland was supported by the U.S.
Army Grant DAMD17-00-1-0033 (Principal Investigator: W.D. Foulkes) and a
grant from the Institut Central des Hopitaux Valaisans, Sion,
Switzerland. The Mayo group was supported by the U.S. National Cancer
Institute (R01CA72818). The University of Southern California study was
supported by the U.S. National Cancer Institute (R01CAS4979) and by the
California Cancer Research Program (99-00524V-102-58). The San Francisco
study was supported by the California Cancer Research Fund
(99-00527V-10182). The Tampere (Finland) study was supported by the
Academy of Finland grant 118413, The Finnish Career Organisitions,
Sigrid Juselius Foundation, Reino Lahtikari Foundation, and The Medical
Research Fund of Tampere University Hospital. The Hannover Prostate
Cancer Study was supported by an intramural Hannelore-Munke stipend to
A. Meyer. The Fred Hutchinson Cancer Research Center, Mayo, Melbourne
Collaborative Cohort Study, Montreal, Tampere, U.K. Genetic Prostate
Cancer Study and Ulm groups are part of the International Consortium for
Prostate Cancer Genetics supported by NIH grant U01 CA089600-04.
NR 20
TC 101
Z9 103
U1 1
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2008
VL 17
IS 8
BP 2052
EP 2061
DI 10.1158/1055-9965.EPI-08-0317
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800032
PM 18708398
ER
PT J
AU Zhang, MD
Huang, WY
Andreotti, G
Gao, YT
Rashid, A
Chen, JB
Sakoda, LC
Shen, MC
Wang, BS
Chanock, S
Hsing, AW
AF Zhang, Mingdong
Huang, Wen-Yi
Andreotti, Gabriella
Gao, Yu-Tang
Rashid, Asif
Chen, Jinbo
Sakoda, Lori C.
Shen, Ming-Chang
Wang, Bing-Sheng
Chanock, Stephen
Hsing, Ann W.
TI Variants of DNA repair genes and the risk of biliary tract cancers and
stones: A populaton-based study in China
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; POLYMORPHISMS; METHYLTRANSFERASE;
GALLSTONES; SHANGHAI; SUSCEPTIBILITY; ASSOCIATION; SMOKING; MGMT
AB Biliary tract cancers, which encompass tumors of the gallbladder, extrahepatic ducts, and ampulla of Vater, are relatively rare tumors with a high fatality rate. Other than a close link with gallstones, the etiology of biliary tract cancers is poorly understood. We conducted a population-based case-control study in Shanghai, China, to examine whether genetic variants in several DNA repair genes are associated with biliary tract cancers or biliary stones. Genomic DNA from 410 patients with biliary tract cancers (236 gallbladder, 127 bile duct, and 47 ampulla of Vater), 891 patients with biliary stones, and 786 healthy subjects randomly selected from the Shanghai population were genotyped for putative functional single nucleotide polymorphisms in four DNA repair genes (MGMT, RAD23B, CCNH, and XRCC3). Of the five single nucleotide polymorphisms examined, only one (MGMT EX5-25C>T, rs1291.7) was associated with biliary tract cancer. Independent of gallstones, subjects carrying the CT genotype of the MGMT EX5-25C>T marker had a significantly reduced risk of gallbladder cancer [odds ratio (OR), 0.63; 95% confidence interval (95%) CI), 0.41-0.97; P = 0.021 and nonsignificant reduced risks of bile duct (OR, 0.61; 95% CI, 0.35-1.06) and ampulla of Vater (OR, 0.85; 95% CI, 0.39-1.87) cancers. However, this marker was not associated with biliary stones, and the other markers examined were not significantly associated with either biliary tract cancers or stones. Findings from this population-based study in Shanghai suggest that MGMT gene variants may alter susceptibility to biliary tract cancer, particularly gallbladder cancer. Confirmation in future studies, however, is required.
C1 [Zhang, Mingdong; Huang, Wen-Yi; Andreotti, Gabriella; Chanock, Stephen; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Zhang, Mingdong] US FDA, Rockville, MD 20857 USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Washington, DC USA.
[Shen, Ming-Chang] Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China.
[Wang, Bing-Sheng] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China.
[Chanock, Stephen] NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA.
RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7058,MSC 7324, Bethesda, MD 20892 USA.
EM hsinga@mail.nih.gov
FU NIH; National Cancer Institute
FX Intramural Research Program of the NIH, National Cancer Institute.
NR 26
TC 11
Z9 11
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2008
VL 17
IS 8
BP 2123
EP 2127
DI 10.1158/1055-9965.EPI-07-2735
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800041
PM 18708406
ER
PT J
AU Figueiredo, JC
Levine, AJ
Grau, MV
Midttun, O
Ueland, PM
Ahnen, DJ
Barry, EL
Tsang, S
Munroe, D
Ali, I
Haile, RW
Sandler, RS
Baron, JA
AF Figueiredo, Jane C.
Levine, A. Joan
Grau, Maria V.
Midttun, Oivind
Ueland, Per M.
Ahnen, Dennis J.
Barry, Elizabeth L.
Tsang, Shirley
Munroe, David
Ali, Iqbal
Haile, Robert W.
Sandler, Robert S.
Baron, John A.
TI Vitamins B(2), B(6), and B(12) and risk of new colorectal adenomas in a
randomized trial of aspirin use and folic acid supplementation
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID METHIONINE SYNTHASE REDUCTASE; METHYLENETETRAHYDROFOLATE REDUCTASE;
PLASMA HOMOCYSTEINE; COLON-CANCER; THYMIDYLATE-SYNTHASE; FOLATE
METABOLISM; GENETIC POLYMORPHISMS; DNA HYPOMETHYLATION;
ALCOHOL-CONSUMPTION; CELL-PROLIFERATION
AB Background: Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas.
Methods: The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association.
Results: We found a borderline significant inverse association with plasma B(6) [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; P(trend) = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetralaydrofolate reductase -C677T and plasma B(2) on risk of all adenomas.
Conclusion: Our results suggest that high levels of PLP and B(2) may protect against colorectal adenomas.
C1 [Figueiredo, Jane C.; Levine, A. Joan; Haile, Robert W.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Grau, Maria V.; Barry, Elizabeth L.; Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community, Hanover, NH 03756 USA.
[Grau, Maria V.; Barry, Elizabeth L.; Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Family Med, Hanover, NH 03756 USA.
[Midttun, Oivind] Bevital AS, Armauer Hansens Hus, Bergen, Norway.
[Ueland, Per M.] Univ Bergen, Pharmacol Sect, Inst Med, Bergen, Norway.
Haukeland Hosp, N-5021 Bergen, Norway.
[Ahnen, Dennis J.] Univ Colorado, Dept Med, Denver, CO USA.
[Tsang, Shirley] SAIC Frederick Inc, Lab Mol Technol, Frederick, MD USA.
[Ali, Iqbal] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Sandler, Robert S.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
RP Figueiredo, JC (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Harlyne J Norris Canc Res Tower,1450 Biggy St Roo, Los Angeles, CA 90033 USA.
EM janefigu@usc.edu
RI Ueland, Per/C-7340-2013
FU National Cancer Institute, NIH [R01-CA-059005, U54-CA-100971]; National
Cancer Institute of Canada
FX National Cancer Institute, NIH grants, R01-CA-059005, and U54-CA-100971;
National Cancer Institute of Canada post-Ph.D. research fellowship
017602 U.C. Figueiredo).
NR 62
TC 19
Z9 21
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2008
VL 17
IS 8
BP 2136
EP 2145
DI 10.1158/1055-9965.EPI-07-2895
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 342RI
UT WOS:000258800800043
PM 18708408
ER
PT J
AU Chakraborty, M
Gelbard, A
Carrasquillo, JA
Yu, S
Mamede, M
Paik, CH
Camphausen, K
Schlom, J
Hodge, JW
AF Chakraborty, Mala
Gelbard, Alexander
Carrasquillo, Jorge A.
Yu, Sarah
Mamede, Marcelo
Paik, Chang H.
Camphausen, Kevin
Schlom, Jeffrey
Hodge, James W.
TI Use of radiolabeled monoclonal antibody to enhance vaccine-mediated
antitumor effects
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE mAb; radiation; Y-90; vaccine; immunotherapy
ID RECOMBINANT ANTICANCER VACCINES; CARCINOEMBRYONIC ANTIGEN GENE; INDUCED
LEUKOCYTE ADHESION; NON-HODGKIN-LYMPHOMA; APOPTOSIS IN-VIVO; HIGH-DOSE
THERAPY; TUMOR-CELLS; T-CELLS; PHASE-I; COSTIMULATORY MOLECULES
AB Radiolabeled monoclonal antibodies (mAb) have demonstrated measurable antitumor effects in hematologic malignancies. This outcome has been more difficult to achieve for solid tumors due, for the most part, to difficulties in delivering sufficient quantities of mAb to the tumor mass. Previous studies have shown that nonlytic levels of external beam radiation can render tumor cells more susceptible to T cell-mediated killing. The goal of these studies was to determine if the selective delivery of a radiolabeled mAb to tumors would modulate tumor cell phenotype so as to enhance vaccine-mediated T-cell killing. Here, mice transgenic for human carcinoembryonic antigen (CEA) were transplanted with a CEA expressing murine carcinoma cell line. Radioimmunotherapy consisted of yttrium-90 (Y-90)-labeled anti-CEA mAb, used either alone or in combination with vaccine therapy. A single dose of Y-90-labeled anti-CEA mAb, in combination with vaccine therapy, resulted in a statistically significant increase in survival in tumor-bearing mice over vaccine or mAb alone; this was shown to be mediated by engagement of the Fas/Fas ligand pathway. Mice receiving the combination therapy also showed a significant increase in the percentage of viable tumor-infiltrating CEA-specific CD8(+) T cells compared to vaccine alone. Mice cured of tumors demonstrated an antigen cascade resulting in CD4(+) and CD8(+) T-cell responses not only for CEA, but for p53 and gp70. These results show that systemic radiotherapy in the form of radiolabeled mAb, in combination with vaccine, promotes effective antitumor response, which may have implications in the design of future clinical trials.
C1 [Chakraborty, Mala; Schlom, Jeffrey; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gelbard, Alexander] Baylor Coll Med, Bobby R Alford Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA.
[Carrasquillo, Jorge A.] Mem Sloan Kettering Canc Ctr, Dept Nucl Med, New York, NY 10021 USA.
[Yu, Sarah; Mamede, Marcelo; Paik, Chang H.] NIH, Dept Nucl Med, Bethesda, MD 20892 USA.
[Camphausen, Kevin] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Carrasquillo, Jorge/E-7120-2010; Hodge, James/D-5518-2015; Mamede,
Marcelo/A-1751-2014;
OI Hodge, James/0000-0001-5282-3154; Mamede, Marcelo/0000-0001-5818-0954;
Carrasquillo, Jorge/0000-0002-8513-5734
FU Intramural NIH HHS
NR 46
TC 22
Z9 23
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 AUG
PY 2008
VL 57
IS 8
BP 1173
EP 1183
DI 10.1007/s00262-008-0449-x
PG 11
WC Oncology; Immunology
SC Oncology; Immunology
GA 304DB
UT WOS:000256089100007
PM 18256832
ER
PT J
AU Kanduc, D
Tessitore, L
Lucchese, G
Kusalik, A
Farber, E
Marincola, FM
AF Kanduc, Darja
Tessitore, Luciana
Lucchese, Guglielmo
Kusalik, Anthony
Farber, Emanuel
Marincola, Francesco M.
TI Sequence uniqueness and sequence variability as modulating factors of
human anti-HCV humoral immune response
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE unique peptide sequences; conserved peptide sequences;
sequence-to-sequence peptide matching; proteasomal cleavages;
HCV-related immunity
ID HEPATITIS-C VIRUS; MOLECULAR MIMICRY; NATURAL-HISTORY; KAPPA-B;
INFECTION; EPITOPES; GLYCOPROTEIN; GENOTYPES; THERAPY; PEPTIDE
AB We recently compared the HCV polyprotein to the human proteome in order to test whether amino acid sequences unique to the virus could represent immunodominant epitopic determinants of the human humoral immune response against HCV. We identified a relatively limited number of HCV fragments with no/low similarity to the human host that represented exclusive HCV motifs. In this study, the peptides corresponding to low/zero similarity sequences were synthesized and assayed with HCV-infected sera. With different patterns, the synthetic HCV peptides corresponding to low/zero similarity sequences were found to be immunoreactive. In particular, the HCV E1 (315-323) HRMAWDMMM, HCV E2/NS1 (547-555) NWFGCTWMN, and HCV NS5 (2638-2646) YDTRCFDST sequences were immunodominant in the HCV-infected cohort under study. These three peptides correspond to sequences that are endowed with low-similarity to the human proteome, are highly conserved among various HCV strains, and have, potentially, a scarce susceptibility to proteolytic attacks. These data may be of help in defining the multiple factors which concur in the modulation of the human immune response against HCV, eventually providing information for the design of effective anti-HCV vaccines.
C1 [Kanduc, Darja; Marincola, Francesco M.] NIH, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA.
[Kanduc, Darja; Lucchese, Guglielmo] Univ Bari, Dept Biochem & Mol Biol Ernesto Quagliariello, Bari, Italy.
[Tessitore, Luciana] Univ A Avogadro, DISCAFF, Novara, Italy.
[Kusalik, Anthony] Univ Saskatchewan, Dept Comp Sci, Saskatoon, SK S7N 0W0, Canada.
[Farber, Emanuel] Univ S Carolina, Dept Pathol, Columbia, SC 29208 USA.
RP Kanduc, D (reprint author), NIH, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bldg 10, Bethesda, MD 20892 USA.
EM kanducd@cc.nih.gov
OI Kanduc, Darja/0000-0003-2111-4608
NR 46
TC 17
Z9 17
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 AUG
PY 2008
VL 57
IS 8
BP 1215
EP 1223
DI 10.1007/s00262-008-0456-y
PG 9
WC Oncology; Immunology
SC Oncology; Immunology
GA 304DB
UT WOS:000256089100011
PM 18256830
ER
PT J
AU Woo, JH
Bour, SH
Dang, T
Lee, YJ
Park, SK
Andreas, E
Kang, SH
Liu, JS
Neville, DM
Frankel, AE
AF Woo, Jung Hee
Bour, Sarah H.
Dang, Tony
Lee, Yu-Jen
Park, Seong Kyu
Andreas, Elissa
Kang, Soo Hyun
Liu, Jen-Sing
Neville, David M., Jr.
Frankel, Arthur E.
TI Preclinical studies in rats and squirrel monkeys for safety evaluation
of the bivalent anti-human T cell immunotoxin, A-dmDT390-bisFv(UCHT1)
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE MTD; diphtheria toxin; UCHT1; CD3 positive
ID TRUNCATED DIPHTHERIA-TOXIN; COLONY-STIMULATING FACTOR; SINGLE-CHAIN
IMMUNOTOXIN; PICHIA-PASTORIS; DENILEUKIN DIFTITOX; LYMPHOPROLIFERATIVE
DISORDER; IMMUNOPHENOTYPIC ANALYSIS; CYNOMOLGUS MONKEYS;
MYCOSIS-FUNGOIDES; SEZARY-SYNDROME
AB The bivalent anti-human T cell immunotoxin A-dmDT390-bisFv(UCHT1) for treatment of patients with T cell malignancies is a single chain fusion protein composed of the catalytic domain and translocation domains of diphtheria toxin fused to two tandem sFv molecules reactive with human CD3 epsilon. This immunotoxin selectively kills CD3 epsilon positive T cells. To determine the maximum tolerated dose (MTD), pharmacokinetics and immunogenicity of A-dmDT390-bisFv(UCHT1), rat and squirrel monkey studies were performed. In both animal studies, animals received either 0, 2.5 (low), 25 (medium), or 56.25 mu g/kg (high) of A-dmDT390-bisFv(UCHT1) intravenously twice daily for four consecutive days. Although transient elevation of liver transaminases in the high groups was observed, the A-dmDT390-bisFv(UCHT1) administration did not affect liver function, renal function, the hemogram, or produce serious organ histopathology. Adverse events included transient lethargy, inappetence and weight loss in high groups. A-dmDT390-bisFv(UCHT1) plasma half life was 26.95 min in rats and 18.33 min in squirrel monkeys. Immune responses to A-dmDT390-bisFv(UCHT1) were minimal in squirrel monkeys and mild in rats. In vitro cytokine release, T cell activation and CD3 epsilon receptor occupancy assays using human PBMC were further performed since rat and squirrel monkey T cells do not react with A-dmDT390-bisFv(UCHT1). A-dmDT390-bisFv(UCHT1) did not induce cytokine release or T cell activation. The A-dmDT390-bisFv(UCHT1) concentration for 50% CD3 epsilon receptor occupancy was 7.4 nM. The MTD of 200 mu g/kg total provides a dose level sufficient for anti-tumor activity in vitro and in a rodent model. Therefore, we propose that this agent is a promising drug for patients with surface CD3(+) T cell malignancies.
C1 [Woo, Jung Hee; Bour, Sarah H.; Dang, Tony; Lee, Yu-Jen; Park, Seong Kyu; Andreas, Elissa; Kang, Soo Hyun; Liu, Jen-Sing; Frankel, Arthur E.] Scott & White Canc Res Inst, Temple, TX 76502 USA.
