FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Concheiro, M
Jones, HE
Johnson, RE
Choo, R
Huestis, MA
AF Concheiro, M.
Jones, H. E.
Johnson, R. E.
Choo, R.
Huestis, M. A.
TI Buprenorphine sublingual tablet pharmacokinetics in plasma, oral fluid
and sweat during treatment of opioid-dependent pregnant
SO THERAPEUTIC DRUG MONITORING
LA English
DT Meeting Abstract
CT 12th International Congress of Therapeutic Drug Monitoring and Clinical
Toxicology
CY OCT 02-06, 2011
CL Stuttgart, GERMANY
DE buprenorphine; norbuprenorphine; oral fluid; plasma; sweat
C1 [Concheiro, M.] Univ Santiago de Compostela, Inst Ciencias Forenses, Santiago De Compostela, Spain.
[Jones, H. E.; Johnson, R. E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Choo, R.] Univ Pittsburgh, Dept Biol, Pittsburgh, PA USA.
[Huestis, M. A.] Natl Inst Drug Abuse, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD AUG
PY 2011
VL 33
IS 4
BP 492
EP 493
PG 2
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 792PY
UT WOS:000292761500107
ER
PT J
AU Ellenstein, A
Kranick, SM
Hallett, M
AF Ellenstein, Aviva
Kranick, Sarah M.
Hallett, Mark
TI An Update on Psychogenic Movement Disorders
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE Movement disorder; Psychogenic; Motor conversion; Somatoform disorder;
Dissociative disorder; Functional disorder; Medically unexplained;
Hysterical; Neurologic symptom; Diagnostic technique
ID COGNITIVE-BEHAVIORAL THERAPY; MOTOR CONVERSION DISORDER; CLINICAL-TRIAL;
DSM-V; PARALYSIS; PHENOMENOLOGY; SYMPTOMS; RECOVERY; STRESS; CORTEX
AB Psychogenic movement disorders (PMD) and other conversion disorders (CD) with apparent neurologic signs (neurologic CD) plague patients and perplex physicians. Due to a lack of objective evidence of underlying brain lesions, CD were largely abandoned by neurologists and remained poorly understood psychiatric diagnoses throughout most of the 20th century. Modern neuroscience now supports increasingly comprehensive biological models for these complex disorders, definitively establishing their place in both neurology and psychiatry. Although it is often clinically useful to distinguish a movement disorder as either "organic" or "psychogenic," this dichotomy is difficult to defend scientifically. Here we describe the neuroimaging and neurophysiologic evidence for dysfunctional neural networks in PMD, explain the diagnostic potential of clinical neurophysiologic testing, discuss the promising if increasingly complex role of neuropsychiatric genetics, and review current treatment strategies.
C1 [Ellenstein, Aviva; Kranick, Sarah M.; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Ellenstein, A (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 7D42,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
EM ellensteina@ninds.nih.gov; mattes1@ninds.nih.gov; hallettm@ninds.nih.gov
FU Intramural NIH HHS [Z01 NS002667-23]
NR 50
TC 11
Z9 12
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD AUG
PY 2011
VL 11
IS 4
BP 396
EP 403
DI 10.1007/s11910-011-0205-z
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 788RU
UT WOS:000292462900006
PM 21559795
ER
PT J
AU Domanski, M
Pocock, S
Bernaud, C
Borer, J
Geller, N
Revkin, J
Zannad, F
AF Domanski, Michael
Pocock, Stuart
Bernaud, Corine
Borer, Jeffrey
Geller, Nancy
Revkin, James
Zannad, Faiez
TI Surrogate endpoints in randomized cardiovascular clinical trials
SO FUNDAMENTAL & CLINICAL PHARMACOLOGY
LA English
DT Review
DE randomized clinical trials; surrogate endpoints
AB Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclusion regarding treatment effect on a CEI requires prior rigorous validation of the surrogate. Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints.
C1 [Domanski, Michael; Geller, Nancy] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Pocock, Stuart] London Sch Hyg & Trop Med, Med Stat Unit, London WC1, England.
[Bernaud, Corine] AstraZeneca, Zaventem, Belgium.
[Borer, Jeffrey] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
[Revkin, James] Pfizer, New York, NY USA.
[Zannad, Faiez] Hop Jeanne Darc, FESC CIC INSERM CHU, F-54200 Toul, France.
RP Domanski, M (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM domanskimj@mail.nih.gov
NR 10
TC 10
Z9 10
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0767-3981
J9 FUND CLIN PHARMACOL
JI Fundam. Clin. Pharmacol.
PD AUG
PY 2011
VL 25
IS 4
BP 411
EP 413
DI 10.1111/j.1472-8206.2010.00865.x
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 788NM
UT WOS:000292451700001
PM 20698890
ER
PT J
AU Mabley, J
Gordon, S
Pacher, P
AF Mabley, Jon
Gordon, Sevelanne
Pacher, Pal
TI Nicotine Exerts an Anti-inflammatory Effect in a Murine Model of Acute
Lung Injury
SO INFLAMMATION
LA English
DT Article
DE inflammation; nicotine; acetylcholine; lung; chemokine
ID ACETYLCHOLINE-RECEPTOR ALPHA-7; RESPIRATORY-DISTRESS-SYNDROME; KAPPA-B;
IN-VIVO; IMPROVES SURVIVAL; INFLAMMATION; ACTIVATION; PATHWAY; MICE;
STIMULATION
AB Activation of the cholinergic anti-inflammatory pathway through direct activation of nicotinic acetylcholine receptors on immune cells can inhibit pro-inflammatory chemokine and cytokine release and thereby protect in a variety of inflammatory diseases. The aim of this study was to investigate whether nicotine treatment protected against acute lung inflammation. Mice challenged with intratracheal lipopolysaccharide (LPS, 50 mu g) were treated with nicotine (0.2 or 0.4 mg/kg, sc). After 24 h, bronchoalveolar lavage fluid (BALF) was obtained to measure leukocyte infiltration, lung edema, and pro-inflammatory chemokine (MIP-1 alpha, MIP-2, and eotaxin) and cytokine (IL-1, IL-6, and TNF-alpha) levels. Nicotine treatment reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by decreased BALF inflammatory cells, myeloperoxidase, and protein. Nicotine also downregulated lung production of pro-inflammatory chemokines and cytokines. These data support the proposal that activation of the cholinergic anti-inflammatory pathway may represent a useful addition to the therapy of acute respiratory distress syndrome.
C1 [Mabley, Jon; Gordon, Sevelanne] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
RP Mabley, J (reprint author), Univ Brighton, Sch Pharm & Biomol Sci, Cockcroft Bldg,Lewes Rd, Brighton BN2 4GJ, E Sussex, England.
EM j.g.Mabley@brighton.ac.uk
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU Intramural NIH HHS [Z01 AA000375-02, Z01 AA000375-03, Z99 AA999999, ZIA
AA000375-04, ZIA AA000375-06]
NR 41
TC 23
Z9 24
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0360-3997
J9 INFLAMMATION
JI Inflammation
PD AUG
PY 2011
VL 34
IS 4
BP 231
EP 237
DI 10.1007/s10753-010-9228-x
PG 7
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 788LR
UT WOS:000292446900002
PM 20625922
ER
PT J
AU Furu, K
Karlstad, O
Skurtveit, S
Haberg, SE
Nafstad, P
London, SJ
Nystad, W
AF Furu, Kari
Karlstad, Oystein
Skurtveit, Svetlana
Haberg, Siri E.
Nafstad, Per
London, Stephanie J.
Nystad, Wenche
TI High validity of mother-reported use of antiasthmatics among children: a
comparison with a population-based prescription database
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Asthma; Children; Mother-reported; Pharmacoepidemiology; Prescription
database; Validity
ID ASTHMA SYMPTOMS; MEDICATION USE; QUESTIONNAIRE; DEFINITIONS;
INFORMATION; AGREEMENT; RECALL; COHORT; ISAAC
AB Objectives: To examine the validity of (1) maternal questionnaire report of children's use of antiasthmatics using a prescription database as the reference standard and (2) dispensed antiasthmatics as a measure of asthma using maternal report of children's asthma as the reference standard.
Study Design and Setting: A total of 3,394 children in the Norwegian Mother and Child Cohort Study aged 7 years were linked to the Norwegian Prescription Database. Maternal report of both children's use of antiasthmatics during the preceding year and the presence of asthma was compared with data on dispensed antiasthmatics.
Results: A total of 2,056 mothers responded and reported use of antiasthmatics during the previous year in 125 of 147 children who had been dispensed antiasthmatics (sensitivity 85.0%). Of the 1,909 children with no dispensed antiasthmatics, 1,848 had no maternal report of antiasthmatic use (specificity 96.8%). Mothers reported current asthma in 133 (6.5% of 2,056) children, including in 122(5.9%) reported as verified by a doctor. Of these 122, 98 had been dispensed antiasthmatics during the preceding year (sensitivity 80.3%). Only 12% of the children without reported asthma were dispensed antiasthmatics.
Conclusion: Mother-reported use of antiasthmatics during the previous year among 7-year-old children is highly valid. Dispensed antiasthmatics would be a useful proxy for the presence of current asthma when disease data are not available. C) 2011 Elsevier Inc. All rights reserved.
C1 [Furu, Kari; Karlstad, Oystein; Skurtveit, Svetlana; Haberg, Siri E.; Nafstad, Per; Nystad, Wenche] Norwegian Inst Publ Hlth, Div Epidemiol, N-0403 Oslo, Norway.
[Furu, Kari] Univ Tromso, Dept Pharm, Tromso, Norway.
[Nafstad, Per] Univ Oslo, Inst Hlth & Soc, Oslo, Norway.
[London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Furu, K (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404, N-0403 Oslo, Norway.
EM kari.furu@fhi.no
OI London, Stephanie/0000-0003-4911-5290; Karlstad,
Oystein/0000-0003-1204-787X
FU Norwegian Ministry of Health, National Institutes of Health/National
Institute of Environmental Health Sciences (NIH/NIEHS) [ES-044008];
NIH/National Institute of Neurological Disorders and Stroke [UO1 NS
047537-01]; Norwegian Research Council (NRC) [151918/S10, 175314];
NIEHS, NIH, Department of Health and Human Services
FX The MoBa is supported by the Norwegian Ministry of Health, National
Institutes of Health/National Institute of Environmental Health Sciences
(NIH/NIEHS) (contract no. ES-044008), NIH/National Institute of
Neurological Disorders and Stroke (grant no. UO1 NS 047537-01), and the
Norwegian Research Council (NRC)/Functional genomics (FUGE) (grant no.
151918/S10). Dr London is supported by the Intramural Research Program,
NIEHS, NIH, Department of Health and Human Services. Ph D student
Karlstad is supported by the NRC (grant no. 175314).
NR 22
TC 24
Z9 24
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD AUG
PY 2011
VL 64
IS 8
BP 878
EP 884
DI 10.1016/j.jclinepi.2010.10.014
PG 7
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 787YU
UT WOS:000292413400009
PM 21232920
ER
PT J
AU Berry, SH
Elliott, MN
Suttorp, M
Bogart, LM
Stoto, MA
Eggers, P
Nyberg, L
Clemens, JQ
AF Berry, Sandra H.
Elliott, Marc N.
Suttorp, Marika
Bogart, Laura M.
Stoto, Michael A.
Eggers, Paul
Nyberg, Leroy
Clemens, J. Quentin
TI Prevalence of Symptoms of Bladder Pain Syndrome/Interstitial Cystitis
Among Adult Females in the United States
SO JOURNAL OF UROLOGY
LA English
DT Article
DE cystitis, interstitial; cross-sectional studies; prevalence; urinary
bladder
ID MANAGED CARE POPULATION; INTERSTITIAL CYSTITIS; NONRESPONSE RATES;
WOMEN; BIAS
AB Purpose: Bladder pain syndrome/interstitial cystitis is a poorly understood condition that can cause serious disability. We provide the first population based symptom prevalence estimate to our knowledge among United States adult females.
Materials and Methods: We developed and validated 2 case definitions to identify bladder pain syndrome/interstitial cystitis symptoms. Beginning in August 2007 we telephoned United States households, seeking adult women with bladder symptoms or a bladder pain syndrome/interstitial cystitis diagnosis. Second stage screening identified those subjects who met case definition criteria. Each completed a 60-minute interview on the severity and impact of bladder symptoms, health care seeking and demographics. Data collection ended in April 2009. Using population and nonresponse weights we calculated prevalence estimates based on definitions spanning a range of sensitivity and specificity. We used United States Census counts to estimate the number of affected women in 2006. The random sample included 146,231 households, of which 131,691 included an adult female. Of these households 32,474 reported an adult female with bladder symptoms or diagnosis, of which 12,752 completed the questionnaire.
Results: Based on the high sensitivity definition 6.53% (95% CI 6.28, 6.79) of women met symptom criteria. Based on the high specificity definition 2.70% (95% CI 2.53, 2.86) of women met the criteria. These percentages translated into 3.3 to 7.9 million United States women 18 years old or older with bladder pain syndrome/ interstitial cystitis symptoms. Symptom severity and impact were comparable to those of adult women with established diagnoses. However, only 9.7% of the women reported being assigned a bladder pain syndrome/interstitial cystitis diagnosis.
Conclusions: Bladder pain syndrome/interstitial cystitis symptoms are widespread among United States women and associated with considerable disability. These results suggest bladder pain syndrome/interstitial cystitis may be underdiagnosed.
C1 [Berry, Sandra H.; Elliott, Marc N.; Suttorp, Marika; Bogart, Laura M.] RAND Corp, Santa Monica, CA 90407 USA.
[Bogart, Laura M.] Childrens Hosp, Boston, MA 02115 USA.
[Stoto, Michael A.] Georgetown Univ, Washington, DC USA.
[Eggers, Paul; Nyberg, Leroy] NIDDK, Bethesda, MD USA.
[Clemens, J. Quentin] Univ Michigan, Ann Arbor, MI 48109 USA.
[Clemens, J. Quentin] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Berry, SH (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90407 USA.
EM berry@rand.org
FU National Institute of Diabetes and Digestive and Kidney Disorders
[U01DK070234-01]
FX Supported by Cooperative Agreement U01DK070234-01 from the National
Institute of Diabetes and Digestive and Kidney Disorders. National
Institute of Diabetes and Digestive and Kidney Disorders staff
participated in study design and analysis. Research protocol approved by
the Human Subjects Protection Committee (FWA00003425). The authors vouch
for the accuracy and completeness of the reported findings.
NR 14
TC 115
Z9 118
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD AUG
PY 2011
VL 186
IS 2
BP 540
EP 544
DI 10.1016/j.juro.2011.03.132
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 789VJ
UT WOS:000292545100059
PM 21683389
ER
PT J
AU Markland, AD
Richter, HE
Fwu, CW
Eggers, P
Kusek, JW
AF Markland, Alayne D.
Richter, Holly E.
Fwu, Chyng-Wen
Eggers, Paul
Kusek, John W.
TI Prevalence and Trends of Urinary Incontinence in Adults in the United
States, 2001 to 2008
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urinary incontinence; risk factors; epidemiology; female; male
ID NUTRITION EXAMINATION SURVEY; TRACT SYMPTOMS; RISK-FACTORS;
NATIONAL-HEALTH; OBESE WOMEN; WEIGHT-LOSS; POPULATION; PREDICTORS;
SURGERY; COHORT
AB Purpose: We estimate trends in the prevalence of urinary incontinence in the adult population of the United States from 2001 through 2008 before and after adjusting for other potential associated factors.
Materials and Methods: We analyzed data on 17,850 adults 20 years old or older who participated in the 2001 to 2008 cycles of the National Health and Nutrition Examination Survey. Any urinary incontinence was defined as a positive response to questions on urine leakage during physical activity, before reaching the toilet and during nonphysical activity. During this period changes in demographic and clinical factors associated with urinary incontinence included age, race/ethnicity, obesity, diabetes and chronic medical conditions (prostate disease in men). Age standardized prevalence estimates and prevalence ORs of urinary incontinence trends were determined using adjusted multivariate models with appropriate sampling weights.
Results: The age standardized prevalence of urinary incontinence in the combined surveys was 51.1% in women and 13.9% in men. Prevalence in women increased from 49.5% in 2001 to 2002, to 53.4% in 2007 to 2008 (P(trend) = 0.01) and in men from 11.5% to 15.1%, respectively (P(trend) = 0.01). In women increased prevalence was partially explained by differences in age, race/ethnicity, obesity, diabetes and select chronic diseases across the survey periods. After adjustment the prevalence OR for 2007 to 2008 vs 2001 to 2002 decreased from 1.22 (95% CI 1.03-1.45) to 1.16 (95% CI 0.99-1.37). In men adjustment for potentially associated factors did not explain the increasing prevalence of urinary incontinence.
Conclusions: The age standardized prevalence of urinary incontinence increased in men and women from 2001 through 2008. Decreasing obesity and diabetes may lessen the burden of urinary incontinence, especially in women.
C1 [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Div Womans Pelv Med & Reconstruct Surg, Birmingham, AL 35249 USA.
[Markland, Alayne D.] Univ Alabama, Dept Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL 35249 USA.
[Markland, Alayne D.] Univ Alabama, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35249 USA.
[Fwu, Chyng-Wen] Social & Sci Syst Inc, Silver Spring, MD USA.
[Eggers, Paul; Kusek, John W.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Richter, HE (reprint author), Univ Alabama, Dept Obstet & Gynecol, Div Womans Pelv Med & Reconstruct Surg, Birmingham, AL 35249 USA.
EM hrichter@uabmc.edu
FU NIDDK NIH HHS [K24 DK068389]
NR 29
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Z9 63
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD AUG
PY 2011
VL 186
IS 2
BP 589
EP 593
DI 10.1016/j.juro.2011.03.114
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 789VJ
UT WOS:000292545100080
PM 21684555
ER
PT J
AU Nager, CW
Sirls, L
Litman, HJ
Richter, H
Nygaard, I
Chai, T
Kraus, S
Zyczynski, H
Kenton, K
Huang, LY
Kusek, J
Lemack, G
AF Nager, Charles W.
Sirls, Larry
Litman, Heather J.
Richter, Holly
Nygaard, Ingrid
Chai, Toby
Kraus, Stephen
Zyczynski, Halina
Kenton, Kim
Huang, Liyuan
Kusek, John
Lemack, Gary
CA Urinary Incontinence Treatment Net
TI Baseline Urodynamic Predictors of Treatment Failure 1 Year After Mid
Urethral Sling Surgery
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urinary incontinence; stress; urodynamics; surgical procedures;
operative
ID FREE VAGINAL TAPE; STRESS URINARY-INCONTINENCE; INTRINSIC SPHINCTER
DEFICIENCY; TRANSOBTURATOR TAPE; MIDURETHRAL SLINGS; RANDOMIZED-TRIAL;
PRESSURE-FLOW; WOMEN
AB Purpose: We determined whether baseline urodynamic study variables predict failure after mid urethral sling surgery.
Materials and Methods: Preoperative urodynamic study variables and postoperative continence status were analyzed in women participating in a randomized trial comparing retropubic to transobturator mid urethral sling. Objective failure was defined by positive standardized stress test, 15 ml or greater on 24-hour pad test, or re-treatment for stress urinary incontinence. Subjective failure criteria were self-reported stress symptoms, leakage on 3-day diary or re-treatment for stress urinary incontinence. Logistic regression was used to assess associations between covariates and failure controlling for treatment group and clinical variables. Receiver operator curves were constructed for relationships between objective failure and measures of urethral function.
Results: Objective continence outcomes were available at 12 months for 565 of 597 (95%) women. Treatment failed in 260 women (245 by subjective criteria, 124 by objective criteria). No urodynamic variable was significantly associated with subjective failure on multivariate analysis. Valsalva leak point pressure, maximum urethral closure pressure and urodynamic stress incontinence were the only urodynamic variables consistently associated with objective failure on multivariate analysis. No specific cut point was determined for predicting failure for Valsalva leak point pressure or maximum urethral closure pressure by ROC. The lowest quartile (Valsalva leak point pressure less than 86 cm H(2)O, maximum urethral closure pressure less than 45 cm H(2)O) conferred an almost 2-fold increased odds of objective failure regardless of sling route (OR 2.23, 1.20-4.14 for Valsalva leak point pressure and OR 1.88, 1.04-3.41 for maximum urethral closure pressure).
Conclusions: Women with a Valsalva leak point pressure or maximum urethral closure pressure in the lowest quartile are nearly 2-fold more likely to experience stress urinary incontinence 1 year after transobturator or retropubic mid urethral sling.
C1 [Nager, Charles W.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA.
[Sirls, Larry] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA.
[Litman, Heather J.; Huang, Liyuan] New England Res Inst, Watertown, MA 02172 USA.
[Richter, Holly] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Nygaard, Ingrid] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Chai, Toby] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA.
[Kusek, John] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Kraus, Stephen] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Lemack, Gary] Univ Texas SW, Dept Urol, Dallas, TX USA.
[Zyczynski, Halina] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
[Kenton, Kim] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA.
RP Nager, CW (reprint author), 9350 Campus Point Dr,Suite 2A,Mailcode 0974, La Jolla, CA 92037 USA.
EM cnager@ucsd.edu
OI Wadie, Bassem/0000-0002-6977-6849
FU National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases
FX The Urinary Incontinence Treatment Network was supported by the National
Institutes of Health/National Institute of Diabetes and Digestive and
Kidney Diseases (see Appendix).
NR 25
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U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD AUG
PY 2011
VL 186
IS 2
BP 597
EP 603
DI 10.1016/j.juro.2011.03.105
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 789VJ
UT WOS:000292545100082
PM 21683412
ER
PT J
AU Denton, PW
Othieno, F
Martinez-Torres, F
Zou, W
Krisko, JF
Fleming, E
Zein, S
Powell, DA
Wahl, A
Kwak, YT
Welch, BD
Kay, MS
Payne, DA
Gallay, P
Appella, E
Estes, JD
Lu, M
Garcia, JV
AF Denton, Paul W.
Othieno, Florence
Martinez-Torres, Francisco
Zou, Wei
Krisko, John F.
Fleming, Elisa
Zein, Sima
Powell, Daniel A.
Wahl, Angela
Kwak, Youn Tae
Welch, Brett D.
Kay, Michael S.
Payne, Deborah A.
Gallay, Philippe
Appella, Ettore
Estes, Jacob D.
Lu, Min
Garcia, J. Victor
TI One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used
According to the CAPRISA 004 Experimental Design Demonstrates Partial
Protection from Vaginal HIV Infection, Validating the BLT Model for
Evaluation of New Microbicide Candidates
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIAL;
PLACEBO-CONTROLLED TRIAL; PHASE-III TRIAL; SHIV TRANSMISSION;
IMMUNE-RESPONSES; REFERENCE VALUES; DOUBLE-BLIND; PREVENTION; INHIBITOR
AB Recent iPrEx clinical trial results provided evidence that systemic preexposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) can partially prevent rectal HIV transmission in humans. Similarly, we have previously demonstrated that systemic administration of the same FTC-TDF combination efficiently prevented rectal transmission in humanized bone marrow/liver/thymus (BLT) mice. The CAPRISA 004 trial recently demonstrated that topical application of the tenofovir could partially prevent vaginal HIV-1 transmission in humans. To further validate the usefulness of the BLT mouse model for testing HIV prevention strategies, we evaluated the topical administration of tenofovir as used in CAPRISA 004 to prevent vaginal HIV transmission in BLT mice. Our results demonstrate that vaginally administered 1% tenofovir significantly reduced HIV transmission in BLT mice (P = 0.002). Together with the results obtained after systemic antiretroviral PrEP, these topical inhibitor data serve to validate the use of humanized BLT mice to evaluate both systemic and topical inhibitors of HIV transmission. Based on these observations, we tested six additional microbicide candidates for their ability to prevent vaginal HIV transmission: a C-peptide fusion inhibitor (C52L), a membrane-disrupting amphipathic peptide inhibitor (C5A), a trimeric D-peptide fusion inhibitor (PIE12-Trimer), a combination of reverse transcriptase inhibitors (FTC-TDF), a thioester zinc finger inhibitor (TC247), and a small-molecule Rac inhibitor (NSC23766). No protection was seen with the Rac inhibitor NSC23766. The thioester compound TC247 offered partial protection. Significant protection was afforded by FTC-TDF, and complete protection was offered by three different peptide inhibitors tested. Our results demonstrate that these effective topical inhibitors have excellent potential to prevent vaginal HIV transmission in humans.
C1 [Denton, Paul W.; Martinez-Torres, Francisco; Zou, Wei; Krisko, John F.; Wahl, Angela; Garcia, J. Victor] Univ N Carolina, Ctr AIDS Res, Dept Internal Med, Div Infect Dis, Chapel Hill, NC 27510 USA.
[Othieno, Florence; Fleming, Elisa; Zein, Sima; Powell, Daniel A.; Kwak, Youn Tae] Univ Texas SW Med Ctr Dallas, Div Infect Dis, Dallas, TX 75390 USA.
[Welch, Brett D.; Kay, Michael S.] Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT 84112 USA.
[Payne, Deborah A.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Gallay, Philippe] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Appella, Ettore] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Estes, Jacob D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Lu, Min] Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA.
RP Garcia, JV (reprint author), Univ N Carolina, Sch Med, UNC Ctr AIDS Res, Div Infect Dis, Genet Med Bldg 2044, Chapel Hill, NC 27599 USA.
EM victor_garcia@med.unc.edu
OI Denton, Paul/0000-0003-2458-8147
FU National Institutes of Health [AI073146, AI071940, AI082637, AI078791,
AI079782, AI68591, AI076168, 5T32AI005284]; National Cancer Institute,
National Institutes of Health [HHSN266200400088C]; UNC Center for AIDS
Research [P30 AI50410]; American Foundation for AIDS Research (amfAR)
[107752-44-RFRL]
FX This work was supported in part with federal funds from National
Institutes of Health grants AI073146 (J.V.G.), AI071940 (J.V.G.),
AI082637 (J.V.G.), AI078791 (P.G.), AI079782 (P.G.), AI68591 (M.L.),
AI076168 (M.S.K.), and 5T32AI005284 (J.F.K.), the National Cancer
Institute, National Institutes of Health, under contract
HHSN266200400088C (J.D.E.), and the UNC Center for AIDS Research Grant
P30 AI50410. This work was supported in part by fellowship number
107752-44-RFRL from the American Foundation for AIDS Research (amfAR)
(P.W.D.).
NR 57
TC 83
Z9 84
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2011
VL 85
IS 15
BP 7582
EP 7593
DI 10.1128/JVI.00537-11
PG 12
WC Virology
SC Virology
GA 788LV
UT WOS:000292447300012
PM 21593172
ER
PT J
AU Rockx, B
Brining, D
Kramer, J
Callison, J
Ebihara, H
Mansfield, K
Feldmann, H
AF Rockx, Barry
Brining, Douglas
Kramer, Joshua
Callison, Julie
Ebihara, Hideki
Mansfield, Keith
Feldmann, Heinz
TI Clinical Outcome of Henipavirus Infection in Hamsters Is Determined by
the Route and Dose of Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HENDRA VIRUS-INFECTION; RESPIRATORY SYNDROME CORONAVIRUS; TO-PERSON
TRANSMISSION; NIPAH VIRUS; RISK-FACTORS; FATAL ENCEPHALITIS;
DISTRESS-SYNDROME; MOUSE MODEL; OUTBREAK; PARAMYXOVIRUS
AB Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.
C1 [Rockx, Barry] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Rockx, Barry] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Rockx, Barry; Callison, Julie; Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Brining, Douglas] NIAID, Div Intramural Res, Rocky Mt Vet Branch, NIH, Hamilton, MT USA.
[Kramer, Joshua; Mansfield, Keith] Harvard Univ, Sch Med, Southborough, MA 01772 USA.
RP Rockx, B (reprint author), Univ Texas Med Branch, Dept Pathol, 301 Univ Blvd, Galveston, TX 77555 USA.
EM barry.rockx@utmb.edu
FU Division of Intramural Research (DIR), NIAID, NIH
FX This study was financially supported by the Division of Intramural
Research (DIR), NIAID, NIH.
NR 38
TC 50
Z9 50
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2011
VL 85
IS 15
BP 7658
EP 7671
DI 10.1128/JVI.00473-11
PG 14
WC Virology
SC Virology
GA 788LV
UT WOS:000292447300019
PM 21593160
ER
PT J
AU McLellan, JS
Yang, YP
Graham, BS
Kwong, PD
AF McLellan, Jason S.
Yang, Yongping
Graham, Barney S.
Kwong, Peter D.
TI Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the
Postfusion Conformation Reveals Preservation of Neutralizing Epitopes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID F-PROTEIN; MONOCLONAL-ANTIBODIES; MEMBRANE-FUSION; ELECTRON-MICROSCOPY;
CRYSTAL-STRUCTURE; HIV-1 GP41; VACCINE; DISEASE; HEMAGGLUTININ;
INFECTION
AB Respiratory syncytial virus (RSV) invades host cells via a type I fusion (F) glycoprotein that undergoes dramatic structural rearrangements during the fusion process. Neutralizing monoclonal antibodies, such as 101F, palivizumab, and motavizumab, target two major antigenic sites on the RSV F glycoprotein. The structures of these sites as peptide complexes with motavizumab and 101F have been previously determined, but a structure for the trimeric RSV F glycoprotein ectodomain has remained elusive. To address this issue, we undertook structural and biophysical studies on stable ectodomain constructs. Here, we present the 2.8-angstrom crystal structure of the trimeric RSV F ectodomain in its postfusion conformation. The structure revealed that the 101F and motavizumab epitopes are present in the postfusion state and that their conformations are similar to those observed in the antibody-bound peptide structures. Both antibodies bound the postfusion F glycoprotein with high affinity in surface plasmon resonance experiments. Modeling of the antibodies bound to the F glycoprotein predicts that the 101F epitope is larger than the linear peptide and restricted to a single protomer in the trimer, whereas motavizumab likely contacts residues on two protomers, indicating a quaternary epitope. Mechanistically, these results suggest that 101F and motavizumab can bind to multiple conformations of the fusion glycoprotein and can neutralize late in the entry process. The structural preservation of neutralizing epitopes in the postfusion state suggests that this conformation can elicit neutralizing antibodies and serve as a useful vaccine antigen.
C1 [McLellan, Jason S.; Yang, Yongping; Graham, Barney S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP McLellan, JS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Rm 2613B, Bethesda, MD 20892 USA.
EM mclellanja@mail.nih.gov
RI McLellan, Jason/A-6874-2010
FU National Institute of Allergy and Infectious Diseases; U.S. Department
of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
FX Support for this work was provided by the Intramural Research Program
(National Institute of Allergy and Infectious Diseases). Use of sector
22 (SER-CAT) at the Advanced Photon Source was supported by the U.S.
Department of Energy, Basic Energy Sciences, Office of Science, under
contract W-31-109-Eng-38.
NR 47
TC 127
Z9 133
U1 24
U2 38
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2011
VL 85
IS 15
BP 7788
EP 7796
DI 10.1128/JVI.00555-11
PG 9
WC Virology
SC Virology
GA 788LV
UT WOS:000292447300030
PM 21613394
ER
PT J
AU Parks, CG
DeRoo, LA
Miller, DB
McCanlies, EC
Cawthon, RM
Sandler, DP
AF Parks, C. G.
DeRoo, L. A.
Miller, D. B.
McCanlies, E. C.
Cawthon, R. M.
Sandler, D. P.
TI Employment and work schedule are related to telomere length in women
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; LIFE-STYLE; CIGARETTE-SMOKING; PERCEIVED STRESS;
HEALTH BEHAVIORS; LONG WORKHOURS; OVERTIME WORK; MORTALITY; ASSOCIATION;
RECOVERY
AB Objectives To examine the association of employment and work schedule with shorter DNA telomeres, a marker of cellular ageing and disease risk factor, and consider whether differences were related to health, behaviours and sociodemographic factors, or varied by stress levels or menopausal status.
Methods This cross-sectional analysis of 608 women aged 35-74 in the Sister Study examined determinants of relative telomere length (rTL) measured by quantitative PCR in leucocyte DNA. Age-adjusted regression models estimated base pair (bp) rTL differences for current and lifetime schedule characteristics (ie, part-time, full-time or overtime hours; multiple jobs; irregular hours; shiftwork; work at night). Covariates included race, smoking, perceived stress, sleep, physical activity, health and menopausal status, education, marital status, live births, children under 18, measured body mass index and urinary stress hormones.
oResults Compared with non-employed women with moderate or substantial past work histories (n=190), those currently working full-time (n=247; median 40 h/week) had a shorter rTL, an age-adjusted difference of -329 bp (95% CI -110 to -548). Longer-duration full-time work was also associated with shorter rTL (age-adjusted difference of -472 bp, 95% CI -786 to -158 for 20+ vs 1-5 years). Findings were not explained by health and demographic covariates. However, rTL differences for working at least full-time were greater in women with higher stress and epinephrine levels.
Conclusions Current and long-term full-time work were associated with shorter rTL, with differences of similar magnitude to smoking and history of heart disease or diabetes. Longitudinal data with specific stress measures are needed to further evaluate the impact of work schedule on rTL.
C1 [Parks, C. G.; DeRoo, L. A.; Sandler, D. P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27599 USA.
[Miller, D. B.] NIOSH, Toxicol & Mol Biol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[McCanlies, E. C.] NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Cawthon, R. M.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, NIH, A3-05,POB 12233, Res Triangle Pk, NC 27599 USA.
EM parks1@mail.nih.gov
RI Miller, Diane/O-2927-2013;
OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018
FU NIH, National Institute of Environmental Health Sciences [Z01 ES044005];
Department of Defense [BC045286]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences (Z01
ES044005), and by Department of Defense Breast Cancer Research Concept
Award (BC045286).
NR 39
TC 19
Z9 19
U1 1
U2 13
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
EI 1470-7926
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD AUG
PY 2011
VL 68
IS 8
BP 582
EP 589
DI 10.1136/oem.2010.063214
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 788MT
UT WOS:000292449800006
PM 21540175
ER
PT J
AU Xu, Y
Deng, Z
O'hUigin, C
Wang, D
Gao, S
Zeng, J
Yang, B
Jin, S
Zou, H
AF Xu, Y.
Deng, Z.
O'hUigin, C.
Wang, D.
Gao, S.
Zeng, J.
Yang, B.
Jin, S.
Zou, H.
TI Characterization and polymorphic analysis of 4.5 kb genomic full-length
HLA-C in the Chinese Han population
SO TISSUE ANTIGENS
LA English
DT Article
DE evolution; genomic full-length; high-fidelity polymerase chain reaction
amplification; human leukocyte antigen C; single-nucleotide
polymorphisms
ID MHC CLASS-I; MAJOR HISTOCOMPATIBILITY COMPLEX; MESSENGER-RNA;
MARROW-TRANSPLANTATION; SURFACE EXPRESSION; UNRELATED DONOR; ALPHA-3
DOMAIN; HEAVY-CHAIN; RECOGNITION; BINDING
AB This study used long-range polymerase chain reaction to sequence 4.5 or 4.3 kb of genomic DNA covering human leukocyte antigen C (HLA-C) and its flanks in 45 Chinese Han subjects to better characterize variation in the gene in a single population. Sequences of 35 HLA-C alleles were obtained from the population, including major alleles of 13 lineages of HLA-C. Four novel alleles, C*03:04:01:02, C*04:01:01:03, C*08:22, and C*17:01:01:02, were identified, and complete full-length sequences of 18 HLA-C alleles were obtained for the first time. All sequences herein reported also represent extensions through the promoter region and the 3'-untranslated region. Fourteen 5'-nucleotide sequences and 14 3'-nucleotide sequences were detected outside the coding region. In total, 316 single-nucleotide polymorphisms unequally distributed in HLA-C subregions were observed. In addition to exons 2 and 3, nucleotide variability was found to be particularly high in exon 5, which encodes the transmembrane region. The differentiation of the C*07 and C*17 lineages in this region accounts for the high variability. The congruence of phylogeny across most regions of the gene suggests that gene conversion or recombination has not markedly influenced divergence between lineages in the evolution of HLA-C.
C1 [Xu, Y.; Deng, Z.; Wang, D.; Gao, S.; Zeng, J.; Yang, B.; Jin, S.; Zou, H.] Shenzhen Blood Ctr, Immunogenet Lab, Shenzhen 518035, Guangdong, Peoples R China.
[O'hUigin, C.] NCI, Genet Core Canc & Inflammat Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Deng, Z (reprint author), Shenzhen Blood Ctr, Immunogenet Lab, Shenzhen 518035, Guangdong, Peoples R China.
EM zhihui_deng@yahoo.com.cn; ohuiginc@mail.nih.gov
FU Guangdong Science and Technology Department [2008B030301277]; Guangdong
Natural Science Fund [9451803501004124]; National Cancer Institute,
National Institutes of Health, Frederick, MD, USA; [HHSN261200800001E]
FX Sample preparation, sequencing analysis, and all experimental work were
conducted at the Shenzhen Blood Center, Shenzhen, Guangdong, China,
which was supported by the Research Fund of Guangdong Science and
Technology Department (Project No. 2008B030301277) and the Guangdong
Natural Science Fund (Project No. 9451803501004124). Additional
phylogenetic analysis was conducted by Dr CO, who was supported by the
National Cancer Institute, National Institutes of Health, Frederick, MD,
USA, with federal funds under HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government.
NR 41
TC 5
Z9 6
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 AUG
PY 2011
VL 78
IS 2
BP 102
EP 114
DI 10.1111/j.1399-0039.2011.01710.x
PG 13
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 788NC
UT WOS:000292450700005
PM 21658009
ER
PT J
AU Li, L
Ding, YY
Wu, ZY
Rotheram-Borus, MJ
Guo, S
AF Li, Li
Ding, Ying Ying
Wu, Zunyou
Rotheram-Borus, Mary Jane
Guo, Sam
CA NIMH Collaborative HIV STD
TI Normative Beliefs and Sexual Risk in China
SO AIDS AND BEHAVIOR
LA English
DT Article
DE China; Normative beliefs; Sexually transmitted infection; Gender roles
ID HIV PREVENTION INTERVENTIONS; TRANSMITTED-DISEASES; SERVICE PROVIDERS;
EXTRAMARITAL SEX; HIDDEN EPIDEMIC; MARKET VENDORS; EASTERN CHINA; SOCIAL
NORMS; CONDOM USE; AT-RISK
AB We examined normative beliefs about multiple sexual partners and social status in China and their association with risky sexual behaviors and sexually transmitted infections (STIs). Self-reported and biological markers of sexual risk were examined among 3,716 market vendors from a city in eastern China. Men who were older or with less education believed having multiple sexual partners was linked to higher social status. Adjusting for demographic characteristics, normative beliefs were significantly associated with having multiple sexual partners, while having multiple sexual partners was significantly associated with STIs. Normative beliefs regarding sexual behaviors may play an important role in individual risk behaviors. Future HIV/STI interventions must address community beliefs about the positive meaning of sexual risks, particularly among men with traditional beliefs about gender roles.
C1 [Li, Li; Ding, Ying Ying; Rotheram-Borus, Mary Jane; Guo, Sam] Univ Calif Los Angeles, Ctr Community Hlth, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
[Wu, Zunyou] China CDC, Natl Ctr AIDS STD Control & Prevent, Beijing, Peoples R China.
[Wu, Zunyou] NIMH, NIMH Collaborat HIV STD Prevent Trial Grp, Bethesda, MD 20892 USA.
RP Li, L (reprint author), Univ Calif Los Angeles, Ctr Community Hlth, Semel Inst Neurosci & Human Behav, 10920 Wilshire Blvd,Suite 350, Los Angeles, CA 90024 USA.
EM lililili@ucla.edu
FU NIAID NIH HHS [AI067854]; NIMH NIH HHS [U10 MH061513, P30 MH058107]
NR 56
TC 4
Z9 4
U1 2
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS behav.
PD AUG
PY 2011
VL 15
IS 6
BP 1251
EP 1258
DI 10.1007/s10461-010-9835-4
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 785YF
UT WOS:000292268400018
PM 20960047
ER
PT J
AU Napoli, N
Pedone, C
Pozzilli, P
Lauretani, F
Bandinelli, S
Ferrucci, L
Incalzi, RA
AF Napoli, Nicola
Pedone, Claudio
Pozzilli, Paolo
Lauretani, Fulvio
Bandinelli, Stefania
Ferrucci, Luigi
Incalzi, Raffaele Antonelli
TI Effect of ghrelin on bone mass density: The In Chianti study
SO BONE
LA English
DT Article
DE Ghrelin; Bone mass; pQCT; Aged, 65 years and older; Cross-sectional
studies
ID SYMPATHETIC-NERVOUS-SYSTEM; MINERAL DENSITY; POSTMENOPAUSAL WOMEN; SERUM
LEPTIN; FAT MASS; PLASMA GHRELIN; BODY-MASS; ADIPONECTIN; OBESITY;
TURNOVER
AB Introduction: Ghrelin is a stomach secreted hormone, believed to play an important role in energy balance and in food intake. Experimental studies have shown a positive effect of ghrelin on bone metabolism, but both in vivo and clinical findings have been contradictory. We aimed to investigate the effect of ghrelin on volumetric BMD in a large cohort of elderly subjects.
Methods: We have studied 401 women (mean age 75.1 years, range 65-94) and 306 men (mean age 73.9 years, range 65-94) from the InChianti study, which included measurements of BMD using quantitative CT of the tibia and of body composition using bio impedancemetry. Serum ghrelin was measured using ELISA. We excluded participants with diabetes, hyperthyroidism, using hormone replacement or glucocorticoid therapy. We evaluated the correlation of ghrelin with total, trabecular, and cortical BMD using Pearson's coefficient, and linear regression models to estimate the association between ghrelin and BMD controlling for potential confounders.
Results: In women, after correction for potential confounders, ghrelin was associated with trabecular BMD (beta = 7.08, P < 0.02), but not with total or cortical BMD. In men, adjusted multivariable models showed a nearly significant association between serum ghrelin and trabecular BMD (beta = 4.99, P = 0.069) and no association with either cortical or total BMD.
Conclusions: Serum ghrelin is positively correlated with trabecular BMD in a cohort of elderly healthy Italian women. The fact that trabecular is more metabolically active than cortical bone and the larger number of females might explain this selective association. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Pedone, Claudio; Incalzi, Raffaele Antonelli] Univ Campus Biomed Roma, Ctr Salute Anziano, Area Geriatria, I-00128 Rome, Italy.
[Napoli, Nicola; Pozzilli, Paolo] Univ Campus Biomed Roma, Div Endocrinol & Diabet, I-00128 Rome, Italy.
[Napoli, Nicola] Washington Univ, Div Bone & Mineral Dis, St Louis, MO USA.
[Lauretani, Fulvio] Univ Hosp Pamm, Geriatr Rehabil Dept, Geriatr Unit, Parma, Italy.
[Lauretani, Fulvio] Univ Hosp Pamm, Geriatr Rehabil Dept, Lab Movement Anal, Parma, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Incalzi, Raffaele Antonelli] Fdn San Raffaele, Cittadella Della Carita, Taranto, Italy.
RP Pedone, C (reprint author), Univ Campus Biomed Roma, Ctr Salute Anziano, Area Geriatria, Via Alvaro del Portillo 21, I-00128 Rome, Italy.
EM c.pedone@unicampus.it
RI Antonelli Incalzi, Raffaele/G-3978-2012; Lauretani, Fulvio/K-5115-2016;
OI Antonelli Incalzi, Raffaele/0000-0003-2100-2075; Napoli,
Nicola/0000-0002-3091-8205; Pedone, Claudio/0000-0003-1847-9032;
Lauretani, Fulvio/0000-0002-5287-9972; Pozzilli,
Paolo/0000-0001-5090-636X
FU Intramural NIH HHS [ZIA AG001050-09]
NR 37
TC 17
Z9 17
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD AUG
PY 2011
VL 49
IS 2
BP 257
EP 263
DI 10.1016/j.bone.2011.03.772
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 787EC
UT WOS:000292358400013
PM 21501701
ER
PT J
AU Goor, RM
Neall, LF
Hoffman, D
Sherry, ST
AF Goor, Robert M.
Neall, Lisa Forman
Hoffman, Douglas
Sherry, Stephen T.
TI A Mathematical Approach to the Analysis of Multiplex DNA Profiles
SO BULLETIN OF MATHEMATICAL BIOLOGY
LA English
DT Article
DE DNA; STR; Multiplex; Electrophoresis; Cubic spline; Inner product; Norm;
Gaussian; OSIRIS; Forensics; Profile; Biomedical
ID CAPILLARY-ELECTROPHORESIS
AB Multiplex DNA profiles are used extensively for biomedical and forensic purposes. However, while DNA profile data generation is automated, human analysis of those data is not, and the need for speed combined with accuracy demands a computer-automated approach to sample interpretation and quality assessment. In this paper, we describe an integrated mathematical approach to modeling the data and extracting the relevant information, while rejecting noise and sample artifacts. We conclude with examples showing the effectiveness of our algorithms.
C1 [Goor, Robert M.; Neall, Lisa Forman; Hoffman, Douglas; Sherry, Stephen T.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Goor, RM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM goorrob@mail.nih.gov
FU NIH, National Library of Medicine
FX We wish to thank Masato Kimura for many valuable discussions. We also
wish to thank John Spouge for his help with the mathematical modeling of
the electrophoresis process. This research was supported by the
Intramural Research Program of the NIH, National Library of Medicine.
NR 12
TC 2
Z9 2
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0092-8240
J9 B MATH BIOL
JI Bull. Math. Biol.
PD AUG
PY 2011
VL 73
IS 8
BP 1909
EP 1931
DI 10.1007/s11538-010-9598-0
PG 23
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA 784MB
UT WOS:000292160300010
PM 21103945
ER
PT J
AU Sales, JD
Lara, FA
Amadeu, TP
Fulco, TD
Nery, JAD
Sampaio, EP
Pinheiro, RO
Sarno, EN
AF de Souza Sales, J.
Lara, F. A.
Amadeu, T. P.
de Oliveira Fulco, T.
da Costa Nery, J. A.
Sampaio, E. P.
Pinheiro, R. O.
Sarno, E. N.
TI The role of indoleamine 2, 3-dioxygenase in lepromatous leprosy
immunosuppression
SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY
LA English
DT Article
DE IDO; IFN-gamma; lepromatous leprosy; monocytes; Mycobacterium leprae
ID NECROSIS-FACTOR-ALPHA; ERYTHEMA-NODOSUM LEPROSUM; REACTIVE T-CELLS;
INTERFERON-GAMMA; DENDRITIC CELLS; 2,3-DIOXYGENASE ACTIVITY; TRYPTOPHAN
CATABOLISM; INTRADERMAL INJECTION; CYTOKINE PRODUCTION; SKIN-LESIONS
AB To elucidate further the possible role of the tryptophan, rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO) in leprosy, the distribution of IDO-positive cells and IDO activity in the skin biopsies and sera of these patients representing the entire spectrum of the disease were studied. An increased number of macrophages/dendritic cells (DC-lineage IDO(+) cells were found in lepromatous (LL) compared to tuberculoid (BT) and reversal reaction (RR) patients. IDO-positive cells showing CD68 and CD86 surface markers predominated in LL lesions, while higher levels of IDO activity were observed in the sera of LL versus BT patients. Tests revealed an increased IDO message in Mycobacterium leprae-stimulated peripheral blood mononuclear cells (PBMC) by real-time polymerase chain reaction (PCR) and increased IDO expression in M. leprae-stimulated CD14(+) cells of both healthy controls (HC) and LL patients, as evaluated via flow cytometry. Increased M. leprae-induced IDO-protein synthesis was also confirmed by Western blot. Based on our in vitro studies, it was confirmed that M. leprae up-regulated IDO expression and activity in HC and LL monocytes. Interferon (IFN)-gamma synergized with M. leprae in promoting IDO expression and activity in monocytes. IDO expression induced by both IFN-gamma and M. leprae was abrogated by 1-methyltryptophan (1-MT). Our data suggest that M. leprae chronic infection activates the suppressive molecule IDO which, in turn, contributes to the specific immunosuppression observed in LL leprosy.
C1 [de Souza Sales, J.; Amadeu, T. P.; de Oliveira Fulco, T.; da Costa Nery, J. A.; Sampaio, E. P.; Pinheiro, R. O.; Sarno, E. N.] Fiocruz MS, Oswaldo Cruz Fdn, Leprosy Lab, BR-21040900 Rio De Janeiro, Brazil.
[Lara, F. A.] Fiocruz MS, Cellular Microbiol Lab, Leprosy Lab, BR-21040900 Rio De Janeiro, Brazil.
[Sampaio, E. P.] NIH, Lab Clin Infect Dis, Ctr Clin, Bethesda, MD 20892 USA.
RP Sarno, EN (reprint author), Fiocruz MS, Oswaldo Cruz Fdn, Leprosy Lab, Av Brasil 4365, BR-21040900 Rio De Janeiro, Brazil.
EM euzenir@ioc.fiocruz.br
RI Amadeu, Thais/C-2152-2013; Lara, Flavio/L-1861-2013
FU National Institutes of Health
FX We would especially like to thank Helen Ferreira for her excellent
technical assistance, Dr Paulo Redner, Dr Daniel Serra de Carvalho,
Ariane Leite de Oliveira, and Danielle Fonseca de Moura for their
insightful discussion of the manuscript and Judy Grevan for editing the
text. This study was partially supported by National Institutes of
Health.
NR 59
TC 14
Z9 14
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-9104
J9 CLIN EXP IMMUNOL
JI Clin. Exp. Immunol.
PD AUG
PY 2011
VL 165
IS 2
BP 251
EP 263
DI 10.1111/j.1365-2249.2011.04412.x
PG 13
WC Immunology
SC Immunology
GA 786WI
UT WOS:000292338200013
ER
PT J
AU Wang, F
Niu, G
Chen, XY
Cao, F
AF Wang, Fu
Niu, Gang
Chen, Xiaoyuan
Cao, Feng
TI Molecular imaging of microRNAs
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Review
DE MicroRNA; Molecular imaging; Reporter gene
ID GENE-EXPRESSION; IN-VIVO; LIVING CELLS; POSTTRANSCRIPTIONAL REGULATION;
TRANSGENE EXPRESSION; ENDOGENOUS MICRORNA; RNA DETECTION; CANCER;
IDENTIFICATION; BIOGENESIS
AB MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that regulate gene expression by targeting mRNAs for either cleavage or translational repression. They have been shown to play important roles in a broad range of biological processes including development, cellular differentiation, proliferation and apoptosis. Conventional detection methods, such as northern blot, real-time PCR or microarray, have been used to assess miRNA expression. However, these techniques require the fixation or lysis of cells, and thus cannot be used to study the dynamic function of miRNAs in living cells. Recent remarkable advances in molecular imaging techniques have provided the capability of noninvasive repeated quantitative imaging of tumour or stem cells in living animals. The current brief discussion focuses on the reporter and fluorescent beacon imaging approaches to visualize miRNA expression in living subjects.
C1 [Wang, Fu; Cao, Feng] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China.
[Wang, Fu] Xidian Univ, Life Sci Res Ctr, Sch Life Sci & Technol, Xian 710071, Peoples R China.
[Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
RP Cao, F (reprint author), Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China.
EM shawn.chen@nih.gov; wind8828@gmail.com
RI Life, MC/M-9554-2013;
OI Wang, Fu/0000-0001-9222-0833
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health; National Basic Research and Development Program of
China (973) [2006CB705700, 2011CB707702]; National Natural Science
Foundation of China [81090272, 81090274, 81000632, 30900334, 30970845];
Fundamental Research Funds for the Central Universities [JY10000910002]
FX This work was supported in part by the Intramural Research Program of
the National Institute of Biomedical Imaging and Bioengineering,
National Institutes of Health, the National Basic Research and
Development Program of China (973) under grant nos. 2006CB705700 and
2011CB707702, the National Natural Science Foundation of China under
grant nos. 81090272, 81090274, 81000632, 30900334 and 30970845, and the
Fundamental Research Funds for the Central Universities under grant no.
JY10000910002.
NR 54
TC 24
Z9 25
U1 6
U2 44
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD AUG
PY 2011
VL 38
IS 8
BP 1572
EP 1579
DI 10.1007/s00259-011-1786-0
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 785ZV
UT WOS:000292272700019
PM 21448701
ER
PT J
AU Hoffer, BJ
AF Hoffer, Barry J.
TI Commentary on chronic infusion of CDNF prevents 6-OHDA-induced deficits
in a rat model of Parkinson's disease. Merja H. Voutilainen et al.
SO EXPERIMENTAL NEUROLOGY
LA English
DT Editorial Material
ID MIDBRAIN DOPAMINERGIC-NEURONS; NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR
GDNF; IN-VIVO; INDUCED DEGENERATION; LIGAND FAMILY; GENE-TRANSFER;
LESION MODEL; BRAIN; 6-HYDROXYDOPAMINE
C1 NIDA, Intramural Res Program, Bethesda, MD USA.
RP Hoffer, BJ (reprint author), NIDA, Intramural Res Program, Bethesda, MD USA.
EM bhoffer@intra.nida.nih.gov
FU NINDS NIH HHS [R01 NS070825]
NR 69
TC 1
Z9 2
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
J9 EXP NEUROL
JI Exp. Neurol.
PD AUG
PY 2011
VL 230
IS 2
BP 162
EP 166
DI 10.1016/j.expneurol.2011.04.015
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 783CF
UT WOS:000292058400002
PM 21554875
ER
PT J
AU Chou, JY
Mansfield, BC
AF Chou, Janice Y.
Mansfield, Brian C.
TI Recombinant AAV-directed gene therapy for type I glycogen storage
diseases
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE AAV; endoplasmic reticulum; gene therapy; glucose homeostasis;
glucose-6-phosphatase; glucose-6-phosphate transporter; glycogen storage
disease; hepatic gene delivery
ID ADENOASSOCIATED VIRUS VECTORS; NONHUMAN PRIMATE LIVER; HIGHLY EFFICIENT
TRANSDUCTION; COLONY-STIMULATING FACTOR; RATE-LIMITING STEP; T-CELL
RESPONSES; GLUCOSE-6-PHOSPHATE TRANSPORTER; VIRAL VECTORS;
IMMUNE-RESPONSES; CANINE MODEL
AB Introduction: Glycogen storage disease (GSD) type Ia and Ib are disorders of impaired glucose homeostasis affecting the liver and kidney. GSD-Ib also affects neutrophils. Current dietary therapies cannot prevent long-term complications. In animal studies, recombinant adeno-associated virus (rAAV) vector-mediated gene therapy can correct or minimize multiple aspects of the disorders, offering hope for human gene therapy.
Areas covered: A summary of recent progress in rAAV-mediated gene therapy for GSD-I; strategies to improve rAAV-mediated gene delivery, transduction efficiency and immune avoidance; and vector refinements that improve expression.
Expert opinion: rAAV-mediated gene delivery to the liver can restore glucose homeostasis in preclinical models of GSD-I, but some long-term complications of the liver and kidney remain. Gene therapy for GSD-Ib is less advanced than for GSD-Ia and only transient correction of myeloid dysfunction has been achieved. A question remains as to whether a single rAAV vector can meet the expression efficiency and tropism required to treat all aspects of GSD-I, or if a multi-pronged approach is needed. An understanding of the strengths and weaknesses of rAAV vectors in the context of strategies to achieve efficient transduction of the liver, kidney and hematopoietic stem cells is required for treating GSD-I.
C1 [Chou, Janice Y.; Mansfield, Brian C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Mansfield, Brian C.] Correlog Syst Inc, Germantown, MD 20876 USA.
RP Chou, JY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA.
EM chouja@mail.nih.gov
OI Mansfield, Brian/0000-0002-8533-2789
FU Eunice Kennedy Shriver National Institute Institute of Child Health and
Human Development, National Institutes of Health
FX This research was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute Institute of Child Health and
Human Development, National Institutes of Health.
NR 109
TC 7
Z9 9
U1 0
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1471-2598
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD AUG
PY 2011
VL 11
IS 8
BP 1011
EP 1024
DI 10.1517/14712598.2011.578067
PG 14
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA 785CG
UT WOS:000292204400004
PM 21504389
ER
PT J
AU Freedman, ND
Murray, LJ
Kamangar, F
Abnet, CC
Cook, MB
Nyren, O
Ye, WM
Wu, AH
Bernstein, L
Brown, LM
Ward, MH
Pandeya, N
Green, AC
Casson, AG
Giffen, C
Risch, HA
Gammon, MD
Chow, WH
Vaughan, TL
Corley, DA
Whiteman, DC
AF Freedman, Neal D.
Murray, Liam J.
Kamangar, Farin
Abnet, Christian C.
Cook, Michael B.
Nyren, Olof
Ye, Weimin
Wu, Anna H.
Bernstein, Leslie
Brown, Linda M.
Ward, Mary H.
Pandeya, Nirmala
Green, Adele C.
Casson, Alan G.
Giffen, Carol
Risch, Harvey A.
Gammon, Marilie D.
Chow, Wong-Ho
Vaughan, Thomas L.
Corley, Douglas A.
Whiteman, David C.
TI Alcohol intake and risk of oesophageal adenocarcinoma: a pooled analysis
from the BEACON Consortium
SO GUT
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; GASTRIC CARDIA CARCINOMAS; ESOPHAGOGASTRIC
JUNCTION; CANCER INCIDENCE; UNITED-STATES; TOBACCO; SMOKING; OBESITY;
METAANALYSIS; CONSUMPTION
AB Background and aims Alcohol intake is a strong and well established risk factor for oesophageal squamous cell carcinoma (OSCC), but the association with oesophageal adenocarcinoma (OA) or adjacent tumours of the oesophagogastric junction (OGJA), remains unclear. Therefore, the association of alcohol intake with OSCC, OA, and OGJA was determined in nine case-control studies and two cohort studies of the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON).
Materials and methods Information was collected on alcohol intake, age, sex, education, body mass index, gastro-oesophageal reflux, and tobacco smoking from each study. Along with 10 854 controls, 1821 OA, and 1837 OGJA, seven studies also collected OSCC cases (n=1016). Study specific ORs and 95% CIs were calculated from multivariate adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models.
Results No increase was observed in the risk of OA or OGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category (>= 7 drinks per day) were 0.97 (95% CI 0.68 to 1.36) for OA and 0.77 (95% CI=0.54 to 1.10) for OGJA. Suggestive findings linked moderate intake (eg, 0.5 to <1 drink per day) to decreased risk of OA (OR 0.63, 95% CI 0.41 to 0.99) and OGJA (OR 0.78, 95% CI 0.62 to 0.99). In contrast, alcohol intake was strongly associated with increased risk of OSCC (OR for >= 7 drinks per day 9.62, 95% CI 4.26 to 21.71).
Conclusions In contrast to OSCC, higher alcohol consumption was not associated with increased risk of either OA or OGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies.
C1 [Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS,Nutr Epidemiol Branch, Rockville, MD 20852 USA.
[Murray, Liam J.] Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
[Nyren, Olof; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
[Brown, Linda M.] RTI Int, Rockville, MD USA.
[Pandeya, Nirmala; Green, Adele C.; Whiteman, David C.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Casson, Alan G.] Univ Saskatchewan, Dept Surg, Saskatoon, SK, Canada.
[Giffen, Carol] Informat Management Serv Inc, Bethesda, MD USA.
[Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Corley, Douglas A.] Northern Calif, Div Res, Oakland, CA USA.
[Corley, Douglas A.] Northern Calif, Oakland Med Ctr, Oakland, CA USA.
RP Freedman, ND (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS,Nutr Epidemiol Branch, 6120 Executive Blvd,EPS 320,MSC 7232, Rockville, MD 20852 USA.
EM freedmanne@mail.nih.gov
RI Cook, Michael/A-5641-2009; Abnet, Christian/C-4111-2015; Freedman,
Neal/B-9741-2015; Whiteman, David/P-2728-2014; Green, Adele/P-2736-2014;
Pandeya, Nirmala/F-8054-2010
OI Cook, Michael/0000-0002-0533-7302; Abnet, Christian/0000-0002-3008-7843;
Freedman, Neal/0000-0003-0074-1098; Whiteman, David/0000-0003-2563-9559;
Green, Adele/0000-0002-2753-4841; Pandeya, Nirmala/0000-0003-1462-4968
FU National Institutes of Health [R01 DK063616, R21DKO77742]; California
Tobacco Related Research Program [3RT-0122, 10RT-0251]; National Cancer
Institute [CA59636]; Nova Scotia Health Research Foundation [N419];
Ireland-Northern Ireland Co-operation Research Project; Northern Ireland
Research & Development Office; Health Research Board, Ireland;
Queensland Cancer Fund; National Health and Medical Research Council
(NHMRC) of Australia [199600]; [R01-CA30022]; [R37-CA41530];
[U01-CA57949]; [U01-CA57983]; [U01-CA57923]; [R01 CA57947-03]
FX This work was supported in part by the Intramural Program of the
National Institutes of Health. The Population Health Study was funded by
the Intramural Program of the National Institutes of Health. The Larynx,
Oesophagus, and Oral Cavity (LEO) Study was funded by grants R01-CA30022
and R37-CA41530 (both awarded to TLV, David Thomas, Scott Davis, Bonnie
Worthington Roberts, Ruth Little, and Mary Rogers). The US Multi-Center
Study was funded by grants U01-CA57949 (awarded to TLV), U01-CA57983
(awarded to MDG), and U01-CA57923 (awarded to HAR). The Swedish
Esophageal Cancer Study was funded by grant number R01 CA57947-03
(awarded to ON and Hans-Olov Adami). The Los Angeles County Multi-ethnic
Case-control Study was funded by grants 3RT-0122 ('Smoking and Risk of
Proximal vs Distal Gastric Cancer', awarded to AHW) and 10RT-0251
('Smoking, microsatellite instability & gastric cancers', awarded to
AHW) from the California Tobacco Related Research Program and grant
CA59636 (awarded to LB) from the National Cancer Institute. The Nebraska
Health Study was funded by the Intramural Program of the National
Institutes of Health. The Nova Scotia Barrett Oesophagus Study was
supported by the Nova Scotia Health Research Foundation ('Molecular
mechanisms and lifestyle risk factor interactions in the pathogenesis of
human esophageal adenocarcinoma', N419, awarded to AGC). The Factors
Influencing the Barrett's Adenocarcinoma Relationship (FINBAR) study was
funded by an Ireland-Northern Ireland Co-operation Research Project
Grant sponsored by the Northern Ireland Research & Development Office,
and the Health Research Board, Ireland (All-Ireland case-control study
of Oesophageal Adenocarcinoma and Barrett's Oesophagus, awarded to LJM
and Harry Comber). The Australian Cancer Study was supported by the
Queensland Cancer Fund and the National Health and Medical Research
Council (NHMRC) of Australia (Program no. 199600, awarded to DCW, ACG,
Nicholas K Hayward, Peter G Parsons, David M Purdie, and Penelope M
Webb). NIH-AARP was funded by the Intramural Program of the National
Institutes of Health. Reported analyses with the Kaiser-Permanente
Multiphasic Health check-up Study were funded by NIH grant number R01
DK063616 (Epidemiology and Incidence of Barrett's Oesophagus, Kaiser
Permanente, awarded to DAC) and NIH grant R21DK077742 (Barrett's
Oesophagus: Risk Factors in Women, awarded to DAC and Nicholas J
Shaheen).
NR 31
TC 44
Z9 44
U1 0
U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD AUG
PY 2011
VL 60
IS 8
BP 1029
EP 1037
DI 10.1136/gut.2010.233866
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 786OQ
UT WOS:000292318200004
PM 21406386
ER
PT J
AU Chen, X
Oppenheim, JJ
AF Chen, Xin
Oppenheim, Joost J.
TI The phenotypic and functional consequences of tumour necrosis factor
receptor type 2 expression on CD4(+) FoxP3(+) regulatory T cells
SO IMMUNOLOGY
LA English
DT Review
DE CD4(+) FoxP3(+) regulatory T cells; CD4(+) FoxP3(-) effector T cells;
immunological phenotype; immunosuppression; tumour necrosis factor
receptor 2
ID TNF-ALPHA THERAPY; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES;
PERIPHERAL-BLOOD; DENDRITIC CELLS; INDUCTION; SUPPRESSION; TOLERANCE;
MECHANISM; P75
AB Cytokine receptors expressed by CD4(+) FoxP3(+) regulatory T cells (Treg cells) not only serve as a phenotypic marker for the identification of this important population of immunosuppressive cells, they also promote the function of Treg cells. CD25, the alpha-chain of interleukin-2 receptor, is a prototype of such a receptor, which enables Treg cells to be activated by interleukin-2. We and others have found that tumour necrosis factor receptor type 2 (TNFR2) is another important cytokine receptor preferentially expressed by Treg cells with important phenotypic and functional roles. TNFR2 is preferentially expressed by highly functional human and mouse Treg cells, and mediates the activating effect of TNF on Treg cells. We review here the studies of the regulation of expression of TNFR2 on functional Treg cells as well as on CD4(+) FoxP3(-) effector T cells (Teff cells). We document the critical role of this receptor in the activation, proliferative expansion and survival of Treg cells. The contribution of TNFR2 expression on Treg and Teff cells to the beneficial and detrimental effects of anti-TNF treatment in autoimmune disorders will also be discussed.
C1 [Chen, Xin] NCI, BSP, SAIC Frederick Inc, Lab Mol Immunoregulat,Canc Inflammat Program,Ctr, Frederick, MD 21702 USA.
RP Chen, X (reprint author), NCI, BSP, SAIC Frederick Inc, Lab Mol Immunoregulat,Canc Inflammat Program,Ctr, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA.
EM chenxin@mail.nih.gov; oppenhej@mail.nih.gov
RI Chen, Xin/I-6601-2015
OI Chen, Xin/0000-0002-2628-4027
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. This research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 53
TC 23
Z9 26
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD AUG
PY 2011
VL 133
IS 4
BP 426
EP 433
DI 10.1111/j.1365-2567.2011.03460.x
PG 8
WC Immunology
SC Immunology
GA 786TZ
UT WOS:000292332100004
PM 21631498
ER
PT J
AU Tooley, PW
Browning, M
Leighty, RM
AF Tooley, Paul W.
Browning, Marsha
Leighty, Robert M.
TI Infectivity and Sporulation of Phytophthora ramorum on Northern Red Oak
and Chestnut Oak
SO JOURNAL OF PHYTOPATHOLOGY
LA English
DT Article
DE ramorum blight; chlamydospore; epidemiology
ID FOREST; SUSCEPTIBILITY; CALIFORNIA; DEATH; RHODODENDRON; PATHOGEN;
INOCULUM
AB We evaluated the effect of moisture period on foliar disease development by Phytophthora ramorum on 2- to 3-year-old northern red oak (Quercus rubra) and chestnut oak (Q. prinus). We also determined the propensity of P. ramorum to form sporangia and chlamydospores on these two host species. Leaves were dip-inoculated with ca. 5000 sporangia/ml of P. ramorum isolate Pr-6 and incubated at 100% relative humidity in dew chambers in darkness for up to 6 days. Several plants were removed each day to a greenhouse, and foliar infection was evaluated on day 7. Sporangia were collected over a 7-day period from diseased foliage in a mist tent. A significant relationship between moisture period and disease incidence was found for both tree species. Chestnut oak exhibited significantly greater disease incidence and severity compared with northern red oak. However, sporulation levels were larger in northern red oak over the 7-day period of sporangia collection, and northern red oak also produced significantly greater numbers of sporangia per square centimetre of lesion area compared with chestnut oak. Chlamydospore production in diseased leaves sampled 1 month following moist incubation was also significantly greater for northern red oak compared with chestnut oak. Knowledge of P. ramorum sporulation capacity in relation to disease incidence and severity on Eastern US oak species will help determine the potential for epidemic development should the pathogen become established in this region.
C1 [Tooley, Paul W.; Browning, Marsha] USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA.
[Leighty, Robert M.] NCI, Data Management Serv, Frederick, MD 21702 USA.
RP Tooley, PW (reprint author), USDA ARS, Foreign Dis Weed Sci Res Unit, 1301 Ditto Ave, Ft Detrick, MD 21702 USA.
EM paul.tooley@ars.usda.gov
NR 26
TC 1
Z9 1
U1 1
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0931-1785
J9 J PHYTOPATHOL
JI J. Phytopathol.
PD AUG
PY 2011
VL 159
IS 7-8
BP 516
EP 521
DI 10.1111/j.1439-0434.2011.01797.x
PG 6
WC Plant Sciences
SC Plant Sciences
GA 786XG
UT WOS:000292340600008
ER
PT J
AU Zhang, F
Niu, G
Lu, GM
Chen, XY
AF Zhang, Fan
Niu, Gang
Lu, Guangming
Chen, Xiaoyuan
TI Preclinical Lymphatic Imaging
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Review
DE Lymphatic imaging; Lymphangiography; Contrast agent; Molecular imaging
ID POSITRON-EMISSION-TOMOGRAPHY; INTERSTITIAL MR-LYMPHOGRAPHY; MAGNETIC
RESONANCE LYMPHANGIOGRAPHY; SUPERPARAMAGNETIC IRON-OXIDE; SOLID LIPID
NANOPARTICLES; PROMOTES TUMOR-METASTASIS; REPORTER GENE-EXPRESSION;
DUAL-MODALITY PET/CT; CELL LUNG-CANCER; GROWTH FACTOR-C
AB Noninvasive in vivo imaging of lymphatic vessels and lymphatic nodes is expected to fulfill the purpose of analyzing lymphatic vessels and their function, understanding molecular mechanisms of lymphangiogenesis and lymphatic spread of tumors, and utilizing lymphatic molecular markers as a prognostic or diagnostic indicator. In this review, we provide a comprehensive summary of in vivo imaging modalities for detecting lymphatic vessels, lymphatic drainage, and lymphatic nodes, which include conventional lymphatic imaging techniques such as dyes and radionuclide scintigraphy as well as novel techniques for lymphatic imaging such as optical imaging, computed tomography, magnetic resonance imaging, ultrasound, positron emission tomography using lymphatic biomarkers, photoacoustic imaging, and combinations of multiple modalities. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve the research of lymphatic vascular system in health and disease states as well as to improve the accuracy of diagnosis in the relevant diseases.
C1 [Zhang, Fan; Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
[Zhang, Fan; Lu, Guangming] Nanjing Univ, Coll Med, Sch Clin, Nanjing Jinling Hosp,Dept Radiol, Nanjing 210002, Peoples R China.
[Niu, Gang] Ctr Clin, Imaging Sci Training Program, Bethesda, MD 20892 USA.
RP Niu, G (reprint author), NIBIB, LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM niug@mail.nih.gov; shawn.chen@nih.gov
RI liang, xue/F-9088-2011
FU National Natural Science Foundation of China (NSFC) [30930028]; 973
grants, China [CB705707]; Radiology and Imaging Sciences Department, NIH
Clinical Center; NIBIB, NIH
FX F. Zhang and G. Lu are supported by the National Natural Science
Foundation of China (NSFC grant No. 30930028) and 973 grants (2006,
CB705707, China). G. Niu is an Imaging Sciences Training Program (ISTP)
Fellow jointly supported by the Radiology and Imaging Sciences
Department, NIH Clinical Center and the Intramural Research Program,
NIBIB, NIH. This research was supported by the Intramural Research
Program of the NIBIB, NIH. We acknowledge Dr. Henry S. Eden for
critically reading this manuscript.
NR 164
TC 19
Z9 20
U1 2
U2 23
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD AUG
PY 2011
VL 13
IS 4
BP 599
EP 612
DI 10.1007/s11307-010-0421-y
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 786LN
UT WOS:000292310000001
PM 20862613
ER
PT J
AU Zhang, F
Xie, J
Liu, G
He, YL
Lu, GM
Chen, XY
AF Zhang, Fan
Xie, Jin
Liu, Gang
He, Yulong
Lu, Guangming
Chen, Xiaoyuan
TI In Vivo MRI Tracking of Cell Invasion and Migration in a Rat Glioma
Model
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Superparamagnetic iron oxide (SPIO) nanoparticles; Cell trafficking;
Glioma; Magnetic resonance imaging (MRI); Tumor invasion and migration
ID MESENCHYMAL STEM-CELLS; BRAIN; TRAFFICKING; MICE; MECHANISMS; EMISSION;
SURVIVAL; PROTEIN; CANCER; TUMORS
AB Malignant brain tumors are characterized by extensive infiltration into the normal brain tissue. Tumor migration is a complicated process which results from the interplay of a number of mechanisms, and the extent to which anatomic structure determined the migration pattern has not been extensively addressed. In the present study, we labeled C6 glioma cells with iron oxide nanoparticles and monitored the fate of the cells in vivo with magnetic resonance imaging (MRI).
C6 glioma cells were labeled with ferumoxide-poly-l-lysine complexes and their migration in the brains of rats tracked by T2-weighted MRI. The same amount of iron-laden cells were implanted into the caudate nucleus (CN) and at the vicinity of anterior commissure (AC), respectively, and MRI was performed during the course of 20-day monitoring period to track tumor growth and migration.
A clear tendency of tumor migration along the white matter fiber tracts was observed in the AC group, which is consistent with the previous reports; by contrast, tumor expanded to but remained confined within the boundary of right hemisphere in the CN group.
We successfully demonstrated the ability of MRI to investigate the impact of anatomical structure on the glioma migration pathway in vivo.
C1 [Zhang, Fan; Lu, Guangming] Nanjing Univ, Coll Med, Sch Clin, Nanjing Jinling Hosp,Dept Radiol, Nanjing 210002, Peoples R China.
[Zhang, Fan; Xie, Jin; Liu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
[He, Yulong] Nanjing Univ, Sch Med, Model Anim Res Ctr, Nanjing 210061, Peoples R China.
RP Lu, GM (reprint author), Nanjing Univ, Coll Med, Sch Clin, Nanjing Jinling Hosp,Dept Radiol, Nanjing 210002, Peoples R China.
EM cjr.luguangming@vip.163.com; shawn.chen@nih.gov
RI liang, xue/F-9088-2011; Xie, Jin/E-8193-2010;
OI Liu, Gang/0000-0002-9475-5134; HE, YULONG/0000-0002-0099-3749
FU 973 grants, China [CB705707]; National Natural Science Foundation, China
[30930028]; NIBIB, NIH
FX F Zhang, Y He, and G Lu are partially supported by 973 grants (2006,
CB705707, China) and National Natural Science Foundation (30930028,
China). F Zhang, J Xie, G Liu, and X Chen are supported by the
Intramural Research Program (IRP) at NIBIB, NIH.
NR 23
TC 14
Z9 16
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD AUG
PY 2011
VL 13
IS 4
BP 695
EP 701
DI 10.1007/s11307-010-0401-2
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 786LN
UT WOS:000292310000010
PM 20717735
ER
PT J
AU Smith, MA
Maris, JM
Lock, R
Kolb, EA
Gorlick, R
Keir, ST
Carol, H
Morton, CL
Reynolds, CP
Kang, MH
Houghton, PJ
AF Smith, Malcolm A.
Maris, John M.
Lock, Richard
Kolb, E. Anders
Gorlick, Richard
Keir, Stephen T.
Carol, Hernan
Morton, Christopher L.
Reynolds, C. Patrick
Kang, Min H.
Houghton, Peter J.
TI Initial Testing (Stage 1) of the Polyamine Analog PG11047 by the
Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; preclinical testing; polyamine
ID TARGETING ORNITHINE-DECARBOXYLASE; POSTRADIOTHERAPY CHEMOTHERAPY;
GLIOBLASTOMA-MULTIFORME; SLEEPING SICKNESS; CANCER CELLS; NEUROBLASTOMA;
INHIBITOR; TRIAL; MYCN; DFMO
AB Background. PG11047 is a novel conformationally restricted analog of the natural polyamine, spermine that lowers cellular endogenous polyamine levels and competitively inhibits natural polyamine functions leading to cancer cell growth inhibition. The activity of PG11047 was evaluated against the PPTP's in vitro and in vivo panels. Procedures. PG11047 was evaluated against the PPTP in vitro panel using 96 hr exposure at concentrations ranging from 10nM to 100 mu M. It was tested against the PPTP in vivo panels at a dose of 100 mg/kg administered by the intraperitoneal route weekly for 6 weeks. Results. In vitro PG11047 demonstrated a concentration-response pattern consistent with cytostatic activity. The median EC(50) for PG11047 was 71 nM. Cell lines of the Ewing sarcoma panel had a lower median EC(50) value compared to the remaining cell lines in the panel, while cell lines of the neuroblastoma panel had a higher median EC(50) value. In vivo PG11047 induced significant differences in EFS distribution compared to control in 5 of 32 (15.6%) of the evaluable solid tumor xenografts and in 0 of 7 (0%) of the evaluable ALL xenografts. The single case of tumor regression occurred in an ependymoma xenograft. Conclusions. Further pediatric development of PG11047 will require better defining a target population and identifying combinations for which there is a tumor-selective cytotoxic effect. The regression observed for an ependymoma xenograft and the exquisite sensitivity of some Ewing sarcoma cell lines to the antiproliferative effects of PG11047 provide leads for further preclinical investigations. Pediatr Blood Cancer 2011; 56: 268-274. (C) 2011 Wiley-Liss, Inc.
C1 [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Morton, Christopher L.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, Room 7025,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM smithm@ctep.nci.nih.gov
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CA21765, CA108786.
NR 26
TC 4
Z9 4
U1 0
U2 2
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD AUG
PY 2011
VL 57
IS 2
BP 268
EP 274
DI 10.1002/pbc.22797
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 786JE
UT WOS:000292301400016
PM 21360650
ER
PT J
AU Rochowski, A
Sun, CX
Glogauer, M
Alter, BP
AF Rochowski, Andrzej
Sun, Chunxiang
Glogauer, Michael
Alter, Blanche P.
TI Neutrophil Functions in Patients With Inherited Bone Marrow Failure
Syndromes
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE inherited bone marrow failure; neutrophil; respiratory burst
ID SHWACHMAN-DIAMOND-SYNDROME; FANCONI-ANEMIA; DYSKERATOSIS-CONGENITA;
FAMILY-MEMBERS; DEFECT; CHEMOTAXIS; LEUKOCYTES; RELEASE; CANCER
AB Background. The inherited bone marrow failure syndromes (IBMFS) include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome (SDS). Previous studies reported decreased neutrophil chemotaxis in patients with SDS; there are no reports of neutrophil function in other IBMFS. In this study we examined neutrophil respiratory burst function in IBMFS patients. Procedure. Samples from 43 IBMFS patients and 61 healthy family members were collected, shipped, and analyzed within 24 hr. We also studied samples from 12 healthy control persons immediately after collection. Neutrophils were stimulated with phorbol 12-myristate acetate (PMA) and N-formyl-methyonyl-leucyl-phenylalanine (fMLP), and respiratory burst analyzed by reduction of dihydro-rhodamine and cytochromec. Results. There was no significant difference in the degree of fMLP or PMA-driven respiratory burst activity between each of the IBMFS subgroups and their respective family members. There was also no difference in respiratory burst activity between any IBMFS, pooled group of all healthy family members and healthy controls. Conclusions. Neutrophil respiratory burst activity from IBMFS patients does not differ from that of healthy family members and controls. Pediatr Blood Cancer. 2011; 57: 306-309. (C) 2010Wiley-Liss, Inc.
C1 [Rochowski, Andrzej; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
[Rochowski, Andrzej] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Sun, Chunxiang; Glogauer, Michael] Univ Toronto, Fac Dent, Canadian Inst Hlth Res Grp Matrix Dynam, Toronto, ON, Canada.
RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Room 7020, Bethesda, MD 20852 USA.
EM alterb@mail.nih.gov
OI Glogauer, Michael/0000-0002-6248-5977
FU NIH; National Cancer Institute
FX Grant sponsor: NIH; Grant sponsor: National Cancer Institute.
NR 21
TC 2
Z9 2
U1 0
U2 4
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD AUG
PY 2011
VL 57
IS 2
BP 306
EP 309
DI 10.1002/pbc.22885
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 786JE
UT WOS:000292301400023
PM 21671367
ER
PT J
AU Ehler, M
Galanis, J
AF Ehler, Martin
Galanis, Jennifer
TI Frame theory in directional statistics
SO STATISTICS & PROBABILITY LETTERS
LA English
DT Article
DE Frames; Directional statistics; Bingham test; Granular rods
ID BI-FRAMES; TIGHT FRAMES; DISTRIBUTIONS; EXPANSIONS; ERASURES; MIXTURE;
ORDER; SHAPE
AB Distinguishing between uniform and non-uniform sample distributions is a common problem in directional data analysis; however for many tests, non-uniform distributions exist that fail uniformity rejection. To predict these distributions, we merge directional statistics with frame theory and find that probabilistic tight frames yield non-uniform distributions that minimize directional potentials, leading to failure of uniformity rejection for the Bingham test. Finally, we apply our results to model patterns found in granular rod experiments. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Ehler, Martin; Galanis, Jennifer] NICHHD, NIH, Sect Med Biophys, Bethesda, MD 20892 USA.
[Ehler, Martin] Univ Maryland, Dept Math, Norbert Wiener Ctr, College Pk, MD 20742 USA.
[Galanis, Jennifer] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel.
[Galanis, Jennifer] Hebrew Univ Jerusalem, Fritz Haber Ctr, IL-91904 Jerusalem, Israel.
RP Ehler, M (reprint author), NICHHD, NIH, Sect Med Biophys, Bethesda, MD 20892 USA.
EM ehlermar@mail.nih.gov; galanis@fh.huji.ac.il
FU National Institute of Child Health and Human Development, National
Institutes of Health; Minerva Foundation, Munich, Germany; NIH/DFG [EH
405/1-1/575910]
FX The authors are supported, in part, by intramural research funds from
the National Institute of Child Health and Human Development, National
Institutes of Health. The Fritz Haber research center is supported by
the Minerva Foundation, Munich, Germany. In addition, ME is supported by
the NIH/DFG Research Career Transition Awards Program (EH
405/1-1/575910).
NR 36
TC 10
Z9 10
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7152
J9 STAT PROBABIL LETT
JI Stat. Probab. Lett.
PD AUG
PY 2011
VL 81
IS 8
BP 1046
EP 1051
DI 10.1016/j.spl.2011.02.027
PG 6
WC Statistics & Probability
SC Mathematics
GA 785MI
UT WOS:000292232700020
ER
PT J
AU Uthus, E
Begaye, A
Ross, S
Zeng, HW
AF Uthus, Eric
Begaye, Adrienne
Ross, Sharon
Zeng, Huawei
TI The von Hippel-Lindau (VHL) Tumor-suppressor Gene is Down-regulated by
Selenium Deficiency in Caco-2 Cells and Rat Colon Mucosa
SO BIOLOGICAL TRACE ELEMENT RESEARCH
LA English
DT Article
DE Tumor-suppressor; DNA methylation; Selenium; Se-methylselenocysteine;
Caco-2 cells; Von Hippel-Lindau; Rat; DNA methylation array
ID ABERRANT CRYPT FORMATION; DNA METHYLATION; DIETARY SELENIUM;
GLUTATHIONE-PEROXIDASE; HISTONE DEACETYLASE; FISHER-344 RATS; SERUM
SELENIUM; CANCER; METABOLISM; RISK
AB To test the hypothesis that selenium affects DNA methylation and hence gene regulation, we employed a methylation array (Panomics) in the human colonic epithelial Caco-2 cell model. The array profiles DNA methylation from promoter regions of 82 human genes. After conditioning cells to repeatedly reduced concentrations of fetal bovine serum, a serum-free culture was established. Se-methylselenocysteine (SeMSC) was added at 0 (deficient Se) or 250 (control Se) nM to cells maintained in DMEM. After 7 days, cells were collected and stored at -80A degrees C until analysis; experiments were replicated three times. Glutathione peroxidase activity was significantly decreased in cells grown in low SeMSC. Cells grown in 250 nM SeMSC had maximal GPx activity. Genomic DNA from cells grown in the low-SeMSC media and media containing 250 nM SeMSC was incubated with methylation-binding protein followed by isolation of methylated DNA. The methylated DNA was labeled with biotin and hybridized to the methylation array. Thus, genes with promoter methylation will produce a higher chemiluminescence signal than those genes with no promoter methylation. Of the genes profiled, the von Hippel-Lindau (VHL) gene was most different as indicated by quantification following chemiluminescence detection demonstrating that the promoter region of VHL was hypermethylated in cells from the low-SeMSC media. To determine whether promoter methylation affected transcription, we isolated RNA from replicate samples and performed real-time RT PCR. VHL (mRNA) was down-regulated (fold change significantly < 1) in cells grown in low SeMSC compared to cells grown in 250 nM SeMSC (control; fold change = 1). We also show that (mRNA) Vhl expression is significantly reduced in mucosa from rats fed a diet deficient in Se. Our results suggest that low Se status affects DNA promoter region methylation and that this can result in down-regulation of the tumor suppressor gene VHL.
C1 [Uthus, Eric; Zeng, Huawei] ARS, USDA, Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
[Begaye, Adrienne] Univ Arizona, Tucson, AZ USA.
[Ross, Sharon] NCI, NIH, Nutr Sci Res Grp, Rockville, MD 20892 USA.
RP Uthus, E (reprint author), ARS, USDA, Human Nutr Res Ctr, POB 9034, Grand Forks, ND 58202 USA.
EM eric.uthus@ars.usda.gov
NR 38
TC 7
Z9 7
U1 0
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0163-4984
J9 BIOL TRACE ELEM RES
JI Biol. Trace Elem. Res.
PD AUG
PY 2011
VL 142
IS 2
BP 223
EP 231
DI 10.1007/s12011-010-8764-4
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 778WY
UT WOS:000291741300012
PM 20632125
ER
PT J
AU Decrausaz, L
Domingos-Pereira, S
Duc, M
Bobst, M
Romero, P
Schiller, JT
Jichlinski, P
Nardelli-Haefliger, D
AF Decrausaz, Loane
Domingos-Pereira, Sonia
Duc, Melanie
Bobst, Martine
Romero, Pedro
Schiller, John T.
Jichlinski, Patrice
Nardelli-Haefliger, Denise
TI Parenteral is more efficient than mucosal immunization to induce
regression of human papillomavirus-associated genital tumors
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human papillomavirus; cervical cancer; genital tumor model; therapeutic
vaccination; mucosal vaccination
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSMITTED VIRAL-INFECTION; REGULATORY
T-CELLS; INTRAEPITHELIAL NEOPLASIA; CPG OLIGODEOXYNUCLEOTIDES;
INTRANASAL IMMUNIZATION; PROTECTIVE IMMUNITY; INTERFERON-GAMMA;
LYMPH-NODES; MICE
AB Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High-risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene-specific therapeutic vaccines are under development to treat HPV-related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell-mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE7(+) CD8(+) and E7-specific Interferon-gamma-secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long-term protection against genital E7-expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7-specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein-based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV-associated genital cancer.
C1 [Nardelli-Haefliger, Denise] CHU Vaudois, Dept Urol, IMUL, CH-1011 Lausanne, Switzerland.
[Decrausaz, Loane; Domingos-Pereira, Sonia; Duc, Melanie; Bobst, Martine; Jichlinski, Patrice; Nardelli-Haefliger, Denise] Univ Lausanne, Lausanne, Switzerland.
[Romero, Pedro] Ludwig Inst Canc Res, Div Clin Oncoimmunol, Lausanne, Switzerland.
[Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Nardelli-Haefliger, D (reprint author), CHU Vaudois, Dept Urol, IMUL, Bugnon 48, CH-1011 Lausanne, Switzerland.
EM dnardell@hospvd.ch
OI nardelli-haefliger, denise/0000-0003-1812-9905
FU Swiss National Science Foundation [310000-112406]; Oncosuisse
[02304-082008]; Fondation Mercier; Fondation Emma Muschamp
FX Grant sponsor: Swiss National Science Foundation; Grant number:
310000-112406; Grant sponsor: Oncosuisse; Grant number: 02304-082008;
Grant sponsor: Fondation Mercier, Fondation Emma Muschamp
NR 50
TC 18
Z9 18
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 1
PY 2011
VL 129
IS 3
BP 762
EP 772
DI 10.1002/ijc.25973
PG 11
WC Oncology
SC Oncology
GA 777HH
UT WOS:000291606000025
PM 21384340
ER
PT J
AU Ellis, JR
Heinrich, B
Mautner, VF
Kluwe, L
AF Ellis, James R., Jr.
Heinrich, Bianca
Mautner, Victor-F.
Kluwe, Lan
TI Effects of Splicing Mutations on NF2-Transcripts: Transcript Analysis
and Information Theoretic Predictions
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID GERM-LINE MUTATIONS; NEUROFIBROMATOSIS 2; NF2 GENE; SITE MUTATIONS;
SEQUENCES; IDENTIFICATION; SEVERITY; DISEASE; EXON
AB This study examined the effects of 22 putative splicing mutations in the NF2 gene by means of transcript analysis and information theory based prediction. Fourteen mutations were within the dinucleotide acceptor and donor regions, often referred to as (AG/GT) sequences. Six were outside these dinucleotide regions but within the more broadly defined splicing regions used in the information theory based model. Two others were in introns and outside the broadly defined regions. Transcript analysis revealed exon skipping or activation of one or more cryptic splicing sites for 17 mutations. No alterations were found for the two intronic mutations and for three mutations in the broadly defined splicing regions. Concordance and partial concordance between the calculated predictions and the results of transcript analysis were found for 14 and 6 mutations, respectively. For two mutations, the predicted alteration was not found in the transcripts. Our results demonstrate that the effects of splicing mutations in NF2 are often complex and that information theory based analysis is helpful in elucidating the consequences of these mutations. (C) 2011 Wiley-Liss, Inc.
C1 [Ellis, James R., Jr.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Heinrich, Bianca] Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, Hamburg, Germany.
[Mautner, Victor-F.; Kluwe, Lan] Univ Med Ctr Hamburg Eppendorf, Dept Oral & Maxillofacial Surg, Hamburg, Germany.
RP Ellis, JR (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jrellis@helix.nih.gov
FU NIH; German Cancer Foundation [108793]
FX Supported by: NIH Intramural Research Program; German Cancer Foundation,
Grant number: 108793
NR 22
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD AUG
PY 2011
VL 50
IS 8
BP 571
EP 584
DI 10.1002/gcc.20876
PG 14
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 777BP
UT WOS:000291588500001
PM 21563229
ER
PT J
AU Venere, M
Fine, HA
Dirks, PB
Rich, JN
AF Venere, Monica
Fine, Howard A.
Dirks, Peter B.
Rich, Jeremy N.
TI Cancer Stem Cells in Gliomas: Identifying and Understanding the Apex
Cell in Cancer's Hierarchy
SO GLIA
LA English
DT Article
DE glioma; cancer stem cell; therapy resistance
ID TUMOR-INITIATING CELLS; ACUTE MYELOID-LEUKEMIA; HUMAN GLIOBLASTOMA; SIDE
POPULATION; GROWTH-FACTOR; HEMATOPOIETIC STEM; PERIVASCULAR NICHE;
PANCREATIC-CANCER; GENE-EXPRESSION; POSITIVE CELLS
AB Neuro-oncology research has rediscovered a complexity of nervous system cancers through the incorporation of cellular heterogeneity into tumor models with cellular subsets displaying stem-cell characteristics. Self-renewing cancer stem cells (CSCs) can propagate tumors and yield nontumorigenic tumor bulk cells that display a more differentiated phenotype. The ability to prospectively isolate and interrogate CSCs is defining molecular mechanisms responsible for the tumor maintenance and growth. The clinical relevance of CSCs has been supported by their resistance to cytotoxic therapies and their promotion of tumor angiogenesis. Although the field of CSC biology is relatively young, continued elucidation of the features of these cells holds promise for the development of novel patient therapies. (C) 2011 Wiley-Liss, Inc.