[Neville, David M., Jr.] NIMH, Biophys Chem Sect, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Woo, JH (reprint author), Scott & White Canc Res Inst, 5701 S Airport Rd, Temple, TX 76502 USA.
EM jwoo@swmail.sw.org
NR 54
TC 14
Z9 14
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD AUG
PY 2008
VL 57
IS 8
BP 1225
EP 1239
DI 10.1007/s00262-008-0457-x
PG 15
WC Oncology; Immunology
SC Oncology; Immunology
GA 304DB
UT WOS:000256089100012
PM 18256829
ER
PT J
AU Colburn, NH
Kensler, TW
AF Colburn, Nancy H.
Kensler, Thomas W.
TI Targeting Transcription Factors for Cancer Prevention-the Case of Nrf2
SO CANCER PREVENTION RESEARCH
LA English
DT Editorial Material
ID NF-KAPPA-B; TUMORIGENESIS; AP-1; MICE; CARCINOGENESIS; INFLAMMATION;
PROMOTION; RESPONSES; THERAPY
C1 [Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21702 USA.
[Kensler, Thomas W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
RP Colburn, NH (reprint author), NCI, Lab Canc Prevent, Bldg 576,Room 101, Frederick, MD 21702 USA.
EM Colburn@ncifcrf.gov
RI Kensler, Thomas/D-8686-2014
OI Kensler, Thomas/0000-0002-6676-261X
NR 18
TC 11
Z9 12
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD AUG
PY 2008
VL 1
IS 3
BP 153
EP 155
DI 10.1158/1940-6207.CAPR-08-0025
PG 3
WC Oncology
SC Oncology
GA 420ME
UT WOS:000264293100002
PM 19138949
ER
PT J
AU Abate-Shen, C
Brown, PH
Colburn, NH
Gerner, EW
Green, JE
Lipkin, M
Nelson, WG
Threadgill, D
AF Abate-Shen, Cory
Brown, Powel H.
Colburn, Nancy H.
Gerner, Eugene W.
Green, Jeffery E.
Lipkin, Martin
Nelson, William G.
Threadgill, David
TI The Untapped Potential of Genetically Engineered Mouse Models in
Chemoprevention Research: Opportunities and Challenges
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID POLYP PREVENTION TRIAL; LI-FRAUMENI-SYNDROME; PROSTATE-CANCER;
TRANSGENIC MICE; ADENOMA RECURRENCE; RNA-INTERFERENCE; BREAST-CANCER;
PROGRESSION; METASTASIS; TUMORS
AB The past decade has witnessed the unveiling of a powerful new generation of genetically engineered mouse ( GEM) models of human cancer, which are proving to be highly effective for elucidating cancer mechanisms and interrogating novel experimental therapeutics. This new generation of GEM models are well suited for chemoprevention research, particularly for investigating progressive stages of carcinogenesis, identifying biomarkers for early detection and intervention, and preclinical assessment of novel agents or combinations of agents. Here we discuss opportunities and challenges for the application of GEM models in prevention research, as well as strategies to maximize their relevance for human cancer.
C1 [Abate-Shen, Cory] Columbia Univ Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, Dept Urol, New York, NY 10032 USA.
[Lipkin, Martin] Cornell Univ, Weill Med Coll, Strang Canc Prevent Ctr, New York, NY 10021 USA.
[Brown, Powel H.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Brown, Powel H.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA.
[Gerner, Eugene W.] Univ Arizona, Arizona Canc Ctr, Dept Cell Biol & Anat, Tucson, AZ USA.
[Green, Jeffery E.] NCI, Canc Biol Lab, Bethesda, MD 20892 USA.
[Nelson, William G.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA.
[Threadgill, David] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Threadgill, David] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Abate-Shen, C (reprint author), Columbia Univ Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, Dept Urol, Room 217A,1130 St Nicholas St, New York, NY 10032 USA.
EM cabateshen@columbia.edu
RI Abate-Shen, Cory/O-2520-2014; Threadgill, David/N-4425-2013
OI Abate-Shen, Cory/0000-0002-5021-0570; Threadgill,
David/0000-0003-3538-1635
FU NIH; Center for Cancer Research; National Cancer Institute; [DOD
W81XWH-06-1-0035]; [UO1 CA84294]; [CA123065]; [N01-CN-43302];
[U54-CA 100926]; [CA101211]
FX Grants DOD W81XWH-06-1-0035 (C. Abate-Shen), UO1 CA84294 (C. Abate-Shen
and W. G. Nelson), CA123065 (E. W. Gerner), N01-CN-43302 and U54-CA
100926 (M. Lipkin), CA101211 (P. H. Brown), and the Intramural Research
Program of the NIH, Center for Cancer Research, National Cancer
Institute (J.E. Green and N.H. Colburn).
NR 46
TC 14
Z9 15
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD AUG
PY 2008
VL 1
IS 3
BP 161
EP 166
DI 10.1158/1940-6207.CAPR-08-0076
PG 6
WC Oncology
SC Oncology
GA 420ME
UT WOS:000264293100004
PM 19138951
ER
PT J
AU Lucia, MS
Darke, AK
Goodman, PJ
La Rosa, FG
Parnes, HL
Ford, LG
Coltman, CA
Thompson, IM
AF Lucia, M. Scott
Darke, Amy K.
Goodman, Phyllis J.
La Rosa, Francisco G.
Parnes, Howard L.
Ford, Leslie G.
Coltman, Charles A., Jr.
Thompson, Ian M.
TI Pathologic Characteristics of Cancers Detected in the Prostate Cancer
Prevention Trial: Implications for Prostate Cancer Detection and
Chemoprevention
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID RADICAL PROSTATECTOMY; MEN; PSA; ANTIGEN; INSIGNIFICANT; FINASTERIDE;
BIOPSY; SENSITIVITY; POPULATION; PREDICTION
AB The Prostate Cancer Prevention Trial (PCPT) showed a risk of prostate cancer at prostate-specific antigen (PSA) <4.0 ng/mL and that prostate cancer risk is reduced by finasteride. A major concern about early detection by PSA and prevention by finasteride is that they may involve biologically inconsequential tumors. We reviewed the pathologic characteristics of prostate biopsies from men in the placebo and finasteride groups of the PCPT. We examined tumor pathology characteristics stratified by level of PSA for men in the placebo group who underwent radical prostatectomy. Seventy-five percent of all cancers and 62% of Gleason score <= 6 cancers in the PCPT met the biopsy criteria for clinically significant tumors. Surrogate measures for tumor volume (number of cores positive, percent cores positive, linear extent, and bilaterality) and risk of perineural invasion were lower in men who received finasteride. The PSA-associated risks of insignificant cancer were 51.7% (PSA, 0-1.0 ng/mL), 33.7% (1.1-2.5 ng/mL), 17.8% (2.6-4.0 ng/mL), and 11.7% (4.1-10 ng/mL). Conversely, the risks of high-grade (Gleason score >= 7) tumors for the same PSA strata were 15.6%, 37.9%, 49.1%, and 52.4%, respectively. These data highlight the dilemma of PSA when used for screening: Lower cutoff levels increase detection of insignificant disease, but cure is more likely, whereas higher cutoff levels make detection of significant cancer more likely, but cure is less likely. Therefore, the effectiveness of finasteride in preventing prostate cancer, including Gleason score <= 6 cancer, with meaningful rates of significant disease in the PCPT suggests that cutoff values for PSA screening should be individualized and that men undergoing screening should be informed of the opportunity to reduce their risk of disease with finasteride.
C1 [Lucia, M. Scott] Univ Colorado Denver, Dept Pathol, Sch Med, Aurora, CO 80045 USA.
[Darke, Amy K.; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Parnes, Howard L.; Ford, Leslie G.] NCI, Bethesda, MD 20892 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
RP Lucia, MS (reprint author), Univ Colorado Denver, Dept Pathol, Sch Med, 12800 E 19th Ave,Mail Stop 8104, Aurora, CO 80045 USA.
EM scott.lucia@uchsc.edu
FU National Cancer Institute Public Health Service grants [CA37429,
CA35178, CA45808]; Merck and Co., Inc.
FX National Cancer Institute Public Health Service grants CA37429, CA35178,
and CA45808. Supplemental funding for analysis of prostatectomy
specimens in this study was provided by Merck and Co., Inc. (Whitehouse
Station, NJ).
NR 31
TC 59
Z9 62
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD AUG
PY 2008
VL 1
IS 3
BP 167
EP 173
DI 10.1158/1940-6207.CAPR-08-0078
PG 7
WC Oncology
SC Oncology
GA 420ME
UT WOS:000264293100005
PM 19138952
ER
PT J
AU Pinsky, P
Parnes, H
Ford, L
AF Pinsky, Paul
Parnes, Howard
Ford, Leslie
TI Estimating Rates of True High-Grade Disease in the Prostate Cancer
Prevention Trial
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID FINASTERIDE
AB The Prostate Cancer Prevention Trial (PCPT) showed a decreased prostate cancer rate but an increased rate of high Gleason grade disease on biopsy for finasteride versus placebo. The results from radical prostatectomy (RP) on 25% of the men undergoing RP have recently been reported and suggest that grading artifacts in biopsy Gleason scoring may have occurred. We used a statistical model to extrapolate the RP Gleason results to all men in the PCPT using a missing-at-random assumption. We estimated the rates of true high-grade (Gleason 7-10) and true low-grade disease, where true Gleason grade is what is (or would have been) found on RP. We also estimated misclassification rates on biopsy of true high-grade and low-grade disease. We show that the rate of upgrading of biopsy low-grade disease to high-grade on RP is a function of misclassification rates as well as the ratio of true low-grade to high-grade disease. The estimated relative risks for true low-grade and true high-grade disease for finasteride compared with placebo were 0.61 (95% confidence interval, 0.51-0.71) and 0.84 (95% confidence interval, 0.68-1.05), respectively. The misclassification rate of true high-grade disease (to low-grade disease on biopsy) was significantly lower for finasteride (34.6%) than for placebo (52.6%). Although misclassification rates differed, upgrading rates were similar in each arm due to the different ratios of true low-grade to high-grade disease in each arm. Results from RP show that misclassification rates on biopsy were higher in the placebo arm and that the rate of true high-grade disease may have been lower in the finasteride arm.
C1 [Pinsky, Paul; Parnes, Howard; Ford, Leslie] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Pinsky, P (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA.
EM pp4f@nih.gov
NR 6
TC 53
Z9 55
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD AUG
PY 2008
VL 1
IS 3
BP 182
EP 186
DI 10.1158/1940-6207.CAPR-07-0007
PG 5
WC Oncology
SC Oncology
GA 420ME
UT WOS:000264293100007
PM 19138954
ER
PT J
AU Ambs, S
Prueitt, RL
Yi, M
Hudson, RS
Howe, TM
Petrocca, F
Wallace, TA
Liu, CG
Volinia, S
Calin, GA
Yfantis, HG
Stephens, RM
Croce, CM
AF Ambs, Stefan
Prueitt, Robyn L.
Yi, Ming
Hudson, Robert S.
Howe, Tiffany M.
Petrocca, Fabio
Wallace, Tiffany A.
Liu, Chang-Gong
Volinia, Stefano
Calin, George A.
Yfantis, Harris G.
Stephens, Robert M.
Croce, Carlo M.
TI Genomic profiling of MicroRNA and messenger RNA reveals deregulated
MicroRNA expression in prostate cancer
SO CANCER RESEARCH
LA English
DT Article
ID CELL-CYCLE ARREST; BREAST-CANCER; E2F1 EXPRESSION; HOST GENES;
APOPTOSIS; LEUKEMIA; MODULATE; TUMORS; DIFFERENTIATION; ADENOCARCINOMA
AB MicroRNAs are small noncoding RNAs that regulate the expression of protein-coding genes. To evaluate the involvement of microRNAs in prostate cancer, we determined genome-wide expression of microRNAs and mRNAs in 60 primary prostate tumors and 16 nontumor prostate tissues. The mRNA analysis revealed that key components of microRNA processing and several microRNA host genes, e.g., MCM7 and C9orj5, were significantly up-regulated in prostate tumors. Consistent with these findings, tumors expressed the miR-106b-25 cluster, which maps to intron 13 of MCM7, and miR-32, which maps to intron 14 of C9orJ5, at significantly higher levels than nontumor prostate. The expression levels of other microRNAs. including a number of miR-106b-25 cluster homologues, were also altered in prostate tumors. Additional differences in microRNA abundance were found between organ-confined tumors and those with extraprostatic disease extension. Lastly, we found evidence that some microRNAs are androgen-regulated and that tumor microRNAs influence transcript abundance of protein-coding target genes in the cancerous prostate. In cell culture, E2F1 and p21/WAFI were identified as targets of miR--106b, Bim of miR-32, and exportin6 and protein tyrosine kinase 9 of miR-1. In summary, microRNA expression becomes altered with the development and progression of prostate cancer. Some of these microRNAs regulate the expression of cancer-related genes in prostate cancer cells.
C1 [Ambs, Stefan; Prueitt, Robyn L.; Hudson, Robert S.; Howe, Tiffany M.; Wallace, Tiffany A.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yi, Ming; Stephens, Robert M.] Sci Applicat Int Corp Frederick Inc, Adv Biomed Comp Ctr, Natl Canc Inst, Frederick, MD USA.
[Petrocca, Fabio; Liu, Chang-Gong; Volinia, Stefano; Croce, Carlo M.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Calin, George A.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Yfantis, Harris G.] Baltimore Vet Affairs Med Ctr, Dept Pathol & Lab Med, Baltimore, MD USA.
RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 3050B, Bethesda, MD 20892 USA.
EM ambss@mail.nih.gov; carlo.croce@osumc.edu
RI Volinia, Stefano/A-3029-2010
OI Volinia, Stefano/0000-0003-0910-3893
FU Intramural NIH HHS [Z01 BC010624-03]; NCI NIH HHS [CA128609, P01
CA081534, R01 CA128609, CA081534]
NR 50
TC 395
Z9 414
U1 1
U2 16
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2008
VL 68
IS 15
BP 6162
EP 6170
DI 10.1158/0008-5472.CAN-08-0144
PG 9
WC Oncology
SC Oncology
GA 333UI
UT WOS:000258177600019
PM 18676839
ER
PT J
AU Goswami, A
Qiu, S
Dexheimer, TS
Ranganathan, P
Burikhanovl, R
Pommier, Y
Rangnekar, VM
AF Goswami, Anindya
Qiu, Shirley
Dexheimer, Thomas S.
Ranganathan, Padhma
Burikhanovl, Ravshan
Pommier, Yves
Rangnekar, Vivek M.
TI Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation
activity
SO CANCER RESEARCH
LA English
DT Article
ID PROTEIN PAR-4; I INHIBITORS; INDUCED APOPTOSIS; OXYGEN RADICALS;
ONCOGENIC RAS; CELLS; CANCER; GENE; CAMPTOTHECIN; EXPRESSION
AB The regulation of DNA relaxation by topoisomerase 1 (TOP1) is essential for DNA replication, transcription, and recombination events. TOPI activity is elevated in cancer cells, yet the regulatory mechanism restraining its activity is not understood. We present evidence that the tumor suppressor protein prostate apoptosis response-4 (Par-4) directly binds to TOPI and attenuates its DNA relaxation activity. Unlike camptothecin, which binds at the TOPI-DNA interface to form cleavage complexes, Par-4 interacts with TOPI via its leucine zipper domain and sequesters TOPI from the DNA. Par-4 knockdown by RNA interference enhances DNA relaxation and gene transcription activities and promotes cellular transformation in a TOPI-dependent manner. Conversely, attenuation of TOPI activity either by RNA interference or Par-4 overexpression impedes DNA relaxation, cell cycle progression, and gene transcription activities and inhibits transformation. Colleclively, our findings suggest that Par-4 serves as an intracellular repressor of TOPI catalytic activity and regulates DNA topology to suppress cellular transformation.
C1 [Goswami, Anindya; Qiu, Shirley; Burikhanovl, Ravshan; Rangnekar, Vivek M.] Univ Kentucky, Dept Radiat Med, Lexington, KY 40536 USA.
[Ranganathan, Padhma; Rangnekar, Vivek M.] Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA.
[Dexheimer, Thomas S.; Pommier, Yves] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA.
[Rangnekar, Vivek M.] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA.
[Rangnekar, Vivek M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Rangnekar, VM (reprint author), Univ Kentucky, Dept Radiat Med, Combs Res Bldg,Room 309,800 Rose St, Lexington, KY 40536 USA.
EM vmrang01@email.uky.edu
FU NCI NIH HHS [CA60872, CA84511, R01 CA105453, CA105453, R01 CA060872, R01
CA060872-10, R01 CA084511]
NR 45
TC 16
Z9 19
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2008
VL 68
IS 15
BP 6190
EP 6198
DI 10.1158/0008-5472.CAN-08-0831
PG 9
WC Oncology
SC Oncology
GA 333UI
UT WOS:000258177600022
PM 18676842
ER
PT J
AU Barkan, D
Kleinman, H
Simmons, JL
Asmussen, H
Kamaraju, AK
Hoenorhoff, MJ
Liu, ZY
Costes, SV
Cho, EH
Lockett, S
Khanna, C
Chambers, AF
Green, JE
AF Barkan, Dalit
Kleinman, Hynda
Simmons, Justin L.