C1 [Venere, Monica; Rich, Jeremy N.] Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Lerner Res Inst, Cleveland, OH 44118 USA.
[Fine, Howard A.] Natl Inst Neurol Disorders & Stroke, Neurooncol Branch, NCI, NIH, Bethesda, MD USA.
[Dirks, Peter B.] Hosp Sick Children, Div Neurosurg, Dev & Stem Cell Biol Program, Arthur & Sonia Labatt Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada.
RP Venere, M (reprint author), Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Lerner Res Inst, NE30,9500 Euclid Ave, Cleveland, OH 44118 USA.
EM venerem@ccf.org; richj@ccf.org
FU National Brain Tumor Society; Goldhirsh Foundation; NIH [NS054276,
CA129958, CA116659, CA154130]; National Research Service [NS058042];
Damon Runyon Cancer Research Foundation; American Brain Tumor
Association; Canadian Cancer Society Research Institute; Canadian
Institutes for Health Research; Ontario Institute for Cancer Research;
Terry Fox Foundation; Hospital for Sick Children Foundation; Jessica's
Footprint Foundation; National Cancer Institute; National Institutes of
Neurological Disorders, and Stroke/National Institutes of Health
FX Grant sponsor: National Brain Tumor Society, Goldhirsh Foundation; Grant
sponsor: NIH; Grant numbers: NS054276, CA129958, CA116659, CA154130;
Grant sponsor: National Research Service Awards; Grant number: NS058042;
Grant sponsors: Damon Runyon Cancer Research Foundation, American Brain
Tumor Association Basic Research Fellowship, Canadian Cancer Society
Research Institute, the Canadian Institutes for Health Research, the
Ontario Institute for Cancer Research, the Terry Fox Foundation, the
Hospital for Sick Children Foundation, Jessica's Footprint Foundation,
National Cancer Institute, National Institutes of Neurological
Disorders, and Stroke/National Institutes of Health.
NR 70
TC 69
Z9 72
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-1491
J9 GLIA
JI Glia
PD AUG
PY 2011
VL 59
IS 8
SI SI
BP 1148
EP 1154
DI 10.1002/glia.21185
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 777CN
UT WOS:000291591800003
PM 21547954
ER
PT J
AU Fitzgerald, ML
Lupica, CR
Pickel, VM
AF Fitzgerald, Megan L.
Lupica, Carl R.
Pickel, Virginia M.
TI Decreased Parvalbumin Immunoreactivity in the Cortex and Striatum of
Mice Lacking the CB1 Receptor
SO SYNAPSE
LA English
DT Article
DE CB1 knockout; caudate putamen; primary motor cortex; medial prefrontal
cortex
ID CALCIUM-BINDING PROTEIN; CANNABINOID RECEPTORS; RAT NEOSTRIATUM;
CONTAINING INTERNEURONS; GABAERGIC INTERNEURONS; CORTICAL INTERNEURONS;
POSTNATAL-DEVELOPMENT; SOMATOSENSORY CORTEX; BASAL GANGLIA; GABA RELEASE
AB Cortical and striatal regions of the brain contain high levels of the cannabinoid-1 (CB1) receptor, the central neuronal mediator of activity-dependent synaptic plasticity evoked by endocannabinoids. The expression levels of parvalbumin, a calcium-binding protein found in fast-spiking interneurons of both regions, may be controlled in part by synaptic activity during critical periods of development. However, there is currently no evidence that CB1 receptor expression affects parvalbumin levels in either cortical or striatal interneurons. To assess this possibility, we examined parvalbumin immunoreactivity in the dorsolateral striatum, primary motor cortex (M1), and prefrontal cortex (PFC) of CB1 knockout and wild-type C57/BL6 mice. Quantitative densitometry showed a significant decrease in parvalbumin immunoreactivity within individual neurons in each of these regions of CB1 knockout mice relative to controls. A significantly lower density (number of cells per unit area) of parvalbumin-labeled neurons was observed in the striatum, but not the cortical regions of CB1 knockout mice. These findings suggest that CB1 receptor deletion may elicit a compensatory mechanism for network homeostasis affecting parvalbumin-containing cortical and striatal interneurons. Synapse 65:827-831, 2011. Published 2011 Wiley-Liss, Inc.(dagger)
C1 [Fitzgerald, Megan L.; Pickel, Virginia M.] Cornell Univ, Div Neurobiol, Dept Neurol & Neurosci, Weill Med Coll, New York, NY 10065 USA.
[Lupica, Carl R.] Natl Inst Drug Abuse, Electrophysiol Res Sect, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Pickel, VM (reprint author), Weill Cornell Med Coll, Div Neurobiol, 407 E 61st St, New York, NY 10065 USA.
EM vpickel@med.cornell.edu
FU National Institutes of Health [1P01 HL096571, MH40342, DA04600, T32 DA
7274]; National Institute on Drug Abuse
FX Contract grant sponsor: National Institutes of Health; Contract grant
numbers: 1P01 HL096571, MH40342, DA04600, T32 DA 7274; Contract grant
sponsor: National Institute on Drug Abuse Intramural Research Program
NR 41
TC 13
Z9 13
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD AUG
PY 2011
VL 65
IS 8
BP 827
EP 831
DI 10.1002/syn.20911
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 777FO
UT WOS:000291601500015
PM 21445945
ER
PT J
AU Malinovsky, Y
Rinott, Y
AF Malinovsky, Yaakov
Rinott, Yosef
TI Best invariant and minimax estimation of quantiles in finite populations
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
DE Monotone transformations; Sampling and estimation strategies; Behavioral
and randomized estimators; Loss functions; Median; Simple random sample
ID RANDOMIZATION; STATISTICS
AB The theoretical literature on quantile and distribution function estimation in infinite populations is very rich, and invariance plays an important role in these studies. This is not the case for the commonly occurring problem of estimation of quantiles in finite populations. The latter is more complicated and interesting because an optimal strategy consists not only of an estimator, but also of a sampling design, and the estimator may depend on the design and on the labels of sampled individuals, whereas in iid sampling, design issues and labels do not exist.
We study the estimation of finite population quantiles, with emphasis on estimators that are invariant under the group of monotone transformations of the data, and suitable invariant loss functions. Invariance under the finite group of permutation of the sample is also considered. We discuss nonrandomized and randomized estimators, best invariant and minimax estimators, and sampling strategies relative to different classes. Invariant loss functions and estimators in finite population sampling have a nonparametric flavor, and various natural combinatorial questions and tools arise as a result. Published by Elsevier B.V.
C1 [Malinovsky, Yaakov] NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Rinott, Yosef] Hebrew Univ Jerusalem, IL-91905 Jerusalem, Israel.
[Rinott, Yosef] LUISS, Rome, Italy.
RP Malinovsky, Y (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM yaakov.malinovsky@nih.gov; rinott@mscc.huji.ac.il
FU Israel Science Foundation [473/04]; National Institutes of Health,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX We thank Gil Kalai for several enlightening discussions of this work,
and three reviewers for many useful comments. This research was
supported in part by Grant no. 473/04 from the Israel Science
Foundation. The first author also supported by the Intramural Research
Program of the National Institutes of Health, Eunice Kennedy Shriver
National Institute of Child Health and Human Development.
NR 29
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD AUG
PY 2011
VL 141
IS 8
BP 2633
EP 2644
DI 10.1016/j.jspi.2011.02.016
PG 12
WC Statistics & Probability
SC Mathematics
GA 770DO
UT WOS:000291067400012
PM 21643478
ER
PT J
AU Di Costanzo, A
Festa, L
Roscigno, G
Vivo, M
Pollice, A
Morasso, M
La Mantia, G
Calabro, V
AF Di Costanzo, Antonella
Festa, Luisa
Roscigno, Giuseppina
Vivo, Maria
Pollice, Alessandra
Morasso, Maria
La Mantia, Girolama
Calabro, Viola
TI A Dominant Mutation Etiologic for Human Tricho-Dento-Osseous Syndrome
Impairs the Ability of DLX3 to Downregulate Delta Np63 alpha
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID HUMAN PRIMARY KERATINOCYTES; HOMEODOMAIN PROTEIN DLX3; HOMEOBOX GENE
DLX3; ECTODERMAL DYSPLASIAS; P53 HOMOLOG; IN-VITRO; P63;
DIFFERENTIATION; PHOSPHORYLATION; EXPRESSION
AB The homeodomain transcription factors play crucial roles in many developmental processes ranging from organization of the body plan to differentiation of individual tissues. The homeodomain protein Distal-less-3 (DLX3) has an essential role in epidermal stratification and development of ectodermal appendages, placenta and bones. A four-nucleotide deletion in the human DLX3 gene is etiologic for the human hereditary tricho-dento-osseous (TDO) ectodermal dysplasia, a dominant syndrome characterized by abnormalities in hair, nails, teeth, and bones. We have previously demonstrated that DLX3 gene expression induces degradation of Delta Np63 alpha, a specific product of the TP63 gene, a master regulator of multi-layered epithelia. Here we show that the DLX3(TDO) mutant protein is unable to promote Delta Np63 alpha protein degradation and impairs the expression of cell cycle regulatory proteins and skin differentiation markers. However, we found that in cell expressing equal amounts of mutant and wild-type DLX3, Delta Np63 alpha protein level is efficiently regulated implying that genetic heterozygosity at the DLX3 locus protects TDO patients from developing severe p63-associated skin defects. J. Cell. Physiol. 226: 2189-2197, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Di Costanzo, Antonella; Festa, Luisa; Roscigno, Giuseppina; Vivo, Maria; Pollice, Alessandra; La Mantia, Girolama; Calabro, Viola] Univ Naples Federico 2, Dept Struct & Mol Biol, Naples, Italy.
[Morasso, Maria] NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA.
RP Calabro, V (reprint author), Univ Naples Federico 2, Dipartimento Biol Strutturale & Funz, Viale Cinzia, I-80126 Naples, Italy.
EM vcalabro@unina.it
FU Associazione Italiana per la Ricerca sul Cancro (AIRC)
FX Contract grant sponsor: Associazione Italiana per la Ricerca sul Cancro
(AIRC).
NR 37
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD AUG
PY 2011
VL 226
IS 8
BP 2189
EP 2197
DI 10.1002/jcp.22553
PG 9
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 762ZJ
UT WOS:000290520900025
PM 21520071
ER
PT J
AU Nemes, E
Lugli, E
Bertoncelli, L
Nasi, M
Pinti, M
Manzini, S
Prati, F
Manzini, L
Del Giovane, C
D'Amico, R
Cossarizza, A
Mussini, C
AF Nemes, Elisa
Lugli, Enrico
Bertoncelli, Linda
Nasi, Milena
Pinti, Marcello
Manzini, Serena
Prati, Francesca
Manzini, Lisa
Del Giovane, Cinzia
D'Amico, Roberto
Cossarizza, Andrea
Mussini, Cristina
TI CD4(+) T-cell differentiation, regulatory T cells and gag-specific T
lymphocytes are unaffected by CD4-guided treatment interruption and
therapy resumption
SO AIDS
LA English
DT Article
DE CD4-guided treatment interruptions; chronic HIV infection; gag-specific
response; regulatory T cells; T-cell activation; T-cell differentiation;
T-cell polyfunctionality
ID HIV-INFECTED PATIENTS; HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE
ANTIRETROVIRAL THERAPY; SCHEDULED TREATMENT INTERRUPTIONS; MONITORED
TREATMENT INTERRUPTION; CD40 LIGAND DYSREGULATION; CD4+COUNT-GUIDED
INTERRUPTION; HIV-1-INFECTED PATIENTS; IMMUNE ACTIVATION; RNA LEVELS
AB Objectives: Despite limiting exposure to antiretroviral drugs, structured treatment interruptions can influence multiple aspects of T-cell immunity, particularly those regarding CD4(+) T lymphocytes. We evaluated the impact of CD4-guided treatment interruption (CD4-GTI) and treatment resumption on regulatory T cells (Tregs), T-lymphocyte activation, differentiation and polyfunctional gag-specific response.
Methods: Patients were analyzed just prior to treatment interruption, at 2 and 6 months after treatment interruption, just prior to treatment resumption and at 2 and 6 months after treatment resumption. Thawed peripheral blood mononuclear cells were stained immediately for phenotype analysis or stimulated with HIV-gag peptides and analyzed by polychromatic flow cytometry.
Results: Treatment interruption resulted in a CD4(+) cell count decrease and plasma viral load (pVL) increase, but did not preclude a good immune reconstitution and a complete suppression of pVL after treatment resumption. Treatment interruption did not influence CD4(+) T-cell differentiation and Treg subsets. During treatment interruption, gag-specific CD4(+) T cells were not lost, although the frequency of HIV-specific CD8(+) cells increased. Most gag-specific CD4(+) T cells were potentially cytotoxic (CD107a(+)) and were not influenced by pVL or by HAART. Most helper (CD154(+)) gag-specific CD4(+) T lymphocytes did not produce interferon-g or interleukin-2.
Conclusion: CD4-GTI did not cause depletion of memory cells, Tregs or HIV-specific CD4(+) cells and, on the contrary, could induce HIV-specific responses. If guided by CD4(+) T-cell count, treatment interruption does not provoke irreversible immune damages. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Cossarizza, Andrea] Univ Modena & Reggio Emilia, Dept Biomed Sci, Chair Immunol, I-41125 Modena, Italy.
[Prati, Francesca; Manzini, Lisa; Mussini, Cristina] Univ Modena & Reggio Emilia, Infect Dis Clin, Azienda Osped, Univ Policlin Modena, I-41125 Modena, Italy.
[Del Giovane, Cinzia; D'Amico, Roberto] Univ Modena & Reggio Emilia, Dept Oncol Hematol & Resp Dis, I-41125 Modena, Italy.
[Lugli, Enrico] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Cossarizza, A (reprint author), Univ Modena & Reggio Emilia, Dept Biomed Sci, Chair Immunol, Via Campi 287, I-41125 Modena, Italy.
EM andrea.cossarizza@unimore.it
RI D'Amico, Roberto/I-8106-2014; Pinti, Marcello/C-9351-2015; Nasi,
Milena/J-4425-2016;
OI D'Amico, Roberto/0000-0002-3211-6687; Pinti,
Marcello/0000-0001-9118-1262; Nasi, Milena/0000-0003-3079-8001;
Cossarizza, Andrea/0000-0002-5381-1558
FU Istituto Superiore di Sanita (Rome, Italy); VI Programma Nazionale di
Ricerca sull'AIDS [40G.62, 40G.43]
FX The authors thank all the patients who participated in this study. This
study has been sponsored by the Istituto Superiore di Sanita (Rome,
Italy), VI Programma Nazionale di Ricerca sull'AIDS, grants No. 40G.62
to A.C. and 40G.43 to C.M. The authors acknowledge Partec GmbH (Germany)
and Space srl (Milan, Italy) for their continuous support.
NR 52
TC 10
Z9 10
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 31
PY 2011
VL 25
IS 12
BP 1443
EP 1453
DI 10.1097/QAD.0b013e328347b5e2
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 791BW
UT WOS:000292636300001
PM 21505295
ER
PT J
AU Kiser, JJ
Rutstein, RM
Samson, P
Graham, B
Aldrovandi, G
Mofenson, LM
Smith, E
Schnittman, S
Fenton, T
Brundage, RC
Fletcher, CV
AF Kiser, Jennifer J.
Rutstein, Richard M.
Samson, Pearl
Graham, Bobbie
Aldrovandi, Grace
Mofenson, Lynne M.
Smith, Elizabeth
Schnittman, Steven
Fenton, Terry
Brundage, Richard C.
Fletcher, Courtney V.
TI Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected
infants, children, and adolescents
SO AIDS
LA English
DT Article
DE atazanavir; children; HIV; pediatrics; pharmacokinetics; protease
inhibitor
ID LOPINAVIR/RITONAVIR; COMBINATION; LAMIVUDINE; TENOFOVIR; RITONAVIR
AB Objective: To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years.
Design: A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children.
Setting: Sites in the United States and South Africa.
Participants: One hundred and ninety-five children enrolled; 172 had evaluable ATV pharmacokinetics on day 7.
Intervention: Children were entered in age, dose, and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred 7 days after starting ATV. ATV doses were increased or decreased if the 24-h area under the concentration time curves (AUC(0-24hr)) were less than 30 or more than 90 mu g x h/ml, respectively.
Main outcomes: Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC(0-24hr) was 60 mu g x h/ml or less, and AUC(0-24hr) and ATV concentrations 24-h postdose (C(24)) were more than 30 mu g x h/ml and at least 60 ng/ml, respectively, in at least 80% of the children, with no individual AUC(0-24hr) less than 15 mu g x h/ml.
Results: Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520 mg/m(2) for those aged more than 2 to 13 years or less and 620 mg/m(2) for those aged more than 13 to 21 years or less. ATV/r capsules satisfied criteria at a dose of 205 mg/m(2) for those aged more than 2 to 21 years or less. ATV/r powder satisfied criteria at a dose of 310 mg/m(2) for those aged more than 2 to 13 years or less, but pharmacokinetics in those aged 2 years or less were highly variable. Conclusion: Body surface area-determined doses of ATV capsules and of ATV/r powder and capsules provide ATV exposures in children of more than 2 years that approximate concentrations in adults receiving ATV/r. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Fletcher, Courtney V.] Univ Nebraska Med Ctr, Coll Pharm, Omaha, NE 68198 USA.
[Kiser, Jennifer J.] Univ Colorado Denver, Aurora, CO USA.
[Rutstein, Richard M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Samson, Pearl; Fenton, Terry] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Graham, Bobbie] Frontier Sci Technol Res Fdn, Amherst, NY USA.
[Aldrovandi, Grace] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Mofenson, Lynne M.] NICHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Smith, Elizabeth] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Schnittman, Steven] Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
[Brundage, Richard C.] Univ Minnesota, Minneapolis, MN USA.
RP Fletcher, CV (reprint author), Univ Nebraska Med Ctr, Coll Pharm, 986000 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM cfletcher@unmc.edu
OI Mofenson, Lynne/0000-0002-2818-9808
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health (NIMH)
[AI068632]; Bristol Myers Squibb; Statistical and Data Analysis Center
at Harvard School of Public Health, under the National Institute of
Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical
Trials Group (PACTG) [U01 AI068616]; IMPAACT Group; NICHD
[N01-DK-9-001/HHSN267200800001C]
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials (IMPAACT) was provided by the National Institute of
Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Mental Health (NIMH) (AI068632).
This study was also supported by Bristol Myers Squibb. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIH. This work was supported by the
Statistical and Data Analysis Center at Harvard School of Public Health,
under the National Institute of Allergy and Infectious Diseases
cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical
Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support
of the sites was provided by the NIAID and the NICHD International and
Domestic Pediatric and Maternal HIV Clinical Trials Network funded by
NICHD (contract number N01-DK-9-001/HHSN267200800001C).
NR 14
TC 12
Z9 12
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 31
PY 2011
VL 25
IS 12
BP 1489
EP 1496
DI 10.1097/QAD.0b013e328348fc41
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 791BW
UT WOS:000292636300006
PM 21610486
ER
PT J
AU Braithwaite, RS
Nucifora, KA
Yiannoutsos, CT
Musick, B
Kimaiyo, S
Diero, L
Bacon, MC
Wools-Kaloustian, K
AF Braithwaite, R. Scott
Nucifora, Kimberly A.
Yiannoutsos, Constantin T.
Musick, Beverly
Kimaiyo, Sylvester
Diero, Lameck
Bacon, Melanie C.
Wools-Kaloustian, Kara
TI Alternative antiretroviral monitoring strategies for HIV-infected
patients in east Africa: opportunities to save more lives?
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; VIRAL LOAD; COST-EFFECTIVENESS; THERAPY;
ADHERENCE; OUTCOMES; PROGRAMS; MODEL
AB Background: Updated World Health Organization guidelines have amplified debate about how resource constraints should impact monitoring strategies for HIV-infected persons on combination antiretroviral therapy (cART). We estimated the incremental benefit and cost effectiveness of alternative monitoring strategies for east Africans with known HIV infection.
Methods: Using a validated HIV computer simulation based on resource-limited data (USAID and AMPATH) and circumstances (east Africa), we compared alternative monitoring strategies for HIV-infected persons newly started on cART. We evaluated clinical, immunologic and virologic monitoring strategies, including combinations and conditional logic (e. g., only perform virologic testing if immunologic testing is positive). We calculated incremental cost-effectiveness ratios (ICER) in units of cost per quality-adjusted life year (QALY), using a societal perspective and a lifetime horizon. Costs were measured in 2008 US dollars, and costs and benefits were discounted at 3%. We compared the ICER of monitoring strategies with those of other resource-constrained decisions, in particular earlier cART initiation (at CD4 counts of 350 cells/mm(3) rather than 200 cells/mm3).
Results: Monitoring strategies employing routine CD4 testing without virologic testing never maximized health benefits, regardless of budget or societal willingness to pay for additional health benefits. Monitoring strategies employing virologic testing conditional upon particular CD4 results delivered the most benefit at willingness-to-pay levels similar to the cost of earlier cART initiation (approximately $2600/QALY). Monitoring strategies employing routine virologic testing alone only maximized health benefits at willingness-to-pay levels (> $4400/QALY) that greatly exceeded the ICER of earlier cART initiation.
Conclusions: CD4 testing alone never maximized health benefits regardless of resource limitations. Programmes routinely performing virologic testing but deferring cART initiation may increase health benefits by reallocating monitoring resources towards earlier cART initiation.
C1 [Braithwaite, R. Scott; Nucifora, Kimberly A.] NYU, Sch Med, Dept Med, Sect Value & Comparat Effectiveness, New York, NY 10012 USA.
[Yiannoutsos, Constantin T.; Musick, Beverly] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN USA.
[Kimaiyo, Sylvester; Diero, Lameck] Moi Univ, Sch Med, Dept Med, Eldoret, Kenya.
[Bacon, Melanie C.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Wools-Kaloustian, Kara] Indiana Univ Sch Med, Dept Med, Indianapolis, IN USA.
RP Braithwaite, RS (reprint author), NYU, Sch Med, Dept Med, Sect Value & Comparat Effectiveness, New York, NY 10012 USA.
EM scott.braithwaite@nyumc.org
FU National Institute of Allergy and Infectious Disease [UO1AI069911-01];
US National Institutes of Health; US NIH
FX This work is supported by National Institute of Allergy and Infectious
Disease Award UO1AI069911-01 (IeDEA East Africa), US National Institutes
of Health. MCB is employed by the US NIH, which provided funding for
this study through a grant. The study sponsor had no role in the study
design, interpretation of data, the writing of the paper, or the
decision to submit the paper for publication.
NR 29
TC 24
Z9 24
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD JUL 30
PY 2011
VL 14
AR 38
DI 10.1186/1758-2652-14-38
PG 13
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 839GN
UT WOS:000296353600001
PM 21801434
ER
PT J
AU Smith, B
Lyakhov, I
Loomis, K
Needle, D
Baxa, U
Yavlovich, A
Capala, J
Blumenthal, R
Puri, A
AF Smith, Brandon
Lyakhov, Ilya
Loomis, Kristin
Needle, Danielle
Baxa, Ulrich
Yavlovich, Amichai
Capala, Jacek
Blumenthal, Robert
Puri, Anu
TI Hyperthermia-triggered intracellular delivery of anticancer agent to
HER2(+) cells by HER2-specific affibody (ZHER2-GS-Cys)-conjugated
thermosensitive liposomes (HER2(+) affisomes)
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Drug delivery; Triggerable liposomes; Targeting; Affibody; Hyperthermia
ID DRUG-DELIVERY; HER2-POSITIVE TUMORS; SENSITIVE LIPOSOME; DOXORUBICIN;
MOLECULES; RECOMBINANT; THERAPY; CANCER; MODEL
AB We previously reported the formulation and physical properties of HER2 (human epidermal growth factor receptor 2)-specific affibody (ZHER2:342-Cys) conjugated thermosensitive liposomes (HER2(+) affisomes). Here we examined localized delivery potential of these affisomes by monitoring cellular interactions, intracellular uptake, and hyperthermia-induced effects on drug delivery. We modified ZHER2:342-Cys by introducing a glycine-serine spacer before the C-terminus cysteine (called ZHER2-GS-Cys) to achieve accessibility to cell surface expressed HER2. This modification did not affect HER2-specific binding and ZHER2-GS-Cys retained its ability to conjugate to the liposomes containing dipalmitoyl phosphatidyl choline: DSPE-PEG2000-Malemide, 96:04 mole ratios (HER2(+) affisomes). HER2(+) affisomes were either (i) fluorescently labeled with rhodamine-PE and calcein or (ii) loaded with an anticancer drug doxorubicin (DOX). Fluorescently labeled HER2(+) affisomes showed at least 10-fold increase in binding to HER2(+) cells (SK-BR-3) when compared to HER2(-) cells ( MDA-MB-468) at 37 degrees C. A competition experiment using free ZHER2-GS-Cys blocked HER2(+) affisome-SK-BR-3 cell associations. Imaging with confocal microscopy showed that HER2(+) affisomes accumulated in the cytosol of SK-BR-3 cells at 37 degrees C Hyperthermia-induced intracellular release experiments showed that the treatment of HER2(+) affisome/SK-BR-3 cell complexes with a 45 degrees C (+/- 1 degrees C) pre-equilibrated buffer resulted in cytosolic delivery of calcein. Substantial calcein release was observed within 20 mm at 45 degrees C, with no effect on cell viability under these conditions. Similarly, DOX-loaded HER2(+) affisomes showed at least 2- to 3-fold higher accumulation of DOX in SK-BR-3 cells as compared to control liposomes. DOX-mediated cytotoxicity was more pronounced in SK-BR-3 cells especially at lower doses of HER2(+) affisomes. Brief exposure of liposome-cell complexes at 45 degrees C prior to the onset of incubations for cell killing assays resulted in enhanced cytotoxicity for affisomes and control liposomes. However, Doxil (a commercially available liposome formulation) showed significantly lower toxicity under identical conditions. Therefore, our data demonstrate that HER2(+) affisomes encompass both targeting and triggering potential and hence may prove to be viable nanodrug delivery carriers for breast cancer treatment. Published by Elsevier B.V.
C1 [Puri, Anu] NCI, Membrane Struct & Funct Sect, CCRNP, NIH, Frederick, MD 21701 USA.
[Lyakhov, Ilya; Capala, Jacek] NCI, Radiat Oncol Branch, CCR, Bethesda, MD 20892 USA.
[Baxa, Ulrich] SAIC Frederick, Electron Microscopy Lab, ATP, Frederick, MD USA.
RP Puri, A (reprint author), NCI, Membrane Struct & Funct Sect, CCRNP, NIH, Bldg 469,Room 216A,POB B,Miller Dr, Frederick, MD 21701 USA.
EM puria@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [HHSN261 200 800 001E]
FX This research was supported [in part] by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN261 200 800 001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. government.
NR 28
TC 37
Z9 41
U1 0
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD JUL 30
PY 2011
VL 153
IS 2
BP 187
EP 194
DI 10.1016/j.jconrel.2011.04.005
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 799UZ
UT WOS:000293312900012
PM 21501640
ER
PT J
AU Polley, MYC
AF Polley, Mei-Yin C.
TI Practical modifications to the time-to-event continual reassessment
method for phase I cancer trials with fast patient accrual and
late-onset toxicities
SO STATISTICS IN MEDICINE
LA English
DT Article
DE phase I clinical trials; Time-to-Event Continual Reassessment Method;
dose finding; late-onset toxicity; adaptive design; Bayesian inference
ID CLINICAL-TRIALS; DOSE-ESCALATION; TITE-CRM; DESIGNS; IMPROVEMENTS
AB The goal of phase I cancer trials is to determine the highest dose of a treatment regimen with an acceptable toxicity rate. Traditional designs for phase I trials, such as the Continual Reassessment Method (CRM) and the 3+3 design, require each patient or a cohort of patients to be fully evaluated for the dose-limiting toxicity (DLT) before new patients can be enrolled. As such, the trial duration may be prohibitively long. The Time-to-Event Continual Reassessment Method (TITE-CRM, Cheung and Chappell, 2000) circumvents this limitation by allowing staggered patient accrual without the need for complete DLT follow-up of previously treated patients. However, in the setting of fast patient accrual and late-onset toxicities, the TITE-CRM results in overly aggressive dose escalation and exposes a considerable number of patients to toxic doses. We examine a modification to the TITE-CRM proposed by the original TITE-CRM creator and propose an alternative approach useful in this setting by incorporating an accrual suspension rule. A simulation study designed based on a neuro-oncology trial indicates that the modified methods provide a much improved degree of safety than the TITE-CRM while maintaining desirable design accuracy. The practical aspects of the proposed designs are discussed. The modifications presented are useful when planning phase I trials involving chemoradiation therapy. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Polley, Mei-Yin C.] NCI, Biometr Res Branch, Rockville, MD 20852 USA.
RP Polley, MYC (reprint author), Execut Plaza N,Room 8124,6130 Execut Blvd, Rockville, MD 20852 USA.
EM polleymc@mail.nih.gov
FU UCSF
FX This work was supported by the UCSF Resource Allocation Program (RAP)
REAC grant. The author is grateful to Professors Kathleen Lamborn and
Michael Prados at UCSF, who served as the author's mentors on this grant
award. The author also wishes to thank the editor, two referees,
Professor Ken Cheung at Columbia University, and members of the
Biostatistics and Computational Biology Core at the UCSF Cancer Center
whose helpful comments and suggestions led to an improved paper.
NR 32
TC 7
Z9 7
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD JUL 30
PY 2011
VL 30
IS 17
BP 2130
EP 2143
DI 10.1002/sim.4255
PG 14
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 792JK
UT WOS:000292739500009
PM 21590790
ER
PT J
AU Blair, KS
Geraci, M
Otero, M
Majestic, C
Odenheimer, S
Jacobs, M
Blair, RJR
Pine, DS
AF Blair, Karina S.
Geraci, Manilla
Otero, Marcela
Majestic, Catherine
Odenheimer, Stephanie
Jacobs, Madeline
Blair, R. J. R.
Pine, Daniel S.
TI Atypical modulation of medial prefrontal cortex to self-referential
comments in generalized social phobia
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Social phobia; fMRI; Self-referentiality; Medial prefrontal cortex;
Amygdala
ID CORTICAL MIDLINE STRUCTURES; ANTERIOR CINGULATE CORTEX;
ANXIETY-DISORDER; AMYGDALA ACTIVATION; FACES; BRAIN; FMRI; CRITICISM;
EMOTION; METAANALYSIS
AB Generalized social phobia (GSP) involves the fear of being negatively evaluated. Previous work suggests that self-referentiality, mediated by the medial prefrontal cortex (MFPC), plays an important role in the disorder. However, it is not clear whether this anomalous MPFC response to self-related information in patients with GSP concerns an increased representation of their own or others' opinions. In this article, we examine whether GSP is associated with increased response to own (1st person) or other individuals' (2nd person) opinions relative to healthy individuals. Unmedicated individuals with GSP (n = 15) and age-. IQ-, and gender-matched comparison individuals (n = 15) read 1st (e.g., I'm ugly), and 2nd (e.g., You're ugly) person viewpoint comments during functional magnetic resonance imaging. We observed significant group-by-viewpoint interactions within the ventral MPFC. Whereas the healthy comparison individuals showed significantly increased (or less decreased) BOLD responses to 1st relative to 2nd person viewpoints, the patients showed significantly increased responses to 2nd relative to 1st person viewpoints. The reduced BOLD responses to 1st person viewpoint comments shown by the patients correlated significantly with severity of social anxiety symptom severity. These results underscore the importance of dysfunctional self-referential processing and MPFC in GSP. We believe that these data reflect a reorganization of self-referential reasoning in the disorder with a self-concept perhaps atypically related to the view of others. Published by Elsevier Ireland Ltd.
C1 [Blair, Karina S.; Geraci, Manilla; Otero, Marcela; Majestic, Catherine; Odenheimer, Stephanie; Jacobs, Madeline; Blair, R. J. R.; Pine, Daniel S.] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Blair, KS (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM peschark@mail.nih.gov
FU NIH, National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Mental Health. The authors have no conflicts
of interest or financial disclosures to report.
NR 60
TC 34
Z9 34
U1 17
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD JUL 30
PY 2011
VL 193
IS 1
BP 38
EP 45
DI 10.1016/j.pscychresns.2010.12.016
PG 8
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 788US
UT WOS:000292470500005
PM 21601433
ER
PT J
AU Takikita, M
Xie, R
Chung, JY
Cho, H
Ylaya, K
Hong, SM
Moskaluk, CA
Hewitt, SM
AF Takikita, Mikiko
Xie, Ran
Chung, Joon-Yong
Cho, Hanbyoul
Ylaya, Kris
Hong, Seung-Mo
Moskaluk, Christopher A.
Hewitt, Stephen M.
TI Membranous expression of Her3 is associated with a decreased survival in
head and neck squamous cell carcinoma
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; FACTOR RECEPTOR
EGFR; BREAST-CANCER; CORRESPONDING METASTASES; FAMILY-MEMBERS;
OVARIAN-CANCER; PRIMARY TUMORS; C-ERBB-2 GENE; THERAPY
AB Background: Head and neck squamous cell carcinoma (HNSCC) still remains a lethal malignancy benefiting from the identification of the new target for early detection and/or development of new therapeutic regimens based on a better understanding of the biological mechanism for treatment. The overexpression of Her2 and Her3 receptors have been identified in various solid tumors, but its prognostic relevance in HNSCC remains controversial.
Methods: Three hundred eighty-seven primary HNSCCs, 20 matching metasis and 17 recurrent HNSCCs were arrayed into tissue microarrays. The relationships between Her2 and Her3 protein expression and clinicopathological parameters/survival of HNSCC patients were analyzed with immunohistochemistry.
Results: Her3 is detected as either a cytoplasmic or a membranous dominant expression pattern whereas Her2 expression showed uniform membranous form. In primary tumor tissues, high membranous Her2 expression level was found in 104 (26.9%) cases while positive membranous and cytoplasmic Her3 expression was observed in 34 (8.8%) and 300 (77.5%) samples, respectively. Membranous Her2 expression was significantly associated with histological grade (P = 0.021), as grade 2 tumors showed the highest positive expression. Membranous Her3 overexpression was significantly prevalent in metastatic tissues compared to primary tumors (P = 0.003). Survival analysis indicates that membranous Her3 expression is significantly associated with worse overall survival (P = 0.027) and is an independent prognostic factor in multivariate analysis (hazard ratio, 1.51; 95% confidence interval, 1.01-2.23; P = 0.040).
Conclusions: These results suggest that membranous Her3 expression is strongly associated with poor prognosis of patients with HNSCC and is a potential candidate molecule for targeted therapy.
C1 [Takikita, Mikiko; Xie, Ran; Cho, Hanbyoul; Ylaya, Kris; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Hong, Seung-Mo] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA.
[Moskaluk, Christopher A.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA 22908 USA.
RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA.
EM genejock@helix.nih.gov
OI Hong, Seung-Mo/0000-0002-8888-6007; Hewitt, Stephen/0000-0001-8283-1788;
Chung, Joon-Yong/0000-0001-5041-5982
FU NIH, National Cancer Institute, Center for Cancer Research; University
of Virginia School of Medicine
FX Collection of the material and TMA construction was supported by The
University of Virginia School of Medicine through fellowship support of
Seung-Mo Hong who collected cases and provided the design for the TMA
construction. Special thanks to Ms. Angela Miller of the Biorepository
and Tissue Research Facility of The University of Virginia for
construction of the TMAs used in this study. This research was supported
by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 47
TC 25
Z9 25
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 29
PY 2011
VL 9
AR 126
DI 10.1186/1479-5876-9-126
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 813AE
UT WOS:000294337000001
PM 21801427
ER
PT J
AU Xiao, XD
Feng, Y
Zhu, ZY
Dimitrov, DS
AF Xiao, Xiaodong
Feng, Yang
Zhu, Zhongyu
Dimitrov, Dimiter S.
TI Identification of a putative Crimean-Congo hemorrhagic fever virus entry
factor
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE CCHFV; Gn; Gc; Nucleolin; Receptor; Receptor-binding domain
ID SURFACE-EXPRESSED NUCLEOLIN; CELL-SURFACE; TARGET-CELLS; PROTEIN;
RECEPTOR; PSEUDOPEPTIDE; GLYCOPROTEINS; LOCALIZATION; HANTAVIRUSES;
REPLICATION
AB Entry of enveloped viruses into cells is initiated by binding of their envelope glycoproteins (Envs) to cell surface-associated receptors. The Crimean-Congo hemorrhagic fever virus (CCHFV) has two Envs, Gn and Gc, with poorly understood role in binding to susceptible cells. We expressed codon optimized Gn and Gc, and identified independently folded soluble Env fragments, one of which (Gc residues 180-300) bound CCHFV susceptible cells supposedly by interacting with a putative receptor. This receptor binding domain (RBD) was used to identify its interacting partner by coimmunoprecipitation and mass spectrometry. Thus we identified the human cell surface nucleolin as a putative CCHFV entry factor. Nucleolin was expressed on all susceptible cells tested but not on the surface of cells resistant to CCHFV infection. Further studies are needed to explore the nucleolin function as a plausible CCHFV receptor and the molecular mechanisms of the Gc-nucleolin interactions. The identification of the CCHFV RBD and its binding partner could provide novel targets for therapy and tools for prevention as well as more complete understanding of the mechanisms of CCHFV entry and pathogenesis. Published by Elsevier Inc.
C1 [Xiao, Xiaodong; Feng, Yang; Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA.
RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA.
EM dimitrdi@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
NIAID
FX We thank Robert Doms and Christopher Broder for providing reagents and
for helpful discussions, and the members of our group for help. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
N01-CO-12400 and the NIAID Biodefense Intramural Program (to D.S.D.).
NR 30
TC 28
Z9 28
U1 1
U2 5
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 JUL 29
PY 2011
VL 411
IS 2
BP 253
EP 258
DI 10.1016/j.bbrc.2011.06.109
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 806LS
UT WOS:000293809900005
PM 21723257
ER
PT J
AU Niu, G
Chen, XY
AF Niu, Gang
Chen, Xiaoyuan
TI Size Effect in Molecular Imaging of Vascular Endothelial Growth Factor
SO CHEMISTRY & BIOLOGY
LA English
DT Editorial Material
ID CANCER
AB Visualizing and quantifying vascular endothelial growth factor (VEGF) levels are crucial factors in understanding the tumor environment and monitoring antiangiogenic treatment. The small peptidic probes described by Fedorova et al. in this issue appear to be superior to antibodies in reflecting the dynamics of VEGF as they facilitate image quantification.
C1 [Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-02]
NR 8
TC 2
Z9 2
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD JUL 29
PY 2011
VL 18
IS 7
BP 819
EP 820
DI 10.1016/j.chembiol.2011.07.002
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809VQ
UT WOS:000294085200002
PM 21802000
ER
PT J
AU Lu, Y
Zha, XM
Kim, EY
Schachtele, S
Dailey, ME
Hall, DD
Strack, S
Green, SH
Hoffman, DA
Hell, JW
AF Lu, Yuan
Zha, Xiang-ming
Kim, Eun Young
Schachtele, Scott
Dailey, Michael E.
Hall, Duane D.
Strack, Stefan
Green, Steven H.
Hoffman, Dax A.
Hell, Johannes W.
TI A Kinase Anchor Protein 150 (AKAP150)-associated Protein Kinase A Limits
Dendritic Spine Density
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LONG-TERM POTENTIATION; NMDA RECEPTOR ACTIVATION; AMPA RECEPTORS;
POSTSYNAPTIC DENSITIES; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; DEPENDENT
PLASTICITY; PKA PHOSPHORYLATION; SYNAPTIC PLASTICITY; SCAFFOLD PROTEIN
AB The A kinase anchor protein AKAP150 recruits the cAMP-dependent protein kinase (PKA) to dendritic spines. Here we show that in AKAP150 (AKAP5) knock-out (KO) mice frequency of miniature excitatory post-synaptic currents (mEPSC) and inhibitory post-synaptic currents (mIPSC) are elevated at 2 weeks and, more modestly, 4 weeks of age in the hippocampal CA1 area versus litter mate WT mice. Linear spine density and ratio of AMPAR to NMDAR EPSC amplitudes were also increased. Amplitude and decay time of mEPSCs, decay time of mIPSCs, and spine size were unaltered. Mice in which the PKA anchoring C-terminal 36 residues of AKAP150 are deleted (D36) showed similar changes. Furthermore, whereas acute stimulation of PKA (2-4 h) increases spine density, prolonged PKA stimulation (48 h) reduces spine density in apical dendrites of CA1 pyramidal neurons in organotypic slice cultures. The data from the AKAP150 mutant mice show that AKAP150-anchored PKA chronically limits the number of spines with functional AMPARs at 2-4 weeks of age. However, synaptic transmission and spine density was normal at 8 weeks in KO and D36 mice. Thus AKAP150-independent mechanisms correct the aberrantly high number of active spines in juvenile AKAP150 KO and D36 mice during development.
C1 [Lu, Yuan; Hall, Duane D.; Strack, Stefan; Hell, Johannes W.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pharmacol, Iowa City, IA 52242 USA.
[Zha, Xiang-ming; Schachtele, Scott; Dailey, Michael E.; Green, Steven H.] Univ Iowa, Coll Liberal Arts & Sci, Dept Biol, Iowa City, IA 52242 USA.
[Lu, Yuan] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA.
[Zha, Xiang-ming] Univ S Alabama, Coll Med, Dept Cell Biol & Neurosci, Mobile, AL 36688 USA.
[Kim, Eun Young; Hoffman, Dax A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Unit, NIH, Bethesda, MD 20892 USA.
[Hell, Johannes W.] Univ Calif Davis, Sch Med, Dept Pharmacol, Davis, CA 95615 USA.
RP Lu, Y (reprint author), Magnuson Clin Ctr, Bldg 10,7D38,10 Ctr Dr, Bethesda, MD 20892 USA.
EM luyuan@mail.nih.gov; jwhell@ucdavis.edu
RI Hoffman, Dax/E-5155-2011
OI Hoffman, Dax/0000-0001-6999-2157
FU National Institutes of Health [DA015916, GM032875, NS043254, NS056244,
NS057714, DC002961, NS035563, NS017502]; American Heart Association
[0655764Z]; University of South Alabama; Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health
FX This work was supported, in whole or in part, by Grants DA015916,
GM032875 (to G. S. M.), NS043254, NS056244, NS057714 (to S. S.),
DC002961 (to S. H. G.), and NS035563, NS017502 (to J. W. H.) from the
National Institutes of Health. This work was also supported by Grant
0655764Z (to M. E. D.) from the American Heart Association, startup
funds from the University of South Alabama (to X. M. Z.), and the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health.
NR 74
TC 14
Z9 14
U1 2
U2 8
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 JUL 29
PY 2011
VL 286
IS 30
BP 26496
EP 26506
DI 10.1074/jbc.M111.254912
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 796UK
UT WOS:000293078200028
PM 21652711
ER
PT J
AU Meruvu, S
Hugendubler, L
Mueller, E
AF Meruvu, Sunitha
Hugendubler, Lynne
Mueller, Elisabetta
TI Regulation of Adipocyte Differentiation by the Zinc Finger Protein
ZNF638
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BINDING NUCLEAR-PROTEIN; TRANSCRIPTIONAL CONTROL; DOMAIN; ZFP423;
FAMILY; MOTIF
AB Zinc finger proteins constitute the largest family of transcription regulators in eukaryotes. These factors are involved in diverse processes in many tissues, including development and differentiation. We report here the characterization of the zinc finger protein ZNF638 as a novel regulator of adipogenesis. ZNF638 is induced early during adipocyte differentiation. Ectopic expression of ZNF638 increases adipogenesis in vitro, whereas its knockdown inhibits differentiation and decreases the expression of adipocyte-specific genes. ZNF638 physically interacts and transcriptionally cooperates with CCAAT/enhancer-binding protein (C/EBP) beta and C/EBP delta. This interaction leads to the expression of peroxisome proliferator-activated receptor gamma, which is the key regulator of adipocyte differentiation. In summary, ZNF638 is a novel and early regulator of adipogenesis that works as a transcription cofactor of C/EBPs.
C1 [Meruvu, Sunitha; Hugendubler, Lynne; Mueller, Elisabetta] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Mueller, E (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Rm 8D12B,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM elisabettam@niddk.nih.gov
FU National Institutes of Health NIDDK
FX This work was supported in whole by the National Institutes of Health
NIDDK Intramural Research Program.
NR 14
TC 20
Z9 25
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 29
PY 2011
VL 286
IS 30
BP 26516
EP 26523
DI 10.1074/jbc.M110.212506
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 796UK
UT WOS:000293078200030
PM 21602272
ER
PT J
AU Dong, SY
Wang, Y
Cassidy-Amstutz, C
Lu, G
Bigler, R
Jezyk, MR
Li, CH
Hall, TMT
Wang, ZF
AF Dong, Shuyun
Wang, Yang
Cassidy-Amstutz, Caleb
Lu, Gang
Bigler, Rebecca
Jezyk, Mark R.
Li, Chunhua
Hall, Traci M. Tanaka
Wang, Zefeng
TI Specific and Modular Binding Code for Cytosine Recognition in
Pumilio/FBF (PUF) RNA-binding Domains
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID YEAST 3-HYBRID SYSTEM; PROTEIN INTERACTIONS; MYOTONIC-DYSTROPHY;
HOMOLOGY DOMAIN; ELEGANS; DISEASE; SMART; MODES; CELLS; VEGF
AB Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for cytosine are unknown. Here we report identification of a cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and the cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.
C1 [Dong, Shuyun; Wang, Yang; Bigler, Rebecca; Wang, Zefeng] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Cassidy-Amstutz, Caleb; Lu, Gang; Jezyk, Mark R.; Hall, Traci M. Tanaka] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Cassidy-Amstutz, Caleb] N Carolina State Univ, Program Bioinformat, Raleigh, NC 27695 USA.
[Li, Chunhua] Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China.
RP Wang, ZF (reprint author), Univ N Carolina, Dept Pharmacol, CB 7365, Chapel Hill, NC 27599 USA.
EM zefeng@med.unc.edu
OI Wang, Zefeng/0000-0002-6605-3637; Dong, Shuyun/0000-0003-2988-6864;
Bigler, Rebecca/0000-0002-0075-6188
FU National Institute of Environmental Health Sciences; Beckman Foundation;
Kimmel Sidney Scholar; United States Department of Energy, Office of
Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
FX This work was supported, in whole or in part, by a grant from the
Intramural Research Program of the National Institute of Environmental
Health Sciences (to T. M. T. H.) and by a grant from the Beckman
Foundation and the Kimmel Sidney Scholar award (to Z.W.).; We thank Dr.
Marvin Wickens (University of Wisconsin) for providing the plasmids and
yeast strains for the Y3H assay. We thank Dr. Rajarshi Chudhury for
suggestions and help in protein purification, Dr. Chen Qiu for help with
RNA binding assays, and Dr. Lars Pedersen and the staff at the SER-CAT
beamline for help with X-ray data collection. Data were collected at
SER-CAT 22-ID beamline at the Advanced Photon Source, Argonne National
Laboratory. Supporting institutions may be found on-line. Use of the
Advanced Photon Source was supported by the United States Department of
Energy, Office of Science, Office of Basic Energy Sciences, under
Contract W-31-109-Eng-38.
NR 34
TC 50
Z9 50
U1 1
U2 13
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 JUL 29
PY 2011
VL 286
IS 30
BP 26732
EP 26742
DI 10.1074/jbc.M111.244889
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 796UK
UT WOS:000293078200050
PM 21653694
ER
PT J
AU Madsen, DH
Ingvarsen, S
Jurgensen, HJ
Melander, MC
Kjoller, L
Moyer, A
Honore, C
Madsen, CA
Garred, P
Burgdorf, S
Bugge, TH
Behrendt, N
Engelholm, LH
AF Madsen, Daniel H.
Ingvarsen, Signe
Jurgensen, Henrik J.
Melander, Maria C.
Kjoller, Lars
Moyer, Amanda
Honore, Christian
Madsen, Charlotte A.
Garred, Peter
Burgdorf, Sven
Bugge, Thomas H.
Behrendt, Niels
Engelholm, Lars H.
TI The Non-phagocytic Route of Collagen Uptake A DISTINCT DEGRADATION
PATHWAY
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PLASMINOGEN-ACTIVATOR RECEPTOR; MACROPHAGE MANNOSE RECEPTOR; TUMOR-CELL
LINES; UROKINASE RECEPTOR; HUMAN-FIBROBLASTS; MONOCLONAL-ANTIBODIES;
ENDOTHELIAL-CELLS; TRANSMEMBRANE GLYCOPROTEIN; BINDING-PROPERTIES;
LECTIN RECEPTOR
AB The degradation of collagens, the most abundant proteins of the extracellular matrix, is involved in numerous physiological and pathological conditions including cancer invasion. An important turnover pathway involves cellular internalization and degradation of large, soluble collagen fragments, generated by initial cleavage of the insoluble collagen fibers. We have previously observed that in primary mouse fibroblasts, this endocytosis of collagen fragments is dependent on the receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180. Others have identified additional mechanisms of collagen uptake, with different associated receptors, in other cell types. These receptors include beta 1-integrins, being responsible for collagen phagocytosis, and the mannose receptor. We have now utilized a newly developed monoclonal antibody against uPARAP/Endo180, which down-regulates the receptor protein level on treated cells, to examine the role of uPARAP/Endo180 as a mediator of collagen internalization by a wide range of cultured cell types. With the exception of macrophages, all cells that proved capable of efficient collagen internalization were of mesenchymal origin and all of these utilized uPARAP/Endo180 for their collagen uptake process. Macrophages internalized collagen in a process mediated by the mannose receptor, a protein belonging to the same protein family as uPARAP/Endo180. beta 1-Integrins were found not to be involved in the endocytosis of soluble collagen, irrespectively of whether this was mediated by uPARAP/Endo180 or the mannose receptor. This further distinguishes these pathways from the phagocytic uptake of particulate collagen.
C1 [Madsen, Daniel H.; Ingvarsen, Signe; Jurgensen, Henrik J.; Melander, Maria C.; Kjoller, Lars; Madsen, Charlotte A.; Behrendt, Niels; Engelholm, Lars H.] Rigshosp, Finsen Lab BRIC, DK-2200 Copenhagen, Denmark.
[Honore, Christian; Garred, Peter] Rigshosp, Dept Clin Immunol, Mol Med Lab, DK-2200 Copenhagen, Denmark.
[Ingvarsen, Signe] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
[Moyer, Amanda; Bugge, Thomas H.] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Burgdorf, Sven] Univ Bonn, Life & Med Sci LIMES Inst, D-53115 Bonn, Germany.
RP Engelholm, LH (reprint author), Copenhagen Bioctr, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark.
EM lhe@finsenlab.dk
OI Madsen, Daniel Hargboel/0000-0002-3183-6201; Engelholm,
Lars/0000-0002-6616-1232
FU National Institutes of Health NIDCR; Danish Cancer Society; Danish
Medical Research Council; Danish Cancer Research Foundation; Lundbeck
Foundation; Danish National Research Foundation (Danish-Chinese Center
for Proteases and Cancer); European Community [201279]; "Grosserer
Alfred Nielsen og Hustrus" foundation; Copenhagen University Hospital;
University of Copenhagen, Faculty of Science
FX This work was supported, in whole or in part, by the National Institutes
of Health NIDCR Intramural Research Program (to A. M. and T. H. B.), the
Danish Cancer Society, the Danish Medical Research Council, the Danish
Cancer Research Foundation, the Lundbeck Foundation, the Danish National
Research Foundation (Danish-Chinese Center for Proteases and Cancer),
European Community's Seventh Framework Programme FP7/2007-2011 Grant
201279 (to N. B.), grants from the Lundbeck Foundation and the
"Grosserer Alfred Nielsen og Hustrus" foundation (to L. H. E.), the
Copenhagen University Hospital (to D. H. M. and H. J. J.), and the
University of Copenhagen, Faculty of Science (to S. I.).
NR 81
TC 45
Z9 45
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 29
PY 2011
VL 286
IS 30
BP 26996
EP 27010
DI 10.1074/jbc.M110.208033
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 796UK
UT WOS:000293078200073
PM 21652704
ER
PT J
AU van Hees, VT
Renstrom, F
Wright, A
Gradmark, A
Catt, M
Chen, KY
Lof, M
Bluck, L
Pomeroy, J
Wareham, NJ
Ekelund, U
Brage, S
Franks, PW
AF van Hees, Vincent T.
Renstrom, Frida
Wright, Antony
Gradmark, Anna
Catt, Michael
Chen, Kong Y.
Lof, Marie
Bluck, Les
Pomeroy, Jeremy
Wareham, Nicholas J.
Ekelund, Ulf
Brage, Soren
Franks, Paul W.
TI Estimation of Daily Energy Expenditure in Pregnant and Non-Pregnant
Women Using a Wrist-Worn Tri-Axial Accelerometer
SO PLOS ONE
LA English
DT Article
ID DOUBLY-LABELED-WATER; PHYSICAL-ACTIVITY; VALIDATION; ADULTS
AB Background: Few studies have compared the validity of objective measures of physical activity energy expenditure (PAEE) in pregnant and non-pregnant women. PAEE is commonly estimated with accelerometers attached to the hip or waist, but little is known about the validity and participant acceptability of wrist attachment. The objectives of the current study were to assess the validity of a simple summary measure derived from a wrist-worn accelerometer (GENEA, Unilever Discover, UK) to estimate PAEE in pregnant and non-pregnant women, and to evaluate participant acceptability.
Methods: Non-pregnant (N = 73) and pregnant (N = 35) Swedish women (aged 20-35 yrs) wore the accelerometer on their wrist for 10 days during which total energy expenditure (TEE) was assessed using doubly-labelled water. PAEE was calculated as 0.96TEE-REE. British participants (N = 99; aged 22-65 yrs) wore accelerometers on their non-dominant wrist and hip for seven days and were asked to score the acceptability of monitor placement (scored 1 [least] through 10 [most] acceptable).
Results: There was no significant correlation between body weight and PAEE. In non-pregnant women, acceleration explained 24% of the variation in PAEE, which decreased to 19% in leave-one-out cross-validation. In pregnant women, acceleration explained 11% of the variation in PAEE, which was not significant in leave-one-out cross-validation. Median (IQR) acceptability of wrist and hip placement was 9(8-10) and 9(7-10), respectively; there was a within-individual difference of 0.47 (p < .001).
Conclusions: A simple summary measure derived from a wrist-worn tri-axial accelerometer adds significantly to the prediction of energy expenditure in non-pregnant women and is scored acceptable by participants.
C1 [van Hees, Vincent T.; Wareham, Nicholas J.; Ekelund, Ulf; Brage, Soren] Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England.
[Renstrom, Frida; Gradmark, Anna; Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Med Sect, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden.
[Renstrom, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Wright, Antony; Bluck, Les] Med Res Council Human Nutr Res, Cambridge, England.
[Catt, Michael] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Chen, Kong Y.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA.
[Lof, Marie] Linkoping Univ, Dept Clin & Expt Med, Div Nutr, Linkoping, Sweden.
[Pomeroy, Jeremy] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
RP van Hees, VT (reprint author), Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England.
EM vincent.vanhees@mrc-epid.cam.ac.uk
RI Brage, Soren/C-6415-2013;
OI Brage, Soren/0000-0002-1265-7355; Franks, Paul/0000-0002-0520-7604;
Chen, Kong/0000-0002-0306-1904
FU LifeGene (Torsten and Ragnar Soderbergs Foundation); Fredrik and Ingrid
Thurings Foundation; Umea University; Vasterbottens regional health
authority
FX This work was supported by Grants from LifeGene (Torsten and Ragnar
Soderbergs Foundation), Fredrik and Ingrid Thurings Foundation, Umea
University Young Investigator's Award, and the Vasterbottens regional
health authority (all grants to PWF). LifeGene is a charity, by which no
commercial interests are involved (https://www.lifegene.se/In-english/).
GENEA monitors in the Swedish study were loaned pro gratis from Unilever
Discover Ltd. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 34
TC 45
Z9 45
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 29
PY 2011
VL 6
IS 7
AR e22922
DI 10.1371/journal.pone.0022922
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 799KV
UT WOS:000293286500052
PM 21829556
ER
PT J
AU Janssen, MJ
Yasuda, RP
Vicini, S
AF Janssen, Megan J.
Yasuda, Robert P.
Vicini, Stefano
TI GABA(A) receptor beta 3 subunit expression regulates tonic current in
developing striatopallidal medium spiny neurons
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE GABA; tonic inhibition; striatum; patch-clamp; Cre-lox genetics
ID CHILDHOOD ABSENCE EPILEPSY; A RECEPTOR; BETA(3) SUBUNIT;
ELECTROPHYSIOLOGICAL PROPERTIES; GABAERGIC INTERNEURONS;
GENE-EXPRESSION; MICE LACKING; NETWORK; MODULATION; ACTIVATION
AB The striatum is a key structure for movement control, but the mechanisms that dictate the output of distinct subpopulations of medium spiny projection neurons (MSNs), striatonigral projecting and dopamine D1 receptor-(D1+) or striatopallidal projecting and dopamine D2 receptor-(D2+) expressing neurons, remains poorly understood. GABA-mediated tonic inhibition largely controls neuronal excitability and action potential firing rates, and we previously suggested with pharmacological analysis that the GABA(A) receptor beta 3 subunit plays a large role in the basal tonic current seen in D2+ MSNs from young mice (Ade et al., 2008; Janssen et al., 2009). In this study, we demonstrated the essential role of the beta 3 GABA(A) receptor subunit in mediating MSN tonic currents using conditional beta 3 subunit knock-out(beta 3f/f(Drd2)) mice. Cre-lox genetics were used to generate mice where Cre recombinase was expressed under the D2 receptor (Drd2) promoter. We show that while the wild-type MSN tonic current pattern demonstrates a high degree of variability, tonic current patterns from beta 3f/f(Drd2) mice are narrow, suggesting that the beta 3 subunit is essential to striatal MSN GABA-mediated tonic current. Our data also suggest that a distinct population of synaptic receptors upregulate due to beta 3 subunit removal. Further, deletion of this subunit significantly decreases the D2+ MSN excitability. These results offer insight for target mechanisms in Parkinson's disease, where symptoms arise due to the imbalance in striatal D1+ and D2+ MSN excitability and output.
C1 [Janssen, Megan J.; Yasuda, Robert P.; Vicini, Stefano] Georgetown Univ, Sch Med, Dept Physiol & Pharmacol, Washington, DC USA.
[Vicini, Stefano] Georgetown Univ, Sch Med, Interdisciplinary Program Neurosci, Washington, DC USA.
RP Janssen, MJ (reprint author), NICHD, Mol Neurobiol Sect, NIH, Bldg 35,Room 2C-1001,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM megan.janssen-schroeder@nih.gov
FU NIH [MH64797]
FX We thank Dr. David Lovinger at the National Institute on Alcoholism and
Alcohol Abuse for providing the BAC-D2-EGFP mice, Dr. Nicole Calakos
from Duke University for the Drd1a-tdTomato mice, and Dr. Baoji Xu at
Georgetown University for providing the Drd2-Cre mice. The authors also
appreciate the technical assistance of Patrick Forcelli and Patrick
Hussman from Georgetown University. Supported by: NIH grant MH64797.
NR 45
TC 13
Z9 13
U1 0
U2 3
PU FRONTIERS RES FOUND
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD JUL 28
PY 2011
VL 5
AR 15
DI 10.3389/fncel.2011.00015
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 886ZY
UT WOS:000299895900001
PM 21847370
ER
PT J
AU Song, G
Hsu, CH
Riemer, C
Zhang, Y
Kim, HL
Hoffmann, F
Zhang, LX
Hardison, RC
Green, ED
Miller, W
AF Song, Giltae
Hsu, Chih-Hao
Riemer, Cathy
Zhang, Yu
Kim, Hie Lim
Hoffmann, Federico
Zhang, Louxin
Hardison, Ross C.
Green, Eric D.
Miller, Webb
CA NISC Comparative Sequencing
TI Conversion events in gene clusters
SO BMC EVOLUTIONARY BIOLOGY
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; TOBACCO-SPECIFIC CARCINOGEN; HUMAN
CYP2A13 GENE; GLOBIN GENES; FUNCTIONAL-CHARACTERIZATION;
METABOLIC-ACTIVATION; SEQUENCE ALIGNMENTS; LUNG ADENOCARCINOMA;
GAMMA-GLOBIN; EVOLUTION
AB Background: Gene clusters containing multiple similar genomic regions in close proximity are of great interest for biomedical studies because of their associations with inherited diseases. However, such regions are difficult to analyze due to their structural complexity and their complicated evolutionary histories, reflecting a variety of large-scale mutational events. In particular, conversion events can mislead inferences about the relationships among these regions, as traced by traditional methods such as construction of phylogenetic trees or multi-species alignments.
Results: To correct the distorted information generated by such methods, we have developed an automated pipeline called CHAP (Cluster History Analysis Package) for detecting conversion events. We used this pipeline to analyze the conversion events that affected two well-studied gene clusters (alpha-globin and beta-globin) and three gene clusters for which comparative sequence data were generated from seven primate species: CCL (chemokine ligand), IFN (interferon), and CYP2abf (part of cytochrome P450 family 2). CHAP is freely available at http://www.bx.psu.edu/miller_lab.
Conclusions: These studies reveal the value of characterizing conversion events in the context of studying gene clusters in complex genomes.
C1 [Song, Giltae; Riemer, Cathy; Zhang, Yu; Kim, Hie Lim; Hardison, Ross C.; Miller, Webb] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
[Hsu, Chih-Hao] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Hoffmann, Federico] Mississippi State Univ, Dept Biochem & Mol Biol, Mississippi State, MS 39760 USA.
[Zhang, Louxin] Natl Univ Singapore, Dept Math, Singapore 117543, Singapore.
[Green, Eric D.] NHGRI, NISC, NIH, Bethesda, MD 20892 USA.
[Green, Eric D.; NISC Comparative Sequencing] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Song, G (reprint author), Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
EM gsong@bx.psu.edu
RI Zhang, Louxin /M-4865-2016; Kim, Hie Lim/E-7393-2017;
OI Zhang, Louxin /0000-0003-0260-824X; Kim, Hie Lim/0000-0003-3080-9524;
Song, Giltae/0000-0001-8796-4678
FU National Human Genome Research Institute [HG02238]; National Institute
of Diabetes, Digestive and Kidney Diseases [DK065806]
FX This work was supported by grant HG02238 to WM from the National Human
Genome Research Institute and grant DK065806 to RCH from the National
Institute of Diabetes, Digestive and Kidney Diseases.
NR 54
TC 7
Z9 7
U1 0
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2148
J9 BMC EVOL BIOL
JI BMC Evol. Biol.
PD JUL 28
PY 2011
VL 11
AR 226
DI 10.1186/1471-2148-11-226
PG 18
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 811DV
UT WOS:000294183300001
PM 21798034
ER
PT J
AU Kotowski, SJ
Hopf, FW
Seif, T
Bonci, A
von Zastrow, M
AF Kotowski, Sarah J.
Hopf, F. Woodward
Seif, Taban
Bonci, Antonello
von Zastrow, Mark
TI Endocytosis Promotes Rapid Dopaminergic Signaling
SO NEURON
LA English
DT Article
ID AGONIST-INDUCED DESENSITIZATION; D1A RECEPTOR RESPONSIVENESS;
PROTEIN-COUPLED RECEPTORS; STRIATAL NEURONS; D-1 RECEPTOR;
PLASMA-MEMBRANE; SYNAPTIC-TRANSMISSION; RECYCLING SIGNAL; PRIMARY
CULTURES; IN-VIVO
AB D(1) dopamine receptors are primary mediators of dopaminergic signaling in the CNS. These receptors internalize rapidly following agonist-induced activation, but the functional significance of this process is unknown. We investigated D(1) receptor endocytosis and signaling in HEK293 cells and cultured striatal neurons using real-time fluorescence imaging and cAMP biosensor technology. Agonist-induced activation of D(1) receptors promoted endocytosis of receptors with a time course overlapping that of acute cAMP accumulation. Inhibiting receptor endocytosis blunted acute D(1) receptor-mediated signaling in both dissociated cells and striatal slice preparations. Although endocytic inhibition markedly attenuated acute cAMP accumulation, inhibiting the subsequent recycling of receptors had no effect. Further, D(1) receptors localized in close proximity to endomembrane-associated trimeric G protein and adenylyl cyclase immediately after endocytosis. Together, these results suggest a previously unanticipated role of endocytosis, and the early endocytic pathway, in supporting rapid dopaminergic neurotransmission.
C1 [Kotowski, Sarah J.; von Zastrow, Mark] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
[Kotowski, Sarah J.; von Zastrow, Mark] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Kotowski, Sarah J.] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA.
[Hopf, F. Woodward; Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Hopf, F. Woodward; Seif, Taban; Bonci, Antonello] Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
[Bonci, Antonello] NIDA, Baltimore, MD 21224 USA.
RP von Zastrow, M (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
EM mark.vonzastrow@ucsf.edu
FU National Institutes of Health [DA-010711, DA-010154, MH-24468,
AAA-015358]; State of California for medical research on alcohol and
substance abuse through the University of California, San Francisco
FX We thank Dr. Martin Lohse (University of Wurzburg, Germany) for
providing the Epac1 cAMPs construct and Dr. Tomas Kirchhausen (Harvard
Medical School) for providing dynasore, used in initial experiments and
instructions for its effective use. Data for this study were collected
at the Nikon Imaging Center (NIC) at the University of California, San
Francisco. We are grateful to Dr. Kurt Thorn, Director of the NIC, for
valuable instruction and advice. We also thank Drs. Guillermo Yudowski
and Kit Wong for advice and assistance and Dr. Jin Tomshine for useful
discussion. This work was supported by grants from the National
Institutes of Health (DA-010711 and DA-010154 to M.Z., MH-24468 to
S.J.K., AAA-015358 to F.W.H.) and funds provided by the State of
California for medical research on alcohol and substance abuse through
the University of California, San Francisco (A.B.).
NR 60
TC 51
Z9 52
U1 2
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 28
PY 2011
VL 71
IS 2
BP 278
EP 290
DI 10.1016/j.neuron.2011.05.036
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 801JF
UT WOS:000293433900012
PM 21791287
ER
PT J
AU Kumar, J
Schuck, P
Mayer, ML
AF Kumar, Janesh
Schuck, Peter
Mayer, Mark L.
TI Structure and Assembly Mechanism for Heteromeric Kainate Receptors
SO NEURON
LA English
DT Article
ID N-TERMINAL DOMAIN; GLUTAMATE-RECEPTOR; NMDA RECEPTORS; LIGAND-BINDING;
AMPA RECEPTORS; ENDOPLASMIC-RETICULUM; PROTEIN INTERACTIONS; SYNAPSE
FORMATION; CRYSTAL-STRUCTURE; EPHB RECEPTORS
AB Native glutamate receptor ion channels are tetrameric assemblies containing two or more different subunits. NMDA receptors are obligate heteromers formed by coassembly of two or three divergent gene families. While some AMPA and kainate receptors can form functional homomeric ion channels, the KA1 and KA2 subunits are obligate heteromers which function only in combination with GluR5-7. The mechanisms controlling glutamate receptor assembly involve an initial step in which the amino terminal domains (ATD) assemble as dimers. Here, we establish by sedimentation velocity that the ATDs of GluR6 and KA2 coassemble as a heterodimer of K(d) 11 nM, 32,000-fold lower than the K(d) for homodimer formation by KA2; we solve crystal structures for the GluR6/KA2 ATD heterodimer and heterotetramer assemblies. Using these structures as a guide, we perform a mutant cycle analysis to probe the energetics of assembly and show that high-affinity ATD interactions are required for biosynthesis of functional heteromeric receptors.
C1 [Kumar, Janesh; Mayer, Mark L.] NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA.
[Schuck, Peter] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, DHHS, Bethesda, MD 20892 USA.
RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA.
EM mayerm@mail.nih.gov
RI Mayer, Mark/H-5500-2013;
OI Schuck, Peter/0000-0002-8859-6966
FU National Cancer Institute [Y1-CO-1020]; National Institute of General
Medical Science [Y1-GM-1104]; U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; NICHD;
NIBIB, NIH, DHHS
FX We thank Carla Glasser and Andrea Balbo for technical assistance and
Drs. Peter Kwong and Yongping Yang for advice with suspension cell
cultures. Nucleic acid sequencing was performed by the NINDS DNA
sequencing facility. Synchrotron diffraction data was collected at the
GM/CA CAT 23 ID-B beamline. GM/CA CAT has been funded in whole or in
part with Federal funds from the National Cancer Institute (Y1-CO-1020)
and the National Institute of General Medical Science (Y1-GM-1104). Use
of the Advanced Photon Source was supported by the U.S. Department of
Energy, Office of Science, Office of Basic Energy Sciences, under
Contract No. DE-AC02-06CH11357. This work was supported by the
intramural research programs of NICHD and NIBIB, NIH, DHHS (M.L.M. and
P.S.).
NR 62
TC 60
Z9 63
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 28
PY 2011
VL 71
IS 2
BP 319
EP 331
DI 10.1016/j.neuron.2011.05.038
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 801JF
UT WOS:000293433900015
PM 21791290
ER
PT J
AU Keele, BF
Estes, JD
AF Keele, Brandon F.
Estes, Jacob D.
TI Barriers to mucosal transmission of immunodeficiency viruses
SO BLOOD
LA English
DT Review
ID SIV VAGINAL TRANSMISSION; INTESTINAL MUCUS BARRIER; FEMALE
RHESUS-MACAQUES; INTRAVAGINAL INOCULATION; HIV-1 INFECTION; HETEROSEXUAL
TRANSMISSION; SEXUAL TRANSMISSION; GENITAL-TRACT; MALE CIRCUMCISION;
DENDRITIC CELLS
AB Lentiviruses such as HIV have a daunting challenge in gaining access to a new host predominantly through the penile, rectal, or vaginal/cervical mucosal tissue after sexual exposure. Multiple mechanisms have evolved to help prevent such infections, including anatomical barriers, innate inhibitors, and adaptive immune responses. For lentiviruses, it appears that in naive or even conventionally vaccinated hosts, typical adaptive immune responses are generally too little and too late to prevent infection. Nevertheless, a combination of anatomical barriers and innate immune responses may limit transmission, especially in patients without predisposing conditions such as mucosal lesions or preexisting sexually transmitted infections. Furthermore, when infection does occur, most often the primary viremia of the acute infection can be traced back genetically to a single founder virus. Unfortunately, even a single virion can establish an infection that will ultimately lead to the demise of the host. This review seeks to describe the biology of and barriers to establishment of systemic, disseminated productive infection with HIV after sexual exposure and to discuss the possible mechanisms leading to infection by a single viral variant. Understanding the initial events of infection, before systemic spread, could provide insights into strategies for reducing acquisition or ameliorating clinical outcome. (Blood. 2011;118(4):839-846)
C1 [Keele, Brandon F.; Estes, Jacob D.] NCI, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Keele, BF (reprint author), NCI, AIDS & Canc Virus Program, SAIC Frederick, 1050 Boyles St, Frederick, MD 21702 USA.
EM keelebf@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN266200400088C]
FX This work was supported with federal funds from the National Cancer
Institute, National Institutes of Health under contract
HHSN266200400088C. This work represents the opinions of the authors and
not necessarily the National Institutes of Health or the Department of
Health and Human Services.
NR 72
TC 41
Z9 41
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 28
PY 2011
VL 118
IS 4
BP 839
EP 846
DI 10.1182/blood-2010-12-325860
PG 8
WC Hematology
SC Hematology
GA 798PC
UT WOS:000293221700009
PM 21555745
ER
PT J
AU Brenchley, JM
Paiardini, M
AF Brenchley, Jason M.
Paiardini, Mirko
TI Immunodeficiency lentiviral infections in natural and non-natural hosts
SO BLOOD
LA English
DT Review
ID CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; HUMORAL IMMUNE-RESPONSES;
ACUTE SIV INFECTION; SOOTY MANGABEYS; HIV-1 INFECTION;
VIRUS-REPLICATION; RHESUS MACAQUES; GASTROINTESTINAL-TRACT; DISEASE
PROGRESSION
AB The host immune system is profoundly affected during the acute phase of progressive immunodeficiency lentiviral infections. Studies of these alterations have been quite restricted in humans because of the limited availability of samples from acutely HIV-infected persons. Therefore, numerous studies have turned attention to nonhuman primate models. Specifically, SIV-infected rhesus macaques (RMs) have been informative for understanding the pathogenesis of HIV infection in humans. Indeed, advantages of the nonhuman primate model include the ability to study the very early events after infection and the ability to retrieve copious amounts of tissues. In addition, nonhuman primates allow for comparative studies between non-natural and natural hosts for SIV, in which SIV infection results in progression, or not, to AIDS, respectively. Although SIV infection of RM is the best model for HIV infection, the immunologic and/or virologic phenomena in SIV-infected RM do not always reflect those seen in HIV-infected humans. Here virologic and immunologic aspects of acute HIV infection of humans and SIV infection of Asian and African nonhuman primates are discussed and compared in relation to how these aspects relate to disease progression. (Blood. 2011;118(4):847-854)
C1 [Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Paiardini, Mirko] Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike,Bldg 4,Rm 301, Bethesda, MD 20892 USA.
EM jbrenchl@mail.nih.gov; mirko.paiardini@emory.edu
FU National Institutes of Health [R01 AI084836]; National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX This work was supported in part by the National Institutes of Health
(grant R01 AI084836; M.P.) and the intramural National Institute of
Allergy and Infectious Diseases, National Institutes of Health program.
NR 100
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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 JUL 28
PY 2011
VL 118
IS 4
BP 847
EP 854
DI 10.1182/blood-2010-12-325936
PG 8
WC Hematology
SC Hematology
GA 798PC
UT WOS:000293221700010
PM 21505193
ER
PT J
AU Machado, RF
Barst, RJ
Yovetich, NA
Hassell, KL
Kato, GJ
Gordeuk, VR
Gibbs, JSR
Little, JA
Schraufnagel, DE
Krishnamurti, L
Girgis, RE
Morris, CR
Rosenzweig, EB
Badesch, DB
Lanzkron, S
Onyekwere, O
Castro, OL
Sachdev, V
Waclawiw, MA
Woolson, R
Goldsmith, JC
Gladwin, MT
AF Machado, Roberto F.
Barst, Robyn J.
Yovetich, Nancy A.
Hassell, Kathryn L.
Kato, Gregory J.
Gordeuk, Victor R.
Gibbs, J. Simon R.
Little, Jane A.
Schraufnagel, Dean E.
Krishnamurti, Lakshmanan
Girgis, Reda E.
Morris, Claudia R.
Rosenzweig, Erika B.
Badesch, David B.
Lanzkron, Sophie
Onyekwere, Onyinye
Castro, Oswaldo L.
Sachdev, Vandana
Waclawiw, Myron A.
Woolson, Rob
Goldsmith, Jonathan C.
Gladwin, Mark T.
CA Walk-PhaSST Investigators Patients
TI Hospitalization for pain in patients with sickle cell disease treated
with sildenafil for elevated TRV and low exercise capacity
SO BLOOD
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; PULMONARY ARTERIAL-HYPERTENSION; SYSTOLIC
HEART-FAILURE; PHARMACOLOGICAL INHIBITION; THERMAL HYPERALGESIA;
INFLAMMATORY PAIN; GENETIC KNOCKOUT; INOS-DEFICIENT; MICE; HEMOLYSIS
AB In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity. A TRV >= 2.7 m/s and a 6-minute walk distance (6MWD) between 150 and 500 m were required for enrollment in this 16-week, double-blind, placebo-controlled sildenafil trial. After 74 of the screened subjects were randomized, the study was stopped early due to a higher percentage of subjects experiencing serious adverse events in the sildenafil arm (45% of sildenafil, 22% of placebo, P =.022). Subject hospitalization for pain was the predominant cause for this difference: 35% with sildenafil compared with 14% with placebo (P =.029). There was no evidence of a treatment effect on 6MWD (placebo-corrected effect -9 m; 95% confidence interval [ 95% CI] -56-38; P = .703), TRV (P = .503), or N-terminal pro-brain natriuretic peptide (P = .410). Sildenafil appeared to increase hospitalization rates for pain in patients with SCD. This study is registered at www.clinicaltrials.gov as NCT00492531. (Blood. 2011;118(4):855-864)
C1 [Gladwin, Mark T.] Univ Pittsburgh, UPMC Montefiore Hosp, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
[Machado, Roberto F.; Schraufnagel, Dean E.] Univ Illinois, Chicago, IL USA.
[Barst, Robyn J.; Rosenzweig, Erika B.] Columbia Univ, New York, NY USA.
[Yovetich, Nancy A.; Woolson, Rob] Rho Inc, Chapel Hill, NC USA.
[Hassell, Kathryn L.; Badesch, David B.] Univ Colorado, Denver, CO 80202 USA.
[Kato, Gregory J.; Sachdev, Vandana] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Gordeuk, Victor R.; Onyekwere, Onyinye; Castro, Oswaldo L.] Howard Univ, Washington, DC 20059 USA.
[Gibbs, J. Simon R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England.
[Little, Jane A.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Krishnamurti, Lakshmanan] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Girgis, Reda E.; Lanzkron, Sophie] Johns Hopkins Univ, Baltimore, MD USA.
[Morris, Claudia R.] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA.
[Waclawiw, Myron A.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA.
RP Gladwin, MT (reprint author), Univ Pittsburgh, UPMC Montefiore Hosp, Div Pulm Allergy & Crit Care Med, NW628,3459 5th Ave, Pittsburgh, PA 15213 USA.
EM gladwinmt@upmc.edu
RI Krishnamurti, Lakshmanan/F-7637-2011; Kato, Gregory/I-7615-2014;
OI Kato, Gregory/0000-0003-4465-3217; Schraufnagel,
Dean/0000-0003-0063-7223
FU NIH [UL1 RR024131]; NIHR Biomedical Research Centre; NHLBI, NIH,
Department of Health and Human Services [HHSN268200617182C]
FX This work was supported in part by an NIH Clinical and Translational
Science Award (UL1 RR024131 to C.R.M.) and a NIHR Biomedical Research
Centre grant (to J.S.R.G.). Study drug and placebo were donated by
Pfizer Inc (New York, NY). This project was funded with federal funds
from the NHLBI, NIH, Department of Health and Human Services, under
contract HHSN268200617182C.
NR 37
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U1 3
U2 8
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 JUL 28
PY 2011
VL 118
IS 4
BP 855
EP 864
DI 10.1182/blood-2010-09-306167
PG 10
WC Hematology
SC Hematology
GA 798PC
UT WOS:000293221700011
PM 21527519
ER
PT J
AU Yang, SC
Liu, F
Wang, QJ
Rosenberg, SA
Morgan, RA
AF Yang, Shicheng
Liu, Fang
Wang, Qiong J.
Rosenberg, Steven A.
Morgan, Richard A.
TI The Shedding of CD62L (L-Selectin) Regulates the Acquisition of Lytic
Activity in Human Tumor Reactive T Lymphocytes
SO PLOS ONE
LA English
DT Article
ID CENTRAL MEMORY; CELL SUBSETS; SECRETORY LYSOSOMES; EFFECTOR FUNCTION;
GENE-EXPRESSION; CD8+T CELLS; RECEPTOR; ADHESION; ANTIGEN;
IDENTIFICATION
AB CD62L/L-selectin is a marker found on naive T cells and further distinguishes central memory (Tcm, CD62L+) from effector memory (Tem, CD62L-) T cells. The regulation of CD62L plays a pivotal role in controlling the traffic of T lymphocytes to and from peripheral lymph nodes. CD62L is shed from the cell membrane following T cell activation, however, the physiological significance of this event remains to be elucidated. In this study, we utilized in vitro generated anti-tumor antigen T cells and melanoma lines as a model to evaluate the dynamics of CD62L shedding and expression of CD107a as a marker of lytic activity. Upon encounter, with matched tumor lines, antigen reactive T cells rapidly lose CD62L expression and this was associated with the acquisition of CD107a. By CD62L ELISA, we confirmed that this transition was mediated by the shedding of CD62L when T cells encountered specific tumor antigen. The introduction of a shedding resistant mutant of CD62L into the tumor antigen-reactive T cell line JKF6 impaired CD107a acquisition following antigen recognition and this was correlated with decreased lytic activity as measured by (51)Cr release assays. The linkage of the shedding of CD62L from the surface of anti-tumor T cells and acquisition of lytic activity, suggests a new function for CD62L in T cell effector functions and anti-tumor activity.
C1 [Yang, Shicheng; Liu, Fang; Wang, Qiong J.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Yang, SC (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute; National
Institutes of Health, Bethesda, Maryland, United States of America
FX This work was supported by Intramural Research Program of the Center for
Cancer Research, National Cancer Institute, and the National Institutes
of Health, Bethesda, Maryland, United States of America. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 49
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Z9 33
U1 0
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 JUL 28
PY 2011
VL 6
IS 7
AR e22560
DI 10.1371/journal.pone.0022560
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 799KC
UT WOS:000293284600018
PM 21829468
ER
PT J
AU Li, FY
Chaigne-Delalande, B
Kanellopoulou, C
Davis, JC
Matthews, HF
Douek, DC
Cohen, JI
Uzel, G
Su, HC
Lenardo, MJ
AF Li, Feng-Yen
Chaigne-Delalande, Benjamin
Kanellopoulou, Chrysi
Davis, Jeremiah C.
Matthews, Helen F.
Douek, Daniel C.
Cohen, Jeffrey I.
Uzel, Gulbu
Su, Helen C.
Lenardo, Michael J.
TI Second messenger role for Mg2+ revealed by human T-cell immunodeficiency
SO NATURE
LA English
DT Article
ID X-CHROMOSOME INACTIVATION; HIV-INFECTION; ACQUIRED-IMMUNODEFICIENCY;
LYMPHOCYTE-PROLIFERATION; MAGNESIUM HOMEOSTASIS; EMBRYONIC-DEVELOPMENT;
SIGNAL-TRANSDUCTION; PERIPHERAL-BLOOD; ACTIVATION; CALCIUM
AB The magnesium ion, Mg2+, is essential for all life as a cofactor for ATP, polyphosphates such as DNA and RNA, and metabolic enzymes, but whether it plays a part in intracellular signalling (as Ca2+ does) is unknown. Here we identify mutations in the magnesium transporter gene, MAGT1, in a novel X-linked human immunodeficiency characterized by CD4 lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation. We demonstrate that a rapid transient Mg2+ influx is induced by antigen receptor stimulation in normal T cells and by growth factor stimulation in non-lymphoid cells. MAGT1 deficiency abrogates the Mg2+ influx, leading to impaired responses to antigen receptor engagement, including defective activation of phospholipase C gamma 1 and a markedly impaired Ca2+ influx in T cells but not B cells. These observations reveal a role for Mg2+ as an intracellular second messenger coupling cell-surface receptor activation to intracellular effectors and identify MAGT1 as a possible target for novel therapeutics.
C1 [Li, Feng-Yen; Chaigne-Delalande, Benjamin; Kanellopoulou, Chrysi; Matthews, Helen F.; Lenardo, Michael J.] NIAID, Mol Dev Sect, Lymphocyte Mol Genet Unit, Immunol Lab,NIH, Bethesda, MD 20892 USA.
[Li, Feng-Yen] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA.
[Davis, Jeremiah C.; Su, Helen C.] NIAID, Human Immunol Dis Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Li, FY (reprint author), NIAID, Mol Dev Sect, Lymphocyte Mol Genet Unit, Immunol Lab,NIH, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases of the US National Institutes of Health
FX We thank L. Zheng, A. Weiss, R. Germain, R. Siegel, F. Wolf and P.
Schwartzberg for critically reading the manuscript; F. Wolf for advice
on magnesium assessments; L. Zheng, C. Lowell and A. Weiss for advice on
experiments and data; H. Jing for making HVS lines from patient cells;
P. Chen for assistance with plasmid DNA preparation; N. Sandler for flow
cytometry assistance; A. Snow and H. Jing for assistance with genomic
DNA library preparation for Solexa sequencing; J. Almenara and Illumina
staff for Solexa assistance; D. Killilea for assistance with MS-ICP data
interpretation; and A. Irani for referring the patients. F.-Y.L. is in
the Medical Scientist Training Program at the University of
California-San Francisco and thanks K. Shannon and J. Toutolmin for
support and encouragement. This work was supported by the Division of
Intramural Research of the National Institute of Allergy and Infectious
Diseases of the US National Institutes of Health.
NR 51
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U1 4
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 28
PY 2011
VL 475
IS 7357
BP 471
EP U63
DI 10.1038/nature10246
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797ZA
UT WOS:000293167900034
PM 21796205
ER
PT J
AU Peterson, KE
Cinelli, MA
Morrell, AE
Mehta, A
Dexheimer, TS
Agama, K
Antony, S
Pommier, Y
Cushman, M
AF Peterson, Katherine E.
Cinelli, Maris A.
Morrell, Andrew E.
Mehta, Akhil
Dexheimer, Thomas S.
Agama, Keli
Antony, Smitha
Pommier, Yves
Cushman, Mark
TI Alcohol-, Diol-, and Carbohydrate-Substituted Indenoisoquinolines as
Topoisomerase I Inhibitors: Investigating the Relationships Involving
Stereochemistry, Hydrogen Bonding, and Biological Activity
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PLANT ANTITUMOR AGENTS; DNA CLEAVAGE; REBECCAMYCIN ANALOGS; NITRATED
INDENOISOQUINOLINES; MJ-III-65 NSC-706744; ANTICANCER AGENTS;
CAMPTOTHECIN; BINDING; INDOLOCARBAZOLE; DERIVATIVES
AB The DNA-relaxing enzyme topoisomerase I (Top 1) can be inhibited by heterocyclic compounds such as indolocarbazoles and indenoisoquinolines. Carbohydrate and hydroxyl-containing side chains are essential for the biological activity of indolocarbazoles. The current study investigated how similar functionalities could be "translated" to the indenoisoquinoline system and how stereochemistry and hydrogen bonding affect biological activity. Herein is described the preparation and assay of indenoisoquinolines substituted with short-chain alcohols, diols, and carbohydrates. Several compounds (including those derived from sugars) display potent Top1 poisoning and antiproliferative activities. The Top1 poisoning activity of diol-substituted indenoisoquinolines is dependent upon stereochemistry. Although the effect is striking, molecular modeling and docking studies do not indicate any reason for the difference in activity due to similar calculated interactions between the ligand and Top1-DNA complex and ambiguity about the binding mode. A stereo chemical dependence was also observed for carbohydrate-derived indenoisoquinolines. Although similar trends were observed in other classes of Top1 inhibitors, the exact nature of this effect has yet to be elucidated.
C1 [Peterson, Katherine E.; Cinelli, Maris A.; Morrell, Andrew E.; Mehta, Akhil; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA.
[Peterson, Katherine E.; Cinelli, Maris A.; Morrell, Andrew E.; Mehta, Akhil; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA.
[Dexheimer, Thomas S.; Agama, Keli; Antony, Smitha; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, Coll Pharm, W Lafayette, IN 47907 USA.
EM cushman@pharmacy.purdue.edu
FU National Institutes of Health (NIH) [UO1 CA89566]; Purdue University;
Purdue Research Foundation [203202]; DCTD, National Cancer Institute
[NO1-CO-56000]; NIH, National Cancer Institute, Center for Cancer
Research
FX This work was made possible by the National Institutes of Health (NIH)
through support with Research Grant UO1 CA89566, by the Frederick N.
Andrews Fellowship sponsored by Purdue University (K.E.P.), and by a
Purdue Research Foundation Grant (no. 203202, MAC.). In vitro
cytotoxicity testing was conducted through the Developmental
Therapeutics Program, DCTD, National Cancer Institute, under contract
NO1-CO-56000. This research was also supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. MAC. thanks Dr. Karl Wood, Evgeny Kiselev, and Dr.
Xiangshu Xiao (Oregon Health and Science University) for valuable
discussions.
NR 68
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Z9 24
U1 1
U2 13
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 JUL 28
PY 2011
VL 54
IS 14
BP 4937
EP 4953
DI 10.1021/jm101338z
PG 17
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 794JO
UT WOS:000292892300001
PM 21710981
ER
PT J
AU Goldsborough, AS
Handley, MD
Dulcey, AE
Pluchino, KM
Kannan, P
Brimacombe, KR
Hall, MD
Griffiths, G
Gottesman, MM
AF Goldsborough, Andrew S.
Handley, Misty D.
Dulcey, Andres E.
Pluchino, Kristen M.
Kannan, Pavitra
Brimacombe, Kyle R.
Hall, Matthew D.
Griffiths, Gary
Gottesman, Michael M.
TI Collateral Sensitivity of Multidrug-Resistant Cells to the Orphan Drug
Tiopronin
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID P-GLYCOPROTEIN; LINES; CANCER; TOXICITY; NEOCARZINOSTATIN; TRANSPORTERS;
EXPRESSION; COLCHICINE; INHIBITORS; TUBULIN
AB A major challenge in the treatment of cancer is multidrug resistance (MDR) that develops during chemotherapy. Here we demonstrate that tiopronin (1), a thiol-substituted N-propanoylglycine derivative, was selectively toxic to a series of cell lines expressing the drug efflux pump P-glycoprotein (P-gp, ABCB1) and MRP1 (ABCC1). Treatment of MDR cells with 1 led to instability of the ABCB1 mRNA and consequently a reduction in P-gp protein, despite functional assays demonstrating that tiopronin does not interact with P-gp. Long-term exposure of P-gp-expressing cells to 1 sensitized them to doxorubicin and paclitaxel, both P-gp substrates. Treatment of MRP1-overexpressing cells with tiopronin led to a significant reduction in MRP1 protein. Synthesis and screening of analogues of tiopronin demonstrated that the thiol functional group was essential for collateral sensitivity while substitution of the amino acid backbone altered but did not destroy specificity, pointing to future development of targeted analogues.
C1 [Goldsborough, Andrew S.; Handley, Misty D.; Pluchino, Kristen M.; Brimacombe, Kyle R.; Hall, Matthew D.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Dulcey, Andres E.; Griffiths, Gary] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD USA.
[Kannan, Pavitra] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM gottesmm@mail.nih.gov
OI Kannan, Pavitra/0000-0002-9170-6062
FU National Institutes of Health; National Cancer Institute; National
Heart, Lung, and Blood Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, and National
Heart, Lung, and Blood Institute. We thank George Leiman for editorial
assistance. We thank King-Leung Fung for the gift of LLC-PK1 cells.