Asmussen, Holly
Kamaraju, Anil K.
Hoenorhoff, Mark J.
Liu, Zi-yao
Costes, Sylvain V.
Cho, Edward H.
Lockett, Stephen
Khanna, Chand
Chambers, Ann F.
Green, Jeffrey E.
TI Inhibition of metastatic outgrowth from single dormant tumor cells by
targeting the cytoskeleton
SO CANCER RESEARCH
LA English
DT Article
ID LIGHT-CHAIN KINASE; BASEMENT-MEMBRANE CULTURES; MAMMARY-CARCINOMA CELLS;
BREAST-CANCER CELLS; IN-VIVO; 3-DIMENSIONAL CULTURE; MALIGNANT
PHENOTYPE; SMOOTH-MUSCLE; BONE-MARROW; GROWTH
AB Metastatic breast cancer may emerge from latent tumor cells that remain dormant at disseminated sites for many years. Identifying mechanisms regulating the switch from dormancy to proliferative metastatic growth has been elusive due to the lack of experimental models of tumor cell dormancy. We characterized the in vitro growth characteristics of cells that exhibit either dormant (D2.0R, MCF-7, and K7M2AS1.46) or proliferative (D2A1, MDA-MB-231, and K7M2) metastatic behavior in vivo. Although these cells proliferate readily in two-dimensional culture, we show that when grown in three-dimensional matrix, distinct growth properties of the cells were revealed that correlate to their dormant or proliferative behavior at metastatic sites in vivo. In three-dimensional culture, cells with dormant behavior in vivo remained cell cycle arrested with elevated nuclear expression of p16 and p27. The transition from quiescence to proliferation of D2A1 cells was dependent on fibronectin production and signaling through integrin beta 1, leading to cytoskeletal reorganization with filamentous actin (F-actin) stress fiber formation. We show that phosphorylation of myosin light chain (MLC) by MLC kinase (MLCK) through integrin beta 1 is required for actin stress fiber formation and proliferative growth. Inhibition of integrin beta 1 or MLCK prevents transition from a quiescent to proliferative state in vitro. Inhibition of MLCK significantly reduces metastatic outgrowth in vivo. These studies show that the switch from dormancy to metastatic growth may be regulated, in part, through epigenetic signaling from the microenvironment, leading to changes in the cytoskeletal architecture of dormant cells. Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch.
C1 [Barkan, Dalit; Simmons, Justin L.; Asmussen, Holly; Kamaraju, Anil K.; Hoenorhoff, Mark J.; Liu, Zi-yao; Green, Jeffrey E.] NCI, Cell Biol & Genet Lab, NIH, Bethesda, MD 20892 USA.
[Kleinman, Hynda] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD USA.
[Khanna, Chand] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Costes, Sylvain V.] Lawrence Livermore Natl Lab, Dept Canc Biol, Berkeley, CA USA.
[Cho, Edward H.; Lockett, Stephen] Sci Applicat Int Corp Frederick, Natl Canc Inst Fredrick, Image Anal Lab, Frederick, MD USA.
[Chambers, Ann F.] London Reg Canc Program, London, ON, Canada.
RP Green, JE (reprint author), NCI, Cell Biol & Genet Lab, NIH, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA.
EM jegreen@nih.gov
RI Costes, Sylvain/D-2522-2013; Chambers, Ann/L-6285-2015; Cho,
Edward/B-3727-2012
OI Costes, Sylvain/0000-0002-8542-2389; Chambers, Ann/0000-0002-9509-5123;
Cho, Edward/0000-0002-0278-334X
FU Intramural NIH HHS [Z01 BC005740-15]
NR 45
TC 152
Z9 154
U1 2
U2 15
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2008
VL 68
IS 15
BP 6241
EP 6250
DI 10.1158/0008-5472.CAN-07-6849
PG 10
WC Oncology
SC Oncology
GA 333UI
UT WOS:000258177600028
PM 18676848
ER
PT J
AU Du, X
Beers, R
FitzGerald, DJ
Pastan, I
AF Du, Xing
Beers, Richard
FitzGerald, David J.
Pastan, Ira
TI Differential cellular internalization of anti-CD19 and-CD22 immunotoxins
results in different cytotoxic activity
SO CANCER RESEARCH
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RICIN-A-CHAIN; PHASE-I TRIAL; ACUTE
LYMPHOBLASTIC-LEUKEMIA; POKEWEED ANTIVIRAL PROTEIN; HUMAN B-CELLS;
ANTI-B4-BLOCKED RICIN; DIFFERENT EPITOPES; MONOCLONAL-ANTIBODIES;
CONTINUOUS-INFUSION
AB B-cell malignancies routinely express surface antigens CD19 and CD22. Immunotoxins against both antigens have been evaluated, and the immunotoxins targeting CD22 are more active. To understand this disparity in cytotoxicity and guide the screening of therapeutic targets, we compared two immunotoxins, FMC63(Fv)-PE38-targeting CD19 and RFB4(Fv)-PE38 (BL22)-targeting CD22. Six lymphoma cell lines have 4- to 9-fold more binding sites per cell for CD19 than for CD22, but BL22 is 4- to 140-fold more active than FMC63(Fv)-PE38, although they have a similar cell binding affinity (Kd, similar to 7 nmol/L). In I hour, large amounts of BL22 are internalized (2- to 3-fold more than the number of CD22 molecules on the cell surface), whereas only 5.2% to 16.6% of surface-bound FMC63(Fv)-PE38 is internalized. The intracellular reservoir of CD22 decreases greatly after immunotoxin internalization, indicating that it contributes to the uptake of BL22. Treatment of cells with cycloheximide does not reduce the internalization of BL22. Both internalized immunotoxins are located in the same vesicles. Our results show that the rapid internalization of large amounts of BL22 bound to CD22 makes CD22 a better therapeutic target than CD19 for immunotoxins and probably for other immunoconjugates that act inside cells.
C1 [Du, Xing; Beers, Richard; FitzGerald, David J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
RI Du, Xing/B-1113-2011
FU Intramural NIH HHS [Z01 BC008753-25, Z01 BC008757-20, Z01 BC010020-12]
NR 50
TC 63
Z9 64
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2008
VL 68
IS 15
BP 6300
EP 6305
DI 10.1158/0008-5472.CAN-08-0461
PG 6
WC Oncology
SC Oncology
GA 333UI
UT WOS:000258177600034
PM 18676854
ER
PT J
AU Das, S
Hahn, Y
Walker, DA
Nagata, S
Willingham, MC
Peehl, DM
Bera, TK
Lee, B
Pastan, I
AF Das, Sudipto
Hahn, Yoonsoo
Walker, Dawn A.
Nagata, Satoshi
Willingham, Mark C.
Peehl, Donna M.
Bera, Tapan K.
Lee, Byungkook
Pastan, Ira
TI Topology of NGEP, a prostate-specific cell: Cell junction protein widely
expressed in many cancers of different grade level
SO CANCER RESEARCH
LA English
DT Article
ID MEMBRANE-PROTEIN; HORMONAL-THERAPY; N-GLYCOSYLATION; ANTIGEN;
RADIOTHERAPY; TISSUES
AB New gene expressed in prostate (NGEP) is a prostate-specific polytopic membrane protein found at high concentrations at cell:cell contact regions. To determine if NGEP is a useful target for antibody-based therapy of prostate cancer, we performed an immunohistochemical analysis of 126 human prostate carcinoma samples using polyclonal anti-NGEP sera and found that 91% of the cancers express NGEP protein. To elucidate the topology of NGEP and guide the development of monoclonal antibodies (mAb) reacting with the extracellular regions of NGEP, a hemagglutinin epitope tag was inserted at several positions within the NGEP sequence. The tagged proteins were expressed in 293T cells and locations of the tags were determined by immunofluorescence in intact or permeabilized cells. The results indicate that NGEP contains eight transmembrane domains with both the NH(2) and COOH termini of NGEP located inside the cell. We produced mAb to three regions that are predicted to be intracellular based on the epitope tag data (amino acids 1-352, 441-501, and 868-933), and as predicted, the mAb only detected the protein in permeabilized cells. NGEP is a glycoprotein with predicted glycosylation sites at N809 and N824. When these residues were converted to glutamine, glycosylation was abolished, confirming that the residues are extracellular. Our findings on the expression and the orientation of the NGEP protein serve as an important framework for the development of mAb targeting the extracellular regions of NGEP that could be used for prostate cancer immunotherapy.
C1 [Das, Sudipto; Hahn, Yoonsoo; Walker, Dawn A.; Nagata, Satoshi; Bera, Tapan K.; Lee, Byungkook; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Willingham, Mark C.] Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA.
[Peehl, Donna M.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010298-10, Z01 BC008759-16]
NR 27
TC 42
Z9 44
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2008
VL 68
IS 15
BP 6306
EP 6312
DI 10.1158/0008-5472.CAN-08-0870
PG 7
WC Oncology
SC Oncology
GA 333UI
UT WOS:000258177600035
PM 18676855
ER
PT J
AU Hsing, AW
Sakoda, LC
Rashid, A
Andreotti, G
Chen, JB
Wang, BS
Shen, MC
Chen, BE
Rosenberg, PS
Zhang, MD
Niwa, S
Chu, L
Welch, R
Yeager, M
Fraumeni, JF
Gao, YT
Chanock, SJ
AF Hsing, Ann W.
Sakoda, Lori C.
Rashid, Asif
Andreotti, Gabriella
Chen, Jinbo
Wang, Bin-Shen
Shen, Ming-Chang
Chen, Bingshu E.
Rosenberg, Philip S.
Zhang, Mingdong
Niwa, Shelley
Chu, Lisa
Welch, Robert
Yeager, Meredith
Fraumeni, Joseph F., Jr.
Gao, Yu-Tang
Chanock, Stephen J.
TI Variants in inflammation genes and the risk of biliary tract cancers and
stones: A population-based study in China
SO CANCER RESEARCH
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; NON-HODGKIN-LYMPHOMA; PROMOTER REGION;
PROSTATE-CANCER; POLYMORPHISMS; SUSCEPTIBILITY; ASSOCIATION; SHANGHAI;
TUMOR; TNF
AB To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.
C1 [Hsing, Ann W.; Andreotti, Gabriella; Chen, Bingshu E.; Rosenberg, Philip S.; Chu, Lisa; Yeager, Meredith; Fraumeni, Joseph F., Jr.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Chu, Lisa] NCI, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA.
[Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Wang, Bin-Shen] Fudan Univ, Zhong Shan Hosp, Dept Surg, Shanghai, Peoples R China.
[Shen, Ming-Chang] Shanghai Tumor Hosp, Shanghai, Peoples R China.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Zhang, Mingdong] US FDA, Silver Spring, MD USA.
[Niwa, Shelley] Westat Corp, Rockville, MD USA.
[Chu, Lisa; Welch, Robert; Chanock, Stephen J.] Natl Canc Inst, Sci Applicat Int Corp Frederick Inc, Adv Technol Program, Core Genotyping Facil, Frederick, MD USA.
RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 5024,MSC 7234, Bethesda, MD 20892 USA.
EM hsinga@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010158-09]; NCI NIH HHS [N01-CO-12400,
N01CO12400]
NR 38
TC 44
Z9 45
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2008
VL 68
IS 15
BP 6442
EP 6452
DI 10.1158/0008-5472.CAN-08-0444
PG 11
WC Oncology
SC Oncology
GA 333UI
UT WOS:000258177600050
PM 18676870
ER
PT J
AU Salnikow, K
Aprelikova, O
Ivanov, S
Tackett, S
Kaczmarek, M
Karaczyn, A
Yee, H
Kasprzak, KS
Niederhuber, J
AF Salnikow, Konstantin
Aprelikova, Olga
Ivanov, Sergey
Tackett, Sean
Kaczmarek, Monika
Karaczyn, Aldona
Yee, Herman
Kasprzak, Kazimierz S.
Niederhuber, John
TI Regulation of hypoxia-inducible genes by ETS1 transcription factor
SO CARCINOGENESIS
LA English
DT Article
ID CARBONIC-ANHYDRASE-IX; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA;
CANCER-THERAPY; CA-IX; EXPRESSION; MARKER; NICKEL; HIF-2-ALPHA; BINDING
AB Hypoxia-inducible factor (HIF-1) regulates the expression of genes that facilitate tumor cell survival by making them more resistant to therapeutic intervention. Recent evidence suggests that the activation of other transcription factors, in cooperation with HIF-1 or acting alone, is involved in the upregulation of hypoxia-inducible genes. Here we report that high cell density, a condition that might mimic the physiologic situation in growing tumor and most probably representing nutritional starvation, upregulates hypoxia-inducible genes. This upregulation can occur in HIF-independent manner since hypoxia-inducible genes carbonic anhydrase 9 (CA9), lysyloxidase like 2 (LOXL2) and n-myc-down regulated 1 (NDRG1)/calcium activated protein (Cap43) can be upregulated by increased cell density under both normoxic and hypoxic conditions in both HIF-1 alpha-proficient and -deficient mouse fibroblasts. Moreover, cell density upregulates the same genes in 1HAEo- and A549 human lung epithelial cells. Searching for other transcription factors involved in the regulation of hypoxia-inducible genes by cell density, we focused our attention on ETS1. As reported previously, members of v-ets erythroblastosis virus E26 oncogene homolog (ETS) family transcription factors participate in the upregulation of hypoxia-inducible genes. Here, we provide evidence that ETS1 protein is upregulated at high cell density in both human and mouse cells. The involvement of ETS1 in the upregulation of hypoxia-inducible genes was further confirmed in a luciferase reporter assay using cotransfection of ETS1 expression vector with NDRG1/Cap43 promoter construct. The downregulation of ETS1 expression with small interfering RNA (siRNA) inhibited the upregulation of CA9 and NDRG1/Cap43caused by increased cell density. Collectively, our data indicate the involvement of ETS1 along with HIF-1 in regulating hypoxia-inducible genes.
C1 [Salnikow, Konstantin; Kaczmarek, Monika; Karaczyn, Aldona; Kasprzak, Kazimierz S.] NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
[Aprelikova, Olga; Tackett, Sean; Niederhuber, John] NCI, Lab Tumor & Stem Cell Biol, Bethesda, MD 20892 USA.
[Yee, Herman] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Ivanov, Sergey] NYU, Sch Med, Dept Cardiothorac Surg, New York, NY 10016 USA.
RP Salnikow, K (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
EM salnikow@ncifcrf.gov
OI Tackett, Sean/0000-0001-5369-7225; Ivanov, Sergey/0000-0001-9770-7237
FU Intramural NIH HHS [Z99 CA999999]
NR 41
TC 23
Z9 25
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2008
VL 29
IS 8
BP 1493
EP 1499
DI 10.1093/carcin/bgn088
PG 7
WC Oncology
SC Oncology
GA 337YR
UT WOS:000258471900004
PM 18381358
ER
PT J
AU Karami, S
Boffetta, P
Rothman, N
Hung, RJ
Stewart, T
Zaridze, D
Navritalova, M
Mates, D
Janout, V
Kollarova, H
Bencko, V
Szeszenia-Dabrowska, N
Holcatova, I
Mukeria, A
Gromiec, J
Chanock, SJ
Brennan, P
Chow, WH
Moore, LE
AF Karami, S.
Boffetta, P.
Rothman, N.
Hung, R. J.
Stewart, T.
Zaridze, D.
Navritalova, M.
Mates, D.
Janout, V.
Kollarova, H.
Bencko, V.
Szeszenia-Dabrowska, N.
Holcatova, I.
Mukeria, A.
Gromiec, J.
Chanock, S. J.
Brennan, P.
Chow, W. -H.
Moore, L. E.
TI Renal cell carcinoma, occupational pesticide exposure and modification
by glutathione S-transferase polymorphisms
SO CARCINOGENESIS
LA English
DT Article
ID RISK-FACTORS; CANCER-RISK; MODIFIERS; CHEMICALS; SMOKING; GSTT1
AB This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan (R) assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00-2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55-10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82-23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.
C1 [Karami, S.; Rothman, N.; Stewart, T.; Chow, W. -H.; Moore, L. E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
[Boffetta, P.; Hung, R. J.; Brennan, P.] Int Agcy Res Canc, F-69008 Lyon, France.
[Zaridze, D.; Mukeria, A.] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia.
[Janout, V.; Kollarova, H.] Palacky Univ, Fac Med, Dept Prevent Med, Olomouc 77515, Czech Republic.
[Bencko, V.; Holcatova, I.] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague 12800, Czech Republic.
[Navritalova, M.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic.
[Szeszenia-Dabrowska, N.] Inst Occupat Med, Dept Epidemiol, PL-90950 Lodz, Poland.
[Mates, D.] Inst Publ Hlth, Bucharest 050643, Romania.
[Chanock, S. J.] NCI, Core Genotyping Facil Adv Technol Ctr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
[Gromiec, J.] Nofer Inst Occupat Med, Dept Chem Hazards, PL-91311 Lodz, Poland.
RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
EM karamis@mail.nih.gov
RI Gromiec, Jan/G-4938-2010; Hung, Rayjean/A-7439-2013; Zaridze,
David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska,
Neonila/F-7190-2010;
OI mates, dana/0000-0002-6219-9807
NR 23
TC 35
Z9 36
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2008
VL 29
IS 8
BP 1567
EP 1571
DI 10.1093/carcin/bgn153
PG 5
WC Oncology
SC Oncology
GA 337YR
UT WOS:000258471900013
PM 18566013
ER
PT J
AU Park, Y
Kubo, A
Komiya, T
Coxon, A
Beebe, K
Neckers, L
Meltzer, PS
Kaye, FJ
AF Park, Yoonsoo
Kubo, Akihito
Komiya, Takefumi
Coxon, Amy
Beebe, Kristin
Neckers, Len
Meltzer, Paul S.
Kaye, Frederic J.
TI Low-penetrant RB allele in small-cell cancer shows geldanamycin
instability and discordant expression with mutant ras
SO CELL CYCLE
LA English
DT Article
DE low penetrance; retinoblastoma; Hsp90 inhibition; geldanamycin;
small-cell cancer
ID RETINOBLASTOMA GENE-PRODUCT; GERM-LINE MUTATIONS; LUNG-CANCER; FAMILIAL
RETINOBLASTOMA; INCOMPLETE PENETRANCE; UNILATERAL RETINOBLASTOMA; MILD
EXPRESSION; PROTEIN; BINDING; PHENOTYPE
AB Certain kindreds with low-penetrant (lp) retinoblastoma carry mutant alleles which retain partial tumor suppressor activity and we previously showed that these alleles exhibit defective, temperature-sensitive binding in yeast. To investigate the molecular basis for incomplete penetrance, we studied three recurrent lp alleles and observed approximately 50% of wildtype activity measured by (i) phosphorylation at key regulatory sites, S780, S795, S807/S811, (ii) transcriptional co-activation, and (iii) 'flat-cell' differentiation in mammalian cells in vivo. In addition, we studied a small-cell carcinoma that is homozygous for the R661W allele providing the first analysis of the effect of a naturally occurring lp allele in a human tumor. While we detected abundant expression of the R661W protein, we noted marked instability of both endogenous and recombinant R661W following treatment in vivo with the Hsp90 inhibitor, geldanamycin and stabilization of R661W following heat shock. In addition, we observed a discordant phenotype in the tumor cells with induction of p16 and loss of cyclin D1 consistent with a null RB status combined with homozygous expression of mutant ras which had not been reported previously for RB (-) small-cell cancer. These findings show that a recurrent missense lp allele retains greater functional activity in vivo than predicted from earlier in vitro assays, proposing a role for stabilizing chaperone-like activity in vivo. In addition, these data suggest that reversible protein instability and the requirement for a cooperating mutation may provide a stochastic explanation for the molecular basis of incomplete penetrance in kindreds carrying these alleles.
C1 [Park, Yoonsoo; Kubo, Akihito; Komiya, Takefumi; Coxon, Amy; Meltzer, Paul S.; Kaye, Frederic J.] Natl Naval Med Ctr, Genet Branch, Bethesda, MD 20889 USA.
[Beebe, Kristin; Neckers, Len] NCI, Canc Res Ctr, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Kaye, FJ (reprint author), Natl Naval Med Ctr, Genet Branch, Bldg 8,Rm 5101, Bethesda, MD 20889 USA.
EM kayef@mail.nih.gov
RI kaye, frederic/E-2437-2011
FU Intramural NIH HHS [Z01 SC007256-19]
NR 51
TC 6
Z9 6
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD AUG 1
PY 2008
VL 7
IS 15
BP 2384
EP 2391
PG 8
WC Cell Biology
SC Cell Biology
GA 343CI
UT WOS:000258829800017
PM 18677112
ER
PT J
AU Thomas, SL
Zhong, DS
Zhou, W
Malik, S
Liotta, D
Snyder, JP
Hamel, E
Giannakakou, P
AF Thomas, Shala L.
Zhong, Diansheng
Zhou, Wei
Malik, Sanna
Liotta, Dennis
Snyder, James P.
Hamel, Ernest
Giannakakou, Paraskevi
TI EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and
inhibits HIF-1
SO CELL CYCLE
LA English
DT Article
DE curcumin; structural analogs; HIF; microtubules; VHL
ID FACTOR-KAPPA-B; CANCER-CELLS; TUMOR-GROWTH; DOWN-REGULATION; TUBULIN;
ANGIOGENESIS; ANTICANCER; APOPTOSIS; PROTEIN; KINASE
AB Curcumin, the yellow pigment of the spice turmeric, has emerged as a promising anticancer agent due to its antiproliferative and anti-angiogenic properties. However, the molecular mechanism of action of this compound remains a subject of debate. In addition, curcumin's low bioavailability and efficacy profile in vivo further hinders its clinical development. This study focuses on the mechanism of action of EF24, a novel curcumin analog with greater than curcumin biological activity and bioavailability, but no increased toxicity. Treatment of MDA-MB231 breast and PC3 prostate cancer cells with EF24 or curcumin led to inhibition of HIF-1 alpha protein levels and, consequently, inhibition of HIF transcriptional activity. This drug-induced HIF inhibition occurred in a VHL-dependent but proteasome-independent manner. We found that, while curcumin inhibited HIF-1 alpha gene transcription, EF24 exerted its activity by inhibiting HIF-1 alpha posttranscriptionally. This result suggested that the two compounds are structurally similar but mechanistically distinct. Another cellular effect that further differentiated the two compounds was the ability of EF24, but not curcumin, to induce microtubule stabilization in cells. EF24 had no stabilizing effect on tubulin polymerization in an in vitro assay using purified bovine brain tubulin, suggesting that the EF24-induced cytoskeletal disruption in cells may be the result of upstream signaling events rather than EF24 direct binding to tubulin. In summary, our study identifies EF24 as a novel curcumin-related compound possessing a distinct mechanism of action, which we believe contributes to the potent anticancer activity of this agent and can be further exploited to investigate the therapeutic potential of EF24.
C1 [Giannakakou, Paraskevi] Cornell Univ, Weill Med Coll, Div Hematol & Med Oncol, New York, NY 10065 USA.
[Thomas, Shala L.] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
[Zhong, Diansheng; Zhou, Wei] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA.
[Malik, Sanna; Liotta, Dennis; Snyder, James P.] Emory Univ, Sch Med, Dept Chem, Atlanta, GA USA.
[Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA.
RP Giannakakou, P (reprint author), Cornell Univ, Weill Med Coll, Div Hematol & Med Oncol, 1300 York Ave,C610C, New York, NY 10065 USA.
EM pag2015@med.cornell.edu
OI Giannakakou, Paraskevi/0000-0001-7378-262X
FU NIH [CA100202, CA114335, CA116676]; [5P01CA116676-020002]
FX We would like to give our thanks to Aurora O'Brate and Vladimir
Belozerov for technical assistance and to Kathleen Kite-Powell for
editorial assistance. The work was supported in part by the NIH grants
CA100202, CA114335, and CA116676 to P. G.; VHL (to JPS); and
5P01CA116676-020002 to W.Z. (W.Z. is an American Cancer Society Research
Scholar and a Georgia Cancer Coalition Distinguished Scholar).
NR 31
TC 52
Z9 55
U1 0
U2 9
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD AUG 1
PY 2008
VL 7
IS 15
BP 2409
EP 2417
PG 9
WC Cell Biology
SC Cell Biology
GA 343CI
UT WOS:000258829800020
PM 18682687
ER
PT J
AU Yang, HT
Yu, HM
Fu, JD
Li, J
Wang, R
Liang, J
Guo, A
Wen, J
Shen, WH
Duan, SM
Boheler, KR
AF Yang, Huangtian
Yu, Huimei
Fu, Ji-Dong
Li, Jun
Wang, Rong
Liang, Ji
Guo, Ang
Wen, Jing
Shen, Wan-Hua
Duan, Shumin
Boheler, Kenneth R.
TI Regulation of Ca2+ signaling during differentiation of embryonic stem
cells into cardiomyocytes and neuronal cells
SO CELL RESEARCH
LA English
DT Meeting Abstract
DE murine embryonic stem cells; calcium signaling; cardiomyogenesis;
neurogenesis; endoplasmic reticulum; type 2 ryanodine receptor
C1 [Yang, Huangtian; Yu, Huimei; Fu, Ji-Dong; Li, Jun; Wang, Rong; Liang, Ji; Guo, Ang] CAS & SJUSM, SIBS, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China.
[Wen, Jing; Shen, Wan-Hua; Duan, Shumin] CAS, SIBS, Inst Neurosci, Shanghai 200031, Peoples R China.
[Boheler, Kenneth R.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
EM htyang@sibs.ac.cn
RI Shen, Wanhua/B-5554-2011
OI Shen, Wanhua/0000-0002-5178-9561
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD AUG
PY 2008
VL 18
SU 1
DI 10.1038/cr.2008.192
PG 1
WC Cell Biology
SC Cell Biology
GA 366AF
UT WOS:000260451000103
ER
PT J
AU Li, W
Ye, Y
AF Li, W.
Ye, Y.
TI Polyubiquitin chains: functions, structures, and mechanisms
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE ubiquitin; polyubiquitination; p97; UBA; proteasome; autophagy
ID UBIQUITIN-ASSOCIATED DOMAINS; KAPPA-B ACTIVATION; AAA-ATPASE;
TRANSCRIPTION FACTOR; U-BOX; MULTIUBIQUITIN CHAIN; CONJUGATING ENZYME;
CRYSTAL-STRUCTURE; PROTEIN; LIGASE
AB Ubiquitin is a highly conserved 76-aminoacid polypeptide that is found throughout the eukaryotic kingdom. The covalent conjugation of ubiquitin (often in the form of a polymer) to substrates governs a variety of biological processes ranging from proteolysis to DNA damage tolerance. The functional flexibility of this post-translational modification has its roots in the existence of a large number of ubiquitinating enzymes that catalyze the formation of distinct ubiquitin polymers, which in turn encode different signals. This review summarizes recent advances in the field with an emphasis on the non-canonical functions of polyubiquitination. We also discuss the potential mechanism of chain linkage specification as well as how structural disparity in ubiquitin polymers may be distinguished by ubiquitin receptors to translate the versatile ubiquitin signals into various cellular functions.
C1 [Li, W.; Ye, Y.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ye, Y (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room 433,5 Ctr Dr, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
FU Intramural NIH HHS [Z01 DK036137-01]
NR 82
TC 109
Z9 114
U1 1
U2 13
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 AUG
PY 2008
VL 65
IS 15
BP 2397
EP 2406
DI 10.1007/s00018-008-8090-6
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 335FJ
UT WOS:000258275900011
PM 18438605
ER
PT J
AU Gupta, PK
Liu, S
Batavia, MP
Leppla, SH
AF Gupta, Pradeep K.
Liu, Shihui
Batavia, Mariska P.
Leppla, Stephen H.
TI The diphthamide modification on elongation factor-2 renders mammalian
cells resistant to ricin
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID RIBOSOME-INACTIVATING PROTEINS; DIPHTHERIA-TOXIN-RESISTANCE;
ADP-RIBOSYLATING TOXINS; HAMSTER OVARY CELLS; SACCHAROMYCES-CEREVISIAE;
FACTOR-II; ANTHRAX TOXIN; TRANSLATION ELONGATION-FACTOR-2; HISTIDINE
PRECURSOR; BIOSYNTHESIS
AB Diphthamide is a post-translational derivative of histidine in protein synthesis elongation factor-2 (eEF-2) that is present in all eukaryotes with no known normal physiological role. Five proteins Dph1-Dph5 are required for the biosynthesis of diphthamide. Chinese hamster ovary (CHO) cells mutated in the biosynthetic genes lack diphthamide and are resistant to bacterial toxins such as diphtheria toxin. We found that diphthamide-deficient cultured cells were threefold more sensitive than their parental cells towards ricin, a ribosome-inactivating protein (RIP). RIPs bind to ribosomes at the same site as eEF-2 and cleave the large ribosomal RNA, inhibiting translation and causing cell death. We hypothesized that one role of diphthamide may be to protect ribosomes, and therefore all eukaryotic life forms, from RIPs, which are widely distributed in nature. A protective role of diphthamide against ricin was further demonstrated by complementation where dph mutant CHO cells transfected with the corresponding DPH gene acquired increased resistance to ricin in comparison with the control-transfected cells, and resembled the parental CHO cells in their response to the toxin. These data show that the presence of diphthamide in eEF-2 provides protection against ricin and suggest the hypothesis that diphthamide may have evolved to provide protection against RIPs.
C1 [Gupta, Pradeep K.; Liu, Shihui; Batavia, Mariska P.; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Leppla, SH (reprint author), NIAID, Lab Bacterial Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sleppla@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000929-05]
NR 36
TC 14
Z9 14
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD AUG
PY 2008
VL 10
IS 8
BP 1687
EP 1694
DI 10.1111/j.1462-5822.2008.01159.x
PG 8
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 326GY
UT WOS:000257647800011
PM 18460012
ER
PT J
AU Schmitt, JE
Lenroot, RK
Wallace, GL
Ordaz, S
Taylor, KN
Kabani, N
Greenstein, D
Lerch, JP
Kendler, KS
Neale, MC
Giedd, JN
AF Schmitt, J. E.
Lenroot, R. K.
Wallace, G. L.
Ordaz, S.
Taylor, K. N.
Kabani, N.
Greenstein, D.
Lerch, J. P.
Kendler, K. S.
Neale, M. C.
Giedd, J. N.
TI Identification of genetically mediated cortical networks: A multivariate
study of pediatric twins and siblings
SO CEREBRAL CORTEX
LA English
DT Article
DE child development; genetics; neuroanatomy; small world
ID PRIMATE CEREBRAL-CORTEX; HUMAN BRAIN; FUNCTIONAL CONNECTIVITY;
THEORETICAL NEUROANATOMY; MRI DATA; ORGANIZATION
AB Structural magnetic resonance imaging data from 308 twins, 64 singleton siblings of twins, and 228 singletons were analyzed using structural equation modeling and selected multivariate methods to identify genetically mediated intracortical associations. Principal components analyses (PCA) of the genetic correlation matrix indicated a single factor accounting for over 60% of the genetic variability in cortical thickness. When covaried for mean global cortical thickness, PCA, cluster analyses, and graph models identified genetically mediated fronto-parietal and occipital networks. Graph theoretical models suggest that the observed genetically mediated relationships follow small world architectural rules. These findings are largely concordant with other multivariate studies of brain structure and function, the twin literature, and current understanding on the role of genes in cortical neurodevelopment.
C1 [Lenroot, R. K.; Wallace, G. L.; Ordaz, S.; Taylor, K. N.; Greenstein, D.; Giedd, J. N.] NIMH, Child Psychiat Branch, Brain Imaging Unit, Bethesda, MD 20892 USA.
[Schmitt, J. E.; Kendler, K. S.; Neale, M. C.] Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA.
[Lerch, J. P.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Kabani, N.] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada.
RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Brain Imaging Unit, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA.
EM jg@nih.gov
RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace,
Gregory/0000-0003-0329-5054
FU Intramural NIH HHS; NIDA NIH HHS [DA-18673, R37 DA018673, R37
DA018673-02, R37 DA018673-03, R37 DA018673-04, R37 DA018673-05]; NIMH
NIH HHS [MH-65322, MH-20030, R01 MH065322, R01 MH065322-01A1, R01
MH065322-02, R01 MH065322-03, R01 MH065322-04, R01 MH065322-05, T32
MH020030, T32 MH020030-01, T32 MH020030-02, T32 MH020030-03, T32
MH020030-04, T32 MH020030-05, T32 MH020030-06, T32 MH020030-07, T32
MH020030-08, T32 MH020030-09, T32 MH020030-10, T32 MH020030-11]
NR 46
TC 89
Z9 91
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD AUG
PY 2008
VL 18
IS 8
BP 1737
EP 1747
DI 10.1093/cercor/bhm211
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 328GV
UT WOS:000257787300001
PM 18234689
ER
PT J
AU Meltzer, JA
Zaveri, HP
Goncharova, II
Distasio, MM
Papademetris, X
Spencer, SS
Spencer, DD
Constable, RT
AF Meltzer, Jed A.
Zaveri, Hitten P.
Goncharova, Irina I.
Distasio, Marcello M.
Papademetris, Xenophon
Spencer, Susan S.
Spencer, Dennis D.
Constable, R. Todd
TI Effects of working memory load on oscillatory power in human
intracranial EEG
SO CEREBRAL CORTEX
LA English
DT Article
DE alpha; BOLD; ECoG; fMRI; gamma; Sternberg; theta
ID FRONTAL MIDLINE THETA; ANTERIOR CINGULATE CORTEX; MEDIAL TEMPORAL-LOBE;
GAMMA-OSCILLATIONS; PREFRONTAL CORTEX; ALPHA-RHYTHM; HUMAN BRAIN;
VISUAL-CORTEX; BOLD RESPONSE; TASK
AB Studies of working memory load effects on human EEG power have indicated divergent effects in different frequency bands. Although gamma power typically increases with load, the load dependency of the lower frequency theta and alpha bands is uncertain. We obtained intracranial electroencephalography measurements from 1453 electrode sites in 14 epilepsy patients performing a Sternberg task, in order to characterize the anatomical distribution of load-related changes across the frequency spectrum. Gamma power increases occurred throughout the brain, but were most common in the occipital lobe. In the theta and alpha bands, both increases and decreases were observed, but with different anatomical distributions. Increases in theta and alpha power were most prevalent in frontal midline cortex. Decreases were most commonly observed in occipital cortex, colocalized with increases in the gamma range, but were also detected in lateral frontal and parietal regions. Spatial overlap with group functional magnetic resonance imaging results was minimal except in the precentral gyrus. These findings suggest that power in any given frequency band is not a unitary phenomenon; rather, reactivity in the same frequency band varies in different brain regions, and may relate to the engagement or inhibition of a given area in a cognitive task.
C1 [Meltzer, Jed A.; Constable, R. Todd] Yale Univ, Interdept Neurosci Program, New Haven, CT 06510 USA.
[Zaveri, Hitten P.; Goncharova, Irina I.; Spencer, Susan S.] Yale Univ, Dept Neurol, New Haven, CT 06510 USA.
[Distasio, Marcello M.; Papademetris, Xenophon; Constable, R. Todd] Yale Univ, Dept Biomed Engn, New Haven, CT 06510 USA.
[Papademetris, Xenophon; Constable, R. Todd] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA.
[Spencer, Dennis D.; Constable, R. Todd] Yale Univ, Dept Neurosurg, New Haven, CT 06510 USA.
RP Meltzer, JA (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bldg 10,Room 5C410,10 Ctr Dr, Bethesda, MD 20852 USA.
EM jed.meltzer@aya.yale.edu
FU NIBIB NIH HHS [R01 EB006494]; NINDS NIH HHS [R01 NS051622]
NR 70
TC 69
Z9 70
U1 1
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD AUG
PY 2008
VL 18
IS 8
BP 1843
EP 1855
DI 10.1093/cercor/bhm213
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 328GV
UT WOS:000257787300010
PM 18056698
ER
PT J
AU Muller, MM
Andersen, SK
Keil, A
AF Mueller, Matthias M.
Andersen, Soren K.
Keil, Andreas
TI Time course of competition for visual processing resources between
emotional pictures and foreground task
SO CEREBRAL CORTEX
LA English
DT Article
DE attention; biased competition; emotion; human EEG
ID SPATIAL SELECTIVE ATTENTION; MOTIVATED ATTENTION; EVOKED POTENTIALS;
FEARFUL FACES; MODULATION; CORTEX; FMRI; ACTIVATION; STIMULI; BRAIN
AB High-arousing emotional stimuli facilitate early visual cortex, thereby acting as strong competitors for processing resources in visual cortex. The present study used an electrophysiological approach for continuously measuring the time course of competition for processing resources in the visual pathway arising from emotionally salient but task-irrelevant input while performing a foreground target detection task. Steady-state visual evoked potentials (SSVEPs) were recorded to rapidly flickering squares superimposed upon neutral and emotionally high-arousing pictures, and variations in SSVEP amplitude over time were calculated. As reflected in SSVEP amplitude and target detection rates, arousing emotional background pictures withdrew processing resources from the detection task compared with neutral ones for several hundred milliseconds after stimulus onset. SSVEP amplitude was found to bear a close temporal relationship with accurate target detection as a function of time after stimulus onset.
C1 [Mueller, Matthias M.; Andersen, Soren K.] Univ Leipzig, Inst Psychol 1, D-04103 Leipzig, Germany.
[Keil, Andreas] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA.
RP Muller, MM (reprint author), Univ Leipzig, Inst Psychol 1, Seeburgstr 14-20, D-04103 Leipzig, Germany.
EM m.mueller@rz.uni-leipzig.de
RI Andersen, Soren K./E-4497-2010; Keil, Andreas/F-9427-2011
OI Andersen, Soren K./0000-0002-7612-0127; Keil,
Andreas/0000-0002-4064-1924
NR 39
TC 65
Z9 66
U1 2
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD AUG
PY 2008
VL 18
IS 8
BP 1892
EP 1899
DI 10.1093/cercor/bhm215
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 328GV
UT WOS:000257787300015
PM 18063562
ER
PT J
AU Hester, R
Barre, N
Murphy, K
Silk, TJ
Mattingley, JB
AF Hester, Robert
Barre, Natalie
Murphy, Kevin
Silk, Tim J.
Mattingley, Jason B.
TI Human medial frontal cortex activity predicts learning from errors
SO CEREBRAL CORTEX
LA English
DT Article
DE anterior cingulate cortex; associative learning; error processing;
functional MRI
ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; PREFRONTAL CORTEX;
HIPPOCAMPAL-FORMATION; COGNITIVE CONTROL; DECISION-MAKING; FUNCTIONAL
MRI; REWARD; PERFORMANCE; SELECTION
AB Learning from errors is a critical feature of human cognition. It underlies our ability to adapt to changing environmental demands and to tune behavior for optimal performance. The posterior medial frontal cortex (pMFC) has been implicated in the evaluation of errors to control behavior, although it has not previously been shown that activity in this region predicts learning from errors. Using functional magnetic resonance imaging, we examined activity in the pMFC during an associative learning task in which participants had to recall the spatial locations of 2-digit targets and were provided with immediate feedback regarding accuracy. Activity within the pMFC was significantly greater for errors that were subsequently corrected than for errors that were repeated. Moreover, pMFC activity during recall errors predicted future responses (correct vs. incorrect), despite a sizeable interval (on average 70 s) between an error and the next presentation of the same recall probe. Activity within the hippocampus also predicted future performance and correlated with error-feedback-related pMFC activity. A relationship between performance expectations and pMFC activity, in the absence of differing reinforcement value for errors, is consistent with the idea that error-related pMFC activity reflects the extent to which an outcome is "worse than expected.".
C1 [Hester, Robert] Univ Queensland, Queensland Brain Inst, Cognit Neurosci Lab, St Lucia, Qld 4072, Australia.
[Barre, Natalie] Univ Melbourne, Sch Behav Sci, Melbourne, Vic 3010, Australia.
[Murphy, Kevin] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Hester, Robert; Silk, Tim J.; Mattingley, Jason B.] Univ Queensland, Sch Psychol, St Lucia, Qld 4072, Australia.
RP Hester, R (reprint author), Univ Queensland, Queensland Brain Inst, Cognit Neurosci Lab, St Lucia, Qld 4072, Australia.
EM r.hester@uq.edu.au
RI Murphy, Kevin/A-1581-2010; Mattingley, Jason/J-1537-2014;
OI Murphy, Kevin/0000-0002-6516-313X; Mattingley,
Jason/0000-0003-0929-9216; Silk, Tim/0000-0002-7290-512X; Hester,
Robert/0000-0003-0982-8026
NR 49
TC 30
Z9 31
U1 2
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD AUG
PY 2008
VL 18
IS 8
BP 1933
EP 1940
DI 10.1093/cercor/bhm219
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 328GV
UT WOS:000257787300019
PM 18063560
ER
PT J
AU Murphy, E
Steenbergen, C
AF Murphy, Elizabeth
Steenbergen, Charles
TI Does inhibition of glycogen synthase kinase protect in mice?
SO CIRCULATION RESEARCH
LA English
DT Editorial Material
DE glycogen synthase kinase; cardioprotection; ischemia; signaling
ID REPERFUSION
C1 [Murphy, Elizabeth] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
RP Murphy, E (reprint author), NHLBI, Vasc Med Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [R01 HL039752, R01
HL039752-20, R01-HL-39752]
NR 8
TC 21
Z9 21
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD AUG 1
PY 2008
VL 103
IS 3
BP 226
EP 228
DI 10.1161/CIRCRESAHA.108.181602
PG 3
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 332PZ
UT WOS:000258096900002
PM 18669927
ER
PT J
AU Ngo, TD
Laeyendecker, O
Morrow, RA
Lai, S
Quinn, TC
AF Ngo, Thoai D.
Laeyendecker, Oliver
Morrow, Rhoda Ashley
Lai, Shenghan
Quinn, Thomas C.
TI Comparison of three commercial immunoassays for detection of herpes
simplex virus type 2 antibodies in commercial sex workers in Yunnan
Province, China
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID LINKED-IMMUNOSORBENT-ASSAY; ENZYME IMMUNOASSAYS; PERFORMANCE; INFECTION;
DISEASE; VERIFICATION; UGANDA; RAKAI; TESTS; ELISA
AB Five hundred commercial sex workers in China were tested for herpes simplex virus type 2 by three immunoassays and Western blotting. Sensitivities for the Focus, Kalon, and Biokit assays were 86.7%, 82.3%, and 34.9%, respectively, and specificities were 91.8%, 94.2%, and 60.1%, respectively. The Focus assay performed optimally at an index of 1.5 (95.2% sensitivity and 93.4% specificity), and the Kalon assay performed optimally at an index of 1.2 (93.3% sensitivity and 95.2% specificity).
C1 [Ngo, Thoai D.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Morrow, Rhoda Ashley] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Lai, Shenghan] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Dept Infect Dis, 1721 E Madison St,Ross Bldg,Room 1159, Baltimore, MD 21205 USA.
EM tquinn@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU Division of Intramural Research; NIAID; NIH
FX This research was supported by the Division of Intramural Research,
NIAID, NIH.
NR 20
TC 4
Z9 4
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD AUG
PY 2008
VL 15
IS 8
BP 1301
EP 1303
DI 10.1128/CVI.00006-08
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 340TF
UT WOS:000258667200023
PM 18508932
ER
PT J
AU Soldin, OP
Dahlin, JRB
Gresham, EG
King, J
Soldin, SJ
AF Soldin, Offie P.
Dahlin, Julia R. B.
Gresham, Eric G.
King, Julia
Soldin, Steven J.
TI IMMULITE (R) 2000 age and sex-specific reference intervals for alpha
fetoprotein, homocysteine, insulin, insulin-like growth factor-1,
insulin-like growth factor binding protein-3, C-peptide, immunoglobulin
E and intact parathyroid hormone
SO CLINICAL BIOCHEMISTRY
LA English
DT Article
DE pediatric; reference intervals; alpha fetoprotein; homocysteine;
insulin; insulin-like growth factor-I; insulin-like growth factor
binding protein-3; C-peptide; immunoglobulin E; parathyroid hormone
ID PEDIATRIC REFERENCE INTERVALS; TANDEM-MASS-SPECTROMETRY; CLINICAL
UTILITY; REFERENCE RANGES; CHILDREN; TRANSFERRIN; RESISTANCE; PREGNANCY;
CORTISOL; IRON
AB Objectives: To determine age and sex-specific pediatric reference intervals for serum alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and parathyroid hormone.
Design and methods: The study was conducted at both Children's National Medical Center and Georgetown University, Washington D.C. Results for the above analytes were obtained from the Children's National Medical Center laboratory information system over the period of 1151 2001-3/8/2007. Patient results using the IMMULITE 2000(R) were accessed and used to establish reference intervals for the analytes studied. All patient identifiers were removed except age and sex. Analysis of the data was performed at Georgetown University in the Bioanalytical Core Laboratory. The data was analyzed using the Hoffmann approach, and was computer adapted. The number of patient samples studied varied with each analyte and were: Alpha fetoprotein (557), homocysteine (924), insulin-like growth factor-I (1352), insulin-like growth factor binding protein-3 (711), insulin (3239), C-peptide (267), immunoglobulin E (2691) and parathyroid hormone (513).
Results and conclusions: This study provides pediatric reference intervals for the eight analytes for children from birth to 18 years of age. All the analytes exhibited at least some age dependence, Sex differences between early and late childhood and adolescence were also frequently found. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
C1 [Soldin, Offie P.; Soldin, Steven J.] Georgetown Univ, Bioanalyt Core Lab, Med Ctr, Dept Med, Washington, DC 20057 USA.
[Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Oncol Physiol, Washington, DC 20057 USA.
[Soldin, Offie P.] US FDA, Ctr Drug Evaluat & Res, Obstet Pharmacol Res Network, Natl Inst Child Hlth & Dev, Rockville, MD 20857 USA.
[Dahlin, Julia R. B.; Gresham, Eric G.; King, Julia; Soldin, Steven J.] George Washington Univ, Dept Pediat & Pathol, Washington, DC USA.
[Dahlin, Julia R. B.; Gresham, Eric G.; King, Julia; Soldin, Steven J.] Childrens Natl Med Ctr, Dept Lab Med, Washington, DC 20010 USA.
RP Soldin, SJ (reprint author), Georgetown Univ, Bioanalyt Core Lab, Med Ctr, Dept Med, 3800 Reservoir Rd, Washington, DC 20057 USA.
EM sjs44@georgetown.edu
FU NCRR NIH HHS [M01 RR020359, M01 RR023942, M01RR-023942]; NICHD NIH HHS
[1 U10HD45993-02, U10 HD045993, U10 HD047890]
NR 25
TC 23
Z9 23
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0009-9120
J9 CLIN BIOCHEM
JI Clin. Biochem.
PD AUG
PY 2008
VL 41
IS 12
BP 937
EP 942
DI 10.1016/j.clinbiochem.2008.04.025
PG 6
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 330ZF
UT WOS:000257980700003
PM 18503765
ER
PT J
AU Sharifi, N
Dahut, WL
Figg, WD
AF Sharifi, Nima
Dahut, William L.
Figg, William D.
TI The genetics of castration-resistant prostate cancer: What can the
germline tell us?
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ANDROGEN-DEPRIVATION THERAPY; RESPONSIVE GENES; HORMONE-THERAPY;
RECEPTOR; TESTOSTERONE; EXPRESSION; RADIATION; BIOLOGY; MEN
AB Androgen deprivation therapy (ADT) is the cornerstone treatment for advanced prostate cancer. Despite frequent responses, the majority of metastatic tumors will progress to castration-resistant prostate cancer. Numerous molecular and genetic perturbations have been described in castration-resistant prostate cancer, which are attributable for gain-of-function changes in the androgen receptor, allowing for cell survival and proliferation with castrate levels of testosterone. The utility of these somatic perturbations, which are selected for in the tumor after ADT, for prognostication of response and response duration in metastatic prostate cancer, is problematic. Here, we discuss recent studies that describe germline polymorphisms that determine the response to ADT. Coding and noncoding germline polymorphisms in genes involved in the androgen pathway affect the response to ADT These polymorphisms require further study and validation. However, they have the potential to be useful for prognosticating the response to ADT, designing clinical trials for patients who have poor germline prognostic features and designing novel therapies targeted against genes that influence the response to ADT.
C1 [Sharifi, Nima] Univ Texas SW Med Ctr Dallas, Div Hematol Oncol, Dallas, TX 75390 USA.
[Dahut, William L.; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Sharifi, N (reprint author), Univ Texas SW Med Ctr Dallas, Div Hematol Oncol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM sharifi@utsouthwestern.edu
RI Figg Sr, William/M-2411-2016
FU Intramural NIH HHS [Z01 BC010627-04]
NR 22
TC 8
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 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2008
VL 14
IS 15
BP 4691
EP 4693
DI 10.1158/1078-0432.CCR-08-0453
PG 3
WC Oncology
SC Oncology
GA 334JD
UT WOS:000258217200004
PM 18676736
ER
PT J
AU Nickerson, ML
Jaeger, E
Shi, Y
Durocher, JA
Mahurkar, S
Zaridze, D
Matveev, V
Janout, V
Kollarova, H
Bencko, V
Navratilova, M
Szeszenia-Dabrowska, N
Mates, D
Mukeria, A
Holcatova, I
Schmidt, LS
Toro, JR
Karami, S
Hung, R
Gerard, GF
Linehan, WM
Merino, M
Zbar, B
Boffetta, P
Brennan, P
Rothman, N
Chow, WH
Waldman, FM
Moore, LE
AF Nickerson, Michael L.
Jaeger, Erich
Shi, Yangu
Durocher, Jeffrey A.
Mahurkar, Sunil
Zaridze, David
Matveev, Vsevolod
Janout, Vladimir
Kollarova, Hellena
Bencko, Vladimir
Navratilova, Marie
Szeszenia-Dabrowska, Neonilia
Mates, Dana
Mukeria, Anush
Holcatova, Ivana
Schmidt, Laura S.
Toro, Jorge R.
Karami, Sara
Hung, Rayjean
Gerard, Gary F.
Linehan, W. Marston
Merino, Maria
Zbar, Berton
Boffetta, Paolo
Brennan, Paul
Rothman, Nathaniel
Chow, Wong-Ho
Waldman, Frederic M.
Moore, Lee E.
TI Improved identification of von Hippel-Lindau gene alterations in clear
cell renal tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SUPPRESSOR GENE; VHL GENE; GERMLINE MUTATIONS; CARCINOMA; CANCER;
KIDNEY; NUCLEASE; CLONING
AB Purpose: To provide a comprehensive, thorough analysis of somatic mutation and promoter hypermethylation of the von Hippel-Lindau (VHL) gene in the cancer genome, unique to clear cell renal cancer (ccRCC). Identify relationships between the prevalence of VK gene alterations and alteration subtypes with patient and tumor characteristics. Experimental Design: As part of a large kidney cancer case-control study conducted in Central Europe, we analyzed VHL mutations and promoter methylation in 205 well-characterized, histologically confirmed patient tumor biopsies using a combination of sensitive, high-throughput methods (endonuclease scanning and Sanger sequencing) and analysis of 11 CpG sites in the VHL promoter.