NR 38
TC 18
Z9 20
U1 2
U2 10
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 JUL 28
PY 2011
VL 54
IS 14
BP 4987
EP 4997
DI 10.1021/jm2001663
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 794JO
UT WOS:000292892300005
PM 21657271
ER
PT J
AU Romagnoli, R
Baraldi, PG
Brancale, A
Ricci, A
Hamel, E
Bortolozzi, R
Basso, G
Viola, G
AF Romagnoli, Romeo
Baraldi, Pier Giovanni
Brancale, Andrea
Ricci, Antonio
Hamel, Ernest
Bortolozzi, Roberta
Basso, Giuseppe
Viola, Giampietro
TI Convergent Synthesis and Biological Evaluation of 2-Amino-4-(3 ',4 ',5
'-trimethoxyphenyl)-5-aryl Thiazoles as Microtubule Targeting Agents
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID COMBRETASTATIN A-4 ANALOGS; LUNG-CANCER CELLS; MITOTIC CATASTROPHE;
MEDICINAL CHEMISTRY; ANTITUMOR-ACTIVITY; TUBULIN; APOPTOSIS; COLCHICINE;
PHOSPHATE; POTENT
AB Combretastatin A-4, a potent tubulin polymerization inhibitor, caused us to synthesize a novel series of 2-amino-4-(3',4',5'-trimethoxyphenyl)-5-aryl thiazoles with the goal of evaluating the effects of substituents on the phenyl at the 5-position of the thiazole skeleton on biological activities. An ethoxy group at the para-position produced the most active compound in the series, with IC(50) values of 0.03-0.9 nM against five of seven cancer cell lines. The most active compounds retained full activity in multidrug resistant cancer cells and acted through the colchicine site of tubulin. Treated cells were arrested in the G2/M phase of the cell cycle, with cell death proceeding through an apoptotic pathway that was only partially caspase-dependent. Preliminary results suggest that, in addition to cell death by apoptosis, cells were also killed via mitotic catastrophe as an alternative cell death mechanism.
C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
[Brancale, Andrea; Ricci, Antonio] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3NB, S Glam, Wales.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro] Univ Padua, Dipartimento Pediat, Lab Oncoematol, I-35131 Padua, Italy.
RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
EM rmr@unife.it; giampietro.viola1@unipd.it
RI Viola, Giampietro/I-4095-2012; Brancale, Andrea/N-9445-2014; Bortolozzi,
Roberta/D-4950-2015; Romagnoli, Romeo/G-9887-2015; Baraldi, Pier
Giovanni/B-7933-2017;
OI Viola, Giampietro/0000-0001-9329-165X; Brancale,
Andrea/0000-0002-9728-3419; Bortolozzi, Roberta/0000-0002-3357-4815;
BASSO, GIUSEPPE/0000-0002-2634-9302
FU Intramural NIH HHS [Z99 CA999999]
NR 59
TC 45
Z9 47
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 JUL 28
PY 2011
VL 54
IS 14
BP 5144
EP 5153
DI 10.1021/jm200392p
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 794JO
UT WOS:000292892300017
PM 21663319
ER
PT J
AU Mueller, S
Yang, XD
Sottero, TL
Gragg, A
Prasad, G
Polley, MY
Weiss, WA
Matthay, KK
Davidoff, AM
DuBois, SG
Haas-Kogan, DA
AF Mueller, Sabine
Yang, Xiaodong
Sottero, Theo L.
Gragg, Ashley
Prasad, Gautam
Polley, Mei-Yin
Weiss, William A.
Matthay, Katherine K.
Davidoff, Andrew M.
DuBois, Steven G.
Haas-Kogan, Daphne A.
TI Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic
neuroblastoma: Efficacy and underlying mechanisms
SO CANCER LETTERS
LA English
DT Article
DE Metastatic neuroblastoma; Radiation; Vorinostat; DNA repair
ID HISTONE DEACETYLASE INHIBITOR; IN-VITRO; CELLS; EXPRESSION;
RADIOSENSITIVITY; ACETYLATION; COMBINATION; PROGRESSION; GLIOMAS
AB Histone deacetylase (HDAC) inhibitors can radiosensitize cancer cells. Radiation is critical in high-risk neuroblastoma treatment, and combinations of HDAC inhibitor vorinostat and radiation are proposed for neuroblastoma trials. Therefore, we investigated radiosensitizing effects of vorinostat in neuroblastoma. Treatment of neuroblastoma cell lines decreased cell viability and resulted in additive effects with radiation. In a murine metastatic neuroblastoma in vivo model vorinostat and radiation combinations decreased tumor volumes compared to single modality. DNA repair enzyme Ku-86 was reduced in several neuroblastoma cells treated with vorinostat. Thus, vorinostat potentiates anti-neoplastic effects of radiation in neuroblastoma possibly due to down-regulation of DNA repair enzyme Ku-86. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Mueller, Sabine; Weiss, William A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Yang, Xiaodong; Sottero, Theo L.; Gragg, Ashley; Prasad, Gautam; Haas-Kogan, Daphne A.] Univ Calif San Francisco, Dept Radiat Oncol, Helen Diller Family Canc Res Ctr, San Francisco, CA 94158 USA.
[Polley, Mei-Yin] NCI, Biometr Res Branch, Rockville, MD 20852 USA.
[Mueller, Sabine; Weiss, William A.; Haas-Kogan, Daphne A.] Univ San Francisco, Dept Neurosurg, San Francisco, CA 94117 USA.
[Davidoff, Andrew M.] St Jude Childrens Hosp, Dept Surg, Memphis, TN 38105 USA.
RP Mueller, S (reprint author), Univ Calif San Francisco, Dept Neurol, 505 Parnassus Ave,M688,Box 0106, San Francisco, CA 94143 USA.
EM muellers@neuropeds.ucsf.edu
OI Weiss, William/0000-0003-2230-9132
FU NIH [PO1 NS-42927-27A2, PO1 CA81403]; NIH Brain Tumor SPORE [P50
CA097257]; NIH/NCRR/OD UCSF-CTSI [KL2 RR024130, NIH-R01CA133091]; Nancy
and Stephen Grand Philanthropic Fund; V Foundation; Dougherty
Foundation; Thrasher Foundation; Alex's Lemonade Stand Foundation;
Campini Foundation
FX This research was supported in part by NIH-PO1 NS-42927-27A2 (DHK), PO1
CA81403 (KKM), NIH Brain Tumor SPORE Grant P50 CA097257 (DHK, MYP, WAW),
NIH/NCRR/OD UCSF-CTSI Grant No. KL2 RR024130 (SGD), NIH-R01CA133091
(WAW), The Nancy and Stephen Grand Philanthropic Fund (DAH-K), The V
Foundation (DHK, KKM, WAW), Dougherty Foundation (KKM), Thrasher
Foundation (WAW, KKM, DHK), Alex's Lemonade Stand Foundation (KKM),
Campini Foundation (SM, KKM, SGD).
NR 21
TC 27
Z9 30
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 JUL 28
PY 2011
VL 306
IS 2
BP 223
EP 229
DI 10.1016/j.canlet.2011.03.010
PG 7
WC Oncology
SC Oncology
GA 771VE
UT WOS:000291188000012
PM 21497989
ER
PT J
AU Keppler-Noreuil, KM
Blumhorst, C
Sapp, JC
Brinckman, D
Johnston, J
Nopoulos, PC
Biesecker, LG
AF Keppler-Noreuil, Kim M.
Blumhorst, Catherine
Sapp, Julie C.
Brinckman, Danielle
Johnston, Jennifer
Nopoulos, Peggy C.
Biesecker, Leslie G.
TI Brain tissue- and region-specific abnormalities on volumetric MRI scans
in 21 patients with Bardet-Biedl syndrome (BBS)
SO BMC MEDICAL GENETICS
LA English
DT Article
ID HUMAN OBESITY SYNDROME; SYNDROME GENE; NULL MICE; CHILDREN;
IDENTIFICATION; MUTATIONS; PHENOTYPE; PROTEINS; MOUSE; ADOLESCENTS
AB Background: Bardet-Biedl syndrome (BBS) is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems.
Methods: A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures.
Results: All 21 patients with BBS were found to have statistically significant region-and tissue-specific patterns of brain abnormalities. There was 1) normal intracranial volume; 2) reduced white matter in all regions of the brain, but most in the occipital region; 3) preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4) reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5) increased cerebrospinal fluid volume.
Conclusions: There are distinct and characteristic abnormalities in tissue-and region-specific volumes of the brain in patients with BBS, which parallel the findings, described in BBS mutant mouse models. Some of these brain abnormalities may be progressive and associated with the reported neurological and behavioral problems. Further future correlation of these MRI scan findings with detailed neurologic and neuropsychological exams together with genotype data will provide better understanding of the pathophysiology of BBS.
C1 [Keppler-Noreuil, Kim M.] Univ Iowa, Dept Pediat, Div Med Genet, Childrens Hosp, Iowa City, IA 52242 USA.
[Blumhorst, Catherine; Sapp, Julie C.; Brinckman, Danielle; Johnston, Jennifer; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Nopoulos, Peggy C.] Univ Iowa, Childrens Hosp, Dept Psychiat, Iowa City, IA 52242 USA.
RP Keppler-Noreuil, KM (reprint author), Univ Iowa, Dept Pediat, Div Med Genet, Childrens Hosp, Iowa City, IA 52242 USA.
EM kim-keppler@uiowa.edu
FU National Human Genome Research Institute, NIH
FX The authors thank the patients and their families, who so generously
gave of their time and without whom this study would not be possible.
The authors also would like to thank Dr. Nick Petronas for his
contribution in the initial planning of selection and acquisition of the
MRI scanners at the NIH. The opinions expressed here are those of the
authors and do not necessarily reflect the opinions of the institutions
to which they are affiliated. This study was supported by funds from the
Intramural Research Programs of the National Human Genome Research
Institute, NIH.
NR 58
TC 12
Z9 12
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JUL 27
PY 2011
VL 12
AR 101
DI 10.1186/1471-2350-12-101
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 814EJ
UT WOS:000294429300001
PM 21794117
ER
PT J
AU Hunsberger, JG
Machado-Vieira, R
Austin, DR
Zarate, C
Chuang, DM
Chen, G
Reed, JC
Manji, HK
AF Hunsberger, Joshua G.
Machado-Vieira, Rodrigo
Austin, Daniel R.
Zarate, Carlos
Chuang, De-Maw
Chen, Guang
Reed, John C.
Manji, Husseini K.
TI Bax inhibitor 1, a modulator of calcium homeostasis, confers affective
resilience
SO BRAIN RESEARCH
LA English
DT Article
DE Bax inhibitor 1; Affective resiliency; Endoplasmic reticulum; Calcium
homeostasis; ER stress
ID ENDOPLASMIC-RETICULUM STRESS; SUBGENUAL PREFRONTAL CORTEX; BIPOLAR
AFFECTIVE-DISORDER; SINGLE T-LYMPHOCYTES; INTRACELLULAR CALCIUM;
ANTIDEPRESSANT ACTION; DEPRESSED-PATIENTS; CATECHOLAMINE DEPLETION;
MAJOR DEPRESSION; CA2+ INFLUX
AB The endoplasmic reticulum (ER) is a critical site for intracellular calcium storage as well as protein synthesis, folding, and trafficking. Disruption of these processes is gaining support for contributing to heritable vulnerability of certain diseases. Here, we investigated Bax inhibitor 1 (BI-1), an anti-apoptotic protein that primarily resides in the ER and associates with B-cell lymphoma 2 (Bcl-2) and Bcl-XL, as an affective resiliency factor through its modulation of calcium homeostasis. We found that trans genic (TG) mice with BI-1 reinforced expression, via the neuronal specific enolase promoter, showed protection against the learned helplessness (LH) paradigm, an animal model to test stress coping. TG mice were also protected against anhedonia following both serotonin and catecholamine depletion as measured in two different models, the female urine sniffing test and the saccharine preference test. In addition, we used primary mouse cortical cultures to explore the ability of BI-1 to influence calcium homeostasis under basal conditions and also following challenge with thapsigargin (THPS), an inhibitor of sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) that disrupts calcium homeostasis. TG neurons showed decreased basal cytosolic calcium levels and decreased Ca(2+) cytosolic accumulation following challenge with THPS as compared to WT neuronal cultures. Together, these data suggest that BI-1, through its actions on calcium homeostasis, may confer affective resiliency in multiple animal models of depression and anhedonia. Published by Elsevier B.V.
C1 [Hunsberger, Joshua G.; Machado-Vieira, Rodrigo; Austin, Daniel R.; Zarate, Carlos; Chuang, De-Maw; Chen, Guang; Manji, Husseini K.] NIMH, NIH, Bethesda, MD 20892 USA.
[Reed, John C.] Sanford Burnham Med Res Inst, La Jolla, CA USA.
RP Hunsberger, JG (reprint author), NIMH, NIH, MSC 1363,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hunsbergerj@mail.nih.gov; machadovieirar@gmail.com;
adaniel@mail.nih.gov; zaratec@mail.nih.gov; chuang@mail.nih.gov;
guangchen@mail.nih.gov; jreed@sanfordburnham.org; hmanji@its.jnj.com
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Chen, Guang/A-2570-2017
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190;
FU NIMH; NIH [AG-015393]
FX This work was funded by the NIMH Intramural Program and by NIH grant
AG-015393. We thank Danielle Warrinllal and Wenji Xu for technical
assistance with mouse breeding and genotyping. We would like to thank
Emily Fessler and Peter Leeds for editorial suggestions. We would like
to thank S Brian Andrews for use of his facility to perform the calcium
experiments.
NR 61
TC 15
Z9 15
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JUL 27
PY 2011
VL 1403
BP 19
EP 27
DI 10.1016/j.brainres.2011.05.067
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 797UY
UT WOS:000293156800003
PM 21718971
ER
PT J
AU Chaudhry, C
Scimemi, A
Kumar, J
AF Chaudhry, Charu
Scimemi, Annalisa
Kumar, Janesh
TI Building and Breaking Interfaces: How a Receptor Takes Shape
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
C1 [Chaudhry, Charu] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Scimemi, Annalisa] NINDS, Synapt Physiol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Chaudhry, C (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, 35 Convent Dr,3B1006, Bethesda, MD 20892 USA.
RI Scimemi, Annalisa/O-5396-2014
OI Scimemi, Annalisa/0000-0003-4975-093X
FU Intramural NIH HHS [Z99 HD999999]
NR 9
TC 0
Z9 0
U1 0
U2 0
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 JUL 27
PY 2011
VL 31
IS 30
BP 10749
EP 10751
DI 10.1523/JNEUROSCI.2312-11.2011
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 798AG
UT WOS:000293171900001
PM 21795526
ER
PT J
AU Tricoire, L
Pelkey, KA
Erkkila, BE
Jeffries, BW
Yuan, XQ
McBain, CJ
AF Tricoire, Ludovic
Pelkey, Kenneth A.
Erkkila, Brian E.
Jeffries, Brian W.
Yuan, Xiaoqing
McBain, Chris J.
TI A Blueprint for the Spatiotemporal Origins of Mouse Hippocampal
Interneuron Diversity
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CAUDAL GANGLIONIC EMINENCE; NITRIC-OXIDE SYNTHASE; FATE MAPPING REVEALS;
AXO-AXONIC CELLS; RAT HIPPOCAMPUS; CORTICAL INTERNEURONS; GABAERGIC
INTERNEURONS; CA1 AREA; PYRAMIDAL CELLS; ADULT-RAT
AB Although vastly outnumbered, inhibitory interneurons critically pace and synchronize excitatory principal cell populations to coordinate cortical information processing. Precision in this control relies upon a remarkable diversity of interneurons primarily determined during embryogenesis by genetic restriction of neuronal potential at the progenitor stage. Like their neocortical counterparts, hippocampal interneurons arise from medial and caudal ganglionic eminence (MGE and CGE) precursors. However, while studies of the early specification of neocortical interneurons are rapidly advancing, similar lineage analyses of hippocampal interneurons have lagged. A "hippocampocentric" investigation is necessary as several hippocampal interneuron subtypes remain poorly represented in the neocortical literature. Thus, we investigated the spatiotemporal origins of hippocampal interneurons using transgenic mice that specifically report MGE- and CGE-derived interneurons either constitutively or inducibly. We found that hippocampal interneurons are produced in two neurogenic waves between E9-E12 and E12-E16 from MGE and CGE, respectively, and invade the hippocampus by E14. In the mature hippocampus, CGE-derived interneurons primarily localize to superficial layers in strata lacunosum moleculare and deep radiatum, while MGE-derived interneurons readily populate all layers with preference for strata pyramidale and oriens. Combined molecular, anatomical, and electrophysiological interrogation of MGE/CGE-derived interneurons revealed that MGE produces parvalbumin-, somatostatin-, and nitric oxide synthase-expressing interneurons including fast-spiking basket, bistratified, axo-axonic, orienslacunosum moleculare, neurogliaform, and ivy cells. In contrast, CGE-derived interneurons contain cholecystokinin, calretinin, vasoactive intestinal peptide, and reelin including non-fast-spiking basket, Schaffer collateral-associated, mossy fiber-associated, trilaminar, and additional neurogliaform cells. Our findings provide a basic blueprint of the developmental origins of hippocampal interneuron diversity.
C1 [Tricoire, Ludovic; Pelkey, Kenneth A.; Erkkila, Brian E.; Jeffries, Brian W.; Yuan, Xiaoqing; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Pelkey, KA (reprint author), Porter Neurosci Res Ctr, 35 Lincoln Dr,MSC 3715, Bethesda, MD 20892 USA.
EM pelkeyk2@mail.nih.gov
FU National Institute of Child Health and Human Development (NICHD)
FX This work was supported by a National Institute of Child Health and
Human Development (NICHD) intramural award (C.J.M.). L.T. is a NIH
Visiting Fellow and a NIH/CNRS European Career Transition Award Fellow.
Daniel Abebe provided expert technical assistance. Microscopy imaging
was performed at the Microscopy and Imaging Core (NICHD-NIH) with the
assistance of Dr. Vincent Schram and at the imaging facility of the
IFR83 (Paris, France) with the assistance of Susanne Bolt and Richard
Schwartzmann. We thank Dr. Gordin V. Ohning for supplying us with the
CCK antibody, Dr. Gabor Szabo for providing the GAD65-GFP mouse line,
Dr. Stuart Anderson for providing the Nkx2-1Cre driver line, and Dr.
Gord Fishell for providing the Olig2CreER and Mash1CreER driver lines as
well as the RCE reporter line.
NR 130
TC 101
Z9 103
U1 0
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 27
PY 2011
VL 31
IS 30
BP 10948
EP 10970
DI 10.1523/JNEUROSCI.0323-11.2011
PG 23
WC Neurosciences
SC Neurosciences & Neurology
GA 798AG
UT WOS:000293171900020
PM 21795545
ER
PT J
AU Hyde, TM
Lipska, BK
Ali, T
Mathew, SV
Law, AJ
Metitiri, OE
Straub, RE
Ye, TZ
Colantuoni, C
Herman, MM
Bigelow, LB
Weinberger, DR
Kleinman, JE
AF Hyde, Thomas M.
Lipska, Barbara K.
Ali, Towhid
Mathew, Shiny V.
Law, Amanda J.
Metitiri, Ochuko E.
Straub, Richard E.
Ye, Tianzhang
Colantuoni, Carlo
Herman, Mary M.
Bigelow, Llewellyn B.
Weinberger, Daniel R.
Kleinman, Joel E.
TI Expression of GABA Signaling Molecules KCC2, NKCC1, and GAD1 in Cortical
Development and Schizophrenia
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GLUTAMIC-ACID DECARBOXYLASE; K-CL COTRANSPORTER; POSTMORTEM HUMAN BRAIN;
GENE-EXPRESSION; RAT-BRAIN; CHLORIDE TRANSPORTERS; NERVOUS-SYSTEM;
MESSENGER-RNAS; NEURONS; HIPPOCAMPUS
AB GABA signaling molecules are critical for both human brain development and the pathophysiology of schizophrenia. We examined the expression of transcripts derived from three genes related to GABA signaling [GAD1 (GAD67 and GAD25), SLC12A2 (NKCC1), and SLC12A5 (KCC2)] in the prefrontal cortex (PFC) and hippocampal formation of a large cohort of nonpsychiatric control human brains (n = 240) across the lifespan (from fetal week 14 to 80 years) and in patients with schizophrenia (n = 30-31), using quantitative RT-PCR. We also examined whether a schizophrenia risk-associated promoter SNP in GAD1 (rs3749034) is related to expression of these transcripts. Our studies revealed that development and maturation of both the PFC and hippocampal formation are characterized by progressive switches in expression from GAD25 to GAD67 and from NKCC1 to KCC2. Previous studies have demonstrated that the former leads to GABA synthesis, and the latter leads to switching from excitatory to inhibitory neurotransmission. In the hippocampal formation, GAD25/GAD67 and NKCC1/KCC2 ratios are increased in patients with schizophrenia, reflecting a potentially immature GABA physiology. Remarkably, GAD25/GAD67 and NKCC1/KCC2 expression ratios are associated with rs3749034 genotype, with risk alleles again predicting a relatively less mature pattern. These findings suggest that abnormalities in GABA signaling critical to brain development contribute to genetic risk for schizophrenia.
C1 [Hyde, Thomas M.; Lipska, Barbara K.; Ali, Towhid; Mathew, Shiny V.; Law, Amanda J.; Metitiri, Ochuko E.; Straub, Richard E.; Ye, Tianzhang; Colantuoni, Carlo; Herman, Mary M.; Bigelow, Llewellyn B.; Weinberger, Daniel R.; Kleinman, Joel E.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,IRP,NIH, Bethesda, MD 20892 USA.
[Hyde, Thomas M.; Colantuoni, Carlo] Johns Hopkins Univ Med Campus, Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Colantuoni, Carlo] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
RP Hyde, TM (reprint author), NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,IRP,NIH, Room 4N306,Bldg 10, Bethesda, MD 20892 USA.
EM hydet@mail.nih.gov
RI Law, Amanda/G-6372-2012; Lipska, Barbara/E-4569-2017;
OI Law, Amanda/0000-0002-2574-1564
FU Intramural NIH HHS [Z01 MH002399-18, ZIA MH002399-23]
NR 53
TC 103
Z9 106
U1 2
U2 13
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 JUL 27
PY 2011
VL 31
IS 30
BP 11088
EP 11095
DI 10.1523/JNEUROSCI.1234-11.2011
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 798AG
UT WOS:000293171900032
PM 21795557
ER
PT J
AU Cea, M
Soncini, D
Fruscione, F
Raffaghello, L
Garuti, A
Emionite, L
Moran, E
Magnone, M
Zoppoli, G
Reverberi, D
Caffa, I
Salis, A
Cagnetta, A
Bergamaschi, M
Casciaro, S
Pierri, I
Damonte, G
Ansaldi, F
Gobbi, M
Pistoia, V
Ballestrero, A
Patrone, F
Bruzzone, S
Nencioni, A
AF Cea, Michele
Soncini, Debora
Fruscione, Floriana
Raffaghello, Lizzia
Garuti, Anna
Emionite, Laura
Moran, Eva
Magnone, Mirko
Zoppoli, Gabriele
Reverberi, Daniele
Caffa, Irene
Salis, Annalisa
Cagnetta, Antonia
Bergamaschi, Micaela
Casciaro, Salvatore
Pierri, Ivana
Damonte, Gianluca
Ansaldi, Filippo
Gobbi, Marco
Pistoia, Vito
Ballestrero, Alberto
Patrone, Franco
Bruzzone, Santina
Nencioni, Alessio
TI Synergistic Interactions between HDAC and Sirtuin Inhibitors in Human
Leukemia Cells
SO PLOS ONE
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; CHRONIC
LYMPHOCYTIC-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; HEMATOLOGIC
MALIGNANCIES; BIOSYNTHESIS INHIBITOR; ANTITUMOR-ACTIVITY;
MELANOMA-CELLS; APOPTOSIS; P53
AB Aberrant histone deacetylase (HDAC) activity is frequent in human leukemias. However, while classical, NAD(+)-independent HDACs are an established therapeutic target, the relevance of NAD(+)-dependent HDACs (sirtuins) in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+)-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527) and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction wasmonitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+) levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+)-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.
C1 [Cea, Michele; Soncini, Debora; Garuti, Anna; Moran, Eva; Zoppoli, Gabriele; Caffa, Irene; Casciaro, Salvatore; Ballestrero, Alberto; Patrone, Franco; Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Cea, Michele; Cagnetta, Antonia] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Boston Novartis Inst BioMed, Cambridge, MA 02138 USA.
[Fruscione, Floriana] ABC, Genoa, Italy.
[Raffaghello, Lizzia; Pistoia, Vito] IRCCS G Gaslini, Lab Oncol, Genoa, Italy.
[Emionite, Laura] Natl Canc Inst, Anim Facil, Genoa, Italy.
[Magnone, Mirko; Salis, Annalisa; Damonte, Gianluca; Bruzzone, Santina] Univ Genoa, Biochem Sect, Dept Expt Med, Genoa, Italy.
[Reverberi, Daniele] Natl Canc Inst, Med Oncol Div C, Genoa, Italy.
[Cagnetta, Antonia; Bergamaschi, Micaela; Pierri, Ivana; Gobbi, Marco] San Martino Hosp, Dept Hematol & Oncol, Genoa, Italy.
[Ansaldi, Filippo] Univ Genoa, Dept Hlth Sci, Genoa, Italy.
RP Cea, M (reprint author), Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
EM A.Nencioni@gmx.net
RI Bruzzone, Santina/A-4264-2015; Zoppoli, Gabriele/B-6935-2016; Caffa,
Irene/J-9835-2016;
OI Bruzzone, Santina/0000-0003-2034-3716; Zoppoli,
Gabriele/0000-0003-3890-5588; Caffa, Irene/0000-0003-1111-9915;
Raffaghello, Lizzia/0000-0003-2357-0607
FU Associazione Italiana per la Ricerca sul Cancro (AIRC); Associazione
Italiana contro le Leucemie-Linfomi e Mieloma; University of Genoa
FX This work was supported by the Associazione Italiana per la Ricerca sul
Cancro (AIRC, AN and LR), the Associazione Italiana contro le
Leucemie-Linfomi e Mieloma, and by the University of Genoa. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 42
TC 30
Z9 32
U1 1
U2 8
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 JUL 27
PY 2011
VL 6
IS 7
AR e22739
DI 10.1371/journal.pone.0022739
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 799JJ
UT WOS:000293282700069
PM 21818379
ER
PT J
AU Johnson, C
Drgon, T
Walther, D
Uhl, GR
AF Johnson, Catherine
Drgon, Tomas
Walther, Donna
Uhl, George R.
TI Genomic Regions Identified by Overlapping Clusters of Nominally-Positive
SNPs from Genome-Wide Studies of Alcohol and Illegal Substance
Dependence
SO PLOS ONE
LA English
DT Article
ID ADDICTION MOLECULAR-GENETICS; SAMPLE-SIZE CALCULATIONS; NICOTINE
DEPENDENCE; POLYSUBSTANCE ABUSERS; MACULAR DEGENERATION; VULNERABILITY
LOCI; SMOKING-CESSATION; ASSOCIATION; GENES; INDIVIDUALS
AB Declaring "replication" from results of genome wide association (GWA) studies is straightforward when major gene effects provide genome-wide significance for association of the same allele of the same SNP in each of multiple independent samples. However, such unambiguous replication is unlikely when phenotypes display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity and when different samples display linkage disequilibria with different fine structures. We seek chromosomal regions that are tagged by clustered SNPs that display nominally-significant association in each of several independent samples. This approach provides one "nontemplate" approach to identifying overall replication of groups of GWA results in the face of difficult genetic architectures. We apply this strategy to 1 M SNP GWA results for dependence on: a) alcohol (including many individuals with dependence on other addictive substances) and b) at least one illegal substance (including many individuals dependent on alcohol). This approach provides high confidence in rejecting the null hypothesis that chance alone accounts for the extent to which clustered, nominally-significant SNPs from samples of the same racial/ethnic background identify the same sets of chromosomal regions. It identifies several genes that are also reported in other independent alcohol-dependence GWA datasets. There is more modest confidence in: a) identification of individual chromosomal regions and genes that are not also identified by data from other independent samples, b) the more modest overlap between results from samples of different racial/ethnic backgrounds and c) the extent to which any gene not identified herein is excluded, since the power of each of these individual samples is modest. Nevertheless, the strong overlap identified among the samples with similar racial/ethnic backgrounds supports contributions to individual differences in vulnerability to addictions that come from newer allelic variants that are common in subsets of current humans.
C1 [Johnson, Catherine; Drgon, Tomas; Walther, Donna; Uhl, George R.] Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
RP Johnson, C (reprint author), Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
EM guhl@intra.nida.nih.gov
FU NCI NIH HHS [P01 CA089392]; NHGRI NIH HHS [U01 HG004422, U01 HG004446];
NIAAA NIH HHS [U10 AA008401]; NIDA NIH HHS [R01 DA013423]
NR 40
TC 22
Z9 22
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 JUL 27
PY 2011
VL 6
IS 7
AR e19210
DI 10.1371/journal.pone.0019210
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 799JJ
UT WOS:000293282700002
PM 21818250
ER
PT J
AU Price, DP
Nagarajan, V
Churbanov, A
Houde, P
Milligan, B
Drake, LL
Gustafson, JE
Hansen, IA
AF Price, David P.
Nagarajan, Vijayaraj
Churbanov, Alexander
Houde, Peter
Milligan, Brook
Drake, Lisa L.
Gustafson, John E.
Hansen, Immo A.
TI The Fat Body Transcriptomes of the Yellow Fever Mosquito Aedes aegypti,
Pre- and Post- Blood Meal
SO PLOS ONE
LA English
DT Article
ID PROTEIN GENE-EXPRESSION; AMINO-ACID-SEQUENCES; DROSOPHILA-MELANOGASTER;
CATHEPSIN-B; SIGNALING CASCADE; IMMUNITY; CDNA; RNA; CARBOXYPEPTIDASE;
ANNOTATION
AB Background: The fat body is the main organ of intermediary metabolism in insects and the principal source of hemolymph proteins. As part of our ongoing efforts to understand mosquito fat body physiology and to identify novel targets for insect control, we have conducted a transcriptome analysis of the fat body of Aedes aegypti before and in response to blood feeding.
Results: We created two fat body non-normalized EST libraries, one from mosquito fat bodies non-blood fed (NBF) and another from mosquitoes 24 hrs post-blood meal (PBM). 454 pyrosequencing of the non-normalized libraries resulted in 204,578 useable reads from the NBF sample and 323,474 useable reads from the PBM sample. Alignment of reads to the existing reference Ae. aegypti transcript libraries for analysis of differential expression between NBF and PBM samples revealed 116,912 and 115,051 matches, respectively. De novo assembly of the reads from the NBF sample resulted in 15,456 contigs, and assembly of the reads from the PBM sample resulted in 15,010 contigs. Collectively, 123 novel transcripts were identified within these contigs. Prominently expressed transcripts in the NBF fat body library were represented by transcripts encoding ribosomal proteins. Thirty-five point four percent of all reads in the PBM library were represented by transcripts that encode yolk proteins. The most highly expressed were transcripts encoding members of the cathepsin b, vitellogenin, vitellogenic carboxypeptidase, and vitelline membrane protein families.
Conclusion: The two fat body transcriptomes were considerably different from each other in terms of transcript expression in terms of abundances of transcripts and genes expressed. They reflect the physiological shift of the pre-feeding fat body from a resting state to vitellogenic gene expression after feeding.
C1 [Price, David P.; Gustafson, John E.; Hansen, Immo A.] New Mexico State Univ, Program Mol Biol, Las Cruces, NM 88003 USA.
[Churbanov, Alexander; Houde, Peter; Milligan, Brook; Drake, Lisa L.; Gustafson, John E.; Hansen, Immo A.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA.
[Hansen, Immo A.] New Mexico State Univ, Inst Appl Biosci, Las Cruces, NM 88003 USA.
[Churbanov, Alexander; Houde, Peter; Milligan, Brook] New Mexico State Univ, Roadrunner Sequencing Lab, Las Cruces, NM 88003 USA.
[Nagarajan, Vijayaraj] NIAID, BCBB, OCICB, OSMO,OD,NIH, Bethesda, MD 20892 USA.
RP Price, DP (reprint author), New Mexico State Univ, Program Mol Biol, Las Cruces, NM 88003 USA.
EM immoh@nmsu.edu
FU NIH/NIGMS [1SC2GM092300-01]; NSF [DBI-0821806]
FX NIH/NIGMS 1SC2GM092300-01 (IAH). NSF DBI-0821806 (PH). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 81
TC 30
Z9 30
U1 0
U2 12
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 JUL 27
PY 2011
VL 6
IS 7
AR e22573
DI 10.1371/journal.pone.0022573
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 799JJ
UT WOS:000293282700042
PM 21818341
ER
PT J
AU Sanford, T
Chung, PH
Reinish, A
Valera, V
Srinivasan, R
Linehan, WM
Bratslavsky, G
AF Sanford, Thomas
Chung, Paul H.
Reinish, Ariel
Valera, Vladimir
Srinivasan, Ramaprasad
Linehan, W. Marston
Bratslavsky, Gennady
TI Molecular Sub-Classification of Renal Epithelial Tumors Using
Meta-Analysis of Gene Expression Microarrays
SO PLOS ONE
LA English
DT Article
ID DNA COPY NUMBER; CELL CARCINOMA; MET PROTOONCOGENE; MUTATIONS; CANCER;
NEOPLASMS; KIDNEY; ONCOCYTOMA; SIGNATURES; MARKER
AB Purpose: To evaluate the accuracy of the sub-classification of renal cortical neoplasms using molecular signatures.
Experimental Design: A search of publicly available databases was performed to identify microarray datasets with multiple histologic sub-types of renal cortical neoplasms. Meta-analytic techniques were utilized to identify differentially expressed genes for each histologic subtype. The lists of genes obtained from the meta-analysis were used to create predictive signatures through the use of a pair-based method. These signatures were organized into an algorithm to sub-classify renal neoplasms. The use of these signatures according to our algorithm was validated on several independent datasets.
Results: We identified three Gene Expression Omnibus datasets that fit our criteria to develop a training set. All of the datasets in our study utilized the Affymetrix platform. The final training dataset included 149 samples represented by the four most common histologic subtypes of renal cortical neoplasms: 69 clear cell, 41 papillary, 16 chromophobe, and 23 oncocytomas. When validation of our signatures was performed on external datasets, we were able to correctly classify 68 of the 72 samples (94%). The correct classification by subtype was 19/20 (95%) for clear cell, 14/14 (100%) for papillary, 17/19 (89%) for chromophobe, 18/19 (95%) for oncocytomas.
Conclusions: Through the use of meta-analytic techniques, we were able to create an algorithm that sub-classified renal neoplasms on a molecular level with 94% accuracy across multiple independent datasets. This algorithm may aid in selecting molecular therapies and may improve the accuracy of subtyping of renal cortical tumors.
C1 [Sanford, Thomas; Chung, Paul H.; Reinish, Ariel; Valera, Vladimir; Srinivasan, Ramaprasad; Linehan, W. Marston; Bratslavsky, Gennady] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Bratslavsky, Gennady] SUNY Syracuse, Upstate Med Univ, Dept Urol, Syracuse, NY USA.
RP Sanford, T (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; United States Federal government [1. Z01 BC011028-01,
2. Z01 BC011038-01, 3. Z01 BC011043-01, 10. Z01 BC 011023]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The study was supported by grants from the United
States Federal government: 1. Z01 BC011028-01 Molecular Genetics RCC; 2.
Z01 BC011038-01 Mol Ther: VHL and FH; and 3. Z01 BC011043-01 Mol Ther:
MET and BHD 10. Z01 BC 011023 Fellowship Training. The U.S. Federal
government had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 40
TC 6
Z9 6
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 27
PY 2011
VL 6
IS 7
AR e21260
DI 10.1371/journal.pone.0021260
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 799JJ
UT WOS:000293282700006
PM 21818257
ER
PT J
AU Volkow, ND
McLellan, TA
AF Volkow, Nora D.
McLellan, Thomas A.
TI Reducing Opioid Abuse and Diversion Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID PAIN
C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA.
[McLellan, Thomas A.] Univ Penn, Sch Med, Penn Ctr Subst Abuse Solut, Philadelphia, PA 19104 USA.
RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Bethesda, MD USA.
EM nvolkow@nida.nih.gov
NR 3
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 27
PY 2011
VL 306
IS 4
BP 382
EP 383
DI 10.1001/jama.2011.1043
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 797KL
UT WOS:000293125800019
ER
PT J
AU Giuliano, AE
Hawes, D
Ballman, KV
Whitworth, PW
Blumencranz, PW
Reintgen, DS
Morrow, M
Leitch, AM
Hunt, KK
McCall, LM
Abati, A
Cote, R
AF Giuliano, Armando E.
Hawes, Debra
Ballman, Karla V.
Whitworth, Pat W.
Blumencranz, Peter W.
Reintgen, Douglas S.
Morrow, Monica
Leitch, A. Marilyn
Hunt, Kelly K.
McCall, Linda M.
Abati, Andrea
Cote, Richard
TI Association of Occult Metastases in Sentinel Lymph Nodes and Bone Marrow
With Survival Among Women With Early-Stage Invasive Breast Cancer
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; PROGNOSTIC-SIGNIFICANCE; CLINICAL-TRIAL;
MICROMETASTASES; DISSECTION; CARCINOMA
AB Context Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathological or clinical examination.
Objective To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow specimens from patients with early-stage breast cancer.
Design, Setting, and Patients From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1 to T2N0M0 invasive breast carcinoma in a prospective observational study.
Interventions All 5210 patients underwent breast-conserving surgery and SLN dissection. Bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). Sentinel lymph node specimens (hematoxylineosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results.
Main Outcome Measures Overall survival (primary end point) and disease-free survival (a secondary end point).
Results Of 5119 SLN specimens (98.3%), 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were positive for tumor. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive for tumors. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7%; 95% confidence interval [CI], 95.0%-96.5% for immunohistochemical negative and 95.1%; 95% CI, 92.7%-97.5% for immunohistochemical positive disease; P=.64; unadjusted hazard ratio [HR], 0.90; 95% CI, 0.59-1.39; P=.64). Bone marrow metastases were associated with decreased overall survival (unadjusted HR for mortality, 1.94; 95% CI, 1.02-3.67; P=.04), but neither immunohistochemical evidence of tumor in SLNs (adjusted HR, 0.88; 95% CI, 0.45-1.71; P=.70) nor immunocytochemical evidence of tumor in bone marrow (adjusted HR, 1.83; 95% CI, 0.79-4.26; P=.15) was statistically significant on multivariable analysis.
Conclusion Among women receiving breast-conserving therapy and SLN dissection, immunohistochemical evidence of SLN metastasis was not associated with overall survival over a median of 6.3 years, whereas occult bone marrow metastasis, although rare, was associated with decreased survival.
C1 [Giuliano, Armando E.] St Johns Hlth Ctr, John Wayne Canc Inst, Div Surg Oncol, Santa Monica, CA USA.
[Hawes, Debra] Univ So Calif, Dept Pathol, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
[Ballman, Karla V.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Whitworth, Pat W.] Nashville Breast Ctr, Nashville, TN USA.
[Blumencranz, Peter W.] Morton Plant Hosp, Clearwater, FL USA.
[Reintgen, Douglas S.] Lakeland Reg Canc Ctr, Lakeland, FL USA.
[Morrow, Monica] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Leitch, A. Marilyn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Hunt, Kelly K.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[McCall, Linda M.] Amer Coll Surg Oncol Grp, Durham, NC USA.
[Abati, Andrea] NCI, Cytopathol Sect, Pathol Lab, Bethesda, MD 20892 USA.
[Cote, Richard] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA.
RP Giuliano, AE (reprint author), Cedars Sinai Med Ctr, 310 N San Vicente Blvd,3rd Floor, Los Angeles, CA 90048 USA.
EM armando.giuliano@cshs.org
OI Ballman, Karla/0000-0002-4492-0357
FU NIH [NCI R01 CA 85840]; US Department of Defense; California Breast
Cancer Research; Whittier Foundation; V-Force; American College of
Surgeons Oncology Group [NCI U10 CA076001]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Giuliano reported that he has
received support from ACOSOG for travel to ACOSOG meetings. Dr Hawes
reported receiving grant support from the NIH and travel support from
ACOSOG and has personal and institutional grants pending from the NIH,
the US Department of Defense, California Breast Cancer Research,
Whittier Foundation, and V-Force. Dr Ballman reported institutional
support from the National Institute of Cancer and other support from
AstraZeneca, Lilly, and Novartis. Dr Whitworth reported travel support
from ACOSOG. Dr Blumencranz reported institutional support from Morton
Plant Hospital, serving on the Florida Society of General Surgeons board
of directors; and institutional payment for lectures from Hologic. Dr
Morrow reported grant support from ACOSOG. Dr Leitch reported travel
support from ACOSOG and institutional support from ACOSOG for capitation
payments for patients enrolled in a study.; This study was supported by
funds from the National Institutes of Health, under the grants entitled
"Bone Marrow and Sentinel Node Micrometastases in Breast Cancer" (NCI
R01 CA 85840; R. Cote, principal investigator) and American College of
Surgeons Oncology Group (NCI U10 CA076001).
NR 24
TC 105
Z9 106
U1 0
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 27
PY 2011
VL 306
IS 4
BP 385
EP 393
DI 10.1001/jama.2011.1034
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 797KL
UT WOS:000293125800024
PM 21791687
ER
PT J
AU Nee, R
Hurst, FP
Dharnidharka, VR
Jindal, RM
Agodoa, LY
Abbott, KC
AF Nee, Robert
Hurst, Frank P.
Dharnidharka, Vikas R.
Jindal, Rahul M.
Agodoa, Lawrence Y.
Abbott, Kevin C.
TI Racial Variation in the Development of Posttransplant
Lymphoproliferative Disorders After Renal Transplantation
SO TRANSPLANTATION
LA English
DT Article
DE United States Renal Data System; Renal transplantation; Cancer
ID PEDIATRIC KIDNEY-TRANSPLANTATION; BARR-VIRUS INFECTION;
NON-HODGKIN-LYMPHOMA; UNITED-STATES; RISK-FACTORS; COLLABORATIVE
TRANSPLANT; MODERN IMMUNOSUPPRESSION; ALLOGRAFT RECIPIENTS;
GRAFT-SURVIVAL; DISEASE
AB Background. We previously reported that posttransplant lymphoproliferative disorders (PTLD) occurred more frequently in non-African American (AF) kidney transplant recipients. An in-depth analysis of racial differences in the development of PTLD has not been reported.
Methods. We assessed Medicare claims for PTLD in a retrospective cohort of 53,719 patients who underwent transplantation from January 2000 to September 2006 and followed up through December 2007.
Results. There were 719 (1.3%) patients with claims for PTLD. Non-AF recipient race (including all races analyzed separately, adjusted hazard ratio [AHR] 1.38, 95% confidence interval [CI] 1.13-1.68), recipient Epstein-Barr virus (EBV) immunoglobulin G (IgG) seronegative status (AHR 1.88, 95% CI 1.53-2.34), and de novo sirolimus (AHR 1.22, 95% CI 1.03-1.45) were associated with an increased risk of PTLD. Furthermore, de novo sirolimus showed a significant interaction with EBV IgG; among EBV IgG-negative recipients, sirolimus use was significant (P=0.003), but among EBV IgG-positive recipients, it was not significant (P=0.18). EBV IgG-seronegative status was significant in all races except for AFs, and racial differences were a significant effect modifier for EBV IgG status and risk of PTLD. Mortality subsequent to PTLD did not differ by race.
Conclusions. AF kidney transplant recipients were at lower risk for PTLD, irrespective of the recipient EBV IgG serostatus. On the contrary, recipient EBV IgG-seronegative status was associated with a higher risk of PTLD in the non-AF population. De novo sirolimus therapy was associated with increased risk of PTLD in EBV IgG-negative recipients, regardless of race.
C1 [Nee, Robert] Walter Reed Army Med Ctr, Dept Nephrol, Serv Nephrol, Washington, DC 20307 USA.
[Nee, Robert; Hurst, Frank P.; Abbott, Kevin C.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA.
[Dharnidharka, Vikas R.] Univ Florida, Coll Med, Div Pediat Nephrol, Gainesville, FL USA.
[Dharnidharka, Vikas R.] Shands Childrens Hosp, Gainesville, FL USA.
[Jindal, Rahul M.] Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA.
[Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD USA.
RP Nee, R (reprint author), Walter Reed Army Med Ctr, Dept Nephrol, Serv Nephrol, 6900 Georgia Ave NW, Washington, DC 20307 USA.
EM robert.nee@us.army.mil
OI Abbott, Kevin/0000-0003-2111-7112
NR 24
TC 10
Z9 10
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD JUL 27
PY 2011
VL 92
IS 2
BP 190
EP 195
DI 10.1097/TP.0b013e3182200e8a
PG 6
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 791AU
UT WOS:000292633000016
PM 21577180
ER
PT J
AU McCaffery, JM
Jablonski, KA
Franks, PW
Dagogo-Jack, S
Wing, RR
Knowler, WC
Delahanty, L
Dabelea, D
Hamman, R
Shuldiner, AR
Florez, JC
AF McCaffery, Jeanne M.
Jablonski, Kathleen A.
Franks, Paul W.
Dagogo-Jack, Sam
Wing, Rena R.
Knowler, William C.
Delahanty, Linda
Dabelea, Dana
Hamman, Richard
Shuldiner, Alan R.
Florez, Jose C.
CA Diabet Prevention Program Res Grp
TI TCF7L2 Polymorphism, Weight Loss and Proinsulin: Insulin Ratio in the
Diabetes Prevention Program
SO PLOS ONE
LA English
DT Article
ID VARIANTS; GENE; POPULATION; SECRETION; ASSOCIATION; CONVERSION;
EVOLUTION; GLUCOSE; RISK
AB Aims: TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses.
Methods: We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults.
Results: We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P, 0.001), higher baseline proinsulin: insulin ratio (p<0.0001) and increased proinsulin: insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms.
Conclusions: The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin: insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.
C1 [McCaffery, Jeanne M.; Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[McCaffery, Jeanne M.; Wing, Rena R.] Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA.
[McCaffery, Jeanne M.; Wing, Rena R.] Brown Med Sch, Providence, RI USA.
[Franks, Paul W.] Lund Univ, Dept Genet & Mol Epidemiol, Malmo, Sweden.
[Dagogo-Jack, Sam] Univ Tennessee, Coll Med, Div Endocrinol Diabet & Metab, Memphis, TN USA.
[Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Delahanty, Linda; Dabelea, Dana] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Hamman, Richard] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Metab, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
RP McCaffery, JM (reprint author), George Washington Univ, Ctr Biostat, Rockville, MD USA.
EM dppmail@bsc.gwu.edu
RI de Bakker, Paul/B-8730-2009; Uwaifo, Gabriel/M-2361-2016;
OI de Bakker, Paul/0000-0001-7735-7858; Uwaifo,
Gabriel/0000-0002-6962-9304; Franks, Paul/0000-0002-0520-7604
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health; NIDDK; Indian Health Service;
Office of Research on Minority Health, the National Institute of Child
Health and Human Development; National Institute on Aging; Centers for
Disease Control and Prevention; American Diabetes Association; McKesson
BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson
Foundation
FX The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) of the National Institutes of Health provided funding to the
clinical centers and the Coordinating Center for the design and conduct
of the study; collection, management, analysis, and interpretation of
the data. The Southwestern American Indian Centers were supported
directly by the NIDDK and the Indian Health Service. The General
Clinical Research Center Program, National Center for Research
Resources, and the Department of Veterans Affairs supported data
collection at many of the clinical centers. Funding for data collection
and participant support was also provided by the Office of Research on
Minority Health, the National Institute of Child Health and Human
Development, the National Institute on Aging, the Centers for Disease
Control and Prevention, and the American Diabetes Association. This
research was also supported, in part, by the intramural research program
of the NIDDK. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.;
Bristol-Myers Squibb and Parke-Davis provided medication; LifeScan Inc.,
Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care,
Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co. and
Quaker Oats Co. donated materials, equipment, or medicines for
concomitant conditions. McKesson BioServices Corp., Matthews Media
Group, Inc., and the Henry M. Jackson Foundation provided support
services under subcontract with the Coordinating Center. There are no
patents, products in development or marketed products to declare. This
does not alter the authors' adherence to all the PLoS ONE policies on
sharing data and materials.
NR 22
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U1 0
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 JUL 26
PY 2011
VL 6
IS 7
AR e21518
DI 10.1371/journal.pone.0021518
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 798BE
UT WOS:000293175100004
PM 21814547
ER
PT J
AU Kato, H
van Ingen, H
Zhou, BR
Feng, HQ
Bustin, M
Kay, LE
Bai, YW
AF Kato, Hidenori
van Ingen, Hugo
Zhou, Bing-Rui
Feng, Hanqiao
Bustin, Michael
Kay, Lewis E.
Bai, Yawen
TI Architecture of the high mobility group nucleosomal protein 2-nucleosome
complex as revealed by methyl-based NMR
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID MOLECULAR-WEIGHT PROTEINS; HMGN PROTEINS; CHROMOSOMAL-PROTEIN; CORE
PARTICLE; HISTONE H1; CHROMATIN; BINDING; ENHANCEMENT; DOCKING; HMG-17
AB Chromatin structure and function are regulated by numerous proteins through specific binding to nucleosomes. The structural basis of many of these interactions is unknown, as in the case of the high mobility group nucleosomal (HMGN) protein family that regulates various chromatin functions, including transcription. Here, we report the architecture of the HMGN2-nucleosome complex determined by a combination of methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy (methyl-TROSY) and mutational analysis. We found that HMGN2 binds to both the acidic patch in the H2A-H2B dimer and to nucleosomal DNA near the entry/exit point, "stapling" the histone core and the DNA. These results provide insight into how HMGNs regulate chromatin structure through interfering with the binding of linker histone H1 to the nucleosome as well as a structural basis of how phosphorylation induces dissociation of HMGNs from chromatin during mitosis. Importantly, our approach is generally applicable to the study of nucleosome-binding interactions in chromatin.
C1 [Kato, Hidenori; Zhou, Bing-Rui; Feng, Hanqiao; Bai, Yawen] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[van Ingen, Hugo; Kay, Lewis E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[van Ingen, Hugo; Kay, Lewis E.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
[van Ingen, Hugo; Kay, Lewis E.] Univ Toronto, Dept Chem, Toronto, ON M5S 1A8, Canada.
[Bustin, Michael] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
RI Zhou, Bing-Rui/D-4766-2009; van Ingen, Hugo/Q-2883-2016; Bustin,
Michael/G-6155-2015
OI van Ingen, Hugo/0000-0002-0808-3811;
FU National Cancer Institute; National Sciences and Engineering Research
Council of Canada; Canadian Institutes of Health Research; JSPS; Niels
Stensen Foundation; Dutch Science Foundation
FX We thank Drs. C. Wu, K. Luger, and T. Richmond for plasmids of histones
and DNA, C. Klee, C. Wu, and M. Lichten for comments on the manuscript,
and A. Bonvin and Y. Postnikov for helpful discussions. This work was
supported by the intramural research program of National Cancer
Institute (to Y.B.) and grants from the National Sciences and
Engineering Research Council of Canada (to L.E.K.) and Canadian
Institutes of Health Research (to L.E.K.). L.E.K. holds a Canada
Research Chair in Biochemistry. H.K. acknowledges a JSPS fellowship and
H.v.I. received support from the Niels Stensen Foundation as well as a
Veni-fellowship from the Dutch Science Foundation.
NR 41
TC 65
Z9 66
U1 1
U2 18
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 JUL 26
PY 2011
VL 108
IS 30
BP 12283
EP 12288
DI 10.1073/pnas.1105848108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797LS
UT WOS:000293129900024
PM 21730181
ER
PT J
AU Kortum, RL
Sommers, CL
Alexander, CP
Pinski, JM
Li, WM
Grinberg, A
Lee, J
Love, PE
Samelson, LE
AF Kortum, Robert L.
Sommers, Connie L.
Alexander, Clayton P.
Pinski, John M.
Li, Wenmei
Grinberg, Alex
Lee, Jan
Love, Paul E.
Samelson, Lawrence E.
TI Targeted Sos1 deletion reveals its critical role in early T-cell
development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Son of Sevenless; beta-selection; conditional knockout; Cre; lymphocyte
signaling
ID DISTINCT SIGNALING PATHWAYS; NUCLEOTIDE EXCHANGE FACTOR; NEGATIVE
SELECTION; THYMOCYTE DEVELOPMENT; ANTIGEN RECEPTOR; TRANSGENIC MICE; RAS
ACTIVATION; TYROSINE KINASES; THYMIC SELECTION; PRE-TCR
AB Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre-T-cell receptor (pre-TCR)-but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR-stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development.
C1 [Kortum, Robert L.; Sommers, Connie L.; Alexander, Clayton P.; Pinski, John M.; Li, Wenmei; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Grinberg, Alex; Lee, Jan; Love, Paul E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM samelson@helix.nih.gov
FU Center for Cancer Research, National Cancer Institute; Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health; National Institute of General Medical
Sciences, National Institutes of Health
FX We thank Pamela Schwartzberg, Jennifer Cannons, Lakshmi Balagopalan, and
B. J. Fowlkes for helpful discussions throughout the project and for
thoughtful reading of the manuscript. We thank Lionel Feigenbaum for the
production of founder Sos1 mice from the ES cells we generated. We also
thank Barbara Taylor for expert assistance with sorting.
RasGRP1-/- mice were a generous gift from James Stone. This
research was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, and the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health. R.L.K. received additional support from a
Pharmacology Research Associate (PRAT) Fellowship, National Institute of
General Medical Sciences, National Institutes of Health.
NR 53
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U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 26
PY 2011
VL 108
IS 30
BP 12407
EP 12412
DI 10.1073/pnas.1104295108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797LS
UT WOS:000293129900045
PM 21746917
ER
PT J
AU Parkhitko, A
Myachina, F
Morrison, TA
Hindi, KM
Auricchio, N
Karbowniczek, M
Wu, JJ
Finkel, T
Kwiatkowski, DJ
Yu, JJ
Henske, EP
AF Parkhitko, Andrey
Myachina, Faina
Morrison, Tasha A.
Hindi, Khadijah M.
Auricchio, Neil
Karbowniczek, Magdalena
Wu, J. Julia
Finkel, Toren
Kwiatkowski, David J.
Yu, Jane J.
Henske, Elizabeth Petri
TI Tumorigenesis in tuberous sclerosis complex is autophagy and
p62/sequestosome 1 (SQSTM1)-dependent
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE metabolism; cell survival; therapy; chloroquine
ID TUMOR-SUPPRESSOR; MTOR PATHWAY; CELL-GROWTH; CANCER; TSC2; GENE;
ACTIVATION; MODEL; P62; ANGIOMYOLIPOMA
AB Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome characterized by benign tumors in multiple organs, including the brain and kidney. TSC-associated tumors exhibit hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), a direct inhibitor of autophagy. Autophagy can either promote or inhibit tumorigenesis, depending on the cellular context. The role of autophagy in the pathogenesis and treatment of the multisystem manifestations of TSC is unknown. We found that the combination of mTORC1 and autophagy inhibition was more effective than either treatment alone in inhibiting the survival of tuberin (TSC2)-null cells, growth of TSC2-null xenograft tumors, and development of spontaneous renal tumors in Tsc2(+/-) mice. Down-regulation of Atg5 induced extensive central necrosis in TSC2-null xenograft tumors, and loss of one allele of Beclin1 almost completely blocked macroscopic renal tumor formation in Tsc2(+/-) mice. Surprisingly, given the finding that lowering autophagy blocks TSC tumorigenesis, genetic down-regulation of p62/sequestosome 1 (SQSTM1), the autophagy substrate that accumulates in TSC tumors as a consequence of low autophagy levels, strongly inhibited the growth of TSC2-null xenograft tumors. These data demonstrate that autophagy is a critical component of TSC tumorigenesis, suggest that mTORC1 inhibitors may have autophagy-dependent prosurvival effects in TSC, and reveal two distinct therapeutic targets for TSC: autophagy and the autophagy target p62/SQSTM1.
C1 [Parkhitko, Andrey; Myachina, Faina; Morrison, Tasha A.; Hindi, Khadijah M.; Yu, Jane J.; Henske, Elizabeth Petri] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Parkhitko, Andrey; Myachina, Faina; Morrison, Tasha A.; Hindi, Khadijah M.; Auricchio, Neil; Kwiatkowski, David J.; Yu, Jane J.; Henske, Elizabeth Petri] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Parkhitko, Andrey] Russian State Med Univ, Dept Mol Biol, Moscow 117997, Russia.
[Auricchio, Neil; Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, Div Translat Med, Boston, MA 02115 USA.
[Karbowniczek, Magdalena] Texas Tech Univ, Sch Pharm, Hlth Sci Ctr, Abilene, TX 79601 USA.
[Wu, J. Julia; Finkel, Toren] NHLBI, Bethesda, MD 20892 USA.
RP Yu, JJ (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
EM jyu13@partners.org; ehenske@partners.org
FU LAM Foundation; Adler Foundation; LAM Treatment Alliance; National
Institute of Diabetes and Digestive and Kidney Diseases [DK51052];
National Heart, Lung, and Blood Institute [HL098216]; National Cancer
Institute [P01 CA120964]
FX We thank Beth Levine for providing the Beclin1+/- mice,
Mustafa Sahin for providing the p62/SQSTM1 shRNA, Craig Thompson and
Julian Lum for providing the Atg5 shRNA, and Michael Jarnik for
performing TEM. This work was supported by the LAM Foundation, the Adler
Foundation, the LAM Treatment Alliance, National Institute of Diabetes
and Digestive and Kidney Diseases Grant DK51052 (to E.P.H.), National
Heart, Lung, and Blood Institute Grant HL098216 (to J.J.Y.), and
National Cancer Institute Grant P01 CA120964 (to D.J.K.). This research
was conducted in partial fulfillment of A.P.'s doctoral degree
requirements at the Department of Molecular Biology, Russian State
Medical University, under the supervision of Dr. Olga Favorova.
NR 50
TC 94
Z9 98
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 JUL 26
PY 2011
VL 108
IS 30
BP 12455
EP 12460
DI 10.1073/pnas.1104361108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797LS
UT WOS:000293129900053
PM 21746920
ER
PT J
AU Middleton, LE
Manini, TM
Simonsick, EM
Harris, TB
Barnes, DE
Tylavsky, F
Brach, JS
Everhart, JE
Yaffe, K
AF Middleton, Laura E.
Manini, Todd M.
Simonsick, Eleanor M.
Harris, Tamara B.
Barnes, Deborah E.
Tylavsky, Frances
Brach, Jennifer S.
Everhart, James E.
Yaffe, Kristine
TI Activity Energy Expenditure and Incident Cognitive Impairment in Older
Adults
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID PHYSICAL-ACTIVITY QUESTIONNAIRES; ALZHEIMERS-DISEASE; EXERCISE;
DEMENTIA; DECLINE; HEALTH; RISK; WOMEN; VARIABILITY; POPULATION
AB Background: Studies suggest that physically active people have reduced risk of incident cognitive impairment in late life. However, these studies are limited by reliance on self-reports of physical activity, which only moderately correlate with objective measures and often exclude activity not readily quantifiable by frequency and duration. The objective of this study was to investigate the relationship between activity energy expenditure (AEE), an objective measure of total activity, and incidence of cognitive impairment.
Methods: We calculated AEE as 90% of total energy expenditure (assessed during 2 weeks using doubly labeled water) minus resting metabolic rate (measured using indirect calorimetry) in 197 men and women (mean age, 74.8 years) who were free of mobility and cognitive impairments at study baseline (1998-1999). Cognitive function was assessed at baseline and 2 or 5 years later using the Modified Mini-Mental State Examination. Cognitive impairment was defined as a decline of at least 1.0 SD (9 points) between baseline and follow-up evaluations.
Results: After adjustment for baseline Modified Mini-Mental State Examination scores, demographics, fatfree mass, sleep duration, self-reported health, and diabetes mellitus, older adults in the highest sex-specific tertile of AEE had lower odds of incident cognitive impairment than those in the lowest tertile (odds ratio, 0.09; 95% confidence interval, 0.01-0.79). There was also a significant dose response between AEE and incidence of cognitive impairment (P=.05 for trend over tertiles).
Conclusions: These findings indicate that greater AEE may be protective against cognitive impairment in a dose-response manner. The significance of overall activity in contrast to vigorous or light activity should be determined.
C1 [Middleton, Laura E.] Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Heart & Stroke Fdn Ctr Stroke Recovery, Toronto, ON M4N 3M5, Canada.
[Manini, Todd M.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Bethesda, MD 20892 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA.
[Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Tylavsky, Frances] Univ Tennessee, Dept Biostat & Epidemiol, Memphis, TN USA.
[Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA.
[Everhart, James E.] NIDDK, Epidemiol & Data Syst Program, Bethesda, MD USA.
RP Middleton, LE (reprint author), Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Heart & Stroke Fdn Ctr Stroke Recovery, 2075 Bayview Ave,A421, Toronto, ON M4N 3M5, Canada.
EM Middleton_l@hotmail.com
RI Middleton, Laura/C-6024-2009
OI Middleton, Laura/0000-0001-8624-3123
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, K01-AG-024069, AG 031155]; National Institutes of Health,
National Institute on Aging; National Institute of Diabetes and
Digestive and Kidney Diseases; Canadian Institute of Health Research
fellowship; National Institute on Aging Claude D. Pepper Center
[P30AG028740]; Alzheimer's Association [IIRG-06-27306]; American
Federation of Aging Research Paul Beeson Career Development Award [K23
AG026766-01]
FX This work was supported by National Institute on Aging (NIA) contracts
N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was also
supported in part by the Intramural Research Program of the National
Institutes of Health, National Institute on Aging, and with additional
support from the National Institute of Diabetes and Digestive and Kidney
Diseases. Dr Middleton is supported by a Canadian Institute of Health
Research fellowship; Dr Manini is supported by grant P30AG028740 from
the National Institute on Aging Claude D. Pepper Center; Dr Barnes was
supported in part by grant K01-AG-024069 from the National Institute on
Aging and grant IIRG-06-27306 from the Alzheimer's Association; Dr Brach
is supported in part by a National Institutes on Aging and American
Federation of Aging Research Paul Beeson Career Development Award (K23
AG026766-01); and Dr Yaffe is supported in part by NIA grant AG 031155
and an Independent Investigator Award from the Alzheimer's Association.
NR 44
TC 58
Z9 61
U1 2
U2 21
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUL 25
PY 2011
VL 171
IS 14
BP 1251
EP 1257
DI 10.1001/archinternmed.2011.277
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 796WN
UT WOS:000293084300007
PM 21771893
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI Pseudodisease, the Next Great Epidemic in Coronary Atherosclerosis?
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID SCREENING-TESTS; NEUROBLASTOMA
C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 10
TC 11
Z9 11
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUL 25
PY 2011
VL 171
IS 14
BP 1268
EP 1269
DI 10.1001/archinternmed.2011.205
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 796WN
UT WOS:000293084300010
PM 21606092
ER
PT J
AU Legros, M
Magori, K
Morrison, AC
Xu, CG
Scott, TW
Lloyd, AL
Gould, F
AF Legros, Mathieu
Magori, Krisztian
Morrison, Amy C.
Xu, Chonggang
Scott, Thomas W.
Lloyd, Alun L.
Gould, Fred
TI Evaluation of Location-Specific Predictions by a Detailed Simulation
Model of Aedes aegypti Populations
SO PLOS ONE
LA English
DT Article
ID YELLOW-FEVER MOSQUITO; LIFE TABLE MODEL; DENGUE VIRUS; PUERTO-RICO;
PERU; DYNAMICS; DIPTERA; VALIDATION; CULICIDAE; IQUITOS
AB Background: Skeeter Buster is a stochastic, spatially explicit simulation model of Aedes aegypti populations, designed to predict the outcome of vector population control methods. In this study, we apply the model to two specific locations, the cities of Iquitos, Peru, and Buenos Aires, Argentina. These two sites differ in the amount of field data that is available for location-specific customization. By comparing output from Skeeter Buster to field observations in these two cases we evaluate population dynamics predictions by Skeeter Buster with varying degrees of customization.
Methodology/Principal Findings: Skeeter Buster was customized to the Iquitos location by simulating the layout of houses and the associated distribution of water-holding containers, based on extensive surveys of Ae. aegypti populations and larval habitats that have been conducted in Iquitos for over 10 years. The model is calibrated by adjusting the food input into various types of containers to match their observed pupal productivity in the field. We contrast the output of this customized model to the data collected from the natural population, comparing pupal numbers and spatial distribution of pupae in the population. Our results show that Skeeter Buster replicates specific population dynamics and spatial structure of Ae. aegypti in Iquitos. We then show how Skeeter Buster can be customized for Buenos Aires, where we only had Ae. aegypti abundance data that was averaged across all locations. In the Argentina case Skeeter Buster provides a satisfactory simulation of temporal population dynamics across seasons.
Conclusions: This model can provide a faithful description of Ae. aegypti populations, through a process of location-specific customization that is contingent on the amount of data available from field collections. We discuss limitations presented by some specific components of the model such as the description of food dynamics and challenges that these limitations bring to model evaluation.
C1 [Legros, Mathieu; Xu, Chonggang; Gould, Fred] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA.
[Legros, Mathieu; Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Magori, Krisztian] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
[Scott, Thomas W.; Lloyd, Alun L.; Gould, Fred] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Lloyd, Alun L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA.
[Lloyd, Alun L.] N Carolina State Univ, Biomath Grad Program, Raleigh, NC 27695 USA.
RP Legros, M (reprint author), N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA.
EM mlegros@ncsu.edu
RI Legros, Mathieu/E-6767-2011; xu, chonggang/B-1256-2012; Lloyd,
Alun/H-4944-2012;
OI Legros, Mathieu/0000-0003-3807-8594; Xu, Chonggang/0000-0002-0937-5744
FU NIH [R01-AI54954-0IA2]; Foundation for the National Institutes of Health
(NIH), through the Grand Challenges in Global Health initiative; Science
and Technology Directory, Department of Homeland Security; Fogarty
International Center, National Institutes of Health
FX This work is funded by an NIH grant R01-AI54954-0IA2 and a grant to the
Regents of the University of California, from the Foundation for the
National Institutes of Health (NIH), through the Grand Challenges in
Global Health initiative to FG. Funding support also came from the
Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directory, Department of Homeland Security,
and Fogarty International Center, National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 52
TC 12
Z9 12
U1 1
U2 18
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 JUL 25
PY 2011
VL 6
IS 7
AR e22701
DI 10.1371/journal.pone.0022701
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 798AP
UT WOS:000293172900069
PM 21799936
ER
PT J
AU Hernandez, L
Paredes, D
Rada, P
AF Hernandez, Luis
Paredes, Daniel
Rada, Pedro
TI Feeding behavior as seen through the prism of brain microdialysis
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Dopamine; Serotonin; Acetylcholine; Norepinephrine; Glutamate; Ingestive
behavior
ID D-ASPARTIC ACID; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; ACCUMBENS
DOPAMINE RELEASE; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA;
OBESE ZUCKER RATS; INCREASES EXTRACELLULAR SEROTONIN; BASOLATERAL
AMYGDALAR NUCLEI; IN-VIVO MICRODIALYSIS; LATERAL HYPOTHALAMUS
AB The knowledge of feeding behavior mechanisms gained through brain microdialysis is reviewed. Most of the chemical changes so far reported concern to the limbic system in rodents. A picture showing increases and decreases of extracellular neurotransmitters correlating to different aspects of feeding behavior is gradually emerging. Depending on the region, the same neurotransmitter may signal opposite aspects of feeding. Dopamine (DA) in the nucleus accumbens (NAC) correlates with food reward, stimulus saliency, and goal directed hyperlocomotion but in the ventromedial hypothalamus DA correlates with satiety and hypolocomotion. The findings accumulated in the last 25 years suggest that the control of a particular function relies on the interaction of several neurotransmitters rather than on a single neurotransmitter. The poor sensitivity of most analytical techniques hinders time and spatial resolution of microdialysis. Therefore, neurochemical correlates of short lasting behaviors are hard to figure out. As new and more sensitive analytical techniques are applied, new neurochemical correlates of feeding show up. Sometimes the proper analytical techniques are simply not available. As a consequence, critical signals such as neuropeptides are not yet completely placed in the puzzle. Despite such limitations, brain microdialysis has yielded a great deal of knowledge on the neurochemical basis of feeding. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Hernandez, Luis; Rada, Pedro] Univ Los Andes, Lab Behav Physiol, Sch Med, Merida 5101A, Venezuela.
[Paredes, Daniel] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Rada, P (reprint author), Univ Los Andes, Lab Behav Physiol, Sch Med, Merida 5101A, Venezuela.
EM radap@ula.ve
RI Paredes , Daniel/L-6610-2013
NR 157
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U1 0
U2 3
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 JUL 25
PY 2011
VL 104
IS 1
SI SI
BP 47
EP 56
DI 10.1016/j.physbeh.2011.04.031
PG 10
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 789AQ
UT WOS:000292486100008
PM 21549733
ER
PT J
AU Tobian, AAR
Quinn, TC
Gray, RH
AF Tobian, Aaron A. R.
Quinn, Thomas C.
Gray, Ronald H.
TI Male circumcision for prevention of oncogenic HPV infection
SO LANCET
LA English
DT Letter
C1 [Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Tobian, Aaron A. R.; Gray, Ronald H.] Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD 21287 USA.
[Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA.
[Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Tobian, AAR (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
EM atobian1@jhmi.edu
FU Intramural NIH HHS [ZIA AI000361-28]; NICHD NIH HHS [R24 HD042854]
NR 6
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD JUL 23
PY 2011
VL 378
IS 9788
BP 314
EP 315
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 803XL
UT WOS:000293615800019
PM 21784258
ER
PT J
AU Kim, S
Bolton, EE
Bryant, SH
AF Kim, Sunghwan
Bolton, Evan E.
Bryant, Stephen H.
TI PubChem3D: Biologically relevant 3-D similarity
SO JOURNAL OF CHEMINFORMATICS
LA English
DT Article
ID HIGH-THROUGHPUT; COMBINATORIAL CHEMISTRY; ACTIVITY-CLIFFS; SHAPE;
INFORMATION; MOLECULES; ASSAYS
AB Background: The use of 3-D similarity techniques in the analysis of biological data and virtual screening is pervasive, but what is a biologically meaningful 3-D similarity value? Can one find statistically significant separation between "active/active" and "active/inactive" spaces? These questions are explored using 734,486 biologically tested chemical structures, 1,389 biological assay data sets, and six different 3-D similarity types utilized by PubChem analysis tools.
Results: The similarity value distributions of 269.7 billion unique conformer pairs from 734,486 biologically tested compounds (all-against-all) from PubChem were utilized to help work towards an answer to the question: what is a biologically meaningful 3-D similarity score? The average and standard deviation for the six similarity measures STST-opt, CTST-opt, ComboT(ST-opt), STCT-opt, CTCT-opt, and ComboT(CT-opt) were 0.54 +/- 0.10, 0.07 +/- 0.05, 0.62 +/- 0.13, 0.41 +/- 0.11, 0.18 +/- 0.06, and 0.59 +/- 0.14, respectively. Considering that this random distribution of biologically tested compounds was constructed using a single theoretical conformer per compound (the "default" conformer provided by PubChem), further study may be necessary using multiple diverse conformers per compound; however, given the breadth of the compound set, the single conformer per compound results may still apply to the case of multi-conformer per compound 3-D similarity value distributions. As such, this work is a critical step, covering a very wide corpus of chemical structures and biological assays, creating a statistical framework to build upon.
The second part of this study explored the question of whether it was possible to realize a statistically meaningful 3-D similarity value separation between reputed biological assay "inactives" and "actives". Using the terminology of noninactive-noninactive (NN) pairs and the noninactive-inactive (NI) pairs to represent comparison of the "active/active" and "active/inactive" spaces, respectively, each of the 1,389 biological assays was examined by their 3-D similarity score differences between the NN and NI pairs and analyzed across all assays and by assay category types. While a consistent trend of separation was observed, this result was not statistically unambiguous after considering the respective standard deviations. While not all "actives" in a biological assay are amenable to this type of analysis, e. g., due to different mechanisms of action or binding configurations, the ambiguous separation may also be due to employing a single conformer per compound in this study. With that said, there were a subset of biological assays where a clear separation between the NN and NI pairs found. In addition, use of combo Tanimoto (ComboT) alone, independent of superposition optimization type, appears to be the most efficient 3-D score type in identifying these cases.
Conclusion: This study provides a statistical guideline for analyzing biological assay data in terms of 3-D similarity and PubChem structure-activity analysis tools. When using a single conformer per compound, a relatively small number of assays appear to be able to separate "active/active" space from "active/inactive" space.
C1 [Kim, Sunghwan; Bolton, Evan E.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, Bethesda, MD 20894 USA.
RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, US Dept HHS, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
RI Kim, Sunghwan/A-6738-2008
OI Kim, Sunghwan/0000-0001-9828-2074
FU National Library of Medicine, National Institutes of Health, U. S.
Department of Health and Human Services
FX We are grateful to the NCBI Systems staff, especially Ron Patterson,
Charlie Cook, and Don Preuss, whose efforts helped make the PubChem3D
project possible. This research was supported (in part) by the
Intramural Research Program of the National Library of Medicine,
National Institutes of Health, U. S. Department of Health and Human
Services. This study utilized the high-performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health, Bethesda, MD. (http://biowulf.nih.gov).
NR 40
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U1 1
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2946
J9 J CHEMINFORMATICS
JI J. Cheminformatics
PD JUL 22
PY 2011
VL 3
AR 26
DI 10.1186/1758-2946-3-26
PG 22
WC Chemistry, Multidisciplinary; Computer Science, Information Systems;
Computer Science, Interdisciplinary Applications
SC Chemistry; Computer Science
GA 891OZ
UT WOS:000300227800001
PM 21781288
ER
PT J
AU Alonso, WJ
Nascimento, FC
Acuna-Soto, R
Schuck-Paim, C
Miller, MA
AF Alonso, Wladimir J.
Nascimento, Francielle C.
Acuna-Soto, Rodolfo
Schuck-Paim, Cynthia
Miller, Mark A.
TI The 1918 influenza pandemic in Florianopolis: A subtropical city in
Brazil
SO VACCINE
LA English
DT Article
DE 1918; Pandemic; Tropics; Influenza
ID MORTALITY
AB Few studies have addressed the impact and dynamics of the 1918-1919 influenza pandemic in tropical and sub-tropical areas. To help cover this gap, we analyzed all death certificates issued from October 1913 to June 1921 in Florianopolis (Brazil), a subtropical state capital with a population of 41,298 inhabitants in 1920. In November and December 1918 (spring) there were a total of 70 and 14 deaths due to influenza and pneumonia, respectively, in contrast to a mean annual mortality attributed to-these causes of 8.1 deaths, usually concentrated between January and August (summer to winter). We also determined the mortality burden due to the pandemic through the analysis of excess mortality during the pandemic period against the baseline mortality in the same months from other years. We obtained a total of 127 deaths (0.33% of the total population), nearly twice the number of deaths documented by death certificates from this period. No other influenza pandemic waves were detected in earlier or subsequent months. Our results confirm the observed patterns of age-shift in mortality in pandemic scenarios, with young adults as the most affected age-group. The pandemic in Florianopolis was further characterized by some specific outcomes: (1) there was a discrete peak in mortality due to renal causes in the initial phase of the pandemic; (2) pandemic influenza did not affect the number of reported bronchitis and bronchiolitis deaths (unusually high in the year preceding the pandemic); and (3) the mortality burden was proportionally lower in Florianopolis than in large urban centers such as Sao Paulo and Rio de Janeiro. We suggest that this latter outcome was the result of an effective and prompt network of voluntary solidarity assistance (as endorsed by contemporaneous documents), which was probably more difficult to implement in larger metropolis. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Alonso, Wladimir J.] NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA.
[Alonso, Wladimir J.; Nascimento, Francielle C.; Schuck-Paim, Cynthia] Origem Sci, Florianopolis, SC, Brazil.
[Nascimento, Francielle C.; Acuna-Soto, Rodolfo] Univ Nacl Autonoma Mexico, Sch Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico.
RP Alonso, WJ (reprint author), NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bldg 16,Stone House,MSC 6705, Bethesda, MD 20892 USA.
EM alonsow@mail.nih.gov
FU Office of Global Health Affairs' International Influenza Unit in the
Office of the Secretary of the Department of Health and Human Services
FX We are grateful to the members of the Municipal Historic Archive
"Professor Oswaldo Rodrigues Cabral" and to the members of the Cemetery
ltacorubi for kindly granting us in situ access to the death
certificates, and for being so helpful in assisting us during this
process. To contribute to the preservation of this historic heritage, we
provided the digitalized files with the death certificates to the
Archive. Access to historic documents for this research were also
granted at "Arquivo Publico de Santa Catarina", "Hospital da
Caridade","Biblioteca Poblica Estadual" and "Center for Research
Libraries" (www.crl.edu/brazil). We also thank Vikash Parekh for his
comments on the manuscript. This research was conducted in the context
of the Multinational Influenza Seasonal Mortality Study (MISMS), an
on-going international collaborative effort to understand influenza
epidemiological and evolutionary patterns, led by the Fogarty
International Center, National Institutes of Health. Funding for this
project comes from the Office of Global Health Affairs' International
Influenza Unit in the Office of the Secretary of the Department of
Health and Human Services.
NR 23
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 22
PY 2011
VL 29
SU 2
BP B16
EP B20
DI 10.1016/j.vaccine.2011.02.047
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 802ZW
UT WOS:000293550500004
PM 21757098
ER
PT J
AU Andreasen, V
Simonsen, L
AF Andreasen, Viggo
Simonsen, Lone
TI The perils of using annual all-cause mortality data to estimate pandemic
influenza burden
SO VACCINE
LA English
DT Article
DE Pandemic influenza; Mortality; Modeling; Global burden
ID UNITED-STATES; WAVE; VACCINATION; COPENHAGEN; DENMARK; DEATHS
AB Measuring the burden of historic pandemics is not straightforward and often must be based on suboptimal mortality data. For example, the critical 1918 pandemic global burden estimate was based on excess in annual all-cause mortality - calculated as the difference between deaths during 1918-1920 and the surrounding 3-year periods. One intriguing result was a similar to 40-fold between-country variation in pandemic mortality burden: similar to 0.2% of Danes died, compared to similar to 8% of populations in some Indian provinces (Murray et al., 2006 [16]).
Using the same methodology and data source we explore the robustness of this methodology for different age-groups. For infants the country estimates varied 100-fold, from 15 to 1500 excess deaths/10,000 population, while for adults >= 45 years estimates ranged from -70 to 170/10,000 population. In contrast, estimates for children, 1-14 years, and adults aged 15-44 years, were far more stable.
We next used detailed mortality data from Copenhagen to compare such estimates to the more precise estimates obtained from monthly mortality time series data and respiratory deaths. We found that the all-cause annual method substantially underestimated due to an unexplained depression in all-cause mortality in Denmark in 1918 and deaths caused by other epidemic diseases during the baseline periods.
We conclude that country estimates for infants and older adults were highly variable by the Murray method due to substantial variability in annual all-cause mortality. A more precise 1918 pandemic burden estimate would be gotten from either focusing analysis on persons age 1-44 who suffered 95% of all pandemic deaths and had a substantial rise over their baseline mortality level, or if possible focus analysis on annual respiratory deaths. For less severe pandemics, including the ongoing 2009 H1N1 pandemic, the use of all-cause mortality data requires careful consideration of excess deaths in defined pandemic periods and a focus on age groups known to be at risk. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Andreasen, Viggo] Roskilde Univ, Dept Sci, Roskilde, Denmark.
[Andreasen, Viggo; Simonsen, Lone] NIH, Fogarty Int Ctr, Bethesda, MD USA.
[Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC 20052 USA.
RP Andreasen, V (reprint author), Roskilde Univ, Dept Sci, Roskilde, Denmark.
EM viggo@ruc.dk
OI Simonsen, Lone/0000-0003-1535-8526
FU Danish Medical Research Council [271-07-0555]; Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX This research was supported in part by a grant 271-07-0555 from the
Danish Medical Research Council and by the RAPIDD program of the Science
& Technology Directorate, Department of Homeland Security, and the
Fogarty International Center, National Institutes of Health.
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 22
PY 2011
VL 29
SU 2
BP B49
EP B55
DI 10.1016/j.vaccine.2011.03.061
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 802ZW
UT WOS:000293550500010
PM 21757104
ER
PT J
AU Chowell, G
Viboud, C
Simonsen, L
Miller, MA
Hurtado, J
Soto, G
Vargas, R
Guzman, MA
Ulloa, M
Munayco, CV
AF Chowell, G.
Viboud, C.
Simonsen, L.
Miller, M. A.
Hurtado, J.
Soto, G.
Vargas, R.
Guzman, M. A.
Ulloa, M.
Munayco, C. V.
TI The 1918-1920 influenza pandemic in Peru
SO VACCINE
LA English
DT Article
DE 1918 influenza pandemic; Peru; Lima; Iquitos; Transmissibility;
Age-specific mortality
ID SPANISH INFLUENZA; MORTALITY IMPACT; WAVE; TRANSMISSIBILITY; PATTERNS;
ILLNESS; EUROPE; NUMBER; CITY; AGE
AB Background: Increasing our knowledge of past influenza pandemic patterns in different regions of the world is crucial to guide preparedness plans against future influenza pandemics. Here, we undertook extensive archival collection efforts from three representative cities of Peru Lima in the central coast, Iquitos in the northeastern Amazon region, Ica in the southern coast to characterize the temporal, age and geographic patterns of the 1918-1920 influenza pandemic in this country.
Materials and methods: We analyzed historical documents describing the 1918-1920 influenza pandemic in Peru and retrieved individual mortality records from local provincial archives for quantitative analysis. We applied seasonal excess mortality models to daily and monthly respiratory mortality rates for 1917-1920 and quantified transmissibility estimates based on the daily growth rate in respiratory deaths. Results: A total of 52,739 individual mortality records were inspected from local provincial archives. We found evidence for an initial mild pandemic wave during July-September 1918 in Lima, identified a synchronized severe pandemic wave of respiratory mortality in all three locations during November 1918-February 1919, and a severe pandemic wave during January 1920-March 1920 in Lima and July-October 1920 in Ica. There was no recrudescent pandemic wave in 1920 in Iquitos. Remarkably, Lima experienced the brunt of the 1918-1920 excess mortality impact during the 1920 recrudescent wave, with all age groups experiencing an increase in all cause excess mortality from 1918-1919 to 1920. Middle age groups experienced the highest excess mortality impact, relative to baseline levels, in the 1918-1919 and 1920 pandemic waves. Cumulative excess mortality rates for the 1918-1920 pandemic period were higher in Iquitos (2.9%) than Lima (1.6%). The mean reproduction number for Lima was estimated in the range 1.3-1.5.
Conclusions: We identified synchronized pandemic waves of intense excess respiratory mortality during November 1918-February 1919 in Lima, Iquitos, Ica, followed by asynchronous recrudescent waves in 1920. Cumulative data from quantitative studies of the 1918 influenza pandemic in Latin American settings have confirmed the high mortality impact associated with this pandemic. Further historical studies in lesser studied regions of Latin America, Africa, and Asia are warranted for a full understanding of the global impact of the 1918 pandemic virus. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Chowell, G.; Miller, M. A.] Arizona State Univ, Math Computat & Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
[Chowell, G.; Viboud, C.; Simonsen, L.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, L.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA.
[Hurtado, J.; Soto, G.; Ulloa, M.; Munayco, C. V.] Peru Minist Salud, Direcc Gen Epidemiol, Lima, Peru.
[Vargas, R.] Hosp Belen, Direcc Reg Salud, La Libertad, Peru.
[Guzman, M. A.] Univ Nacl Amazonia Peruana, Iquitos, Peru.
RP Chowell, G (reprint author), Arizona State Univ, Math Computat & Modeling Sci Ctr, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
EM gchowell@asu.edu
RI Munayco, Cesar/G-9990-2013; Chowell, Gerardo/F-5038-2012;
OI Munayco, Cesar/0000-0001-7872-8913; Chowell,
Gerardo/0000-0003-2194-2251; Simonsen, Lone/0000-0003-1535-8526
FU Intramural NIH HHS [Z99 TW999999]
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JUL 22
PY 2011
VL 29
SU 2
BP B21
EP B26
DI 10.1016/j.vaccine.2011.02.048
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 802ZW
UT WOS:000293550500005
PM 21757099
ER
PT J
AU Saglanmak, N
Andreasen, V
Simonsen, L
Molbak, K
Miller, MA
Viboud, C
AF Saglanmak, Neslihan
Andreasen, Viggo
Simonsen, Lone
Molbak, Kare
Miller, Mark A.
Viboud, Cecile
TI Gradual changes in the age distribution of excess deaths in the years
following the 1918 influenza pandemic in Copenhagen: Using
epidemiological evidence to detect antigenic drift
SO VACCINE
LA English
DT Article
DE 1918 Influenza pandemic; Excess mortality; Age shift; Antigenic drift;
Copenhagen
ID MORTALITY; VACCINATION; IMPACT; WAVE
AB Background: The 1918 influenza pandemic was associated with an unusual age pattern of mortality, with most deaths occurring among young adults. Few studies have addressed changes in the age distribution for influenza-related mortality in the pre-pandemic and post-pandemic period, which has implications for pandemic preparedness. In the present paper, we analyse the age patterns of influenza-related excess mortality in the decades before and after the 1918 pandemic, using detailed historic surveillance data from Copenhagen.
Methods: Weekly age-specific rates of respiratory mortality and influenza-like-illnesses were compiled for 1904-1937. Seasonal excess rates of morbidity and mortality attributable to influenza were calculated using a seasonal regression approach. To characterize the age patterns of influenza-related deaths in individual seasons, we used two rate ratio (RR) measures representing ratios of excess mortality rates between age groups and influenza seasons.
Results: Individuals aged 15-64 years experienced sharply elevated excess respiratory mortality rates in the 1918-1919 and 1919-1920 pandemic periods, compared to pre-pandemic seasons (RR for excess mortality in the fall of 1918 = 67 relative to inter-pandemic seasons). Of all excess respiratory deaths occurring during 1918-1919,84% were reported in individuals 15-64 years. By contrast, seniors over 65 years of age experienced no measurable excess mortality during 1918-1919 and moderate excess mortality in the recrudescent pandemic wave of 1919-1920. The first post-pandemic season associated with high excess mortality rates in individuals over 65 years was 1928-1929, with 73% of excess deaths occurring among seniors. We estimate that the age patterns of influenza-related mortality returned to pre-pandemic levels after 1925, based on trends in the rate ratio of excess respiratory mortality in people under and over 65 years.
Conclusions: The unusual elevation of excess respiratory mortality rates in young and middle-aged adults was confined to the first three years of A/H1N1 virus circulation 1918-1920; the rapid return to "epidemic" mortality pattern in this age group was probably due to high attack rates and build-up of immunity. In contrast, seniors were completely spared from pandemic mortality during 1918-1919, likely due to childhood exposure to an A/H1-like influenza virus. The rise in excess mortality rates in seniors in the recrudescent pandemic wave of 1919-1920 may suggest the emergence of an early influenza A/H1N1 drift variant. Subsequent drift events may have been associated with the particularly severe 1928-1929 epidemic in Denmark and elsewhere. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Saglanmak, Neslihan; Andreasen, Viggo] Roskilde Univ Ctr, DK-4000 Roskilde, Denmark.
[Saglanmak, Neslihan; Andreasen, Viggo; Simonsen, Lone; Miller, Mark A.; Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Washington, DC USA.
[Molbak, Kare] Statens Serum Inst, Copenhagen, Denmark.
RP Saglanmak, N (reprint author), Roskilde Univ Ctr, IMFUFA NSM Bygning 27,Univ Vej 1,Postboks 260, DK-4000 Roskilde, Denmark.
EM neslihan@ruc.dk
OI Molbak, Kare/0000-0002-3100-4990; Simonsen, Lone/0000-0003-1535-8526
FU Fogarty International Center, National Institutes of Health; Office of
Global Health Affairs' International Influenza Unit, Office of the
Secretary, Department of Health and Human Services; Danish Council for
Independent Research-Medical Sciences; Science & Technology Directorate,
Department of Homeland Security
FX This work was conducted in the context of the Multinational Influenza
Seasonal Mortality Study (MISMS), an on-going international
collaborative effort to understand influenza epidemiological and
evolutionary patterns (http://www.origem.info/misms/index.php). This
effort is supported in part by Fogarty International Center, National
Institutes of Health and the Office of Global Health Affairs'
International Influenza Unit, Office of the Secretary, Department of
Health and Human Services. NS was partly sponsored by The Danish Council
for Independent Research-Medical Sciences. LS and VA acknowledge support
from the RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security. The authors would like to thank the
four anonymous reviewers for their time in reviewing the manuscript.
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PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 22
PY 2011
VL 29
SU 2
BP B42
EP B48
DI 10.1016/j.vaccine.2011.02.065
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 802ZW
UT WOS:000293550500009
PM 21757103
ER
PT J
AU Simonsen, L
Viboud, C
Chowell, G
Andreasen, V
Olson, DR
Parekh, V
Molbak, K
Miller, MA
AF Simonsen, Lone
Viboud, Cecile
Chowell, Gerardo
Andreasen, Viggo
Olson, Donald R.
Parekh, Vikash
Molbak, Kare
Miller, Mark A.
TI The need for interdisciplinary studies of historic pandemics
SO VACCINE
LA English
DT Editorial Material
ID EXTRACORPOREAL MEMBRANE-OXYGENATION; INFLUENZA MORTALITY; H1N1
INFLUENZA; WAVE
C1 [Simonsen, Lone] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
[Andreasen, Viggo] Roskilde Univ Ctr, Roskilde, Denmark.
[Olson, Donald R.] Int Soc Dis Surveillance, Brighton, MA 02135 USA.
[Molbak, Kare] Statens Serum Inst, Copenhagen, Denmark.
RP Simonsen, L (reprint author), NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM lone@gwu.edu
RI Chowell, Gerardo/F-5038-2012;
OI Chowell, Gerardo/0000-0003-2194-2251; Molbak, Kare/0000-0002-3100-4990;
Simonsen, Lone/0000-0003-1535-8526
NR 32
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 22
PY 2011
VL 29
SU 2
BP B1
EP B5
DI 10.1016/j.vaccine.2011.03.094
PG 5
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 802ZW
UT WOS:000293550500001
PM 21757096
ER
PT J
AU Hall, JA
Grainger, JR
Spencer, SP
Belkaid, Y
AF Hall, Jason A.
Grainger, John R.
Spencer, Sean P.
Belkaid, Yasmine
TI The Role of Retinoic Acid in Tolerance and Immunity
SO IMMUNITY
LA English
DT Review
ID REGULATORY T-CELLS; CD103(+) DENDRITIC CELLS; VITAMIN-A-DEFICIENCY;
INFLAMMATORY-BOWEL-DISEASE; LAMINA-PROPRIA; IN-VIVO; SMALL-INTESTINE;
X-RECEPTOR; TH17 CELLS; FUNCTIONAL SPECIALIZATION
AB Vitamin A elicits a broad array of immune responses through its metabolite, retinoic acid (RA). Recent evidence indicates that loss of RA leads to impaired immunity, whereas excess RA can potentially promote inflammatory disorders. In this review, we discuss recent advances showcasing the crucial contributions of RA to both immunological tolerance and the elicitation of adaptive immune responses. Further, we provide a comprehensive overview of the cell types and factors that control the production of RA and discuss how host perturbations may affect the ability of this metabolite to control tolerance and immunity or to instigate pathology.