Results: We identified mutations in 82.4% of cases, the highest VHL gene mutation prevalence reported to date. Analysis of 11 VHL promoter CpG sites revealed that 8.3% of tumors were hypermethylated and all were mutation negative. In total, 91% of ccRCCs exhibited alteration of the gene through genetic or epigenetic mechanisms. Analysis of patient and tumor characteristics revealed that certain mutation subtypes were significantly associated with Fuhrman nuclear grade, metastasis, node positivity, and self-reported family history of RCC.
Conclusion: Detection of VHL gene alterations using these accurate, sensitive, and practical methods provides evidence that the vast majority of histologically confirmed ccRCC tumors possess genetic or epigenetic alteration of the VHL gene and support the hypothesis that VHL alteration is an early event in ccRCC carcinogenesis. These findings also indicate that VHL molecular subtypes can provide a sensitive marker of tumor heterogeneity among histologically similar ccRCC cases for etiologic, prognostic, and translational studies.
C1 [Toro, Jorge R.; Karami, Sara; Rothman, Nathaniel; Chow, Wong-Ho; Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
[Jaeger, Erich; Waldman, Frederic M.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
[Zaridze, David; Matveev, Vsevolod; Mukeria, Anush] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Janout, Vladimir; Kollarova, Hellena] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic.
[Bencko, Vladimir; Holcatova, Ivana] Charles Univ Prague, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Navratilova, Marie] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
[Schmidt, Laura S.] Natl Can Inst Frederick, Basic Res Program, Sci Applicat Int Corp, Frederick, MD USA.
[Zbar, Berton] NCI, Immunobiol Lab, NIH, Frederick, MD 21701 USA.
[Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20852 USA.
[Hung, Rayjean] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Hung, Rayjean; Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS Room 8102, Bethesda, MD 20852 USA.
EM mrnick@frontiernet.net; moorele@mail.nih.gov
RI Hung, Rayjean/A-7439-2013; Zaridze, David/K-5605-2013; Janout,
Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010;
OI mates, dana/0000-0002-6219-9807
FU Intramural NIH HHS [Z01 SC006659-25]; NCI NIH HHS [CA102600, N01
CO012400, N01-CO-12400, R01 CA102600]
NR 31
TC 216
Z9 225
U1 2
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2008
VL 14
IS 15
BP 4726
EP 4734
DI 10.1158/1078-0432.CCR-07-4921
PG 9
WC Oncology
SC Oncology
GA 334JD
UT WOS:000258217200009
PM 18676741
ER
PT J
AU Mackall, CL
Rhee, EH
Read, EJ
Khuu, HM
Leitman, SF
Bernstein, D
Tesso, M
Long, LM
Grindler, D
Merino, M
Kopp, W
Tsokos, M
Berzofsky, JA
Helman, LJ
AF Mackall, Crystal L.
Rhee, Eunice H.
Read, Elizabeth J.
Khuu, Hanh M.
Leitman, Susan F.
Bernstein, Donna
Tesso, Merertu
Long, Lauren M.
Grindler, David
Merino, Margret
Kopp, William
Tsokos, Maria
Berzofsky, Jay A.
Helman, Lee J.
TI A pilot study of consolidative immunotherapy in patients with high-risk
pediatric sarcomas
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HIGH-DOSE THERAPY; PRIMITIVE NEUROECTODERMAL TUMOR;
BONE-MARROW-TRANSPLANTATION; PULSED DENDRITIC CELLS; TOTAL-BODY
IRRADIATION; STAGE-IV MELANOMA; T-CELLS; EWINGS-SARCOMA; INTERGROUP
RHABDOMYOSARCOMA; ALVEOLAR RHABDOMYOSARCOMA
AB Purpose: Patients with metastatic or recurrent Ewing's sarcoma family of tumors and alveolar rhabdomyosarcoma have < 25% 5-year survival in most studies. This study administered a novel immunotherapy regimen aimed at consolidating remission in these patients.
Experimental Design: Fifty-two patients with translocation positive, recurrent, or metastatic Ewing's sarcoma family of tumors or alveolar rhabdomyosarcoma underwent prechemotherapy cell harvest via apheresis for potential receipt of immunotherapy. Following completion of standard multimodal therapy, 30 patients ultimately initiated immunotherapy and were sequentially assigned to three cohorts. All cohorts received autologous T cells, influenza vaccinations, and dendritic cells pulsed with peptides derived from tumor-specific translocation breakpoints and E7, a peptide known to bind HLA-A2. Cohort 1 received moderate-dose recombinant human interleukin-2 (rhIL-2), cohort 2 received low-dose rhIL-2, and cohort 3 did not receive rhIL-2.
Results: All immunotherapy recipients generated influenza-specific immune responses, whereas immune responses to the translocation breakpoint peptides occurred in 39%, and only 25% of HLA-A2(+) patients developed E7-specific responses. Toxicity was minimal. Intention-to-treat analysis revealed a 31% 5-year overall survival for all patients apheresed (median potential follow-up 7.3 years) with a 43% 5-year overall survival for patients initiating immunotherapy.
Conclusions: Consoliclative immunotherapy is a scientifically based and clinically practical approach for integrating immunotherapy into a multimodal regimen for chemoresponsive cancer. Patients receiving immunotherapy experienced minimal toxicity and favorable survival. The robust influenza immune responses observed suggest that postchemotherapy immune incompetence will not fundamentally limit this approach. Future studies will seek to increase efficacy by using more immunogenic antigens and more potent dendritic cells.
C1 [Mackall, Crystal L.; Rhee, Eunice H.; Bernstein, Donna; Long, Lauren M.; Grindler, David; Merino, Margret; Helman, Lee J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Tsokos, Maria] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Read, Elizabeth J.; Khuu, Hanh M.] NIH, Cell Proc Sect, Bethesda, MD 20892 USA.
[Leitman, Susan F.] NIH, Apheresis Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Tesso, Merertu] HarrisTech Serv Corp, Colorado Springs, CO USA.
[Kopp, William] SAIC Frederick Inc, NCI, Clin Support Lab, Frederick, MD USA.
RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, 10-CRC lW-3940,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA.
EM cm35c@nih.gov
FU Intramural NIH HHS [Z01 SC010289-08]; PHS HHS [N01-C0-12400]
NR 53
TC 66
Z9 76
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2008
VL 14
IS 15
BP 4850
EP 4858
DI 10.1158/1078-0432.CCR-07-4065
PG 9
WC Oncology
SC Oncology
GA 334JD
UT WOS:000258217200026
PM 18676758
ER
PT J
AU Acton, RT
Barton, JC
Passmore, LV
Adams, PC
Mclaren, GD
Leiendecker-Foster, C
Speechley, MR
Harris, EL
Castro, O
Reiss, JA
Snively, BM
Harrison, BW
Mclaren, CE
AF Acton, Ronald T.
Barton, James C.
Passmore, Leah V.
Adams, Paul C.
Mclaren, Gordon D.
Leiendecker-Foster, Catherine
Speechley, Mark R.
Harris, Emily L.
Castro, Oswaldo
Reiss, Jacob A.
Snively, Beverly M.
Harrison, Barbara W.
Mclaren, Christine E.
TI Accuracy of family history of hemochromatosis or iron overload: The
Hemochromatosis and Iron Overload Screening Study
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
ID HEREDITARY HEMOCHROMATOSIS; RISK; DISEASE; SURVIVAL; HEALTH; DEATH;
HEIRS
AB Background & Aims: The aim of this study was to assess the analytic validity of self-reported family history of hemochromatosis or iron overload. Methods: A total of 141 probands, 549 family members, and 641 controls participated in the primary care Hemochromatosis and Iron Overload Screening Study. Participants received a postscreening clinical examination and completed questionnaires about personal and family histories of hemochromatosis or iron overload, arthritis, diabetes, liver disease, and heart disease. We evaluated sensitivities and specificities of proband-reported family history, and concordance of HFE genotype C282Y/C282Y in probands and siblings who reported having hemochromatosis or iron overload. Results: The sensitivities of proband-reported family history ranged from 81.4% for hemochromatosis or iron overload to 18.4% for liver disease; specificities for diabetes, liver disease, and heart disease were greater than 94%. Hemochromatosis or iron overload was associated with a positive family history across all racial/ethnic groups in the study (odds ratio, 14.53; 95% confidence intervals, 7.41-28.49; P <.0001) and among Caucasians (odds ratio, 16.98; 95% confidence intervals, 7.53-38.32; P <.0001). There was 100% concordance of HFE genotype C282Y/C282Y in 6 probands and 8 of their siblings who reported having hemochromatosis or iron overload. Conclusions: Self-reported family history of hemochromatosis or iron overload can be used to identify individuals whose risk of hemochromatosis or iron overload and associated conditions is increased. These individuals could benefit from further evaluation with iron phenotyping and HFE mutation analysis.
C1 [Acton, Ronald T.] Univ Alabama, Dept Microbiol, Birmingham, AL 35209 USA.
[Acton, Ronald T.] Univ Alabama, Dept Med, Birmingham, AL 35209 USA.
[Acton, Ronald T.] Univ Alabama, Dept Genet, Birmingham, AL 35209 USA.
[Acton, Ronald T.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35209 USA.
[Acton, Ronald T.] Univ Alabama, Dept Int Hlth, Birmingham, AL 35209 USA.
[Barton, James C.] So Iron Disorders Ctr, Birmingham, AL USA.
[Passmore, Leah V.; Snively, Beverly M.] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA.
[Adams, Paul C.] London Hlth Sci Ctr, Dept Med, London, ON, Canada.
[Mclaren, Gordon D.] 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.
[Leiendecker-Foster, Catherine] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Speechley, Mark R.] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada.
[Harris, Emily L.] NHGRI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Harrison, Barbara W.] Howard Univ, Div Med Genet, Washington, DC 20059 USA.
[Castro, Oswaldo] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Reiss, Jacob A.] Kaiser Permanente NW, Dept Genet, Portland, OR USA.
[Mclaren, Christine E.] Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA.
RP Acton, RT (reprint author), Univ Alabama, Dept Microbiol, 265 MCLM,1530 3rd Ave S, Birmingham, AL 35209 USA.
EM acton@uab.edu
FU NCI NIH HHS [P30 CA062203]; NCRR NIH HHS [M01 RR010284, M01 RR000032,
M01-RR00032, M01-RR10284, M01 RR000827]; NHLBI NIH HHS [UH1 HL003679,
UH1-HL03679-05, N01 HC005192, N01-HC-05189, N01HC05191, N01-HC-05188,
N01HC05190, N01-HC-05186, N01HC05185, N01HC05189, N01HC05188,
N01HC05186, N01HV48141, N01-HC-05191, N01-HC-05190, N01-HC-05185,
HV48141]
NR 30
TC 6
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD AUG
PY 2008
VL 6
IS 8
BP 934
EP 938
DI 10.1016/j.cgh.2008.04.003
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 335LQ
UT WOS:000258292500019
PM 18585964
ER
PT J
AU Svenson, JL
EuDaly, J
Ruiz, P
Korach, KS
Gilkeson, GS
AF Svenson, John L.
EuDaly, Jackie
Ruiz, Phil
Korach, Kenneth S.
Gilkeson, Gary S.
TI Impact of estrogen receptor deficiency on disease expression in the
NZM2410 lupus prone mouse
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE lupus; estrogen receptors; renal disease; autoimmunity
ID SEX-HORMONES; NULL MICE; AUTOIMMUNE-DISEASE; ERYTHEMATOSUS; APOPTOSIS;
SLE; MECHANISMS; ANTIBODIES; INDUCTION; RESPONSES
AB Systemic lupus erythematosus (SLE) occurs nine times more often in females than mates. The purpose of this study was to determine the impact of estrogen receptor (ER) null genotypes on disease in lupus prone NZM2410 (NZM) and MRL/lpr mice, as a method to define the role of estrogen receptor signaling in lupus. ER alpha deficient NZM females, but not mates, had significantly prolonged survival, reduced proteinuria, renal pathology scores and serum urea nitrogen levels compared to wildtype mice, despite higher serum anti-dsDNA levels. ER alpha deficient. MRL/lpr female, but not mate, mice also had significantly less proteinuria and renal pathology scores with no effect on autoantibody levels. Deficiency of ER beta had no effect on disease in either strain or sex. Taken together, these data demonstrate a key rote for ER alpha, but not ER 3, in the development of lupus like disease, but not autoimmunity, in female NZM and MRL/lpr mice. Published by Elsevier Inc.
C1 [Svenson, John L.; EuDaly, Jackie; Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Ruiz, Phil] Univ Miami, Sch Med, Dept Pathol, Miami, FL 33136 USA.
[Korach, Kenneth S.] NIEHS, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Gilkeson, GS (reprint author), Med Univ S Carolina, 96 Jonathan Lucas St,Suite 912,POB 250637, Charleston, SC 29425 USA.
EM gilkeson@musc.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU Intramural NIH HHS [Z01 ES070065-32]
NR 24
TC 40
Z9 40
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD AUG
PY 2008
VL 128
IS 2
BP 259
EP 268
DI 10.1016/j.clim.2008.03.508
PG 10
WC Immunology
SC Immunology
GA 330LA
UT WOS:000257941400016
PM 18514033
ER
PT J
AU Walsh, TJ
Kontoyiannis, DP
AF Walsh, Thomas J.
Kontoyiannis, Dimitrios P.
TI What is the role of combination therapy in management of zygomycosis?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID COLONY-STIMULATING FACTOR; B LIPID COMPLEX; PLUS AMPHOTERICIN-B;
INVASIVE ASPERGILLOSIS; SALVAGE THERAPY; GRANULOCYTE TRANSFUSIONS;
PULMONARY ASPERGILLOSIS; ANTIFUNGAL THERAPY; PEDIATRIC-PATIENTS;
CANDIDA-ALBICANS
C1 [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, CRC, Bethesda, MD 20892 USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, CRC, Rm 1-5750, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
NR 40
TC 17
Z9 18
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 1
PY 2008
VL 47
IS 3
BP 372
EP 374
DI 10.1086/589858
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 322UH
UT WOS:000257400300009
PM 18558877
ER
PT J
AU Hare, CB
Mellors, J
Krambrink, A
Su, ZH
Skiest, D
Margolis, DM
Patel, SS
Barnas, D
Frenkel, L
Coombs, RW
Aweeka, F
Morse, GD
Haas, DW
Boltz, V
Palmer, S
Coffin, J
Havlir, DV
AF Hare, C. Bradley
Mellors, John
Krambrink, Amy
Su, Zhaohui
Skiest, Daniel
Margolis, David M.
Patel, Sheran S.
Barnas, Douglas
Frenkel, Lisa
Coombs, Robert W.
Aweeka, Francesca
Morse, Gene D.
Haas, David W.
Boltz, Valerie
Palmer, Sarah
Coffin, John
Havlir, Diane V.
TI Detection of nonnucleoside reverse-transcriptase inhibitor-resistant
HIV-1 after discontinuation of virologically suppressive antiretroviral
therapy
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DRUG-RESISTANCE; TREATMENT INTERRUPTION;
INFECTED PATIENTS; INTERMITTENT; PERSISTENCE; VIREMIA; EFAVIRENZ;
EVOLUTION; FAILURE
AB Using standard and ultrasensitive techniques, we detected nonnucleoside reverse-transcriptase inhibitor-associated resistance mutations in 11 (20%) of 54 subjects who discontinued virologically suppressive nonnucleoside reverse-transcriptase inhibitor-containing antiretroviral therapy. Resistance was detected in 45% and 14% of subjects with a baseline human immunodeficiency virus type 1 RNA level of 51-400 copies/mL and <= 50 copies/mL, respectively. Mutations remained detectable for at least 48 weeks in some subjects.
C1 [Hare, C. Bradley] Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, San Francisco, CA 94110 USA.
[Mellors, John; Patel, Sheran S.; Barnas, Douglas] Univ Pittsburgh, Pittsburgh, PA USA.
[Krambrink, Amy; Su, Zhaohui] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Skiest, Daniel] Baystate Med Ctr, Springfield, MA USA.
[Margolis, David M.] Univ N Carolina, Chapel Hill, NC USA.
[Frenkel, Lisa; Coombs, Robert W.] Univ Washington, Seattle, WA 98195 USA.
[Morse, Gene D.] SUNY Buffalo, Buffalo, NY 14260 USA.
[Haas, David W.] Vanderbilt Univ, Nashville, TN USA.
[Boltz, Valerie; Palmer, Sarah; Coffin, John] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Hare, CB (reprint author), Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA.