C1 [Hall, Jason A.; Grainger, John R.; Spencer, Sean P.; Belkaid, Yasmine] NIAID, Mucosal Immun Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Hall, Jason A.; Spencer, Sean P.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA.
RP Hall, JA (reprint author), NIAID, Mucosal Immun Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM halljas@niaid.nih.gov; ybelkaid@mail.nih.gov
OI Grainger, John/0000-0002-4052-5923
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Office of Dietary
Supplements
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, and the Office of Dietary Supplements. We thank E. Wohlfert and
T. Hand for helpful discussions and critical reading of the manuscript.
NR 129
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U1 2
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUL 22
PY 2011
VL 35
IS 1
BP 13
EP 22
DI 10.1016/j.immuni.2011.07.002
PG 10
WC Immunology
SC Immunology
GA 797EM
UT WOS:000293107300006
PM 21777796
ER
PT J
AU Checkley, MA
Luttge, BG
Freed, EO
AF Checkley, Mary Ann
Luttge, Benjamin G.
Freed, Eric O.
TI HIV-1 Envelope Glycoprotein Biosynthesis, Trafficking, and Incorporation
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
DE HIV-1; retrovirus; envelope glycoprotein; assembly; trafficking
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP41 CYTOPLASMIC TAIL; TYPE-1
TRANSMEMBRANE PROTEIN; PRENYLATED RAB ACCEPTOR; CELL-CELL FUSION;
C-TERMINAL TAIL; CHOLESTEROL-BINDING COMPOUND; POLARIZED
EPITHELIAL-CELLS; MEMBRANE-SPANNING DOMAIN; AMINO-ACID SUBSTITUTIONS
AB The HIV-1 envelope (Env) glycoproteins play an essential role in the virus replication cycle by mediating the fusion between viral and cellular membranes during the entry process. The Env glycoproteins are synthesized as a polyprotein precursor (gp160) that is cleaved by cellular proteases to the mature surface glycoprotein gp120 and the transmembrane glycoprotein gp41. During virus assembly, the gp120/gp41 complex is incorporated as heterotrimeric spikes into the lipid bilayer of nascent virions. These gp120/gp41 complexes then initiate the infection process by binding receptor and coreceptor on the surface of target cells. Much is currently known about the HIV-1 Env glycoprotein trafficking pathway and the structure of gp120 and the extracellular domain of gp41. However, the mechanism by which the Env glycoprotein complex is incorporated into virus particles remains incompletely understood. Genetic data support a major role for the cytoplasmic tail of gp41 and the matrix domain of Gag in Env glycoprotein incorporation. Still to be defined are the identities of host cell factors that may promote Env incorporation and the role of specific membrane microdomains in this process. Here, we review our current understanding of HIV-1 Env glycoprotein trafficking and incorporation into virions. Published by Elsevier Ltd.
C1 [Checkley, Mary Ann; Luttge, Benjamin G.; Freed, Eric O.] NCI Frederick, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI Frederick, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535,Room 108,1050 Boyles St, Frederick, MD 21702 USA.
EM efreed@nih.gov
FU National Institutes of Health; National Cancer Institute, Center for
Cancer Research; Intramural AIDS Targeted Antiviral Program
FX We thank P. D. Kwong, S. Subramaniam, A. Ono, J. D. Steckbeck, R.
Montelaro, C. K. Leonard, and T. J. Gregory for permission to reproduce
or adapt published figures. We are grateful to M. Johnson and members of
the Freed laboratory for helpful discussions. Research in our laboratory
is supported by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research and by the Intramural AIDS Targeted Antiviral Program.
NR 307
TC 137
Z9 139
U1 5
U2 44
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUL 22
PY 2011
VL 410
IS 4
SI SI
BP 582
EP 608
DI 10.1016/j.jmb.2011.04.042
PN 1
PG 27
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 804SJ
UT WOS:000293674000009
PM 21762802
ER
PT J
AU Goicochea, NL
Datta, SAK
Ayaluru, M
Kao, C
Rein, A
Dragnea, B
AF Goicochea, Nancy L.
Datta, Siddhartha A. K.
Ayaluru, Murali
Kao, Cheng
Rein, Alan
Dragnea, Bogdan
TI Structure and Stoichiometry of Template-Directed Recombinant HIV-1 Gag
Particles
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE HIV Gag; nanoparticle; templated virus assembly; liquid crystal;
electron microscopy
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ASSEMBLY IN-VITRO; NUCLEOCAPSID PROTEIN;
ELECTRON CRYOTOMOGRAPHY; 3-DIMENSIONAL STRUCTURE; GOLD NANOPARTICLES;
MATRIX PROTEIN; CAPSIDS; DOMAIN; CORE
AB Size polydispersity of immature human immunodeficiency virus type 1 (HIV-1) particles represents a challenge for traditional methods of biological ultrastructural analysis. An in vitro model for immature HIV-1 particles constructed from recombinant Gag proteins lacking residues 16-99 and the p6 domain assembled around spherical nanoparticles functionalized with DNA. This template-directed assembly approach led to a significant reduction in size polydispersity and revealed previously unknown structural features of immature-like HIV-1 particles. Electron microscopy and image reconstruction of these particles suggest that the Gag shell formed from different protein regions that are connected by a "scar"-an extended defect connecting the edges of two continuous, regularly packed protein layers. Thus, instead of a holey protein array, the experimental model presented here appears to consist of a continuous array of similar to 5000 proteins enveloping the core, in which regular regions are separated by extended areas of disorder. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Datta, Siddhartha A. K.; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Goicochea, Nancy L.; Dragnea, Bogdan] Indiana Univ, Dept Chem, Bloomington, IN 47405 USA.
[Ayaluru, Murali; Kao, Cheng] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM reina@mail.nih.gov; dragnea@indiana.edu
RI Murali, Ayaluru/G-3401-2014;
OI Murali, Ayaluru/0000-0001-6406-6840; Datta,
Siddhartha/0000-0002-4098-7490
FU National Science Foundation [0832651, 0708590]; National Institutes of
Health [GM081029]; NIH, National Cancer Institute, Center for Cancer
Research
FX We gratefully acknowledge support from the National Science Foundation
(grants 0832651 and 0708590) and the National Institutes of Health
(grant GM081029). This work was also supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 56
TC 13
Z9 13
U1 0
U2 12
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 JUL 22
PY 2011
VL 410
IS 4
SI SI
BP 667
EP 680
DI 10.1016/j.jmb.2011.04.012
PN 1
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 804SJ
UT WOS:000293674000014
PM 21762807
ER
PT J
AU Begum, N
Hockman, S
Manganiello, VC
AF Begum, Najma
Hockman, Steven
Manganiello, Vincent C.
TI Phosphodiesterase 3A (PDE3A) Deletion Suppresses Proliferation of
Cultured Murine Vascular Smooth Muscle Cells (VSMCs) via Inhibition of
Mitogen-activated Protein Kinase (MAPK) Signaling and Alterations in
Critical Cell Cycle Regulatory Proteins
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEOTIDE PHOSPHODIESTERASES; DIFFERENTIAL REGULATION; INSULIN
REGULATION; MESANGIAL CELLS; GROWTH-FACTOR; NITRIC-OXIDE; CAMP;
EXPRESSION; MIGRATION; ATHEROSCLEROSIS
AB Cyclic nucleotide phosphodiesterase 3 (PDE3) is an important regulator of cyclic adenosine monophosphate (cAMP) signaling within the cardiovascular system. In this study, we examined the role of PDE3A and PDE3B isoforms in regulation of growth of cultured vascular smooth muscle cells (VSMCs) and the mechanisms by which they may affect signaling pathways that mediate mitogen-induced VSMC proliferation. Serum-and PDGF-induced DNA synthesis in VSMCs grown from aortas of PDE3A-deficient (3A-KO) mice was markedly less than that in VSMCs from PDE3A wild type (3A-WT) and PDE3B-deficient (3B-KO) mice. The reduced growth response was accompanied by significantly less phosphorylation of extracellular signal-regulated kinase (ERK) in 3A-KO VSMCs, most likely due to a combination of greater site-specific inhibitory phosphorylation of Raf-1(Ser-259) by protein kinase A (PKA) and enhanced dephosphorylation of ERKs due to elevated mitogen-activated protein kinase phosphatase 1 (MKP-1). Furthermore, 3A-KO VSMCs, compared with 3A-WT, exhibited higher basal PKA activity and cAMP response element-binding protein (CREB) phosphorylation, higher levels of p53 and p53 phosphorylation, and elevated p21 protein together with lower levels of Cyclin-D1 and retinoblastoma (Rb) protein and Rb phosphorylation. Adenoviral overexpression of inactive CREB partially restored growth effects of serum in 3A-KO VSMCs. In contrast, exposure of 3A-WT VSMCs to VP16 CREB (active CREB) was associated with inhibition of serum-induced DNA synthesis similar to that in untreated 3A-KO VSMCs. Transfection of 3A-KO VSMCs with p53 siRNA reduced p21 and MKP-1 levels and completely restored growth without affecting amounts of Cyclin-D1 and Rb phosphorylation. We conclude that PDE3A regulates VSMC growth via two complementary pathways, i.e. PKA-catalyzed inhibitory phosphorylation of Raf-1 with resulting inhibition of MAPK signaling and PKA/CREB-mediated induction of p21, leading to G(0)/G(1) cell cycle arrest, as well as by increased accumulation of p53, which induces MKP-1, p21, and WIP1, leading to inhibition of G(1) to S cell cycle progression.
C1 [Begum, Najma; Hockman, Steven; Manganiello, Vincent C.] NHLBI, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Begum, N (reprint author), NHLBI, Cardiovasc Pulm Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 5N322,MSC-1076, Bethesda, MD 20892 USA.
EM begumn@mail.nih.gov
FU National Institutes of Health through NHLBI
FX This work was supported, in whole or in part, by the National Institutes
of Health through the Intramural Research Program of the NHLBI.
NR 53
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Z9 21
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 JUL 22
PY 2011
VL 286
IS 29
BP 26238
EP 26249
DI 10.1074/jbc.M110.214155
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 796SS
UT WOS:000293073000081
PM 21632535
ER
PT J
AU Bailey, JA
Ray, B
Greig, NH
Lahiri, DK
AF Bailey, Jason A.
Ray, Balmiki
Greig, Nigel H.
Lahiri, Debomoy K.
TI Rivastigmine Lowers A beta and Increases sAPP alpha Levels, Which
Parallel Elevated Synaptic Markers and Metabolic Activity in
Degenerating Primary Rat Neurons
SO PLOS ONE
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; MILD COGNITIVE IMPAIRMENT;
ALZHEIMERS-DISEASE; CHOLINESTERASE-INHIBITORS; PRESYNAPTIC PROTEINS;
HIPPOCAMPAL-NEURONS; GLUCOSE-METABOLISM; PEPTIDE LEVELS; MESSENGER-RNA;
CELL-LINES
AB Overproduction of amyloid-beta (A beta) protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD). Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence A beta precursor protein (APP) processing and A beta production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and A beta on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP) and A beta. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased a-secretase cleaved sAPP alpha and decreased A beta secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the a-secretase pathway in degenerating neuronal cultures, which mirrors the trend of synaptic proteins, and metabolic activity.
C1 [Bailey, Jason A.; Ray, Balmiki; Lahiri, Debomoy K.] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN USA.
[Greig, Nigel H.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Bailey, JA (reprint author), Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN USA.
EM dlahiri@iupui.edu
FU National Institutes of Health [R01-AG18379, R01-AG18884]; National
Institute on Aging; Novartis
FX This research is supported by National Institutes of Health grants
(R01-AG18379 and R01-AG18884) to DKL and the Intramural Research Program
of the National Institute on Aging (NHG). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.; I have read the journal's policy and
have the following conflict: Dr. Lahiri is a member of the scientific
advisory board of QR Pharma, Inc, Randon, PA. He was previously a
receipient of a grant from Novartis. Currently, he and the other
co-authors of this study are declaring no financial relationship with
Novartis, and this past relationship does not interfere with the PLoS
ONE policies on sharing of data and materials.
NR 62
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U1 1
U2 7
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 JUL 22
PY 2011
VL 6
IS 7
AR e21954
DI 10.1371/journal.pone.0021954
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797BJ
UT WOS:000293097300008
PM 21799757
ER
PT J
AU Devine, MJ
Kaganovich, A
Ryten, M
Mamais, A
Trabzuni, D
Manzoni, C
McGoldrick, P
Chan, D
Dillman, A
Zerle, J
Horan, S
Taanman, JW
Hardy, J
Marti-Masso, JF
Healey, D
Schapira, AH
Wolozin, B
Bandopadhyay, R
Cookson, MR
van der Brug, MP
Lewis, PA
AF Devine, Michael J.
Kaganovich, Alice
Ryten, Mina
Mamais, Adamantios
Trabzuni, Daniah
Manzoni, Claudia
McGoldrick, Philip
Chan, Diane
Dillman, Allissa
Zerle, Julia
Horan, Susannah
Taanman, Jan-Willem
Hardy, John
Marti-Masso, Jose-Felix
Healey, Daniel
Schapira, Anthony H.
Wolozin, Benjamin
Bandopadhyay, Rina
Cookson, Mark R.
van der Brug, Marcel P.
Lewis, Patrick A.
TI Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model
Systems or Human Brain Tissue
SO PLOS ONE
LA English
DT Article
ID PARKINSONS-DISEASE; PHOSPHORYLATION; PROTEINS; HEALTH; 4E-BP
AB Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.
C1 [Devine, Michael J.; Ryten, Mina; Mamais, Adamantios; Trabzuni, Daniah; Manzoni, Claudia; Zerle, Julia; Hardy, John; Bandopadhyay, Rina; Lewis, Patrick A.] UCL Inst Neurol, Dept Mol Neurosci, London, England.
[Kaganovich, Alice; Dillman, Allissa; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Mamais, Adamantios; Bandopadhyay, Rina] UCL Inst Neurol, Rita Lila Weston Inst, London, England.
[Mamais, Adamantios; Bandopadhyay, Rina] UCL Inst Neurol, Queen Sq Brain Bank, London, England.
[McGoldrick, Philip] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London, England.
[Chan, Diane; Wolozin, Benjamin] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA.
[Horan, Susannah; Taanman, Jan-Willem; Healey, Daniel; Schapira, Anthony H.] UCL Inst Neurol, Dept Clin Neurosci, London, England.
[Marti-Masso, Jose-Felix] Hosp Donastia, San Sebastian, Spain.
[van der Brug, Marcel P.] Scripps Res Inst, Jupiter, FL USA.
RP Devine, MJ (reprint author), UCL Inst Neurol, Dept Mol Neurosci, London, England.
EM mvanderb@scripps.edu; p.lewis@ion.ucl.ac.uk
RI Hardy, John/C-2451-2009; Taanman, Jan/A-5379-2011; Lewis ,
Patrick/C-3674-2009; manzoni, claudia/F-4831-2014; Bandopadhyay, Rina
/C-7926-2009; Trabzuni, Daniah/C-4034-2012; Marti Masso, Jose
Felix/D-8619-2013;
OI Taanman, Jan/0000-0002-5476-9785; Trabzuni, Daniah/0000-0003-4826-9570;
Marti Masso, Jose Felix/0000-0001-8428-4386; Lewis,
Patrick/0000-0003-4537-0489; Devine, Mike/0000-0001-6076-3382
FU Medical Research Council [G0800437]; Parkinson's UK [F-1002]; Brain
Research Trust; Michael J. Fox foundation; Wellcome/MRC Parkinson's
Disease Consortium; National Institute on Aging
FX This work was funded by the Medical Research Council (fellowship
G0800437, MJD), Parkinson's UK (fellowship F-1002, PAL), Brain Research
Trust and the Michael J. Fox foundation. It was supported in part by the
Wellcome/MRC Parkinson's Disease Consortium grant and by the intramural
program of the National Institute on Aging. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 24
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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 JUL 22
PY 2011
VL 6
IS 7
AR e22489
DI 10.1371/journal.pone.0022489
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797BJ
UT WOS:000293097300053
PM 21799870
ER
PT J
AU Duncan, CJA
Sheehy, SH
Ewer, KJ
Douglas, AD
Collins, KA
Halstead, FD
Elias, SC
Lillie, PJ
Rausch, K
Aebig, J
Miura, K
Edwards, NJ
Poulton, ID
Hunt-Cooke, A
Porter, DW
Thompson, FM
Rowland, R
Draper, SJ
Gilbert, SC
Fay, MP
Long, CA
Zhu, DM
Wu, YM
Martin, LB
Anderson, CF
Lawrie, AM
Hill, AVS
Ellis, RD
AF Duncan, Christopher J. A.
Sheehy, Susanne H.
Ewer, Katie J.
Douglas, Alexander D.
Collins, Katharine A.
Halstead, Fenella D.
Elias, Sean C.
Lillie, Patrick J.
Rausch, Kelly
Aebig, Joan
Miura, Kazutoyo
Edwards, Nick J.
Poulton, Ian D.
Hunt-Cooke, Angela
Porter, David W.
Thompson, Fiona M.
Rowland, Ros
Draper, Simon J.
Gilbert, Sarah C.
Fay, Michael P.
Long, Carole A.
Zhu, Daming
Wu, Yimin
Martin, Laura B.
Anderson, Charles F.
Lawrie, Alison M.
Hill, Adrian V. S.
Ellis, Ruth D.
TI Impact on Malaria Parasite Multiplication Rates in Infected Volunteers
of the Protein-in-Adjuvant Vaccine AMA1-C1/Alhydrogel+CPG 7909
SO PLOS ONE
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM MALARIA;
POLYMERASE-CHAIN-REACTION; BLOOD-STAGE VACCINE; GROWTH-RATES; INHIBITORY
ANTIBODIES; CLINICAL-TRIAL; VIRUS ANKARA; PHASE; VITRO
AB Background: Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria.
Methods: In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes.
Results: A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9]).
Conclusions: Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers.
C1 [Duncan, Christopher J. A.; Sheehy, Susanne H.; Lillie, Patrick J.; Poulton, Ian D.; Hunt-Cooke, Angela; Porter, David W.; Thompson, Fiona M.; Rowland, Ros; Lawrie, Alison M.; Hill, Adrian V. S.] Univ Oxford, Jenner Inst, Ctr Clin Vaccinol & Trop Med, Oxford, England.
[Ewer, Katie J.; Douglas, Alexander D.; Collins, Katharine A.; Halstead, Fenella D.; Elias, Sean C.; Edwards, Nick J.; Draper, Simon J.; Gilbert, Sarah C.; Hill, Adrian V. S.] Univ Oxford, Jenner Inst Labs, Oxford, England.
[Rausch, Kelly; Aebig, Joan; Miura, Kazutoyo; Fay, Michael P.; Long, Carole A.; Zhu, Daming; Wu, Yimin; Martin, Laura B.; Anderson, Charles F.; Ellis, Ruth D.] NIAID, Bethesda, MD 20892 USA.
RP Duncan, CJA (reprint author), Univ Oxford, Jenner Inst, Ctr Clin Vaccinol & Trop Med, Oxford, England.
EM christopher.duncan@ndm.ox.ac.uk
RI Draper, Simon/F-1758-2011; Duncan, Christopher/A-2018-2012; Douglas,
Alexander/E-7040-2012; Martin, Laura/N-1789-2013; Ewer,
Katie/B-4328-2011;
OI Draper, Simon/0000-0002-9415-1357; Fay, Michael P./0000-0002-8643-9625;
Duncan, Christopher/0000-0003-4181-2315; Douglas,
Alexander/0000-0002-5410-7562; Martin, Laura/0000-0002-4431-4381; Ewer,
Katie/0000-0001-9827-9836; Edwards, Nick/0000-0002-7030-7839; Gilbert,
Sarah/0000-0002-6823-9750; Lillie, Patrick/0000-0002-4811-4774; Collins,
Katharine/0000-0002-7080-2215
FU National Institute of Allergy and Infectious Disease, National
Institutes of Health; UK National Institute for Health Research (NIHR)
Oxford Biomedical Research Centre; Wellcome Trust [RTEI0, 089455/2/09/2]
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Disease, National
Institutes of Health, the UK National Institute for Health Research
(NIHR) Oxford Biomedical Research Centre and the Wellcome Trust.
C.J.A.D. and A. D. D. hold Wellcome Trust Training Fellowships for
Clinicians in Basic Sciences (grant numbers RTEI0 and 089455/2/09/2
respectively). A. V. S. H., S. C. G. and S.J.D. are Jenner Institute
Investigators. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 45
TC 41
Z9 41
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 JUL 22
PY 2011
VL 6
IS 7
AR e22271
DI 10.1371/journal.pone.0022271
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 797BJ
UT WOS:000293097300024
PM 21799809
ER
PT J
AU Prince, T
Neckers, L
AF Prince, Thomas
Neckers, Len
TI A Network of Its Own: The Unique Interactome of the Hsp90 Cochaperone,
Sba1/p23
SO MOLECULAR CELL
LA English
DT Editorial Material
ID COMPLEX; CHAPERONE; PROTEIN; P23
AB In this issue of Molecular Cell, Echtenkamp et al. (2011) show that the molecular chaperone Sba1/p23, thought to function primarily as a key modulator of the Hsp90 chaperone complex, also operates in its own sphere of influence outside of its obligations to Hsp90.
C1 [Prince, Thomas; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM neckers@nih.gov
FU Intramural NIH HHS [Z01 SC010074-12, Z99 CA999999, ZIA SC010074-15, Z01
SC010074-13, ZIA SC010074-14]
NR 10
TC 2
Z9 2
U1 4
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 JUL 22
PY 2011
VL 43
IS 2
BP 159
EP 160
DI 10.1016/j.molcel.2011.07.005
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 797TG
UT WOS:000293152400002
PM 21777805
ER
PT J
AU Chernova, TA
Romanyuk, AV
Karpova, TS
Shanks, JR
Ali, M
Moffatt, N
Howie, RL
O'Dell, A
McNally, JG
Liebman, SW
Chernoff, YO
Wilkinson, KD
AF Chernova, Tatiana A.
Romanyuk, Andrey V.
Karpova, Tatiana S.
Shanks, John R.
Ali, Moiez
Moffatt, Nela
Howie, Rebecca L.
O'Dell, Andrew
McNally, James G.
Liebman, Susan W.
Chernoff, Yury O.
Wilkinson, Keith D.
TI Prion Induction by the Short-Lived, Stress-Induced Protein Lsb2 Is
Regulated by Ubiquitination and Association with the Actin Cytoskeleton
SO MOLECULAR CELL
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; YEAST PRION; PSI+ PRION; ENDOCYTIC PATHWAY;
ARP2/3 COMPLEX; SYSTEM; SUP35; PIN+; AGGREGATION; PROPAGATION
AB Yeast prions are self-perpetuating, ON-rich amyloids that control heritable traits and serve as a model for mammalian amyloidoses. De novo prion formation by overproduced prion protein is facilitated by other aggregated ON-rich protein(s) and is influenced by alterations of protein homeostasis. Here we explore the mechanism by which the Las17-binding protein Lsb2 (Pin3) promotes conversion of the translation termination factor Sup35 into its prion form, [PSI(+)]. We show that Lsb2 localizes with some Sup35 aggregates and that Lsb2 is a short-lived protein whose levels are controlled via the ubiquitin-proteasome system and are dramatically increased by stress. Loss of Lsb2 decreases stability of [PSI(+)] after brief heat shock. Mutations interfering with Lsb2 ubiquitination increase prion induction, while a mutation eliminating association of Lsb2 with the actin cytoskeleton blocks its aggregation and prion-inducing ability. These findings directly implicate the UPS and actin cytoskeleton in regulating prions via a stress-inducible QN-rich protein.
C1 [Chernova, Tatiana A.; Shanks, John R.; Ali, Moiez; Moffatt, Nela; Wilkinson, Keith D.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA.
[Romanyuk, Andrey V.; Howie, Rebecca L.; Chernoff, Yury O.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
[Romanyuk, Andrey V.; Howie, Rebecca L.; Chernoff, Yury O.] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA.
[Karpova, Tatiana S.; McNally, James G.] NCI, Ctr Canc Res, Core Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express,NIH, Bethesda, MD 20892 USA.
[O'Dell, Andrew; Liebman, Susan W.] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA.
RP Wilkinson, KD (reprint author), Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA.
EM genekdw@emory.edu
RI Chernoff, Yury/J-2833-2014;
OI Chernoff, Yury/0000-0002-8934-9051
FU NIH [GM30308, GM58763, GM56350]
FX We thank S. Lindquist, J. Frydman, D. Rotin, M. French, L. Hicke, M.
Hochstrasser, and R. Parker for reagents; N. Russel, N. Degtyareva, and
Z. Astakhova for helpful discussion; and D. Kiktev and G. Newnam for
technical help. This work was supported by the grants GM30308 (K.D.W.),
GM58763 (Y.O.C.), and GM56350 (S.W.L.) from NIH. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of NIH.
NR 44
TC 44
Z9 46
U1 1
U2 6
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 JUL 22
PY 2011
VL 43
IS 2
BP 242
EP 252
DI 10.1016/j.molcel.2011.07.001
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 797TG
UT WOS:000293152400011
PM 21777813
ER
PT J
AU Buxton, DB
AF Buxton, Denis B.
TI Nanotechnology Research Support at the National Heart, Lung, and Blood
Institute
SO CIRCULATION RESEARCH
LA English
DT Article
ID ABDOMINAL AORTIC-ANEURYSMS; MAGNETIC-RESONANCE; GROWTH; ATHEROSCLEROSIS
C1 NHLBI, Basic & Early Translat Res Program, Div Cardiovasc Sci, DCVS, Bethesda, MD 20892 USA.
RP Buxton, DB (reprint author), NHLBI, Basic & Early Translat Res Program, Div Cardiovasc Sci, DCVS, Rockledge 2,Room 8216,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM db225a@nih.gov
OI Buxton, Denis/0000-0003-3077-6435
NR 27
TC 3
Z9 3
U1 0
U2 4
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 JUL 22
PY 2011
VL 109
IS 3
BP 250
EP 254
DI 10.1161/RES.0b013e31822a97cd
PG 5
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 795FG
UT WOS:000292958200004
PM 21778434
ER
PT J
AU Kaiser, J
Varmus, H
AF Kaiser, Jocelyn
Varmus, Harold
TI Newsmaker Interview: Harold Varmus - Piloting Cancer Research With a
Shrinking Budget
SO SCIENCE
LA English
DT Editorial Material
C1 [Varmus, Harold] NIH, Bethesda, MD 20892 USA.
[Varmus, Harold] NCI, Bethesda, MD 20892 USA.
NR 0
TC 4
Z9 5
U1 0
U2 3
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 JUL 22
PY 2011
VL 333
IS 6041
BP 397
EP 397
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 795FR
UT WOS:000292959600014
ER
PT J
AU Neunuebel, MR
Chen, Y
Gaspar, AH
Backlund, PS
Yergey, A
Machner, MP
AF Neunuebel, M. Ramona
Chen, Yang
Gaspar, Andrew H.
Backlund, Peter S., Jr.
Yergey, Alfred
Machner, Matthias P.
TI De-AMPylation of the Small GTPase Rab1 by the Pathogen Legionella
pneumophila
SO SCIENCE
LA English
DT Article
ID EFFECTOR PROTEIN DRRA; ENDOPLASMIC-RETICULUM; VESICULAR TRANSPORT;
BINDING; SYSTEM; MUTANTS
AB The bacterial pathogen Legionella pneumophila exploits host cell vesicle transport by transiently manipulating the activity of the small guanosine triphosphatase (GTPase) Rab1. The effector protein SidM recruits Rab1 to the Legionella-containing vacuole (LCV), where it activates Rab1 and then AMPylates it by covalently adding adenosine monophosphate (AMP). L. pneumophila GTPase-activating protein LepB inactivates Rab1 before its removal from LCVs. Because LepB cannot bind AMPylated Rab1, the molecular events leading to Rab1 inactivation are unknown. We found that the effector protein SidD from L. pneumophila catalyzed AMP release from Rab1, generating de-AMPylated Rab1 accessible for inactivation by LepB. L. pneumophila mutants lacking SidD were defective for Rab1 removal from LCVs, identifying SidD as the missing link connecting the processes of early Rab1 accumulation and subsequent Rab1 removal during infection.
C1 [Neunuebel, M. Ramona; Chen, Yang; Gaspar, Andrew H.; Machner, Matthias P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Backlund, Peter S., Jr.; Yergey, Alfred] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biomed Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA.
[Chen, Yang] Peking Univ, Ctr Hlth Sci, Beijing 100191, Peoples R China.
RP Machner, MP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM machnerm@mail.nih.gov
RI Machner, Matthias/G-2758-2015;
OI Machner, Matthias/0000-0002-6971-7451
FU NIH
FX We thank G. Storz, S. Gottesman, J. Bonifacino, J. Neunuebel, and M.
Barzik for critical reading and insightful discussion and R. Isberg and
V. Losick for kindly providing reagents. This work was supported by the
Intramural Research Program of the NIH.
NR 20
TC 105
Z9 110
U1 1
U2 18
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 JUL 22
PY 2011
VL 333
IS 6041
BP 453
EP 456
DI 10.1126/science.1207193
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 795FR
UT WOS:000292959600046
PM 21680813
ER
PT J
AU Ascierto, PA
Marincola, FM
AF Ascierto, Paolo A.
Marincola, Francesco M.
TI Combination therapy: the next opportunity and challenge of medicine
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID MONOTHERAPY; MELANOMA
AB From an historical point of view, combination therapy was the basis for the care of important diseases like infection diseases or cancer. Today the "cocktail drug" of the Highly Active Anti Retroviral Therapy (HAART) has reduced the death for HIV infection changing the outcome of such disease. Moreover, the combination of different strategies changed the course of transplants (both in haematology and surgical transplant). Different diseases with high social impact including cardiovascular, metabolic (obesity, hypercholesterolaemia and diabetes) and autoimmune diseases, have better results with combinations of different drug classes of drugs. After recent successes in the immunotherapy field (Sepuleucel-T, ipilimumab) and the new promising small molecule therapies, cancer should be the next challenge for combination strategies.
C1 [Ascierto, Paolo A.] Fdn G Pascale, Med Oncol & Innovat Therapies Unit, Ist Nazl Studio & Cura Tumori, Naples, Italy.
[Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
RP Ascierto, PA (reprint author), Fdn G Pascale, Med Oncol & Innovat Therapies Unit, Ist Nazl Studio & Cura Tumori, Naples, Italy.
EM paolo.ascierto@gmail.com
NR 18
TC 16
Z9 17
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 21
PY 2011
VL 9
AR 115
DI 10.1186/1479-5876-9-115
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 808SR
UT WOS:000293999200001
PM 21777474
ER
PT J
AU Aguila, JR
Liao, WB
Yang, JC
Avila, C
Hagag, N
Senzel, L
Ma, YP
AF Aguila, Jerell R.
Liao, Wenbin
Yang, Jianchang
Avila, Cecilia
Hagag, Nabil
Senzel, Lisa
Ma, Yupo
TI SALL4 is a robust stimulator for the expansion of hematopoietic stem
cells
SO BLOOD
LA English
DT Article
ID EX-VIVO EXPANSION; EARLY EMBRYONIC-DEVELOPMENT; CORD BLOOD;
LEUKEMIC-CELLS; DIFFERENTIATION; PLURIPOTENCY; REGULATOR; MICE
AB HSCs are rare cells that have the unique ability to self-renew and differentiate into cells of all hematopoietic lineages. The lack of donors and current inability to rapidly and efficiently expand HSCs are roadblocks in the development of successful cell therapies. Thus, the challenge of ex vivo human HSC expansion remains a fertile and critically important area of investigation. Here, we show that either SALL4A- or SALL4B-transduced human HSCs obtained from the mobilized peripheral blood are capable of rapid and efficient expansion ex vivo by > 10 000-fold for both CD34(+)/CD38(-) and CD34(+)/CD38(+) cells in the presence of appropriate cytokines. We found that these cells retained hematopoietic precursor cell immunophenotypes and morphology as well as normal in vitro or vivo potential for differentiation. The SALL4-mediated expansion was associated with enhanced stem cell engraftment and long-term repopulation capacity in vivo. Also, we demonstrated that constitutive expression of SALL4 inhibited granulocytic differentiation and permitted expansion of undifferentiated cells in 32D myeloid progenitors. Furthermore, a TAT-SALL4B fusion rapidly expanded CD34(+) cells, and it is thus feasible to translate this study into the clinical setting. Our findings provide a new avenue for investigating mechanisms of stem cell self-renewal and achieving clinically significant expansion of human HSCs. (Blood. 2011;118(3):576-585)
C1 [Aguila, Jerell R.; Liao, Wenbin; Hagag, Nabil; Senzel, Lisa; Ma, Yupo] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA.
[Yang, Jianchang] NCI, Div Lab Med, Las Vegas, NV USA.
[Avila, Cecilia] SUNY Stony Brook, Dept Obstet & Gynecol, Stony Brook, NY 11794 USA.
RP Ma, YP (reprint author), SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA.
EM yupo.ma@stonybrook.edu
RI Liao, Wenbin/A-7146-2012
FU National Institutes of Health [NIH R01HL087948, NIH 7R01HL087948-04]
FX This work is supported in part by a grant from the National Institutes
of Health (NIH R01HL087948; Y.M.) and an NIH research fellowship for
postdoctoral training (NIH 7R01HL087948-04; J.A.).
NR 24
TC 46
Z9 50
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 JUL 21
PY 2011
VL 118
IS 3
BP 576
EP 585
DI 10.1182/blood-2011-01-333641
PG 10
WC Hematology
SC Hematology
GA 795IG
UT WOS:000292967300018
PM 21602528
ER
PT J
AU Du, M
Butchi, NB
Woods, T
Peterson, KE
AF Du, Min
Butchi, Niranjan B.
Woods, Tyson
Peterson, Karin E.
TI Poly-Thymidine Oligonucleotides Mediate Activation of Murine Glial Cells
Primarily Through TLR7, Not TLR8
SO PLOS ONE
LA English
DT Article
ID TOLL-LIKE RECEPTOR-7; CEREBROSPINAL-FLUID; IMMUNE-RESPONSES; DENDRITIC
CELLS; INNATE IMMUNITY; RECOGNITION; OLIGODEOXYNUCLEOTIDES; AGONISTS;
BRAIN; TOLL-LIKE-RECEPTOR-8
AB The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS) remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated by alternate ligands, which include vaccinia virus DNA, phosphothioate oligodeoxynucleotides (ODNs) or the combination of phosphothioate poly-thymidine oligonucleotides (pT-ODNs) with TLR7/8 agonists. In the current study, we analyzed the ability of pT-ODNs to induce activation of murine glial cells in the presence or absence of TLR7/8 agonists. We found that TLR7/8 agonists induced the expression of glial cell activation markers and induced the production of multiple proinflammatory cytokines and chemokines in mixed glial cultures. In contrast, pT-ODNs alone induced only low level expression of two cytokines, CCL2 and CXCL10. The combination of pT-ODNs along with TLR7/8 agonists induced a synergistic response with substantially higher levels of proinflammatory cytokines and chemokines compared to CL075. This enhancement was not due to cellular uptake of the agonist, indicating that the pT-ODN enhancement of cytokine responses was due to effects on an intracellular process. Interestingly, this response was also not due to synergistic stimulation of both TLR7 and TLR8, as the loss of TLR7 abolished the activation of glial cells and cytokine production. Thus, pT-ODNs act in synergy with TLR7/8 agonists to induce strong TLR7-dependent cytokine production in glial cells, suggesting that the combination of pT-ODNs with TLR7 agonists may be a useful mechanism to induce pronounced glial activation in the CNS.
C1 [Du, Min; Butchi, Niranjan B.; Woods, Tyson; Peterson, Karin E.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Du, M (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
EM petersonka@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
FU National Institutes of Health; National Center for Research Resources
[IP20RR020159]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and by National Center for Research
Resources Grant IP20RR020159. No additional external funding was
received for this funding. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
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Z9 6
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 21
PY 2011
VL 6
IS 7
AR e22454
DI 10.1371/journal.pone.0022454
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 795FA
UT WOS:000292956800059
PM 21811614
ER
PT J
AU Gilbert-Sirieix, M
Makoukji, J
Kimura, S
Talbot, M
Caillou, B
Massaad, C
Massaad-Massade, L
AF Gilbert-Sirieix, Marie
Makoukji, Joelle
Kimura, Shioko
Talbot, Monique
Caillou, Bernard
Massaad, Charbel
Massaad-Massade, Liliane
TI Wnt/beta-Catenin Signaling Pathway Is a Direct Enhancer of Thyroid
Transcription Factor-1 in Human Papillary Thyroid Carcinoma Cells
SO PLOS ONE
LA English
DT Article
ID BETA-CATENIN; NUCLEAR-LOCALIZATION; MOLECULAR-MECHANISM; CANCER-CELLS;
EXPRESSION; GENE; TARGET; LINES; TTF-1; OVEREXPRESSION
AB The Wnt/beta-catenin signaling pathway is involved in the normal development of thyroid gland, but its disregulation provokes the appearance of several types of cancers, including papillary thyroid carcinomas (PTC) which are the most common thyroid tumours. The follow-up of PTC patients is based on the monitoring of serum thyroglobulin levels which is regulated by the thyroid transcription factor 1 (TTF-1): a tissue-specific transcription factor essential for the differentiation of the thyroid. We investigated whether the Wnt/beta-catenin pathway might regulate TTF-1 expression in a human PTC model and examined the molecular mechanisms underlying this regulation. Immunofluorescence analysis, real time RT-PCR and Western blot studies revealed that TTF-1 as well as the major Wnt pathway components are co-expressed in TPC-1 cells and human PTC tumours. Knocking-down the Wnt/beta-catenin components by siRNAs inhibited both TTF-1 transcript and protein expression, while mimicking the activation of Wnt signaling by lithium chloride induced TTF-1 gene and protein expression. Functional promoter studies and ChIP analysis showed that the Wnt/beta-catenin pathway exerts its effect by means of the binding of beta-catenin to TCF/LEF transcription factors on the level of an active TCF/LEF response element at [2798, 2792 bp] in TTF-1 promoter. In conclusion, we demonstrated that the Wnt/beta-catenin pathway is a direct and forward driver of the TTF-1 expression. The localization of TCF-4 and TTF-1 in the same area of PTC tissues might be of clinical relevance, and justifies further examination of these factors in the papillary thyroid cancers follow-up.
C1 [Gilbert-Sirieix, Marie; Massaad-Massade, Liliane] Inst Gustave Roussy, CNRS, UMR 8203, Villejuif, France.
[Makoukji, Joelle; Massaad, Charbel] Univ Paris 05, CNRS, UMR 8194, Paris, France.
[Kimura, Shioko] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Talbot, Monique; Caillou, Bernard] Inst Gustave Roussy, CNRS, UMR 8200, Villejuif, France.
RP Gilbert-Sirieix, M (reprint author), Inst Gustave Roussy, CNRS, UMR 8203, Villejuif, France.
EM liliane.massade@igr.fr
FU Centre National de la Recherche Scientifique; University Paris 11;
Institut Gustave Roussy
FX This work was supported by the Centre National de la Recherche
Scientifique, by the University Paris 11, and by Institut Gustave
Roussy. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 44
TC 9
Z9 10
U1 0
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 JUL 21
PY 2011
VL 6
IS 7
AR e22280
DI 10.1371/journal.pone.0022280
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 795FA
UT WOS:000292956800037
PM 21814573
ER
PT J
AU Vargovic, P
Ukropec, J
Laukova, M
Cleary, S
Manz, B
Pacak, K
Kvetnansky, R
AF Vargovic, Peter
Ukropec, Jozef
Laukova, Marcela
Cleary, Susannah
Manz, Bernhard
Pacak, Karel
Kvetnansky, Richard
TI Adipocytes as a new source of catecholamine production
SO FEBS LETTERS
LA English
DT Article
DE Adipocyte; Endogenous catecholamine; Catecholamine biosynthetic enzyme;
Gene expression
ID PHENYLETHANOLAMINE-N-METHYLTRANSFERASE; WHITE ADIPOSE-TISSUE; NEURAL
CREST; RAT-HEART; EXPRESSION; FAT; STRESS; CELLS; GENE
AB Catecholamines are an important regulator of lipolysis in adipose tissue. Here we show that rat adipocytes, isolated from mesenteric adipose tissue, express genes of catecholamine biosynthetic enzymes and produce catecholamines de novo. Administration of tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, in vitro significantly reduced concentration of catecholamines in isolated adipocytes. We hypothesize that the sympathetic innervation of adipose tissues is not the only source of catecholamines, since adipocytes also have the capacity to produce both norepinephrine and epinephrine. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
C1 [Vargovic, Peter; Laukova, Marcela; Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, Lab Stress Res, SK-83306 Bratislava, Slovakia.
[Ukropec, Jozef] Slovak Acad Sci, Inst Expt Endocrinol, Diabet & Metab Res Lab, SK-83306 Bratislava, Slovakia.
[Manz, Bernhard] LDN Lab Diagnost Nord, D-48531 Nordhorn, Germany.
[Cleary, Susannah; Pacak, Karel] NICHD, Sect Med Neuroendocrinol, NIH, Bethesda, MD USA.
RP Vargovic, P (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Lab Stress Res, Vlarska 3, SK-83306 Bratislava, Slovakia.
EM peter.vargovic@gmail.com
FU Slovak Research and Development Agency [APVV-0148-06, APVV-0088-10];
VEGA [2/0188/09, 2/0036/11]; [Transmed1-26240120008-ERDF]
FX This research was supported by Slovak Research and Development Agency
(No. APVV-0148-06 and APVV-0088-10), Transmed1-26240120008-ERDF and VEGA
Grants (2/0188/09 and 2/0036/11).
NR 27
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD JUL 21
PY 2011
VL 585
IS 14
BP 2279
EP 2284
DI 10.1016/j.febslet.2011.06.001
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 792TK
UT WOS:000292772800024
PM 21689652
ER
PT J
AU Gurnev, PA
Rostovtseva, TK
Bezrukov, SM
AF Gurnev, Philip A.
Rostovtseva, Tatiana K.
Bezrukov, Sergey M.
TI Tubulin-blocked state of VDAC studied by polymer and ATP partitioning
SO FEBS LETTERS
LA English
DT Article
DE Voltage-dependent anion channel; Selectivity; PEG; Mitochondria;
Microtubule; Planar lipid bilayer
ID DEPENDENT ANION CHANNEL; MITOCHONDRIAL CHANNEL; VOLUME CHANGES;
PORE-SIZE; SELECTIVITY; TRANSPORT; DYNAMICS
AB Recently reported functional interaction between voltage-dependent anion channel of the outer mitochondrial membrane, VDAC, and dimeric tubulin is observed as a reversible channel blockage. Using partitioning of poly-(ethylene glycol)s of different molecular weights and reversal potential measurements, we probe the size and ion selectivity of the fully open and tubulin-blocked states of VDAC reconstituted into planar lipid bilayers. While the effective radius of the channel decreases by only a factor of 1.34 +/- 0.15, the selectivity reverses from initially anionic to cationic. Directly measuring ATP partitioning we demonstrate that these changes prohibit ATP from entering the channel in its tubulin-blocked state. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
C1 [Gurnev, Philip A.; Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Rostovtseva, TK (reprint author), NICHD, NIH, 9000 Rockville Pike,Bldg 9,Rm 1E-106, Bethesda, MD 20892 USA.
EM rostovtt@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH
FX Authors thank Kely Sheldon for VDAC purification. This study was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH.
NR 25
TC 25
Z9 25
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD JUL 21
PY 2011
VL 585
IS 14
BP 2363
EP 2366
DI 10.1016/j.febslet.2011.06.008
PG 4
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 792TK
UT WOS:000292772800038
PM 21722638
ER
PT J
AU Stuber, GD
Sparta, DR
Stamatakis, AM
van Leeuwen, WA
Hardjoprajitno, JE
Cho, S
Tye, KM
Kempadoo, KA
Zhang, F
Deisseroth, K
Bonci, A
AF Stuber, Garret D.
Sparta, Dennis R.
Stamatakis, Alice M.
van Leeuwen, Wieke A.
Hardjoprajitno, Juanita E.
Cho, Saemi
Tye, Kay M.
Kempadoo, Kimberly A.
Zhang, Feng
Deisseroth, Karl
Bonci, Antonello
TI Excitatory transmission from the amygdala to nucleus accumbens
facilitates reward seeking
SO NATURE
LA English
DT Article
ID MIDBRAIN DOPAMINE NEURONS; BASOLATERAL AMYGDALA; COCAINE-SEEKING;
BEHAVIOR; CORE; RELEASE; DISCONNECTION; INVOLVEMENT; MOTIVATION;
INTERFACE
AB The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence(1-5,21-23). The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours(4,6,7,24,25), but our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural-circuit elements of this pathway selectively during behaviour. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibres from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. Here we show that optical stimulation of the pathway from the BLA to the NAc in mice reinforces behavioural responding to earn additional optical stimulation of these synaptic inputs. Optical stimulation of these glutamatergic fibres required intra-NAc dopamine D1-type receptor signalling, but not D2-type receptor signalling. Brief optical inhibition of fibres from the BLA to the NAc reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behaviour. Moreover, although optical stimulation of glutamatergic fibres from the medial prefrontal cortex to the NAc also elicited reliable excitatory synaptic responses, optical self-stimulation behaviour was not observed by activation of this pathway. These data indicate that whereas the BLA is important for processing both positive and negative affect, the glutamatergic pathway from the BLA to the NAc, in conjunction with dopamine signalling in the NAc, promotes motivated behavioural responding. Thus, optogenetic manipulation of anatomically distinct synaptic inputs to the NAc reveals functionally distinct properties of these inputs in controlling reward-seeking behaviours.
C1 [Stuber, Garret D.; Sparta, Dennis R.; Stamatakis, Alice M.] Univ N Carolina, UNC Neurosci Ctr, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Stuber, Garret D.; Sparta, Dennis R.; Stamatakis, Alice M.] Univ N Carolina, UNC Neurosci Ctr, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA.
[Stuber, Garret D.; Sparta, Dennis R.; van Leeuwen, Wieke A.; Hardjoprajitno, Juanita E.; Cho, Saemi; Tye, Kay M.; Kempadoo, Kimberly A.; Bonci, Antonello] Univ Calif San Francisco, Wheeler Ctr Neurobiol Drug Addict, Dept Neurol, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94608 USA.
[Tye, Kay M.; Zhang, Feng; Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Tye, Kay M.; Zhang, Feng; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Stuber, GD (reprint author), Univ N Carolina, UNC Neurosci Ctr, Dept Psychiat, Chapel Hill, NC 27599 USA.
EM gstuber@med.unc.edu
RI Tye, Kay/J-6158-2013; Stuber, Garret/E-1160-2011
OI Tye, Kay/0000-0002-2435-0182;
FU NARSAD; ABMRF; Foundation of Hope; NIDA [DA029325]; Psychiatry
Department at UNC Chapel Hill; State of California through the
University of California at San Francisco; [F32AA018610]
FX We thank J. Phillips, V. Kharazia, A. Adamantidis and H.-C. Tsai for
assistance and advice. We also thank V. Gukassyan and the UNC
Neuroscience Center microscopy core facility. This study was supported
by funds from NARSAD, ABMRF, The Foundation of Hope, and NIDA
(DA029325), by startup funds provided by the Psychiatry Department at
UNC Chapel Hill (G. D. S.) and by the State of California through the
University of California at San Francisco (A. B.). D. R. S. was
supported by F32AA018610.
NR 26
TC 276
Z9 280
U1 6
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 377
EP U129
DI 10.1038/nature10194
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200042
PM 21716290
ER
PT J
AU Hessa, T
Sharma, A
Mariappan, M
Eshleman, HD
Gutierrez, E
Hegde, RS
AF Hessa, Tara
Sharma, Ajay
Mariappan, Malaiyalam
Eshleman, Heather D.
Gutierrez, Erik
Hegde, Ramanujan S.
TI Protein targeting and degradation are coupled for elimination of
mislocalized proteins
SO NATURE
LA English
DT Article
ID SIGNAL RECOGNITION PARTICLE; CYTOSOLIC PRION PROTEIN; QUALITY-CONTROL
PATHWAY; ENDOPLASMIC-RETICULUM; TRANSLOCATION CHANNEL; MEMBRANE;
NEURODEGENERATION; ER; CONTRIBUTES; SEQUENCE
AB A substantial proportion of the genome encodes membrane proteins that are delivered to the endoplasmic reticulum by dedicated targeting pathways(1). Membrane proteins that fail targeting must be rapidly degraded to avoid aggregation and disruption of cytosolic protein homeostasis(2,3). The mechanisms of mislocalized protein (MLP) degradation are unknown. Here we reconstitute MLP degradation in vitro to identify factors involved in this pathway. We find that nascent membrane proteins tethered to ribosomes are not substrates for ubiquitination unless they are released into the cytosol. Their inappropriate release results in capture by the Bag6 complex, a recently identified ribosome-associating chaperone(4). Bag6-complex-mediated capture depends on the presence of unprocessed or non-inserted hydrophobic domains that distinguish MLPs from potential cytosolic proteins. A subset of these Bag6 complex 'clients' are transferred to TRC40 for insertion into the membrane, whereas the remainder are rapidly ubiquitinated. Depletion of the Bag6 complex selectively impairs the efficient ubiquitination of MLPs. Thus, by its presence on ribosomes that are synthesizing nascent membrane proteins, the Bag6 complex links targeting and ubiquitination pathways. We propose that such coupling allows the fast tracking of MLPs for degradation without futile engagement of the cytosolic folding machinery.
C1 [Hessa, Tara; Sharma, Ajay; Mariappan, Malaiyalam; Eshleman, Heather D.; Gutierrez, Erik; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Gutierrez, Erik] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
RP Hegde, RS (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM hegde.science@gmail.com
RI mariappan, malaiyalam/K-9024-2012;
OI Hegde, Ramanujan/0000-0001-8338-852X
FU National Institutes of Health; Wenner-Gren Foundations
FX We are grateful to E. Whiteman and X. Li for carrying out the initial
experiments for parts of this project, S. W. Kang, S. Shao, and Z. Zhang
for discussions, P. Sengupta, J. Magadan, and C. Ott for constructs, J.
Taunton and J. Garrison for cotransin, S. Shao for comments on the
manuscript, and Y. Ye for discussions and sharing results before
publication. This work was supported by the Intramural Research Program
of the National Institutes of Health (R. S. H.) and a postdoctoral
fellowship from The Wenner-Gren Foundations (T.H.).
NR 38
TC 94
Z9 95
U1 4
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 21
PY 2011
VL 475
IS 7356
BP 394
EP U154
DI 10.1038/nature10181
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794PA
UT WOS:000292911200046
PM 21743475
ER
PT J
AU Polak, JF
Pencina, MJ
Pencina, KM
O'Donnell, CJ
Wolf, PA
D'Agostino, RB
AF Polak, Joseph F.
Pencina, Michael J.
Pencina, Karol M.
O'Donnell, Christopher J.
Wolf, Philip A.
D'Agostino, Ralph B., Sr.
TI Carotid-Wall Intima-Media Thickness and Cardiovascular Events
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; ATHEROSCLEROSIS RISK; ARTERIAL-WALL;
MYOCARDIAL-INFARCTION; FRAMINGHAM RISK; PREDICTION; STROKE; COMMUNITIES;
POPULATION; PLAQUE
AB Background
Intima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.
Methods
We measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.
Results
A total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P = 0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P = 0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).
Conclusions
The maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort.
C1 [Polak, Joseph F.] Tufts Med Ctr, Dept Radiol, Boston, MA 02111 USA.
[Pencina, Michael J.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Pencina, Karol M.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Wolf, Philip A.] Boston Univ, Dept Med & Neurol, Boston, MA 02215 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Framingham, MA USA.
RP Polak, JF (reprint author), Tufts Med Ctr, Dept Radiol, 800 Washington St,Box 299, Boston, MA 02111 USA.
EM jpolak@tuftsmedicalcenter.org
FU National Heart, Lung, and Blood Institute [R01 HL069003, HL081352,
N01-HC-25195]; Abbott
FX Supported by grants from the National Heart, Lung, and Blood Institute
(R01 HL069003 and HL081352, to Dr. Polak) and its Framingham Heart Study
(N01-HC-25195).; Dr. Pencina reports receiving fees for board membership
from Abbott. No other potential conflict of interest relevant to this
article was reported.
NR 36
TC 281
Z9 295
U1 3
U2 8
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 21
PY 2011
VL 365
IS 3
BP 213
EP 221
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 794QI
UT WOS:000292915500005
PM 21774709
ER
PT J
AU Kim, S
Bolton, EE
Bryant, SH
AF Kim, Sunghwan
Bolton, Evan E.
Bryant, Stephen H.
TI PubChem3D: Shape compatibility filtering using molecular shape
quadrupoles
SO JOURNAL OF CHEMINFORMATICS
LA English
DT Article
ID GAUSSIAN DESCRIPTION; MOLAR VOLUMES; INFORMATION
AB Background: PubChem provides a 3-D neighboring relationship, which involves finding the maximal shape overlap between two static compound 3-D conformations, a computationally intensive step. It is highly desirable to avoid this overlap computation, especially if it can be determined with certainty that a conformer pair cannot meet the criteria to be a 3-D neighbor. As such, PubChem employs a series of pre-filters, based on the concept of volume, to remove approximately 65% of all conformer neighbor pairs prior to shape overlap optimization. Given that molecular volume, a somewhat vague concept, is rather effective, it leads one to wonder: can the existing PubChem 3-D neighboring relationship, which consists of billions of shape similar conformer pairs from tens of millions of unique small molecules, be used to identify additional shape descriptor relationships? Or, put more specifically, can one place an upper bound on shape similarity using other "fuzzy" shape-like concepts like length, width, and height?
Results: Using a basis set of 4.18 billion 3-D neighbor pairs identified from single conformer per compound neighboring of 17.1 million molecules, shape descriptors were computed for all conformers. These steric shape descriptors included several forms of molecular volume and shape quadrupoles, which essentially embody the length, width, and height of a conformer. For a given 3-D neighbor conformer pair, the volume and each quadrupole component (Q(x), Q(y), and Q(z)) were binned and their frequency of occurrence was examined. Per molecular volume type, this effectively produced three different maps, one per quadrupole component (Q(x), Q(y), and Q(z)), of allowed values for the similarity metric, shape Tanimoto (ST) >= 0.8. The efficiency of these relationships (in terms of true positive, true negative, false positive and false negative) as a function of ST threshold was determined in a test run of 13.2 billion conformer pairs not previously considered by the 3-D neighbor set. At an ST >= 0.8, a filtering efficiency of 40.4% of true negatives was achieved with only 32 false negatives out of 24 million true positives, when applying the separate Q(x), Q(y), and Q(z) maps in a series (Q(xyz)). This efficiency increased linearly as a function of ST threshold in the range 0.8-0.99. The Q(x) filter was consistently the most efficient followed by Q(y) and then by Q(z). Use of a monopole volume showed the best overall performance, followed by the self-overlap volume and then by the analytic volume.
Application of the monopole-based Q(xyz) filter in a "real world" test of 3-D neighboring of 4,218 chemicals of biomedical interest against 26.1 million molecules in PubChem reduced the total CPU cost of neighboring by between 24-38% and, if used as the initial filter, removed from consideration 48.3% of all conformer pairs at almost negligible computational overhead.
Conclusion: Basic shape descriptors, such as those embodied by size, length, width, and height, can be highly effective in identifying shape incompatible compound conformer pairs. When performing a 3-D search using a shape similarity cut-off, computation can be avoided by identifying conformer pairs that cannot meet the result criteria. Applying this methodology as a filter for PubChem 3-D neighboring computation, an improvement of 31% was realized, increasing the average conformer pair throughput from 154,000 to 202,000 per second per CPU core.
C1 [Kim, Sunghwan; Bolton, Evan E.; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
RP Bolton, EE (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
RI Kim, Sunghwan/A-6738-2008
OI Kim, Sunghwan/0000-0001-9828-2074
FU National Library of Medicine, National Institutes of Health, U.S.
Department of Health and Human Services
FX We are grateful to the NCBI Systems staff, especially Ron Patterson,
Charlie Cook, and Don Preuss, whose efforts helped make the PubChem3D
project possible. This research was supported by the Intramural Research
Program of the National Library of Medicine, National Institutes of
Health, U.S. Department of Health and Human Services.
NR 20
TC 7
Z9 7
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2946
J9 J CHEMINFORMATICS
JI J. Cheminformatics
PD JUL 20
PY 2011
VL 3
AR 25
DI 10.1186/1758-2946-3-25
PG 14
WC Chemistry, Multidisciplinary; Computer Science, Information Systems;
Computer Science, Interdisciplinary Applications
SC Chemistry; Computer Science
GA 891OX
UT WOS:000300227600001
PM 21774809
ER
PT J
AU Yedavalli, VSRK
Jeang, KT
AF Yedavalli, Venkat S. R. K.
Jeang, Kuan-Teh
TI Matrin 3 is a co-factor for HIV-1 Rev in regulating post-transcriptional
viral gene expression
SO RETROVIROLOGY
LA English
DT Article
DE Matrin 3; HIV-1; Rev; RNA export; nuclear matrix protein
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONSTITUTIVE TRANSPORT ELEMENT;
MESSENGER-RNA EXPORT; NUCLEAR-PORE COMPLEX; PROTEIN INTERACTIONS;
SPLICING FACTOR; TYPE-1; ORGANIZATION; ARCHITECTURE; MICROENVIRONMENTS
AB Post-transcriptional regulation of HIV-1 gene expression is mediated by interactions between viral transcripts and viral/cellular proteins. For HIV-1, post-transcriptional nuclear control allows for the export of intron-containing RNAs which are normally retained in the nucleus. Specific signals on the viral RNAs, such as instability sequences (INS) and Rev responsive element (RRE), are binding sites for viral and cellular factors that serve to regulate RNA-export. The HIV-1 encoded viral Rev protein binds to the RRE found on unspliced and incompletely spliced viral RNAs. Binding by Rev directs the export of these RNAs from the nucleus to the cytoplasm. Previously, Rev co-factors have been found to include cellular factors such as CRM1, DDX3, PIMT and others. In this work, the nuclear matrix protein Matrin 3 is shown to bind Rev/RRE-containing viral RNA. This binding interaction stabilizes unspliced and partially spliced HIV-1 transcripts leading to increased cytoplasmic expression of these viral RNAs.
C1 [Yedavalli, Venkat S. R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU NIAID; office of the Director, NIH
FX Work in KTJ's laboratory was supported in part by Intramural funds from
NIAID, and by the Intramural AIDS Targeted Antiviral Program (IATAP)
from the office of the Director, NIH. We thank members of KTJ's
laboratory for reading and commenting on the manuscript, and Barbara
Felber for sharing several critical reagents. We are grateful to Anna
Kula and Alessandro Marcello for sharing data in their paper prior to
publication [75].
NR 75
TC 25
Z9 25
U1 0
U2 9
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 JUL 20
PY 2011
VL 8
AR 61
DI 10.1186/1742-4690-8-61
PG 10
WC Virology
SC Virology
GA 813FY
UT WOS:000294353400002
PM 21771347
ER
PT J
AU Ro, HJ
Dawid, IB
AF Ro, Hyunju
Dawid, Igor B.
TI Modulation of Tcf3 repressor complex composition regulates cdx4
expression in zebrafish
SO EMBO JOURNAL
LA English
DT Article
DE caudal body domain; Cdx4; E4f1; Tcf3; Wnt signalling
ID HOX GENE-EXPRESSION; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE
MYELOID-LEUKEMIA; E3 UBIQUITIN LIGASE; TRANSCRIPTION FACTOR;
BETA-CATENIN; CELL FATE; OVERLAPPING FUNCTIONS; AXIS SPECIFICATION;
IN-VIVO
AB The caudal homeobox (cdx) gene family is critical for specification of caudal body formation and erythropoiesis. In zebrafish, cdx4 expression is controlled by the Wnt pathway, but the molecular mechanism of this regulation is not fully understood. Here, we provide evidence that Tcf3 suppresses cdx4 expression through direct binding to multiple sites in the cdx4 gene regulatory region. Tcf3 requires corepressor molecules such as Groucho (Gro)/TLE and HDAC1 for activity. Using zebrafish embryos and cultured mammalian cells, we show that the transcription factor E4f1 derepresses cdx4 by dissociating corepressor proteins from Tcf3 without inhibiting its binding to cis-regulatory sites in the DNA. Further, the E3 ubiquitin ligase Lnx2b, acting as a scaffold protein irrespective of its enzymatic activity, counteracts the effects of E4f1. We propose that the modulation of Tcf3 repressor function by E4f1 assures precise and robust regulation of cdx4 expression in the caudal domain of the embryo. The EMBO Journal ( 2011) 30, 2894- 2907. doi:10.1038/emboj.2011.184; Published online 10 June 2011
C1 [Ro, Hyunju; Dawid, Igor B.] NICHHD, Mol Genet Lab, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, Program Genom Differentiat, NIH, Bldg 6,Rm 413,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM idawid@nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health
FX We thank M Rath and J Gonzales for help with fish maintenance. We
especially thank Dr RI Dorsky for the Tcf3a antibody and Drs S-Y Choi,
DE Ayer and A Chitnis for other reagents. This work was supported by the
Intramural Research Program of the National Institute of Child Health
and Human Development, National Institutes of Health.
NR 74
TC 12
Z9 13
U1 0
U2 6
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 JUL 20
PY 2011
VL 30
IS 14
BP 2894
EP 2907
DI 10.1038/emboj.2011.184
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 808HZ
UT WOS:000293970100015
PM 21666599
ER
PT J
AU Berezhkovskii, AM
Lizunov, VA
Zimmerberg, J
Bezrukov, SM
AF Berezhkovskii, Alexander M.
Lizunov, Vladimir A.
Zimmerberg, Joshua
Bezrukov, Sergey M.
TI Functional Role for Transporter Isoforms in Optimizing Membrane
Transport
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID CHANNELS; BINDING
AB Quantitative analysis of carrier parameters demonstrates that with decreasing substrate concentration the optimal strength of substrate-carrier interaction which maximizes the flux across the membrane increases and requires less fine-tuning than at higher concentrations of the substrate.
C1 [Lizunov, Vladimir A.; Zimmerberg, Joshua; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Berezhkovskii, Alexander M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol,NIH, Bethesda, MD USA.
RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM bezrukos@mail.nih.gov
FU National Institutes of Health; Center for Information Technology; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, Center for Information Technology, and
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 15
TC 1
Z9 1
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JUL 20
PY 2011
VL 101
IS 2
BP L14
EP L16
DI 10.1016/j.bpj.2011.06.004
PG 3
WC Biophysics
SC Biophysics
GA 797VT
UT WOS:000293158900004
PM 21767474
ER
PT J
AU Benko, W
Ries, M
Wiggs, EA
Brady, RO
Schiffmann, R
FitzGibbon, EJ
AF Benko, William
Ries, Markus
Wiggs, Edythe A.
Brady, Roscoe O.
Schiffmann, Raphael
FitzGibbon, Edmond J.
TI The Saccadic and Neurological Deficits in Type 3 Gaucher Disease
SO PLOS ONE
LA English
DT Article
ID OPTOKINETIC NYSTAGMUS; SUPERIOR COLLICULUS; CLINICAL-TRIALS; NORMATIVE
DATA; CHILDREN; PATHOPHYSIOLOGY; ABNORMALITIES; MOVEMENTS; MIGLUSTAT;
ENZYME
AB Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8-28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials. Trial Registration: ClinicalTrials.gov NCT00001289
C1 [Benko, William; Wiggs, Edythe A.; Brady, Roscoe O.; Schiffmann, Raphael] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA.
[Ries, Markus] Univ Childrens Hosp, Heidelberg, Germany.
[Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA.
[FitzGibbon, Edmond J.] NEI, NIH, Bethesda, MD 20892 USA.
RP Benko, W (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA.
EM Raphael.Schiffmann@Baylorhealth.edu
OI Ries, Markus/0000-0002-5054-5741
FU National Institutes of Health (NINDS, NEI); Genzyme Corporation; Shire
HGT; Amicus Therapeutics
FX This work was supported only by the Intramural Program of the National
Institutes of Health (NINDS, NEI). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.; Research grants and honoraria from
Genzyme Corporation, Shire HGT and Amicus Therapeutics.
NR 29
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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 JUL 20
PY 2011
VL 6
IS 7
AR e22410
DI 10.1371/journal.pone.0022410
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794WE
UT WOS:000292931200052
PM 21799847
ER
PT J
AU Schleicher, SM
Thotala, DK
Linkous, AG
Hu, R
Leahy, KM
Yazlovitskaya, EM
Hallahan, DE
AF Schleicher, Stephen M.
Thotala, Dinesh K.
Linkous, Amanda G.
Hu, Rong
Leahy, Kathleen M.
Yazlovitskaya, Eugenia M.
Hallahan, Dennis E.
TI Autotaxin and LPA Receptors Represent Potential Molecular Targets for
the Radiosensitization of Murine Glioma through Effects on Tumor
Vasculature
SO PLOS ONE
LA English
DT Article
ID LYSOPHOSPHATIDIC ACID RECEPTORS; CANCER METASTASIS; CELL MOTILITY; AKT;
PATHWAY; IDENTIFICATION; ANGIOGENESIS; MECHANISMS; INVASION; ANALOGS
AB Despite wide margins and high dose irradiation, unresectable malignant glioma (MG) is less responsive to radiation and is uniformly fatal. We previously found that cytosolic phospholipase A2 (cPLA(2)) is a molecular target for radiosensitizing cancer through the vascular endothelium. Autotaxin (ATX) and lysophosphatidic acid (LPA) receptors are downstream from cPLA(2) and highly expressed in MG. Using the ATX and LPA receptor inhibitor, alpha-bromomethylene phosphonate LPA (BrP-LPA), we studied ATX and LPA receptors as potential molecular targets for the radiosensitization of tumor vasculature in MG. Treatment of Human Umbilical Endothelial cells (HUVEC) and mouse brain microvascular cells bEND. 3 with 5 mu mol/L BrP-LPA and 3 Gy irradiation showed decreased clonogenic survival, tubule formation, and migration. Exogenous addition of LPA showed radioprotection that was abrogated in the presence of BrP-LPA. In co-culture experiments using bEND. 3 and mouse GL-261 glioma cells, treatment with BrP-LPA reduced Akt phosphorylation in both irradiated cell lines and decreased survival and migration of irradiated GL-261 cells. Using siRNA to knock down LPA receptors LPA1, LPA2 or LPA3 in HUVEC, we demonstrated that knockdown of LPA2 but neither LPA1 nor LPA3 led to increased viability and proliferation. However, knockdown of LPA1 and LPA3 but not LPA2 resulted in complete abrogation of tubule formation implying that LPA1 and LPA3 on endothelial cells are likely targets of BrP-LPA radiosensitizing effect. Using heterotopic tumor models of GL-261, mice treated with BrP-LPA and irradiation showed a tumor growth delay of 6.8 days compared to mice treated with irradiation alone indicating that inhibition of ATX and LPA receptors may significantly improve malignant glioma response to radiation therapy. These findings identify ATX and LPA receptors as molecular targets for the development of radiosensitizers for MG.
C1 [Schleicher, Stephen M.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Yazlovitskaya, Eugenia M.] Vanderbilt Univ, Dept Med, Div Nephrol, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Linkous, Amanda G.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
[Thotala, Dinesh K.; Hu, Rong; Leahy, Kathleen M.; Hallahan, Dennis E.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA.
[Hallahan, Dennis E.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA.
[Hallahan, Dennis E.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
RP Schleicher, SM (reprint author), Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
EM dhallahan@radonc.wustl.edu
FU U.S. National Cancer Institute [1R01CA140220-02, 5R01CA125757-06,
7R01CA112385-0]; Siteman Cancer Research Award; Elizabeth and James
McDonnell III Endowment; Howard Hughes Medical Institute-Ivy Foundation;
Department of Radiation Oncology Startup Funds
FX This work was supported by U.S. National Cancer Institute grants
1R01CA140220-02, 5R01CA125757-06, 7R01CA112385-0, Siteman Cancer
Research Award, Elizabeth and James McDonnell III Endowment (D.
Hallahan), Howard Hughes Medical Institute-Ivy Foundation Research
Training Fellowship (www.hhmi.org) (S. Schleicher), and Department of
Radiation Oncology Startup Funds (D. Thotala). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 39
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 20
PY 2011
VL 6
IS 7
AR e22182
DI 10.1371/journal.pone.0022182
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794WE
UT WOS:000292931200033
PM 21799791
ER
PT J
AU van Bemmel, DM
Boffetta, P
Liao, LM
Berndt, SI
Menashe, I
Yeager, M
Chanock, S
Karami, S
Zaridze, D
Matteev, V
Janout, V
Kollarova, H
Bencko, V
Navratilova, M
Szeszenia-Dabrowska, N
Mates, D
Slamova, A
Rothman, N
Han, SS
Rosenberg, PS
Brennan, P
Chow, WH
Moore, LE
AF van Bemmel, Dana M.
Boffetta, Paolo
Liao, Linda M.
Berndt, Sonja I.
Menashe, Idan
Yeager, Meredith
Chanock, Stephen
Karami, Sara
Zaridze, David
Matteev, Vsevolod
Janout, Vladimir
Kollarova, Hellena
Bencko, Vladimir
Navratilova, Marie
Szeszenia-Dabrowska, Neonilia
Mates, Dana
Slamova, Alena
Rothman, Nathaniel
Han, Summer S.
Rosenberg, Philip S.
Brennan, Paul
Chow, Wong-Ho
Moore, Lee E.
TI Comprehensive Analysis of 5-Aminolevulinic Acid Dehydrogenase (ALAD)
Variants and Renal Cell Carcinoma Risk among Individuals Exposed to Lead
SO PLOS ONE
LA English
DT Article
ID AMINOLEVULINATE DEHYDRATASE POLYMORPHISM; BLOOD LEAD; GENETIC
SUSCEPTIBILITY; KIDNEY CANCER; WORKERS; POPULATION; PORPHYRIA; SMOKING;
EASTERN; EUROPE
AB Background: Epidemiologic studies are reporting associations between lead exposure and human cancers. A polymorphism in the 5-aminolevulinic acid dehydratase (ALAD) gene affects lead toxicokinetics and may modify the adverse effects of lead.
Methods: The objective of this study was to evaluate single-nucleotide polymorphisms (SNPs) tagging the ALAD region among renal cancer cases and controls to determine whether genetic variation alters the relationship between lead and renal cancer. Occupational exposure to lead and risk of cancer was examined in a case-control study of renal cell carcinoma (RCC). Comprehensive analysis of variation across the ALAD gene was assessed using a tagging SNP approach among 987 cases and 1298 controls. Occupational lead exposure was estimated using questionnaire-based exposure assessment and expert review. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression.
Results: The adjusted risk associated with the ALAD variant rs8177796(CT/TT) was increased (OR = 1.35, 95%CI = 1.05-1.73, p-value = 0.02) when compared to the major allele, regardless of lead exposure. Joint effects of lead and ALAD rs2761016 suggest an increased RCC risk for the homozygous wild-type and heterozygous alleles ((OR)-O-GG = 2.68, 95%CI = 1.17-6.12, p = 0.01; (OR)-O-GA = 1.79, 95%CI = 1.06-3.04 with an interaction approaching significance (p(int) = 0.06).. No significant modification in RCC risk was observed for the functional variant rs1800435((K68N)). Haplotype analysis identified a region associated with risk supporting tagging SNP results.
Conclusion: A common genetic variation in ALAD may alter the risk of RCC overall, and among individuals occupationally exposed to lead. Further work in larger exposed populations is warranted to determine if ALAD modifies RCC risk associated with lead exposure.
C1 [van Bemmel, Dana M.] NCI, Canc Prevent Fellowship Program, Off Director, Bethesda, MD 20892 USA.
[van Bemmel, Dana M.; Liao, Linda M.; Berndt, Sonja I.; Menashe, Idan; Karami, Sara; Rothman, Nathaniel; Han, Summer S.; Rosenberg, Philip S.; Chow, Wong-Ho; Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Yeager, Meredith; Chanock, Stephen] NCI, Core Genotyping Facil, Gaithersburg, MD USA.
[Boffetta, Paolo; Brennan, Paul] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo; Brennan, Paul] Int Prevent Res Inst, Lyon, France.
[Zaridze, David; Matteev, Vsevolod] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Janout, Vladimir; Kollarova, Hellena] Palacky Univ, Dept Prevent Med, Fac Med, CR-77147 Olomouc, Czech Republic.
[Bencko, Vladimir; Slamova, Alena] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic.
[Navratilova, Marie] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Lodz, Poland.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
RP van Bemmel, DM (reprint author), NCI, Canc Prevent Fellowship Program, Off Director, Bethesda, MD 20892 USA.
EM vanbemmeld@mail.nih.gov
RI Liao, Linda/B-3960-2011; Zaridze, David/K-5605-2013; Janout,
Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010;
OI Liao, Linda/0000-0002-1923-5294; mates, dana/0000-0002-6219-9807
FU NIH (National Cancer Institute Division of Cancer Epidemiology and
Genetics and the National Institute of Environmental Health Sciences)
FX This research was supported by the Intramural Research Program of the
NIH (National Cancer Institute Division of Cancer Epidemiology and
Genetics and the National Institute of Environmental Health Sciences).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
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U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 20
PY 2011
VL 6
IS 7
AR e20432
DI 10.1371/journal.pone.0020432
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794WE
UT WOS:000292931200002
PM 21799727
ER
PT J
AU Trunova, S
Baek, B
Giniger, E
AF Trunova, Svetlana
Baek, Brian
Giniger, Edward
TI Cdk5 Regulates the Size of an Axon Initial Segment-Like Compartment in
Mushroom Body Neurons of the Drosophila Central Brain
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CYCLIN-DEPENDENT KINASE-5; CELL-ADHESION MOLECULE; K+ CHANNEL; IN-VIVO;
MEMBRANE; POLARITY; ANKYRIN; P35; LOCALIZATION; EXCITABILITY
AB The axon initial segment (AIS) is the specialized compartment of vertebrate axons where action potentials are initiated. Despite longtime attention to the unique functions of this compartment, the mechanisms that regulate AIS formation and maintenance are not known. Here, we identify a novel compartment in Drosophila mushroom body neurons that mirrors the molecular hallmarks of the vertebrate AIS as judged by accumulation of the anchoring protein Ankyrin1, presence of a specialized actin cytoskeleton, exclusion of both axon-specific and somatodendritic-specific cell surface proteins, and accumulation of a unique combination of voltage-gated ion channels. Using pharmacological treatments, we show that, similar to the vertebrate AIS, the integrity of this region of gamma-neurons and its ability to tether membrane proteins depends on an intact actin cytoskeleton. We further show that Cdk5/p35 kinase regulates the formation and maintenance of the putative AIS by controlling the position of its distal boundary. Thus, boosting Cdk5 activity in gamma-neurons extends the AIS by as much as 100%, while eliminating Cdk5 activity causes the domain to shrink proximally or disappear altogether. These data demonstrate that Cdk5/p35 kinase is a key regulator of the development and maintenance of the AIS in Drosophila.
C1 [Trunova, Svetlana; Baek, Brian; Giniger, Edward] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Giniger, E (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 35 Convent Dr,Room 1C1002, Bethesda, MD 20892 USA.
EM ginigere@ninds.nih.gov
RI Giniger, Edward/C-1764-2015
OI Giniger, Edward/0000-0002-8340-6158
FU NINDS, NIH [Z01 NS003106]
FX This work was supported by the Basic Neuroscience Program of the NINDS
Intramural Research Program, NIH Grant Z01 NS003106. We thank Morgan
Sheng and Bruce Tempel for helpful discussion; Stephen Wincovitch for
help with confocal microscopy; and Ben White, Mark Stopfer, Julie
Simpson, Chi-hon Lee, and the Giniger Laboratory for comments on this
manuscript. We also thank Ben White, Ron Dubreuil, Liqun Luo, Yasushi
Hiromi, and Andreas Prokop for providing reagents and especially thank
Julie Simpson for sharing unpublished Elk and Shal transgenic strains.
NR 41
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Z9 20
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 JUL 20
PY 2011
VL 31
IS 29
BP 10451
EP 10462
DI 10.1523/JNEUROSCI.0117-11.2011
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 794SH
UT WOS:000292921100006
PM 21775591
ER
PT J
AU Murata, K
Imai, M
Nakanishi, S
Watanabe, D
Pastan, I
Kobayashi, K
Nihira, T
Mochizuki, H
Yamada, S
Mori, K
Yamaguchi, M
AF Murata, Koshi
Imai, Maki
Nakanishi, Shigetada
Watanabe, Dai
Pastan, Ira
Kobayashi, Kazuto
Nihira, Tomoko
Mochizuki, Hideki
Yamada, Shuichi
Mori, Kensaku
Yamaguchi, Masahiro
TI Compensation of Depleted Neuronal Subsets by New Neurons in a Local Area
of the Adult Olfactory Bulb
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID METABOTROPIC GLUTAMATE-RECEPTOR; CELL-ADHESION MOLECULE;
CENTRAL-NERVOUS-SYSTEM; GRANULE CELLS; SUBVENTRICULAR ZONE; INTERNEURON
SUBTYPES; SYNAPTIC INTEGRATION; NEWBORN NEURONS; STEM-CELLS;
NEUROGENESIS
AB In the olfactory bulb (OB), loss of preexisting granule cells (GCs) and incorporation of adult-born new GCs continues throughout life. GCs consist of distinct subsets. Here, we examined whether the loss and incorporation of GC subsets are coordinated in the OB. We classified GCs into mGluR2-expressing and -negative subsets and selectively ablated mGluR2-expressing GCs in a local area of the OB with immunotoxin-mediated cell ablation method. The density of mGluR2-expressing GCs showed considerable recovery within several weeks after the ablation. During recovery, an mGluR2-expressing new GC subset was preferentially incorporated over an mGluR2-negative new GC subset in the area of ablation, whereas the preferential incorporation was not observed in the intact area. The area-specific preferential incorporation of mGluR2-expressing new GCs occurred for BrdU analog-and retrovirus-labeled adult-born cells as well as for neonate-derived transplanted cells. The mGluR2-expressing new GCs in the ablated area were synaptically incorporated into the local bulbar circuit. The spine size of mGluR2-expressing new GCs in the ablated area was larger than that of those in the intact area. In contrast, mGluR2-negative new GCs did not show ablated area-specific spine enlargement. These results indicate that local OB areas have a mechanism to coordinate the loss and incorporation of GC subsets by compensatory incorporation of new GC subsets, which involves subset-specific cellular incorporation and subset-specific regulation of spine size.
C1 [Yamaguchi, Masahiro] Univ Tokyo, Grad Sch Med, Dept Physiol, Bunkyo Ku, Tokyo 1130033, Japan.
[Nakanishi, Shigetada] Osaka Biosci Inst, Dept Syst Biol, Osaka 5650874, Japan.
[Watanabe, Dai] Kyoto Univ, Fac Med, Dept Biol Sci, Kyoto 6068501, Japan.
[Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kobayashi, Kazuto] Med Univ, Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan.
[Nihira, Tomoko; Mochizuki, Hideki] Kitasato Univ, Sch Med, Dept Neurol, Kanagawa 2520374, Japan.
[Yamada, Shuichi] Kyoto Univ, Inst Virus Res, Dept Cell Biol, Lab Signal Transduct, Kyoto 6068507, Japan.
[Murata, Koshi; Mori, Kensaku; Yamaguchi, Masahiro] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Tokyo 1130033, Japan.
RP Yamaguchi, M (reprint author), Univ Tokyo, Grad Sch Med, Dept Physiol, Bunkyo Ku, Hongo 7-3-1, Tokyo 1130033, Japan.
EM yamaguti@m.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology, Japan;
Japan Society for the Promotion of Science (JSPS), Japan; JSPS; NIH,
National Cancer Institute, Center for Cancer Research
FX This work was supported by a Grant-in-Aid for Scientific Research on
Priority Areas from the Ministry of Education, Culture, Sports, Science,
and Technology, Japan (K.Mo., M.Y.) and a Grant-in-Aid for Scientific
Research from Japan Society for the Promotion of Science (JSPS), Japan
(K.Mo., M.Y.). K. Mu. was supported by JSPS Research Fellowship for
Young Scientists. This research was also supported in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. We thank Dr. K. Sawamoto and Dr. N. Kaneko
for technical assistance with cell transplantation, Dr. M. Onodera for
retroviral vectors, and the members of the Department of Physiology at
the University of Tokyo for valuable discussion and comments.
NR 60
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Z9 11
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 JUL 20
PY 2011
VL 31
IS 29
BP 10540
EP 10557
DI 10.1523/JNEUROSCI.1285-11.2011
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA 794SH
UT WOS:000292921100014
PM 21775599
ER
PT J
AU Rudebeck, PH
Murray, EA
AF Rudebeck, Peter H.
Murray, Elisabeth A.
TI Dissociable Effects of Subtotal Lesions within the Macaque Orbital
Prefrontal Cortex on Reward-Guided Behavior
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FRONTAL-LOBE DAMAGE; ORBITOFRONTAL CORTEX; DECISION-MAKING;
RHESUS-MONKEYS; NEUROTOXIC LESIONS; AMYGDALA; PERFORMANCE; EXTINCTION;
CHOICES; TASK
AB The macaque orbital prefrontal cortex (PFo) has been implicated in a wide range of reward-guided behaviors essential for efficient foraging. The PFo, however, is not a homogeneous structure. Two major subregions, distinct by their cytoarchitecture and connections to other brain structures, compose the PFo. One subregion encompasses Walker's areas 11 and 13 and the other centers on Walker's area 14. Although it has been suggested that these subregions play dissociable roles in reward-guided behavior, direct neuropsychological evidence for this hypothesis is limited. To explore the independent contributions of PFo subregions to behavior, we studied rhesus monkeys (Macaca mulatta) with restricted excitotoxic lesions targeting either Walker's areas 11/13 or area 14. The performance of these two groups was compared to that of a group of unoperated controls on a series of reward-based tasks that has been shown to be sensitive to lesions of the PFo as a whole (Walker's areas 11, 13, and 14). Lesions of areas 11/13, but not area 14, disrupted the rapid updating of object value during selective satiation. In contrast, lesions targeting area 14, but not areas 11/13, impaired the ability of monkeys to learn to stop responding to a previously rewarded object. Somewhat surprisingly, neither lesion disrupted performance on a serial object reversal learning task, although aspiration lesions of the entire PFo produce severe deficits on this task. Our data indicate that anatomically defined subregions within macaque PFo make dissociable contributions to reward-guided behavior.
C1 [Rudebeck, Peter H.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Rudebeck, PH (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, 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 National Institute of Mental Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health. We thank Dawn Lundgren, Emily
Howland, and Anna Prescott for assistance with data collection, Richard
Saunders and Rachel Reoli for help performing surgery, and Steve Wise
and Janine Simmons for useful comments on the manuscript. We also thank
the staff of the Nuclear Magnetic Resonance Facility, National Institute
of Neurological Disorder and Stroke, and the Laboratory of Diagnostic
and Radiology Research, as well as Megan Malloy for assistance in
obtaining the MR scans.
NR 40
TC 69
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U1 1
U2 11
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 20
PY 2011
VL 31
IS 29
BP 10569
EP 10578
DI 10.1523/JNEUROSCI.0091-11.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 794SH
UT WOS:000292921100016
PM 21775601
ER
PT J
AU Wendler, D
AF Wendler, David
TI Research Enrollment and Informed Consent Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM dwendler@nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 20
PY 2011
VL 306
IS 3
BP 266
EP 266
DI 10.1001/jama.2011.986
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 794BS
UT WOS:000292870500015
ER
PT J
AU Hadigan, C
Kottilil, S
AF Hadigan, Colleen
Kottilil, Shyamasundaran
TI Hepatitis C Virus Infection and Coinfection With Human Immunodeficiency
Virus Challenges and Advancements in Management
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; ALPHA-2A PLUS RIBAVIRIN; CHRONIC HCV
INFECTION; GENOTYPE 1 INFECTION; PEGINTERFERON ALPHA-2A; UNITED-STATES;
DOUBLE-BLIND; PEGYLATED INTERFERON-ALPHA-2A; NONALCOHOLIC
STEATOHEPATITIS; FIBROSIS PROGRESSION
AB Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) both emerged in the second half of the 20th century, and chronic infection with these agents is among the greatest challenges facing health care in the United States and worldwide. Despite tremendous advances in treatment and management of HIV and HCV, individuals with HIV/HCV coinfection experience a more complicated disease course and treatment. Recognition of the important role that host factors, such as IL28B genotype, have in response to HCV therapy and the emergence of new effective therapies for HCV are actively reshaping the standard of care. These advances may translate into more effective treatment and management of patients with chronic HCV and HIV coinfection in the years ahead.
C1 [Hadigan, Colleen; Kottilil, Shyamasundaran] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Hadigan, C (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11C103, Bethesda, MD 20892 USA.
EM hadiganc@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases
FX The National Institute of Allergy and Infectious Diseases Intramural
Research Program funded preparation of the manuscript.
NR 63
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U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 20
PY 2011
VL 306
IS 3
BP 294
EP 301
DI 10.1001/jama.2011.975
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 794BS
UT WOS:000292870500022
PM 21771990
ER
PT J
AU Kristinsson, SY
Bjorkholm, M
Hultcrantz, M
Derolf, AR
Landgren, O
Goldin, LR
AF Kristinsson, Sigurdur Y.
Bjorkholm, Magnus
Hultcrantz, Malin
Derolf, Asa R.
Landgren, Ola
Goldin, Lynn R.
TI Chronic Immune Stimulation Might Act As a Trigger for the Development of
Acute Myeloid Leukemia or Myelodysplastic Syndromes
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID THERAPY-RELATED MYELODYSPLASIA; WALDENSTROM MACROGLOBULINEMIA;
HEMATOPOIETIC MALIGNANCIES; RHEUMATOID-ARTHRITIS; HODGKIN-LYMPHOMA;
RISK-FACTORS; AUTOIMMUNE; DISORDERS; SWEDEN; TRANSFORMATION
AB Purpose
Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) often present with infections, but there are little data to assess whether a personal history of selected infections may act as pathogenic triggers. To additionally expand our knowledge on the role of immune stimulation in the causation of AML and MDS, we have conducted a large, population-based study to evaluate the risk of AML and MDS associated with a prior history of a broad range of infections or autoimmune diseases.
Patients and Methods
By using population-based central registries in Sweden, we included 9,219 patients with AML, 1,662 patients with MDS, and 42,878 matched controls. We used logistic regression to calculate odds ratios (ORs) and 95% CIs for the association of AML or MDS with infectious and/or autoimmune diseases.
Results
Overall, a history of any infectious disease was associated with a significantly increased risk of both AML (OR, 1.3; 95% CI, 1.2 to 1.4) and MDS (OR, 1.3; 95% CI, 1.1 to 1.5). These associations were significant even when we limited infections to those occurring 3 or more years before AML/MDS. A previous history of any autoimmune disease was associated with a 1.7-fold (95% CI, 1.5 to 1.9) increased risk for AML and 2.1-fold (95% CI, 1.7 to 2.6) increased risk for MDS. A large range of conditions were each significantly associated with AML and MDS.
Conclusion
Our novel findings indicate that chronic immune stimulation acts as a trigger for AML/MDS development. The underlying mechanisms may also be due to a common genetic predisposition or an effect of treatment for infections/autoimmune conditions. J Clin Oncol 29:2897-2903. (C) 2011 by American Society of Clinical Oncology
C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Hultcrantz, Malin; Derolf, Asa R.; Landgren, Ola] Karolinska Univ Hosp Solna, Stockholm, Sweden.
[Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Hultcrantz, Malin; Derolf, Asa R.; Landgren, Ola] Karolinska Inst, Stockholm, Sweden.
[Landgren, Ola; Goldin, Lynn R.] NCI, NIH, Bethesda, MD 20892 USA.
RP Kristinsson, SY (reprint author), Karolinska Univ Hosp, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
EM sigurdur.kristinsson@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU Swedish Cancer Society; Stockholm County Council; Karolinska Institutet
Foundations; National Cancer Institute, National Institutes of Health;
Adolf H. Lundin Charitable foundation
FX Supported by grants from the Swedish Cancer Society, the Stockholm
County Council, the Karolinska Institutet Foundations, the Intramural
Research Program of the National Cancer Institute, National Institutes
of Health, and the Adolf H. Lundin Charitable foundation.
NR 31
TC 58
Z9 62
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 JUL 20
PY 2011
VL 29
IS 21
BP 2897
EP 2903
DI 10.1200/JCO.2011.34.8540
PG 7
WC Oncology
SC Oncology
GA 793KF
UT WOS:000292819700019
PM 21690473
ER
PT J
AU Simon, R
AF Simon, Richard
TI Does Topoisomerase II-Alpha Gene Amplification Provide Useful
Information for Treatment Selection in Patients With Breast Carcinoma?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 NCI, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Bethesda, MD 20892 USA.
NR 4
TC 1
Z9 1
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 JUL 20
PY 2011
VL 29
IS 21
BP 2941
EP 2941
DI 10.1200/JCO.2011.34.9795
PG 1
WC Oncology
SC Oncology
GA 793KF
UT WOS:000292819700025
PM 21670460
ER
PT J
AU Daher, M
Lacouture, ME
Rathkopf, D
Maki, RG
Keohan, ML
Gansukh, B
Chen, H
Abou-Alfa, GK
AF Daher, May
Lacouture, Mario E.
Rathkopf, Dana
Maki, Robert G.
Keohan, Mary Louise
Gansukh, Bolorsukh
Chen, Helen
Abou-Alfa, Ghassan K.
TI Case Series of Dermatologic Events Associated With the Insulin-Like
Growth Factor Receptor 1 Inhibitor Cixutumumab
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID IRON-DEFICIENCY ANEMIA; FACTOR-I RECEPTOR; PYCNODYSOSTOSIS; KOILONYCHIA;
HORMONE; DISEASE; CANCER; SKIN; IGF
C1 [Daher, May] Amer Univ Beirut, Beirut, Lebanon.
[Lacouture, Mario E.; Rathkopf, Dana; Maki, Robert G.; Keohan, Mary Louise; Gansukh, Bolorsukh; Abou-Alfa, Ghassan K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Chen, Helen] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Daher, M (reprint author), Amer Univ Beirut, Beirut, Lebanon.
OI Rathkopf, Dana/0000-0002-4503-7582
FU National Cancer Institute (NCI) [3U01CA069856-15S1, CA148260, CA008747,
NO1-CM62206]; American Society of Clinical Oncology Foundation-NCI
FX Supported by Grant No. 3U01CA069856-15S1, National Cancer Institute
(NCI) ACTNOW funding award, Early Clinical Trials of New Anti-Cancer
Agents With Phase I Emphasis (D. R.), NCI Grants No. CA148260, CA008747,
American Society of Clinical Oncology Foundation-NCI Clinical Team
Leader Award (R. G. M.), and Grant No. NO1-CM62206, NCI Phase II
Contract (Memorial Sloan-Kettering Cancer Center; G. K. A., R. G. M.)