EM chare@php.ucsf.edu
OI Margolis, David/0000-0001-5714-0002
FU NCRR NIH HHS [M01 RR000044, M01 RR000046, M01 RR000047, M01 RR000095,
M01 RR000096, RR00044, RR00046, RR00047, RR00095, RR00096]; NIAID NIH
HHS [AI25859, AI 32782, AI068634, AI25868, AI25897, AI25903, AI25915,
AI27658, AI27660, AI27661, AI27663, AI27664, AI27665, AI27666, AI27670,
AI27673, AI27757, AI32783, AI34853, AI38858, AI39156, AI46339, AI46370,
AI46381, AI46386, AI46736, AI50410, AI68634, P30 AI027757, P30 AI050410,
R21 AI065288, R21 AI065288-01A1, U01 AI025859, U01 AI025868, U01
AI025897, U01 AI025903, U01 AI025915, U01 AI027658, U01 AI027660, U01
AI027661, U01 AI027663, U01 AI027664, U01 AI027665, U01 AI027666, U01
AI027670, U01 AI027673, U01 AI032782, U01 AI032783, U01 AI034853, U01
AI038858, U01 AI039156, U01 AI046339, U01 AI046370, U01 AI046381, U01
AI046386, U01 AI068634, UM1 AI068634]
NR 16
TC 22
Z9 22
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 1
PY 2008
VL 47
IS 3
BP 421
EP 424
DI 10.1086/589867
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 322UH
UT WOS:000257400300018
PM 18558886
ER
PT J
AU Patterson, TF
Walsh, TJ
AF Patterson, Thomas F.
Walsh, Thomas J.
TI Treatment of aspergillosis - Reply to Karthaus
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID ANTIFUNGAL PROPHYLAXIS; HEMATOLOGICAL MALIGNANCIES; NEUTROPENIC
PATIENTS; FLUCONAZOLE; ITRACONAZOLE; POSACONAZOLE; METAANALYSIS;
RECIPIENTS; TRIALS
C1 [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Infect Dis, San Antonio, TX 78229 USA.
[Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA.
RP Patterson, TF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med Infect Dis, 7703 Floyd Curl Dr,MSC 7881, San Antonio, TX 78229 USA.
EM patterson@uthscsa.edu
NR 9
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 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 1
PY 2008
VL 47
IS 3
BP 427
EP 428
DI 10.1086/589924
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 322UH
UT WOS:000257400300020
ER
PT J
AU O'Mahony, D
Peikarz, RL
Bandettini, WP
Arai, AE
Wilson, WH
Bates, SE
AF O'Mahony, Deirdre
Peikarz, Richard L.
Bandettini, W. Patricia
Arai, Andrew E.
Wilson, Wyndham H.
Bates, Susan E.
TI Cardiac involvement with lymphoma: A review of the literature
SO CLINICAL LYMPHOMA & MYELOMA
LA English
DT Article
DE bortezomib; diffuse large B-cell lymphoma; metastasis; mycosis fungoides
ID STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; HEART; TUMORS;
CHEMOTHERAPY; PERICARDIUM; METASTASES; RITUXIMAB; RELAPSE; BIOPSY
AB Current literature suggests that the incidence of cardiac involvement by lymphoma as identified by autopsy varies widely, ranging from 8.7% to 20%. Historically, many cases might have been clinically undetected; however, improved imaging techniques increasingly identify cardiac involvement incidentally. In addition, newer agents resulting in improved cancer therapy outcomes might alter the prevalence and location of metastatic deposits to include more unusual disease sites, including intracardiac locations. We present 2 cases and a review of the literature.
C1 [O'Mahony, Deirdre; Wilson, Wyndham H.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Peikarz, Richard L.; Bates, Susan E.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Bandettini, W. Patricia; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP O'Mahony, D (reprint author), NCI, Metab Branch, NIH, Bldg 10-CRC Room 4E-5330,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM omahonyd@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX This research was supported, in part, by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
for Cancer Research.
NR 40
TC 15
Z9 16
U1 0
U2 2
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1557-9190
J9 CLIN LYMPHOMA MYELOM
JI Clin. Lymphoma Myeloma
PD AUG
PY 2008
VL 8
IS 4
BP 249
EP 252
DI 10.3816/CLM.2008.n.034
PG 4
WC Oncology
SC Oncology
GA 341NK
UT WOS:000258721000012
PM 18765314
ER
PT J
AU Nijboer, F
Sellers, EW
Mellinger, J
Jordan, MA
Matuz, T
Furdea, A
Halder, S
Mochty, U
Krusienski, DJ
Vaughan, TM
Wolpaw, JR
Birbaumer, N
Kubler, A
AF Nijboer, F.
Sellers, E. W.
Mellinger, J.
Jordan, M. A.
Matuz, T.
Furdea, A.
Halder, S.
Mochty, U.
Krusienski, D. J.
Vaughan, T. M.
Wolpaw, J. R.
Birbaumer, N.
Kuebler, A.
TI A P300-based brain-computer interface for people with amyotrophic
lateral sclerosis
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE amyotrophic lateral sclerosis; electroencephalogram; brain-computer
interface; event-related potentials; P300; rehabilitation
ID P300 SPELLER; BCI; PERFORMANCE; COMMUNICATION
AB Objective: The current study evaluates the efficacy of a P300-based brain-computer interface (BCI) communication device for individuals with advanced ALS.
Methods: Participants attended to one cell of a N x N matrix while the N rows and N columns flashed randomly. Each cell of the matrix contained one character. Every flash of an attended character served as a rare event in an oddball sequence and elicited a P300 response. Classification coefficients derived using a stepwise linear discriminant function were applied to the data after each set of flashes. The character receiving the highest discriminant score was presented as feedback.
Results: In Phase I, six participants used a 6 x 6 matrix on 12 separate days with a mean rate of 1.2 selections/min and mean online and offline accuracies of 62% and 82%, respectively. In Phase II, four participants used either a 6 x 6 or a 7 x 7 matrix to produce novel and spontaneous statements with a mean online rate of 2.1 selections/min and online accuracy of 79%. The amplitude and latency of the P300 remained stable over 40 weeks.
Conclusions: Participants could communicate with the P300-based BCI and performance was stable over many months.
Significance: BCIs could provide an alternative communication and control technology in the daily lives of people severely disabled by ALS. (c) 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Nijboer, F.; Mellinger, J.; Jordan, M. A.; Matuz, T.; Furdea, A.; Halder, S.; Mochty, U.; Birbaumer, N.; Kuebler, A.] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany.
[Sellers, E. W.; Vaughan, T. M.] New York State Dept Hlth, Wadsworth Ctr, Lab Nervous Syst Disorders, Albany, NY 12237 USA.
[Krusienski, D. J.] Univ N Florida, Jacksonville, FL USA.
[Birbaumer, N.] NINDS, NIH, Human Cort Physiol Unit, Bethesda, MD 20892 USA.
RP Nijboer, F (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany.
EM femke.nijboer@uni-tuebingen.de
RI Halder, Sebastian/G-3745-2012;
OI Kubler, Andrea/0000-0003-4876-0415
FU NIBIB NIH HHS [EB00856, R01 EB000856, R01 EB000856-01, R01 EB000856-02,
R01 EB000856-03, R01 EB000856-04, R01 EB000856-05]; NICHD NIH HHS [R01
HD030146-06, HD30146, R01 HD030146, R01 HD030146-07, R01 HD030146-08,
R01 HD030146-09, R01 HD030146-10]
NR 23
TC 276
Z9 283
U1 4
U2 42
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD AUG
PY 2008
VL 119
IS 8
BP 1909
EP 1916
DI 10.1016/j.clinph.2008.03.034
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 331PD
UT WOS:000258023300027
PM 18571984
ER
PT J
AU Peters, JM
Hollingshead, HE
Gonzalez, FJ
AF Peters, Jeffrey M.
Hollingshead, Holly E.
Gonzalez, Frank J.
TI Role of peroxisome-proliferator-activated receptor beta/delta (PPAR
beta/delta) in gastrointestinal tract function and disease
SO CLINICAL SCIENCE
LA English
DT Review
DE colon cancer; differentiation; gastrointestinal tract; inflammatory
bowel disease; nuclear receptor; peroxisome-proliferator-activated
receptor beta/delta (PPAR beta/delta)
ID ACID-BINDING-PROTEIN; COLORECTAL-CANCER CELLS; NONSTEROIDAL
ANTIINFLAMMATORY DRUGS; INTESTINAL POLYP FORMATION; INDUCED COLON
CARCINOGENESIS; VASCULAR ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; OMEGA-6
FATTY-ACIDS; APC-DEFICIENT MICE; NF-KAPPA-B
AB PPAR beta/delta (peroxisome-proliferator-activated receptor beta/delta) is one of three PPARs in the nuclear hormone receptor superfamily that are collectively involved in the control of lipid homoeostasis among other functions. PPAR beta/delta not only acts as a ligand-activated transcription factor, but also affects signal transduction by interacting with other transcription factors such as NF-kappa B (nuclear factor kappa B). Constitutive expression of PPAR beta/delta in the gastrointestinal tract is very high compared with other tissues and its potential physiological roles in this tissue include homoeostatic regulation of intestinal cell proliferation/differentiation and modulation of inflammation associated with inflammatory bowel disease and colon cancer. Analysis of mouse epithelial cells in the intestine and colon has clearly demonstrated that ligand activation of PPAR beta/delta induces terminal differentiation. The PPAR beta/delta target genes mediating this effect are currently unknown. Emerging evidence suggests that PPAR beta/delta can suppress inflammatory bowel disease through PPAR beta/delta-dependent and ligand-independent down-regulation of inflammatory signalling. However, the role of PPAR beta/delta in colon carcinogenesis remains controversial, as conflicting evidence suggests that ligand activation of PPAR beta/delta can either potentiate or attenuate this disease. In the present review, we summarize the role of PPAR beta/delta in gastrointestinal physiology and disease with an emphasis on findings in experimental models using both high-affinity ligands and null-mouse models.
C1 [Peters, Jeffrey M.; Hollingshead, Holly E.] Penn State Univ, Dept Vet Biomed Sci, University Pk, PA 16802 USA.
[Peters, Jeffrey M.; Hollingshead, Holly E.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Peters, Jeffrey M.; Hollingshead, Holly E.] Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet Biomed Sci, University Pk, PA 16802 USA.
EM jmp21@psu.edu
RI Peters, Jeffrey/D-8847-2011
FU Intramural NIH HHS [Z01 BC005708-16]; NCI NIH HHS [R01 CA097999, R01
CA124533, R01 CA97999]
NR 178
TC 67
Z9 67
U1 1
U2 5
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0143-5221
J9 CLIN SCI
JI Clin. Sci.
PD AUG
PY 2008
VL 115
IS 3-4
BP 107
EP 127
DI 10.1042/CS20080022
PG 21
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 334YD
UT WOS:000258256800004
PM 18616431
ER
PT J
AU Drevets, WC
Savitz, J
AF Drevets, Wayne C.
Savitz, Jonathan
TI The Subgenual Anterior Cingulate Cortex in Mood Disorders
SO CNS SPECTRUMS
LA English
DT Review
ID MAJOR DEPRESSIVE DISORDER; MEDIAL PREFRONTAL CORTEX; REGIONAL CEREBRAL
METABOLISM; VOXEL-BASED MORPHOMETRY; TREATMENT-RESISTANT DEPRESSION;
GLIAL-CELL DENSITY; BIPOLAR DISORDER; GLUCOSE-METABOLISM; UNIPOLAR
DEPRESSION; SLEEP-DEPRIVATION
AB The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD. subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.
C1 [Drevets, Wayne C.] NIMH, Div Intramural Res Programs, Sect Neuroimaging Mood & Anxiety Disorders, Mol Imaging Branch, Bethesda, MD 20892 USA.
RP Drevets, WC (reprint author), NIMH, Div Intramural Res Programs, Sect Neuroimaging Mood & Anxiety Disorders, Mol Imaging Branch, 15K North Dr,Room 210, Bethesda, MD 20892 USA.
EM drevetsw@mail.nih.gov
RI Savitz, Jonathan/C-3088-2009
OI Savitz, Jonathan/0000-0001-8143-182X
FU Intramural NIH HHS [Z01 MH002790-06]
NR 111
TC 376
Z9 381
U1 9
U2 50
PU M B L COMMUNICATIONS, INC
PI NEW YORK
PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA
SN 1092-8529
J9 CNS SPECTRUMS
JI CNS Spectr.
PD AUG
PY 2008
VL 13
IS 8
BP 663
EP 681
PG 23
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 360VE
UT WOS:000260085400005
PM 18704022
ER
PT J
AU Zhu, PJ
Zheng, W
Auld, DS
Jadhav, A
MacArthur, R
Olson, KR
Peng, K
Dotimas, H
Austin, CP
Inglese, J
AF Zhu, Ping Jun
Zheng, Wei
Auld, Douglas S.
Jadhav, Ajit
MacArthur, Ryan
Olson, Keith R.
Peng, Kun
Dotimas, Hyna
Austin, Christopher P.
Inglese, James
TI A miniaturized glucocorticoid receptor translocation assay using
enzymatic fragment complementation evaluated with qHTS
SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
LA English
DT Article
DE qHTS; HTS; EFC; PubChem; glucocorticoid receptor; nuclear translocation;
suspension cells
ID THROUGHPUT SCREENING ASSAYS; CELL-BASED ASSAY; NUCLEAR TRANSLOCATION;
STEROID-HORMONE; DRUG-THERAPY; ACTIVATION; BINDING; ACETYLATION; RU486;
HSP90
AB Nuclear translocation is an important step in glucocorticoid receptor (GR) signaling and assays that measure this process allow the identification of nuclear receptor ligands independent of subsequent functional effects. To facilitate the identification of GR-translocation agonists, an enzyme fragment complementation (EFC) cell-based assay was scaled to a 1536-well plate format to evaluate 9,920 compounds using a quantitative high throughput screening (qHTS) strategy where compounds are assayed at multiple concentrations. In contrast to conventional assays of nuclear translocation the qHTS assay described here was enabled on a standard luminescence microplate reader precluding the requirement for imaging methods. The assay uses beta-galactosidase a complementation to indirectly detect GR-translocation in CHO-K1 cells. 1536-well assay miniaturization included the elimination of a media aspiration step, and the optimized assay displayed a Z' of 0.55. qHTS yielded EC50 values for all 9,920 compounds and allowed us to retrospectively examine the dataset as a single concentration-based screen to estimate the number of false positives and negatives at typical activity thresholds. For example, at a 9 mu M screening concentration, the assay showed an accuracy that is comparable to typical cell-based assays as judged by the occurrence of false positives that we determined to be 1.3% or 0.3%, for a 3 sigma or 6 sigma threshold, respectively. This corresponds to a confirmation rate of similar to 30% or similar to 50%, respectively. The assay was consistent with glucocorticoid pharmacology as scaffolds with close similarity to dexamethasone were identified as active, while, for example, steroids that act as ligands to other nuclear receptors such as the estrogen receptor were found to be inactive.
C1 [Zhu, Ping Jun; Zheng, Wei; Auld, Douglas S.; Jadhav, Ajit; MacArthur, Ryan; Austin, Christopher P.; Inglese, James] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Olson, Keith R.; Peng, Kun; Dotimas, Hyna] DiscoveRx Inc, Fremont, CA USA.
RP Inglese, J (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM jinglese@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural NIH HHS [Z01 HG200319-04]
NR 46
TC 12
Z9 12
U1 0
U2 2
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1386-2073
EI 1875-5402
J9 COMB CHEM HIGH T SCR
JI Comb. Chem. High Throughput Screen
PD AUG
PY 2008
VL 11
IS 7
BP 545
EP 559
DI 10.2174/138620708785204045
PG 15
WC Biochemical Research Methods; Chemistry, Applied; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA 351SM
UT WOS:000259446200007
PM 18694391
ER
PT J
AU Becker, RE
Greig, NH
AF Becker, Robert E.
Greig, Nigel H.
TI Alzheimer's disease drug development in 2008 and beyond: Problems and
opportunities
SO CURRENT ALZHEIMER RESEARCH
LA English
DT Article
ID SAMPLE-SIZE REQUIREMENTS; CLINICAL-TRIALS FAIL; DOUBLE-BLIND;
MEASUREMENT ERROR; CHOLINESTERASE-INHIBITORS; HEALTHY-VOLUNTEERS;
RATING-SCALE; METRIFONATE; HEPTYLPHYSOSTIGMINE; CERTIFICATION
AB Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs.
New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers' abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development.
C1 [Becker, Robert E.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Becker, RE (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 5th Floor BRC Bldg,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM rebecker2008@comcast.net
FU National Institute on Aging, NIH
FX The authors are supported in part by the Intramural Research Program of
the National Institute on Aging, NIH. The views expressed within this
article are those of the authors and may not represent those of the
National Institute on Aging, NIH.
NR 67
TC 33
Z9 35
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 1567-2050
J9 CURR ALZHEIMER RES
JI Curr. Alzheimer Res.
PD AUG
PY 2008
VL 5
IS 4
BP 346
EP 357
DI 10.2174/156720508785132299
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 341TR
UT WOS:000258738500001
PM 18690832
ER
PT J
AU Blumberg, PM
Kedei, N
Lewin, NE
Yang, D
Czifra, G
Pu, Y
Peach, ML
Marquez, VE
AF Blumberg, P. M.
Kedei, N.
Lewin, N. E.
Yang, D.
Czifra, G.
Pu, Y.
Peach, M. L.
Marquez, V. E.