NR 18
TC 4
Z9 4
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2011
VL 29
IS 21
BP E638
EP E640
DI 10.1200/JCO.2010.34.5116
PG 3
WC Oncology
SC Oncology
GA 793KF
UT WOS:000292819700008
PM 21606420
ER
PT J
AU Liu, CL
Liu, AY
Halabi, S
AF Liu, Chunling
Liu, Aiyi
Halabi, Susan
TI A min-max combination of biomarkers to improve diagnostic accuracy
SO STATISTICS IN MEDICINE
LA English
DT Article
DE area under curves; linear combinations; receiver operating
characteristic (ROC) curve; robustness; sensitivity; specificity
ID CHARACTERISTIC ROC CURVES; TESTS; AREA; MARKERS; CANCER
AB Diagnostic accuracy can be improved considerably by combining multiple biomarkers. Although the likelihood ratio provides optimal solution to combination of biomarkers, the method is sensitive to distributional assumptions which are often difficult to justify. Alternatively simple linear combinations can be considered whose empirical solution may encounter intensive computation when the number of biomarkers is relatively large. Moreover, the optimal linear combinations derived under multivariate normality may suffer substantial loss of efficiency if the distributions are apart from normality. In this paper, we propose a new approach that linearly combines the minimum and maximum values of the biomarkers. Such combination only involves searching for a single combination coefficient that maximizes the area under the receiver operating characteristic (ROC) curves and is thus computation-effective. Simulation results show that the min-max combination may yield larger partial or full area under the ROC curves and is more robust against distributional assumptions. The methods are illustrated using the growth-related hormones data from the Growth and Maturation in Children with Autism or Autistic Spectrum Disorder Study (Autism/ASD Study). Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Liu, Chunling; Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
[Liu, Chunling] Hong Kong Polytech Univ, Dept Appl Math, Hong Kong, Hong Kong, Peoples R China.
[Halabi, Susan] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27708 USA.
RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
EM liua@mail.nih.gov
OI Liu, Aiyi/0000-0002-6618-5082
FU National Institute of Child Health and Human Development (NICHD);
National Institutes of Health (NIH)
FX Research of the first two authors was supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD), the National Institutes of
Health (NIH). The authors thank Dr James L. Mills and Dr Kai F. Yu for
helpful discussions on the autism data example. The authors thank the
Editor, Associate Editor, and two referees for their constructive
comments, and Dr Paul Albert for helpful discussions.
NR 14
TC 15
Z9 15
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD JUL 20
PY 2011
VL 30
IS 16
BP 2005
EP 2014
DI 10.1002/sim.4238
PG 10
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 791UH
UT WOS:000292691300006
PM 21472763
ER
PT J
AU Lippincott-Schwartz, J
AF Lippincott-Schwartz, Jennifer
TI Bridging Structure and Process in Developmental Biology through New
Imaging Technologies
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
ID LEFT-RIGHT ASYMMETRY; ILLUMINATION MICROSCOPY; FLUORESCENT PROTEIN;
LIVING CELLS; PLANE ILLUMINATION; RESOLUTION; RECONSTRUCTION;
MORPHOGENESIS; CANCER; PROBES
AB Many unexpected discoveries in developmental biology have depended on advancement of imaging technologies to visualize developmental processes as they unfold across multiple spatial and temporal scales. This essay surveys the recent advances in imaging, highlighting emerging capabilities with an eye toward those poised to have the greatest impact on developmental biology.
C1 Eunice Kennedy Shriver Inst Child Hlth & Human De, NIH, Bethesda, MD 20892 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Inst Child Hlth & Human De, NIH, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov
FU Intramural NIH HHS [ZIA HD001609-19]
NR 45
TC 10
Z9 10
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
EI 1878-1551
J9 DEV CELL
JI Dev. Cell
PD JUL 19
PY 2011
VL 21
IS 1
SI SI
BP 5
EP 10
DI 10.1016/j.devcel.2011.06.030
PG 6
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 799TY
UT WOS:000293310200003
PM 21763598
ER
PT J
AU Martinou, JC
Youle, RJ
AF Martinou, Jean-Claude
Youle, Richard J.
TI Mitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial
Dynamics
SO DEVELOPMENTAL CELL
LA English
DT Review
ID CYTOCHROME-C RELEASE; PROGRAMMED CELL-DEATH; OUTER-MEMBRANE
PERMEABILIZATION; STRESS-INDUCED APOPTOSIS; LIPIDIC PORE FORMATION;
BAX-DERIVED PEPTIDE; PROAPOPTOTIC BAX; BH3-ONLY PROTEINS;
SUBCELLULAR-LOCALIZATION; EMBRYONIC-DEVELOPMENT
AB Mitochondria participate in apoptosis through a range of mechanisms that vary between vertebrates and invertebrates. In vertebrates, they release intermembrane space proteins, such as cytochrome c, to promote caspase activation in the cytosol. This process is the result of the loss of integrity of the outer mitochondrial membrane caused by proapoptotic members of the Bcl-2 family. This event is always accompanied by a fissioning of the organelle. Fission of mitochondria has also been reported to participate in apoptosis in Drosophila and Caenorhabditis elegans. However, in these organisms, mitochondrial membrane permeabilization does not occur and the mechanism by which mitochondrial dynamics participates in cell death remains elusive.
C1 [Martinou, Jean-Claude] Univ Geneva, Dept Cell Biol, Fac Sci, CH-1211 Geneva 4, Switzerland.
[Martinou, Jean-Claude; Youle, Richard J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Martinou, JC (reprint author), Univ Geneva, Dept Cell Biol, Fac Sci, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.
EM jean-claude.martinou@unige.ch; youler@ninds.nih.gov
FU Swiss National Foundation [31003A-124968/1]; Oncosuisse; Geneva
Department of Education; NINDS, NIH
FX We thank Drs. Megan Cleland and Soojay Banerjee for help with artwork.
J.-C.M is supported by the Swiss National Foundation (subsidy
31003A-124968/1), Oncosuisse, and the Geneva Department of Education.
R.J.Y. is supported by the Intramural Program of the NINDS, NIH.
NR 116
TC 501
Z9 568
U1 21
U2 152
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 JUL 19
PY 2011
VL 21
IS 1
SI SI
BP 92
EP 101
DI 10.1016/j.devcel.2011.06.017
PG 10
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 799TY
UT WOS:000293310200016
PM 21763611
ER
PT J
AU De Leon, JT
Iwai, A
Feau, C
Garcia, Y
Balsiger, HA
Storer, CL
Suro, RM
Garza, KM
Lee, S
Kim, YS
Chen, Y
Ning, YM
Riggs, DL
Fletterick, RJ
Guy, RK
Trepel, JB
Neckers, LM
Cox, MB
AF De Leon, Johanny Tonos
Iwai, Aki
Feau, Clementine
Garcia, Yenni
Balsiger, Heather A.
Storer, Cheryl L.
Suro, Raquel M.
Garza, Kristine M.
Lee, Sunmin
Kim, Yeong Sang
Chen, Yu
Ning, Yang-Min
Riggs, Daniel L.
Fletterick, Robert J.
Guy, R. Kiplin
Trepel, Jane B.
Neckers, Leonard M.
Cox, Marc B.
TI Targeting the regulation of androgen receptor signaling by the heat
shock protein 90 cochaperone FKBP52 in prostate cancer cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE immunophilin; FKBP4; steroid hormone receptor
ID HSP90; COMPENDIUM; EXPRESSION; REPORTER; BINDING; LINES; OLD
AB Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function. The lead compound, termed MJC13, inhibits AR function by preventing hormone-dependent dissociation of the Hsp90-FKBP52-AR complex, which results in less hormone-bound receptor in the nucleus. Assays in early and late stage human prostate cancer cells demonstrated that MJC13 inhibits AR-dependent gene expression and androgen-stimulated prostate cancer cell proliferation.
C1 [De Leon, Johanny Tonos; Garcia, Yenni; Balsiger, Heather A.; Storer, Cheryl L.; Suro, Raquel M.; Garza, Kristine M.; Cox, Marc B.] Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA.
[De Leon, Johanny Tonos; Garcia, Yenni; Balsiger, Heather A.; Storer, Cheryl L.; Suro, Raquel M.; Garza, Kristine M.; Cox, Marc B.] Univ Texas El Paso, Border Biomed Res Ctr, El Paso, TX 79968 USA.
[Iwai, Aki; Neckers, Leonard M.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Feau, Clementine; Guy, R. Kiplin] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA.
[Lee, Sunmin; Kim, Yeong Sang; Trepel, Jane B.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Chen, Yu] Univ S Florida, Dept Mol Med, Tampa, FL 33612 USA.
[Ning, Yang-Min] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Riggs, Daniel L.] Mayo Clin Arizona, Scottsdale, AZ 85259 USA.
[Fletterick, Robert J.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
RP Cox, MB (reprint author), Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA.
EM mbcox@utep.edu
RI Guy, Rodney/J-7107-2013
OI Guy, Rodney/0000-0002-9638-2060
FU Border Biomedical Research Center's [National Center for Research
Resources/National Institutes of Health (NIH)] [5G12RR008124]; National
Institute of General Medical Sciences, NIH [SC1GM084863]; Research
Initiative for Scientific Enhancement [R25GM069621]; National Science
Foundation [HRD-0832951]; American Lebanese Syrian Associated Charities;
St. Jude Children's Research Hospital; NIH [DK58080]; Department of
Defense [PC060344-W81XWH-07-1-0073]; National Cancer Institute
FX We thank Brian Freeman, Charles Sawyers, Robert Reiter, David Toft, and
Donald Tindall for providing reagents. The authors are grateful to David
Smith and Charles Miller for critically reading the manuscript. We thank
the Border Biomedical Research Center's [Grant 5G12RR008124, National
Center for Research Resources/National Institutes of Health (NIH)]
Biomolecule Analysis Core Facility, Tissue Culture Core Facility, and
the DNA Analysis Core Facility for the use of the instruments. This
project was also supported in part by American Recovery and Reinvestment
Act funds through Grant SC1GM084863 to M. B. C. from the National
Institute of General Medical Sciences, NIH. J.T.D.L. was supported by
Research Initiative for Scientific Enhancement (R25GM069621) and
National Science Foundation Louis Stokes Alliances for Minority
Participation (HRD-0832951) fellowships. R. K. G. and C. F. were
supported by the American Lebanese Syrian Associated Charities, St. Jude
Children's Research Hospital, the NIH (DK58080), and the Department of
Defense Prostate Cancer Research Program (PC060344-W81XWH-07-1-0073). A.
I., S. L., Y.S.K., Y.N., J.B.T., and L.M.N. were supported by funds from
the Intramural Research Program of the National Cancer Institute.
NR 20
TC 54
Z9 54
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 19
PY 2011
VL 108
IS 29
BP 11878
EP 11883
DI 10.1073/pnas.1105160108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794DY
UT WOS:000292876900038
PM 21730179
ER
PT J
AU Kimble, JB
Sorrell, E
Shao, HX
Martin, PL
Perez, DR
AF Kimble, J. Brian
Sorrell, Erin
Shao, Hongxia
Martin, Philip L.
Perez, Daniel Roberto
TI Compatibility of H9N2 avian influenza surface genes and 2009 pandemic
H1N1 internal genes for transmission in the ferret model
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE TRIG cassette; preparedness; infection; pathology; ecology
ID A VIRUS; HUMAN INFECTION; SWINE; HEMAGGLUTININ; ORIGIN; REASSORTMENT;
PATHOGENESIS; REPLICATION; POULTRY; H3N2
AB In 2009, a novel H1N1 influenza (pH1N1) virus caused the first influenza pandemic in 40 y. The virus was identified as a triple reassortant between avian, swine, and human influenza viruses, highlighting the importance of reassortment in the generation of viruses with pandemic potential. Previously, we showed that a reassortant virus composed of wild-type avian H9N2 surface genes in a seasonal human H3N2 backbone could gain efficient respiratory droplet transmission in the ferret model. Here we determine the ability of the H9N2 surface genes in the context of the internal genes of a pH1N1 virus to efficiently transmit via respiratory droplets in ferrets. We generated reassorted viruses carrying the HA gene alone or in combination with the NA gene of a prototypical H9N2 virus in the background of a pH1N1 virus. Four reassortant viruses were generated, with three of them showing efficient respiratory droplet transmission. Differences in replication efficiency were observed for these viruses; however, the results clearly indicate that H9N2 avian influenza viruses and pH1N1 viruses, both of which have occasionally infected pigs, have the potential to reassort and generate novel viruses with respiratory transmission potential in mammals.
C1 [Kimble, J. Brian; Sorrell, Erin; Shao, Hongxia; Perez, Daniel Roberto] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA.
[Kimble, J. Brian; Sorrell, Erin; Shao, Hongxia; Perez, Daniel Roberto] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Martin, Philip L.] NCI, Ctr Adv Preclin Res, Sci Applicat Int Corp, Frederick, MD 21702 USA.
RP Perez, DR (reprint author), Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA.
EM dperez1@umd.edu
RI Wei, Jianjian/F-7788-2011;
OI Wei, Jianjian/0000-0001-8859-8462; Perez, Daniel/0000-0002-6569-5689
FU Centers for Disease Control and Prevention-Department of Health and
Human Services [1U01CI000355-01]; National Institute of Food and
Agriculture-US Department of Agriculture [2007-04981]; National
Institute of Allergy and Infectious Diseases-National Institutes of
Health [HHSN266200700010C]; US Department of Agriculture-Agricultural
Research Service
FX We thank Troy Sutton, Lindomar Pena, and Yonas Araya for their help with
animal studies; Jianqiang Ye for assistance with the ELISA assays; Amy
Vincent for her assistance with the immunohistochemistry protocol; and
Theresa Wolter-Marth and Andrea Ferrero for coordination of animal
studies. This research was funded by Grants 1U01CI000355-01 from the
Centers for Disease Control and Prevention-Department of Health and
Human Services and 2007-04981 from the National Institute of Food and
Agriculture-US Department of Agriculture, and Contract HHSN266200700010C
from the National Institute of Allergy and Infectious Diseases-National
Institutes of Health, and a Cooperative Agreement from the US Department
of Agriculture-Agricultural Research Service.
NR 27
TC 66
Z9 68
U1 1
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 JUL 19
PY 2011
VL 108
IS 29
BP 12084
EP 12088
DI 10.1073/pnas.1108058108
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794DY
UT WOS:000292876900073
PM 21730147
ER
PT J
AU Zhou, XM
Izumi, Y
Burg, MB
Ferraris, JD
AF Zhou, Xiaoming
Izumi, Yuichiro
Burg, Maurice B.
Ferraris, Joan D.
TI Rac1/osmosensing scaffold for MEKK3 contributes via phospholipase
C-gamma 1 to activation of the osmoprotective transcription factor NFAT5
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE osmotic stress; MAPK
ID OSMOTIC RESPONSE ELEMENT; NACL-INDUCED ACTIVATION; FACTOR TONEBP/OREBP;
INDUCED PHOSPHORYLATION; NUCLEAR-LOCALIZATION; GROWTH-FACTOR;
KIDNEY-CELLS; P38 KINASE; PROTEIN; RAC1
AB Separate reports that hypertonicity activates p38 via a Rac1-OSMMEKK3- MKK3-p38 pathway and that p38a contributes to activation of TonEBP/OREBP led us to the hypothesis that Rac1 might activate TonEBP/OREBP via p38. The present studies examine that possibility. High NaCl is hypertonic. We find that siRNA knockdown of Rac1 reduces high NaCl-induced increase of TonEBP/OREBP transcriptional activity (by reducing its transactivating activity but not its nuclear localization). Similarly, siRNA knockdown of osmosensing scaffold for MEKK3 (OSM) also reduces high NaCl-dependent TonEBP/OREBP transcriptional and transactivating activities. Simultaneous siRNA knockdown of Rac1 and OSM is not additive in reduction of TonEBP/OREBP transcriptional activity, indicating a common pathway. However, siRNA knockdown of MKK3 does not reduce TonEBP/OREBP transcriptional activity, although siRNA knockdown of MKK6 does. Nevertheless, the effect of Rac1 on TonEBP/OREBP is also independent of MKK6 because it occurs in MKK6-null cells. Furthermore, we find that siRNA knockdown of Rac1 or OSM actually increases activity (phosphorylation) of p38, rather than decreasing it, as previously reported. Thus, the effect of Rac1 on TonEBP/OREBP is independent of p38. We find instead that phospholipase C-gamma 1 (PLC-gamma 1) is involved. When transfected into PLC gamma 1- null mouse embryonic fibroblast cells, catalytically active Rac1 does not increase TonEBP/OREBP transcriptional activity unless PLC-gamma 1 is reconstituted. Similarly, dominant-negative Rac1 also does not inhibit TonEBP/OREBP in PLC-gamma 1-null cells unless PLC-gamma 1 is reconstituted. We conclude that Rac1/OSM supports TonEBP/OREBP activity and that this activity is mediated via PLC-gamma 1, not p38.
C1 [Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Izumi, Yuichiro; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Zhou, XM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Room A3060, Bethesda, MD 20814 USA.
EM xiazhou@usuhs.mil; maurice_burg@nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Department of Health and Human Services; Uniformed Services
University of the Health Sciences, Department of Defense [CO83WU]
FX We thank Dr. Roger J. Davis for MKK6-/- MEFs, Dr. Graham
Carpenter for PLC-gamma 1+/+ and PLC-gamma 1-/-
MEFs, Dr. Andras Kapus for Rac1 mutant constructs, and Dr. Norman P.
Curthoys for pTRE2-Flag-dnMKK6 plasmid. This study was supported by the
Intramural Research Program of the National Heart, Lung, and Blood
Institute, National Institutes of Health, Department of Health and Human
Services and by Grant CO83WU from the Uniformed Services University of
the Health Sciences, Department of Defense.
NR 40
TC 14
Z9 15
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 JUL 19
PY 2011
VL 108
IS 29
BP 12155
EP 12160
DI 10.1073/pnas.1108107108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794DY
UT WOS:000292876900085
PM 21712438
ER
PT J
AU Dalet, A
Robbins, PF
Stroobant, V
Vigneron, N
Li, YF
El-Gamil, M
Hanada, K
Yang, JC
Rosenberg, SA
Van den Eynde, BJ
AF Dalet, Alexandre
Robbins, Paul F.
Stroobant, Vincent
Vigneron, Nathalie
Li, Yong F.
El-Gamil, Mona
Hanada, Ken-ichi
Yang, James C.
Rosenberg, Steven A.
Van den Eynde, Benoit J.
TI An antigenic peptide produced by reverse splicing and double asparagine
deamidation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antigen processing; peptide splicing; tumor antigen
ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; I-RESTRICTED
EPITOPE; OPEN READING FRAME; ENDOPLASMIC-RETICULUM; HLA-A2 MELANOMAS;
ENVELOPE GLYCOPROTEIN; PROCESSING PATHWAY; TYROSINASE EPITOPE;
INTERFERON-GAMMA
AB A variety of unconventional translational and posttranslational mechanisms contribute to the production of antigenic peptides, thereby increasing the diversity of the peptide repertoire presented by MHC class I molecules. Here, we describe a class I-restricted peptide that combines several posttranslational modifications. It is derived from tyrosinase and recognized by tumor-infiltrating lymphocytes isolated from a melanoma patient. This unusual antigenic peptide is made of two noncontiguous tyrosinase fragments that are spliced together in the reverse order. In addition, it contains two aspartate residues that replace the asparagines encoded in the tyrosinase sequence. We confirmed that this peptide is naturally presented at the surface of melanoma cells, and we showed that its processing sequentially requires translation of tyrosinase into the endoplasmic reticulum and its retrotranslocation into the cytosol, where deglycosylation of the two asparagines by peptide-N-glycanase turns them into aspartates by deamidation. This process is followed by cleavage and splicing of the appropriate fragments by the standard proteasome and additional transport of the resulting peptide into the endoplasmic reticulum through the transporter associated with antigen processing (TAP).
C1 [Dalet, Alexandre; Stroobant, Vincent; Vigneron, Nathalie; Van den Eynde, Benoit J.] Catholic Univ Louvain, Ludwig Inst Canc Res, Brussels Branch, B-1200 Brussels, Belgium.
[Dalet, Alexandre; Stroobant, Vincent; Vigneron, Nathalie; Van den Eynde, Benoit J.] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium.
[Robbins, Paul F.; Li, Yong F.; El-Gamil, Mona; Hanada, Ken-ichi; Yang, James C.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20854 USA.
RP Van den Eynde, BJ (reprint author), Catholic Univ Louvain, Ludwig Inst Canc Res, Brussels Branch, B-1200 Brussels, Belgium.
EM Benoit.Vandeneynde@bru.licr.org
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
FU European Community [LSHC-2006-518234]; Walloon Region Programme
d'Excellence CIBLES; Fonds J. Maisin (Belgium); Fondation contre le
Cancer (Belgium); Fonds National de la Recherche Scientifique (FNRS;
Belgium); FNRS
FX We thank Luc Pilotte and Aline Depasse for excellent technical
assistance and Julie Klein for editorial assistance. This work was
supported by the European Community under Sixth Framework Program Grant
LSHC-2006-518234 (Cancer Immunotherapy), the Walloon Region Programme
d'Excellence CIBLES, the Fonds J. Maisin (Belgium), the Fondation contre
le Cancer (Belgium), and the Fonds National de la Recherche Scientifique
(FNRS; Belgium). A.D. is supported by a Televie fellowship from the
FNRS, and N.V. is a post-doctoral researcher with the FNRS.
NR 55
TC 25
Z9 25
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 JUL 19
PY 2011
VL 108
IS 29
BP E323
EP E331
DI 10.1073/pnas.1101892108
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 794DY
UT WOS:000292876900009
PM 21670269
ER
PT J
AU Combs, GF
Watts, JC
Jackson, MI
Johnson, LK
Zeng, HW
Scheett, AJ
Uthus, EO
Schomburg, L
Hoeg, A
Hoefig, CS
Davis, CD
Milner, JA
AF Combs, Gerald F., Jr.
Watts, Jennifer C.
Jackson, Matthew I.
Johnson, LuAnn K.
Zeng, Huawei
Scheett, Angela J.
Uthus, Eric O.
Schomburg, Lutz
Hoeg, Antonia
Hoefig, Carolin S.
Davis, Cindy D.
Milner, John A.
TI Determinants of selenium status in healthy adults
SO NUTRITION JOURNAL
LA English
DT Article
ID GLUTATHIONE-PEROXIDASE-ACTIVITY; SELENOPROTEIN-P; CANCER PREVENTION;
3'-UNTRANSLATED REGION; PLASMA SELENIUM; PROSTATE-CANCER; VITAMIN-E;
SUPPLEMENTATION; EXPRESSION; TRIAL
AB Background: Selenium (Se) status in non-deficient subjects is typically assessed by the Se contents of plasma/serum. That pool comprises two functional, specific selenoprotein components and at least one non-functional, non-specific components which respond differently to changes in Se intake. A more informative means of characterizing Se status in non-deficient individuals is needed.
Methods: Multiple biomarkers of Se status (plasma Se, serum selenoprotein P [SEPP1], plasma glutathione peroxidase activity [GPX3], buccal cell Se, urinary Se) were evaluated in relation to selenoprotein genotypes (GPX1, GPX3, SEPP1, SEP15), dietary Se intake, and parameters of single-carbon metabolism in a cohort of healthy, non-Se-deficient men (n = 106) and women (n = 155).
Conclusions: Plasma Se concentration was 142.0 +/- 23.5 ng/ml, with GPX3 and serum-derived SEPP1 calculated to comprise 20% and 34%, respectively, of that total. The balance, comprised of non-specific components, accounted for virtually all of the interindividual variation in total plasma Se. Buccal cell Se was associated with age and plasma homocysteine (hCys), but not plasma Se. SEPP1 showed a quadratic relationship with body mass index, peaking at BMI 25-30. Urinary Se was greater in women than men, and was associated with metabolic body weight (kg(0.75)), plasma folate, vitamin B-12 and hCys (negatively). One GPX1 genotype (679T/T) was associated with significantly lower plasma Se levels than other allelic variants. Selenium intake, estimated from food frequency questionnaires, did not predict Se status as indicated by any biomarker. These results show that genotype, methyl-group status and BMI contribute to variation in Se biomarkers in Se-adequate individuals.
C1 [Combs, Gerald F., Jr.; Watts, Jennifer C.; Jackson, Matthew I.; Johnson, LuAnn K.; Zeng, Huawei; Scheett, Angela J.; Uthus, Eric O.] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
[Schomburg, Lutz; Hoeg, Antonia; Hoefig, Carolin S.] Inst Expt Endokrinol, Berlin, Germany.
[Davis, Cindy D.; Milner, John A.] NCI, Nutr Sci Res Grp, Nutr & Canc Program, Bethesda, MD 20892 USA.
RP Combs, GF (reprint author), USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA.
EM gerald.combs@ars.usda.gov
NR 53
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U1 0
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2891
J9 NUTR J
JI Nutr. J.
PD JUL 18
PY 2011
VL 10
AR 75
DI 10.1186/1475-2891-10-75
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 812CY
UT WOS:000294266500001
PM 21767397
ER
PT J
AU Xiao, S
Kumar, M
Yang, XL
Akkoyunlu, M
Collins, PL
Samal, SK
Pal, U
AF Xiao, Sa
Kumar, Manish
Yang, Xiuli
Akkoyunlu, Mustafa
Collins, Peter L.
Samal, Siba K.
Pal, Utpal
TI A host-restricted viral vector for antigen-specific immunization against
Lyme disease pathogen
SO VACCINE
LA English
DT Article
DE Borrelia burgdorferi; Newcastle disease virus; Lyme disease;
Immunization; Vaccine
ID OUTER-SURFACE PROTEIN; AVIAN INFLUENZA-VIRUS; NEWCASTLE-DISEASE;
BORRELIA-BURGDORFERI; VACCINE VECTOR; ACTIVE IMMUNIZATION;
RESPIRATORY-TRACT; FOREIGN GENE; OSPC; MICE
AB Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two B. burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. By contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (10(8) cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Xiao, Sa; Kumar, Manish; Yang, Xiuli; Samal, Siba K.; Pal, Utpal] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA.
[Akkoyunlu, Mustafa] US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Dept Vet Med, Bldg 795,Room 1341, College Pk, MD 20742 USA.
EM ssamal@umd.edu; upal@umd.edu
RI Akkoyunlu, Mustafa/I-5712-2012; Pal, Utpal/I-5265-2015
FU NIH/NIAID [AI080615, AR055323, N01A060009]; NIH
FX This research was supported in part by NIH/NIAID Awards (AI080615 and
AR055323), NIH/NIAID Contract N01A060009 and NIH Intramural Research
Program. We sincerely thank Alexis Smith for her excellent assistance
with this study.
NR 65
TC 7
Z9 8
U1 0
U2 2
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 JUL 18
PY 2011
VL 29
IS 32
BP 5294
EP 5303
DI 10.1016/j.vaccine.2011.05.010
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 808OB
UT WOS:000293987200028
PM 21600949
ER
PT J
AU Ellong, EN
Soni, KG
Bui, QT
Sougrat, R
Golinelli-Cohen, MP
Jackson, CL
AF Ellong, Emy Njoh
Soni, Krishnakant G.
Quynh-Trang Bui
Sougrat, Rachid
Golinelli-Cohen, Marie-Pierre
Jackson, Catherine L.
TI Interaction between the Triglyceride Lipase ATGL and the Arf1 Activator
GBF1
SO PLOS ONE
LA English
DT Article
ID NUCLEOTIDE EXCHANGE FACTORS; CHANARIN-DORFMAN-SYNDROME; ADP-RIBOSYLATION
FACTORS; TRANS-GOLGI NETWORK; LIPID DROPLETS; SACCHAROMYCES-CEREVISIAE;
PROTEIN; LIPOLYSIS; FAMILY; PATATIN
AB The Arf1 exchange factor GBF1 (Golgi Brefeldin A resistance factor 1) and its effector COPI are required for delivery of ATGL (adipose triglyceride lipase) to lipid droplets (LDs). Using yeast two hybrid, co-immunoprecipitation in mammalian cells and direct protein binding approaches, we report here that GBF1 and ATGL interact directly and in cells, through multiple contact sites on each protein. The C-terminal region of ATGL interacts with N-terminal domains of GBF1, including the catalytic Sec7 domain, but not with full-length GBF1 or its entire N-terminus. The N-terminal lipase domain of ATGL (called the patatin domain) interacts with two C-terminal domains of GBF1, HDS (Homology downstream of Sec7) 1 and HDS2. These two domains of GBF1 localize to lipid droplets when expressed alone in cells, but not to the Golgi, unlike the full-length GBF1 protein, which localizes to both. We suggest that interaction of GBF1 with ATGL may be involved in the membrane trafficking pathway mediated by GBF1, Arf1 and COPI that contributes to the localization of ATGL to lipid droplets.
C1 [Ellong, Emy Njoh; Quynh-Trang Bui; Golinelli-Cohen, Marie-Pierre; Jackson, Catherine L.] CNRS, Lab Enzymol & Biochim Struct, Gif Sur Yvette, France.
[Soni, Krishnakant G.; Sougrat, Rachid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA.
RP Ellong, EN (reprint author), CNRS, Lab Enzymol & Biochim Struct, Bat 34, Gif Sur Yvette, France.
EM jackson@ijm.univ-paris-diderot.fr
RI Jackson, Catherine/A-3421-2013; Golinelli, Marie-Pierre/K-4287-2013;
OI Jackson, Catherine/0000-0002-0843-145X; Golinelli,
Marie-Pierre/0000-0002-6738-8631; Sougrat, Rachid/0000-0001-6476-1886
FU ANR; CNRS; Fondation pour la Recherche Medicale (FRM); NICHD; Ministere
de l'Enseignement Superieur et de la Recherche
FX This work was funded by a grant from the ANR (Chaire d'Excellence), the
CNRS, the Fondation pour la Recherche Medicale (FRM), and the Intramural
Program of NICHD. ENE was supported by a fellowship from the Ministere
de l'Enseignement Superieur et de la Recherche. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
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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 JUL 18
PY 2011
VL 6
IS 7
AR e21889
DI 10.1371/journal.pone.0021889
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 793HY
UT WOS:000292812400019
PM 21789191
ER
PT J
AU Taha, TE
James, MM
Hoover, DR
Sun, J
Laeyendecker, O
Mullis, CE
Kumwenda, JJ
Lingappa, JR
Auvert, B
Morrison, CS
Mofensen, LM
Taylor, A
Fowler, MG
Kumenda, NI
Eshleman, SH
AF Taha, E. Taha
James, Maria M.
Hoover, Donald R.
Sun, Jin
Laeyendecker, Oliver
Mullis, Caroline E.
Kumwenda, Johnstone J.
Lingappa, Jairam R.
Auvert, Bertran
Morrison, Charles S.
Mofensen, Lynne M.
Taylor, Allan
Fowler, Mary G.
Kumenda, Newton I.
Eshleman, Susan H.
TI Association of recent HIV infection and in-utero HIV-1 transmission
SO AIDS
LA English
DT Article
DE HIV; incidence; Malawi; mother-to-child transmission; multiassay
algorithm
ID CAPTURE ENZYME-IMMUNOASSAY; TO-CHILD TRANSMISSION; PERINATAL
TRANSMISSION; PREGNANT-WOMEN; PREVENTION; RISK; AFRICA; TRIAL; RNA;
PROPHYLAXIS
AB Objective: We previously developed a multiassay algorithm (MAA) to identify recent HIV infection that includes the BED-capture enzyme immunoassay, an avidity assay based on the Genetic Systems HIV-1/HIV-2+O enzyme immunoassay, CD4 cell count, and HIV viral load. We used this MAA to evaluate the association between recent maternal HIV infection and in-utero transmission of HIV.
Methods: Plasma samples were collected at delivery from 2561 HIV-infected women in the postexposure prophylaxis of infants-Malawi trial. The MAA described above was used to identify women with recent HIV infection. Logistic regression models assessed association between recent HIV infection and in-utero HIV transmission (defined as a positive infant HIV DNA test at birth).
Results: Seventy-three women were identified as recently infected using the MAA. Those women were younger and had lower parity than women who were identified as not recently infected using the MAA (P<0.0001 for age and parity). The frequency of in-utero HIV transmission was 17.8% among women identified as recently infected, compared with 6.7% among women identified as not recently infected (13/73 vs. 166/2488, P = 0.001). In a multivariate model, three factors were independently associated with in-utero HIV transmission: recent infection [adjusted odds ratio (AOR): 2.49, 95% confidence interval (CI): 1.30-4.78, P = 0.006], log(10) HIV viral load at delivery (AOR: 2.01, 95% CI: 1.60-2.51, P<0.0001), and younger age (per 10 year increase, AOR: 0.66, 95% CI: 0.43-0.93, P = 0.02).
Conclusion: Results obtained using a MAA suggest that recent maternal HIV acquisition is strongly associated with in-utero HIV transmission, independent of HIV viral load at delivery. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [James, Maria M.; Fowler, Mary G.; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Taha, E. Taha; Sun, Jin; Kumenda, Newton I.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Healthcare Policy & Aging Res, Piscataway, NJ USA.
[Laeyendecker, Oliver] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Laeyendecker, Oliver; Mullis, Caroline E.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Kumwenda, Johnstone J.] Univ Malawi, Dept Med, Coll Med, Blantyre, Malawi.
[Lingappa, Jairam R.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Lingappa, Jairam R.] Univ Washington, Dept Med, Seattle, WA USA.
[Lingappa, Jairam R.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Auvert, Bertran] INSERM, U1018, CESP, Villejuif, France.
[Auvert, Bertran] Hop Ambroise Pare, AP HP, Boulogne, France.
[Auvert, Bertran] Univ Versailles, Guyancourt, France.
[Morrison, Charles S.] Family Hlth Int, Clin Sci, Durham, NC USA.
[Mofensen, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
[Taylor, Allan] Ctr Dis Control & Prevent, Epidemiol Branch, Div HIV AIDS Prevent, Atlanta, GA USA.
RP Eshleman, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Ross Bldg,Room 646,720 Rutland Ave, Baltimore, MD 21205 USA.
EM seshlem@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU International Maternal Pediatric Adolescent AIDS Clinical Trials
(IMPAACT) Group [U01-AI068633]; American Recovery and Reinvestment Act
award [3U01AI068632-05S3]; National Institute of Allergy and Infectious
Diseases (NIAID), National Institutes of Health (NIH); National
Institute on Drug Abuse, National Institutes of Health (NIH); National
Institute of Mental Health, National Institutes of Health (NIH); Office
of AIDS Research, National Institutes of Health (NIH); Department of
Health and Human Services (DHHS) [U01AI068613]; Centers for Disease
Control and Prevention [U50/CCU022061]; Partners in Prevention HSV/HIV
Transmission Study [26469]; Hormonal Contraception and HIV Acquisition
(HC-HIV) Study [N01-HD-0-3310]; Division of Intramural Research, NIAID,
NIH
FX The sources of support are as follows: First, International Maternal
Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, American
Recovery and Reinvestment Act award (cooperative agreement
3U01AI068632-05S3). Second, The HPTN sponsored by the National Institute
of Allergy and Infectious Diseases (NIAID), the National Institute on
Drug Abuse, the National Institute of Mental Health, and the Office of
AIDS Research, of the National Institutes of Health (NIH), Department of
Health and Human Services (DHHS) (U01AI068613). Third, The Centers for
Disease Control and Prevention (cooperative agreement U50/CCU022061).
Fourth, IMPAACT Group (U01-AI068633). Fifth, The Partners in Prevention
HSV/HIV Transmission Study (grant #26469, Bill and Melinda Gates
Foundation). Sixth, the Hormonal Contraception and HIV Acquisition
(HC-HIV) Study (contract N01-HD-0-3310 through Family Health
International, The Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), NIH, DHHS). Seventh, The Division
of Intramural Research, NIAID, NIH.
NR 43
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Z9 10
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 17
PY 2011
VL 25
IS 11
BP 1357
EP 1364
DI 10.1097/QAD.0b013e3283489d45
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 784UO
UT WOS:000292183900002
PM 21572305
ER
PT J
AU Chandwani, S
Beeler, J
Li, H
Audet, S
Smith, B
Moye, J
Nalin, D
Krasinski, K
AF Chandwani, Sulachni
Beeler, Judy
Li, Hong
Audet, Susette
Smith, Betsy
Moye, John
Nalin, David
Krasinski, Keith
CA PACTG 225 Study Team
TI Safety and Immunogenicity of Early Measles Vaccination in Children Born
to HIV-Infected Mothers in the United States: Results of Pediatric AIDS
Clinical Trials Group (PACTG) Protocol 225
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT Global Technical Consultation to Assess the Feasibility of Measles
Eradication
CY JUL 28-30, 2010
CL Washington, DC
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; MATERNAL
ANTIBODY; IMMUNE-RESPONSES; IMMUNIZATION; INFANTS; VACCINES; CELL;
REVACCINATION; TITERS
AB Background. PACTG (Pediatric AIDS Clinical Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus infected (HIV-infected) (POS) and uninfected (NEC) children in the pre-highly active antiretroviral therapy (pre-HAART) period.
Methods. Plaque-reduction neutralization (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (similar to 3 years of age).
Results. The 110 subjects included: 65 2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n = 175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n = 2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers >= 120 mlU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mlU/mL, respectively; P = .023). At similar to 3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers >= 120 mlU/mL. Prevaccination titers >= 25 mlU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers >= 120 mlU/mL (56% vs 90%; P = .004).
Conclusions. Among HIV-infected children pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children.
C1 [Chandwani, Sulachni; Krasinski, Keith] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA.
[Li, Hong] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Beeler, Judy; Audet, Susette] US FDA, Bethesda, MD 20014 USA.
[Smith, Betsy] NIAID, Bethesda, MD 20892 USA.
[Moye, John] NICHHD, Bethesda, MD 20892 USA.
[Nalin, David] Merck Vaccine Div, West Point, PA USA.
RP Chandwani, S (reprint author), NYU, Dept Pediat, Sch Med, 550 1st Ave,8W46 NB Bldg, New York, NY 10016 USA.
EM sulachni.chandwani@nyumc.org
OI moye, john/0000-0001-9976-8586
FU NIAID [U01 AI068632]; Division of Microbiology and Infectious Diseases
(DMID); Centers for Disease Control and Prevention; Statistical and Data
Analysis Center at Harvard School of Public Health, under the National
Institute of Allergy and Infectious Diseases [5 U01 AI41110]; PACTG;
International Maternal Pediatric Adolescent AIDS Clinical Trials
(IMPAACT) Group [1 U01 AI068616]; National Institutes of Health (NIH);
NICHD; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health (NIMH)
[AI068632]; NICHD [N01-DK-9-001/HHSN267200800001C]
FX J. B. is employed by CBER and FDA and receives financial support from
NIAID and Division of Microbiology and Infectious Diseases (DMID) for
other activities outside of this study. D. N. is a retired director of
Vaccine Scientific Affairs, Merck Vaccine Division, and holds stocks and
stock options in Merck Pharmaceuticals.; This article is part of a
supplement entitled "Global Progress Toward Measles Eradication and
Prevention of Rubella and Congenital Rubella Syndrome," which was
sponsored by the Centers for Disease Control and Prevention.; This work
was supported by the Statistical and Data Analysis Center at Harvard
School of Public Health, under the National Institute of Allergy and
Infectious Diseases cooperative agreement #5 U01 AI41110 with the PACTG,
and #1 U01 AI068616 with the International Maternal Pediatric Adolescent
AIDS Clinical Trials (IMPAACT) Group, and was also supported in part by
a grant from National Institutes of Health (NIH) and NICHD (K. K.).
Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Mental Health (NIMH) (AI068632).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH. Support of the
sites was provided by the NIAID and NICHD International and Domestic
Pediatric and Maternal HIV Clinical Trials Network funded by NICHD
(contract number N01-DK-9-001/HHSN267200800001C). Merck Vaccine Division
supplied the Attenuvax and MMRII vaccines.
NR 40
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U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2011
VL 204
SU 1
BP S179
EP S189
DI 10.1093/infdis/jir089
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 802YT
UT WOS:000293547600023
PM 21666159
ER
PT J
AU de Mendizabal, NV
Carneiro, J
Sole, RV
Goni, J
Bragard, J
Martinez-Forero, I
Martinez-Pasamar, S
Sepulcre, J
Torrealdea, J
Bagnato, F
Garcia-Ojalvo, J
Villoslada, P
AF Velez de Mendizabal, Nieves
Carneiro, Jorge
Sole, Ricard V.
Goni, Joaquin
Bragard, Jean
Martinez-Forero, Ivan
Martinez-Pasamar, Sara
Sepulcre, Jorge
Torrealdea, Javier
Bagnato, Francesca
Garcia-Ojalvo, Jordi
Villoslada, Pablo
TI Modeling the effector - regulatory T cell cross-regulation reveals the
intrinsic character of relapses in Multiple Sclerosis
SO BMC SYSTEMS BIOLOGY
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; SELF-TOLERANCE; DISEASE;
ACTIVATION; INFECTION; FOXP3; EXACERBATIONS; GLYCOPROTEIN; INFLAMMATION;
SUPPRESSION
AB Background: The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS). Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e. g. failure in central tolerance, activation by pathogens) that are able to trigger the immune system.
Results: The model represents five concepts: central tolerance (T-cell generation by the thymus), T-cell activation, T-cell memory, cross-regulation (negative feedback) between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system.
Conclusion: The relapsing dynamic in MS derives from the emergent properties of the immune system operating in a pathological state, a fact that has implications for predicting disease course and developing new therapies for MS.
C1 [Martinez-Pasamar, Sara; Villoslada, Pablo] Hosp Clin Barcelona, Ctr Neuroimmunol, Dept Neurosci, Inst Biomed Res August Pi Sunyer IDIBAPS, E-08036 Barcelona, Spain.
[Velez de Mendizabal, Nieves; Goni, Joaquin; Bragard, Jean; Martinez-Forero, Ivan; Sepulcre, Jorge] Univ Navarra, CIMA, Div Neurosci, Pamplona 31008, Spain.
[Velez de Mendizabal, Nieves; Torrealdea, Javier] Univ Basque Country, Comp Sci & Artificial Intelligence Dept, San Sebastian 20018, Spain.
[Carneiro, Jorge] Inst Gulbenkian Ciencias, Theoret Immunol Grp, P-2780156 Oeiras, Portugal.
[Sole, Ricard V.] Univ Pompeu Fabra, Complex Syst Lab, Barcelona 08003, Spain.
[Bagnato, Francesca] NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA.
[Garcia-Ojalvo, Jordi] Univ Politecn Cataluna, Dept Fis & Engn Nucl, Terrassa 08222, Spain.
RP Villoslada, P (reprint author), Hosp Clin Barcelona, Ctr Neuroimmunol, Dept Neurosci, Inst Biomed Res August Pi Sunyer IDIBAPS, Villarroel 170, E-08036 Barcelona, Spain.
EM pvilloslada@clinic.ub.es
RI Garcia-Ojalvo, Jordi/A-4574-2009; BRAGARD, Jean/C-8086-2012; Carneiro,
Jorge/E-1369-2013; Sole, Ricard/I-3379-2015;
OI Garcia-Ojalvo, Jordi/0000-0002-3716-7520; BRAGARD,
Jean/0000-0003-3450-9609; Carneiro, Jorge/0000-0002-7520-3406;
Villoslada, Pablo/0000-0002-8735-6119
FU European Commission [043241, 212877]; Spanish Ministry of Health
[PI060117, RD07/0060/0000-01]; MEC [FIS2005-06912-C02]; NINDS-NIH
FX This work was supported by the European Commission (NEST-Pathfinder
program: "ComplexDis" grant, contract number: 043241 and ITNMC program:
"UEPHA*MS" grant, contract number: 212877) and the Spanish Ministry of
Health (PI060117 and RD07/0060/0000-01) to PV and JGO. NV is a fellow of
the Programa de Formacion de Investigadores del Departamento de
Educacion, Universidades e Investigacion, Gobierno Vasco (BFI05.9 AE).
JB acknowledges the support of the MEC through the grant:
FIS2005-06912-C02, DINCARD. JG is a fellow of Government of Navarra. Dr
Bagnato's contribution to this work was supported by the Intramural
Research Program of the NINDS-NIH. All authors read and approved the
final manuscript. The authors have no conflicting financial interests to
disclose.
NR 61
TC 9
Z9 9
U1 2
U2 12
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 JUL 15
PY 2011
VL 5
AR 114
DI 10.1186/1752-0509-5-114
PG 15
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 807NJ
UT WOS:000293905400001
ER
PT J
AU Liu, BY
Wei, L
Meyerle, C
Tuo, JS
Sen, HN
Li, ZY
Chakrabarty, S
Agron, E
Chan, CC
Klein, ML
Chew, E
Ferris, F
Nussenblatt, RB
AF Liu, Baoying
Wei, Lai
Meyerle, Catherine
Tuo, Jingsheng
Sen, H. Nida
Li, Zhiyu
Chakrabarty, Sagarika
Agron, Elvira
Chan, Chi-Chao
Klein, Michael L.
Chew, Emily
Ferris, Frederick
Nussenblatt, Robert B.
TI Complement component C5a Promotes Expression of IL-22 and IL-17 from
Human T cells and its Implication in Age-related Macular Degeneration
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID GROWTH-FACTOR-BETA; FACTOR-H POLYMORPHISM; CHOROIDAL NEOVASCULARIZATION;
FACTOR-B; DIFFERENTIATION; ACTIVATION; GAMMA; RISK; INTERLEUKIN-6;
INFLAMMATION
AB Background: Age related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH), the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a) have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD.
Methods: Human peripheral blood mononuclear cells (PBMCs) were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500.
Results: We show that C5a promotes interleukin (IL)-22 and IL-17 expression by human CD4(+) T cells. This effect is dependent on B7, IL-1 beta and IL-6 expression from monocytes. We have also found that C5a could protect human CD4(+) cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls.
Conclusions: Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD.
C1 [Liu, Baoying; Wei, Lai; Tuo, Jingsheng; Sen, H. Nida; Li, Zhiyu; Chakrabarty, Sagarika; Chan, Chi-Chao; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Meyerle, Catherine; Agron, Elvira; Chew, Emily; Ferris, Frederick] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
[Klein, Michael L.] Oregon Hlth & Sci Univ, Macular Degenerat Ctr, Casey Eye Inst, Portland, OR 97239 USA.
[Klein, Michael L.] Oregon Hlth & Sci Univ, Leonard Christensen Eye Pathol Lab, Casey Eye Inst, Portland, OR 97239 USA.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
RI Wei, Lai/D-1088-2014;
OI Tuo, Jingsheng/0000-0002-1372-7810
FU NIH, National Eye Institute
FX We thank Dr. Anthony Adamis for kindly providing the C5aR antagonist;
Rafael Villasmil for assistance with flow cytometric cell sorting; This
research was supported by the Intramural Research Program of NIH,
National Eye Institute.
NR 44
TC 49
Z9 50
U1 2
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 15
PY 2011
VL 9
AR 111
DI 10.1186/1479-5876-9-111
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 807RP
UT WOS:000293917700001
PM 21762495
ER
PT J
AU Chikkaveeraiah, BV
Mani, V
Patel, V
Gutkind, JS
Rusling, JF
AF Chikkaveeraiah, Bhaskara V.
Mani, Vigneshwaran
Patel, Vyomesh
Gutkind, J. Silvio
Rusling, James F.
TI Microfluidic electrochemical immunoarray for ultrasensitive detection of
two cancer biomarker proteins in serum
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Microfluidics; Immunoarray; Cancer biomarkers; Off-line protein capture;
Gold nanoparticles; Paramagnetic beads
ID PROSTATE-SPECIFIC ANTIGEN; CARBON NANOTUBE FOREST; SIGNAL AMPLIFICATION;
IMMUNOSENSOR; IMMUNOASSAYS; TECHNOLOGY; SYSTEMS; ARRAYS; SENSOR; CHIP
AB A microfluidic electrochemical immunoassay system for multiplexed detection of protein cancer biomarkers was fabricated using a molded polydimethylsiloxane channel and routine machined parts interfaced with a pump and sample injector. Using off-line capture of analytes by heavily-enzyme-labeled 1 mu m superparamagnetic particle (MP)-antibody bioconjugates and capture antibodies attached to an 8-electrode measuring chip, simultaneous detection of cancer biomarker proteins prostate specific antigen (PSA) and interleukin-6 (IL-6) in serum was achieved at sub-pg mL(-1) levels. MPs were conjugated with similar to 90,000 antibodies and similar to 200,000 horseradish peroxidase (HRP) labels to provide efficient off-line capture and high sensitivity. Measuring electrodes feature a layer of 5 nm glutathione-decorated gold nanoparticles to attach antibodies that capture MP-analyte bioconjugates. Detection limits of 0.23 pg mL(-1) for PSA and 0.30 pg mL(-1) for IL-6 were obtained in diluted serum mixtures. PSA and IL-6 biomarkers were measured in serum of prostate cancer patients in total assay time 1.15 h and sensor array results gave excellent correlation with standard enzyme-linked immunosorbent assays (ELISA). These microfluidic immunosensors employing nanostructured surfaces and off-line analyte capture with heavily labeled paramagnetic particles hold great promise for accurate, sensitive multiplexed detection of diagnostic cancer biomarkers. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Chikkaveeraiah, Bhaskara V.; Mani, Vigneshwaran; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA.
[Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Rusling, James F.] Univ Connecticut Hlth Ctr, Sch Chem, Dept Cell Biol, Farmington, CT 06032 USA.
[Rusling, James F.] Natl Univ Ireland, Galway, Ireland.
RP Rusling, JF (reprint author), Univ Connecticut, Dept Chem, 55 N Eagleville Rd, Storrs, CT 06269 USA.
EM james.rusling@uconn.edu
RI Gutkind, J. Silvio/A-1053-2009
FU NIEHS/NIH [ES013557]; Science Foundation Ireland
FX This work was supported by PHS grant ES013557 from NIEHS/NIH, and by a
Walton Research Fellowship awarded by Science Foundation Ireland to JFR.
We thank Debra Rood and Lawrence K. Silbart for assistance with ELISA
measurements.
NR 59
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U1 16
U2 193
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD JUL 15
PY 2011
VL 26
IS 11
BP 4477
EP 4483
DI 10.1016/j.bios.2011.05.005
PG 7
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA 797DG
UT WOS:000293104100035
PM 21632234
ER
PT J
AU Morris, AM
Masur, H
AF Morris, Alison M.
Masur, Henry
TI A Serologic Test to Diagnose Pneumocystis Pneumonia: Are We There Yet?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID BETA-D-GLUCAN; OPPORTUNISTIC INFECTIONS; ANTIRETROVIRAL THERAPY;
JIROVECII; SERUM; AIDS; CARINII; UTILITY; WALL
C1 [Masur, Henry] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Morris, Alison M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
RP Masur, H (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA.
EM hmasur@nih.gov
NR 15
TC 8
Z9 9
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 JUL 15
PY 2011
VL 53
IS 2
BP 203
EP 204
DI 10.1093/cid/cir348
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 796BA
UT WOS:000293024000015
PM 21690629
ER
PT J
AU Rope, AF
Wang, K
Evjenth, R
Xing, JC
Johnston, JJ
Swensen, JJ
Johnson, WE
Moore, B
Huff, CD
Bird, LM
Carey, JC
Opitz, JM
Stevens, CA
Jiang, T
Schank, C
Fain, HD
Robison, R
Dalley, B
Chin, S
South, ST
Pysher, TJ
Jorde, LB
Hakonarson, H
Lillehaug, JR
Biesecker, LG
Yandell, M
Arnesen, T
Lyon, GJ
AF Rope, Alan F.
Wang, Kai
Evjenth, Rune
Xing, Jinchuan
Johnston, Jennifer J.
Swensen, Jeffrey J.
Johnson, W. Evan
Moore, Barry
Huff, Chad D.
Bird, Lynne M.
Carey, John C.
Opitz, John M.
Stevens, Cathy A.
Jiang, Tao
Schank, Christa
Fain, Heidi Deborah
Robison, Reid
Dalley, Brian
Chin, Steven
South, Sarah T.
Pysher, Theodore J.
Jorde, Lynn B.
Hakonarson, Hakon
Lillehaug, Johan R.
Biesecker, Leslie G.
Yandell, Mark
Arnesen, Thomas
Lyon, Gholson J.
TI Using VAAST to Identify an X-Linked Disorder Resulting in Lethality in
Male Infants Due to N-Terminal Acetyltransferase Deficiency
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ALPHA-ACETYLTRANSFERASE; SEQUENCING DATA; HUMAN GENOME; MUTATIONS; ARD1;
VARIANTS; PROTEINS; CANCER; YEAST; MAP
AB We have identified two families with a previously undescribed lethal X-linked disorder of infancy; the disorder comprises a distinct combination of an aged appearance, craniofacial anomalies, hypotonia, global developmental delays, cryptorchidism, and cardiac arrhythmias. Using X chromosome exon sequencing and a recently developed probabilistic algorithm aimed at discovering disease-causing variants, we identified in one family a c.109T>C (p.Ser37Pro) variant in NAA 10, a gene encoding the catalytic subunit of the major human N-terminal acetyltransferase (NAT). A parallel effort on a second unrelated family converged on the same variant. The absence of this variant in controls, the amino acid conservation of this region of the protein, the predicted disruptive change, and the co-occurrence in two unrelated families with the same rare disorder suggest that this is the pathogenic mutation. We confirmed this by demonstrating a significantly impaired biochemical activity of the mutant hNaa10p, and from this we conclude that a reduction in acetylation by hNaa10p causes this disease. Here we provide evidence of a human genetic disorder resulting from direct impairment of N-terminal acetylation, one of the most common protein modifications in humans.
C1 [Rope, Alan F.; Carey, John C.; South, Sarah T.] Univ Utah, Sch Med, Dept Pediat Med Genet, Salt Lake City, UT 84112 USA.
[Wang, Kai; Hakonarson, Hakon] Univ Utah, Sch Med, Ctr Appl Genom, Salt Lake City, UT 84112 USA.
[Evjenth, Rune; Lillehaug, Johan R.; Arnesen, Thomas] Univ Bergen, Dept Mol Biol, N-5020 Bergen, Norway.
[Xing, Jinchuan; Moore, Barry; Huff, Chad D.; Opitz, John M.; Jorde, Lynn B.; Yandell, Mark] Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA.
[Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Swensen, Jeffrey J.; Opitz, John M.; Chin, Steven; Pysher, Theodore J.] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA.
[Swensen, Jeffrey J.; South, Sarah T.] ARUP Labs, Salt Lake City, UT 84112 USA.
[Johnson, W. Evan; Schank, Christa] Brigham Young Univ, Dept Stat, Provo, UT 84602 USA.
[Bird, Lynne M.] Rady Childrens Hosp, San Diego, CA 92123 USA.
[Bird, Lynne M.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92123 USA.
[Opitz, John M.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA.
[Opitz, John M.] Univ Utah, Dept Neurol, Salt Lake City, UT 84112 USA.
[Stevens, Cathy A.] Univ Tennessee, Coll Med, Dept Pediat, Chattanooga, TN 38163 USA.
[Jiang, Tao] BGI Shenzhen, Shenzhen 518083, Peoples R China.
[Jiang, Tao] Shenzhen Univ, Sch Med, Genome Res Inst, Shenzhen 510860, Peoples R China.
[Fain, Heidi Deborah; Robison, Reid] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA.
[Dalley, Brian] Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Arnesen, Thomas] Haukeland Hosp, Dept Surg, N-5021 Bergen, Norway.
[Lyon, Gholson J.] New York Univ Child Study Ctr, New York, NY 10016 USA.
RP Lyon, GJ (reprint author), Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
EM lyong1@email.chop.edu
RI Xing, Jinchuan/A-2489-2012; Lyon, Gholson/D-2765-2014;
OI Lyon, Gholson/0000-0002-5869-0716; Arnesen, Thomas/0000-0002-3005-147X
FU CCTS at the University of Utah [UL1RR025764]; National Cancer Institute
[P30CA042014]; Research Council of Norway [197136]; Norwegian Cancer
Society; National Human Genome Research Institute (NHGRI)
[1RC2HG005619]; NIH/National Center for Research Resources [UL1
RR025774]; NIH/NHGRI [K99HG005846]; NHGRI [5R01HG5692]; NHGRI, NIH
FX We express our gratitude to the families for their extraordinary
cooperation and assistance. We also thank David Nix, Nina Glomnes, and
Whitney Fitts for advice and/or technical assistance with family 1. Exon
capture and sequencing for family 1 was paid for by the Department of
Psychiatry, University of Utah (to G.J.L.). Collection of DNA and
phenotyping for family 1 was supported by the Clinical Genetics Research
Program: Phenotyping Core, under CCTS grant UL1RR025764 at the
University of Utah. The University of Utah Microarray and Genomic
Analysis core facility was supported by award number P30CA042014 from
the National Cancer Institute. Functional analyses were supported by the
Research Council of Norway (grant 197136 to T.A.) and the Norwegian
Cancer Society (to J.R.L. and T.A.). B.M. and M.Y. were supported by
National Human Genome Research Institute (NHGRI) 1RC2HG005619, K.W. by a
pilot/methodological study award from NIH/National Center for Research
Resources grant UL1 RR025774, J.X. by NIH/NHGRI K99HG005846, and W.E.J.
by NHGRI 5R01HG5692. The research on family 2 was supported by
Intramural Funds of the NHGRI, NIH (L.G.B.). These authors thank
Danielle Brinkman for the initial consenting and records gathering for
family 2 and Caitlin Krause and Jamie Teer for technical support.
NR 48
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U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 15
PY 2011
VL 89
IS 1
BP 28
EP 43
DI 10.1016/j.ajhg.2011.05.017
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 796HF
UT WOS:000293041700003
PM 21700266
ER
PT J
AU Kullo, IJ
Ding, KY
Shameer, K
McCarty, CA
Jarvik, GR
Denny, JC
Ritchie, MD
Ye, Z
Crosslin, DR
Chisholm, RL
Manolio, TA
Chute, CG
AF Kullo, Iftikhar J.
Ding, Keyue
Shameer, Khader
McCarty, Catherine A.
Jarvik, Gail R.
Denny, Joshua C.
Ritchie, Marylyn D.
Ye, Zi
Crosslin, David R.
Chisholm, Rex L.
Manolio, Teri A.
Chute, Christopher G.
TI Complement Receptor 1 Gene Variants Are Associated with Erythrocyte
Sedimentation Rate
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MALARIA; DISEASE; PROTEIN; INFLAMMATION;
POLYMORPHISM; EXPRESSION; PROTECTION; REGULATOR
AB The erythrocyte sedimentation rate (ESR), a commonly performed test of the acute phase response, is the rate at which erythrocytes sediment in vitro in 1 hr. The molecular basis of erythrocyte sedimentation is unknown. To identify genetic variants associated with ESR, we carried out a genome-wide association study of 7607 patients in the Electronic Medical Records and Genomics (eMERGE) network. The discovery cohort consisted of 1979 individuals from the Mayo Clinic, and the replication cohort consisted of 5628 individuals from the remaining four eMERGE sites. A nonsynonymous SNP, rs6691117 (Val -> IIe), in the complement receptor 1 gene (CR1) was associated with ESR (discovery cohort p = 7 x 10(-12), replication cohort p = 3 x 10(-14), combined cohort p = 9 x 10(-24)). We imputed 61 SNPs in CR1, and a "possibly damaging" SNP (rs2274567, His -> Arg) in linkage disequilibrium (r(2) = 0.74) with rs6691117 was also associated with ESR (discovery p = 5 x 10(-11), replication p = 7 x 10(-17), and combined cohort p = 2 x 10(-25)). The two nonsynonymous SNPs in CR1 are near the C3b/C4b binding site, suggesting a possible mechanism by which the variants may influence ESR. In conclusion, genetic variation in CR1, which encodes a protein that clears complement-tagged inflammatory particles from the circulation, influences interindividual variation in ESR, highlighting an association between the innate immunity pathway and erythrocyte interactions.
C1 [Kullo, Iftikhar J.; Ding, Keyue; Shameer, Khader; Ye, Zi] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA.
[McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI 54449 USA.
[Jarvik, Gail R.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Jarvik, Gail R.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Denny, Joshua C.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA.
[Denny, Joshua C.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37232 USA.
[Ritchie, Marylyn D.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet, Nashville, TN 37231 USA.
[Crosslin, David R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Chisholm, Rex L.] Northwestern Univ, Ctr Genet Med, Chicago, IL 60611 USA.
[Manolio, Teri A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Chute, Christopher G.] Mayo Clin, Rochester, MN 55905 USA.
RP Kullo, IJ (reprint author), Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA.
EM kullo.iftikhar@mayo.edu
RI Ritchie, Marylyn/C-1114-2012; Jarvik, Gail/N-6476-2014; Khader,
Shameer/J-2564-2016
OI Jarvik, Gail/0000-0002-6710-8708;
FU National Human Genome Research Institute (NHGRI); National Institute of
General Medical Sciences (NIGMS) [U01-HG-04599, U01-HG-004610,
U01-HG-004608, U01HG004609, U01-HG-04603]
FX The authors acknowledge Elizabeth Pugh for helpful discussions. The
eMERGE Network was initiated and funded by the National Human Genome
Research Institute (NHGRI), with additional funding from National
Institute of General Medical Sciences (NIGMS) through the following
grants: U01-HG-04599 (Mayo Clinic), U01-HG-004610 (Group Health
Cooperative), U01-HG-004608 (Marshfield Clinic), U01HG004609
(Northwestern University), and U01-HG-04603 (Vanderbilt University, also
serving as the Administrative Coordinating Center).
NR 37
TC 37
Z9 37
U1 0
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 15
PY 2011
VL 89
IS 1
BP 131
EP 138
DI 10.1016/j.ajhg.2011.05.019
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 796HF
UT WOS:000293041700011
PM 21700265
ER
PT J
AU Hanson, D
Murray, PG
O'Sullivan, J
Urquhart, J
Daly, S
Bhaskar, SS
Biesecker, LG
Skae, M
Smith, C
Cole, T
Kirk, J
Chandler, K
Kingston, H
Donnai, D
Clayton, PE
Black, GCM
AF Hanson, Dan
Murray, Philip G.
O'Sullivan, James
Urquhart, Jill
Daly, Sarah
Bhaskar, Sanjeev S.
Biesecker, Leslie G.
Skae, Mars
Smith, Claire
Cole, Trevor
Kirk, Jeremy
Chandler, Kate
Kingston, Helen
Donnai, Dian
Clayton, Peter E.
Black, Graeme C. M.
TI Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting
that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human
Growth
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID OBSCURIN-LIKE-1; DOMAIN; P53
AB 3-M syndrome, a primordial growth disorder, is associated with mutations in CUL7 and OBSL1. Exome sequencing now identifies mutations in CCDC8 as a cause of 3-M syndrome. CCDC8 is a widely expressed gene that is transcriptionally associated to CUL7 and OBSL1 and coimmunoprecipitation indicates a physical interaction between CCDC8 and OBSL1 but not CUL7. We propose that CUL7, OBSL1, and CCDC8 are members of a pathway controlling mammalian growth.
C1 [Hanson, Dan; Murray, Philip G.; O'Sullivan, James; Urquhart, Jill; Daly, Sarah; Bhaskar, Sanjeev S.; Chandler, Kate; Kingston, Helen; Donnai, Dian; Black, Graeme C. M.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Biomed Res Ctr, Genet Med Res Grp, Manchester M13 9WL, Lancs, England.
[Hanson, Dan; Murray, Philip G.; O'Sullivan, James; Urquhart, Jill; Daly, Sarah; Bhaskar, Sanjeev S.; Chandler, Kate; Kingston, Helen; Donnai, Dian; Black, Graeme C. M.] Cent Manchester Fdn Trust, St Marys Hosp, Manchester M13 9WL, Lancs, England.
[Hanson, Dan; Murray, Philip G.; Clayton, Peter E.] Univ Manchester, Sch Biomed, Dept Endocrinol, MAHSC, Manchester M13 9WL, Lancs, England.
[Murray, Philip G.; O'Sullivan, James; Urquhart, Jill; Daly, Sarah; Bhaskar, Sanjeev S.; Skae, Mars; Chandler, Kate; Kingston, Helen; Donnai, Dian; Clayton, Peter E.; Black, Graeme C. M.] Cent Manchester Univ Hosp Fdn Trust, Manchester M13 9WL, Lancs, England.
[Biesecker, Leslie G.] NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20814 USA.
[Smith, Claire] E Lancashire Hosp NHS Trust, Royal Blackburn Hosp, Blackburn BB2 3HH, Lancs, England.
[Cole, Trevor] Birmingham Womens Hosp, W Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England.
[Kirk, Jeremy] Birmingham Childrens Hosp, Dept Paediat Endocrinol, Birmingham B4 6NH, W Midlands, England.
RP Black, GCM (reprint author), Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Biomed Res Ctr, Genet Med Res Grp, Manchester M13 9WL, Lancs, England.
EM graeme.black@manchester.ac.uk
RI Urquhart, Jill/G-2282-2015;
OI Urquhart, Jill/0000-0002-5788-5511; Murray, Philip/0000-0002-1480-1576;
Clayton, Peter/0000-0003-1225-4537; Black, Graeme/0000-0001-8727-6592
FU National Institute of Health Research Manchester Biomedical Research
Centre; National Human Genome Research Institute of the NIH
FX We thank all healthcare professionals contributing to the care of
families described here. Support from the National Institute of Health
Research Manchester Biomedical Research Centre is acknowledged. P.G.M.
is a Medical Research Council (UK) Clinical Research Fellow. The NISC
Comparative Sequencing Program and the ClinSeq study are funded by the
National Human Genome Research Institute of the NIH.
NR 21
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U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 15
PY 2011
VL 89
IS 1
BP 148
EP 153
DI 10.1016/j.ajhg.2011.05.028
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 796HF
UT WOS:000293041700013
PM 21737058
ER
PT J
AU Lynch, CD
Louis, GMB
Lahti, MC
Pekow, PS
Nasca, PC
Cohen, B
AF Lynch, Courtney D.
Louis, Germaine M. Buck
Lahti, Maureen C.
Pekow, Penelope S.
Nasca, Philip C.
Cohen, Bruce
TI The Birth Certificate as an Efficient Means of Identifying Children
Conceived With the Help of Infertility Treatment
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE birth certificates; child development; epidemiologic methods; fertility
agents, female; fertilization in vitro
ID ASSISTED REPRODUCTIVE TECHNOLOGY; HEALTH; STATE
AB Recent work suggests that infertility treatment is associated with adverse child health outcomes. In exploring various methods of assembling a cohort of children conceived by infertility treatment, the authors conducted a validation study of the assisted reproductive technology and infertility drug use check boxes on the Massachusetts birth certificate. Using 2001 and 2002 data, the authors conducted telephone interviews with 399 women whose child's birth certificate had at least one of the boxes checked along with 185 women who were over age 42 years or who delivered twins or higher order multiples to compare the check box information with maternal report. Among the 579 women with available information, the birth certificate was fully concordant with respect to infertility treatment status for 271 (47%) women, partially concordant for 248 (43%) women, and discordant for 60 (10%) women. Agreement between the birth certificate and maternal report was good for singletons (weighted kappa = 0.66) but was found to be very poor among twins and higher order multiples (weighted kappa = 0.05). The authors concluded that birth certificates are an efficient means of locating children conceived with the help of infertility treatment but that they are not appropriate for identifying type of treatment.
C1 [Lynch, Courtney D.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Lahti, Maureen C.; Pekow, Penelope S.] Univ Massachusetts, Amherst, NY USA.
[Nasca, Philip C.] SUNY Albany, Albany, NY 12222 USA.
[Cohen, Bruce] Massachusetts Dept Publ Hlth, Boston, MA USA.
RP Lynch, CD (reprint author), Ohio State Univ, Coll Med, Dept Obstet & Gynecol, 395 W 12th Ave,Room 580, Columbus, OH 43210 USA.
EM courtney.lynch@osumc.edu
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Funding for this project was provided by intramural research funds from
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 13
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U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 15
PY 2011
VL 174
IS 2
BP 211
EP 218
DI 10.1093/aje/kwr036
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 792VN
UT WOS:000292778600011
PM 21705488
ER
PT J
AU Meyer, TE
Fox, SD
Issaq, HJ
Xu, X
Chu, LW
Veenstra, TD
Hsing, AW
AF Meyer, Tamra E.
Fox, Stephen D.
Issaq, Haleem J.
Xu, Xia
Chu, Lisa W.
Veenstra, Timothy D.
Hsing, Ann W.
TI A Reproducible and High-Throughput HPLC/MS Method To Separate Sarcosine
from alpha- and beta-Alanine and To Quantify Sarcosine in Human Serum
and Urine
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; PROSTATE-CANCER; LIQUID-CHROMATOGRAPHY; MARKER
AB While sarcosine was recently identified as a potential urine biomarker for prostate cancer, further studies have cast doubt on its utility to diagnose this condition. The inconsistent results may be due to the fact that alanine and sarcosine coelute on an HPLC reversed-phase column and the mass spectrometer cannot differentiate between the two isomers, since the same parent/product ions are generally used to measure them. In this study, we developed a high-throughput liquid chromatography-mass spectrometry (LC-MS) method that resolves sarcosine from alanine isomers, allowing its accurate quantification in human serum and urine. Assay reproducibility was determined using the coefficient of variation (CV) and intraclass correlation coefficient (ICC) in serum aliquots from 10 subjects and urine aliquots from 20 subjects across multiple analytic runs. Paired serum/urine samples from 42 subjects were used to evaluate sarcosine serum/urine correlation. Both urine and serum assays gave high sensitivity (limit of quantitation of 5 ng/mL) and reproducibility (serum assay, intra- and interassay CVs < 3% and ICCs > 99%; urine assay, intra-assay CV = 7.7% and ICC = 98.2% and interassay CV = 12.3% and ICC = 94.2%). In conclusion, this high-throughput LC-MS method is able to resolve sarcosine from alpha- and beta-alanine and is useful for quantifying sarcosine in serum and urine samples.
C1 [Meyer, Tamra E.; Chu, Lisa W.; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Fox, Stephen D.; Issaq, Haleem J.; Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Meyer, TE (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM Tamra.E.Meyer@us.army.mil; foxsd@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We thank Shelley Niwa and Ann Truelove of Westat for their help with
study and sample management. This project has been funded in whole or in
part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract HHSN261200800001E. T.E.M. and
S.D.F. contributed equally to this work. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 11
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U1 1
U2 38
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 JUL 15
PY 2011
VL 83
IS 14
BP 5735
EP 5740
DI 10.1021/ac201003r
PG 6
WC Chemistry, Analytical
SC Chemistry
GA 794JN
UT WOS:000292892000036
PM 21635006
ER
PT J
AU de Groot, JF
Piao, Y
Tran, H
Gilbert, M
Wu, HK
Liu, J
Bekele, BN
Cloughesy, T
Mehta, M
Robins, HI
Lassman, A
DeAngelis, L
Camphausen, K
Chen, A
Yung, WKA
Prados, M
Wen, PY
Heymach, JV
AF de Groot, John F.
Piao, Yuji
Hai Tran
Gilbert, Mark
Wu, Hua-Kang
Liu, Jun
Bekele, B. Nebiyou
Cloughesy, Tim
Mehta, Minesh
Robins, H. Ian
Lassman, Andrew
DeAngelis, Lisa
Camphausen, Kevin
Chen, Alice
Yung, W. K. A.
Prados, Michael
Wen, Patrick Y.
Heymach, John V.
TI Myeloid Biomarkers Associated with Glioblastoma Response to Anti-VEGF
Therapy with Aflibercept
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; CARBONIC-ANHYDRASE-IX; PHASE-II; IN-VIVO;
TUMOR ANGIOGENESIS; MALIGNANT GLIOMA; CANCER-PATIENTS; RECTAL-CANCER;
BEVACIZUMAB; CELLS
AB Purpose: VEGF and infiltrating myeloid cells are known regulators of tumor angiogenesis and vascular permeability in glioblastoma. We investigated potential blood-based markers associated with radiographic changes to aflibercept, which binds VEGF and placental growth factor (PlGF) in patients with recurrent glioblastoma.
Experimental Design: In this single-arm phase II trial, aflibercept was given intravenously every two weeks until disease progression. Plasma and peripheral blood mononuclear cells were collected at baseline and 24 hours, 14 days, and 28 days posttreatment. Plasma cytokines and angiogenic factors were quantified by using ELISA and multiplex bead assays, and myeloid cells were assessed by flow cytometry in a subset of patients.
Results: Circulating levels of VEGF significantly decreased 24 hours after treatment with aflibercept, coincident with radiographic response observed by MRI. PlGF initially decreased 24 hours posttreatment but increased significantly by days 14 and 28. Lower baseline levels of PlGF, elevated baseline levels of CTACK/CCL27, MCP3/CCL7, MIF, and IP-10/CXCL10, and a decrease in VEGFR1(+) monocytes from baseline to 24 hours were all associated with improved response. Tumor progression was associated with increases in circulating matrix metalloproteinase 9.
Conclusions: These data suggest that decreases in VEGF posttreatment are associated with radiographic response to aflibercept. Elevated baseline chemokines of monocyte lineage in responding patients supports a role for myeloid cells and chemokines as potential biomarkers and regulators of glioma angiogenesis. Clin Cancer Res; 17(14); 4872-81. (C) 2011 AACR.
C1 [de Groot, John F.; Piao, Yuji; Gilbert, Mark; Yung, W. K. A.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Hai Tran; Wu, Hua-Kang; Heymach, John V.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA.
[Liu, Jun; Bekele, B. Nebiyou] Univ Texas MD Anderson Canc Ctr, Dept Appl Math & Biostat, Houston, TX 77030 USA.
[Cloughesy, Tim] Univ Calif Los Angeles, Los Angeles, CA USA.
[Mehta, Minesh; Robins, H. Ian] Univ Wisconsin, Madison, WI USA.
[Lassman, Andrew; DeAngelis, Lisa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Chen, Alice] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
RP de Groot, JF (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, 1515 Holcombe Blvd,Unit 431, Houston, TX 77030 USA.
EM jdegroot@mdanderson.org
OI mehta, minesh/0000-0002-4812-5713
FU AstraZeneca; Adnexus; Exelixis; Genentech; Bayer; Merck; Schering
Plough; Tomotherapy; Keryx; Bristol Myers-Squibb; Campus Bio LP;
Cephalon; Eisai; Imclone; Novartis; Merck/EMD; NIH: NABTC [U01-CA62399];
ASCO; [1R21A126127]
FX J.F. de Groot: commercial research grants, AstraZeneca, Adnexus,
Exelixis; consultant/advisory board, Genentech. M. Gilbert:
consultant/advisory board, Genentech. M. Mehta: stock options,
Tomotherapy, Pharmacyclics; consultant/advisory board, Genentech,
Adnexus, Bayer, Merck, Schering Plough, Tomotherapy, Stemina. A.
Lassman: commercial research grants, Genentech, Keryx;
consultant/advisory board, Bristol Myers-Squibb, Campus Bio LP,
Cephalon, Eisai, Genentech, Imclone, Merck, Schering Plough. WKA Yung:
commercial research grant, Novartis; consultant/advisory board,
Genentech, Merck/EMD, Schering Plough. The other authors disclosed no
potential conflicts of interest.; The clinical trial was funded by the
NIH: NABTC # U01-CA62399. Correlative studies supported in part by
1R21A126127 and an ASCO Career Development Award, both to J.F. de Groot.
NR 38
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U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2011
VL 17
IS 14
BP 4872
EP 4881
DI 10.1158/1078-0432.CCR-11-0271
PG 10
WC Oncology
SC Oncology
GA 793JI
UT WOS:000292816900027
PM 21632852
ER
PT J
AU Meissner, HI
Klabunde, CN
Han, PK
Benard, VB
Breen, N
AF Meissner, Helen I.
Klabunde, Carrie N.
Han, Paul K.
Benard, Vicki B.
Breen, Nancy
TI Breast Cancer Screening Beliefs, Recommendations, and Practices
SO CANCER
LA English
DT Article
DE breast cancer; mammography; primary care; physicians; screening
ID NATIONAL-SURVEY; MAMMOGRAPHY USE; UNITED-STATES; PHYSICIANS; US; TRENDS;
PERCEPTIONS; LITIGATION; EXPERIENCE; IMPACT
AB BACKGROUND: Primary care physicians (PCPs) play a key role in breast cancer screening, yet no current data exist regarding PCP practices. METHODS: The authors analyzed a nationally representative survey of PCPs that was fielded during September 2006 to May 2007 to investigate PCP breast cancer screening beliefs, recommendations, and practices. RESULTS: Most of the 1212 PCPs who participated in the survey (80%) reported that mammography for average-risk women aged >= 50 years was very effective in reducing cancer mortality, and 54% reported that it was very effective for women ages 40 to 49 years. Fewer respondents reported that clinical breast examination (CBE) or breast self-examination (BSE) was very effective, but the majority rated CBE and BSE as somewhat effective. The majority of PCPs routinely recommended mammography, CBE, and BSE to patients aged >= 40 years. In multivariate models, family/general practitioners (odds ratio [OR], 2.23; 95% confidence interval [Cl], 1.57-3.17 for mammography; OR, 4.42; 95% Cl, 2.60-7.52 for CBE) and internal medicine specialists (OR, 3.21; 95% Cl, 2.21-4.66 for mammography; OR, 5.34; 95% Cl, 3.21-8.88 for CBE) were more likely to recommend an upper age limit for screening than obstetrician/gynecologists. Physicians who reported that US Preventive Services Task Force guidelines were very influential were more likely to recommend an age at which they no longer recommend mammography and CBE. CONCLUSIONS: To the authors' knowledge, the current study is the first national study in over 2 decades to report the breast cancer screening practices of PCPs and provides baseline data for monitoring the impact of changes in clinical practice guidelines. The current findings suggested that virtually all PCPs routinely recommend mammography, CBE, and BSE to their patients aged >= 40 years, although recommendations vary by primary care specialty. Cancer 2011;117:3101-11. Published 2011 by the American Cancer Society*
C1 [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Off Director, Bethesda, MD 20892 USA.
[Klabunde, Carrie N.; Breen, Nancy] Natl Canc Inst Bethesda, Div Canc Control & Populat Sci, Bethesda, MD USA.
[Han, Paul K.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Scarborough, ME USA.
[Benard, Vicki B.] Ctr Dis Control & Prevent Atlanta, Div Canc Prevent & Control, Atlanta, GA USA.
RP Meissner, HI (reprint author), NIH, Off Behav & Social Sci Res, Off Director, 31 Ctr Dr,Bldg 31,Room B1C19, Bethesda, MD 20892 USA.
EM meissneh@od.nih.gov
OI Han, Paul/0000-0003-0165-1940
FU National Cancer Institute [N02-PC-51308]; Centers for Disease Control
and Prevention [Y3-PC-6017-01]; Agency for Healthcare Research and
Quality [Y3-PC-5019-01, Y3-PC-5019-02]
FX Funding support for the survey was provided by the National Cancer
Institute (contract number N02-PC-51308), the Centers for Disease
Control and Prevention (interagency agreement number Y3-PC-6017-01), and
the Agency for Healthcare Research and Quality (interagency agreement
numbers Y3-PC-5019-01 and Y3-PC-5019-02).
NR 31
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U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 15
PY 2011
VL 117
IS 14
BP 3101
EP 3111
DI 10.1002/cncr.25873
PG 11
WC Oncology
SC Oncology
GA 789SQ
UT WOS:000292537000007
PM 21246531
ER
PT J
AU Du, XLL
Lin, CC
Johnson, NJ
Altekruse, S
AF Du, Xianglin L.
Lin, Charles C.
Johnson, Norman J.
Altekruse, Sean
TI Effects of Individual-Level Socioeconomic Factors on Racial Disparities
in Cancer Treatment and Survival
SO CANCER
LA English
DT Article
DE cancer; socioeconomic status; racial disparities; treatment; survival
ID AFRICAN-AMERICAN; BREAST-CANCER; OLDER WOMEN; DIAGNOSIS; METAANALYSIS;
MORTALITY; HEALTH; RACE; EPIDEMIOLOGY; SURVEILLANCE
AB BACKGROUND: This is the first study to use the linked National Longitudinal Mortality Study and Surveillance, Epidemiology, and End Results (SEER) data to determine the effects of individual-level socioeconomic factors (health insurance, education, income, and poverty status) on racial disparities in receiving treatment and in survival. METHODS: This study included 13,234 cases diagnosed with the 8 most common types of cancer (female breast, colorectal, prostate, lung and bronchus, uterine cervix, ovarian, melanoma, and urinary bladder) at age >= 25 years, identified from the National Longitudinal Mortality Study-SEER data during 1973 to 2003. Kaplan-Meier methods and Cox regression models were used for survival analysis. RESULTS: Three-year all-cause observed survival for cases diagnosed with local-stage cancers of the >= 8 leading tumors combined was >82% regardless of race/ethnicity. More favorable survival was associated with higher socioeconomic status. Compared with whites, blacks were less likely to receive first-course cancer-directed surgery, perhaps reflecting a less favorable stage distribution at diagnosis. Hazard ratio (HR) for cancer-specific mortality was significantly higher among blacks compared with whites (HR, 1.2; 95% confidence interval [Cl], 1.143) after adjusting for age, sex, and tumor stage, but not after further controlling for socioeconomic factors and treatment (HR, 1.0; 95% Cl, 0.9-1.1). HRs for all-cause mortality among patients with breast cancer and for cancer-specific mortality in patients with prostate cancer were significantly higher for blacks compared with whites after adjusting for socioeconomic factors, treatment, and patient and tumor characteristics. CONCLUSIONS: Favorable survival was associated with higher socioeconomic status. Racial disparities in survival persisted after adjusting for individual-level socioeconomic factors and treatment for patients with breast and prostate cancer. Cancer 2011;117:3242-51.0 (C) 2011 American Cancer Society.
C1 [Du, Xianglin L.] Univ Texas Houston, Sch Publ Hlth, Div Epidemiol, Houston, TX 77030 USA.
[Lin, Charles C.; Johnson, Norman J.] US Bur Census, Suitland, MD USA.
[Altekruse, Sean] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Du, XLL (reprint author), Univ Texas Houston, Sch Publ Hlth, Div Epidemiol, 1200 Herman Pressler Dr, Houston, TX 77030 USA.
EM Xianglin.L.Du@uth.tmc.edu
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [Y01 PC009021, Y01
PC009021-13]
NR 25
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U1 2
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 15
PY 2011
VL 117
IS 14
BP 3242
EP 3251
DI 10.1002/cncr.25854
PG 10
WC Oncology
SC Oncology
GA 789SQ
UT WOS:000292537000024
PM 21264829
ER
PT J
AU Purdue, MP
Lan, Q
Bagni, R
Hocking, WG
Baris, D
Reding, DJ
Rothman, N
AF Purdue, Mark P.
Lan, Qing
Bagni, Rachel
Hocking, William G.
Baris, Dalsu
Reding, Douglas J.
Rothman, Nathaniel
TI Prediagnostic Serum Levels of Cytokines and Other Immune Markers and
Risk of Non-Hodgkin Lymphoma
SO CANCER RESEARCH
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; B-CELL LYMPHOMA; INTERLEUKIN-1 RECEPTOR
ANTAGONIST; SOLUBLE TNF RECEPTORS; IN-VIVO; INTERLYMPH-CONSORTIUM;
RELEASE; CD27; AIDS; POLYMORPHISMS
AB Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), it is unclear whether subclinical immune system function influences lymphomagenesis. To address this question, we conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate whether circulating levels of cytokines and other immune markers are associated with future risk of NHL. Selected cytokines [interleukin (IL)-4, IL-6, IL-10, and TNF-alpha] and other immune markers [soluble TNF receptor 1 (sTNF-R1), sTNF-R2, C-reactive protein, and sCD27] were measured in prediagnostic serum specimens from 297 incident NHL cases and 297 individually matched controls. ORs and 95% confidence intervals (CI) relating quartiles of analyte concentration to NHL risk were calculated by using conditional logistic regression. Statistically significant associations with increased NHL risk were observed for elevated serum levels of sTNF-R1 (quartile 4 vs. quartile 1: OR 1.7, 95% CI: 1.1-2.8; P(trend) = 0.02) and sCD27 (OR = 5.3, 95% CI: 2.9-9.4; P(trend) < 0.0001). These associations remained in analyses of cases diagnosed longer than 6 years following blood collection (sTNF-R1: OR = 2.1, 95% CI: 1.0-4.0, P(trend) = 0.01; sCD27: OR 4.1, 95% CI: 1.9-8.5, P(trend) = 0.0001). Elevated levels of IL-10, TNF-alpha and sTNF-R2 were also significantly associated with increased risk of NHL overall; however, these associations weakened with increasing time from blood collection to case diagnosis and were null for cases diagnosed longer than 6 years postcollection. Our findings for sTNF-R1 and sCD27, possible markers for inflammatory and B-cell stimulatory states, respectively, support a role for subclinical inflammation and chronic B-cell stimulation in lymphomagenesis. Cancer Res; 71(14); 4898-907. (C) 2011 AACR.
C1 [Purdue, Mark P.; Lan, Qing; Baris, Dalsu; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bagni, Rachel] NCI, Protein Express Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Hocking, William G.; Reding, Douglas J.] Marshfield Clin Fdn Med Res & Educ, Dept Hematol Oncol, Marshfield, WI USA.
RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS 8114,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM purduem@mail.nih.gov
RI Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Hocking, William/0000-0002-0690-3759
FU Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS; National Cancer
Institute, NIH [HHSN261200800001E]
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and by contracts from the
Division of Cancer Prevention, National Cancer Institute, NIH, DHHS.
This project has been funded in whole or in part with federal funds from
the National Cancer Institute, NIH under Contract No. HHSN261200800001E.
NR 49
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U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2011
VL 71
IS 14
BP 4898
EP 4907
DI 10.1158/0008-5472.CAN-11-0165
PG 10
WC Oncology
SC Oncology
GA 792QN
UT WOS:000292763700017
PM 21632552
ER
PT J
AU Chiu, WT
Lee, HT
Huang, FJ
Aldape, KD
Yao, J
Steeg, PS
Chou, CY
Lu, ZM
Xie, KP
Huang, SY
AF Chiu, Wen-Tai
Lee, Hsueh-Te
Huang, Feng-Ju
Aldape, Kenneth D.
Yao, Jun
Steeg, Patricia S.
Chou, Cheng-Yang
Lu, Zhimin
Xie, Keping
Huang, Suyun
TI Caveolin-1 Upregulation Mediates Suppression of Primary Breast Tumor
Growth and Brain Metastases by Stat3 Inhibition
SO CANCER RESEARCH
LA English
DT Article
ID MAP KINASE CASCADE; CANCER-CELLS; DOWN-REGULATION; SIGNAL-TRANSDUCTION;
GENE-EXPRESSION; IN-VIVO; MICE; ACTIVATION; MELANOMA; INVASION
AB Stat3 activation has been implicated as an important driver of brain metastasis in breast cancer, but the critical targets of Stat3 in this process are yet to be fully defined. In this study, we identified the lipid raft organizing protein Caveolin-1 (Cav-1) as a critical genetic target of Stat3 in this process. In human breast cancers, we found that activated Stat3 correlated with attenuation of Cav-1 in brain metastases relative to primary tumors. Cav-1 promoter activity and gene expression were increased by overexpressing an activated form of Stat3 but decreased by attenuation of Stat3 activity or expression. We identified putative Stat3-binding elements in the Cav-1 promoter and showed a direct repression of Cav-1 transcription by Stat3. Reciprocally, we showed that strategies to increase or decrease Cav-1 expression were sufficient to attenuate or promote breast cancer cell invasion. Furthermore, increased expression of Cav-1 phenocopied the effects of Stat3 activation in blocking primary tumor growth and abrogating formation of brain metastases. Collectively, our findings provide clinical and mechanistic evidence that Cav-1 is a critical target for suppression by Stat3 in driving invasion and metastasis of breast cancer cells. Cancer Res; 71(14); 4932-43. (C) 2011 AACR.
C1 [Huang, Suyun] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Unit 1004, Houston, TX 77030 USA.
[Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Yao, Jun; Lu, Zhimin] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Xie, Keping] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Huang, Feng-Ju; Xie, Keping; Huang, Suyun] Univ Texas Grad Sch Biomed Sci, Program Canc Biol, Houston, TX USA.
[Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chiu, Wen-Tai; Chou, Cheng-Yang] Natl Cheng Kung Univ, Coll Med, Dept Obstet & Gynecol, Tainan 70101, Taiwan.
RP Huang, SY (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Unit 1004, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM suhuang@mdanderson.org
FU U.S. Department of Defense [W81XWH-06-2-0033]; American Cancer Society;
National Cancer Institute Cancer Center [CA 16672]
FX The work was supported by U.S. Department of Defense Breast Cancer
Research Program Center of Excellence Award Grant W81XWH-06-2-0033,
American Cancer Society Research Scholar Grant, and National Cancer
Institute Cancer Center Support Grant CA 16672.
NR 49
TC 29
Z9 32
U1 1
U2 11
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 JUL 15
PY 2011
VL 71
IS 14
BP 4932
EP 4943
DI 10.1158/0008-5472.CAN-10-4249
PG 12
WC Oncology
SC Oncology
GA 792QN
UT WOS:000292763700020
PM 21622714
ER
PT J
AU Yan, HH
Pickup, M
Pang, YL
Gorska, AE
Li, ZY
Chytil, A
Geng, YP
Gray, JW
Moses, HL
Yang, L
AF Yan, Hannah H.
Pickup, Michael
Pang, Yanli
Gorska, Agnieszka E.
Li, Zhaoyang
Chytil, Anna
Geng, Yipeng
Gray, Jerome W.
Moses, Harold L.
Yang, Li
TI Myeloid Suppressor Cells Regulate the Lung Environment-Response
SO CANCER RESEARCH
LA English
DT Letter
C1 [Yan, Hannah H.; Pang, Yanli; Li, Zhaoyang; Yang, Li] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA.
[Pickup, Michael; Gorska, Agnieszka E.; Chytil, Anna; Geng, Yipeng; Moses, Harold L.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA.
[Geng, Yipeng; Gray, Jerome W.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA.
[Pickup, Michael; Gorska, Agnieszka E.; Chytil, Anna; Moses, Harold L.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
RP Yang, L (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bldg 37,Room 3134C,37 Convent Dr,MSC 4258, Bethesda, MD 20876 USA.
EM yangl3@mail.nih.gov
NR 3
TC 1
Z9 1
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 JUL 15
PY 2011
VL 71
IS 14
BP 5052
EP 5053
DI 10.1158/0008-5472.CAN-11-0688
PG 2
WC Oncology
SC Oncology
GA 792QN
UT WOS:000292763700032
ER
PT J
AU Kochetov, AV
Volkova, OA
Poliakov, A
Dubchak, I
Rogozin, IB
AF Kochetov, Alex V.
Volkova, Oxana A.
Poliakov, Alexander
Dubchak, Inna
Rogozin, Igor B.
TI Tandem termination signal in plant mRNAs
SO GENE
LA English
DT Article
DE mRNA; Arabidopsis thaliana; Oryza sativa; Stop codon; Tandem
terminators; Readthrough
ID STOP CODON READTHROUGH; TRANSLATION START SITES;
SACCHAROMYCES-CEREVISIAE; READ-THROUGH; HUMAN GENOME;
DROSOPHILA-MELANOGASTER; PROTEIN; GENES; YEAST; IDENTIFICATION
AB It was proposed that if some mRNA characteristics resulted in a low efficiency of termination signal, an additional closely located stop codon (tandem stop codons) could be used to prevent the harmful readthrough. However, the role of tandem terminators in higher eukaryotes was not verified and remains hypothetical. In this work the sequence features of Arabidopsis thaliana and Oryza sativa mRNAs were analyzed. It was found that plant mRNAs with UGA terminator were characterized by a higher frequency of nonsense codons in the first triplet position of 3'-UTR that could result from a weak natural selection for "reserve" stop signal. Interestingly, the presence of tandem stop codons positively correlated with a specific amino acid composition in the C-terminal position of the encoded proteins. In particular, C-terminal glycine positively correlated with significantly higher frequencies of reserve terminators at the beginning positions of 3'-UTR in UGA-containing mRNAs. This finding coincides with some earlier observations concerning the role of glycine and its codons in inefficient termination of translation and recoding (e.g., 2A oligopeptide). (C) 2011 Elsevier B.V. All rights reserved.
C1 [Kochetov, Alex V.; Volkova, Oxana A.; Rogozin, Igor B.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
[Kochetov, Alex V.; Volkova, Oxana A.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
[Poliakov, Alexander; Dubchak, Inna] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
[Poliakov, Alexander; Dubchak, Inna] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
[Rogozin, Igor B.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Kochetov, AV (reprint author), Russian Acad Sci, Inst Cytol & Genet, Lavrentieva Ave 10, Novosibirsk 630090, Russia.
EM ak@bionet.nsc.ru; ov@bionet.nsc.ru; AVPoliakov@lbl.gov;
ildubchak@lbl.gov; rogozin@ncbi.nlm.nih.gov
RI Kochetov, Alex/R-9689-2016
OI Kochetov, Alex/0000-0003-3151-5181
FU Russian Ministry of Science Education [2.1.1/10551 (2.1.1/6382),
02.740.11.0705, 02.740.11.0277, P721]; Russian Academy of Sciences
(Molecular and Cellular Biology); DHHS (NIH, National Library of
Medicine); Office of Science of the U.S. Department of Energy
[DE-AC02-05CH11231]
FX We are grateful to Prof. Lev L Kisselev for discussions. This work was
supported by Russian Ministry of Science & Education (2.1.1/10551
(2.1.1/6382); 02.740.11.0705; 02.740.11.0277; P721), the Program of
Russian Academy of Sciences (Molecular and Cellular Biology) and
intramural funds of the DHHS (NIH, National Library of Medicine). The
authors are also grateful to SD RAS Complex Integration Program for
partial support. The work conducted by the U.S. Department of Energy
Joint Genome Institute (ID. and A.P.) was supported by the Office of
Science of the U.S. Department of Energy under Contract No.
DE-AC02-05CH11231.
NR 45
TC 1
Z9 1
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD JUL 15
PY 2011
VL 481
IS 1
BP 1
EP 6
DI 10.1016/j.gene.2011.04.002
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 791NP
UT WOS:000292672200001
PM 21539902
ER
PT J
AU Tebbenkamp, ATN
Green, C
Xu, GL
Denovan-Wright, EM
Rising, AC
Fromholt, SE
Brown, HH
Swing, D
Mandel, RJ
Tessarollo, L
Borchelt, DR
AF Tebbenkamp, Andrew T. N.
Green, Cameron
Xu, Guilian
Denovan-Wright, Eileen M.
Rising, Aaron C.
Fromholt, Susan E.
Brown, Hilda H.
Swing, Debbie
Mandel, Ronald J.
Tessarollo, Lino
Borchelt, David R.
TI Transgenic mice expressing caspase-6-derived N-terminal fragments of
mutant huntingtin develop neurologic abnormalities with predominant
cytoplasmic inclusion pathology composed largely of a smaller
proteolytic derivative
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MOUSE MODEL; INTRANUCLEAR INCLUSIONS; REDUCES TOXICITY; CASPASE
CLEAVAGE; MOTOR DEFICITS; DISEASE; POLYGLUTAMINE; GENE; AGGREGATION;
REPEAT
AB Recent studies have implicated an N-terminal caspase-6 cleavage product of mutant huntingtin (htt) as an important mediator of toxicity in Huntington's disease (HD). To directly assess the consequences of such fragments on neurologic function, we produced transgenic mice that express a caspase-6 length N-terminal fragment of mutant htt (N586) with both normal (23Q) and disease (82Q) length glutamine repeats. In contrast to mice expressing N586-23Q, mice expressing N586-82Q accumulate large cytoplasmic inclusion bodies that can be visualized with antibodies to epitopes throughout the N586 protein. However, biochemical analyses of aggregated mutant huntingtin in these mice demonstrated that the inclusion bodies are composed largely of a much smaller htt fragment (terminating before residue 115), with lesser amounts of full-length N586-82Q fragments. Mice expressing the N586-82Q fragment show symptoms typical of previously generated mice expressing mutant huntingtin fragments, including failure to maintain weight, small brain weight and reductions in specific mRNAs in the striatum. Uniquely, these N586-82Q mice develop a progressive movement disorder that includes dramatic deficits in motor performance on the rotarod and ataxia. Our findings suggest that caspase-6-derived fragments of mutant htt are capable of inducing novel HD-related phenotypes, but these fragments are not terminal cleavage products as they are subject to further proteolysis. In this scenario, mutant htt fragments derived from caspase 6, or possibly other proteases, could mediate HD pathogenesis via a 'hit and run' type of mechanism in which caspase-6, or other larger N-terminal fragments, mediate a neurotoxic process before being cleaved to a smaller fragment that accumulates pathologically.
C1 [Tebbenkamp, Andrew T. N.; Green, Cameron; Xu, Guilian; Rising, Aaron C.; Fromholt, Susan E.; Brown, Hilda H.; Mandel, Ronald J.; Borchelt, David R.] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA.
[Green, Cameron; Xu, Guilian; Fromholt, Susan E.; Brown, Hilda H.; Borchelt, David R.] Univ Florida, Santa Fe Hlth Alzheimers Dis Res Ctr, McKnight Brain Inst, Gainesville, FL 32610 USA.
[Denovan-Wright, Eileen M.] Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 1X5, Canada.
[Swing, Debbie; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Neural Dev Sect, Frederick, MD 21702 USA.
RP Borchelt, DR (reprint author), Univ Florida, Dept Neurosci, 100 Newell Dr,Rm L1-100, Gainesville, FL 32610 USA.
EM borchelt@mbi.ufl.edu
OI Tebbenkamp, Andrew/0000-0002-9015-3427
FU Huntington's Disease Society of America; CHDI Coalition for a Cure; NIH,
Center for Cancer Research, National Cancer Institute
FX This work was supported by the Huntington's Disease Society of America
and the CHDI Coalition for a Cure (A.T.N.T. and D.R.B.) and the
Intramural Research Program of the NIH, Center for Cancer Research,
National Cancer Institute (for D.S. and L.T.).
NR 43
TC 23
Z9 24
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2011
VL 20
IS 14
BP 2770
EP 2782
DI 10.1093/hmg/ddr176
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 790AG
UT WOS:000292560300007
PM 21515588
ER
PT J
AU Chung, CC
Ciampa, J
Yeager, M
Jacobs, KB
Berndt, SI
Hayes, RB
Gonzalez-Bosquet, J
Kraft, P
Wacholder, S
Orr, N
Yu, K
Hutchinson, A
Boland, J
Chen, Q
Feigelson, HS
Thun, MJ
Diver, WR
Albanes, D
Virtamo, J
Weinstein, S
Schumacher, FR
Cancel-Tassin, G
Cussenot, O
Valeri, A
Andriole, GL
Crawford, ED
Haiman, CA
Henderson, BE
Kolonel, L
Le Marchand, L
Siddiq, A
Riboli, E
Key, TJ
Kaaks, R
Isaacs, WB
Isaacs, SD
Gronberg, H
Wiklund, F
Xu, JF
Vatten, LJ
Hveem, K
Njolstad, I
Gerhard, DS
Tucker, M
Hoover, RN
Fraumeni, JF
Hunter, DJ
Thomas, G
Chatterjee, N
Chanock, SJ
AF Chung, Charles C.
Ciampa, Julia
Yeager, Meredith
Jacobs, Kevin B.
Berndt, Sonja I.
Hayes, Richard B.
Gonzalez-Bosquet, Jesus
Kraft, Peter
Wacholder, Sholom
Orr, Nick
Yu, Kai
Hutchinson, Amy
Boland, Joseph
Chen, Quan
Feigelson, Heather Spencer
Thun, Michael J.
Diver, W. Ryan
Albanes, Demetrius
Virtamo, Jarmo
Weinstein, Stephanie
Schumacher, Fredrick R.
Cancel-Tassin, Geraldine
Cussenot, Olivier
Valeri, Antoine
Andriole, Gerald L.
Crawford, E. David
Haiman, Christopher A.
Henderson, Brian E.
Kolonel, Laurence
Le Marchand, Loic
Siddiq, Afshan
Riboli, Elio
Key, Tim J.
Kaaks, Rudolf
Isaacs, William B.
Isaacs, Sarah D.
Gronberg, Henrik
Wiklund, Fredrik
Xu, Jianfeng
Vatten, Lars J.
Hveem, Kristian
Njolstad, Inger
Gerhard, Daniela S.
Tucker, Margaret
Hoover, Robert N.
Fraumeni, Joseph F., Jr.
Hunter, David J.
Thomas, Gilles
Chatterjee, Nilanjan
Chanock, Stephen J.
TI Fine mapping of a region of chromosome 11q13 reveals multiple
independent loci associated with risk of prostate cancer
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; RECOMBINATION HOTSPOTS;
LINKAGE DISEQUILIBRIUM; GENETIC-VARIATION; COMMON VARIANT;
BREAST-CANCER; IDENTIFIES 5; POPULATION; MYEOV
AB Genome-wide association studies have identified prostate cancer susceptibility alleles on chromosome 11q13. As part of the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, the region flanking the most significant marker, rs10896449, was fine mapped in 10 272 cases and 9123 controls of European origin (10 studies) using 120 common single nucleotide polymorphisms (SNPs) selected by a two-staged tagging strategy using HapMap SNPs. Single-locus analysis identified 18 SNPs below genome-wide significance (P < 10(-8)) with rs10896449 the most significant (P = 7.94 x 10(-19)). Multi-locus models that included significant SNPs sequentially identified a second association at rs12793759 [odds ratio (OR) = 1.14, P = 4.76 x 10(-5), adjusted P = 0.004] that is independent of rs10896449 and remained significant after adjustment for multiple testing within the region. rs10896438, a proxy of previously reported rs12418451 (r(2) = 0.96), independent of both rs10896449 and rs12793759 was detected (OR = 1.07, P = 5.92 x 10(-3), adjusted P = 0.054). Our observation of a recombination hotspot that separates rs10896438 from rs10896449 and rs12793759, and low linkage disequilibrium (rs10896449-rs12793759, r(2) = 0.17; rs10896449-rs10896438, r(2) = 0.10; rs12793759-rs10896438, r(2) = 0.12) corroborate our finding of three independent signals. By analysis of tagged SNPs across similar to 123 kb using next generation sequencing of 63 controls of European origin, 1000 Genome and HapMap data, we observed multiple surrogates for the three independent signals marked by rs10896449 (n = 31), rs10896438 (n = 24) and rs12793759 (n = 8). Our results indicate that a complex architecture underlying the common variants contributing to prostate cancer risk at 11q13. We estimate that at least 63 common variants should be considered in future studies designed to investigate the biological basis of the multiple association signals.
C1 [Chung, Charles C.; Gonzalez-Bosquet, Jesus; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Ctr NCI,Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
[Chung, Charles C.; Ciampa, Julia; Yeager, Meredith; Jacobs, Kevin B.; Berndt, Sonja I.; Hayes, Richard B.; Gonzalez-Bosquet, Jesus; Wacholder, Sholom; Orr, Nick; Yu, Kai; Hutchinson, Amy; Boland, Joseph; Chen, Quan; Albanes, Demetrius; Weinstein, Stephanie; Tucker, Margaret; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Hunter, David J.; Thomas, Gilles; Chatterjee, Nilanjan; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Gerhard, Daniela S.] NCI, Off Canc Genom, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Yeager, Meredith; Jacobs, Kevin B.; Hutchinson, Amy; Boland, Joseph; Chen, Quan] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Hayes, Richard B.] NYU Sch Med, Dept Environm Med, New York, NY USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA.
[Schumacher, Fredrick R.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Feigelson, Heather Spencer; Thun, Michael J.; Diver, W. Ryan] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] Hop Tenon, AP HP, Ctr Rech Pathol Prostat, F-75970 Paris, France.
[Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Crawford, E. David] Univ Colorado, Dept Surg, Denver, CO 80202 USA.
[Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Kolonel, Laurence; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
[Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England.
[Key, Tim J.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Kaaks, Rudolf] German Canc Res Ctr, Div Clin Epidemiol, Heidelberg, Germany.
[Isaacs, William B.; Isaacs, Sarah D.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA.
[Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Vatten, Lars J.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7034 Trondheim, Norway.
[Njolstad, Inger] Univ Tromso, Inst Community Med, Tromso, Norway.
[Hunter, David J.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA.
[Thomas, Gilles] Univ Lyon 1, F-69365 Lyon, France.
RP Chanock, SJ (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Ctr NCI,Dept Hlth & Human Serv,NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov
RI Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015;
OI Hayes, Richard/0000-0002-0918-661X; Cancel-Tassin,
Geraldine/0000-0002-9583-6382
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health (NIH); [CA129684]; [HHSN261200800001E]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health (NIH). The project was partially funded in
part using grant CA129684 to J.X. and Contract Number HHSN261200800001E.
NR 41
TC 25
Z9 25
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2011
VL 20
IS 14
BP 2869
EP 2878
DI 10.1093/hmg/ddr189
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 790AG
UT WOS:000292560300015
PM 21531787
ER
PT J
AU Tse, KP
Su, WH
Yang, ML
Cheng, HY
Tsang, NM
Chang, KP
Hao, SP
Shugart, YY
Chang, YS
AF Tse, Ka-Po
Su, Wen-Hui
Yang, Min-lee
Cheng, Hsiao-Yun
Tsang, Ngan-Ming
Chang, Kai-Ping
Hao, Sheng-Po
Shugart, Yin Yao
Chang, Yu-Sun
TI A gender-specific association of CNV at 6p21.3 with NPC susceptibility
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID COPY NUMBER VARIATION; GENOME-WIDE ASSOCIATION; HIDDEN-MARKOV MODEL; SNP
GENOTYPING DATA; NASOPHARYNGEAL CARCINOMA; GENETIC POLYMORPHISMS; RISK;
CANCER; EPIDEMIOLOGY; POPULATION
AB Copy number variations (CNVs), a major source of human genetic polymorphism, have been suggested to have an important role in genetic susceptibility to common diseases such as cancer, immune diseases and neurological disorders. Nasopharyngeal carcinoma (NPC) is a multifactorial tumor closely associated with genetic background and with a male preponderance over female (3:1). Previous genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that are associated with NPC susceptibility. Here, we sought to explore the possible association of CNVs with NPC predisposition. Utilizing genome-wide SNP-based arrays and five CNV-prediction algorithms, we identified eight regions with CNV that were significantly overrepresented in NPC patients compared with healthy controls. These CNVs included six deletions (on chromosomes 3, 6, 7, 8 and 19), and two duplications (on chromosomes 7 and 12). Among them, the CNV located at chromosome 6p21.3, with single-copy deletion of the MICA and HCP5 genes, showed the highest association with NPC. Interestingly, it was more specifically associated with an increased NPC risk among males. This gender-specific association was replicated in an independent case-control sample using a self-established deletion-specific polymerase chain reaction strategy. To the best of our knowledge, this is the first study to explore the role of constitutional CNVs in NPC, using a genome-wide platform. Moreover, we identified eight novel candidate regions with CNV that merit future investigation, and our results suggest that similar to neuroblastoma and prostate cancer, genetic structural variations might contribute to NPC predisposition.
C1 [Tse, Ka-Po; Su, Wen-Hui; Yang, Min-lee; Cheng, Hsiao-Yun; Chang, Yu-Sun] Chang Gung Univ, Chang Gung Mol Med Res Ctr, Tao Yuan 333, Taiwan.
[Su, Wen-Hui] Chang Gung Univ, Dept Biomed Sci, Grad Inst Biomed Sci, Tao Yuan 333, Taiwan.
[Yang, Min-lee] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48105 USA.
[Yang, Min-lee] Univ Michigan, Dept Stat, Ann Arbor, MI 48105 USA.
[Tsang, Ngan-Ming] Chang Gung Mem Hosp Lin Kou, Dept Radiat Oncol, Tao Yuan 333, Taiwan.
[Chang, Kai-Ping; Hao, Sheng-Po] Chang Gung Mem Hosp Lin Kou, Dept Otolaryngol, Tao Yuan 333, Taiwan.
[Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Shugart, Yin Yao] Johns Hopkins Med Sch, Dept Pediat, Baltimore, MD 21205 USA.
RP Chang, YS (reprint author), 259 Wen Hwa 1st Rd, Tao Yuan 333, Taiwan.
EM ysc@mail.cgu.edu.tw
FU Ministry of Education; National Science Council [NSC 94-2314-B-182A-188,
94-3112-B-182-005, 95-2320-B-182-001, 97-3112-B-182-008]; Chang Gung
Memorial Hospital, Taiwan [CMRPD150961, CMRPG360221]
FX This work was supported by grants from the Ministry of Education (to
Chang Gung University), the National Science Council (NSC
94-2314-B-182A-188, 94-3112-B-182-005, 95-2320-B-182-001 and
97-3112-B-182-008) and Chang Gung Memorial Hospital (CMRPD150961 and
CMRPG360221), Taiwan.
NR 35
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2011
VL 20
IS 14
BP 2889
EP 2896
DI 10.1093/hmg/ddr191
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 790AG
UT WOS:000292560300017
PM 21536588
ER
PT J
AU Phillips, MD
Mukhopadhyay, M
Poscablo, C
Westphal, H
AF Phillips, Matthew D.
Mukhopadhyay, Mahua
Poscablo, Cristina
Westphal, Heiner
TI Dkk1 and Dkk2 regulate epicardial specification during mouse heart
development
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Mouse; Heart; Congenital; Dkk1; Dkk2; Wnt
ID BETA-CATENIN; WNT; DIFFERENTIATION; DISEASE; PROGENITORS; INDUCTION;
DICKKOPF1; SIGNALS; FAMILY; CELLS
AB Background: Dkk1 and Dkk2 interact with LRP5 and LRP6 to modulate canonical Wnt signaling during development, and are known to be expressed in the developing heart. However, a loss-of-function mutation in either gene by itself produces no discernable heart phenotype.
Methods: Using standard husbandry techniques, Dkk1 null and Dkk2 null mouse lines were crossed to create double null embryos, which we examined using histological and immunohistochemical methods.
Results: Double null embryos die perinatally, with a gross head phenotype reminiscent of Dkk1 null embryos. Upon examination of late stage hearts, we observe myocardial defects including ventricular septal defects. At earlier stages, double mutant hearts show myocardial and epicardial hyperplasia. Myocardial hypertrophy is associated with a moderate increase in cell proliferation, but epicardial hypercellularity is not. Rather, the field of proepicardial precursor cells near the liver shows a broadening of expression for the cardiac-specific gap junction protein Connexin 43.
Conclusions: Dkk1 and Dkk2 both inhibit Wnt signaling to regulate early myocardial proliferation and each can compensate for the loss of the other in that role. Wnt signaling regulates myocardial proliferation in both heart fields at early stages. Additionally, Wnt signaling is sufficient to increase proepicardial specification as measured by Connexin 43 expression, resulting in a hypercellular epicardium and perhaps contributing to later defects. Published by Elsevier Ireland Ltd.
C1 [Phillips, Matthew D.; Mukhopadhyay, Mahua; Poscablo, Cristina; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Program Genom Dev, NIH,HHS, Bethesda, MD 20892 USA.
RP Westphal, H (reprint author), NICHD, Lab Mammalian Genes & Dev, NIH, 6B-4B413 Ctr Dr, Bethesda, MD 20892 USA.
EM hw@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX We thank Mrs. Rui Lin for genotyping and Dr. Margaret Kirby for helpful
discussions. This research was supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health. The authors of
this manuscript have certified that they comply with the Principles of
Ethical Publishing in the International Journal of Cardiology [25].
NR 25
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U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JUL 15
PY 2011
VL 150
IS 2
BP 186
EP 192
DI 10.1016/j.ijcard.2010.04.007
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 789VO
UT WOS:000292545700027
PM 20439124
ER
PT J
AU Taubenberger, JK
Morens, DM
Krause, RM
Fauci, AS
AF Taubenberger, Jeffery K.
Morens, David M.
Krause, Richard M.
Fauci, Anthony S.
TI In Memoriam: Edwin D. Kilbourne, MD, 1920-2011
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID RECOMBINANT INFLUENZA-VIRUS; PULMONARY COMPLICATIONS; VACCINE;
INFECTION; IMMUNITY
C1 [Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Morens, David M.; Fauci, Anthony S.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA.
[Krause, Richard M.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis Sect, Infect Dis Lab, NIH, Bldg 33,Room 3E19A-2, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
NR 24
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U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2011
VL 204
IS 2
BP 185
EP 187
DI 10.1093/infdis/jir245
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790AZ
UT WOS:000292562200004
ER
PT J
AU West, SK
Munoz, B
Mkocha, H
Gaydos, CA
Quinn, TC
AF West, Sheila K.
Munoz, Beatriz
Mkocha, Harran
Gaydos, Charlotte A.
Quinn, Thomas C.
TI Number of Years of Annual Mass Treatment With Azithromycin Needed to
Control Trachoma in Hyper-endemic Communities in Tanzania
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CHLAMYDIA-TRACHOMATIS; HYPERENDEMIC COMMUNITY; ANTIBIOTIC-TREATMENT;
INFECTIOUS TRACHOMA; REDUCTION
AB Background. The World Health Organization recommends mass treatment as part of a trachoma control strategy. However, scant empirical data from hyperendemic communities exist on the number of rounds of treatment needed to reach a goal of <5% prevalence in children. We determined the prevalence of trachoma and infection with Chlamydia trachomatis in communities after 3-7 years of annual mass treatment in Tanzania.
Methods. Seventy-one communities with trachoma and annual azithromycin coverage data were enrolled. A cross-sectional survey of >= 100 randomly selected children aged <5 years in each community was performed. Children were examined for clinical trachoma, and swab samples were taken for determination of ocular C. trachomatis infection.
Results. After 3 years of mass treatment, the prevalence of trachoma decreased in a linear fashion with number of years of mass treatment, whereas decreased prevalences of C. trachomatis infection were related to the extent of the previous year's azithromycin coverage. Our model suggests that, for communities with baseline trachoma prevalence of 50% and annual treatment coverage of 75%, >7 years of annual mass treatment will be needed to reach a prevalence of trachoma of <5%.
Conclusions. Country programs in trachoma-endemic regions must realistically expect that several years of annual mass treatment may be necessary to eliminate trachoma.
C1 [West, Sheila K.; Munoz, Beatriz] Johns Hopkins Med Inst, Dept Opthalmol, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21205 USA.
[Gaydos, Charlotte A.; Quinn, Thomas C.] Johns Hopkins Med Inst, Int Chlamydia Lab, Div Infect Dis, Baltimore, MD 21205 USA.
[Quinn, Thomas C.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania.
RP West, SK (reprint author), Johns Hopkins Univ Hosp, Wilmer Eye Inst, Wilmer Rm 129,600 N Wolfe St, Baltimore, MD 21287 USA.
EM shwest@jhmi.edu
FU National Eye Institute [EY16429]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases
FX This work was funded by a grant from the National Eye Institute
(EY16429) and the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases. S. K. W. is a Research to Prevent
Blindness Senior Scientific Investigator.
NR 19
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U1 0
U2 2
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 JUL 15
PY 2011
VL 204
IS 2
BP 268
EP 273
DI 10.1093/infdis/jir257
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790AZ
UT WOS:000292562200016
PM 21673038
ER
PT J
AU Imamichi, H
DeGray, G
Dewar, RL
Mannon, P
Yao, M
Chairez, C
Sereti, I
Kovacs, JA
AF Imamichi, Hiromi
DeGray, Gerald
Dewar, Robin L.
Mannon, Peter
Yao, Michael
Chairez, Cheryl
Sereti, Irini
Kovacs, Joseph A.
TI Lack of Compartmentalization of HIV-1 Quasispecies Between the Gut and
Peripheral Blood Compartments
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL THERAPY;
INTESTINAL-MUCOSA; LYMPHOID-TISSUE; T-CELLS; INFECTION; EXPRESSION;
LYMPHOCYTES; ACTIVATION
AB Compartmental differences in human immunodeficiency virus type 1 (HIV-1) between the gut and peripheral blood and within the gut were examined. Biopsy specimens from the colon and ileum and peripheral blood samples were collected from chronically HIV-1-infected individuals. HIV-1 envelope sequences were examined from cell-associated DNA and RNA and virion RNA. Phylogenetic analysis revealed no evidence of compartmentalization of HIV-1 between the gut and peripheral blood and within the gut (colon and ileum). HIV-1 sequences detected in the gut were transcriptionally active and were also found in peripheral blood from matching time points, providing evidence of ongoing virus production in the gut and equilibrium of HIV-1 between the gut and peripheral blood compartments.
C1 [Imamichi, Hiromi; Chairez, Cheryl; Sereti, Irini] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[DeGray, Gerald; Dewar, Robin L.] NCI, Clin Serv Program, SAIC Frederick, Frederick, MD 21701 USA.
[Mannon, Peter; Yao, Michael] NIAID, Host Def Lab, Bethesda, MD 20892 USA.
[Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Imamichi, H (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bldg 550,Room 201-A,POB B, Frederick, MD 21702 USA.
EM himamichi@nih.gov
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN261200800001E]; National Institute of Allergy and Infectious
Disease (NIAID), NIH [HHSN261200800001E]; NIAID; NIH Clinical Center
FX This work was supported by the National Cancer Institute, National
Institutes of Health (NIH; contract HHSN261200800001E); the National
Institute of Allergy and Infectious Disease (NIAID), NIH (contract
HHSN261200800001E); and the Intramural Research Program of NIAID and the
NIH Clinical Center.
NR 16
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U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2011
VL 204
IS 2
BP 309
EP 314
DI 10.1093/infdis/jir259
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790AZ
UT WOS:000292562200021
PM 21673043
ER
PT J
AU Dahiya, N
Becker, KG
Wood, WH
Zhang, YQ
Morin, PJ
AF Dahiya, Neetu
Becker, Kevin G.
Wood, William H., III
Zhang, Yongqing
Morin, Patrice J.
TI Claudin-7 Is Frequently Overexpressed in Ovarian Cancer and Promotes
Invasion
SO PLOS ONE
LA English
DT Article
ID JUNCTION PROTEIN CLAUDIN-7; PROSTATE-SPECIFIC ANTIGEN; SQUAMOUS-CELL
CARCINOMA; REDUCED EXPRESSION; COLORECTAL-CANCER; EPITHELIAL-CELLS;
TIGHT JUNCTIONS; ADHESION MOLECULE; BARRIER FUNCTION; GENE-EXPRESSION
AB Background: Claudins are tight junction proteins that are involved in tight junction formation and function. Previous studies have shown that claudin-7 is frequently upregulated in epithelial ovarian cancer (EOC) along with claudin-3 and claudin-4. Here, we investigate in detail the expression patterns of claudin-7, as well as its possible functions in EOC.
Methodology/Principal Findings: A total of 95 ovarian tissue samples (7 normal ovarian tissues, 65 serous carcinomas, 11 clear cell carcinomas, 8 endometrioid carcinomas and 4 mucinous carcinomas) were studied for claudin-7 expression. In real-time RT-PCR analysis, the gene for claudin-7, CLDN7, was found to be upregulated in all the tumor tissue samples studied. Similarly, immunohistochemical analysis and western blotting showed that claudin-7 protein was significantly overexpressed in the vast majority of EOCs. Small interfering RNA-mediated knockdown of claudin-7 in ovarian cancer cells led to significant changes in gene expression as measured by microarrays and validated by RT-PCR and immunoblotting. Analyses of the genes differentially expressed revealed that the genes altered in response to claudin-7 knockdown were associated with pathways implicated in various molecular and cellular functions such as cell cycle, cellular growth and proliferation, cell death, development, and cell movement. Through functional experiments in vitro, we found that both migration and invasion were altered in cells where CLDN7 had been knocked down or overexpressed. Interestingly, claudin-7 expression was associated with a net increase in invasion, but also with a decrease in migration.
Conclusion/Significance: Our work shows that claudin-7 is significantly upregulated in EOC and that it may be functionally involved in ovarian carcinoma invasion. CLDN7 may therefore represent potential marker for ovarian cancer detection and a target for therapy.
C1 [Dahiya, Neetu; Morin, Patrice J.] NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA.
[Becker, Kevin G.; Wood, William H., III; Zhang, Yongqing] NIA, Res Resource Branch, Baltimore, MD 21224 USA.
[Morin, Patrice J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
RP Dahiya, N (reprint author), NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA.
EM morinp@mail.nih.gov
RI Dahiya, Neetu/E-5208-2011;
OI Becker, Kevin/0000-0002-6794-6656
FU National Institutes of Health, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
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U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 15
PY 2011
VL 6
IS 7
AR e22119
DI 10.1371/journal.pone.0022119
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 793HT
UT WOS:000292811700025
PM 21789222
ER
PT J
AU Glesner, J
Wunschmann, S
Li, M
Gustchina, A
Wlodawer, A
Himly, M
Chapman, MD
Pomes, A
AF Glesner, Jill
Wuenschmann, Sabina
Li, Mi
Gustchina, Alla
Wlodawer, Alexander
Himly, Martin
Chapman, Martin D.
Pomes, Anna
TI Mechanisms of Allergen-Antibody Interaction of Cockroach Allergen Bla g
2 with Monoclonal Antibodies That Inhibit IgE Antibody Binding
SO PLOS ONE
LA English
DT Article
ID MAGNETIC-RESONANCE STRUCTURE; FLUORESCENT MULTIPLEX ARRAY; SITE-DIRECTED
MUTAGENESIS; DUST-MITE ALLERGEN; MAJOR ALLERGEN; CARBOHYDRATE
DETERMINANTS; MUTATIONAL ANALYSIS; CRYSTAL-STRUCTURE; GRASS-POLLEN;
AMINO-ACID
AB Background: Cockroach allergy is strongly associated with asthma, and involves the production of IgE antibodies against inhaled allergens. Reports of conformational epitopes on inhaled allergens are limited. The conformational epitopes for two specific monoclonal antibodies (mAb) that interfere with IgE antibody binding were identified by X-ray crystallography on opposite sites of the quasi-symmetrical cockroach allergen Bla g 2.
Methodology/Principal Findings: Mutational analysis of selected residues in both epitopes was performed based on the Xray crystal structures of the allergen with mAb Fab/Fab9 fragments, to investigate the structural basis of allergen-antibody interactions. The epitopes of Bla g 2 for the mAb 7C11 or 4C3 were mutated, and the mutants were analyzed by SDS-PAGE, circular dichroism, and/or mass spectrometry. Mutants were tested for mAb and IgE antibody binding by ELISA and fluorescent multiplex array. Single or multiple mutations of five residues from both epitopes resulted in almost complete loss of mAb binding, without affecting the overall folding of the allergen. Preventing glycosylation by mutation N268Q reduced IgE binding, indicating a role of carbohydrates in the interaction. Cation-p interactions, as well as electrostatic and hydrophobic interactions, were important for mAb and IgE antibody binding. Quantitative differences in the effects of mutations on IgE antibody binding were observed, suggesting heterogeneity in epitope recognition among cockroach allergic patients.
Conclusions/Significance: Analysis by site-directed mutagenesis of epitopes identified by X-ray crystallography revealed an overlap between monoclonal and IgE antibody binding sites and provided insight into the B cell repertoire to Bla g 2 and the mechanisms of allergen-antibody recognition, including involvement of carbohydrates.
C1 [Glesner, Jill; Wuenschmann, Sabina; Chapman, Martin D.; Pomes, Anna] INDOOR Biotechnol Inc, Charlottesville, VA USA.
[Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD USA.
[Li, Mi; Gustchina, Alla; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA.
[Himly, Martin] Salzburg Univ, Div Allergy & Immunol, Dept Mol Biol, A-5020 Salzburg, Austria.
RP Glesner, J (reprint author), INDOOR Biotechnol Inc, Charlottesville, VA USA.
EM apomes@inbio.com
RI Himly, Martin/D-1568-2015;
OI Himly, Martin/0000-0001-5416-085X; Pomes, Anna/0000-0002-8729-1829
FU National Institute of Allergy and Infectious Diseases [RO1AI077653];
NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, NIH [HHSN261200800001E]; NIAID/NIH
FX This project was supported in part by Award Number RO1AI077653 from the
National Institute of Allergy and Infectious Diseases
(http://www.niaid.nih.gov), in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research, and
in part with Federal funds from the National Cancer Institute, NIH,
under Contract No. HHSN261200800001E. The content of this publication is
solely the responsibility of the authors and does not necessarily
represent the official views or policies of the Department of Health and
Human Services, nor does the mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; The authors JG,
SW, MDC and AP are employed by Indoor Biotechnologies, Inc. MDC is the
president and owner of the company. AP is the contact PI of the RO1 from
the NIAID/NIH that finances this study. This does not alter the authors'
adherence to all the PLoS ONE policies on sharing data and materials.
NR 38
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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 JUL 15
PY 2011
VL 6
IS 7
AR e22223
DI 10.1371/journal.pone.0022223
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 793HT
UT WOS:000292811700035
PM 21789239
ER
PT J
AU Luo, AH
Tahsili-Fahadan, P
Wise, RA
Lupica, CR
Aston-Jones, G
AF Luo, Alice H.
Tahsili-Fahadan, Pouya
Wise, Roy A.
Lupica, Carl R.
Aston-Jones, Gary
TI Linking Context with Reward: A Functional Circuit from Hippocampal CA3
to Ventral Tegmental Area
SO SCIENCE
LA English
DT Article
ID DOPAMINE NEURONS; COCAINE-SEEKING; NUCLEUS; RAT; REPRESENTATIONS;
STIMULATION; PROJECTIONS; AFFERENTS; RELAPSE; MEMORY
AB Reward-motivated behavior is strongly influenced by the learned significance of contextual stimuli in the environment. However, the neural pathways that mediate context-reward relations are not well understood. We have identified a circuit from area CA3 of dorsal hippocampus to ventral tegmental area (VTA) that uses lateral septum (LS) as a relay. Theta frequency stimulation of CA3 excited VTA dopamine (DA) neurons and inhibited non-DA neurons. DA neuron excitation was likely mediated by disinhibition because local antagonism of g-aminobutyric acid receptors blocked responses to CA3 stimulation. Inactivating components of the CA3-LS-VTA pathway blocked evoked responses in VTA and also reinstatement of cocaine-seeking by contextual stimuli. This transsynaptic link between hippocampus and VTA appears to be an important substrate by which environmental context regulates goal-directed behavior.
C1 [Luo, Alice H.; Wise, Roy A.] Natl Inst Drug Abuse, Behav Neurosci Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Tahsili-Fahadan, Pouya; Aston-Jones, Gary] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Lupica, Carl R.] Natl Inst Drug Abuse, Electrophysiol Res Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Luo, AH (reprint author), Natl Inst Drug Abuse, Behav Neurosci Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
EM alice_luo@hotmail.com
RI Wise, Roy/A-6465-2012
FU U.S. Public Health Service [R37-DA006214, F31-MH071093]; National
Institute on Drug Abuse
FX We thank B. Bingham and J. See for assistance with the initial
anatomical experiments; R. Fallon, G. Sartor, L. Zhang, S. Mahler, K.
Moussawi, R. Smith, and T. Smith for assistance with behavioral studies;
C. Backman and W. Freed for use of their microscopy equipment; and C.
Mejias-Aponte for his programming expertise and thoughtful comments.
This work was supported by U.S. Public Health Service grant awards
R37-DA006214 and F31-MH071093, and the National Institute on Drug Abuse
Intramural Research Program. The anatomical data were gathered at the
University of Pennsylvania.
NR 17
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U1 5
U2 32
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 JUL 15
PY 2011
VL 333
IS 6040
BP 353
EP 357
DI 10.1126/science.1204622
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 792HF
UT WOS:000292732000046
PM 21764750
ER
PT J
AU Jiang, WZ
Chai, NR
Maric, D
Bielekova, B
AF Jiang, Wenzheng
Chai, Noo Ri
Maric, Dragan
Bielekova, Bibiana
TI Unexpected Role for Granzyme K in CD56(bright) NK Cell-Mediated
Immunoregulation of Multiple Sclerosis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
CENTRAL-NERVOUS-SYSTEM; REGULATORY T-CELLS; PERIPHERAL-BLOOD;
DIFFERENTIAL EXPRESSION; INTERFERON-BETA; LYMPH-NODES; PERFORIN;
DACLIZUMAB
AB Functional NK cell deficiencies are associated with autoimmune diseases, including multiple sclerosis. NK cells can promote or inhibit adaptive immunity via either cytokine production or cytotoxicity toward immature dendritic cells and activated T cells. In humans, this immunoregulatory role resides in the CD56(bright) NK cell subset, which is selectively expanded by daclizumab, a CD25-blocking Ab that suppresses multiple sclerosis-associated inflammation. The objective of this study was to investigate the molecular mechanisms underlying the cytotoxicity of NK cells toward activated T cells. We demonstrated that NK cells induce caspase-independent apoptosis that requires NK cell degranulation and causes mitochondrial dysfunction in activated T cells. Although both granzyme A and granzyme K (GrK) can mediate this form of apoptosis, quantitatively we observed preferential transfer of GrK to target cells. Consequently, gene silencing of GrK in the NK-92 cell line, which retains functional characteristics of CD56(bright) NK cells, profoundly inhibited the ability of NK-92 cells to kill activated syngeneic T cells. Finally, we demonstrated that daclizumab treatment significantly enhanced this newly defined mechanism of cytotoxicity by CD56(bright) NK cells. Our study describes the important physiological role that GrK plays in immunoregulation of adaptive immunity in humans and indicates that therapeutic exploitation of this pathway is beneficial in controlling autoimmunity. The Journal of Immunology, 2011, 187: 781-790.
C1 [Jiang, Wenzheng; Chai, Noo Ri; Bielekova, Bibiana] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Jiang, Wenzheng] E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bldg 10,Room 5C103, Bethesda, MD 20892 USA.
EM Bibi.Bielekova@nih.gov
FU National Institute of Neurological Disorders and Stroke/National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke/National
Institutes of Health.
NR 46
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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 JUL 15
PY 2011
VL 187
IS 2
BP 781
EP 790
DI 10.4049/jimmunol.1100789
PG 10
WC Immunology
SC Immunology
GA 788NF
UT WOS:000292451000024
PM 21666061
ER
PT J
AU Choi, S
Schwartz, RH
AF Choi, Seeyoung
Schwartz, Ronald H.
TI Impairment of Immunological Synapse Formation in Adaptively Tolerant T
Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MEDIATES RAP1-INDUCED ADHESION; MICROTUBULE-ORGANIZING CENTER;
ANTIGEN-PRESENTING CELLS; INTEGRIN ACTIVATION; IMMUNE SYNAPSE;
CYTOSKELETAL REORGANIZATION; RECEPTOR MICROCLUSTERS; ACTIN
POLYMERIZATION; SIGNALING PROTEINS; ADAPTER PROTEIN
AB Adaptive tolerance is a hyporesponsive state in which lymphocyte Ag receptor signaling becomes desensitized after prolonged in vivo encounter with Ag. The molecular mechanisms underlying this hyporesponsive state in T cells are not fully understood, although a major signaling block has been shown to be present at the level of ZAP70 phosphorylation of linker for activation of T cells (LAT). In this study, we investigated the ability of adaptively tolerant mouse T cells to form conjugates with Ag-bearing APCs and to translocate signaling molecules into the interface between the T cells and APCs. Compared with naive or preactivated T cells, adaptively tolerant T cells showed no dramatic impairment in their formation of conjugates with APCs. In contrast, there was a large impairment in immunological synapse formation. Adaptively tolerant T cells were defective in their translocation of signaling molecules, such as ZAP70, LAT, and phospholipase C gamma 1, into the T cell-APC contact sites. Although Ag-induced activation of VAV1 was normal, VAV's recruitment into the synapse was also impaired. Interestingly, expressions of both IL-2-inducible T cell kinase and growth factor receptor-bound protein 2-related adaptor downstream of SHC were decreased by 60-80% in adaptively tolerant T cells. These decreases, in addition to the impairment in LAT phosphorylation by ZAP70, appear to be the major impediments to the phosphorylation of SLP76 (SRC homology 2 domain-containing leukocyte protein of 76 kDa) and the recruitment of VAV1, which are important for stable immunological synapse formation. The Journal of Immunology, 2011, 187: 805-816.
C1 [Schwartz, Ronald H.] NIAID, Cellular & Mol Immunol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, Dept Hlth & Human Serv, NIH, Bldg 4,Room 111,MSC 0420, Bethesda, MD 20892 USA.
EM rs34r@niaid.nih.gov
FU National Institutes of Health
FX This work was supported by the National Institutes of Health Intramural
Research Program.
NR 69
TC 3
Z9 3
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 JUL 15
PY 2011
VL 187
IS 2
BP 805
EP 816
DI 10.4049/jimmunol.1003314
PG 12
WC Immunology
SC Immunology
GA 788NF
UT WOS:000292451000026
PM 21685322
ER
PT J
AU Killebrew, JR
Perdue, N
Kwan, A
Thornton, AM
Shevach, EM
Campbell, DJ
AF Killebrew, Justin R.
Perdue, Nikole
Kwan, Alan
Thornton, Angela M.
Shevach, Ethan M.
Campbell, Daniel J.
TI A Self-Reactive TCR Drives the Development of Foxp3(+) Regulatory T
Cells That Prevent Autoimmune Disease
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RECEPTOR TRANSGENIC MICE; DENDRITIC CELLS; PERIPHERAL TOLERANCE; CLONAL
DELETION; IN-VIVO; ANTIGEN; MAINTENANCE; THYMUS; HOMEOSTASIS; EXPRESSION
AB Although Foxp3(+) regulatory T cells (Tregs) are thought to express autoreactive TCRs, it is not clear how individual TCRs influence Treg development, phenotype, and function in vivo. We have generated TCR transgenic mice (termed SFZ70 mice) using Tcra and Tcrb genes cloned from an autoreactive CD4(+) T cell isolated from a Treg-deficient scurfy mouse. The SFZ70 TCR recognizes a cutaneous autoantigen and drives development of both conventional CD4(+) Foxp3(-) T cells (T-conv) and Foxp3(+) Tregs. SFZ70 Tregs display an activated phenotype evidenced by robust proliferation and expression of skin-homing molecules such as CD103 and P-selectin ligand. Analysis of Foxp3-deficient SFZ70 mice demonstrates that Tregs inhibit T-conv cell expression of tissue-homing receptors and their production of proinflammatory cytokines. In addition, Treg suppression of SFZ70 T-conv cells can be overcome by nonspecific activation of APCs. These results provide new insights into the differentiation and function of tissue-specific Tregs in vivo and provide a tractable system for analyzing the molecular requirements of Treg-mediated tolerance toward a cutaneous autoantigen. The Journal of Immunology, 2011, 187: 861-869.
C1 [Killebrew, Justin R.; Perdue, Nikole; Kwan, Alan; Campbell, Daniel J.] Benaroya Res Inst, Program Immunol, Seattle, WA 98101 USA.
[Killebrew, Justin R.; Campbell, Daniel J.] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA.
[Thornton, Angela M.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Campbell, DJ (reprint author), Benaroya Res Inst, Program Immunol, 1201 9th Ave, Seattle, WA 98101 USA.
EM campbell@benaroyaresearch.org
FU National Institutes of Health [AR055695, DK072295, AI067750]; Cancer
Research Institute Predoctoral Emphasis Pathway in Tumor Immunology
FX This work was supported by National Institutes of Health Grants
AR055695, DK072295, and AI067750 (to D.J.C.). J.R.K. was supported in
part by the Cancer Research Institute Predoctoral Emphasis Pathway in
Tumor Immunology.
NR 45
TC 17
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 JUL 15
PY 2011
VL 187
IS 2
BP 861
EP 869
DI 10.4049/jimmunol.1004009
PG 9
WC Immunology
SC Immunology
GA 788NF
UT WOS:000292451000032
PM 21690323
ER
PT J
AU Li, F
Folk, JE
Cheng, KJ
Kurimura, M
Deck, JA
Deschamps, JR
Rothman, RB
Dersch, CM
Jacobson, AE
Rice, KC
AF Li, Feng
Folk, John E.
Cheng, Kejun
Kurimura, Muneaki
Deck, Jason A.
Deschamps, Jeffrey R.
Rothman, Richard B.
Dersch, Christina M.
Jacobson, Arthur E.
Rice, Kenner C.
TI Probes for narcotic receptor mediated phenomena. 43. Synthesis of the
ortho-a and para-a, and improved synthesis and optical resolution of the
ortho-b and para-b oxide-bridged phenylmorphans: Compounds with moderate
to low opioid-receptor affinity
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE ortho-a and ortho-b oxide-bridged; phenylmorphans; para-a and para-b
oxide-bridged; phenylmorphans; Synthesis; Optical resolution
ID N-PHENETHYL ANALOGS; ISOMERS
AB N-Phenethyl-substituted ortho-a and para-a oxide-bridged phenylmorphans have been obtained through an improved synthesis and their binding affinity examined at the various opioid receptors. Although the N-phenethyl substituent showed much greater affinity for mu- and kappa-opioid receptors than their N-methyl relatives (e. g., K(i) = 167 nM and 171 nM at mu- and kappa-receptors vs > 2800 and 7500 nM for the N-methyl ortho-a oxide-bridged phenylmorphan), the a-isomers were not examined further because of their relatively low affinity. The N-phenethyl substituted ortho-b and para-b oxide-bridged phenylmorphans were also synthesized and their enantiomers were obtained using supercritical fluid chromatography. Of the four enantiomers, only the (+)-ortho-b isomer had moderate affinity for mu- and kappa-receptors (K(i) = 49 and 42 nM, respectively, and it was found to also have moderate mu- and kappa-opioid antagonist activity in the [(35)S]GTP-gamma-S assay (K(e) = 31 and 26 nM). (C) 2011 Published by Elsevier
C1 [Li, Feng; Folk, John E.; Cheng, Kejun; Kurimura, Muneaki; Deck, Jason A.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Li, Feng; Folk, John E.; Cheng, Kejun; Kurimura, Muneaki; Deck, Jason A.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Deschamps, Jeffrey R.] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA.
[Deschamps, Jeffrey R.] NIH, Ctr Mol Modeling, Div Computat Biosci, CIT,DHHS, Bethesda, MD 20892 USA.
NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Chem Biol Res Branch,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Rice, KC (reprint author), NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, 5625 Fishers Lane,Room 4N03, Bethesda, MD 20892 USA.
EM kr21f@nih.gov
OI Deschamps, Jeffrey/0000-0001-5845-0010
FU NIH of the National Institute on Drug Abuse (NIDA); National Institute
of Alcohol Abuse and Alcoholism; NIDA through Naval Research Laboratory
(NRL) [Y1-DA1101]
FX The work 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) and the National Institute of Alcohol
Abuse and Alcoholism. The Clinical Psychopharmacology Section, CBRB,
NIDA, was supported by the NIH Intramural Research Program of the
National Institute on Drug Abuse (NIDA). We thank the Averica Discovery
Services, J.P. Kiplinger, President, Worcester, MA, for carrying out the
supercritical fluid chromatography used to obtain the enantiomers of 16
and 19. We also thank Dr. Klaus Gawrisch and Dr. Walter Teague
(Laboratory of Membrane Biochemistry and Biophysics, NIAAA, for NMR
spectral data. The authors express their thanks to Noel Whittaker and
Wesley White, Laboratory of Analytical Chemistry, NIDDK, for mass
spectral data and 1H NMR spectral data. The X-ray
crystallographic work was supported by NIDA through an Interagency
Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL).
NR 17
TC 3
Z9 3
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2011
VL 19
IS 14
BP 4330
EP 4337
DI 10.1016/j.bmc.2011.05.035
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 786JD
UT WOS:000292301200018
PM 21684752
ER
PT J
AU Ahmed, SK
Etoga, JLG
Patel, SA
Bridges, RJ
Thompson, CM
AF Ahmed, S. Kaleem
Etoga, Jean-Louis G.
Patel, Sarjubhai A.
Bridges, Richard J.
Thompson, Charles M.
TI Use of the hydantoin isostere to produce inhibitors showing selectivity
toward the vesicular glutamate transporter versus the obligate exchange
transporter system x(c)(-)
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Hydantoin scaffolds; Glutamate; System x(c)(-); Inhibitor; VGLUT
ID QUINOLINE-2,4-DICARBOXYLIC ACIDS; BRAIN-FUNCTION; RECEPTORS
AB Evidence was acquired prior to suggest that the vesicular glutamate transporter (VGLUT) but not other glutamate transporters were inhibited by structures containing a weakly basic a-amino group. To test this hypothesis, a series of analogs using a hydantoin (pK(a) similar to 9.1) isostere were synthesized and analyzed as inhibitors of VGLUT and the obligate cystine-glutamate transporter (system x(c)(-)). Of the hydantoin analogs tested, a thiophene-5-carboxaldehyde analog 2l and a bis-hydantoin 4b were relatively strong inhibitors of VGLUT reducing uptake to less than 6% of control at 5 mM but few inhibited system x(c)(-) greater than 50% of control. The benzene-2,4-disulfonic acid analog 2b and p-diaminobenzene analog 2e were also good hydantoin-based inhibitors of VGLUT reducing uptake by 11% and 23% of control, respectively, but neither analog was effective as a system x(c)(-) inhibitor. In sum, a hydantoin isostere adds the requisite chemical properties needed to produce selective inhibitors of VGLUT. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Ahmed, S. Kaleem; Thompson, Charles M.] Univ Montana, Core Lab Neuromol Prod, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
[Etoga, Jean-Louis G.] Univ Montana, Dept Chem & Biochem, Missoula, MT 59812 USA.
[Patel, Sarjubhai A.; Bridges, Richard J.; Thompson, Charles M.] Univ Montana, COBRE Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
[Thompson, Charles M.] ATERIS Technol LLC, Missoula, MT 59802 USA.
RP Thompson, CM (reprint author), Univ Montana, Core Lab Neuromol Prod, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
EM charles.thompson@umontana.edu
RI Ahmed, Syed/I-5530-2013
FU Core Laboratory for Neuromolecular Production [P30 NS055022, NS058229,
NS30570, NS42077]; COBRE Center for Structural and Functional
Neuroscience [NIH P20-RR015583]; [NS38248]
FX This research was supported by NS38248 (CMT), the Core Laboratory for
Neuromolecular Production P30 NS055022 (CMT), NS058229 (ATERIS
Technologies LLC), NS30570 (RJB), NS42077 (RJB) and the COBRE Center for
Structural and Functional Neuroscience (NIH P20-RR015583).
NR 31
TC 8
Z9 8
U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUL 15
PY 2011
VL 21
IS 14
BP 4358
EP 4362
DI 10.1016/j.bmcl.2011.05.018
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 784VM
UT WOS:000292186400052
PM 21669531
ER
PT J
AU Yang, X
Beason-Held, L
Resnick, SM
Landman, BA
AF Yang, Xue
Beason-Held, Lori
Resnick, Susan M.
Landman, Bennett A.
TI Biological parametric mapping with robust and non-parametric statistics
SO NEUROIMAGE
LA English
DT Article
DE Structure-function relationships; Statistical parametric mapping;
Biological parametric mapping; Robust regression; Non-parametric
regression
ID LEAST-SQUARES; BRAIN; REGRESSION; IMAGES; UNIVARIATE; SERIES; TESTS
AB Mapping the quantitative relationship between structure and function in the human brain is an important and challenging problem. Numerous volumetric, surface, regions of interest and voxelwise image processing techniques have been developed to statistically assess potential correlations between imaging and non-imaging metrices. Recently, biological parametric mapping has extended the widely popular statistical parametric mapping approach to enable application of the general linear model to multiple image modalities (both for regressors and regressands) along with scalar valued observations. This approach offers great promise for direct, voxelwise assessment of structural and functional relationships with multiple imaging modalities. However, as presented, the biological parametric mapping approach is not robust to outliers and may lead to invalid inferences (e.g., artifactual low p-values) due to slight mis-registration or variation in anatomy between subjects. To enable widespread application of this approach, we introduce robust regression and non-parametric regression in the neuroimaging context of application of the general linear model. Through simulation and empirical studies, we demonstrate that our robust approach reduces sensitivity to outliers without substantial degradation in power. The robust approach and associated software package provide a reliable way to quantitatively assess voxelwise correlations between structural and functional neuroimaging modalities. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Yang, Xue; Landman, Bennett A.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Beason-Held, Lori; Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA.
[Landman, Bennett A.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
RP Landman, BA (reprint author), Vanderbilt Univ EECS, 2301 Vanderbilt Pl,POB 351679 Stn B, Nashville, TN 37235 USA.
EM bennett.landman@vanderbilt.edu
FU NIH/NINDS [1R01NS056307, 1R21NS064534]; NIH, National Institute on Aging
and by Research and Development [N01-AG-3-2124]
FX Grant Support: NIH/NINDS 1R01NS056307 and NIH/NINDS 1R21NS064534. This
project was supported in part by grants NIH/NINDS1R01 NS056307 and
NIH/NINDS1R21NS064534, the Intramural Research Program of the NIH,
National Institute on Aging and by Research and Development Contract
N01-AG-3-2124.
NR 27
TC 11
Z9 11
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUL 15
PY 2011
VL 57
IS 2
BP 423
EP 430
DI 10.1016/j.neuroimage.2011.04.046
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 781TU
UT WOS:000291960200017
PM 21569856
ER
PT J
AU Goldsmith, J
Crainiceanu, CM
Caffo, BS
Reich, DS
AF Goldsmith, Jeff
Crainiceanu, Ciprian M.
Caffo, Brian S.
Reich, Daniel S.
TI Penalized functional regression analysis of white-matter tract profiles
in multiple sclerosis
SO NEUROIMAGE
LA English
DT Article
DE Multiple sclerosis; Diffusion tensor imaging; Magnetization transfer
ratio; Regression methods; Functional data analysis
ID DIFFUSION TENSOR TRACTOGRAPHY; CORTICOSPINAL TRACT; QUANTITATIVE MRI;
CORPUS-CALLOSUM; DISABILITY; IMPAIRMENT; MORPHOMETRY; STATISTICS;
TRACKING; DISEASE
AB Diffusion tensor imaging (DTI) enables noninvasive parcellation of cerebral white matter into its component fiber bundles or tracts. These tracts often subserve specific functions, and damage to the tracts can therefore result in characteristic forms of disability. Attempts to quantify the extent of tract-specific damage have been limited in part by substantial spatial variation of imaging properties from one end of a tract to the other, variation that can be compounded by the effects of disease. Here, we develop a "penalized functional regression" procedure to analyze spatially normalized tract profiles, which powerfully characterize such spatial variation. The central idea is to identify and emphasize portions of a tract that are more relevant to a clinical outcome score, such as case status or degree of disability. The procedure also yields a "tract abnormality score" for each tract and MRI index studied. Importantly, the weighting function used in this procedure is constrained to be smooth, and the statistical associations are estimated using generalized linear models. We test the method on data from a cross-sectional MRI and functional study of 115 multiple-sclerosis cases and 42 healthy volunteers, considering a range of quantitative MRI indices, white-matter tracts, and clinical outcome scores, and using training and testing sets to validate the results. We show that attention to spatial variation yields up to 15% (mean across all tracts and MRI indices: 6.4%) improvement in the ability to discriminate multiple sclerosis cases from healthy volunteers. Our results confirm that comprehensive analysis of white-matter tract-specific imaging data improves with knowledge and characterization of the normal spatial variation. Published by Elsevier Inc.
C1 [Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Goldsmith, Jeff; Crainiceanu, Ciprian M.; Caffo, Brian S.] Johns Hopkins Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
[Reich, Daniel S.] Johns Hopkins Sch Med, Dept Radiol, Bethesda, MD 20892 USA.
[Reich, Daniel S.] Johns Hopkins Sch Med, Dept Neurol, Bethesda, MD 20892 USA.
RP Reich, DS (reprint author), NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, 10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA.
EM jgoldsmi@jhsph.edu; ccrainic@jhsph.edu; bcaffo@jhsph.edu;
daniel.reich@nih.gov
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU National Institutes of Health (National Institute of Neurological
Disorders and Stroke) [K99NS064098, R01NS060910, R01EB012547,
P41RR015241]; National Multiple Sclerosis Society [TR3760A3]; EMD Serono
FX The authors thank Peter Calabresi, Peter van Zijl, Seth Smith, Eliza
Gordon-Lipkin, Sheena Farrell, Terri Brawner, Kathleen Kahl, and Ivana
Kusevic, all of whom were instrumental in collecting the data for this
study. Jonathan Farrell and Bennett Landman provided assistance with
image processing. The study was supported by the National Institutes of
Health (the Intramural Research Program of the National Institute of
Neurological Disorders and Stroke as well as grants K99NS064098,
R01NS060910, R01EB012547, and P41RR015241); the National Multiple
Sclerosis Society (grant TR3760A3): and an unrestricted grant from EMD
Serono to support data collection. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the funding agencies.
NR 36
TC 13
Z9 13
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUL 15
PY 2011
VL 57
IS 2
BP 431
EP 439
DI 10.1016/j.neuroimage.2011.04.044
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 781TU
UT WOS:000291960200018
PM 21554962
ER
PT J
AU Goloshevsky, AG
Wu, CWH
Dodd, SJ
Koretsky, AP
AF Goloshevsky, Artem G.
Wu, Carolyn W. -H.
Dodd, Stephen J.
Koretsky, Alan P.
TI Mapping cortical representations of the rodent forepaw and hindpaw with
BOLD fMRI reveals two spatial boundaries
SO NEUROIMAGE
LA English
DT Article
DE BOLD; CBV; fMRI; Rat; Electrical stimulation; Cortical representation;
Induced cortical plasticity; Peripheral denervation; Histochemical
staining
ID PRIMARY SOMATOSENSORY CORTEX; CEREBRAL-BLOOD-FLOW; ISO-ORIENTATION
COLUMNS; LEVEL-DEPENDENT SIGNAL; FUNCTIONAL MRI; GRADIENT-ECHO;
SPIN-ECHO; CYTOCHROME-OXIDASE; NEURONAL-ACTIVITY; VISUAL-CORTEX
AB Electrical stimulation of the rat forepaw and hindpaw was employed to study the spatial distribution of BOLD fMRI. Averaging of multiple fMRI sessions significantly improved the spatial stability of the BOLD signal and enabled quantitative determination of the boundaries of the BOLD fMRI maps. The averaged BOLD fMRI signal was distributed unevenly over the extent of the map and the data at the boundaries could be modeled with major and minor spatial components. Comparison of three-dimensional echo-planar imaging (EPI) fMRI at isotropic 300 pm resolution demonstrated that the border locations of the major spatial component of BOLD signal did not overlap between the forepaw and hindpaw maps. Interestingly, the border positions of the minor BOLD fMRI spatial components extended significantly into neighboring representations. Similar results were found for cerebral blood volume (CBV) weighted fMRI obtained using iron oxide particles, suggesting that the minor spatial components may not be due to vascular mislocalization typically associated with BOLD fMRI. Comparison of the BOLD fMRI maps of the forepaw and hindpaw to histological determination of these representations using cytochrome oxidase (CO) staining demonstrated that the major spatial component of the BOLD fMRI activation maps accurately localizes the borders. Finally, 2-3 weeks following peripheral nerve denervation, cortical reorganization/plasticity at the boundaries of somatosensory limb representations in adult rat brain was studied. Denervation of the hindpaw caused a growth in the major component of forepaw representation into the adjacent border of hindpaw representation, such that fitting to two components no longer led to a better fit as compared to using one major component. The border of the representation after plasticity was the same as the border of its minor component in the absence of any plasticity. It is possible that the minor components represent either vascular effects that extend from the real neuronal representations or the neuronal communication between neighboring regions. Either way the results will be useful for studying mechanisms of plasticity that cause alterations in the boundaries of neuronal representations. Published by Elsevier Inc.
C1 [Koretsky, Alan P.] NINDS, LFMI, NIH, Bethesda, MD 20892 USA.
RP Koretsky, AP (reprint author), NINDS, LFMI, NIH, Bldg 10,Rm B1D728,10 Ctr Dr, Bethesda, MD 20892 USA.
EM koretskya@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NINDS, NIH
FX The authors would like to thank Nadia Bouraoud for animal preparation
and physiology. This work was supported by the intramural research
program of NINDS, NIH.
NR 75
TC 5
Z9 5
U1 0
U2 7
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 JUL 15
PY 2011
VL 57
IS 2
BP 526
EP 538
DI 10.1016/j.neuroimage.2011.04.002
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 781TU
UT WOS:000291960200027
PM 21504796
ER
PT J
AU Hurst, FP
Belur, P
Nee, R
Agodoa, LY
Patel, P
Abbott, KC
Jindal, RM
AF Hurst, Frank P.
Belur, Pallavi
Nee, Robert
Agodoa, Lawrence Y.
Patel, Purav
Abbott, Kevin C.
Jindal, Rahul M.
TI Poor Outcomes Associated With Neutropenia After Kidney Transplantation:
Analysis of United States Renal Data System
SO TRANSPLANTATION
LA English
DT Article
DE Neutropenia after kidney transplantation; Granulocyte colony-stimulating
factors; United States Renal Data System
ID MYCOPHENOLATE-MOFETIL; ALLOGRAFT RECIPIENTS; RISK-FACTORS; LEUKOPENIA;
THROMBOCYTOPENIA; MANAGEMENT; THERAPY; DISEASE
AB Background. Posttransplant neutropenia (PTN) is relatively common after kidney transplantation, and may result in a reduction of immunosuppression, which may precipitate acute rejection. Granulocyte colony-stimulating factors (GCSF) have been used to treat PTN, although outcomes associated with use of this medication in this population are unknown.
Methods. In a retrospective cohort of 41,705 adult Medicare primary patients transplanted from January 2001 to June 2006, we assessed Medicare claims for neutropenia, leukopenia, and GCSF use, respectively. Outcomes included allograft loss and death.
Results. There were 6043 (14.5%) patients with claims for PTN. Factors associated with PTN included female gender, Caucasian ethnicity, ischemic heart disease, donor cytomegalovirus positive, deceased donor, expanded donor criteria, delayed graft function, elevated panel reactive antibody, higher human leukocyte antigen mismatch, and later year of transplant. Thymoglobulin induction, tacrolimus, and mycophenolate mofetil were also associated. PTN was less frequent among patients with congestive heart failure, recipient cytomegalovirus positive, and interleukin-2 induction. PTN was associated with increased risk of allograft loss (adjusted hazard ratio, 1.59; 95% confidence interval, 1.43-1.76; P<0.001) and death (adjusted hazard ratio, 1.74; 95% confidence interval, 1.59-1.90; P<0.001). Of the 6043 patients with PTN, 740 (12.2%) received GCSF. Patients who received GCSF had a lower risk of death on unadjusted analysis, but this only trended towards significance after adjustment.
Conclusions. Neutropenia after renal transplantation is common and is associated with an increased risk of allograft loss and death. GCSF was used in 12% of cases and did not increase risk of allograft loss. Strategies to avoid PTN and greater use of GCSF may be indicated to prevent graft loss and death.
C1 [Jindal, Rahul M.] Walter Reed AMC, Div Organ Transplant, Washington, DC USA.
[Hurst, Frank P.; Belur, Pallavi; Nee, Robert; Abbott, Kevin C.] Walter Reed Army Med Ctr, Div Nephrol, Washington, DC 20307 USA.
[Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD USA.
[Patel, Purav] Med Univ Lublin, Lublin, Poland.
[Jindal, Rahul M.] George Washington Univ, Dept Med, Washington, DC USA.
RP Jindal, RM (reprint author), Walter Reed AMC, Div Organ Transplant, Washington, DC USA.
EM jindalr@msn.com
OI Abbott, Kevin/0000-0003-2111-7112
NR 24
TC 17
Z9 17
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD JUL 15
PY 2011
VL 92
IS 1
BP 36
EP 40
DI 10.1097/TP.0b013e31821c1e70
PG 5
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 780JY
UT WOS:000291853300009
PM 21512429
ER
PT J
AU Makarova, KS
Aravind, L
Wolf, YI
Koonin, EV
AF Makarova, Kira S.
Aravind, L.
Wolf, Yuri I.
Koonin, Eugene V.
TI Unification of Cas protein families and a simple scenario for the origin
and evolution of CRISPR-Cas systems
SO BIOLOGY DIRECT
LA English
DT Article
ID T7 RNA-POLYMERASE; DNA-POLYMERASES; ANTIVIRAL DEFENSE; GENETIC ELEMENTS;
STRUCTURAL BASIS; IMMUNE-SYSTEM; PROKARYOTES; IDENTIFICATION;
SUPERFAMILY; SEQUENCE
AB Background: The CRISPR-Cas adaptive immunity systems that are present in most Archaea and many Bacteria function by incorporating fragments of alien genomes into specific genomic loci, transcribing the inserts and using the transcripts as guide RNAs to destroy the genome of the cognate virus or plasmid. This RNA interference-like immune response is mediated by numerous, diverse and rapidly evolving Cas (CRISPR-associated) proteins, several of which form the Cascade complex involved in the processing of CRISPR transcripts and cleavage of the target DNA. Comparative analysis of the Cas protein sequences and structures led to the classification of the CRISPR-Cas systems into three Types (I, II and III).
Results: A detailed comparison of the available sequences and structures of Cas proteins revealed several unnoticed homologous relationships. The Repeat-Associated Mysterious Proteins (RAMPs) containing a distinct form of the RNA Recognition Motif (RRM) domain, which are major components of the CRISPR-Cas systems, were classified into three large groups, Cas5, Cas6 and Cas7. Each of these groups includes many previously uncharacterized proteins now shown to adopt the RAMP structure. Evidence is presented that large subunits contained in most of the CRISPR-Cas systems could be homologous to Cas10 proteins which contain a polymerase-like Palm domain and are predicted to be enzymatically active in Type III CRISPR-Cas systems but inactivated in Type I systems. These findings, the fact that the CRISPR polymerases, RAMPs and Cas2 all contain core RRM domains, and distinct gene arrangements in the three types of CRISPR-Cas systems together provide for a simple scenario for origin and evolution of the CRISPR-Cas machinery. Under this scenario, the CRISPR-Cas system originated in thermophilic Archaea and subsequently spread horizontally among prokaryotes.
Conclusions: Because of the extreme diversity of CRISPR-Cas systems, in-depth sequence and structure comparison continue to reveal unexpected homologous relationship among Cas proteins. Unification of Cas protein families previously considered unrelated provides for improvement in the classification of CRISPR-Cas systems and a reconstruction of their evolution.
Open peer review: This article was reviewed by Malcolm White (nominated by Purficacion Lopez-Garcia), Frank Eisenhaber and Igor Zhulin. For the full reviews, see the Reviewers' Comments section.
C1 [Makarova, Kira S.; Aravind, L.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU US Department of Health and Human Services (National Library of
Medicine, NIH)
FX The authors' research is supported by the intramural funds of the US
Department of Health and Human Services (National Library of Medicine,
NIH).
NR 69
TC 189
Z9 199
U1 17
U2 82
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 JUL 14
PY 2011
VL 6
AR 38
DI 10.1186/1745-6150-6-38
PG 27
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 803DW
UT WOS:000293562600001
PM 21756346
ER
PT J
AU Skinner, J
Kotliarov, Y
Varma, S
Mine, KL
Yambartsev, A
Simon, R
Huyen, Y
Morgun, A
AF Skinner, Jeff
Kotliarov, Yuri
Varma, Sudhir
Mine, Karina L.
Yambartsev, Anatoly
Simon, Richard
Huyen, Yentram
Morgun, Andrey
TI Construct and Compare Gene Coexpression Networks with DAPfinder and
DAPview
SO BMC BIOINFORMATICS
LA English
DT Article
ID FALSE DISCOVERY RATE; RECEPTOR GENE; BRAIN-TUMORS; EXPRESSION; GROWTH;
CANCER; AMPLIFICATION; DEPENDENCY; PROFILES; EGFR
AB Background: DAPfinder and DAPview are novel BRB-ArrayTools plug-ins to construct gene coexpression networks and identify significant differences in pairwise gene-gene coexpression between two phenotypes.
Results: Each significant difference in gene-gene association represents a Differentially Associated Pair (DAP). Our tools include several choices of filtering methods, gene-gene association metrics, statistical testing methods and multiple comparison adjustments. Network results are easily displayed in Cytoscape. Analyses of glioma experiments and microarray simulations demonstrate the utility of these tools.
Conclusions: DAPfinder is a new friendly-user tool for reconstruction and comparison of biological networks.
C1 [Skinner, Jeff; Varma, Sudhir; Huyen, Yentram] NIAID, BCBB, OCICB, NIH, Bethesda, MD 20892 USA.
[Kotliarov, Yuri] NCI, Neurooncol Branch CHIAI, NINDS, NIH, Bethesda, MD 20892 USA.
[Mine, Karina L.] Univ Fed Sao Paulo, Dept Pediat, Setor Imunogenet, Sao Paulo, Brazil.
[Yambartsev, Anatoly] Univ Sao Paulo, IME, Sao Paulo, Brazil.
[Simon, Richard] NCI, BRB, DCTD, NIH, Bethesda, MD 20892 USA.
[Morgun, Andrey] NIAID, Ghost Lab, TCTMS, LCMI,NIH, Bethesda, MD 20892 USA.
RP Huyen, Y (reprint author), NIAID, BCBB, OCICB, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM huyeny@niaid.nih.gov; anemorgun@hotmail.com
RI Varma, Sudhir/N-8763-2014; Kotliarov, Yuri/B-6938-2017;
OI Varma, Sudhir/0000-0002-4096-4782; Skinner, Jeff/0000-0001-5697-0442
FU Department of Intramural Research (DIR); Office of the Director (OD) at
NIAID, NIH
FX This work was supported by funding from the Department of Intramural
Research (DIR) and the Office of the Director (OD) at NIAID, NIH. Vivek
Gopalan, Supriya Menezes and Ming-Chung Li helped with the initial
coding of DAPfinder. Vijay Nagarajan and Michael Dolan helped produce
and edit the figures. Natalia Shulzenko discussed biological questions
motivating our tool.
NR 37
TC 9
Z9 9
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUL 14
PY 2011
VL 12
AR 286
DI 10.1186/1471-2105-12-286
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 801DN
UT WOS:000293416700001
PM 21756334
ER
PT J
AU Cooper, KG
Winfree, S
Malik-Kale, P
Jolly, C
Ireland, R
Knodler, LA
Steele-Mortimer, O
AF Cooper, Kendal G.
Winfree, Seth
Malik-Kale, Preeti
Jolly, Carrie
Ireland, Robin
Knodler, Leigh A.
Steele-Mortimer, Olivia
TI Activation of Akt by the Bacterial Inositol Phosphatase, SopB, is
Wortmannin Insensitive
SO PLOS ONE
LA English
DT Article
ID PROTEIN-KINASE B; PLECKSTRIN-HOMOLOGY DOMAINS; INTESTINAL
EPITHELIAL-CELLS; HOST-CELL; PLASMA-MEMBRANE; SALMONELLA-TYPHIMURIUM;
SUSTAINED ACTIVATION; INHIBITORS; PATHWAY; SIGD
AB Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85 alpha and p85 beta by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P(2) rather than phosphoinositide (3,4,5) P(3). Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway.
C1 [Cooper, Kendal G.; Winfree, Seth; Malik-Kale, Preeti; Jolly, Carrie; Ireland, Robin; Knodler, Leigh A.; Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Labs, Hamilton, MT USA.
RP Cooper, KG (reprint author), Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
EM omortimer@niaid.nih.gov
FU National Institutes of Allergy and Infectious Disease, National
Institutes of Health
FX Work in the laboratory was supported by the Intramural Research Program
of the National Institutes of Allergy and Infectious Disease, National
Institutes of Health. No other current external funding sources
supported this study. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 65
TC 11
Z9 12
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 14
PY 2011
VL 6
IS 7
AR e22260
DI 10.1371/journal.pone.0022260
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 793HP
UT WOS:000292811300059
PM 21779406
ER
PT J
AU Robidart, JC
Roque, A
Song, PF
Girguis, PR
AF Robidart, Julie C.
Roque, Annelys
Song, Pengfei
Girguis, Peter R.
TI Linking Hydrothermal Geochemistry to Organismal Physiology:
Physiological Versatility in Riftia pachyptila from Sedimented and
Basalt-hosted Vents
SO PLOS ONE
LA English
DT Article
ID EAST PACIFIC RISE; TUBE-WORM; GUAYMAS BASIN; ROSE GARDEN;
CHEMOAUTOTROPHIC SYMBIONTS; CARBONIC-ANHYDRASE; METABOLITE UPTAKE;
INORGANIC CARBON; ACID CYCLE; SULFIDE
AB Much of what is known regarding Riftia pachyptila physiology is based on the wealth of studies of tubeworms living at diffuse flows along the fast-spreading, basalt-hosted East Pacific Rise (EPR). These studies have collectively suggested that Riftia pachyptila and its chemoautotrophic symbionts are physiologically specialized, highly productive associations relying on hydrogen sulfide and oxygen to generate energy for carbon fixation, and the symbiont's nitrate reduction to ammonia for energy and biosynthesis. However, Riftia also flourish in sediment-hosted vents, which are markedly different in geochemistry than basalt-hosted systems. Here we present data from shipboard physiological studies and global quantitative proteomic analyses of Riftia pachyptila trophosome tissue recovered from tubeworms residing in the EPR and the Guaymas basin, a sedimented, hydrothermal vent field. We observed marked differences in symbiont nitrogen metabolism in both the respirometric and proteomic data. The proteomic data further suggest that Riftia associations in Guaymas may utilize different sulfur compounds for energy generation, may have an increased capacity for energy storage, and may play a role in degrading exogenous organic carbon. Together these data reveal that Riftia symbionts are far more physiologically plastic than previously considered, and that contrary to previous assertions-Riftia do assimilate reduced nitrogen in some habitats. These observations raise new hypotheses regarding adaptations to the geochemical diversity of habitats occupied by Riftia, and the degree to which the environment influences symbiont physiology and evolution.
C1 [Robidart, Julie C.] Univ Calif Santa Cruz, Dept Ocean Sci, Santa Cruz, CA 95064 USA.
[Roque, Annelys] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Song, Pengfei; Girguis, Peter R.] Harvard Univ, Cambridge, MA 02138 USA.
RP Robidart, JC (reprint author), Univ Calif Santa Cruz, Dept Ocean Sci, Santa Cruz, CA 95064 USA.
EM pgirguis@oeb.harvard.edu
FU National Science Foundation [OCE-0623383, OCE-0732369]
FX This project was supported by grants from the National Science
Foundation to PRG (OCE-0623383 and OCE-0732369, http://www.nsf.gov/).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 74
TC 10
Z9 10
U1 5
U2 40
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 JUL 14
PY 2011
VL 6
IS 7
AR e21692
DI 10.1371/journal.pone.0021692
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 793HP
UT WOS:000292811300012
PM 21779334
ER
PT J
AU Srinivasula, S
Lempicki, RA
Adelsberger, JW
Huang, CY
Roark, J
Lee, PI
Rupert, A
Stevens, R
Sereti, I
Lane, HC
Di Mascio, M
Kovacs, JA
AF Srinivasula, Sharat
Lempicki, Richard A.
Adelsberger, Joseph W.
Huang, Chiung-Yu
Roark, Joshua
Lee, Philip I.
Rupert, Adam
Stevens, Randy
Sereti, Irini
Lane, H. Clifford
Di Mascio, Michele
Kovacs, Joseph A.
TI Differential effects of HIV viral load and CD4 count on proliferation of
naive and memory CD4 and CD8 T lymphocytes
SO BLOOD
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE
ACTIVATION; INFECTED PATIENTS; TYPE-1 INFECTION; RHESUS MACAQUES; CELL
TURNOVER; KINETICS; TRANSLOCATION; DYNAMICS
AB We previously showed that HIV infection leads to expansion of a rapidly proliferating pool (s(1)) of CD4 and CD8 T lymphocytes. In the current study, we used in vivo labeling with bromodeoxyuridine to characterize the kinetics of naive, memory, and activated (HLA-DR(+)/CD38(+)) subpopulations of CD4 and CD8 T lymphocytes, and to examine the relationship between kinetic parameters and baseline CD4 counts, HIV viral load, potential markers of microbial translocation, and cytokine levels. Activated cells showed the highest proliferation rates, followed by effector and central memory cells, with naive cells showing the lowest rates, for both CD4 and CD8 T cells. HIV viral load correlated with s(1) of CD4 and CD8 effector memory cells, as well as CD8 naive cells, whereas CD4 cell counts correlated inversely with naive CD4 s(1). Endotoxin levels showed a weak negative association with CD4 but not CD8 s(1). INF-gamma and TNF-alpha were associated with s(1) for CD4 and CD8 cells, respectively. Thus, HIV is the primary driving force behind the activation and proliferation of most subsets of both CD4 and CD8 T lymphocytes, whereas naive CD4 cell proliferation likely represents a homeostatic response. Microbial translocation does not appear to play an important role in this proliferation. (Blood.2011;118(2):262-270)
C1 [Srinivasula, Sharat; Roark, Joshua] NCI, Biostat Res Branch, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Lempicki, Richard A.; Adelsberger, Joseph W.; Rupert, Adam; Stevens, Randy] NCI, Appl & Dev Res Directorate, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Huang, Chiung-Yu; Di Mascio, Michele] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Philip I.; Sereti, Irini; Lane, H. Clifford] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Kovacs, Joseph A.] NIH Clin Ctr, Crit Care Med Dept, NIH, Bethesda, MD USA.
RP Srinivasula, S (reprint author), 6700A Rockledge Dr,Rm 5227, Bethesda, MD 20817 USA.
EM srinivasulas@mail.nih.gov
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU National Institutes of Health Clinical Center; National Institute of
Allergy and Infectious Diseases; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This work was supported by the Intramural Research Programs of the
National Institutes of Health Clinical Center and the National Institute
of Allergy and Infectious Diseases and supported in part by the National
Cancer Institute, National Institutes of Health (contract
HHSN261200800001E).
NR 35
TC 27
Z9 29
U1 1
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 JUL 14
PY 2011
VL 118
IS 2
BP 262
EP 270
DI 10.1182/blood-2011-02-335174
PG 9
WC Hematology
SC Hematology
GA 792IB
UT WOS:000292735100010
PM 21562041
ER
PT J
AU Hanash, AM
Kappel, LW
Yim, NL
Nejat, RA
Goldberg, GL
Smith, OM
Rao, UK
Dykstra, L
Na, IK
Holland, AM
Dudakov, JA
Liu, C
Murphy, GF
Leonard, WJ
Heller, G
van den Brink, MRM
AF Hanash, Alan M.
Kappel, Lucy W.
Yim, Nury L.
Nejat, Rebecca A.
Goldberg, Gabrielle L.
Smith, Odette M.
Rao, Uttam K.
Dykstra, Lindsay
Na, Il-Kang
Holland, Amanda M.
Dudakov, Jarrod A.
Liu, Chen
Murphy, George F.
Leonard, Warren J.
Heller, Glenn
van den Brink, Marcel R. M.
TI Abrogation of donor T-cell IL-21 signaling leads to tissue-specific
modulation of immunity and separation of GVHD from GVL
SO BLOOD
LA English
DT Article
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CHRONIC
VIRAL-INFECTION; TUMOR ACTIVITY; INTERLEUKIN-21; LEUKEMIA; CANCER;
DIFFERENTIATION; EXPRESSION; ORGAN
AB IL-21 is a proinflammatory cytokine produced by Th17 cells. Abrogation of IL-21 signaling has recently been shown to reduce GVHD while retaining graft-versus-leukemia/lymphoma (GVL) responses. However, the mechanisms by which IL-21 may lead to a separation of GVHD and GVL remain incompletely understood. In a murine MHC-mismatched BM transplantation model, we observed that IL-21 receptor knockout (IL-21R KO) donor T cells mediate decreased systemic and gastro-intestinal GVHD in recipients of a transplant. This reduction in GVHD was associated with expansion of transplanted donor regulatory T cells and with tissue-specific modulation of Th-cell function. IL-21R KO and wild-type donor T cells showed equivalent alloactivation, but IL-21R KO T cells showed decreased infiltration and inflammatory cytokine production within the mesenteric lymph nodes. However, Th-cell cytokine production was maintained peripherally, and IL-21R KO T cells mediated equivalent immunity againstA20 and P815 hematopoietic tumors. In summary, abrogation of IL-21 signaling in donor T cells leads to tissue-specific modulation of immunity, such that gastrointestinal GVHD is reduced, but peripheral T-cell function and GVL capacity are retained. IL-21 is thus an exciting target for therapeutic intervention and improvement of clinical transplantation outcomes. (Blood. 2011; 118(2): 446-455)
C1 [van den Brink, Marcel R. M.] Mem Sloan Kettering Canc Ctr, Zuckerman Res Ctr 1419, Dept Med, New York, NY 10021 USA.
[Kappel, Lucy W.; Yim, Nury L.; Nejat, Rebecca A.; Goldberg, Gabrielle L.; Smith, Odette M.; Rao, Uttam K.; Dykstra, Lindsay; Na, Il-Kang; Holland, Amanda M.; Dudakov, Jarrod A.; van den Brink, Marcel R. M.] Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10021 USA.
[Kappel, Lucy W.; Holland, Amanda M.; van den Brink, Marcel R. M.] Weill Cornell Med Coll, Dept Immunol & Microbial Pathogenesis, New York, NY USA.
[Na, Il-Kang] Charite CBF Univ Med Berlin, Dept Hematol & Oncol, Berlin, Germany.
[Liu, Chen] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA.
[Murphy, George F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Program Dermatopathol, Boston, MA 02115 USA.
[Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Heller, Glenn] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
RP van den Brink, MRM (reprint author), Mem Sloan Kettering Canc Ctr, Zuckerman Res Ctr 1419, Dept Med, 418 E 69th St, New York, NY 10021 USA.
EM vandenbm@mskcc.org
OI Murphy, George/0000-0003-3464-793X; Dudakov, Jarrod/0000-0001-6220-5632
FU National Institutes of Health [RO1-HL069929, RO1-CA107096, RO1-AI080455,
PO1-CA33049, R01-HL095075]; NHLBI; Lymphoma Foundation; Alex's Lemonade
Stand; Leukemia and Lymphoma Society; Ryan Gibson Foundation; Elsa U.
Pardee Foundation; Byrne Fund; Emerald Foundation; Experimental
Therapeutics Center of Memorial Sloan-Kettering Cancer Center; Mrs Alice
Goodwin and the Commonwealth Foundation for Cancer Research
FX This work was supported by the National Institutes of Health (awards
RO1-HL069929, RO1-CA107096, RO1-AI080455, PO1-CA33049, and R01-HL095075
(M.R.M.v.d.B.), as well the NHLBI Intramural Research Program (W.J.L.)
and by the Lymphoma Foundation, Alex's Lemonade Stand, the Leukemia and
Lymphoma Society, the Ryan Gibson Foundation, the Elsa U. Pardee
Foundation, the Byrne Fund, the Emerald Foundation, and The Experimental
Therapeutics Center of Memorial Sloan-Kettering Cancer Center funded by
Mr William H. Goodwin and Mrs Alice Goodwin and the Commonwealth
Foundation for Cancer Research (M.R.M.v.d.B.). A. M. Hanash was
supported through the Research Training Award for Fellows from the
American Society of Hematology.
NR 54
TC 33
Z9 35
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 JUL 14
PY 2011
VL 118
IS 2
BP 446
EP 455
DI 10.1182/blood-2010-07-294785
PG 10
WC Hematology
SC Hematology
GA 792IB
UT WOS:000292735100031
PM 21596854
ER
PT J
AU Gu, ZL
Yakel, JL
AF Gu, Zhenglin
Yakel, Jerrel L.
TI Timing-Dependent Septal Cholinergic Induction of Dynamic Hippocampal
Synaptic Plasticity
SO NEURON
LA English
DT Article
ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE;
ALPHA-7-CONTAINING NICOTINIC RECEPTORS; ALZHEIMERS-DISEASE;
ACETYLCHOLINE-RECEPTORS; PYRAMIDAL CELLS; SK CHANNELS; MEMORY;
INHIBITION
AB Cholinergic modulation of hippocampal synaptic plasticity has been studied extensively by applying receptor agonists or blockers; however, the effect of rapid physiological cholinergic stimuli on plasticity is largely unknown. Here, we report that septal cholinergic input, activated either by electrical stimulation or via an optogenetic approach, induced different types of hippocampal Schaffer collateral (SC) to CA1 synaptic plasticity, depending on the timing of cholinergic input relative to the SC input. When the cholinergic input was activated 100 or 10 ms prior to SC stimulation, it resulted in alpha 7 nAChR-dependent long-term potentiation (LTP) or short-term depression, respectively. When the cholinergic stimulation was delayed until 10 ms after the SC stimulation, a muscarinic AChR-dependent LTP was induced. Moreover, these various forms of plasticity were disrupted by A beta exposure. These results have revealed the remarkable temporal precision of cholinergic functions, providing a novel mechanism for information processing in cholinergic-dependent higher cognitive functions.
C1 [Gu, Zhenglin; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, US Dept HHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM yakel@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX We thank Patricia Lamb for animal genotyping and plasmid preparation,
Drs. Negin Martin and Charles Romeo for virus packaging, Dr. James M.
Wilson at University of Pennsylvania for providing the AAV serotype 9
helper plasmid, and Charles J. Tucker and Agnus Janoshazi for assistance
with fluorescent microscopy. We also thank Drs. Serena Dudek, David
Armstrong, Patricia Jensen, and Lutz Birnbaumer for discussions and
critical reading of the manuscript. This research was supported by the
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences.
NR 55
TC 104
Z9 105
U1 0
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 14
PY 2011
VL 71
IS 1
BP 155
EP 165
DI 10.1016/j.neuron.2011.04.026
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 793FQ
UT WOS:000292806200014
PM 21745645
ER
PT J
AU Burch, LH
AF Burch, Lauranell H.
TI MUC5B Promoter Polymorphism and Pulmonary Fibrosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
RP Burch, LH (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
EM burchl@niehs.nih.gov
NR 2
TC 2
Z9 2
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 14
PY 2011
VL 365
IS 2
BP 178
EP 178
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 791SP
UT WOS:000292685500022
PM 21751916
ER
PT J
AU Chung, SM
Himmel, DM
Jiang, JK
Wojtak, K
Bauman, JD
Rausch, JW
Wilson, JA
Beutler, JA
Thomas, CJ
Arnold, E
Le Grice, SFJ
AF Chung, Suhman
Himmel, Daniel M.
Jiang, Jian-Kang
Wojtak, Krzysztof
Bauman, Joseph D.
Rausch, Jason W.
Wilson, Jennifer A.
Beutler, John A.
Thomas, Craig J.
Arnold, Eddy
Le Grice, Stuart F. J.
TI Synthesis, Activity, and Structural Analysis of Novel
alpha-Hydroxytropolone Inhibitors of Human Immunodeficiency Virus
Reverse Transcriptase-Associated Ribonuclease H
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HIV RNASE-H; SMALL-MOLECULE INHIBITORS; MAXIMUM-LIKELIHOOD;
CRYSTAL-STRUCTURE; PROTEIN MODELS; MUTATIONS; MECHANISM; ACID; SITE;
REPLACEMENT
AB The alpha-hydroxytroplone, manicol (5,7-dihydroxy-2-isopropenyl-9-methyl-1,2,3,4-tetrahydro-benzocyclohepten-6-one), potently and specifically inhibits ribonuclease H (RNase H) activity of human immunodeficiency virus reverse transcriptase (HIV RT) in vitro. However, manicol was ineffective in reducing virus replication in culture. Ongoing efforts to improve the potency and specificity over the lead compound led us to synthesize 14 manicol derivatives that retain the divalent metal-chelating alpha-hydroxytropolone pharmacophore. These efforts were augmented by a high resolution structure of p66/p51. HIV-1 RT containing the nonnucleoside reverse transcriptase inhibitor (NNRTI), TMC278 and manicol in the DNA polymerase and RNase H active sites, respectively. We demonstrate here that several modified alpha-hydroxytropolones exhibit antiviral activity at noncytotoxic concentrations. Inclusion of RNase H active site mutants indicated that manicol analogues can occupy an additional site in or around the DNA polymerase catalytic center. Collectively, our studies will promote future structure-based design of improved alpha-hydroxytropolones to complement the NRTI and NNRTI currently in clinical use.
C1 [Chung, Suhman; Rausch, Jason W.; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Himmel, Daniel M.; Wojtak, Krzysztof; Bauman, Joseph D.; Arnold, Eddy] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Himmel, Daniel M.; Wojtak, Krzysztof; Bauman, Joseph D.; Arnold, Eddy] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
[Jiang, Jian-Kang; Thomas, Craig J.] NIH Chem Genom Ctr, Rockville, MD 20850 USA.
[Wilson, Jennifer A.; Beutler, John A.] NCI, Mol Discovery Program, Frederick, MD 21702 USA.
RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM legrices@mail.nih.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU National Cancer Institute, National Institutes of Health; Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research; National Human Genome Research Institute; NIH [AI
27690]
FX S.C., J.R., J.B., J.W., and S.L.G. are supported by the Intramural
Research Program of the National Cancer Institute, National Institutes
of Health. J.J. and C.T. were 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. D. M.H. and E.A. were supported by NIH MERIT
Award AI 27690.
NR 53
TC 44
Z9 45
U1 0
U2 9
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 JUL 14
PY 2011
VL 54
IS 13
BP 4462
EP 4473
DI 10.1021/jm2000757
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 788YF
UT WOS:000292479600012
PM 21568335
ER
PT J
AU Buckholtz, NS
AF Buckholtz, Neil S.
TI PERSPECTIVE In search of biomarkers
SO NATURE
LA English
DT Editorial Material
ID ALZHEIMERS ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL
INSTITUTE; RECOMMENDATIONS; DISEASE
C1 NIA, Dementias Aging Branch, Div Neurosci, Bethesda, MD 20892 USA.
RP Buckholtz, NS (reprint author), NIA, Dementias Aging Branch, Div Neurosci, Bethesda, MD 20892 USA.
EM buckholn@nia.nih.gov
NR 3
TC 15
Z9 15
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 14
PY 2011
VL 475
IS 7355
BP S8
EP S8
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791UA
UT WOS:000292690500004
PM 21760582
ER
PT J
AU Hunt, PR
Son, TG
Wilson, MA
Yu, QS
Wood, WH
Zhang, YQ
Becker, KG
Greig, NH
Mattson, MP
Camandola, S
Wolkow, CA
AF Hunt, Piper R.