TI Wealth of opportunity - The C1 domain as a target for drug development
SO CURRENT DRUG TARGETS
LA English
DT Review
DE protein kinase C; phorbol ester; RasGRP; bryostatin; C1 domain
ID PROTEIN-KINASE-C; CONFORMATIONALLY CONSTRAINED ANALOGS; PHORBOL
12-MYRISTATE 13-ACETATE; B-CELL LYMPHOMA; CD-1 MOUSE SKIN; NONPROMOTING
12-DEOXYPHORBOL 13-ESTERS; DIACYLGLYCEROL DAG; TUMOR PROMOTION;
PKC-DELTA; BIOLOGICAL RESPONSES
AB The diacylglycerol-responsive C1 domains of protein kinase C and of the related classes of signaling proteins represent highly attractive targets for drug development. The signaling functions that are regulated by C1 domains are central to cellular control, thereby impacting many pathological conditions. Our understanding of the diacylglycerol signaling pathways provides great confidence in the utility of intervention in these pathways for treatment of cancer and other conditions. Multiple compounds directed at these signaling proteins, including compounds directed at the C1 domains, are currently in clinical trials, providing strong validation for these targets. Extensive understanding of the structure and function of C1 domains, coupled with detailed insights into the molecular details of ligand - C1 domain interactions, provides a solid basis for rational and semi-rational drug design. Finally, the complexity of the factors contributing to ligand - C1 domain interactions affords abundant opportunities for manipulation of selectivity; indeed, substantially selective compounds have already been identified.
C1 [Blumberg, P. M.; Kedei, N.; Lewin, N. E.; Yang, D.; Czifra, G.; Pu, Y.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Peach, M. L.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Marquez, V. E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4048,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA.
EM blumberp@dc37a.nci.nih.gov
FU Intramural NIH HHS [Z01 BC005270-27, Z01 BC005270-26, ZIA BC005270-28];
NCI NIH HHS [N01CO12400, N01-CO-12400]
NR 119
TC 52
Z9 52
U1 0
U2 8
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-4501
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PD AUG
PY 2008
VL 9
IS 8
BP 641
EP 652
DI 10.2174/138945008785132376
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 341UZ
UT WOS:000258742000005
PM 18691011
ER
PT J
AU Shida, D
Takabe, K
Kapitonov, D
Milstien, S
Spiegel, S
AF Shida, Dai
Takabe, Kazuaki
Kapitonov, Dmitri
Milstien, Sheldon
Spiegel, Sarah
TI Targeting SphK1 as a new strategy against cancer
SO CURRENT DRUG TARGETS
LA English
DT Review
DE sphingosine kinase; cancer; transactivation; angiogenesis
ID EPIDERMAL-GROWTH-FACTOR; SPHINGOSINE KINASE-1 EXPRESSION; HUMAN
BREAST-CANCER; SQUAMOUS-CELL CARCINOMA; PROTEIN-COUPLED RECEPTOR;
GENE-EXPRESSION; ENDOTHELIAL-CELLS; MULTIDRUG-RESISTANCE;
COLORECTAL-CANCER; INDUCED APOPTOSIS
AB Sphingolipid metabolites have emerged as critical players in a number of fundamental biological processes. Among them, sphingosine-1-phosphate (S1P) promotes cell survival and proliferation, in contrast to ceramide and sphingosine, which induce cell growth arrest and apoptosis. These sphingolipids with opposing functions are interconvertible inside cells, suggesting that a finely tuned balance between them can determine cell fate. Sphingosine kinases (SphKs), which catalyze the phosphorylation of sphingosine to S1P, are critical regulators of this balance. Of the two identified SphKs, sphingosine kinase type 1 (SphK1) has been shown to regulate various processes important for cancer progression and will be the focus of this review, since much less is known of biological functions of SphK2, especially in cancer. SphK1 is overexpressed in various types of cancers and upregulation of SphK1 has been associated with tumor angiogenesis and resistance to radiation and chemotherapy. Many growth factors, through their tyrosine kinase receptors (RTKs), stimulate SphK1 leading to a rapid increase in S1P. This S1P in turn can activate S1P receptors and their downstream signaling. Conversely, activation of S1P receptors can induce transactivation of various RTKs. Thus, SphK1 may play important roles in S1P receptor RTK amplification loops. Here we review the role of SphK1 in tumorigenesis, hormonal therapy, chemotherapy resistance, and as a prognostic marker. We will also review studies on the effects of SphK inhibitors in cells in vitro and in animals in vivo and in some clinical trials and highlight the potential of SphK1 as a new target for cancer therapeutics.
C1 [Shida, Dai; Kapitonov, Dmitri; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA.
[Shida, Dai; Takabe, Kazuaki; Kapitonov, Dmitri; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA 23298 USA.
[Takabe, Kazuaki] Virginia Commonwealth Univ, Sch Med, Div Surg Oncol, Dept Surg, Richmond, VA 23298 USA.
[Milstien, Sheldon] NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, 1101 E Marshall St,2011 Sanger Hall, Richmond, VA 23298 USA.
EM sspiegel@vcu.edu
FU Intramural NIH HHS; NCI NIH HHS [R01 CA061774, R01 CA061774-15,
R01CA61774]; NIAID NIH HHS [R01 AI050094, R01 AI050094-06A2,
R01AI50094]; NIGMS NIH HHS [R37 GM043880-18, 5T-32GM008695-08, R37
GM043880, R37GM043880, T32 GM008695]
NR 116
TC 143
Z9 154
U1 0
U2 12
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1389-4501
J9 CURR DRUG TARGETS
JI Curr. Drug Targets
PD AUG
PY 2008
VL 9
IS 8
BP 662
EP 673
DI 10.2174/138945008785132402
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 341UZ
UT WOS:000258742000007
PM 18691013
ER
PT J
AU Peavy, RD
Metcalfe, DD
AF Peavy, Richard D.
Metcalfe, Dean D.
TI Understanding the mechanisms of anaphylaxis
SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Review
DE allergic reaction; anaphylaxis; mast cells
ID MAST-CELL ACTIVATION; FC-EPSILON-RI; SRC FAMILY KINASES; ALLERGIC
RESPONSES; METHYLENE-BLUE; MURINE MODELS; MICE LACKING; FYN KINASE;
MASTOCYTOSIS; LESSONS
AB Purpose of review
The present review considers recent reports that identify the roles of key intermediate signaling components and mediators during and after mast cell activation and degranulation leading to anaphylaxis.
Recent findings
Mechanisms of anaphylaxis are becoming better understood as the interaction of several regulatory systems in the mast cell activation and degranulation signaling cascade. Multiple tyrosine kinases, activated after immunoglobulin E binding to the high-affinity receptors for immunoglobulin E (Fc epsilon RI), exert both positive and negative regulation on the signaling cascade, which may vary with genetic background or mutations in signaling proteins. Calcium influx, the essential, proximal intracellular event leading to mast cell degranulation, is controlled also by both negative and positive regulation through calcium channels. Sphingosine-1-phosphate is emerging as a newly realized mediator of anaphylaxis, acting as a signaling component within the mast cell and as a circulating mediator.
Summary
Anaphylaxis is a systemic reaction involving multiple organ systems, but it is believed that it may be influenced by cellular events in mast cells and basophils resulting in the release of mediators. Therefore, understanding the mechanisms of mast cell activation and degranulation is critical to understanding the mechanisms of anaphylaxis. Recent reports have identified important regulatory components of the signaling cascade and, consequently, potential targets for therapeutic intervention.
C1 [Peavy, Richard D.; Metcalfe, Dean D.] NIAID, NIH, Allerg Dis Res Lab, DIR, Bethesda, MD 20892 USA.
RP Peavy, RD (reprint author), NIAID, NIH, Allerg Dis Res Lab, DIR, 10 Ctr Dr,Room 11C207,MS-1881, Bethesda, MD 20892 USA.
EM peavyr@niaid.nih.gov
FU Intramural NIH HHS [, NIH0013412243]; PHS HHS [NIH0013412243]
NR 48
TC 50
Z9 50
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-4050
J9 CURR OPIN ALLERGY CL
JI Curr. Opin. Allergy Clin. Immunol.
PD AUG
PY 2008
VL 8
IS 4
BP 310
EP 315
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA 328DJ
UT WOS:000257777500006
PM 18596587
ER
PT J
AU Bonifacino, JS
Hurley, JH
AF Bonifacino, Juan S.
Hurley, James H.
TI Retromer
SO CURRENT OPINION IN CELL BIOLOGY
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; POLYMERIC IMMUNOGLOBULIN RECEPTOR;
TRANS-GOLGI NETWORK; WNT-PRODUCING CELLS; TO-TGN TRANSPORT; SORTING
NEXIN-1; MAMMALIAN RETROMER; RETROGRADE TRANSPORT; REQUIRES RETROMER;
ENDOSOMAL LOCALIZATION
AB The retromer is a heteropentameric complex that associates with the cytosolic face of endosomes and mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network. The mammalian retromer complex comprises a sorting nexin dimer composed of a still undefined combination of SNX1, SNX2, SNX5 and SNX6, and a cargo-recognition trimer composed of Vps26, Vps29 and Vps35. The SNX subunits contain PX and BAR domains that allow binding to PI(3)P enriched, highly curved membranes of endosomal vesicles and tubules, while Vps26, Vps29 and Vps35 have arrestin, phosphoesterase and alpha-solenoid folds, respectively. Recent studies have implicated retromer in a broad range of physiological, developmental and pathological processes, underscoring the critical nature of retrograde transport mediated by this complex.
C1 [Hurley, James H.] NIDDK, Mol Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Bonifacino, Juan S.] NICHHD, Cell Biol & Metab Program, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU Intramural NIH HHS [Z01 HD001607-16]
NR 82
TC 274
Z9 277
U1 5
U2 25
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0955-0674
J9 CURR OPIN CELL BIOL
JI Curr. Opin. Cell Biol.
PD AUG
PY 2008
VL 20
IS 4
BP 427
EP 436
DI 10.1016/j.ceb.2008.03.009
PG 10
WC Cell Biology
SC Cell Biology
GA 336HC
UT WOS:000258353900010
PM 18472259
ER
PT J
AU Shvartsman, SY
Coppey, M
Berezhkovskii, AM
AF Shvartsman, Stanislav Y.
Coppey, Mathieu
Berezhkovskii, Alexander M.
TI Dynamics of maternal morphogen gradients in Drosophila
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Review
ID RECEPTOR TYROSINE KINASE; TERMINAL BODY PATTERN; GENE-EXPRESSION; BICOID
PROTEIN; TORSO; NUCLEAR; EMBRYO; EMBRYOGENESIS; DOMAINS; CONSEQUENCES
AB The first direct studies of morphogen gradients were done in the end of 1980s, in the early Drosophila embryo, which is patterned under the action of four maternally determined morphogens. Since the early studies of maternal morphogens were done with fixed embryos, they were viewed as relatively static signals. Several recent studies analyze dynamics of the anterior, dorsoventral, and terminal patterning signals. The results of these quantitative studies provide critical tests of classical models and reveal new modes of morphogen regulation and readout in one of the most extensively studied patterning systems.
C1 [Shvartsman, Stanislav Y.; Coppey, Mathieu] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA.
[Shvartsman, Stanislav Y.; Coppey, Mathieu] Princeton Univ, Lewis Sigler Inst Integrat Gen, Princeton, NJ 08544 USA.
[Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Shvartsman, SY (reprint author), Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA.
EM stas@Princeton.edu
FU NIH [P50 GM071508, R01GM078079]; NSF CAREER award; Intramural Research
Program of the NIH; Center for Information Technology
FX We thank A Boettiger, R De Lotto, O Grimm, G Jimenez, Y Kim, J
Lippincott-Schwartz, M Mavrakis, Z Paroush, E Wiesehaus, and T Schupbach
for helpful discussions. SYS was supported by the P50 GM071508 and
R01GM078079 NIH grants and the NSF CAREER award. AMB was supported by
the Intramural Research Program of the NIH, Center for Information
Technology.
NR 40
TC 13
Z9 13
U1 0
U2 5
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD AUG
PY 2008
VL 18
IS 4
BP 342
EP 347
DI 10.1016/j.gde.2008.06.002
PG 6
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 369NF
UT WOS:000260700500010
PM 18602472
ER
PT J
AU Bridge, H
Cumming, BG
AF Bridge, Holly
Cumming, Bruce G.
TI Representation of binocular surfaces by cortical neurons
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID INFERIOR TEMPORAL NEURONS; VISUAL-CORTEX; AREA V4; DEPTH DISCRIMINATION;
V1 NEURONS; DISPARITY; ORIENTATION; MACAQUE; RESPONSES; SLANT
AB Useful representations of the three-dimensional (M) world go beyond assigning depth to individual points, building maps of surfaces and shapes. Studies in a wide range of extrastriate cortical areas have shown that single neurons show selective responses to 3D surfaces. The extent to which this advances the representation beyond that provided by the earliest binocular signals requires careful evaluation. We conclude that current data are not sufficient to identify distinctive contributions from different cortical areas to the binocular representation of 3D surfaces.
C1 [Cumming, Bruce G.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
[Bridge, Holly] Univ Oxford, Dept Clin Neurol, FMRIB Ctr, Oxford OX1 2JD, England.
RP Cumming, BG (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA.
EM bgc@lsr.nei.nih.gov
OI Bridge, Holly/0000-0002-8089-6198
NR 25
TC 9
Z9 9
U1 0
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD AUG
PY 2008
VL 18
IS 4
BP 425
EP 430
DI 10.1016/j.conb.2008.09.003
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 381UM
UT WOS:000261561400013
PM 18809495
ER
PT J
AU Da Ros, VG
Maldera, JA
Willis, WD
Cohen, DJ
Goulding, EH
Gelman, DM
Rubinstein, M
Eddy, EM
Cuasnicu, PS
AF Da Ros, Vanina G.
Maldera, Julieta A.
Willis, William D.
Cohen, Debora J.
Goulding, Eugenia H.
Gelman, Diego M.
Rubinstein, Marcelo
Eddy, Edward M.
Cuasnicu, Patricia S.
TI Impaired sperm fertilizing ability in mice lacking Cysteine-RIch
Secretory Protein 1 (CRISP1)
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE sperm; egg; fertilization; CRISP
ID MEDIATES GAMETE FUSION; RAT EPIDIDYMAL PROTEIN; EGG FUSION;
CYSTEINE-RICH-SECRETORY-PROTEIN-4 CRISP4; COMPLEMENTARY SITES; GENE;
LOCALIZATION; GLYCOPROTEIN; CAPACITATION; SPERMATOZOA
AB Mammalian fertilization is a complex multi-step process mediated by different molecules present on both gametes. Epididymal Protein CRISP1, a member of the Cysteine-RIch Secretory Protein (CRISP) family, was identified by our laboratory and postulated to participate in both sperm-zona pellucida (ZP) interaction and gamete fusion by binding to egg-complementary sites. To elucidate the functional role of CRISP1 in vivo, we disrupted the Crisp1 gene and evaluated the effect on animal fertility and several sperm parameters. Male and female Crisp1(-/-) animals exhibited no differences in fertility compared to controls. Sperm motility and the ability to undergo a spontaneous or progesterone-induced acrosome reaction were neither affected in Crisp1(-/-) mice. However, the level of protein tyrosine phosphorylation during capacitation was clearly lower in mutant sperm than in controls. In vitro fertilization assays showed that Crisp1(-/-) sperm also exhibited a significantly reduced ability to penetrate both ZP-intact and ZP-free eggs. Moreover, when ZP-free eggs were simultaneously inseminated with Crisp1(+/+) and Crisp1(-/-) sperm in a competition assay, the mutant sperm exhibited a greater disadvantage in their fusion ability. Finally, the finding that the fusion ability of Crisp1(-/-) sperm was further inhibited by the presence of CRISP1 OF CRISP2 during gamete co-incubation, supports that another CRISP cooperates with CRISP1 during fertilization and might compensate for its lack in the mutant mice. Together, these results indicate that CRISP proteins are players in the mammalian fertilization process. To our knowledge this is the first knockout mice generated for a CRISP protein. The information obtained might have important functional implications for other members of the widely distributed and evolutionarily conserved CRISP family. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Da Ros, Vanina G.; Maldera, Julieta A.; Cohen, Debora J.; Cuasnicu, Patricia S.] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, RA-1428 Buenos Aires, DF, Argentina.
[Willis, William D.; Goulding, Eugenia H.; Eddy, Edward M.] Natl Inst Environm Hlth Sci, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA.
[Gelman, Diego M.; Rubinstein, Marcelo] Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, RA-1428 Buenos Aires, DF, Argentina.
[Rubinstein, Marcelo] Univ Buenos Aires, Fac Ciencias Exactas & Nat, RA-1428 Buenos Aires, DF, Argentina.
RP Cuasnicu, PS (reprint author), Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Vuelta Obligado 2490, RA-1428 Buenos Aires, DF, Argentina.
EM cuasnicu@dna.uba.ar
OI Da Ros, Vanina Gabriela/0000-0003-2367-0042
FU Intramural NIH HHS [Z01 ES070076-21]
NR 40
TC 66
Z9 67
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 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD AUG 1
PY 2008
VL 320
IS 1
BP 12
EP 18
DI 10.1016/j.ydbio.2008.03.015
PG 7
WC Developmental Biology
SC Developmental Biology
GA 335AF
UT WOS:000258262500002
PM 18571638
ER
EF