Son, Tae Gen
Wilson, Mark A.
Yu, Quian-Sheng
Wood, William H.
Zhang, Yongqing
Becker, Kevin G.
Greig, Nigel H.
Mattson, Mark P.
Camandola, Simonetta
Wolkow, Catherine A.
TI Extension of Lifespan in C. elegans by Naphthoquinones That Act through
Stress Hormesis Mechanisms
SO PLOS ONE
LA English
DT Article
ID NEMATODE CAENORHABDITIS-ELEGANS; HEAT-SHOCK PROTEINS; OXIDATIVE-STRESS;
SACCHAROMYCES-CEREVISIAE; ADAPTIVE RESPONSE; GENE-EXPRESSION; FACTOR
SKN-1; LONGEVITY; RESISTANCE; DAF-16
AB Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC) transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.
C1 [Hunt, Piper R.; Son, Tae Gen; Wilson, Mark A.; Mattson, Mark P.; Camandola, Simonetta; Wolkow, Catherine A.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Yu, Quian-Sheng; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Wood, William H.; Zhang, Yongqing; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Hunt, PR (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM camandolasi@grc.nia.nih.gov; wolkowca@gmail.com
RI Mattson, Mark/F-6038-2012; Hunt, Piper/G-1555-2012;
OI Hunt, Piper/0000-0003-0538-7606; Becker, Kevin/0000-0002-6794-6656
FU National Institute of Aging [Z01 AG000320]
FX This work was funded by the National Institute of Aging Intramural
Research Program, Z01 AG000320. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 56
TC 23
Z9 26
U1 1
U2 28
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 JUL 13
PY 2011
VL 6
IS 7
AR e21922
DI 10.1371/journal.pone.0021922
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 792WQ
UT WOS:000292781500023
PM 21765926
ER
PT J
AU Ma, BY
Tsai, CJ
Haliloglu, T
Nussinov, R
AF Ma, Buyong
Tsai, Chung-Jung
Haliloglu, Turkan
Nussinov, Ruth
TI Dynamic Allostery: Linkers Are Not Merely Flexible
SO STRUCTURE
LA English
DT Review
ID MEDIATOR SUBUNIT MED1/TRAP220; HSP70 MOLECULAR CHAPERONES; SCF UBIQUITIN
LIGASE; GLUCOCORTICOID-RECEPTOR; ENERGY LANDSCAPE; DNA-BINDING;
TRANSCRIPTIONAL ACTIVATION; CONFORMATIONAL SELECTION;
DIHYDROFOLATE-REDUCTASE; STRUCTURAL INSIGHTS
AB Most proteins consist of multiple domains. How do linkers efficiently transfer information between sites that are on different domains to activate the protein? Mere flexibility only implies that the conformations would be sampled. For fast timescales between triggering events and cellular response, which often involves large conformational change, flexibility on its own may not constitute a good solution. We posit that successive conformational states along major allosteric propagation pathways are pre-encoded in linker sequences where each state is encoded by the previous one. The barriers between these states that are hierarchically populated are lower, achieving faster timescales even for large conformational changes. We further propose that evolution has optimized the linker sequences and lengths for efficiency, which explains why mutations in linkers may affect protein function and review the literature in this light.
C1 [Ma, Buyong; Tsai, Chung-Jung; Nussinov, Ruth] NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Haliloglu, Turkan] Bogazici Univ, Polymer Res Ctr, TR-34342 Bebek, Turkey.
[Haliloglu, Turkan] Bogazici Univ, Dept Chem Engn, TR-34342 Bebek, Turkey.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM ruthnu@helix.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU TUBA (Turkish Academy of Sciences); State Planning organization DPT
[2009K120520]; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX T.H. acknowledges support from TUBA (Turkish Academy of Sciences) and
State Planning organization DPT (2009K120520). This project has been
funded in whole or in part with Federal funds from the National Cancer
Institute, National Institutes of Health, under contract number
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported (in part) by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 117
TC 109
Z9 109
U1 6
U2 55
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD JUL 13
PY 2011
VL 19
IS 7
BP 907
EP 917
DI 10.1016/j.str.2011.06.002
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 792ZO
UT WOS:000292789300004
PM 21742258
ER
PT J
AU Schweimer, K
Prasch, S
Sujatha, PS
Bubunenko, M
Gottesman, ME
Rosch, P
AF Schweimer, Kristian
Prasch, Stefan
Sujatha, Pagadala Santhanam
Bubunenko, Mikhail
Gottesman, Max E.
Roesch, Paul
TI NusA Interaction with the alpha Subunit of E-coli RNA Polymerase Is via
the UP Element Site and Releases Autoinhibition
SO STRUCTURE
LA English
DT Article
ID ESCHERICHIA-COLI NUSA; ELONGATION-FACTOR NUSA; CARBOXY-TERMINAL DOMAINS;
PROTEIN CONTACT SITE; LAMBDA N PROTEIN; DNA-BINDING; PHAGE-LAMBDA;
MYCOBACTERIUM-TUBERCULOSIS; TRANSCRIPTION TERMINATION; CRYSTAL-STRUCTURE
AB Elongating Escherichia coli RNAP is modulated by NusA protein. The C-terminal domain (CTD) of the RNAP alpha subunit (alpha CTD) interacts with the acidic CTD 2 (AR2) of NusA, releasing the autoinhibitory blockade of the NusA S1-KH1-KH2 motif and allowing NusA to bind nascent nut spacer RNA. We determined the solution conformation of the AR2:alpha CTD complex. The alpha CTD residues that interface with AR2 are identical to those that recognize UP promoter elements A nusA-Delta AR2 mutation does not affect UP-dependent rrnH transcription initiation in vivo. Instead, the mutation inhibits Rho-dependent transcription termination at phage gamma tR1, which lies adjacent to the gamma nutR sequence. The Rho-dependent gamma timm terminator, which is not preceded by a nut sequence, is fully functional. We propose that constitutive binding of NusA-Delta AR2 to gamma nutR occludes Rho. In addition, the mutation confers a dominant defect in exiting stationary phase.
C1 [Gottesman, Max E.] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Schweimer, Kristian; Prasch, Stefan; Sujatha, Pagadala Santhanam; Roesch, Paul] Univ Bayreuth, Lehrstuhl Biopolymere, D-95447 Bayreuth, Germany.
[Schweimer, Kristian; Prasch, Stefan; Sujatha, Pagadala Santhanam; Roesch, Paul] Univ Bayreuth, Forschungszentrum Biomakromol, D-95447 Bayreuth, Germany.
[Bubunenko, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Bubunenko, Mikhail] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Gottesman, Max E.] Columbia Univ, Med Ctr, Inst Canc Res, New York, NY 10032 USA.
RP Gottesman, ME (reprint author), Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
EM meg8@columbia.edu; roesch@unibt.de
RI Rosch, Paul/I-5445-2014
OI Rosch, Paul/0000-0003-3330-2446
FU Deutsche Forschungsgemeinschaft [Ro617/17-1]; NIH [GM037219]; National
Institutes of Health, National Cancer Institute, Center for Cancer
Research; Trans National Institutes of Health/Food and Drug
Administration; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX Financial support by the Deutsche Forschungsgemeinschaft to PR
(Ro617/17-1) and by NIH to M.E.G. (GM037219) is gratefully acknowledged.
This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research, and in part by a Trans National Institutes of
Health/Food and Drug Administration Intramural Biodefense Program Grant
of National Institutes of Allergy and Infectious Disease (to Donald L.
Court). This project has been also partly funded with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 56
TC 16
Z9 16
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD JUL 13
PY 2011
VL 19
IS 7
BP 945
EP 954
DI 10.1016/j.str.2011.03.024
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 792ZO
UT WOS:000292789300007
PM 21742261
ER
PT J
AU Ziogas, A
Horick, NK
Kinney, AY
Lowery, JT
Domchek, SM
Isaacs, C
Griffin, CA
Moorman, PG
Edwards, KL
Hill, DA
Berg, JS
Tomlinson, GE
Anton-Culver, H
Strong, LC
Kasten, CH
Finkelstein, DM
Plon, SE
AF Ziogas, Argyrios
Horick, Nora K.
Kinney, Anita Y.
Lowery, Jan T.
Domchek, Susan M.
Isaacs, Claudine
Griffin, Constance A.
Moorman, Patricia G.
Edwards, Karen L.
Hill, Deirdre A.
Berg, Jonathan S.
Tomlinson, Gail E.
Anton-Culver, Hoda
Strong, Louise C.
Kasten, Carol H.
Finkelstein, Dianne M.
Plon, Sharon E.
TI Clinically Relevant Changes in Family History of Cancer Over Time
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID BREAST-CANCER; COLORECTAL-CANCER; HIGH-RISK; INHERITANCE; ONSET; WOMEN
AB Context Knowledge of family cancer history is important for assessing cancer risk and guiding screening recommendations.
Objective To quantify how often throughout adulthood clinically significant changes occur in cancer family history that would result in recommendations for earlier or intense screening.
Design and Setting Descriptive study examining baseline and follow-up family history data from participants in the Cancer Genetics Network (CGN), a US national population-based cancer registry, between 1999 and 2009.
Participants Adults with a personal history, family history, or both of cancer enrolled in the CGN through population-based cancer registries. Retrospective colorectal, breast, and prostate cancer screening-specific analyses included 9861, 2547, and 1817 participants, respectively; prospective analyses included 1533, 617, and 163 participants, respectively. Median follow-up was 8 years (range, 0-11 years). Screening-specific analyses excluded participants with the cancer of interest.
Main Outcome Measures Percentage of individuals with clinically significant family histories and rate of change over 2 periods: (1) retrospectively, from birth until CGN enrollment and (2) prospectively, from enrollment to last follow-up.
Results Retrospective analysis revealed that the percentages of participants who met criteria for high-risk screening based on family history at ages 30 and 50 years, respectively, were as follows: for colorectal cancer, 2.1% (95% confidence interval [CI], 1.8%-2.4%) and 7.1%(95% CI, 6.5%-7.6%); for breast cancer, 7.2%(95% CI, 6.1%-8.4%) and 11.4% (95% CI, 10.0%-12.8%); and for prostate cancer, 0.9%(95% CI, 0.5%-1.4%) and 2.0% (95% CI, 1.4%-2.7%). In prospective analysis, the numbers of participants who newly met criteria for high-risk screening based on family history per 100 persons followed up for 20 years were 2 (95% CI, 0-7) for colorectal cancer, 6 (95% CI, 2-13) for breast cancer, and 8 (95% CI, 3-16) for prostate cancer. The rate of change in cancer family history was similar for colorectal and breast cancer between the 2 analyses.
Conclusion Clinically relevant family history of colorectal, breast, and prostate cancer that would result in recommendations for earlier or intense cancer screening increases between ages 30 and 50 years, although the absolute rate is low for prostate cancer. JAMA. 2011; 306(2): 172-178
C1 [Ziogas, Argyrios; Anton-Culver, Hoda] Univ Calif Irvine, Irvine, CA 92717 USA.
[Horick, Nora K.; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Finkelstein, Dianne M.] Harvard Univ, Boston, MA 02115 USA.
[Kinney, Anita Y.] Huntsman Canc Inst, Salt Lake City, UT USA.
[Kinney, Anita Y.] Univ Utah, Salt Lake City, UT USA.
[Lowery, Jan T.] Univ Colorado, Aurora, CO USA.
[Domchek, Susan M.] Univ Penn, Philadelphia, PA 19104 USA.
[Isaacs, Claudine] Georgetown Univ, Washington, DC USA.
[Griffin, Constance A.] Johns Hopkins Univ, Baltimore, MD USA.
[Moorman, Patricia G.] Duke Univ, Med Ctr, Durham, NC USA.
[Edwards, Karen L.] Univ Washington, Seattle, WA 98195 USA.
[Hill, Deirdre A.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Berg, Jonathan S.] Univ N Carolina, Chapel Hill, NC USA.
[Tomlinson, Gail E.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
[Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Strong, Louise C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Plon, Sharon E.] Baylor Coll Med, Houston, TX 77030 USA.
[Kasten, Carol H.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Finkelstein, DM (reprint author), 50 Staniford St,Ste 560, Boston, MA 02114 USA.
EM dfinkel-stein@partners.org
FU National Cancer Institute [U01CA078284, U24CA078134, U24CA078164,
U24CA078156, U24CA078148, U24CA078146, U24CA078174, U24CA078157,
U24CA078142, HHSN2612007440000C]
FX The CGN is supported by grants U01CA078284, U24CA078134, U24CA078164,
U24CA078156, U24CA078148, U24CA078146, U24CA078174, U24CA078157, and
U24CA078142 and contract HHSN2612007440000C from the National Cancer
Institute.
NR 21
TC 16
Z9 17
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 13
PY 2011
VL 306
IS 2
BP 172
EP 178
DI 10.1001/jama.2011.955
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 791CO
UT WOS:000292639400024
PM 21750294
ER
PT J
AU Suffredini, AF
Munford, RS
AF Suffredini, Anthony F.
Munford, Robert S.
TI Novel Therapies for Septic Shock Over the Past 4 Decades
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID GRAM-NEGATIVE BACTEREMIA; ACTIVATED PROTEIN-C; RANDOMIZED
CONTROLLED-TRIAL; ILL ADULT PATIENTS; SEVERE SEPSIS; SURVIVING SEPSIS;
SYSTEMIC INFLAMMATION; ENDOTOXIN; CAMPAIGN; EFFICACY
AB Infections that result in shock and organ failure are a major public health problem worldwide. Severe sepsis and septic shock affect patients of all ages and often complicate chronic diseases. They are the major causes of death in critical care units and contribute substantially to hospital inpatient costs. Translating the scientific advances of the last 4 decades into clinical practice has been challenging. Despite many attempts to develop new therapies, the basic elements of treatment have not changed since the 1960s. In this Grand Rounds, we summarize the results of the clinical trials conducted during the last 4 decades, discuss some lessons learned, and suggest possible directions for future investigation. JAMA. 2011;306(2):194-199 www.jama.com
C1 [Suffredini, Anthony F.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Munford, Robert S.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Suffredini, AF (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 2C145, Bethesda, MD 20892 USA.
EM asuffredini@cc.nih.gov
FU Clinical Center, Intramural Research and the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This study was supported by the Clinical Center, Intramural Research
Program and the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health.
NR 49
TC 47
Z9 52
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 13
PY 2011
VL 306
IS 2
BP 194
EP 199
DI 10.1001/jama.2011.909
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 791CO
UT WOS:000292639400027
PM 21750297
ER
PT J
AU Cereda, V
Vergati, M
Huen, NY
di Bari, MG
Jochems, C
Intrivici, C
Gulley, JL
Apelian, D
Schlom, J
Tsang, KY
AF Cereda, Vittore
Vergati, Matteo
Huen, Ngar-Yee
di Bari, Maria Giovanna
Jochems, Caroline
Intrivici, Chiara
Gulley, James L.
Apelian, David
Schlom, Jeffrey
Tsang, Kwong Y.
TI Maturation of human dendritic cells with Saccharomyces cerevisiae
(yeast) reduces the number and function of regulatory T cells and
enhances the ratio of antigen-specific effectors to regulatory T cells
SO VACCINE
LA English
DT Article
DE Saccharomyces cerevisiae; Regulatory T cells; Human dendritic cells
ID WHOLE RECOMBINANT YEAST; PERIPHERAL-BLOOD; CARCINOEMBRYONIC ANTIGEN;
COSTIMULATORY MOLECULES; IMMUNE TOLERANCE; FOXP3 EXPRESSION;
TUMOR-ANTIGENS; GENE-TRANSFER; CANCER; RESPONSES
AB We compared the effects of yeast-treated human dendritic cells (DCs) with CD40L-matured human DCs for the induction of effector cells and the number and functionality of CD4(+)CD25(+)CD127(-)FoxP3(+) regulatory T cells (Tregs). DCs were treated with yeast or CD40L and cocultured with isolated autologous CD4(+) T cells. CD4(+)CD25(+)CD127(-) T cells isolated from the coculture of CD4(+) T cells plus yeast-treated DCs (yeast coculture) had a lower expression of FoxP3 and decreased suppressive function compared to CD4(+)CD25(+)CD127(-) T cells isolated from the coculture of CD4(+) T cells plus CD40L-treated DCs (CD40L coculture). Also, compared to the CD4OL coculture, the yeast coculture showed increases in the ratio of CD4(+)CD25(+) activated T cells to Tregs and in the production of Th1-related cytokines (IL-2, TNF-alpha, IFN-gamma) and IL-6. In addition, yeast-treated DCs used as antigen-presenting cells (APCs) incubated with the tumor antigen CEA enhanced the proliferation of CEA-specific CD4(+) T cells compared to the use of CD40L-matured DCs used as APCs. This is the first study to report on the role of yeast-treated/matured human DCs in reducing Treg frequency and functionality and in enhancing effector to Treg ratios. These results provide an additional rationale for the use of yeast as a vector in cancer vaccines. Published by Elsevier Ltd.
C1 [Cereda, Vittore; Vergati, Matteo; Huen, Ngar-Yee; di Bari, Maria Giovanna; Jochems, Caroline; Intrivici, Chiara; Gulley, James L.; Schlom, Jeffrey; Tsang, Kwong Y.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Apelian, David] GlobeImmune Inc, Louisville, CO 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 Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Center for Cancer Research, National Cancer Institute, NIH
FX Grant support: Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, NIH.
NR 50
TC 10
Z9 10
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 JUL 12
PY 2011
VL 29
IS 31
BP 4992
EP 4999
DI 10.1016/j.vaccine.2011.04.101
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 796HX
UT WOS:000293043500016
PM 21569810
ER
PT J
AU Yao, X
Hamilton, RG
Weng, NP
Xue, QL
Bream, JH
Li, HF
Tian, J
Yeh, SH
Resnick, B
Xu, XY
Walston, J
Fried, LP
Leng, SX
AF Yao, Xu
Hamilton, Robert G.
Weng, Nan-ping
Xue, Qian-Li
Bream, Jay H.
Li, Huifen
Tian, Jing
Yeh, Shu-Hui
Resnick, Barbara
Xu, Xiyan
Walston, Jeremy
Fried, Linda P.
Leng, Sean X.
TI Frailty is associated with impairment of vaccine-induced antibody
response and increase in post-vaccination influenza infection in
community-dwelling older adults
SO VACCINE
LA English
DT Article
DE Frailty; Influenza immunization; Antibody response; Influenza infection;
Influenza-like illness; Older adults
ID CELLULAR IMMUNE-RESPONSES; MORTALITY BENEFITS; CONTROLLED TRIAL; SERUM
INTERLEUKIN-6; GERIATRIC SYNDROME; ELDERLY-PEOPLE; UNITED-STATES;
INFLAMMATION; PROTECTION; WOMEN
AB Annual immunization with a trivalent inactivated vaccine (TIV) is considered efficacious for prevention of seasonal influenza in older adults. However, significant controversy exists in the current literature regarding the clinical effectiveness of TIV immunization in this highly heterogeneous population. Frailty is an important geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability to stressors. Using a validated set of frailty criteria, we conducted a prospective observational study to evaluate TIV-induced strain-specific hemagglutination inhibition (HI) antibody titers and post-vaccination rates of influenza-like illness (ILI) and infection in frail and nonfrail older adults. The results indicate that frailty was associated with significant impairment in TIV-induced strain-specific HI titers and increased rates of ILI and laboratory-confirmed influenza infection. These findings suggest that assessing frailty status in the elderly may identify those who are less likely to respond to TIV immunization and be at higher risk for seasonal influenza and its complications. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Yao, Xu; Xue, Qian-Li; Li, Huifen; Tian, Jing; Walston, Jeremy; Leng, Sean X.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med, Baltimore, MD 21224 USA.
[Yao, Xu; Xue, Qian-Li; Li, Huifen; Tian, Jing; Walston, Jeremy; Leng, Sean X.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21224 USA.
[Bream, Jay H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Weng, Nan-ping] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
[Resnick, Barbara] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
[Xu, Xiyan] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA.
[Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
RP Leng, SX (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Div Geriatr Med & Gerontol,Dept Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA.
EM sleng1@jhmi.edu
FU National Institute on Aging; American Federation for Aging Research;
John A. Hartford Foundation; Atlantic Philanthropies; Starr Foundation
FX Sean Leng is a current recipient of the Paul Beeson Career Development
Award in Aging Research, K23 AG028963, (supported by the National
Institute on Aging, the American Federation for Aging Research, The John
A. Hartford Foundation, The Atlantic Philanthropies, The Starr
Foundation and an anonymous donor).
NR 45
TC 39
Z9 40
U1 1
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 JUL 12
PY 2011
VL 29
IS 31
BP 5015
EP 5021
DI 10.1016/j.vaccine.2011.04.077
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 796HX
UT WOS:000293043500019
PM 21565245
ER
PT J
AU Koshiol, J
Gulley, ML
Zhao, Y
Rubagotti, M
Marincola, FM
Rotunno, M
Tang, W
Bergen, AW
Bertazzi, PA
Roy, D
Pesatori, AC
Linnoila, I
Dittmer, D
Goldstein, AM
Caporaso, NE
McShane, LM
Wang, E
Landi, MT
AF Koshiol, J.
Gulley, M. L.
Zhao, Y.
Rubagotti, M.
Marincola, F. M.
Rotunno, M.
Tang, W.
Bergen, A. W.
Bertazzi, P. A.
Roy, D.
Pesatori, A. C.
Linnoila, I.
Dittmer, D.
Goldstein, A. M.
Caporaso, N. E.
McShane, L. M.
Wang, E.
Landi, M. T.
TI Epstein-Barr virus microRNAs and lung cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Epstein-Barr virus; lung cancer; microRNA; microarray; qPCR
ID PRIMARY EFFUSION LYMPHOMA; PARAFFIN-EMBEDDED TISSUE; IN-SITU
HYBRIDIZATION; CELL-LINES; EXPRESSION; CARCINOMAS; SURVIVAL;
INFLAMMATION; ANTIBODIES; NEOPLASMS
AB BACKGROUND: We conducted the first analysis of viral microRNAs (miRNAs) in lung cancer, with a focus on Epstein-Barr virus (EBV).
METHODS: We evaluated viral miRs with a two-channel oligo-array targeting mature, anti-sense miRNAs in 290 cases. In 48 cases, we compared microarray and real-time quantitative PCR (qPCR) expression for three EBV miRNAs. We tested for EBV DNA, RNA, and protein in tumour tissue from six cases with and six cases without strong qPCR-based evidence of EBV miRNAs.
RESULTS: The EBV miRNAs strongly differentiated between adenocarcinoma and squamous cell carcinoma using the microarray (P<0.01 for 9 out of 16 EBV miRNAs). However, microarray and qPCR measurements of BART1, BART2, and BHRF1-3 expression were not significantly correlated (P = 0.53, 0.94, and 0.47, respectively). Although qPCR provided substantial evidence of EBV miRNAs in 7 out of 48 cases, only 1 of these 7 cases had detectable EBV DNA in tumour tissue. None had detectable EBV RNA or protein by histochemical stains.
CONCLUSION: In a comprehensive evaluation of EBV miRNA, DNA, RNA, and protein in lung cancer, we found little evidence of EBV in lung tumour tissue. Discrepancies between microarray- and qPCR-based strategies highlight the difficulty of validating molecular markers of disease. Our results do not support a role of EBV in lung cancer. British Journal of Cancer (2011) 105, 320-326. doi: 10.1038/bjc.2011.221 www.bjcancer.com Published online 7 June 2011 (C) 2011 Cancer Research UK
C1 [Koshiol, J.; Goldstein, A. M.; Caporaso, N. E.; Landi, M. T.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gulley, M. L.; Tang, W.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Gulley, M. L.; Tang, W.] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC USA.
[Zhao, Y.; McShane, L. M.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Rubagotti, M.; Bertazzi, P. A.; Pesatori, A. C.] Univ Milan, Dept Occupat & Environm Hlth, EPOCA Epidemiol Res Ctr, Milan, Italy.
[Rubagotti, M.; Bertazzi, P. A.; Pesatori, A. C.; Wang, E.] Fdn IRCCS Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy.
[Marincola, F. M.] NIH, IDIS, Dept Transfus Med, Ctr Clin,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Rotunno, M.; Dittmer, D.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bergen, A. W.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[Roy, D.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA.
[Linnoila, I.] NIH, Natl Inst Hlth Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Marincola, F. M.] NIH, CHI, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Koshiol, J (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM koshiolj@mail.nih.gov
RI bertazzi, pietro alberto/D-5039-2017;
OI bertazzi, pietro alberto/0000-0003-3475-2449; Bergen,
Andrew/0000-0002-1237-7644; pesatori, angela/0000-0002-0261-3252
FU NCI NIH HHS [P01 CA019014]
NR 49
TC 8
Z9 9
U1 1
U2 8
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 JUL 12
PY 2011
VL 105
IS 2
BP 320
EP 326
DI 10.1038/bjc.2011.221
PG 7
WC Oncology
SC Oncology
GA 791SE
UT WOS:000292684200018
PM 21654679
ER
PT J
AU Bergsagel, PL
Kuehl, WM
AF Bergsagel, P. Leif
Kuehl, W. Michael
TI Comprehensive Identification of Somatic Mutations in Chronic Lymphocytic
Leukemia
SO CANCER CELL
LA English
DT Editorial Material
ID ACUTE MYELOID-LEUKEMIA; DNMT3A; GENOME
C1 [Kuehl, W. Michael] NCI, Genet Branch, Bethesda, MD 20892 USA.
[Bergsagel, P. Leif] Mayo Clin Arizona, Comprehens Canc Ctr, Scottsdale, AZ USA.
RP Kuehl, WM (reprint author), NCI, Genet Branch, Bethesda, MD 20892 USA.
EM wmk@helix.nih.gov
FU Intramural NIH HHS [Z99 CA999999, ZIA BC010910-03]; NCI NIH HHS [R01
CA133966]; NIA NIH HHS [R01 AG020686]
NR 9
TC 3
Z9 3
U1 2
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD JUL 12
PY 2011
VL 20
IS 1
BP 5
EP 7
DI 10.1016/j.ccr.2011.06.023
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 793CK
UT WOS:000292797800003
PM 21741593
ER
PT J
AU Gupta, N
Stopfer, M
AF Gupta, Nitin
Stopfer, Mark
TI Olfactory Coding: Giant Inhibitory Neuron Governs Sparse Odor Codes
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID MUSHROOM BODY; SYSTEM; OSCILLATIONS; INTERNEURON; LOCUST; CORTEX
AB Electrophysiological investigations in locusts have revealed that the sparseness of odor representations, in the brain region expected to mediate olfactory learning, is shaped by a unique inhibitory neuron.
C1 [Gupta, Nitin; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Gupta, N (reprint author), NICHHD, NIH, Bldg 35,35 Lincoln Dr,Rm 3A-102,Msc 3715, Bethesda, MD 20892 USA.
EM stopferm@mail.nih.gov
OI Gupta, Nitin/0000-0002-8408-3848
NR 14
TC 2
Z9 2
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD JUL 12
PY 2011
VL 21
IS 13
BP R504
EP R506
DI 10.1016/j.cub.2011.05.044
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 793FI
UT WOS:000292805400010
PM 21741586
ER
PT J
AU Shiao, YH
Leighty, RM
Wang, CJ
Ge, X
Crawford, EB
Spurrier, JM
McCann, SD
Fields, JR
Fornwald, L
Riffle, L
Driver, C
Quinones, OA
Wilson, RE
Kasprzak, KS
Travlos, GS
Alvord, WG
Anderson, LM
AF Shiao, Yih-Horng
Leighty, Robert M.
Wang, Cuiju
Ge, Xin
Crawford, Erik B.
Spurrier, Joshua M.
McCann, Sean D.
Fields, Janet R.
Fornwald, Laura
Riffle, Lisa
Driver, Craig
Quinones, Octavio A.
Wilson, Ralph E.
Kasprzak, Kazimierz S.
Travlos, Gregory S.
Alvord, W. Gregory
Anderson, Lucy M.
TI Ontogeny-Driven rDNA Rearrangement, Methylation, and Transcription, and
Paternal Influence
SO PLOS ONE
LA English
DT Article
ID RNA-POLYMERASE-I; RIBOSOMAL-RNA; EPIGENETIC INHERITANCE;
GENE-EXPRESSION; EVOLUTION; MICE; MECHANISMS; COMPONENT; PROMOTER;
DISEASE
AB Gene rearrangement occurs during development in some cell types and this genome dynamics is modulated by intrinsic and extrinsic factors, including growth stimulants and nutrients. This raises a possibility that such structural change in the genome and its subsequent epigenetic modifications may also take place during mammalian ontogeny, a process undergoing finely orchestrated cell division and differentiation. We tested this hypothesis by comparing single nucleotide polymorphism-defined haplotype frequencies and DNA methylation of the rDNA multicopy gene between two mouse ontogenic stages and among three adult tissues of individual mice. Possible influences to the genetic and epigenetic dynamics by paternal exposures were also examined for Cr(III) and acid saline extrinsic factors. Variables derived from litters, individuals, and duplicate assays in large mouse populations were examined using linear mixed-effects model. We report here that active rDNA rearrangement, represented by changes of haplotype frequencies, arises during ontogenic progression from day 8 embryos to 6-week adult mice as well as in different tissue lineages and is modifiable by paternal exposures. The rDNA methylation levels were also altered in concordance with this ontogenic progression and were associated with rDNA haplotypes. Sperm showed highest level of methylation, followed by lungs and livers, and preferentially selected haplotypes that are positively associated with methylation. Livers, maintaining lower levels of rDNA methylation compared with lungs, expressed more rRNA transcript. In vitro transcription demonstrated haplotype-dependent rRNA expression. Thus, the genome is also dynamic during mammalian ontogeny and its rearrangement may trigger epigenetic changes and subsequent transcriptional controls, that are further influenced by paternal exposures.
C1 [Shiao, Yih-Horng; Wang, Cuiju; Crawford, Erik B.; Spurrier, Joshua M.; McCann, Sean D.; Fields, Janet R.; Kasprzak, Kazimierz S.; Anderson, Lucy M.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
[Leighty, Robert M.; Quinones, Octavio A.; Alvord, W. Gregory] Data Management Serv Inc, Frederick, MD USA.
[Ge, Xin; Fornwald, Laura; Riffle, Lisa; Driver, Craig] Sci Applicat Int Corp Frederick, Frederick, MD USA.
[Wilson, Ralph E.; Travlos, Gregory S.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Shiao, YH (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
EM shiaoy@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. This
project was also funded in part with Federal funds from the National
Cancer Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. No additional external funding received for this study.
NR 35
TC 8
Z9 8
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 JUL 12
PY 2011
VL 6
IS 7
AR e22266
DI 10.1371/journal.pone.0022266
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791WM
UT WOS:000292699000034
PM 21765958
ER
PT J
AU Stone, N
Pangilinan, F
Molloy, AM
Shane, B
Scott, JM
Ueland, PM
Mills, JL
Kirke, PN
Sethupathy, P
Brody, LC
AF Stone, Nicole
Pangilinan, Faith
Molloy, Anne M.
Shane, Barry
Scott, John M.
Ueland, Per Magne
Mills, James L.
Kirke, Peader N.
Sethupathy, Praveen
Brody, Lawrence C.
TI Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites
in One-Carbon Metabolism Genes
SO PLOS ONE
LA English
DT Article
ID NEURAL-TUBE DEFECTS; METHYLENETETRAHYDROFOLATE REDUCTASE; CHROMOSOMAL
LOCALIZATION; MICROBIOLOGICAL ASSAY; METHIONINE SYNTHASE;
FOLATE-DEFICIENCY; CELLULAR UPTAKE; MITOCHONDRIAL; EXPRESSION; RECEPTOR
AB One-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid metabolism and cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer and neural tube defects. MicroRNAs (miRNAs) are similar to 22 nt RNA regulators that have been implicated in a wide array of basic cellular processes, such as differentiation and metabolism. Accordingly, mis-regulation of miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility of OCM regulation by miRNAs. Using computational miRNA target prediction methods and Monte-Carlo based statistical analyses, we identified two candidate miRNA "master regulators" (miR-22 and miR-125) and one candidate pair of "master co-regulators" (miR-344-5p/484 and miR-488) that may influence the expression of a significant number of genes involved in OCM. Interestingly, miR-22 and miR-125 are significantly up-regulated in cells grown under low-folate conditions. In a complementary analysis, we identified 15 single nucleotide polymorphisms (SNPs) that are located within predicted miRNA target sites in OCM genes. We genotyped these 15 SNPs in a population of healthy individuals (age 18-28, n = 2,506) that was previously phenotyped for various serum metabolites related to OCM. Prior to correction for multiple testing, we detected significant associations between TCblR rs9426 and methylmalonic acid (p = 0.045), total homocysteine levels (tHcy) (p = 0.033), serum B12 (p < 0.0001), holo transcobalamin (p < 0.0001) and total transcobalamin (p < 0.0001); and between MTHFR rs1537514 and red blood cell folate (p < 0.0001). However, upon further genetic analysis, we determined that in each case, a linked missense SNP is the more likely causative variant. Nonetheless, our Monte-Carlo based in silico simulations suggest that miRNAs could play an important role in the regulation of OCM.
C1 [Stone, Nicole; Pangilinan, Faith; Sethupathy, Praveen; Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Molloy, Anne M.; Scott, John M.] Trinity Coll Dublin, Sch Immunol & Biochem, Dublin, Ireland.
[Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Ueland, Per Magne] Univ Bergen, Pharmacol Sect, Inst Med, Bergen, Norway.
[Ueland, Per Magne] Univ Bergen, Haukeland Univ Hosp, Bergen, Norway.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Kirke, Peader N.] Hlth Res Board Ireland, Child Hlth Epidemiol Unit, Dublin, Ireland.
RP Stone, N (reprint author), Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA.
EM sethupathyp@mail.nih.gov; lbrody@mail.nih.gov
RI Ueland, Per/C-7340-2013;
OI Molloy, Anne/0000-0002-1688-9049
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development; National Human Genome Research
Institute
FX This study was supported by the Intramural Research Programs of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, and the National Human Genome
Research Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 63
TC 13
Z9 17
U1 0
U2 12
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 JUL 12
PY 2011
VL 6
IS 7
AR e21851
DI 10.1371/journal.pone.0021851
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791WM
UT WOS:000292699000013
PM 21765920
ER
PT J
AU Engel, A
Shewmaker, F
Edskes, HK
Dyda, F
Wickner, RB
AF Engel, Abbi
Shewmaker, Frank
Edskes, Herman K.
Dyda, Fred
Wickner, Reed B.
TI Amyloid of the Candida albicans Ure2p Prion Domain Is Infectious and Has
an In-Register Parallel beta-Sheet Structure
SO BIOCHEMISTRY
LA English
DT Article
ID SOLID-STATE NMR; SACCHAROMYCES-CEREVISIAE; YEAST PRION; SUP35 PROTEIN;
PSI+ PRION; PROPAGATION; GENERATION; CHAPERONE; HSP104; CONSERVATION
AB Ure2p of Candida albicans (Ure2(albicans) or CaUre2p) can be a prion in Saccharomyces cerevisiae, but Ure2p of Candida glabrata (Ure2(glabrata)) cannot, even though the Ure2(glabrata) N-terminal. domain is more similar to that of the S. cerevisiae Ure2p (Ure2(cerevisiae)) than Ure2(albicans) is. We show that the N-terminal N/Q-rich prion domain of Ure2(albicans) forms amyloid that is infectious, transmitting [URE3alb] to S. cerevisiae cells expressing only C. albicans Ure2p. Using solid-state nuclear magnetic resonance of selectively labeled C. albicans Ure2p(1-9), we show that this infectious amyloid has an in-register parallel beta-sheet structure, like that of the S. cerevisiae Ure2p prion domain and other S. cerevisiae prion amyloids. In contrast, the N/Q-rich N-terminal domain of Ure2(glabrata) does not readily form amyloid, and that formed upon prolonged incubation is not infectious.
C1 [Engel, Abbi; Shewmaker, Frank; Edskes, Herman K.; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Engel, Abbi] Georgetown Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20057 USA.
RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr,MSC0830, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health
FX This work was supported by the Intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health.
NR 64
TC 12
Z9 15
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUL 12
PY 2011
VL 50
IS 27
BP 5971
EP 5978
DI 10.1021/bi200142x
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 788FK
UT WOS:000292430600001
PM 21634787
ER
PT J
AU Sharma, S
Findlay, GM
Bandukwala, HS
Oberdoerffer, S
Baust, B
Li, ZG
Schmidt, V
Hogan, PG
Sacks, DB
Rao, A
AF Sharma, Sonia
Findlay, Gregory M.
Bandukwala, Hozefa S.
Oberdoerffer, Shalini
Baust, Beate
Li, Zhigang
Schmidt, Valentina
Hogan, Patrick G.
Sacks, David B.
Rao, Anjana
TI Dephosphorylation of the nuclear factor of activated T cells (NFAT)
transcription factor is regulated by an RNA-protein scaffold complex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID LONG NONCODING RNAS; GENE-EXPRESSION; CHROMATIN; IQGAP1; COACTIVATOR;
CALCIUM; BINDING; FAMILY
AB Nuclear factor of activated T cells (NFAT) proteins are Ca(2+)-regulated transcription factors that control gene expression in many cell types. NFAT proteins are heavily phosphorylated and reside in the cytoplasm of resting cells; when cells are stimulated by a rise in intracellular Ca(2+), NFAT proteins are dephosphorylated by the Ca(2+)/calmodulin-dependent phosphatase calcineurin and translocate to the nucleus to activate target gene expression. Here we show that phosphorylated NFAT1 is present in a large cytoplasmic RNA-protein scaffold complex that contains a long intergenic noncoding RNA (lincRNA), NRON [noncoding (RNA) repressor of NFAT]; a scaffold protein, IQ motif containing GTPase activating protein (IQGAP); and three NFAT kinases, casein kinase 1, glycogen synthase kinase 3, and dual specificity tyrosine phosphorylation regulated kinase. Combined knockdown of NRON and IQGAP1 increased NFAT dephosphorylation and nuclear import exclusively after stimulation, without affecting the rate of NFAT rephosphorylation and nuclear export; and both NRON-depleted T cells and T cells from IQGAP1-deficient mice showed increased production of NFAT-dependent cytokines. Our results provide evidence that a complex of lincRNA and protein forms a scaffold for a latent transcription factor and its regulatory kinases, and support an emerging consensus that lincRNAs that bind transcriptional regulators have a similar scaffold function.
C1 [Sharma, Sonia; Findlay, Gregory M.; Bandukwala, Hozefa S.; Oberdoerffer, Shalini; Baust, Beate; Hogan, Patrick G.; Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA.
[Sharma, Sonia; Findlay, Gregory M.; Bandukwala, Hozefa S.; Oberdoerffer, Shalini; Baust, Beate; Hogan, Patrick G.; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Li, Zhigang; Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Schmidt, Valentina] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA.
RP Rao, A (reprint author), La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
EM arao@idi.harvard.edu
OI Sacks, David/0000-0003-3100-0735
FU National Institutes of Health (NIH) [AI40127, AI84167, CA93645,
DK62040]; American Cancer Society; Canadian Institutes of Health
Research; Leukemia and Lymphoma Society; Lady Tata Memorial Fund;
Children's Hospital, Boston
FX We thank Danya Machnes for technical support and members of the Rao lab
for valuable discussions. This work was funded by National Institutes of
Health (NIH) grants AI40127 and AI84167 (to A. R.), NIH Grant CA93645
(to D. B. S.) and NIH Grant DK62040 and a Research Scholar Grant from
the American Cancer Society (to V. S.), a Fellowship from the Canadian
Institutes of Health Research and a Special Fellowship from the Leukemia
and Lymphoma Society (S. S.), a fellowship from the Lady Tata Memorial
Fund (H. S. B.), and a postdoctoral training grant from the Joint
Program in Transfusion Biology and Medicine, Children's Hospital, Boston
(S.O.).
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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 JUL 12
PY 2011
VL 108
IS 28
BP 11381
EP 11386
DI 10.1073/pnas.1019711108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791BO
UT WOS:000292635200024
PM 21709260
ER
PT J
AU Harris, A
Borgnia, MJ
Shi, D
Bartesaghi, A
He, HF
Pejchal, R
Kang, Y
Depetris, R
Marozsan, AJ
Sanders, RW
Klasse, PJ
Milne, JLS
Wilson, IA
Olson, WC
Moore, JP
Subramaniam, S
AF Harris, Audray
Borgnia, Mario J.
Shi, Dan
Bartesaghi, Alberto
He, Haifeng
Pejchal, Robert
Kang, Yun (Kenneth)
Depetris, Rafael
Marozsan, Andre J.
Sanders, Rogier W.
Klasse, Per Johan
Milne, Jacqueline L. S.
Wilson, Ian A.
Olson, William C.
Moore, John P.
Subramaniam, Sriram
TI Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope
glycoproteins display the same closed and open quaternary molecular
architectures
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE viral entry; cryoelectron microscopy; HIV spike; HIV vaccine; AIDS
vaccine
ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODIES;
MONOCLONAL-ANTIBODIES; GP120; COMPLEX; ELICITATION; REVEALS; SUBTYPE;
BINDING; TARGET
AB The initial step in HIV-1 infection occurs with the binding of cell surface CD4 to trimeric HIV-1 envelope glycoproteins (Env), a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120). The design of soluble versions of trimeric Env that display structural and functional properties similar to those observed on intact viruses is highly desirable from the viewpoint of designing immunogens that could be effective as vaccines against HIV/AIDS. Using cryoelectron tomography combined with subvolume averaging, we have analyzed the structure of SOSIP gp140 trimers, which are cleaved, solubilized versions of the ectodomain of trimeric HIV-1 Env. We show that unliganded gp140 trimers adopt a quaternary arrangement similar to that displayed by native unliganded trimers on the surface of intact HIV-1 virions. When complexed with soluble CD4, Fab 17b, which binds to gp120 at its chemokine coreceptor binding site, or both soluble CD4 and 17b Fab, gp140 trimers display an open conformation in which there is an outward rotation and displacement of each gp120 protomer. We demonstrate that the molecular arrangements of gp120 trimers in the closed and open conformations of the soluble trimer are the same as those observed for the closed and open states, respectively, of trimeric gp120 on intact HIV-1 BaL virions, establishing that soluble gp140 trimers can be designed to mimic the quaternary structural transitions displayed by native trimeric Env.
C1 [Harris, Audray; Borgnia, Mario J.; Shi, Dan; Bartesaghi, Alberto; Milne, Jacqueline L. S.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[He, Haifeng] FEI Co, Hillsboro, OR 97124 USA.
[Pejchal, Robert; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
[Pejchal, Robert; Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Kang, Yun (Kenneth); Marozsan, Andre J.; Olson, William C.] Progen Pharmaceut, Tarrytown, NY 10591 USA.
[Depetris, Rafael; Sanders, Rogier W.; Klasse, Per Johan; Moore, John P.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU National Cancer Institute; NIH [AI36082, 45463]; International AIDS
Vaccine Initiative; NIH HIV Vaccine Research and Design [P01 AI-082362]
FX We thank Steven Fellini and colleagues for assistance with use of the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health (NIH) (http://biowulf.nih.gov); Dr.
Dennis Burton (The Scripps Research Institute) for providing 17b
antibody; and A. M. Cupo, A.A. Ouattara, and L. Pagel for excellent
technical assistance. This work was supported by the Center for Cancer
Research at the National Cancer Institute, NIH and by NIH Grants AI36082
and 45463; by the International AIDS Vaccine Initiative; and by NIH HIV
Vaccine Research and Design Grant P01 AI-082362.
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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 JUL 12
PY 2011
VL 108
IS 28
BP 11440
EP 11445
DI 10.1073/pnas.1101414108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791BO
UT WOS:000292635200034
PM 21709254
ER
PT J
AU Johmura, Y
Soung, NK
Park, JE
Yu, LR
Zhou, M
Bang, JK
Kim, BY
Veenstra, TD
Erikson, RL
Lee, KS
AF Johmura, Yoshikazu
Soung, Nak-Kyun
Park, Jung-Eun
Yu, Li-Rong
Zhou, Ming
Bang, Jeong K.
Kim, Bo-Yeon
Veenstra, Timothy D.
Erikson, Raymond L.
Lee, Kyung S.
TI Regulation of microtubule-based microtubule nucleation by mammalian
polo-like kinase 1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE mitosis; spindle assembly; polo-box domain; distributive
phosphorylation; Ser/Thr protein kinase
ID MITOTIC SPINDLE; GAMMA-TUBULIN; BOX DOMAIN; HUMAN-CELLS; COMPLEX; PLK1;
CENTROSOME; CYTOKINESIS; RECRUITMENT; AUGMIN
AB Bipolar spindle formation is pivotal for accurate segregation of mitotic chromosomes during cell division. A growing body of evidence suggests that, in addition to centrosome-and chromatin-based microtubule (MT) nucleation, MT-based MT nucleation plays an important role for proper bipolar spindle formation in various eukaryotic organisms. Although a recently discovered Augmin complex appears to play a central role in this event, how Augmin is regulated remains unknown. Here we provide evidence that a mammalian polo-like kinase 1 (Plk1) localizes to mitotic spindles and promotes MT-based MT nucleation by directly regulating Augmin. Mechanistically, we demonstrated that Cdc2-dependent phosphorylation on a gamma-tubulin ring complex (gamma-TuRC) recruitment protein, Nedd1/GCP-WD, at the previously uncharacterized S460 residue induces the Nedd1-Plk1 interaction. This step appeared to be critical to allow Plk1 to phosphorylate the Hice1 subunit of the Augmin complex to promote the Augmin-MT interaction and MT-based MT nucleation from within the spindle. Loss of either the Nedd1 S460 function or the Plk1-dependent Hice1 phosphorylation impaired both the Augmin-MT interaction and gamma-tubulin recruitment to the spindles, thus resulting in improper bipolar spindle formation that ultimately leads to mitotic arrest and apoptotic cell death. Thus, via the formation of the Nedd1-Plk1 complex and subsequent Augmin phosphorylation, Plk1 regulates spindle MT-based MT nucleation to accomplish normal bipolar spindle formation and mitotic progression.
C1 [Erikson, Raymond L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Johmura, Yoshikazu; Soung, Nak-Kyun; Park, Jung-Eun; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Soung, Nak-Kyun; Kim, Bo-Yeon] Korea Res Inst Biosci & Biotechnol, Chem Biol Res Ctr, Ochang 363883, Chung Buk, South Korea.
[Yu, Li-Rong] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Ctr Prote, Jefferson, AR 72079 USA.
[Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Bang, Jeong K.] Korean Basic Sci Inst, Div Magnet Resonance, Ochang 363883, Chung Bak, South Korea.
RP Erikson, RL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM erikson@mcb.harvard.edu; kyunglee@mail.nih.gov
FU National Cancer Institute; Food and Drug Administration (FDA); Korea
Basic Science Institute [T3022B]; Ministry of Education, Science and
Technology of Korea
FX We are grateful to Mary Dasso, Dan L. Sackett, and Yasuhiko Terada for
critical reading of the manuscript; Gohta Goshima, Jens Luders, Andreas
Merdes, Dan L. Sackett, Tim Stearns, Ryota Uehara, and Michael B. Yaffe
for reagents and technical assistance; and Susan Garfield, Valarie Barr,
Brian Svedberg, and Elise Shumsky for their assistance in confocal and
time-lapse microscopies. This work was supported in part by National
Cancer Institute intramural grants (to K. S. L. and T. D. V.), a Food
and Drug Administration (FDA) grant (to L.-R.Y.), Korea Basic Science
Institute's high field NMR research program Grant T3022B (To J.K.B.),
and the World Class Institute research program of the National Research
Foundation of Korea, funded by the Ministry of Education, Science and
Technology of Korea (B.Y.K.).
NR 27
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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 JUL 12
PY 2011
VL 108
IS 28
BP 11446
EP 11451
DI 10.1073/pnas.1106223108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791BO
UT WOS:000292635200035
PM 21690413
ER
PT J
AU Grati, M
Kachar, B
AF Grati, M'hamed
Kachar, Bechara
TI Myosin VIIa and sans localization at stereocilia upper tip-link density
implicates these Usher syndrome proteins in mechanotransduction
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID VESTIBULAR HAIR-CELLS; INNER-EAR; ADAPTATION; ACTIN; MUTATIONS;
HARMONIN; BUNDLE; TRANSDUCTION; CADHERIN-23; MECHANISMS
AB In the most accepted model for hair cell mechanotransduction, a cluster of myosin motors located at the stereocilia upper tip-link density (UTLD) keeps the tip-link under tension at rest. Both myosin VIIa (MYO7A) and myosin 1c have been implicated in mechanotransduction based on functional studies. However, localization studies are conflicting, leaving open the question of which myosin localizes at the UTLD and generates the tip-link resting tension. Using immunofluorescence, we now show that MYO7A and sans, a MYO7A-interacting protein, cluster at the UTLD. Analysis of the immunofluorescence intensity indicates that eight or more MYO7A molecules are present at each UTLD, consistent with a direct role for MYO7A in maintaining tip-link tension. MYO7A and sans localization at the UTLD is confirmed by transfection of hair cells with GFP-tagged constructs for these proteins. Cotransfection studies in a heterologous system show that MYO7A, sans, and the UTLD protein harmonin-b form a tripartite complex and that each protein is capable of interacting with one another independently. We propose that MYO7A, sans, and harmonin-b form the core components of the UTLD molecular complex. In this complex, MYO7A is likely the motor element that pulls on CDH23 to exert tension on the tip-link.
C1 [Grati, M'hamed; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
RP Kachar, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD 20892 USA.
EM kacharb@nidcd.nih.gov
FU National Institute on Deafness and Other Communication
Disorders-National Institutes of Health
FX We thank Drs. L. Andrade, F. Salles, S. Ebrahim, U. Manor, and Y. Dai
for help with experiments and with the manuscript. This work was
supported by the Intramural Program of the National Institute on
Deafness and Other Communication Disorders-National Institutes of
Health.
NR 42
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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 JUL 12
PY 2011
VL 108
IS 28
BP 11476
EP 11481
DI 10.1073/pnas.1104161108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791BO
UT WOS:000292635200040
PM 21709241
ER
PT J
AU Dahirel, V
Shekhar, K
Pereyra, F
Miura, T
Artyomov, M
Talsania, S
Allen, TM
Altfeld, M
Carrington, M
Irvine, DJ
Walker, BD
Chakraborty, AK
AF Dahirel, Vincent
Shekhar, Karthik
Pereyra, Florencia
Miura, Toshiyuki
Artyomov, Mikita
Talsania, Shiv
Allen, Todd M.
Altfeld, Marcus
Carrington, Mary
Irvine, Darrell J.
Walker, Bruce D.
Chakraborty, Arup K.
TI Coordinate linkage of HIV evolution reveals regions of immunological
vulnerability
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cytotoxic T-lymphocyte response; elite controllers; random matrix theory
ID T-CELL RESPONSES; IMMUNODEFICIENCY-VIRUS TYPE-1; ELITE CONTROLLERS;
VACCINE DESIGN; RHESUS-MONKEYS; INFECTION; DETERMINANTS; ASSOCIATIONS;
MUTATIONS; PROTEINS
AB Cellular immune control of HIV is mediated, in part, by induction of single amino acid mutations that reduce viral fitness, but compensatory mutations limit this effect. Here, we sought to determine if higher order constraints on viral evolution exist, because some coordinately linked combinations of mutations may hurt viability. Immune targeting of multiple sites in such a multidimensionally conserved region might render the virus particularly vulnerable, because viable escape pathways would be greatly restricted. We analyzed available HIV sequences using a method from physics to reveal distinct groups of amino acids whose mutations are collectively coordinated ("HIV sectors"). From the standpoint of mutations at individual sites, one such group in Gag is as conserved as other collectively coevolving groups of sites in Gag. However, it exhibits higher order conservation indicating constraints on the viability of viral strains with multiple mutations. Mapping amino acids from this group onto protein structures shows that combined mutations likely destabilize multiprotein structural interactions critical for viral function. Persons who durably control HIV without medications preferentially target the sector in Gag predicted to be most vulnerable. By sequencing circulating viruses from these individuals, we find that individual mutations occur with similar frequency in this sector as in other targeted Gag sectors. However, multiple mutations within this sector are very rare, indicating previously unrecognized multidimensional constraints on HIV evolution. Targeting such regions with higher order evolutionary constraints provides a novel approach to immunogen design for a vaccine against HIV and other rapidly mutating viruses.
C1 [Dahirel, Vincent; Shekhar, Karthik; Pereyra, Florencia; Allen, Todd M.; Altfeld, Marcus; Carrington, Mary; Irvine, Darrell J.; Walker, Bruce D.; Chakraborty, Arup K.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02129 USA.
[Dahirel, Vincent; Shekhar, Karthik; Pereyra, Florencia; Allen, Todd M.; Altfeld, Marcus; Carrington, Mary; Irvine, Darrell J.; Walker, Bruce D.; Chakraborty, Arup K.] Harvard Univ, Boston, MA 02129 USA.
[Dahirel, Vincent; Shekhar, Karthik; Talsania, Shiv; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Dahirel, Vincent; Artyomov, Mikita; Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Irvine, Darrell J.; Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Artyomov, Mikita] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia.
[Talsania, Shiv] Univ Loughborough, Dept Chem Engn, Loughborough LE11 3TU, Leics, England.
[Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Irvine, Darrell J.; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Miura, Toshiyuki] Univ Tokyo, Inst Med Sci, Tokyo 1088639, Japan.
RP Walker, BD (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02129 USA.
EM bwalker@partners.org; arupc@mit.edu
RI Allen, Todd/F-5473-2011
FU Ragon Institute; National Institutes of Health [RO130914, PO1 AI074415,
HHSN261200800001E]; Howard Hughes Medical Institute; Mark and Lisa
Schwartz Foundation; National Cancer Institute
FX We thank D. Barouch and H. Eisen for valuable discussions. Financial
support was provided by the Ragon Institute, a National Institutes of
Health Director's Pioneer Award (to A. K. C.), National Institutes of
Health Grants RO130914 (to B. D. W.) and PO1 AI074415 (to M. Altfeld and
T. M. A.), The Howard Hughes Medical Institute (B. D. W.) and the Mark
and Lisa Schwartz Foundation (B. D. W.) This project has been funded in
whole or in part with federal funds from the National Cancer Institute,
National Institutes of Health, under Contract HHSN261200800001E.
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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 JUL 12
PY 2011
VL 108
IS 28
BP 11530
EP 11535
DI 10.1073/pnas.1105315108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791BO
UT WOS:000292635200049
PM 21690407
ER
PT J
AU Hwang, J
Kita, R
Kwon, HS
Choi, EH
Lee, SH
Udey, MC
Morasso, MI
AF Hwang, Joonsung
Kita, Ryosuke
Kwon, Hyouk-Soo
Choi, Eung Ho
Lee, Seung Hun
Udey, Mark C.
Morasso, Maria I.
TI Epidermal ablation of Dlx3 is linked to IL-17-associated skin
inflammation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE barrier function; psoriasis; inflammatory diseases; homeobox
transcription factor; mouse model
ID LIVER-X-RECEPTORS; CORNIFIED ENVELOPE; ATOPIC-DERMATITIS; BARRIER
FUNCTION; T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; PSORIASIS PATHOGENESIS;
MOUSE MODELS; IN-VIVO; KERATINOCYTES
AB In an effort to understand the role of Distal-less 3 (Dlx3) in cutaneous biology and pathophysiology, we generated and characterized a mouse model with epidermal ablation of Dlx3. K14cre;Dlx3(Kin/f) mice exhibited epidermal hyperproliferation and abnormal differentiation of keratinocytes. Results from subsequent analyses revealed cutaneous inflammation that featured accumulation of IL-17-producing CD4(+) T, CD8(+) T, and gamma delta T cells in the skin and lymph nodes of K14cre;Dlx3(Kin/f) mice. The gene expression signature of K14cre; Dlx3(Kin/f) skin shared features with lesional psoriatic skin, and Dlx3 expression was markedly and selectively decreased in psoriatic skin. Interestingly, cultured Dlx3 null keratinocytes triggered cytokine production that is potentially linked to inflammatory responses in K14cre; Dlx3(Kin/f) mice. Thus, Dlx3 ablation in epidermis is linked to altered epidermal differentiation, barrier development, and IL-17-associated skin inflammation. This model provides a platform that will allow the systematic exploration of the contributions of keratinocytes to cutaneous inflammation.
C1 [Hwang, Joonsung; Kita, Ryosuke; Morasso, Maria I.] NIAMSD, Dev Skin Biol Sect, NIH, Bethesda, MD 20892 USA.
[Kwon, Hyouk-Soo; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Choi, Eung Ho] Yonsei Univ, Wonju Coll Med, Dept Dermatol, Wonju 220701, South Korea.
[Lee, Seung Hun] Yonsei Univ, Coll Med, Dept Dermatol, Seoul 135720, South Korea.
RP Morasso, MI (reprint author), NIAMSD, Dev Skin Biol Sect, NIH, Bethesda, MD 20892 USA.
EM morassom@mail.nih.gov
FU NIAMS; Center for Cancer Research of the NCI at the National Institutes
of Health
FX We thank Dr. J. Chae, Dr. O. Duverger, Dr. J. Okano, and Mr. A. Lee of
the National Institute of Arthritis, Musculoskeletal and Skin Diseases
(NIAMS) and the NIAMS Light Imaging Section staff, for technical
assistance; Dr. H. J. Kim, Dr. S. E. Lee, and Dr. H. J. Lee of Yonsei
University for materials; Dr. S. Yuspa and Dr. C. Cataisson (NCI) for
helpful comments on the manuscript; and Dr. A. Oshima and other members
of the Laboratory of Cancer Biology and Genetics, National Cancer
Institute (NCI) for helpful discussions. This study was supported by the
NIAMS Intramural Research Program and the Center for Cancer Research of
the NCI at the National Institutes of Health.
NR 51
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U2 2
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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 JUL 12
PY 2011
VL 108
IS 28
BP 11566
EP 11571
DI 10.1073/pnas.1019658108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791BO
UT WOS:000292635200055
PM 21709238
ER
PT J
AU Cohen, JE
Lee, PR
Chen, S
Li, W
Fields, RD
AF Cohen, Jonathan E.
Lee, Philip R.
Chen, Shan
Li, Wei
Fields, R. Douglas
TI MicroRNA regulation of homeostatic synaptic plasticity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE activity-dependent development; posttranscriptional gene regulation;
presynaptic terminal
ID DENDRITIC SPINE DEVELOPMENT; LONG-TERM POTENTIATION; VESICLE PROTEIN 2A;
HIPPOCAMPAL-NEURONS; EXPRESSION; BRAIN; SYNAPSES; NEUROTRANSMISSION;
IDENTIFICATION; INACTIVITY
AB Homeostatic mechanisms are required to control formation and maintenance of synaptic connections to maintain the general level of neural impulse activity within normal limits. How genes controlling these processes are co-coordinately regulated during homeostatic synaptic plasticity is unknown. MicroRNAs (miRNAs) exert regulatory control over mRNA stability and translation and may contribute to local and activity-dependent posttranscriptional control of synapse-associated mRNAs. However, identifying miRNAs that function through posttranscriptional gene silencing at synapses has remained elusive. Using a bioinformatics screen to identify sequence motifs enriched in the 3'UTR of rapidly destabilized mRNAs, we identified a developmentally and activity-regulated miRNA (miR-485) that controls dendritic spine number and synapse formation in an activity-dependent homeostatic manner. We find that many plasticity-associated genes contain predicted miR-485 binding sites and further identify the presynaptic protein SV2A as a target of miR-485. miR-485 negatively regulated dendritic spine density, postsynaptic density 95 (PSD-95) clustering, and surface expression of GluR2. Furthermore, miR-485 overexpression reduced spontaneous synaptic responses and transmitter release, as measured by miniature excitatory postsynaptic current (EPSC) analysis and FM 1-43 staining. SV2A knockdown mimicked the effects of miR-485, and these effects were reversed by SV2A overexpression. Moreover, 5 d of increased synaptic activity induced homeostatic changes in synaptic specializations that were blocked by a miR-485 inhibitor. Our findings reveal a role for this previously uncharacterized miRNA and the presynaptic protein SV2A in homeostatic plasticity and nervous system development, with possible implications in neurological disorders (e. g., Huntington and Alzheimer's disease), where miR-485 has been found to be dysregulated.
C1 [Cohen, Jonathan E.; Lee, Philip R.; Fields, R. Douglas] Eunice Kennedy Shriver Natl Inst Child & Human De, Sect Nervous Syst Dev & Plast, NIH, Bethesda, MD 20892 USA.
[Chen, Shan; Li, Wei] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA.
RP Fields, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child & Human De, Sect Nervous Syst Dev & Plast, NIH, Bethesda, MD 20892 USA.
EM fieldsd@mail.nih.gov
RI Moyal, Elizabeth/A-9802-2015
OI Moyal, Elizabeth/0000-0002-6593-9276
FU National Institute of Child Health and Human Development; National Eye
Institute
FX We are grateful to Drs. David Bredt and Robert J. Wenthold for
PSD-95-GFP and Robert Malinow for pCl-SEP-GluR2(R) used in this study.
This work was supported by the National Institute of Child Health and
Human Development and the National Eye Institute Intramural Research
Program.
NR 45
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U2 14
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 JUL 12
PY 2011
VL 108
IS 28
BP 11650
EP 11655
DI 10.1073/pnas.1017576108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791BO
UT WOS:000292635200069
PM 21697510
ER
PT J
AU Yaniv, Y
Juhaszova, M
Wang, S
Fishbein, KW
Zorov, DB
Sollott, SJ
AF Yaniv, Yael
Juhaszova, Magdalena
Wang, Su
Fishbein, Kenneth W.
Zorov, Dmitry B.
Sollott, Steven J.
TI Analysis of Mitochondrial 3D-Deformation in Cardiomyocytes during Active
Contraction Reveals Passive Structural Anisotropy of Orthogonal Short
Axes
SO PLOS ONE
LA English
DT Article
ID PERMEABILITY TRANSITION PORE; RAT VENTRICULAR MYOCYTES; CARDIAC
MYOCYTES; MATRIX VOLUME; HEART-MITOCHONDRIA; OSMOTIC STRENGTH;
PAPILLARY-MUSCLE; LEFT ATRIUM; LENGTH; MEMBRANE
AB The cardiomyocyte cytoskeleton, composed of rigid and elastic elements, maintains the isolated cell in an elongated cylindrical shape with an elliptical cross-section, even during contraction-relaxation cycles. Cardiomyocyte mitochondria are micron-sized, fluid-filled passive spheres distributed throughout the cell in a crystal-like lattice, arranged in pairs sandwiched between the sarcomere contractile machinery, both longitudinally and radially. Their shape represents the extant 3-dimensional (3D) force-balance. We developed a novel method to examine mitochondrial 3D-deformation in response to contraction and relaxation to understand how dynamic forces are balanced inside cardiomyocytes. The variation in transmitted light intensity induced by the periodic lattice of myofilaments alternating with mitochondrial rows can be analyzed by Fourier transformation along a given cardiomyocyte axis to measure mitochondrial deformation along that axis. This technique enables precise detection of changes in dimension of similar to 1% in similar to 1 mu m (long-axis) structures with 8 ms time-resolution. During active contraction (1 Hz stimulation), mitochondria deform along the length-and width-axes of the cell with similar deformation kinetics in both sarcomere and mitochondrial structures. However, significant deformation anisotropy (without hysteresis) was observed between the orthogonal short-axes (i.e., width and depth) of mitochondria during electrical stimulation. The same degree of deformation anisotropy was also found between the myocyte orthogonal short-axes during electrical stimulation. Therefore, the deformation of the mitochondria reflects the overall deformation of the cell, and the apparent stiffness and stress/strain characteristics of the cytoskeleton differ appreciably between the two cardiomyocyte orthogonal short-axes. This method may be applied to obtaining a better understanding of the dynamic force-balance inside cardiomyocytes and of changes in the spatial stiffness characteristics of the cytoskeleton that may accompany aging or pathological conditions.
C1 [Yaniv, Yael; Juhaszova, Magdalena; Wang, Su; Zorov, Dmitry B.; Sollott, Steven J.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD USA.
[Fishbein, Kenneth W.] NIA, Lab Clin Invest, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD USA.
RP Yaniv, Y (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD USA.
EM sollotts@mail.nih.gov
RI Yaniv, Yael/B-3311-2015;
OI Yaniv, Yael/0000-0002-5183-6284; Fishbein, Kenneth/0000-0002-6353-4603
FU National Institutes of Health, National Institute on Aging
FX This work was supported entirely by the Intramural Research Program of
the National Institutes of Health, National Institute on Aging. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 53
TC 13
Z9 13
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 11
PY 2011
VL 6
IS 7
AR e21985
DI 10.1371/journal.pone.0021985
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791QY
UT WOS:000292680900021
PM 21779362
ER
PT J
AU Finkel, T
AF Finkel, Toren
TI Signal transduction by reactive oxygen species
SO JOURNAL OF CELL BIOLOGY
LA English
DT Review
ID ELEGANS LIFE-SPAN; MN SUPEROXIDE-DISMUTASE; TYROSINE-PHOSPHATASE 1B;
EPIDERMAL-GROWTH-FACTOR; STEM-CELL HOMEOSTASIS; ATM-DEFICIENT MICE;
OXIDATIVE STRESS; HYDROGEN-PEROXIDE; MITOCHONDRIAL DYSFUNCTION;
ATAXIA-TELANGIECTASIA
AB Although historically viewed as purely harmful, recent evidence suggests that reactive oxygen species (ROS) function as important physiological regulators of intracellular signaling pathways. The specific effects of ROS are modulated in large part through the covalent modification of specific cysteine residues found within redox-sensitive target proteins. Oxidation of these specific and reactive cysteine residues in turn can lead to the reversible modification of enzymatic activity. Emerging evidence suggests that ROS regulate diverse physiological parameters ranging from the response to growth factor stimulation to the generation of the inflammatory response, and that dysregulated ROS signaling may contribute to a host of human diseases.
C1 NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
FU National Institutes of Health; Ellison Medical Foundation
FX This work was supported by National Institutes of Health Intramural
funds and a grant from the Ellison Medical Foundation.
NR 98
TC 596
Z9 624
U1 18
U2 116
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 JUL 11
PY 2011
VL 194
IS 1
BP 7
EP 15
DI 10.1083/jcb.201102095
PG 9
WC Cell Biology
SC Cell Biology
GA 792RZ
UT WOS:000292768200003
PM 21746850
ER
PT J
AU Schuster, SJ
Neelapu, SS
Gause, BL
Janik, JE
Muggia, FM
Gockerman, JP
Winter, JN
Flowers, CR
Nikcevich, DA
Sotomayor, EM
McGaughey, DS
Jaffe, ES
Chong, EA
Reynolds, CW
Berry, DA
Santos, CF
Popa, MA
McCord, AM
Kwak, LW
AF Schuster, Stephen J.
Neelapu, Sattva S.
Gause, Barry L.
Janik, John E.
Muggia, Franco M.
Gockerman, Jon P.
Winter, Jane N.
Flowers, Christopher R.
Nikcevich, Daniel A.
Sotomayor, Eduardo M.
McGaughey, Dean S.
Jaffe, Elaine S.
Chong, Elise A.
Reynolds, Craig W.
Berry, Donald A.
Santos, Carlos F.
Popa, Mihaela A.
McCord, Amy M.
Kwak, Larry W.
TI Vaccination With Patient-Specific Tumor-Derived Antigen in First
Remission Improves Disease-Free Survival in Follicular Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; COLONY-STIMULATING FACTOR; B-CELL LYMPHOMA;
IDIOTYPE VACCINATION; PHASE-III; IMMUNE-RESPONSES; MYELOMA PROTEINS;
STAGE-III; TRIAL; CYCLOPHOSPHAMIDE
AB Purpose
Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial.
Patients and Methods
Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control.
Results
Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients.
Conclusion
Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.
C1 [Kwak, Larry W.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA.
[Schuster, Stephen J.; Chong, Elise A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Gause, Barry L.; Janik, John E.; Jaffe, Elaine S.; Reynolds, Craig W.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Muggia, Franco M.] NYU, Sch Med, Inst Canc, New York, NY USA.
[Gockerman, Jon P.] Duke Univ, Ctr Comprehens Canc, Durham, NC USA.
[Winter, Jane N.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Flowers, Christopher R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Nikcevich, Daniel A.] SMDC Canc Ctr, Duluth, MN USA.
[Nikcevich, Daniel A.] Duluth Community Clin Oncol, Duluth, MN USA.
[Sotomayor, Eduardo M.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Santos, Carlos F.; Popa, Mihaela A.; McCord, Amy M.] Biovest Int, Tampa, FL USA.
[McGaughey, Dean S.] Virginia Oncol Associates, Norfolk, VA USA.
RP Kwak, LW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, 1515 Holcombe Blvd,Unit 429, Houston, TX 77030 USA.
EM lkwak@mdanderson.org
RI Flowers, Christopher/F-1953-2010;
OI Flowers, Christopher/0000-0002-9524-3990; Jaffe,
Elaine/0000-0003-4632-0301; Muggia, Franco/0000-0003-0703-9146
FU National Cancer Institute; Biovest International; Millennium
Pharmaceuticals; Berlex/Bayer Pharmaceuticals; Celgene
FX Supported by the National Cancer Institute and Biovest International.;
Research Funding: Stephen J. Schuster, Biovest International; Sattva S.
Neelapu, Biovest International; Franco M. Muggia, Biovest International;
Jane N. Winter, Biovest International; Christopher R. Flowers, Biovest
International, Millennium Pharmaceuticals, Berlex/Bayer Pharmaceuticals;
Larry W. Kwak, Celgene
NR 37
TC 122
Z9 125
U1 1
U2 12
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2011
VL 29
IS 20
BP 2787
EP 2793
DI 10.1200/JCO.2010.33.3005
PG 7
WC Oncology
SC Oncology
GA 789IH
UT WOS:000292508500019
PM 21632504
ER
PT J
AU Chen, Z
Zhang, B
Albert, PS
AF Chen, Zhen
Zhang, Bo
Albert, Paul S.
TI A joint modeling approach to data with informative cluster size:
Robustness to the cluster size model
SO STATISTICS IN MEDICINE
LA English
DT Article
DE shared parameter models; non-ignorable dropout; developmental toxicity;
random cluster size; informative number of observations
ID SUBUNIT-SPECIFIC OUTCOMES; LINEAR MIXED MODELS; LONGITUDINAL DATA;
LIKELIHOOD APPROACH; MISSPECIFICATION
AB In many biomedical and epidemiological studies, data are often clustered due to longitudinal follow up or repeated sampling. While in some clustered data the cluster size is pre-determined, in others it may be correlated with the outcome of subunits, resulting in informative cluster size. When the cluster size is informative, standard statistical procedures that ignore cluster size may produce biased estimates. One attractive framework for modeling data with informative cluster size is the joint modeling approach in which a common set of random effects are shared by both the outcome and cluster size models. In addition to making distributional assumptions on the shared random effects, the joint modeling approach needs to specify the cluster size model. Questions arise as to whether the joint modeling approach is robust to misspecification of the cluster size model. In this paper, we studied both asymptotic and finite-sample characteristics of the maximum likelihood estimators in joint models when the cluster size model is misspecified. We found that using an incorrect distribution for the cluster size may induce small to moderate biases, while using a misspecified functional form for the shared random parameter in the cluster size model results in nearly unbiased estimation of outcome model parameters. We also found that there is little efficiency loss under this model misspecification. A developmental toxicity study was used to motivate the research and to demonstrate the findings. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Chen, Zhen; Zhang, Bo; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
RP Chen, Z (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM chenzhe@mail.nih.gov
FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research is support by the Intramural Research Program of the NIH,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development. The authors thank the two anonymous referees and the
Associate Editor for very useful comments that improved the presentation
of the paper. They also thank the Center for Information Technology, the
National Institutes of Health, for providing access to the
high-performance computational capabilities of the Biowulf Linux
cluster.
NR 22
TC 6
Z9 6
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD JUL 10
PY 2011
VL 30
IS 15
BP 1825
EP 1836
DI 10.1002/sim.4239
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 777EM
UT WOS:000291598600004
PM 21495060
ER
PT J
AU Melief, CJM
O'Shea, JJ
Stroncek, DF
AF Melief, Cornelis J. M.
O'Shea, John J.
Stroncek, David F.
TI Summit on cell therapy for cancer: The importance of the interaction of
multiple disciplines to advance clinical therapy
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
ID NATURAL-KILLER-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; CD8(+) T-CELLS;
METASTATIC MELANOMA; ADOPTIVE IMMUNOTHERAPY; GENETIC-MODIFICATION;
MYELOID-LEUKEMIA; VIVO EXPANSION; PHASE-II; NK CELLS
AB The field of cellular therapy of cancer is moving quickly and the issues involved with its advancement are complex and wide ranging. The growing clinical applications and success of adoptive cellular therapy of cancer has been due to the rapid evolution of immunology, cancer biology, gene therapy and stem cell biology and the translation of advances in these fields from the research laboratory to the clinic. The continued development of this field is dependent on the exchange of ideas across these diverse disciplines, the testing of new ideas in the research laboratory and in animal models, the development of new cellular therapies and GMP methods to produce these therapies, and the testing of new adoptive cell therapies in clinical trials. The Summit on Cell Therapy for Cancer to held on November 1 and 2, 2011 at the National Institutes of Health (NIH) campus will include a mix of perspectives, concepts and ideas related to adoptive cellular therapy that are not normally presented together at any single meeting. This novel assembly will generate new ideas and new collaborations and possibly increase the rate of advancement of this field.
C1 [Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Melief, Cornelis J. M.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RC Leiden, Netherlands.
[O'Shea, John J.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr MSC 1288,Bldg 10,Room 3C720, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
FU Society for Immunotherapy of Cancer (SITC)
FX This summit is sponsored by Society for Immunotherapy of Cancer (SITC)
in conjunction with the following participating organizations: AABB
(formerly the American Association of Blood Banks), American Society for
Blood and Marrow Transplantation (ASBMT), American Society of Gene &
Cell Therapy (ASGCT) and Cancer Immunotherapy Trials Network (CITN).
NR 36
TC 2
Z9 2
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 8
PY 2011
VL 9
AR 107
DI 10.1186/1479-5876-9-107
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 810UM
UT WOS:000294153000001
PM 21740581
ER
PT J
AU Sviridov, DO
Ikpot, IZ
Stonik, J
Drake, SK
Amar, M
Osei-Hwedieh, DO
Piszczek, G
Turner, S
Remaley, AT
AF Sviridov, D. O.
Ikpot, I. Z.
Stonik, J.
Drake, S. K.
Amar, M.
Osei-Hwedieh, D. O.
Piszczek, G.
Turner, S.
Remaley, A. T.
TI Helix stabilization of amphipathic peptides by hydrocarbon stapling
increases cholesterol efflux by the ABCA1 transporter
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Apolipoproteins; Peptides; Atherosclerosis; Cholesterol efflux; High
density lipoproteins
ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; MIMETIC PEPTIDES; CORONARY
ATHEROSCLEROSIS; LIPID EFFLUX; SPECIFICITY; TRIAL; D-4F; MICE
AB Apolipoprotein mimetic peptides are short amphipathic peptides that efflux cholesterol from cells by the ABCA1 transporter and are being investigated as therapeutic agents for cardiovascular disease. We examined the role of helix stabilization of these peptides in cholesterol efflux. A 23-amino acid long peptide (Ac-VLESFKVSFLSALEEYTKKLNTQ-NH2) based on the last helix of apoA-I (A10) was synthesized, as well as two variants, S1A10 and S2A10, in which the third and fourth and third and fifth turn of each peptide, respectively, were covalently joined by hydrocarbon staples. By CD spectroscopy, the stapled variants at 24 degrees C were more helical in aqueous buffer than A10 (A10 17%, S1A10 62%, S2A10 97%). S1A10 and S2A10 unlike A10 were resistant to proteolysis by pepsin and chymotrypsin. S1A10 and S2A10 showed more than a 10-fold increase in cholesterol efflux by the ABCA1 transporter compared to A10. In summary, hydrocarbon stapling of amphipathic peptides increases their helicity, makes them resistant to proteolysis and enhances their ability to promote cholesterol efflux by the ABCA1 transporter, indicating that this peptide modification may be useful in the development of apolipoprotein mimetic peptides. Published by Elsevier Inc.
C1 [Sviridov, D. O.; Ikpot, I. Z.; Stonik, J.; Amar, M.; Osei-Hwedieh, D. O.; Remaley, A. T.] NHLBI, Lipoprotein Metab Sect, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA.
[Drake, S. K.] NIH, Dept Crit Care Med, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Piszczek, G.] NHLBI, Biophys Core Facil, NIH, Bethesda, MD 20892 USA.
[Turner, S.] KineMed Inc, Alameda, CA USA.
RP Remaley, AT (reprint author), NHLBI, Lipoprotein Metab Sect, Cardiopulm Branch, NIH, Bldg 10,Room 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA.
EM aremaley1@cc.nih.gov
FU National Institutes of Health
FX Research was supported by intramural NHLBI research funds from the
National Institutes of Health.
NR 33
TC 26
Z9 26
U1 1
U2 16
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 JUL 8
PY 2011
VL 410
IS 3
BP 446
EP 451
DI 10.1016/j.bbrc.2011.05.154
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 793CJ
UT WOS:000292797700013
PM 21672528
ER
PT J
AU Tano, JY
Smedlund, K
Lee, R
Abramowitz, J
Birnbaumer, L
Vazquez, G
AF Tano, Jean-Yves
Smedlund, Kathryn
Lee, Robert
Abramowitz, Joel
Birnbaumer, Lutz
Vazquez, Guillermo
TI Impairment of survival signaling and efferocytosis in TRPC3-deficient
macrophages
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE TRPC proteins; Calcium influx; Calcium channels; Macrophage survival;
Apoptosis
ID ENDOTHELIAL-CELLS; TRPC3 CHANNELS; ACTIVATION; ATHEROSCLEROSIS;
APOPTOSIS; INCREASES; PROTEINS; CALCIUM; DISEASE
AB We have recently shown that in macrophages proper operation of the survival pathways phosphatidylin-ositol-3-kinase (PI3K)/AKT and nuclear factor kappa B (NFkB) has an obligatory requirement for constitutive, non-regulated Ca(2+) influx. In the present work we examined if Transient Receptor Potential Canonical 3 (TRPC3), a member of the TRPC family of Ca(2+)-permeable cation channels, contributes to the constitutive Ca(2+) influx that supports macrophage survival. We used bone marrow-derived macrophages obtained from TRPC3(-/-) mice to determine the activation status of survival signaling pathways, apoptosis and their efferocytic properties. Treatment of TRPC3(+/+) macrophages with the pro-apoptotic cytokine TNF alpha induced time-dependent phosphorylation of I kappa B alpha, AKT and BAD, and this was drastically reduced in TRPC3(-/-) macrophages. Compared to TRPC3(+/+) cells TRPC3(-/-) macrophages exhibited reduced constitutive cation influx, increased apoptosis and impaired efferocytosis. The present findings suggest that macrophage TRPC3, presumably through its constitutive function, contributes to survival signaling and efferocytic properties. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Tano, Jean-Yves; Smedlund, Kathryn; Lee, Robert; Vazquez, Guillermo] Univ Toledo, Coll Med, Dept Physiol & Pharmacol, Toledo, OH 43614 USA.
[Tano, Jean-Yves; Smedlund, Kathryn; Lee, Robert; Vazquez, Guillermo] Univ Toledo, Coll Med, Ctr Diabet & Endocrine Res, Toledo, OH 43614 USA.
[Abramowitz, Joel; Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Dept Signal Transduct, Lab Membrane Signaling, Res Triangle Pk, NC 27709 USA.
RP Vazquez, G (reprint author), Univ Toledo, Coll Med, Dept Physiol & Pharmacol, 3000 Arlington Av,UTHSC Mail Stop 1008,Hlth Sci C, Toledo, OH 43614 USA.
EM Guillermo.Vazquez@utoledo.edu
RI Abramowitz, Joel/A-2620-2015;
OI Smedlund, Kathryn/0000-0002-5746-8419
FU American Heart Association [SDG0635250N]; University of Toledo College
of Medicine
FX This work was supported by American Heart Association (SDG0635250N to
G.V.) and University of Toledo College of Medicine.
NR 20
TC 19
Z9 19
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 8
PY 2011
VL 410
IS 3
BP 643
EP 647
DI 10.1016/j.bbrc.2011.06.045
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 793CJ
UT WOS:000292797700047
PM 21684255
ER
PT J
AU Zoabi, M
Sadeh, R
de Bie, P
Marquez, VE
Ciechanover, A
AF Zoabi, Muhammad
Sadeh, Ronen
de Bie, Prim
Marquez, Victor E.
Ciechanover, Aaron
TI PRAJA1 is a ubiquitin ligase for the polycomb repressive complex 2
proteins (vol 408, pg 393, 2011)
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Correction
C1 [Zoabi, Muhammad; Sadeh, Ronen; de Bie, Prim; Ciechanover, Aaron] Technion Israel Inst Technol, Rappaport Fac Med, Ctr Vasc & Tumor Biol, IL-31096 Haifa, Israel.
[Zoabi, Muhammad; Sadeh, Ronen; de Bie, Prim; Ciechanover, Aaron] Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel.
[Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Ciechanover, A (reprint author), Technion Israel Inst Technol, Rappaport Fac Med, Ctr Vasc & Tumor Biol, IL-31096 Haifa, Israel.
EM c_tzachy@netvision.net.il
NR 1
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 8
PY 2011
VL 410
IS 3
BP 705
EP 705
DI 10.1016/j.bbrc.2011.06.037
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 793CJ
UT WOS:000292797700058
ER
PT J
AU Biddie, SC
John, S
Sabo, PJ
Thurman, RE
Johnson, TA
Schiltz, RL
Miranda, TB
Sung, MH
Trump, S
Lightman, SL
Vinson, C
Stamatoyannopoulos, JA
Hager, GL
AF Biddie, Simon C.
John, Sam
Sabo, Pete J.
Thurman, Robert E.
Johnson, Thomas A.
Schiltz, R. Louis
Miranda, Tina B.
Sung, Myong-Hee
Trump, Saskia
Lightman, Stafford L.
Vinson, Charles
Stamatoyannopoulos, John A.
Hager, Gordon L.
TI Transcription Factor AP1 Potentiates Chromatin Accessibility and
Glucocorticoid Receptor Binding
SO MOLECULAR CELL
LA English
DT Article
ID NF-KAPPA-B; DNA-BINDING; IN-VIVO; RETINOIC ACID; C-JUN; PROTEIN;
ACTIVATION; GENE; REPRESSION; SEQUENCE
AB Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with coregulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate that a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state. Combining DNasel accessibility and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding. We propose a model in which the basal occupancy of transcription factors acts to prime chromatin and direct inducible transcription factors to select regions in the genome.
C1 [Biddie, Simon C.; John, Sam; Johnson, Thomas A.; Schiltz, R. Louis; Miranda, Tina B.; Sung, Myong-Hee; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Sabo, Pete J.; Thurman, Robert E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Biddie, Simon C.; Lightman, Stafford L.] Univ Bristol, Henry Wellcome Labs Neurosci & Endocrinol, Fac Med & Dent, Bristol BS1 3NY, Avon, England.
[Trump, Saskia] UFZ Helmholtz Ctr Environm Res, Dept Environm Immunol, D-04318 Leipzig, Germany.
RP John, S (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, B602,Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA.
EM sam@mail.nih.gov; jstam@uw.edu; hagerg@exchange.nih.gov
OI Biddie, Simon/0000-0002-8253-0253
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; NIH [1RC2HG005654]; Needham Cooper Postgraduate
Medicine Scholarship
FX We thank Stephanie Morris, Lars Grontved, and Raffaella Nativio for
critical reading of the manuscript. This research was supported, in
part, by the Intramural Research Program of the National Institutes of
Health (NIH), National Cancer Institute, Center for Cancer Research, and
NIH Grant #1RC2HG005654 (to J.A.S.). S.C.B was supported, in part, by
The Needham Cooper Postgraduate Medicine Scholarship. The authors thank
Michael Radonovich for technical assistance and Richard Sandstrom for
help with data submission.
NR 42
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U1 6
U2 20
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 JUL 8
PY 2011
VL 43
IS 1
BP 145
EP 155
DI 10.1016/j.molcel.2011.06.016
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 792EN
UT WOS:000292723400015
PM 21726817
ER
PT J
AU O'Brien, TR
Everhart, JE
Morgan, TR
Lok, AS
Chung, RT
Shao, YW
Shiffman, ML
Dotrang, M
Sninsky, JJ
Bonkovsky, HL
Pfeiffer, RM
AF O'Brien, Thomas R.
Everhart, James E.
Morgan, Timothy R.
Lok, Anna S.
Chung, Raymond T.
Shao, Yongwu
Shiffman, Mitchell L.
Dotrang, Myhanh
Sninsky, John J.
Bonkovsky, Herbert L.
Pfeiffer, Ruth M.
CA HALT-C Trial Grp
TI An IL28B Genotype-Based Clinical Prediction Model for Treatment of
Chronic Hepatitis C
SO PLOS ONE
LA English
DT Article
ID CHRONIC HCV INFECTION; LONG-TERM TREATMENT; INTERFERON-ALPHA;
VIRUS-INFECTION; GENETIC-VARIATION; PEGYLATED INTERFERON; RIBAVIRIN;
PEGINTERFERON; TELAPREVIR; THERAPY
AB Background: Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables.
Methods: HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC).
Results: Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p <.0001); the model also included HCV RNA (log10 IU/ml), AST:ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p < 0.001). Subjects with a predicted probability of SVR < 10% had an observed SVR rate of 3.8%; subjects with a predicted probability > 10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study.
Conclusion: A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC.
C1 [O'Brien, Thomas R.; Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
[Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA.
[Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit,Med Serv, Boston, MA USA.
[Shao, Yongwu] Informat Management Serv Inc, Silver Spring, MD USA.
[Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA.
[Dotrang, Myhanh] CSC, Rockville, MD USA.
[Sninsky, John J.] Celera Corp, Alameda, CA USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA.
[Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
RP O'Brien, TR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM obrient@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011;
OI Yang, Shuman/0000-0002-9638-0890
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institute of Allergy and Infectious Diseases (NIAID);
National Cancer Institute (NCI); National Center for Minority Health and
Health Disparities; National Center for Research Resources, National
Institutes of Health; Hoffmann-La Roche, Inc.; Celera Corporation
through National Institutes of Health; National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics;
University of Massachusetts Medical Center, Worcester, MA
[N01-DK-9-2326]; University of Connecticut Health Center, Farmington, CT
[M01RR-06192]; Saint Louis University School of Medicine, St Louis, MO
[N01-DK-w9-2324]; Massachusetts General Hospital, Boston, MA
[N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University of Colorado
Denver, School of Medicine, Aurora, CO [N01-DK-9-2327, M01RR-00051, 1
UL1 RR 025780-01]; University of California Irvine, Irvine, CA
[N01-DK-9-2320, M01RR-00827]; University of Texas Southwestern Medical
Center, Dallas, TX [N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01];
University of Southern California, Los Angeles, CA [N01-DK-9-2325,
M01RR-00043]; University of Michigan Medical Center, Ann Arbor, MI
[N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth
University Health System, Richmond, VA [N01-DK-9-2322, M01RR-00065];
Vertex Pharmaceuticals; Merck; Schering Plough Corporation; WAKO
Diagnostics; Bristol-Myers Squibb; Gilead and Eisai Pharmaceuticals;
Novartis; Romark; Biolex; Conatus; Glaxo SmithKline; Globeimmune; Human
Genome Sciences; Idenix; Roche; Tibotec; Valeant; Wyeth; Zymogenetics;
Novartis Pharmaceuticals
FX This study was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy
and Infectious Diseases (NIAID), the National Cancer Institute (NCI),
the National Center for Minority Health and Health Disparities, General
Clinical Research Center and Clinical and Translational Science Center
grants from the National Center for Research Resources, National
Institutes of Health. Employees of NIDDK and NCI played a role in study
design, data collection and analysis, decision to publish, and
preparation of the manuscript. Additional funding to conduct this study
was supplied by Hoffmann-La Roche, Inc., and Celera Corporation through
Cooperative Research and Development Agreements (CRADA) with the
National Institutes of Health. The present study was also supported by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
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. Yongwu Shao was employed by
Information Management Services, Silver Spring; Myhanh Dotrang by CSC,
Rockville; and John J. Sninsky by Celera Corporation, Alameda. These
authors played a role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. Contract and
grant numbers: University of Massachusetts Medical Center, Worcester,
MA: (Contract N01-DK-9-2326); University of Connecticut Health Center,
Farmington, CT: (Grant M01RR-06192); Saint Louis University School of
Medicine, St Louis, MO: (Contract N01-DK-w9-2324); Massachusetts General
Hospital, Boston, MA: (Contract N01-DK-9-2319, Grant M01RR-01066; Grant
1 UL1 RR025758-01, Harvard Clinical and Translational Science Center);
University of Colorado Denver, School of Medicine, Aurora, CO: (Contract
N01-DK-9-2327, Grant M01RR-00051, Grant 1 UL1 RR 025780-01); University
of California Irvine, Irvine, CA: (Contract N01-DK-9-2320, Grant
M01RR-00827); University of Texas Southwestern Medical Center, Dallas,
TX: (Contract N01-DK-9-2321, Grant M01RR-00633, Grant 1 UL1 RR024982-01,
North and Central Texas Clinical and Translational Science Initiative);
University of Southern California, Los Angeles, CA: (Contract
N01-DK-9-2325, Grant M01RR-00043); University of Michigan Medical
Center, Ann Arbor, MI: (Contract N01-DK-9-2323, Grant M01RR-00042, Grant
1 UL1 RR024986, Michigan Center for Clinical and Health Research);
Virginia Commonwealth University Health System, Richmond, VA: (Contract
N01-DK-9-2322, Grant M01RR-00065).; The authors wish to report the
following relationships that might appear to represent a potential
conflict: John J. Sninsky is employed by Celera Corporation, Alameda. T.
R. Morgan is on the speaker's bureau and receives research support from
Hoffmann-La Roche, Inc.; is a consultant, serves on an advisory board,
and receives research support from Vertex Pharmaceuticals; serves on an
advisory board for Gilead Sciences; and receives research support from
Merck, Schering Plough Corporation, and WAKO Diagnostics. A. S. Lok is a
consultant for Hoffmann-La Roche, Inc., Abbott and Gilead; and receives
research support from Schering-Plough Corporation, Bristol-Myers Squibb,
Gilead and Eisai Pharmaceuticals. R. T. Chung receives research support
from Hoffmann-La Roche, Inc.; receives research support from
Schering-Plough, Novartis, and Romark; and is a consultant for Vertex
Pharmaceuticals, Merck, Pfizer, Astellas, Novartis, and Gilead. M. L.
Shiffman is a consultant for Celera Corporation, Hoffmann-La Roche,
Inc., and National Genome Sciences; has attended advisor meetings with
Anadys, Biolex, Bristol-Myers-Squibb, Conatus, Globeimmune, Human Genome
Sciences, Novartis, Roche, Romark, Pfizer, Schering-Plough, Valeant,
Vertex and Zymogenetics; is a speaker for Roche and Schering-Plough; is
on the data safety monitoring boards with Abbott and Anadys; and has
received research support from Biolex, Conatus, Glaxo SmithKline,
Globeimmune, Human Genome Sciences, Idenix, Roche, Romark, Tibotec,
Valeant, Vertex, Wyeth and Zymogenetics. J. J. Sninsky is an employee of
Celera Corporation. H. L. Bonkovsky receives research support from
Hoffmann-La Roche, Inc.; is a consultant for Boehringer-Ingelheim; is a
consultant and on the advisory board for Clinuvel, Inc.; is a
consultant, advisory board member and receives research support from
Novartis Pharmaceuticals; is a consultant and on the speakers' bureau
for Lundbeck Pharmaceuticals; and receives research support from Vertex
Pharmaceuticals. There are no patents, products in development or
marketed products to declare. This does not alter the authors' adherence
to all the PLoS ONE policies on sharing data and materials. Authors with
no financial relationships related to this project are: T. R. O'Brien,
J. E. Everhart, Y. Shao, M. Dotrang, and R. M. Pfeiffer.
NR 27
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 8
PY 2011
VL 6
IS 7
AR e20904
DI 10.1371/journal.pone.0020904
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791IA
UT WOS:000292657200005
PM 21760886
ER
PT J
AU Cookson, MR
AF Cookson, Mark R.
TI A Feedforward Loop Links Gaucher and Parkinson's Diseases?
SO CELL
LA English
DT Editorial Material
ID ALPHA-SYNUCLEIN
C1 NIA, Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Cookson, MR (reprint author), NIA, Gene Express Unit, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
NR 10
TC 4
Z9 4
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 8
PY 2011
VL 146
IS 1
BP 9
EP 11
DI 10.1016/j.cell.2011.06.031
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 789TN
UT WOS:000292539300001
PM 21729776
ER
PT J
AU Shao, SC
Hegde, RS
AF Shao, Sichen
Hegde, Ramanujan S.
TI A Flip Turn for Membrane Protein Insertion
SO CELL
LA English
DT Editorial Material
ID EXIT TUNNEL; RIBOSOME; INTEGRATION; TOPOLOGY
C1 [Shao, Sichen; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Shao, Sichen] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
RP Hegde, RS (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM hegde.science@gmail.com
OI Shao, Sichen/0000-0003-2679-5537; Hegde, Ramanujan/0000-0001-8338-852X
FU Intramural NIH HHS [ZIA HD008862-02]
NR 10
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Z9 3
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 8
PY 2011
VL 146
IS 1
BP 13
EP 15
DI 10.1016/j.cell.2011.06.028
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 789TN
UT WOS:000292539300003
PM 21729778
ER
PT J
AU Mazzulli, JR
Xu, YH
Sun, Y
Knight, AL
McLean, PJ
Caldwell, GA
Sidransky, E
Grabowski, GA
Krainc, D
AF Mazzulli, Joseph R.
Xu, You-Hai
Sun, Ying
Knight, Adam L.
McLean, Pamela J.
Caldwell, Guy A.
Sidransky, Ellen
Grabowski, Gregory A.
Krainc, Dimitri
TI Gaucher Disease Glucocerebrosidase and alpha-Synuclein Form a
Bidirectional Pathogenic Loop in Synucleinopathies
SO CELL
LA English
DT Article
ID PARKINSONS-DISEASE; FIBRIL FORMATION; MOUSE MODELS; MUTATIONS;
NEURODEGENERATION; DEFICIENCY; MECHANISM; OLIGOMERS; CATECHOLS; ENZYME
AB Parkinson's disease (PD), an adult neurodegenerative disorder, has been clinically linked to the lysosomal storage disorder Gaucher disease (GD), but the mechanistic connection is not known. Here, we show that functional loss of GD-linked glucocerebrosidase (GCase) in primary cultures or human iPS neurons compromises lysosomal protein degradation, causes accumulation of alpha-synuclein (alpha-syn), and results in neurotoxicity through aggregation-dependent mechanisms. Glucosylceramide (GlcCer), the GCase substrate, directly influenced amyloid formation of purified alpha-syn by stabilizing soluble oligomeric intermediates. We further demonstrate that alpha-syn inhibits the lysosomal activity of normal GCase in neurons and idiopathic PD brain, suggesting that GCase depletion contributes to the pathogenesis of sporadic synucleinopathies. These findings suggest that the bidirectional effect of alpha-syn and GCase forms a positive feedback loop that may lead to a self-propagating disease. Therefore, improved targeting of GCase to lysosomes may represent a specific therapeutic approach for PD and other synucleinopathies.
C1 [Mazzulli, Joseph R.; McLean, Pamela J.; Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA.
[Xu, You-Hai; Sun, Ying; Grabowski, Gregory A.] Cincinnati Childrens Hosp, Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA.
[Xu, You-Hai; Sun, Ying; Grabowski, Gregory A.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA.
[Knight, Adam L.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA.
[Caldwell, Guy A.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurol, Birmingham, AL 35294 USA.
[Caldwell, Guy A.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurobiol, Birmingham, AL 35294 USA.
[Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Krainc, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA.
EM krainc@mgh.helix.harvard.edu
FU National Institutes of Health [R01NS051303, F32NS066730]; National
Institute of Neurological Disorders and Stroke [R01DK36729]; National
Human Genome Research Institute
FX We thank Harry Ischiropoulos for pCDNA3.1 human alpha-syn plasmids and
syn303 antibody, Benoit I. Giasson for the SNL-1 antibody, and Kimberly
Kegel for technical advice on liposome formation. This work was
supported by National Institutes of Health grants R01NS051303 (D.K.) and
F32NS066730 (J.R.M.) from the National Institute of Neurological
Disorders and Stroke, R01DK36729 (G.A.G.), and the Intramural Programs
of the National Human Genome Research Institute and the National
Institutes of Health (E.S.).
NR 38
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U1 8
U2 37
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 8
PY 2011
VL 146
IS 1
BP 37
EP 52
DI 10.1016/j.cell.2011.06.001
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 789TN
UT WOS:000292539300005
PM 21700325
ER
PT J
AU Chang, AHK
Jeong, J
Levine, RL
AF Chang, Allen H. K.
Jeong, Jinsook
Levine, Rodney L.
TI Iron Regulatory Protein 2 Turnover through a Nonproteasomal Pathway
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ELEMENT-BINDING-PROTEIN; DEPENDENT DEGRADATION; ACONITASE ACTIVITY;
MOLECULAR CONTROL; RNA-BINDING; CELL-DEATH; HOMEOSTASIS; IRP2;
TRANSFERRIN; INHIBITION
AB Iron regulatory protein 2 (IRP2) controls the synthesis of many proteins involved in iron metabolism, and the level of IRP2 itself is regulated by varying the rate of its degradation. The proteasome is known to mediate degradation, with specificity conferred by an iron-sensing E3 ligase. Most studies on the degradation of IRP2 have employed cells overexpressing IRP2 and also rendered iron deficient to further increase IRP2 levels. We utilized a sensitive, quantitative assay for IRP2, which allowed study of endogenous IRP2 degradation in HEK293A cells under more physiologic conditions. We found that under these conditions, the proteasome plays only a minor role in the degradation of IRP2, with almost all the IRP2 being degraded by a nonproteasomal pathway. This new pathway is calcium-dependent but is not mediated by calpain. Elevating the cellular level of IRP2 by inducing iron deficiency or by transfection causes the proteasomal pathway to account for the major fraction of IRP2 degradation. We conclude that under physiological, iron-sufficient conditions, the steady-state level of IRP2 in HEK293A cells is regulated by the nonproteasomal pathway.
C1 [Chang, Allen H. K.; Jeong, Jinsook; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Levine, RL (reprint author), Bldg 50,Room 2351,MSC 8012, Bethesda, MD 20892 USA.
EM rlevine@nih.gov
RI Levine, Rodney/D-9885-2011
FU NHLBI, National Institutes of Health [1Z01 HL000225]
FX This work was supported by the Intramural Research Program of the NHLBI,
National Institutes of Health, (Project no. 1Z01 HL000225).
NR 33
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Z9 4
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 8
PY 2011
VL 286
IS 27
BP 23698
EP 23707
DI 10.1074/jbc.M110.216788
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 786HO
UT WOS:000292294900011
PM 21558272
ER
PT J
AU Ghosh, S
Vassilev, AP
Zhang, JM
Zhao, YM
DePamphilis, ML
AF Ghosh, Soma
Vassilev, Alex P.
Zhang, Junmei
Zhao, Yingming
DePamphilis, Melvin L.
TI Assembly of the Human Origin Recognition Complex Occurs through
Independent Nuclear Localization of Its Components
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DNA-REPLICATION; ORC6 PROTEIN; IN-VIVO; CELLS; BINDING; ARCHITECTURE;
RECRUITMENT; CENTROSOME; INITIATION; SEQUENCE
AB Initiation of eukaryotic genome duplication begins when a six-subunit origin recognition complex (ORC) binds to DNA. However, the mechanism by which this occurs in vivo and the roles played by individual subunits appear to differ significantly among organisms. Previous studies identified a soluble human ORC(2-5) complex in the nucleus, an ORC(1-5) complex bound to chromatin, and an Orc6 protein that binds weakly, if at all, to other ORC subunits. Here we show that stable ORC(1-6) complexes also can be purified from human cell extracts and that Orc6 and Orc1 each contain a single nuclear localization signal that is essential for nuclear localization but not for ORC assembly. The Orc6 nuclear localization signal, which is essential for Orc6 function, is facilitated by phosphorylation at its cyclin-dependent kinase consensus site and by association with Kpna6/1, nuclear transport proteins that did not co-purify with other ORC subunits. These and other results support a model in which Orc6, Orc1, and ORC(2-5) are transported independently to the nucleus where they can either assemble into ORC(1-6) or function individually.
C1 [Ghosh, Soma; Vassilev, Alex P.; DePamphilis, Melvin L.] NICHD, NIH, Bethesda, MD 20892 USA.
[Zhang, Junmei] Univ Texas SW Med Ctr Dallas, Prot Chem Technol Ctr, Dallas, TX 75390 USA.
[Zhao, Yingming] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA.
RP DePamphilis, ML (reprint author), NICHD, NIH, Bldg 6-3A-15,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM depamphm@mail.nih.gov
FU National Institutes of Health (NICHD)
FX This work was supported, in whole or in part, by National Institutes of
Health intramural research programs (NICHD).
NR 41
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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 JUL 8
PY 2011
VL 286
IS 27
BP 23831
EP 23841
DI 10.1074/jbc.M110.215988
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 786HO
UT WOS:000292294900026
PM 21555516
ER
PT J
AU Nady, N
Lemak, A
Walker, JR
Avvakumov, GV
Kareta, MS
Achour, M
Xue, S
Duan, SL
Allali-Hassani, A
Zuo, XB
Wang, YX
Bronner, C
Chedin, F
Arrowsmith, CH
Dhe-Paganon, S
AF Nady, Nataliya
Lemak, Alexander
Walker, John R.
Avvakumov, George V.
Kareta, Michael S.
Achour, Mayada
Xue, Sheng
Duan, Shili
Allali-Hassani, Abdellah
Zuo, Xiaobing
Wang, Yun-Xing
Bronner, Christian
Chedin, Frederic
Arrowsmith, Cheryl H.
Dhe-Paganon, Sirano
TI Recognition of Multivalent Histone States Associated with
Heterochromatin by UHRF1 Protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RESIDUAL DIPOLAR COUPLINGS; EMBRYONIC STEM-CELLS; DNA METHYLATION;
BINDING-PROTEIN; STRUCTURAL BASIS; PERICENTROMERIC HETEROCHROMATIN;
MULTIDOMAIN PROTEIN; 3-WAY DECOMPOSITION; LYSINE METHYLATION;
MAMMALIAN-CELLS
AB Histone modifications and DNA methylation represent two layers of heritable epigenetic information that regulate eukaryotic chromatin structure and gene activity. UHRF1 is a unique factor that bridges these two layers; it is required for maintenance DNA methylation at hemimethylated CpG sites, which are specifically recognized through its SRA domain and also interacts with histone H3 trimethylated on lysine 9 (H3K9me3) in an unspecified manner. Here we show that UHRF1 contains a tandem Tudor domain (TTD) that recognizes H3 tail peptides with the heterochromatin-associated modification state of trimethylated lysine 9 and unmodified lysine 4 (H3K4me0/K9me3). Solution NMR and crystallographic data reveal the TTD simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first Tudor subdomain and unmodified H3K4 within a groove between the tandem subdomains. The subdomains undergo a conformational adjustment upon peptide binding, distinct from previously reported mechanisms for dual histone mark recognition. Mutant UHRF1 protein deficient for H3K4me0/K9me3 binding shows altered localization to heterochromatic chromocenters and fails to reduce expression of a target gene, p16(INK4A), when overexpressed. Our results demonstrate a novel recognition mechanism for the combinatorial readout of histone modification states associated with gene silencing and add to the growing evidence for coordination of, and cross-talk between, the modification states of H3K4 and H3K9 in regulation of gene expression.
C1 [Nady, Nataliya; Lemak, Alexander; Duan, Shili; Arrowsmith, Cheryl H.] Univ Toronto, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON M5G 1L7, Canada.
[Nady, Nataliya; Lemak, Alexander; Duan, Shili; Arrowsmith, Cheryl H.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
[Walker, John R.; Avvakumov, George V.; Xue, Sheng; Allali-Hassani, Abdellah; Arrowsmith, Cheryl H.; Dhe-Paganon, Sirano] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
[Kareta, Michael S.; Chedin, Frederic] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
[Achour, Mayada; Bronner, Christian] Fac Pharm, CNRS UMR7213, Lab Biophoton & Pharmacol, F-67401 Illkirch Graffenstaden, France.
[Zuo, Xiaobing; Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA.
[Dhe-Paganon, Sirano] Univ Toronto, Dept Physiol, Toronto, ON M5G 1L5, Canada.
RP Arrowsmith, CH (reprint author), 101 Coll St,Ste 700, Toronto, ON M5G 1L7, Canada.
EM carrow@uhnres.utoronto.ca; sirano.dhepaganon@utoronto.ca
RI Zuo, Xiaobing/F-1469-2010;
OI Kareta, Michael/0000-0002-6980-9065; Zuo, Xiaobing/0000-0002-0134-4804
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [DE-AC02-98CH10886, DE-AC02-06CH11357]; Canadian Institutes for
Health Research (CIHR) [1097737]; Canadian Foundation for Innovation,
Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline,
Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario
Innovation Trust; Ontario Ministry for Research and Innovation;
MerckCo., Inc.; Novartis Research Foundation; Swedish Agency for
Innovation Systems; Swedish Foundation for Strategic Research; Wellcome
Trust; Ontario Ministry of Health and Long Term Care; Cancer Research
Coordinating Committee; California Institute of Regenerative Medicine
FX Use of the National Synchrotron Light Source, Brookhaven National
Laboratory was supported by the U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences under Contract
DE-AC02-98CH10886. Use of the Advanced Photon Source was supported by
the U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Contract DE-AC02-06CH11357. The Structural Genomics
Consortium is a registered charity (1097737) that receives funds from
the Canadian Institutes for Health Research (CIHR), the Canadian
Foundation for Innovation, Genome Canada through the Ontario Genomics
Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice
Wallenberg Foundation, the Ontario Innovation Trust, the Ontario
Ministry for Research and Innovation, Merck&Co., Inc., the Novartis
Research Foundation, the Swedish Agency for Innovation Systems, the
Swedish Foundation for Strategic Research, and the Wellcome Trust. This
work was supported in part by the Ontario Ministry of Health and Long
Term Care (to C. H. A.), the Cancer Research Coordinating Committee (to
F. C.), a Stem Cell training grant from the California Institute of
Regenerative Medicine (to M. S. K.). a Frederick Banting and Charles
Best Canada Doctoral Research Award from the CIHR (to N. N.).
NR 72
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U1 1
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 8
PY 2011
VL 286
IS 27
BP 24300
EP 24311
DI 10.1074/jbc.M111.234104
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 786HO
UT WOS:000292294900071
PM 21489993
ER
PT J
AU Marshall, E
Zarin, D
AF Marshall, Eliot
Zarin, Deborah
TI Unseen World of Clinical Trials Emerges From U.S. Database
SO SCIENCE
LA English
DT Editorial Material
C1 [Zarin, Deborah] NIH, Bethesda, MD 20892 USA.
NR 0
TC 4
Z9 4
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 JUL 8
PY 2011
VL 333
IS 6039
BP 145
EP 145
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 789GG
UT WOS:000292502700013
ER
PT J
AU Utreras, E
Terse, A
Keller, J
Iadarola, MJ
Kulkarni, AB
AF Utreras, Elias
Terse, Anita
Keller, Jason
Iadarola, Michael J.
Kulkarni, Ashok B.
TI Resveratrol inhibits Cdk5 activity through regulation of p35 expression
SO MOLECULAR PAIN
LA English
DT Article
DE Cdk5; resveratrol; TNF-alpha?alpha; pain; Egr-1; ERK1/2; analgesic
ID NF-KAPPA-B; DIABETIC NEUROPATHIC PAIN; CYCLIN-DEPENDENT KINASES; INDUCED
ACTIVATION; MAP KINASE; PC12 CELLS; MOUSE SKIN; TNF-ALPHA; HYPERALGESIA;
TRANSCRIPTION
AB Background: We have previously reported that cyclin-dependent kinase 5 (Cdk5) participates in the regulation of nociceptive signaling. Through activation of the ERK1/2 pathway, Tumor Necrosis Factor-alpha (TNF-alpha) induces expression of Egr-1. This results in the sustained and robust expression of p35, a coactivator of Cdk5, in PC12 cells, thereby increasing Cdk5 kinase activity. The aim of our present study was to test whether resveratrol, a polyphenolic compound with known analgesic activity, can regulate Cdk5/p35 activity.
Results: Here we used a cell-based assay in which a p35 promoter-luciferase construct was stably transfected in PC12 cells. Our studies demonstrate that resveratrol inhibits p35 promoter activity and also blocks the TNF-alpha mediated increase in Cdk5 activity in PC12 cells. Resveratrol also inhibits p35 expression and blocks the TNF-alpha mediated increase in Cdk5 activity in DRG neurons. In the presence of resveratrol, the MEK inhibitor decreased p35 promoter activity, whereas the inhibitors of p38 MAPK, JNK and NF-kappa B increased p35 promoter activity, indicating that these pathways regulate p35 expression differently. The TNF-alpha-mediated increase in Egr-1 expression was decreased by resveratrol treatment with a concomitant reduction in p35 expression and protein levels, resulting in reduced Cdk5 kinase activity.
Conclusions: We demonstrate here that resveratrol regulates p35 promoter activity in PC12 cells and DRG neurons. Most importantly, resveratrol blocks the TNF-alpha-mediated increase in p35 promoter activity, thereby reducing p35 expression and subsequent Cdk5 kinase activity. This new molecular mechanism adds to the known analgesic effects of resveratrol and confirms the need for identifying new analgesics based on their ability to inhibit Cdk5 activity for effective treatment of pain.
C1 [Utreras, Elias; Terse, Anita; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Keller, Jason; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, Bethesda, MD 20892 USA.
RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Bldg 30,Rm 130,MSC 4395, Bethesda, MD 20892 USA.
EM ak40m@nih.gov
RI utreras, elias/I-1038-2013
OI utreras, elias/0000-0002-1004-0466
FU Division of Intramural Research, NIDCR, NIH
FX We would like to thank Dr. Michaela Prochazkova for helpful discussions
and Shelagh Powers for expert editorial assistance. These studies were
supported by the Division of Intramural Research, NIDCR, NIH.
NR 50
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Z9 16
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-8069
J9 MOL PAIN
JI Mol. Pain
PD JUL 7
PY 2011
VL 7
AR 49
DI 10.1186/1744-8069-7-49
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 813BO
UT WOS:000294341700001
PM 21736731
ER
PT J
AU Ko, SU
Tolea, MI
Hausdorff, JM
Ferrucci, L
AF Ko, Seung-uk
Tolea, Magdalena I.
Hausdorff, Jeffrey M.
Ferrucci, Luigi
TI Sex-specific differences in gait patterns of healthy older adults:
Results from the Baltimore Longitudinal Study of Aging
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Sex difference in gait; Aging; Kinematics; Kinetics; Mechanical work
expenditure
ID GROUND REACTION FORCE; GENDER-DIFFERENCES; WALKING SPEED; KNEE
OSTEOARTHRITIS; YOUNG-ADULTS; AGE; PARAMETERS
AB The effects of normal aging and orthopedic conditions on gait patterns during customary walking have been extensively investigated. Empirical evidence supports the notion that sex differences exist in the gait patterns of young adults but it is unclear as to whether sex differences exist in older adults. The aim of this study was to investigate sex-specific differences in gait among older adults. Study participants were 336 adults (50-96 years; 162 women) enrolled in the Baltimore Longitudinal Study of Aging (BLSA) who completed walking tasks at self-selected speed without assistance. After adjusting for significant covariates, women walked with higher cadence (p=0.01) and shorter stride length (p=0.006) compared to men, while gait speed was not significantly related to sex. Women also had less hip range of motion (ROM: p=0.004) and greater ankle ROM (p<0.001) in the sagittal-plane, and greater hip ROM (p=0.004) in the frontal-plane. Hip absorptive mechanical work expenditure (MWE) of the women was greater in the sagittal-plane (p<0.001) and lower in the frontal-plane (p<0.001), compared to men. In summary, women's gait is characterized by greater ankle ROM than men while men tend to have greater hip ROM than women. Characterizing unique gait patterns of women and men with aging may be beneficial for detecting the early stages of gait abnormalities that may lead to pathology. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Ko, Seung-uk] Chonnam Natl Univ, Dept Mech Engn, Yeosu 550749, Jeonnam, South Korea.
[Tolea, Magdalena I.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Hausdorff, Jeffrey M.] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel.
[Hausdorff, Jeffrey M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Ko, SU (reprint author), Chonnam Natl Univ, Dept Mech Engn, 50 Daehak Ro, Yeosu 550749, Jeonnam, South Korea.
EM seunguk.ko@gmail.com
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging. Data for these analyses were
obtained from the Baltimore Longitudinal Study of Aging, a study
performed by the National Institute on Aging.
NR 26
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U1 0
U2 10
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 JUL 7
PY 2011
VL 44
IS 10
BP 1974
EP 1979
DI 10.1016/j.jbiomech.2011.05.005
PG 6
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 796JQ
UT WOS:000293048000021
PM 21601861
ER
PT J
AU Lanoy, E
Rosenberg, PS
Fily, F
Lascaux, AS
Martinez, V
Partisani, M
Poizot-Martin, I
Rouveix, E
Engels, EA
Costagliola, D
Goedert, JJ
AF Lanoy, Emilie
Rosenberg, Philip S.
Fily, Fabien
Lascaux, Anne-Sophie
Martinez, Valerie
Partisani, Maria
Poizot-Martin, Isabelle
Rouveix, Elisabeth
Engels, Eric A.
Costagliola, Dominique
Goedert, James J.
CA FHDH-ANRS Co4
TI HIV-associated Hodgkin lymphoma during the first months on combination
antiretroviral therapy
SO BLOOD
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECONSTITUTION INFLAMMATORY SYNDROME;
UNITED-STATES; CANCER-RISK; PERIPHERAL-BLOOD; T-CELLS; AIDS; DISEASE;
COHORT; ERA
AB Hodgkin lymphoma (HL) incidence with HIV infection may have increased with the introduction of combination antiretroviral therapy (cART), suggesting that immune reconstitution may contribute to some cases. We evaluated HL risk with cART during the first months of treatment. With 187 HL cases among 64 368 HIV patients in France, relative rates (RRs) and 95% confidence intervals (CIs) of HL were estimated using Poisson models for duration of cART, CD4 count, and HIV load, with and without adjustment for demographic/clinical covariates. HL risk was unrelated to cART use overall, but it was related to time intervals after cART initiation (P = .006). Risk was especially and significantly elevated in months 1-3 on cART (RR 2.95, CI 1.64-5.31), lower in months 4-6 (RR 1.63), and null with longer use (RR 1.00). CD4 count was strongly associated with HL risk (P < 10(-6)), with the highest HL incidence at 50-99 CD4 cells/mm(3). With adjustment for CD4 count and covariates, HL risk was elevated, but not significantly (RR 1.42), in months 1-3 on cART. HIV load had no added effect. HL risk increased significantly soon after cART initiation, which was largely explained by the CD4 count. Further studies of HIV-associated HL are needed. (Blood. 2011;118(1):44-49)
C1 [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Rockville, MD 20852 USA.
[Lanoy, Emilie; Costagliola, Dominique] INSERM, Paris, France.
[Lanoy, Emilie; Costagliola, Dominique] Univ Paris 06, Paris, France.
[Fily, Fabien] Ctr Hosp Univ Pontchaillou, Serv Malad Infect & Reanimat Med, Rennes, France.
[Lascaux, Anne-Sophie] Hop Henri Mondor, Dept Clin Immunol, F-94010 Creteil, France.
[Martinez, Valerie] Hop Antoine Beclere, AP HP, Serv Med Interne, Clamart, France.
[Partisani, Maria] Hop Univ, Ctr Soins Infect VIH, Strasbourg, France.
[Poizot-Martin, Isabelle] Hop St Marguerite, Unite Le Ctr Informat & Soins Immunodeficience Hu, Marseille, France.
[Rouveix, Elisabeth] Hop Ambroise Pare, Serv Med 5, Boulogne, France.
[Costagliola, Dominique] Grp Hosp Pitie Salpetriere, AP HP, Serv Malad Infect & Trop, F-75634 Paris, France.
RP Goedert, JJ (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 6120 Executive Blvd,Rm 7068, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
RI Lanoy, Emilie/A-8541-2011; Costagliola, Dominique/H-5849-2011
OI Lanoy, Emilie/0000-0002-4789-7770; Costagliola,
Dominique/0000-0003-0765-0869
FU Agence Nationale de Recherches sur le SIDA et les hepatites (ANRS);
INSERM; French Ministry of Health; National Cancer Institute, National
Institutes of Health (Bethesda, MD)
FX The French Hospital Database on HIV is supported by Agence Nationale de
Recherches sur le SIDA et les hepatites (ANRS), INSERM, and the French
Ministry of Health. This work was also supported by the Intramural
Research Program of the National Cancer Institute, National Institutes
of Health (Bethesda, MD).
NR 35
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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 JUL 7
PY 2011
VL 118
IS 1
BP 44
EP 49
DI 10.1182/blood-2011-02-339275
PG 6
WC Hematology
SC Hematology
GA 789HI
UT WOS:000292505900010
PM 21551234
ER
PT J
AU Delabie, J
Holte, H
Vose, JM
Ullrich, F
Jaffe, ES
Savage, KJ
Connors, JM
Rimsza, L
Harris, NL
Muller-Hermelink, K
Rudiger, T
Coiffier, B
Gascoyne, RD
Berger, F
Tobinai, K
Au, WY
Liang, R
Montserrat, E
Hochberg, EP
Pileri, S
Federico, M
Nathwani, B
Armitage, JO
Weisenburger, DD
AF Delabie, Jan
Holte, Harald
Vose, Julie M.
Ullrich, Fred
Jaffe, Elaine S.
Savage, Kerry J.
Connors, Joseph M.
Rimsza, Lisa
Harris, Nancy L.
Mueller-Hermelink, Konrad
Ruediger, Thomas
Coiffier, Bertrand
Gascoyne, Randy D.
Berger, Francoise
Tobinai, Kensei
Au, Wing Y.
Liang, Raymond
Montserrat, Emili
Hochberg, Ephraim P.
Pileri, Stefano
Federico, Massimo
Nathwani, Bharat
Armitage, James O.
Weisenburger, Dennis D.
TI Enteropathy-associated T-cell lymphoma: clinical and histological
findings from the International Peripheral T-Cell Lymphoma Project
SO BLOOD
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; CELIAC-DISEASE; INTESTINAL LYMPHOMAS; MALIGNANCY;
MODEL; SPRUE
AB Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)-cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria. Clinical correlations and survival analyses were performed. EATL comprised 5.4% of all lymphomas in the study and was most common in Europe (9.1%), followed by North America (5.8%) and Asia (1.9%). EATL type 1 was more common (66%) than type 2 (34%), and was especially frequent in Europe (79%). A clinical diagnosis of celiac sprue was made in 32.2% of the patients and was associated with both EATL type 1 and type 2. The median overall survival was only 10 months, and the median failure-free survival was only 6 months. The International Prognostic Index (IPI) was not as good a predictor of survival as the Prognostic Index for Peripheral T-Cell Lymphoma (PIT). Clinical sprue predicted for adverse survival independently of the PIT. Neither EATL subtype nor other biologic parameters accurately predicted survival. Our study confirms the poor prognosis of patients with EATL and the need for improved treatment options. (Blood. 2011;118(1):148-155)
C1 [Delabie, Jan] Univ Hosp Oslo, Dept Pathol, Oslo, Norway.
[Holte, Harald] Univ Hosp Oslo, Dept Oncol, Oslo, Norway.
[Vose, Julie M.; Armitage, James O.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
[Ullrich, Fred] Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE USA.
[Jaffe, Elaine S.] NCI, Dept Pathol, Bethesda, MD 20892 USA.
[Savage, Kerry J.; Connors, Joseph M.] British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Rimsza, Lisa] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mueller-Hermelink, Konrad] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany.
[Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, Karlsruhe, Germany.
[Coiffier, Bertrand] Ctr Hosp Lyon Sud, Dept Hematol, Lyon, France.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada.
[Berger, Francoise] Ctr Hosp Lyon Sud, Dept Pathol, Lyon, France.
[Tobinai, Kensei] Natl Canc Ctr, Hematol & Stem Cell Transplantat Div, Tokyo, Japan.
[Au, Wing Y.; Liang, Raymond] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Montserrat, Emili] Univ Barcelona Hosp, Inst Hematol & Oncol, Barcelona, Spain.
[Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA.
[Pileri, Stefano] Univ Bologna Hosp, Dept Pathol, Bologna, Italy.
[Federico, Massimo] Univ Modena & Reggio Emilia, Dept Oncol & Haematol, Modena, Italy.
[Nathwani, Bharat] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA.
[Nathwani, Bharat] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
RP Delabie, J (reprint author), Univ Oslo, Norwegian Radium Hosp, Dept Pathol, N-0310 Oslo, Norway.
EM jan.delabie@medisin.uio.no
RI Federico, Massimo/A-6801-2012; Federico, Massimo/J-5984-2014;
OI Federico, Massimo/0000-0002-9889-3796; Federico,
Massimo/0000-0002-5074-3262; Delabie, Jan/0000-0001-5023-0689; Jaffe,
Elaine/0000-0003-4632-0301
NR 34
TC 82
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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 JUL 7
PY 2011
VL 118
IS 1
BP 148
EP 155
DI 10.1182/blood-2011-02-335216
PG 8
WC Hematology
SC Hematology
GA 789HI
UT WOS:000292505900021
PM 21566094
ER
PT J
AU Bhat, KL
Markham, GD
Larkin, JD
Bock, CW
AF Bhat, Krishna L.
Markham, George D.
Larkin, Joseph D.
Bock, Charles W.
TI Thermodynamics of Boroxine Formation from the Aliphatic Boronic Acid
Monomers R-B(OH)(2) (R = H, H3C, H2N, HO, and F): A Computational
Investigation
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID POLARIZABLE CONTINUUM MODEL; QUADRATIC CONFIGURATION-INTERACTION;
CORRELATED MOLECULAR CALCULATIONS; ORTHORHOMBIC METABORIC ACID; METHYL
TRANSFER-REACTIONS; CROSS-COUPLING REACTIONS; INTERNAL LEWIS-BASE;
GAUSSIAN-BASIS SETS; WAVE-FUNCTIONS; ORGANOBORON COMPOUNDS
AB Boroxines are the six-membered cydotrimeric dehydration products of organoboronic acids, 3R-B(OH)(2) R3B3O3 + 3H(2)O, and in recent years have emerged as a useful class of organoboron molecules with applications in organic synthesis both as reagents and catalysts, as structural components in boronic-acid-derived pharmaceutical agents, and as anion acceptors and electrolyte additives for battery materials [Korich, A. L.; Iovine, P. M. Dalton Trans. 2010, 39, 1423 1431]. Second-order Moller-Plesset perturbation theory, in conjunction with the Dunning-Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets, was used to investigate the structures and relative energies of the endo-exo, anti, and syn conformers of the aliphatic boronic acids R B(OH)(2) (R = H, H3C, H2N, HO, and F), as well as the thermodynamics of their boroxine formation; single-point calculations at the MP2/aug-cc-pVQZ, MP2/aug-cc-pV5Z, and CCSD(T)/aug-cc-pVTZ levels using the MP2/aug-cc-pVTZ optimized geometries were also performed in selected cases. The endo-exo conformer was generally lowest in energy in vacuo, as well as in PCM and CPCM models of aqueous and carbon tetrachloride media. The values of Delta H-298(0) for boroxine formation via dehydration from the endo-exo conformers of these aliphatic boronic acids ranged from -2.9 for (H2N)(3)B3O3 to +12.2 kcal/mol for H3B3O3 at the MP2/aug-cc-pVTZ level in vacuo; for H3B3O3, the corresponding values in PCM/UFF implicit carbon tetrachloride and aqueous media were +11.2 and +9.8 kcal/mol, respectively. On the basis of our calculations, we recommend that Delta H-f(298 K) for boroxine listed in the JANAF compilation needs to be revised from -290.0 to approximately -277.0 kcal/mol.
C1 [Bock, Charles W.] Philadelphia Univ, Dept Chem & Biochem, Sch Sci & Hlth, Philadelphia, PA 19144 USA.
[Bhat, Krishna L.] Widener Univ, Dept Chem, Chester, PA 19013 USA.
[Markham, George D.] Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA.
[Larkin, Joseph D.] NHLBI, NIH, Bethesda, MD 20851 USA.
RP Bock, CW (reprint author), Philadelphia Univ, Dept Chem & Biochem, Sch Sci & Hlth, Sch House Lane & Henry Ave, Philadelphia, PA 19144 USA.
EM bock.charles@gmail.com
FU NIH, NHLBI; NIH [GM31186]; NCI [CA06927]; Commonwealth of Pennsylvania
FX This research was supported in part (J.D.L.) by the Intramural Research
Program of the NIH, NHLBI. G.D.M. would like to thank the NIH (GM31186)
and NCI (CA06927) for financial support of this work, which was also
supported by an appropriation from the Commonwealth of Pennsylvania. The
High Performance Computing Facility at the Fox Chase Cancer Center and
the PQS Cluster Facility at Philadelphia University were used for the
calculations described in this article. This study also utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health, Bethesda, MD
(http://biowulf.nih.gov).
NR 124
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U1 2
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1089-5639
J9 J PHYS CHEM A
JI J. Phys. Chem. A
PD JUL 7
PY 2011
VL 115
IS 26
BP 7785
EP 7793
DI 10.1021/jp202409m
PG 9
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 786CQ
UT WOS:000292281300043
PM 21650154
ER
PT J
AU Pastor, RW
MacKerell, AD
AF Pastor, R. W.
MacKerell, A. D., Jr.
TI Development of the CHARMM Force Field for Lipids
SO JOURNAL OF PHYSICAL CHEMISTRY LETTERS
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; DEUTERIUM MAGNETIC-RESONANCE; FATTY ACYL
CHAINS; COMPUTER-SIMULATION; SURFACE-TENSION; LIQUID/LIQUID INTERFACES;
CONSTANT-PRESSURE; LIQUID-CRYSTAL; BILAYER; MEMBRANES
AB The development of the CHARMM additive all-atom lipid force field (FF) is traced from the early 1990s to the most recent version (C36) published in 2010. Though simulations with early versions yielded useful results, they failed to reproduce two important quantities, a zero surface tension at the experimental bilayer surface area and the signature splitting of the deuterium order parameters in the glycerol and upper chain carbons. Systematic optimization of parameters based on high-level quantum mechanical data and free-energy simulations have resolved these issues, and bilayers with a wide range of lipids can be simulated in tensionless ensembles using C36. Issues associated with other all-atom lipid FFs, success and limitations in the C36 FF, and ongoing developments are also discussed.
C1 [MacKerell, A. D., Jr.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
RP MacKerell, AD (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM alex@outerbanks.umaryland.edu
OI MacKerell, Alex/0000-0001-8287-6804
FU NIH [GM070855, GM072558, GM015101]; University of Maryland
Computer-Aided Drug Design Center; NIH, National Heart, Lung and Blood
Institute
FX We thank our many collaborators involved in this now two-decade project,
especially Bernard Brooks, Scott Feller, Jeffery Klauda, Benoit Roux,
Douglas Tobias, and Richard Venable. Experimentalists Michael Brown,
Klaus Gawrisch, Stuart McLaughlin, John Nagle, and Stephen White have
also been indispensible for providing data, often before publication,
and helping us understand it. Financial support from the NIH (GM070855,
GM072558, and GM015101 to A.D.M.) and the University of Maryland
Computer-Aided Drug Design Center are appreciated. This research was
supported in part by the Intramural Research Program of the NIH,
National Heart, Lung and Blood Institute.
NR 50
TC 94
Z9 95
U1 3
U2 39
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7185
J9 J PHYS CHEM LETT
JI J. Phys. Chem. Lett.
PD JUL 7
PY 2011
VL 2
IS 13
BP 1526
EP 1532
DI 10.1021/jz200167q
PG 7
WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science,
Multidisciplinary; Physics, Atomic, Molecular & Chemical
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 794JW
UT WOS:000292893400007
PM 21760975
ER
PT J
AU Radoshitzky, SR
Longobardi, LE
Kuhn, JH
Retterer, C
Dong, L
Clester, JC
Kota, K
Carra, J
Bavari, S
AF Radoshitzky, Sheli R.
Longobardi, Lindsay E.
Kuhn, Jens H.
Retterer, Cary
Dong, Lian
Clester, Jeremiah C.
Kota, Krishna
Carra, John
Bavari, Sina
TI Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1
Binding and Cell Entry
SO PLOS ONE
LA English
DT Article
ID HEMORRHAGIC-FEVER ARENAVIRUSES; GP-C; SUBTILASE SKI-1/S1P; SIGNAL
PEPTIDE; IDENTIFICATION; CLEAVAGE; JUNIN
AB Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1). TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association. We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells. We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry. Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction. Our findings also open avenues for the rational development of viral entry inhibitors.
C1 [Radoshitzky, Sheli R.; Longobardi, Lindsay E.; Retterer, Cary; Dong, Lian; Clester, Jeremiah C.; Kota, Krishna; Carra, John; Bavari, Sina] USAMRIID, Div Toxicol, Frederick, MD USA.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Frederick, MD USA.
RP Radoshitzky, SR (reprint author), USAMRIID, Div Toxicol, Frederick, MD USA.
EM sina.bavari@amedd.army.mil
RI Kuhn, Jens H./B-7615-2011
OI Kuhn, Jens H./0000-0002-7800-6045
FU Joint Science and Technology Office Transformational Medical
Technologies [TMTI0048_09_RD_T]; Defense Threat Reduction Agency
[4.10022_08_RD_B]; NIAID [HHSN272200200016I]
FX This research was partially supported by the Joint Science and
Technology Office Transformational Medical Technologies (proposal #
TMTI0048_09_RD_T) and Defense Threat Reduction Agency (proposal
#4.10022_08_RD_B) to SB. JHK performed this work as an employee of
Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute
under its prime contract with NIAID, Contract No. HHSN272200200016I. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 26
TC 13
Z9 13
U1 0
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 JUL 7
PY 2011
VL 6
IS 7
AR e21398
DI 10.1371/journal.pone.0021398
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791HI
UT WOS:000292655400005
PM 21750710
ER
PT J
AU Wentzensen, N
Black, A
Jacobs, K
Yang, HP
Berg, CD
Caporaso, N
Peters, U
Ragard, L
Buys, SS
Chanock, S
Hartge, P
AF Wentzensen, Nicolas
Black, Amanda
Jacobs, Kevin
Yang, Hannah P.
Berg, Christine D.
Caporaso, Neil
Peters, Ulrike
Ragard, Lawrence
Buys, Saundra S.
Chanock, Stephen
Hartge, Patricia
TI Genetic Variation on 9p22 Is Associated with Abnormal Ovarian Ultrasound
Results in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening
Trial
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; RANDOMIZED-TRIAL;
RISK-FACTORS
AB Background: A recent ovarian cancer genome-wide association study (GWAS) identified a locus on 9p22 associated with reduced ovarian cancer risk. The single nucleotide polymorphism (SNP) markers localize to the BNC2 gene, which has been associated with ovarian development.
Methods: We analyzed the association of 9p22 SNPs with transvaginal ultrasound (TVU) screening results and CA-125 blood levels from participants without ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO); 1,106 women with adequate ultrasound screening results and available genotyping information were included in the study.
Results: We observed a significantly increased risk of abnormal suspicious TVU results for seven SNPs on 9p22, with odds ratios between 1.68 (95% CI: 1.04-2.72) for rs4961501 and 2.10 (95% CI: 1.31-3.38) for rs12379183. Associations were restricted to abnormal suspicious findings at the first TVU screen. We did not observe an association between 9p22 SNPs and CA-125 levels.
Conclusions: Our findings suggest that 9p22 SNPs, which were found to be associated with decreased risk of ovarian cancer in a recent GWAS, are associated with sonographically detectable ovarian abnormalities. Our results corroborate the relevance of the 9p22 locus for ovarian biology. Further studies are required to understand the complex relationship between screening abnormalities and ovarian carcinogenesis and to evaluate whether this locus can influence the risk stratification of ovarian cancer screening.
C1 [Wentzensen, Nicolas; Black, Amanda; Yang, Hannah P.; Caporaso, Neil; Chanock, Stephen; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Jacobs, Kevin; Chanock, Stephen] NCI, Core Genotyping Facil, Rockville, MD USA.
[Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Ragard, Lawrence] Westat Corp, Rockville, MD USA.
[Buys, Saundra S.] Huntsman Canc Inst, Div Oncol, Salt Lake City, UT USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
EM wentzenn@mail.nih.gov
RI Berg , Christine/K-1047-2014
FU Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and by contracts from the
Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 22
TC 5
Z9 5
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 JUL 7
PY 2011
VL 6
IS 7
AR e21731
DI 10.1371/journal.pone.0021731
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791HI
UT WOS:000292655400014
PM 21750727
ER
PT J
AU Collins, PY
Patel, V
Joestl, SS
March, D
Insel, TR
Daar, AS
AF Collins, Pamela Y.
Patel, Vikram
Joestl, Sarah S.
March, Dana
Insel, Thomas R.
Daar, Abdallah S.
CA Sci Advisory Board
Executive Comm Grand Challenges Gl
TI Grand challenges in global mental health
SO NATURE
LA English
DT Editorial Material
ID PRIORITIES; CONSENSUS; SERVICES; DEMENTIA
C1 [Collins, Pamela Y.; Joestl, Sarah S.; March, Dana] NIMH, Off Res Dispair & Global Mental Hlth, Bethesda, MD USA.
[Patel, Vikram] London Sch Hyg & Trop Med UK, Ctr Global Mental Hlth, Sangath, Goa, India.
[Daar, Abdallah S.] Univ Toronto, Toronto, ON, Canada.
[Daar, Abdallah S.] McLaughlin Rotman Ctr Global Hlth, Toronto, ON, Canada.
RP Collins, PY (reprint author), NIMH, Off Res Dispair & Global Mental Hlth, Bethesda, MD USA.
EM pamela.collins@nih.gov; a.daar@utoronto.ca
RI Hall, Wayne/A-3283-2008; Durkin, Maureen/B-7834-2015;
OI Hall, Wayne/0000-0003-1984-0096; Kapur, Shitij/0000-0002-2231-2924;
Patel, Vikram/0000-0003-1066-8584; Bordin, Isabel A./0000-0002-3173-5419
FU Intramural NIH HHS [Z99 MH999999]; NICHD NIH HHS [P30 HD003352];
Wellcome Trust [079113, 091834]
NR 16
TC 577
Z9 595
U1 9
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 7
PY 2011
VL 475
IS 7354
BP 27
EP 30
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 788RE
UT WOS:000292461300013
PM 21734685
ER
PT J
AU Han, YH
Kang, Y
Torres-Jerez, I
Cheung, F
Town, CD
Zhao, PX
Udvardi, MK
Monteros, MJ
AF Han, Yuanhong
Kang, Yun
Torres-Jerez, Ivone
Cheung, Foo
Town, Christopher D.
Zhao, Patrick X.
Udvardi, Michael K.
Monteros, Maria J.
TI Genome-wide SNP discovery in tetraploid alfalfa using 454 sequencing and
high resolution melting analysis
SO BMC GENOMICS
LA English
DT Article
ID MEDICAGO-TRUNCATULA; CROP LEGUMES; DNA; MARKERS; SATIVA; GENE; MAP
AB Background: Single nucleotide polymorphisms (SNPs) are the most common type of sequence variation among plants and are often functionally important. We describe the use of 454 technology and high resolution melting analysis (HRM) for high throughput SNP discovery in tetraploid alfalfa (Medicago sativa L.), a species with high economic value but limited genomic resources.
Results: The alfalfa genotypes selected from M. sativa subsp. sativa var. 'Chilean' and M. sativa subsp. falcata var. 'Wisfal', which differ in water stress sensitivity, were used to prepare cDNA from tissue of clonally-propagated plants grown under either well-watered or water-stressed conditions, and then pooled for 454 sequencing. Based on 125.2 Mb of raw sequence, a total of 54,216 unique sequences were obtained including 24,144 tentative consensus (TCs) sequences and 30,072 singletons, ranging from 100 bp to 6,662 bp in length, with an average length of 541 bp. We identified 40,661 candidate SNPs distributed throughout the genome. A sample of candidate SNPs were evaluated and validated using high resolution melting (HRM) analysis. A total of 3,491 TCs harboring 20,270 candidate SNPs were located on the M. truncatula (MT 3.5.1) chromosomes. Gene Ontology assignments indicate that sequences obtained cover a broad range of GO categories.
Conclusions: We describe an efficient method to identify thousands of SNPs distributed throughout the alfalfa genome covering a broad range of GO categories. Validated SNPs represent valuable molecular marker resources that can be used to enhance marker density in linkage maps, identify potential factors involved in heterosis and genetic variation, and as tools for association mapping and genomic selection in alfalfa.
C1 [Han, Yuanhong; Monteros, Maria J.] Samuel Roberts Noble Fdn Inc, Forage Improvement Div, Ardmore, OK 73401 USA.
[Kang, Yun; Torres-Jerez, Ivone; Zhao, Patrick X.; Udvardi, Michael K.] Samuel Roberts Noble Fdn Inc, Div Plant Biol, Ardmore, OK 73401 USA.
[Cheung, Foo] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
[Cheung, Foo; Town, Christopher D.] J Craig Venter Inst, Rockville, MD 20850 USA.
RP Monteros, MJ (reprint author), Samuel Roberts Noble Fdn Inc, Forage Improvement Div, 2510 Sam Noble Pkwy, Ardmore, OK 73401 USA.
EM mjmonteros@noble.org
FU Samuel Roberts Noble Foundation; Oklahoma Bioenergy Center; Forage
Genetics International
FX This study was supported by The Samuel Roberts Noble Foundation, grants
from the Oklahoma Bioenergy Center to M.J. Monteros and M. K. Udvardi,
and a grant from Forage Genetics International to M.J. Monteros. We
would like to thank Shelby Bidwell for uploading the 454 sequences to
Genebank and assisting in sequence assembly, Cook Ly for assistance with
preparing figures, and Mark Sorrells for providing comments on the
manuscript.
NR 36
TC 37
Z9 39
U1 4
U2 25
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 6
PY 2011
VL 12
AR 350
DI 10.1186/1471-2164-12-350
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 806ZF
UT WOS:000293856300001
ER
PT J
AU Basseville, A
Preisser, L
Trecesson, SD
Boisdron-Celle, M
Gamelin, E
Coqueret, O
Morel, A
AF Basseville, Agnes
Preisser, Laurence
Trecesson, Sophie de Carne
Boisdron-Celle, Michele
Gamelin, Erick
Coqueret, Olivier
Morel, Alain
TI Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to
detoxification pathway in colon cancer cells
SO MOLECULAR CANCER
LA English
DT Article
ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; ST JOHNS WORT;
NUCLEAR RECEPTOR; 7-ETHYL-10-HYDROXYCAMPTOTHECIN SN-38;
GLUCOCORTICOID-RECEPTOR; MULTIDRUG-RESISTANCE; ANTICANCER AGENTS; HUMAN
HEPATOCYTES; MALIGNANT GLIOMA
AB Background: Resistance to chemotherapy remains one of the principle obstacles to the treatment of colon cancer. In order to identify the molecular mechanism of this resistance, we investigated the role of the steroid and xenobiotic receptor (SXR) in the induction of drug resistance. Indeed, this nuclear receptor plays an important role in response to xenobiotics through the upregulation of detoxification genes. Following drug treatments, SXR is activated and interacts with the retinoid X receptor (RXR) to induce expression of some genes involved in drug metabolism such as phase I enzyme (like CYP), phase II enzymes (like UGT) and transporters (e.g. MDR1).
Results: In this study, we have shown that endogenous SXR is activated in response to SN-38, the active metabolite of the anticancer drug irinotecan, in human colon cancer cell lines. We have found that endogenous SXR translocates into the nucleus and associates with RXR upon SN-38 treatment. Using ChIP, we have demonstrated that endogenous SXR, following its activation, binds to the native promoter of the CYP3A4 gene to induce its expression. RNA interference experiments confirmed SXR involvement in CYP3A4 overexpression and permitted us to identify CYP3A5 and MRP2 transporter as SXR target genes. As a consequence, cells overexpressing SXR were found to be less sensitive to irinotecan treatment.
Conclusions: Altogether, these results suggest that the SXR pathway is involved in colon cancer irinotecan resistance in colon cancer cell line via the upregulation of select detoxification genes.
C1 [Basseville, Agnes; Preisser, Laurence; Trecesson, Sophie de Carne; Boisdron-Celle, Michele; Gamelin, Erick; Coqueret, Olivier; Morel, Alain] Univ Angers, Canc Ctr Paul Papin, INSERM, U892, F-49033 Angers, France.
[Basseville, Agnes] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Morel, A (reprint author), Univ Angers, Canc Ctr Paul Papin, INSERM, U892, 2 Rue Moll, F-49033 Angers, France.
EM Alain.Morel@ico.unicancer.fr
RI preisser, laurence/K-7583-2015; Coqueret, Olivier/K-9660-2015
OI Coqueret, Olivier/0000-0002-2843-7867
FU Ligue Contre le Cancer
FX We wish to thank Anne Lise Poirier for her statistical expertise and Dr
Susan Bates for allowing us to complete the experiments in her lab. This
work was supported by grants from the Ligue Contre le Cancer (equipes
labelisees 2007, O.C. and E.G. and comite du Maine et Loire).
NR 55
TC 23
Z9 23
U1 1
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 JUL 6
PY 2011
VL 10
AR 80
DI 10.1186/1476-4598-10-80
PG 12
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 797PK
UT WOS:000293139600001
PM 21733184
ER
PT J
AU Collins, FS
AF Collins, Francis S.
TI Reengineering Translational Science: The Time Is Right
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID HUMAN-GENOME; DRUG DEVELOPMENT; DISEASE; TRIAL; PROTECTION; DISCOVERY;
ONCOLOGY; LESSONS; IMPROVE; PROJECT
AB Despite dramatic advances in the molecular pathogenesis of disease, translation of basic biomedical research into safe and effective clinical applications remains a slow, expensive, and failure-prone endeavor. To pursue opportunities for disruptive translational innovation, the U. S. National Institutes of Health (NIH) intends to establish a new entity, the National Center for Advancing Translational Sciences (NCATS). The mission of NCATS is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of diseases and conditions. The new center's activities will complement, and not compete with, translational research being carried out at NIH and elsewhere in the public and private sectors.
C1 NIH, Off Director, Bethesda, MD 20892 USA.
RP Collins, FS (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA.
EM francis.collins@nih.gov
NR 55
TC 141
Z9 145
U1 1
U2 34
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUL 6
PY 2011
VL 3
IS 90
AR 90cm17
DI 10.1126/scitranslmed.3002747
PG 6
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795NZ
UT WOS:000292982200001
PM 21734173
ER
PT J
AU Zustiak, SP
Nossal, R
Sackett, DL
AF Zustiak, Silviya P.
Nossal, Ralph
Sackett, Dan L.
TI Hindered Diffusion in Polymeric Solutions Studied by Fluorescence
Correlation Spectroscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PROTEIN DIFFUSION; LIVING CELLS; CROWDED ENVIRONMENT; ANOMALOUS
DIFFUSION; CYTOPLASM; BINDING; DISSOCIATION; MOBILITY; POLYELECTROLYTE;
RIBONUCLEASE
AB Diffusion of molecules in the crowded and charged interior of the cell has long been of interest for understanding cellular processes. Here, we introduce a model system of hindered diffusion that includes both crowding and binding. In particular, we obtained the diffusivity of the positively charged protein, ribonuclease A (RNase), in solutions of dextrans of various charges (binding) and concentrations (crowding), as well as combinations of both, in a buffer of physiological ionic strength. Using fluorescence correlation spectroscopy, we observed that the diffusivity of RNase was unaffected by the presence of positively charged or neutral dextrans in the dilute regime but was affected by crowding at higher polymer concentrations. Conversely, protein diffusivity was significantly reduced by negatively charged dextrans, even at 0.4 mu M (0.02% w/v) dextran. The diffusivity of RNase decreased with increasing concentrations of negative dextran, and the amount of bound RNase increased until it reached a plateau of similar to 80% bound RNase. High salt concentrations were used to establish the electrostatic nature of the binding. Binding of RNase to the negatively charged dextrans was further confirmed by ultrafiltration.
C1 [Zustiak, Silviya P.; Nossal, Ralph; Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Dev, Program Phys Biol, NIH, Bethesda, MD USA.
RP Zustiak, SP (reprint author), Eunice Kennedy Shriver Natl Inst Child Dev, Program Phys Biol, NIH, Bethesda, MD USA.
EM zustiaksp@mail.mih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This work was supported by funds from the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 42
TC 20
Z9 20
U1 0
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUL 6
PY 2011
VL 101
IS 1
BP 255
EP 264
DI 10.1016/j.bpj.2011.05.035
PG 10
WC Biophysics
SC Biophysics
GA 790EQ
UT WOS:000292571700029
PM 21723836
ER
PT J
AU Yadav, H
Quijano, C
Kamaraju, AK
Gavrilova, O
Malek, R
Chen, WP
Zerfas, P
Duan, ZG
Wright, EC
Stuelten, C
Sun, P
Lonning, S
Skarulis, M
Sumner, AE
Finkel, T
Rane, SG
AF Yadav, Hariom
Quijano, Celia
Kamaraju, Anil K.
Gavrilova, Oksana
Malek, Rana
Chen, Weiping
Zerfas, Patricia
Duan Zhigang
Wright, Elizabeth C.
Stuelten, Christina
Sun, Peter
Lonning, Scott
Skarulis, Monica
Sumner, Anne E.
Finkel, Toren
Rane, Sushil G.
TI Protection from Obesity and Diabetes by Blockade of TGF-beta/Smad3
Signaling
SO CELL METABOLISM
LA English
DT Article
ID GROWTH-FACTOR-BETA; BROWN ADIPOSE-TISSUE; PLASMINOGEN-ACTIVATOR
INHIBITOR-1; DIET-INDUCED OBESITY; TGF-BETA; TRANSFORMING
GROWTH-FACTOR-BETA-1; ADIPOCYTE DIFFERENTIATION; TARGETED DISRUPTION;
GENETIC-CONTROL; WHITE FAT
AB Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-beta/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3-deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3(-/-) white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3(-/-) adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-1 alpha expression. We observe significant correlation between TGF-beta 1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-beta signaling protects mice from obesity, diabetes, and hepatic steatosis. Together, these results demonstrate that TGF-beta signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-beta activity might be an effective treatment strategy for obesity and diabetes.
C1 [Yadav, Hariom; Kamaraju, Anil K.; Malek, Rana; Skarulis, Monica; Sumner, Anne E.; Rane, Sushil G.] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
[Quijano, Celia; Finkel, Toren] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] Mouse Metab Core Lab, Bethesda, MD 20892 USA.
[Chen, Weiping] Genom Core Facil, Bethesda, MD 20892 USA.
[Zerfas, Patricia] Off Director, Off Res Serv, Bethesda, MD 20892 USA.
[Duan Zhigang; Wright, Elizabeth C.] NIDDK, Off Res Serv, Bethesda, MD 20892 USA.
[Stuelten, Christina] NCI, Bethesda, MD 20892 USA.
[Sun, Peter] NIAID, NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
[Lonning, Scott] Genzyme Corp, Framingham, MA 01701 USA.
[Quijano, Celia] Univ Republica, Dept Bioquim, Fac Med, Montevideo, Uruguay.
RP Rane, SG (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, South Dr & Old Georgetown Rd, Bethesda, MD 20892 USA.
EM ranes@mail.nih.gov
FU NIH
FX This work is dedicated to the memory of G.S. Rane. The authors
appreciate the support of members of the Rane laboratory. The authors
thank Alexandra McPherron (NIDDK) for advice. The technical support
provided by George Poy, Madia Ricks, Anita Tambay, Ugochi Ukegbu,
Richard Chen, Alice Franks, Janet Lee, William Jou, Tatyana Chanturiya,
and Kevin Wang is greatly appreciated. This work was supported by funds
from the NIH intramural program.
NR 47
TC 153
Z9 157
U1 1
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD JUL 6
PY 2011
VL 14
IS 1
BP 67
EP 79
DI 10.1016/j.cmet.2011.04.013
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 790JB
UT WOS:000292583200010
PM 21723505
ER
PT J
AU Tang, M
Pelkey, KA
Ng, D
Ivakine, E
McBain, CJ
Salter, MW
McInnes, RR
AF Tang, Man
Pelkey, Kenneth A.
Ng, David
Ivakine, Evgueni
McBain, Chris J.
Salter, Michael W.
McInnes, Roderick R.
TI Neto1 Is an Auxiliary Subunit of Native Synaptic Kainate Receptors
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MOSSY-FIBER SYNAPSES; LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS;
PYRAMIDAL CELLS; HIGH-AFFINITY; CAENORHABDITIS-ELEGANS; GLUR6-DEFICIENT
MICE; EXCITATORY SYNAPSES; HIPPOCAMPAL-NEURONS; NMDA RECEPTORS
AB Ionotropic glutamate receptors of AMPA, NMDA, and kainate receptor (KAR) subtypes mediate fast excitatory synaptic transmission in the vertebrate CNS. Auxiliary proteins have been identified for AMPA and NMDA receptor complexes, but little is known about KAR complex proteins. We previously identified the CUB (complement C1r/C1s, Uegf, Bmpl) domain protein, Neto1, as an NMDA receptor-associated polypeptide. Here, we show that Neto1 is also an auxiliary subunit for endogenous synaptic KARs. We found that Neto1 and KARs coimmunoprecipitated from brain lysates, from postsynaptic densities (PSDs) and, in a manner dependent on Neto1 CUB domains, when coexpressed in heterologous cells. In Neto1-null mice, there was an similar to 50% reduction in the abundance of GluK2-KARs in hippocampal PSDs. Neto1 strongly localized to CA3 stratum lucidum, and loss of Neto1 resulted in a selective deficit in KAR-mediated neurotransmission at mossy fiber-CA3 pyramidal cell (MF-CA3) synapses: KAR-mediated EPSCs in Neto1-null mice were reduced in amplitude and decayed more rapidly than did those in wild-type mice. In contrast, the loss of Neto2, which also localizes to stratum lucidum and interacts with KARs, had no effect on KAR synaptic abundance or MF-CA3 transmission. Indeed, MF-CA3 KAR deficits in Neto1/Neto2-double-null mutant mice were indistinguishable from Neto1 single-null mice. Thus, our findings establish Neto1 as an auxiliary protein required for synaptic function of KARs. The ability of Neto1 to regulate both NMDARs and KARs reveals a unique dual role in controlling synaptic transmission by serving as an auxiliary protein for these two classes of ionotropic glutamate receptors in a synapse-specific fashion.
C1 [McInnes, Roderick R.] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada.
[Tang, Man; Ng, David; Ivakine, Evgueni; McInnes, Roderick R.] Hosp Sick Children, Res Inst, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada.
[Salter, Michael W.] Hosp Sick Children, Res Inst, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada.
[Tang, Man; Ng, David; McInnes, Roderick R.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Salter, Michael W.] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada.
[Pelkey, Kenneth A.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
[McInnes, Roderick R.] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada.
RP McInnes, RR (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada.
EM mike.salter@utoronto.ca; rod.mcinnes@mcgill.ca
FU Canadian Institutes of Health Research [MOP-7315, IOP-54037]; NICHD
FX This study was supported by Grants MOP-7315 and IOP-54037 from the
Canadian Institutes of Health Research to R.R.M., and an NICHD
Intramural award to C.J.M.; R.R.M. and M.W.S. hold Canada Research
Chairs; M.W.S. is an International Research Scholar of the Howard Hughes
Medical Institute. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript. We thank L. Ploder, R. Szilard, D. Mahuran, and R.
Reithmeier for technical advice; and K. Roche for the FLAG-GluK2 plasmid
construct.
NR 63
TC 39
Z9 40
U1 0
U2 16
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 JUL 6
PY 2011
VL 31
IS 27
BP 10009
EP 10018
DI 10.1523/JNEUROSCI.6617-10.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 789OE
UT WOS:000292524400024
PM 21734292
ER
PT J
AU Whitby, LR
Ando, Y
Setola, V
Vogt, PK
Roth, BL
Boger, DL
AF Whitby, Landon R.
Ando, Yoshio
Setola, Vincent
Vogt, Peter K.
Roth, Bryan L.
Boger, Dale L.
TI Design, Synthesis, and Validation of a beta-Turn Mimetic Library
Targeting Protein-Protein and Peptide-Receptor Interactions
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PHASE COMBINATORIAL SYNTHESIS; IMINODIACETIC ACID LIBRARIES;
MOLECULAR-DYNAMICS METHODS; OLEFIN METATHESIS REACTION; SMALL
ORGANIC-MOLECULES; DNA-BINDING MOLECULES; MU-OPIOID RECEPTOR;
CONFORMATIONAL-ANALYSIS; PARALLEL SYNTHESIS; SOLID-PHASE
AB The design and synthesis of a beta-turn mimetic library as a key component of a small-molecule library targeting the major recognition motifs involved in protein-protein interactions is described. Analysis of a geometric characterization of 10 245 beta-turns in the protein data bank (PDB) suggested that trans-pyrrolidine-3,4-dicarboxamide could serve as an effective and synthetically accessible library template. This was confirmed by initially screening select compounds against a series of peptide-activated GPCRs that recognize a beta-turn structure in their endogenous ligands. This validation study was highlighted by identification of both nonbasic and basic small molecules with high affinities (K-i = 390 and 23 nM, respectively) for the K-opioid receptor (KOR). Consistent with the screening capabilities of collaborators and following the design validation, the complete library was assembled as 210 mixtures of 20 compounds, providing a total of 4200 compounds designed to mimic all possible permutations of 3 of the 4 residues in a naturally occurring beta-turn. Unique to the design and because of the C-2 symmetry of the template, a typical 20 x 20 x 20-mix (8000 compounds prepared as 400 mixtures of 20 compounds) needed to represent 20 variations in the side chains of three amino acid residues reduces to a 210 x 20-mix, thereby simplifying the library synthesis and subsequent screening. The library was prepared using a solution-phase synthetic protocol with liquid liquid or liquid solid extractions for purification and conducted on a scale that insures its long-term availability for screening campaigns. Screening the library against the human opioid receptors (KOR, MOR, and DOR) identified not only the activity of library members expected to mimic the opioid receptor peptide ligands but also additional side-chain combinations that provided enhanced receptor binding selectivities (>100-fold) and affinities (as low as = 80 nM for KOR). A key insight to emerge from the studies is that the phenol of Tyr in endogenous ligands bearing the H-Tyr-Pro-Trp/Phe-Phe-NH2 beta-turn is important for MOR binding but may not be important for KOR (accommodated, but not preferred) and that the resulting selectivity for KOR observed with its removal can be increased by replacing the phenol OH with a chlorine substituent, further enhancing KOR affinity.
C1 [Whitby, Landon R.; Ando, Yoshio; Vogt, Peter K.; Boger, Dale L.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Whitby, Landon R.; Ando, Yoshio; Vogt, Peter K.; Boger, Dale L.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Setola, Vincent; Roth, Bryan L.] Univ N Carolina, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27514 USA.
RP Boger, DL (reprint author), Scripps Res Inst, Dept Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM boger@scripps.edu
RI Roth, Bryan/F-3928-2010;
OI Vogt, Peter K/0000-0002-4519-7500
FU National Institutes of Health [CA078045, R01 DA017204, R01DA027170]
FX We gratefully acknowledge the financial support of the National
Institutes of Health (CA078045, D.L.B. and P.K.V.; R01 DA017204,
R01DA027170, the Michael Hooker Distinguished Professorship and the NIMH
Psychoactive Drug Screening Program Contract, BLit). L.RW. is a Skaggs
Fellow.
NR 118
TC 32
Z9 32
U1 0
U2 39
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 JUL 6
PY 2011
VL 133
IS 26
BP 10184
EP 10194
DI 10.1021/ja201878v
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA 792BN
UT WOS:000292715600046
PM 21609016
ER
PT J
AU Stany, MP
Vathipadiekal, V
Ozbun, L
Stone, RL
Mok, SC
Xue, H
Kagami, T
Wang, YW
McAlpine, JN
Bowtell, D
Gout, PW
Miller, DM
Gilks, CB
Huntsman, DG
Ellard, SL
Wang, YZ
Vivas-Mejia, P
Lopez-Berestein, G
Sood, AK
Birrer, MJ
AF Stany, Michael P.
Vathipadiekal, Vinod
Ozbun, Laurent
Stone, Rebecca L.
Mok, Samuel C.
Xue, Hui
Kagami, Takashi
Wang, Yuwei
McAlpine, Jessica N.
Bowtell, David
Gout, Peter W.
Miller, Dianne M.
Gilks, C. Blake
Huntsman, David G.
Ellard, Susan L.
Wang, Yu-Zhuo
Vivas-Mejia, Pablo
Lopez-Berestein, Gabriel
Sood, Anil K.
Birrer, Michael J.
TI Identification of Novel Therapeutic Targets in Microdissected Clear Cell
Ovarian Cancers
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; INTERFERING
RNA DELIVERY; IN-VIVO; FACTOR EXPRESSION; GENE-EXPRESSION;
ANTITUMOR-ACTIVITY; TYROSINE KINASE; FACTOR RECEPTOR; CARCINOMA
AB Clear cell ovarian cancer is an epithelial ovarian cancer histotype that is less responsive to chemotherapy and carries poorer prognosis than serous and endometrioid histotypes. Despite this, patients with these tumors are treated in a similar fashion as all other ovarian cancers. Previous genomic analysis has suggested that clear cell cancers represent a unique tumor subtype. Here we generated the first whole genomic expression profiling using epithelial component of clear cell ovarian cancers and normal ovarian surface specimens isolated by laser capture microdissection. All the arrays were analyzed using BRB ArrayTools and PathwayStudio software to identify the signaling pathways. Identified pathways validated using serous, clear cell cancer cell lines and RNAi technology. In vivo validations carried out using an orthotopic mouse model and liposomal encapsulated siRNA. Patient-derived clear cell and serous ovarian tumors were grafted under the renal capsule of NOD-SCID mice to evaluate the therapeutic potential of the identified pathway. We identified major activated pathways in clear cells involving in hypoxic cell growth, angiogenesis, and glucose metabolism not seen in other histotypes. Knockdown of key genes in these pathways sensitized clear cell ovarian cancer cell lines to hypoxia/glucose deprivation. In vivo experiments using patient derived tumors demonstrate that clear cell tumors are exquisitely sensitive to antiangiogenesis therapy (i.e. sunitinib) compared with serous tumors. We generated a histotype specific, gene signature associated with clear cell ovarian cancer which identifies important activated pathways critical for their clinicopathologic characteristics. These results provide a rational basis for a radically different treatment for ovarian clear cell patients.
C1 [Stany, Michael P.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Vathipadiekal, Vinod; Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Vathipadiekal, Vinod; Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA USA.
[Ozbun, Laurent] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stone, Rebecca L.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Mok, Samuel C.] Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Boston, MA 02115 USA.
[Xue, Hui; Kagami, Takashi; Wang, Yuwei; Gout, Peter W.; Wang, Yu-Zhuo] British Columbia Canc Agcy, Living Tumor Lab, Vancouver, BC V5Z 4E6, Canada.
[McAlpine, Jessica N.; Miller, Dianne M.] Univ British Columbia, Dept Obstet & Gynecol, Div Gynecol Oncol, Vancouver, BC V5Z 1M9, Canada.
[Bowtell, David] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Gilks, C. Blake; Huntsman, David G.] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver Gen Hosp, Dept Pathol,Genet Pathol Evaluat Ctr, Vancouver, BC V5Z 4E6, Canada.
[Ellard, Susan L.] British Columbia Canc Agcy So Interior, Dept Med Oncol, Kelowna, BC, Canada.
[Wang, Yu-Zhuo] Univ British Columbia, Dept Urol Sci, Vancouver, BC V5Z 1M9, Canada.
[Wang, Yu-Zhuo] Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V5Z 1M9, Canada.
[Vivas-Mejia, Pablo; Lopez-Berestein, Gabriel] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA.
RP Stany, MP (reprint author), Walter Reed Army Med Ctr, Washington, DC 20307 USA.
EM mbirrer@partners.org
RI Bowtell, David/H-1007-2016;
OI Bowtell, David/0000-0001-9089-7525; Vathipadiekal,
Vinod/0000-0002-8181-6890
FU National Cancer Institute at the National Institutes of the Health;
OvCaRe (an initiative of the Vancouver General Hospital and University
of BC Hospital Foundation and the BC Cancer Foundation); BC Cancer
Foundation; Pfizer Canada
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute at the National Institutes of the Health
(MJB) and OvCaRe (an initiative of the Vancouver General Hospital and
University of BC Hospital Foundation and the BC Cancer Foundation)
(YZW), the BC Cancer Foundation and Pfizer Canada
(Investigator-initiated project, SLE and YZW). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript. No additional external funding was
received for this study.
NR 53
TC 37
Z9 37
U1 0
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 JUL 6
PY 2011
VL 6
IS 7
AR e21121
DI 10.1371/journal.pone.0021121
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 791AK
UT WOS:000292632000007
PM 21754983
ER
PT J
AU Liu, MH
Eiden, MV
AF Liu, Meihong
Eiden, Maribeth V.
TI The receptors for gibbon ape leukemia virus and amphotropic murine
leukemia virus are not downregulated in productively infected cells
SO RETROVIROLOGY
LA English
DT Article
ID AMINO-ACID TRANSPORTER; AVIAN-LEUKOSIS VIRUS; ROUS SARCOMA VIRUS;
SUPERINFECTION INTERFERENCE; ENVELOPE GLYCOPROTEIN; SURFACE RECEPTOR;
HOST-RANGE; RETROVIRUSES; PARTICLES; PROTEINS
AB Background: Over the last several decades it has been noted, using a variety of different methods, that cells infected by a specific gammaretrovirus are resistant to infection by other retroviruses that employ the same receptor; a phenomenon termed receptor interference. Receptor masking is thought to provide an earlier means of blocking superinfection, whereas receptor down regulation is generally considered to occur in chronically infected cells.
Results: We used replication-competent GFP-expressing viruses containing either an amphotropic murine leukemia virus (A-MLV) or the gibbon ape leukemia virus (GALV) envelope. We also constructed similar viruses containing fluorescence-labeled Gag proteins for the detection of viral particles. Using this repertoire of reagents together with a wide range of antibodies, we were able to determine the presence and availability of viral receptors, and detect viral envelope proteins and particles presence on the cell surface of chronically infected cells.
Conclusions: A-MLV or GALV receptors remain on the surface of chronically infected cells and are detectable by respective antibodies, indicating that these receptors are not downregulated in these infected cells as previously proposed. We were also able to detect viral envelope proteins on the infected cell surface and infected cells are unable to bind soluble A-MLV or GALV envelopes indicating that receptor binding sites are masked by endogenously expressed A-MLV or GALV viral envelope. However, receptor masking does not completely prevent A-MLV or GALV superinfection.
C1 [Liu, Meihong; Eiden, Maribeth V.] NIMH, Sect Mol Virol, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
RP Eiden, MV (reprint author), NIMH, Sect Mol Virol, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
EM eidenm@mail.nih.gov
FU NIMH
FX We thank Karen B. Farrell for technical advice; Jim Nagle and Debbie
Kauffmann at the NINDS Sequencing Facility (National Institutes of
Health) for sequencing; Parisa Moghaddam-Taaheri for experimental help;
Jon Marsh and Jill Russ for supervising FACS operation and Vincent
Schram and Lynne Holtzclaw in the Microscropy & Imaging Core, NICHD, NIH
for technical guidance in confocal microscope and Wenqin Xu for her
thoughtful comments and editorial assistance. NIMH intramural funding
supported this work.
NR 39
TC 2
Z9 2
U1 0
U2 3
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 JUL 5
PY 2011
VL 8
AR 53
DI 10.1186/1742-4690-8-53
PG 14
WC Virology
SC Virology
GA 792FO
UT WOS:000292726100001
PM 21729311
ER
PT J
AU Lam, CSP
Lyass, A
Kraigher-Krainer, E
Massaro, JM
Lee, DS
Ho, JE
Levy, D
Redfield, MM
Pieske, BM
Benjamin, EJ
Vasan, RS
AF Lam, Carolyn S. P.
Lyass, Asya
Kraigher-Krainer, Elisabeth
Massaro, Joseph M.
Lee, Douglas S.
Ho, Jennifer E.
Levy, Daniel
Redfield, Margaret M.
Pieske, Burkert M.
Benjamin, Emelia J.
Vasan, Ramachandran S.
TI Cardiac Dysfunction and Noncardiac Dysfunction as Precursors of Heart
Failure With Reduced and Preserved Ejection Fraction in the Community
SO CIRCULATION
LA English
DT Article
DE echocardiography; epidemiology; heart failure; risk factors
ID OBSTRUCTIVE PULMONARY-DISEASE; DIASTOLIC DYSFUNCTION; SYSTOLIC
DYSFUNCTION; ELDERLY-PATIENTS; NATURAL-HISTORY; OF-CARDIOLOGY;
FRAMINGHAM; DIAGNOSIS; HEALTH; METAANALYSIS
AB Background-Heart failure (HF) is a clinical syndrome characterized by signs and symptoms involving multiple organ systems. Longitudinal data demonstrating that asymptomatic cardiac dysfunction precedes overt HF are scarce, and the contribution of noncardiac dysfunction to HF progression is unclear. We hypothesized that subclinical cardiac and noncardiac organ dysfunction would accelerate the manifestation of HF.
Methods and Results-We studied 1038 participants of the Framingham Heart Study original cohort (mean age, 76 +/- 5 years; 39% men) with routine assessment of left ventricular systolic and diastolic function. Major noncardiac organ systems were assessed with the use of serum creatinine (renal), serum albumin (hepatic), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1:FVC ratio; pulmonary), hemoglobin concentration (hematologic/oxygen-carrying capacity), and white blood cell count (systemic inflammation). On follow-up (mean, 11 years), there were 248 incident HF events (146 in women). After adjustment for established HF risk factors, antecedent left ventricular systolic dysfunction (hazard ratio, 2.33; 95% confidence interval, 1.43 to 3.78) and diastolic dysfunction (hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.71) were associated with increased HF risk. After adjustment for cardiac dysfunction, higher serum creatinine, lower FEV1:FVC ratios, and lower hemoglobin concentrations were associated with increased HF risk (all P < 0.05); serum albumin and white blood cell count were not. Subclinical dysfunction in each noncardiac organ system was associated with a 30% increased risk of HF (P = 0.013).
Conclusions-Antecedent cardiac dysfunction and noncardiac organ dysfunction are associated with increased incidence of HF, supporting the notion that HF is a progressive syndrome and underscoring the importance of noncardiac factors in its occurrence. (Circulation. 2011;124:24-30.)
C1 [Lam, Carolyn S. P.; Lyass, Asya; Massaro, Joseph M.; Lee, Douglas S.; Ho, Jennifer E.; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Lyass, Asya] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Kraigher-Krainer, Elisabeth; Pieske, Burkert M.] Graz Univ, Dept Cardiol, Graz, Austria.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Lam, Carolyn S. P.; Redfield, Margaret M.] Mayo Clin, Rochester, MN USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM vasan@bu.edu
RI Lee, Douglas/J-4315-2014;
OI Massaro, Joseph/0000-0002-2682-4812; Ho, Jennifer/0000-0002-7987-4768;
Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Heart, Lung and Blood Institute [NO1-HC-25195]; Canadian
Institutes of Health Research
FX This work was supported by the National Heart, Lung and Blood Institute
(contract NO1-HC-25195). Dr Lee was supported by a clinician-scientist
award from the Canadian Institutes of Health Research.
NR 32
TC 91
Z9 95
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 5
PY 2011
VL 124
IS 1
BP 24
EP U85
DI 10.1161/CIRCULATIONAHA.110.979203
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 787KO
UT WOS:000292375200016
PM 21670229
ER
PT J
AU Brindley, MA
Hunt, CL
Kondratowicz, AS
Bowman, J
Sinn, PL
McCray, PB
Quinn, K
Weller, ML
Chiorini, JA
Maury, W
AF Brindley, Melinda A.
Hunt, Catherine L.
Kondratowicz, Andrew S.
Bowman, Jill
Sinn, Patrick L.
McCray, Paul B., Jr.
Quinn, Kathrina
Weller, Melodie L.
Chiorini, John A.
Maury, Wendy
TI Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without
direct interactions with the viral glycoprotein
SO VIROLOGY
LA English
DT Article
DE Axl; Filovirus; Ebolavirus; Marburgvirus; Virus entry; Tyrosine kinase
receptors
ID VESICULAR STOMATITIS-VIRUS; VASCULAR SMOOTH-MUSCLE;
HUMAN-IMMUNODEFICIENCY-VIRUS; DC-SIGN; ENDOTHELIAL-CELLS; CELLULAR
ENTRY; GAS6; INFECTION; PROTEIN; ACTIVATION
AB In a bioinformatics-based screen for cellular genes that enhance Zaire ebolavirus (ZEBOV) transduction, AXL mRNA expression strongly correlated with ZEBOV infection. A series of cell lines and primary cells were identified that require Axl for optimal ZEBOV entry. Using one of these cell lines, we identified ZEBOV entry events that are Axl-dependent. Interactions between ZEBOV-GP and the Axl ectodomain were not detected in immunoprecipitations and reduction of surface-expressed Axl by RNAi did not alter ZEBOV-GP binding, providing evidence that Axl does not serve as a receptor for the virus. However, RNAi knock down of Axl reduced ZEBOV pseudovirion internalization and alpha-Axl antisera inhibited pseudovirion fusion with cellular membranes. Consistent with the importance of Axl for ZEBOV transduction, Axl transiently co-localized on the surface of cells with ZEBOV virus particles and was internalized during virion transduction. In total, these findings indicate that endosomal uptake of filoviruses is facilitated by Axl. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Brindley, Melinda A.; Hunt, Catherine L.; Kondratowicz, Andrew S.; Bowman, Jill; Maury, Wendy] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA.
[Sinn, Patrick L.; McCray, Paul B., Jr.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Quinn, Kathrina; Weller, Melodie L.; Chiorini, John A.] NIH, Mol Physiol & Therapeut Branch, Natl Dent & Craniofacial Res Branch, Bethesda, MD 20892 USA.
RP Maury, W (reprint author), Univ Iowa, Dept Microbiol, 3-750 Bowen Sci Bldg, Iowa City, IA 52242 USA.
EM wendy-maury@uiowa.edu
FU NIH NIDCR; NIH NIAID; [NIHAI064526]; [AI073330]; [NIHHL075363];
[NIHT32 A1007533]
FX This work was supported by NIHAI064526 and AI073330 (W.M.), NIHHL075363
(P.B.M.) and intramural NIH NIAID biodefense and NIH NIDCR grants to
J.A.C. M.A.B. and A.S.K. were supported through NIHT32 A1007533, a
training grant in molecular virology.
NR 55
TC 44
Z9 45
U1 0
U2 8
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 JUL 5
PY 2011
VL 415
IS 2
BP 83
EP 94
DI 10.1016/j.virol.2011.04.002
PG 12
WC Virology
SC Virology
GA 778OH
UT WOS:000291713500002
PM 21529875
ER
PT J
AU Joshi, A
Garg, H
Ablan, S
Freed, EO
Nagashima, K
Manjunath, N
Shankar, P
AF Joshi, Anjali
Garg, Himanshu
Ablan, Sherimay
Freed, Eric O.
Nagashima, Kunio
Manjunath, N.
Shankar, Premlata
TI Targeting the HIV entry, assembly and release pathways for anti-HIV gene
therapy
SO VIROLOGY
LA English
DT Article
DE HIV; Gag; Envelope; Virus assembly; HIV entry; Dominant negative; Gene
therapy
ID IMMUNODEFICIENCY-VIRUS TYPE-1; WILD-TYPE VIRUS; GP41 CYTOPLASMIC TAIL;
ZINC-FINGER NUCLEASES; GAG-MEMBRANE-BINDING; VIRAL MESSENGER-RNA;
BYSTANDER APOPTOSIS; ENVELOPE GLYCOPROTEINS; PARTICLE-PRODUCTION; ENV
PROTEINS
AB Targeting the HIV entry and assembly pathways holds promise for development of novel anti-HIV gene therapy vectors. We characterized discrete dominant negative (DN) Gag and Envelope mutants for their anti-HIV-1 activity. We show here that capsid mutants (Q155N and Y164A) are more potent inhibitors of WT HIV than the matrix mutant 1GA. Both the Envelope mutants tested, V513E and R515A, were equally effective and a combination of Gag and Envelope DN genes significantly enhanced potency. Interestingly, the DN mutants acted at multiple steps in the virus life cycle rather than solely disrupting virus release or infection. Inhibition mediated by R515A could be partially attributed to the Envelope cytoplasmic tail, as deletion of R515A tail partially abrogated its DN effect. Finally, the Y164A/R515A double mutant expressed in a lentiviral vector was effective at inhibiting HIV replication in CD34+ hematopoietic stem cell-derived macrophages, demonstrating the therapeutic potential of our approach. Published by Elsevier Inc.
C1 [Joshi, Anjali; Garg, Himanshu; Manjunath, N.; Shankar, Premlata] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Ctr Excellence Infect Dis, El Paso, TX 79905 USA.
[Joshi, Anjali; Garg, Himanshu] Texas Tech Univ, Hlth Sci Ctr, Dept Pediat, El Paso, TX 79905 USA.
[Ablan, Sherimay; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Nagashima, Kunio] NCI, Electron Microscope Lab, Res Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
RP Joshi, A (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Ctr Excellence Infect Dis, El Paso, TX 79905 USA.
EM anjali.joshi@ttuhsc.edu; premlata.shankar@ttuhsc.edu
FU NIH [AI071882, AI08053]
FX This work was supported by NIH grants AI071882 and AI08053 to P.S. We
thank F. Soheilian for expert technical assistance and V. Bokyo and
Wei-Shau Hu for kindly providing the pNL4-3/Gag-mRFP. The HIV-Ig, GFP
expressing lentiviral vector TyefEGFP and TZM-bl cells were obtained
from the NIH AIDS Research and Reference Reagent Program. A.J. and H.G.
designed and conducted the experiments, performed the research,
contributed reagents, analyzed the data, and wrote the paper. S.A.
conducted the experiments and reviewed the manuscript, K.N. conducted
the experiments, E.F. contributed vital expertise and critically
reviewed the data and manuscript, and M.N. and P.S. contributed vital
reagents and reviewed the manuscript.
NR 49
TC 4
Z9 6
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 JUL 5
PY 2011
VL 415
IS 2
BP 95
EP 106
DI 10.1016/j.virol.2011.03.028
PG 12
WC Virology
SC Virology
GA 778OH
UT WOS:000291713500003
PM 21529874
ER
PT J
AU Young, TS
Young, DD
Ahmad, I
Louis, JM
Benkovic, SJ
Schultz, PG
AF Young, Travis S.
Young, Douglas D.
Ahmad, Insha
Louis, John M.
Benkovic, Stephen J.
Schultz, Peter G.
TI Evolution of cyclic peptide protease inhibitors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE unnatural amino acid; protein translation; bacterial selection
ID ESCHERICHIA-COLI; IN-VIVO; BIOSYNTHESIS; ANTIBIOTICS; SELECTION; SYSTEM;
DISCOVERY; LIBRARY; BINDING; SCREEN
AB We report a bacterial system for the evolution of cyclic peptides that makes use of an expanded set of amino acid building blocks. Orthogonal aminoacyl-tRNA synthetase/tRNA(CUA) pairs, together with a split intein system were used to biosynthesize a library of ribosomal peptides containing amino acids with unique structures and reactivities. This peptide library was subsequently used to evolve an inhibitor of HIV protease using a selection based on cellular viability. Two of three cyclic peptides isolated after two rounds of selection contained the keto amino acid p-benzoylphenylalanine (pBzF). The most potent peptide (G12: GIXVSL; X = pBzF) inhibited HIV protease through the formation of a covalent Schiff base adduct of the pBzF residue with the.-amino group of Lys 14 on the protease. This result suggests that an expanded genetic code can confer an evolutionary advantage in response to selective pressure. Moreover, the combination of natural evolutionary processes with chemically biased building blocks provides another strategy for the generation of biologically active peptides using microbial systems.
C1 [Benkovic, Stephen J.] Penn State Univ, Dept Chem, Wartik Lab 414, University Pk, PA 16802 USA.
[Young, Travis S.; Young, Douglas D.; Ahmad, Insha; Schultz, Peter G.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Young, Travis S.; Young, Douglas D.; Ahmad, Insha; Schultz, Peter G.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Louis, John M.] NIH, Chem Phys Lab, NIDDK, Bethesda, MD 20892 USA.
RP Benkovic, SJ (reprint author), Penn State Univ, Dept Chem, Wartik Lab 414, University Pk, PA 16802 USA.
EM schultz@scripps.edu
FU National Institutes of Health (NIH) [5R01GM062159, F32CA144213];
National Institute of Diabetes and Digestive and Kidney Diseases, NIH;
Office of the Director, NIH; Achievement Rewards for College Scientists
Scholarship
FX The authors would like to thank Xuemei Han and the Yates Lab for aid in
MS characterization, as well as Virginia Seely and Emily Remba for
manuscript preparation and submission. This work was funded by Grant
5R01GM062159 from the National Institutes of Health (NIH) (to P. G. S.)
and supported in part by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, NIH and the
Intramural AIDS-Targeted Program of the Office of the Director, NIH.
This is manuscript 21197 of The Scripps Research Institute. D.D.Y. is
grateful for an NIH Fellowship F32CA144213 and T.S.Y. is grateful for an
Achievement Rewards for College Scientists Scholarship.
NR 37
TC 48
Z9 51
U1 0
U2 26
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 JUL 5
PY 2011
VL 108
IS 27
BP 11052
EP 11056
DI 10.1073/pnas.1108045108
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 787LC
UT WOS:000292376700031
PM 21690365
ER
PT J
AU Burton, DR
Hessell, AJ
Keele, BF
Klasse, PJ
Ketas, TA
Moldt, B
Dunlop, DC
Poignard, P
Doyle, LA
Cavacini, L
Veazey, RS
Moore, JP
AF Burton, Dennis R.
Hessell, Ann J.
Keele, Brandon F.
Klasse, Per Johan
Ketas, Thomas A.
Moldt, Brian
Dunlop, D. Cameron
Poignard, Pascal
Doyle, Lara A.
Cavacini, Lisa
Veazey, Ronald S.
Moore, John P.
TI Limited or no protection by weakly or nonneutralizing antibodies against
vaginal SHIV challenge of macaques compared with a strongly neutralizing
antibody
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE binding antibodies; passive immunization
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; RHESUS
MACAQUES; ENVELOPE GLYCOPROTEIN; HIV VACCINES; IN-VITRO; INFECTION;
BINDING; TRANSMISSION; MONKEYS
AB To guide vaccine design, we assessed whether human monoclonal antibodies (MAbs) b12 and b6 against the CD4 binding site (CD4bs) on HIV-1 gp120 and F240 against an immundominant epitope on gp41 could prevent vaginal transmission of simian HIV (SHIV)-162P4 to macaques. The two anti-gp120 MAbs have similar monomeric gp120-binding properties, measured in vitro, but b12 is strongly neutralizing and b6 is not. F240 is nonneutralizing. Applied vaginally at a high dose, the strongly neutralizing MAb b12 provided sterilizing immunity in seven of seven animals, b6 in zero of five animals, and F240 in two of five animals. Compared with control animals, the protection by b12 achieved statistical significance, whereas that caused by F240 did not. For two of three unprotected F240-treated animals there was a trend toward lowered viremia. The potential protective effect of F240 may relate to the relatively strong ability of this antibody to capture infectious virions. Additional passive transfer experiments also indicated that the ability of the administered anti-gp120 MAbs to neutralize the challenge virus was a critical influence on protection. Furthermore, when data from all of the experiments were combined, there was a significant increase in the number of founder viruses establishing infection in animals receiving MAb b6, compared with other nonprotected macaques. Thus, a gp120-binding, weakly neutralizing MAb to the CD4bs was, at best, completely ineffective at protection. A nonneutralizing antibody to gp41 may have a limited capacity to protect, but the results suggest that the central focus of HIV-1 vaccine research should be on the induction of potently neutralizing antibodies.
C1 [Burton, Dennis R.; Hessell, Ann J.; Moldt, Brian; Dunlop, D. Cameron; Poignard, Pascal] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.; Hessell, Ann J.; Moldt, Brian; Dunlop, D. Cameron; Poignard, Pascal] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[Burton, Dennis R.; Dunlop, D. Cameron] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02114 USA.
[Hessell, Ann J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
[Keele, Brandon F.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Klasse, Per Johan; Ketas, Thomas A.; Moore, John P.] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA.
[Doyle, Lara A.; Veazey, Ronald S.] Tulane Univ, Sch Med, Tulane Natl Primate Res Ctr, Covington, LA 70433 USA.
[Cavacini, Lisa] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA.
RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM burton@scripps.edu; jpm2003@med.cornell.edu
RI poignard, pascal/N-6678-2013
FU International AIDS Vaccine Initiative; National Institutes of Health
[U19 AI76982, R37 AI36082, AI33292, AI1055332]; National Cancer
Institute, National Institutes of Health [HHSN266200400088C]; Alfred
Benzon Foundation
FX We thank Athe Tsibris and Steven Wolinsky for contributing founder virus
data for the gel control group (Fig. 4); Leo Stamatatos for the
SHIV-162P4 challenge stock; and Kelsi Rasmussen and Janell LeBlanc for
their technical support. The animal studies were funded by the
International AIDS Vaccine Initiative, with additional support by
National Institutes of Health Cooperative Agreement U19 AI76982 (to
J.P.M.); in vitro studies were also supported by National Institutes of
Health Grants R37 AI36082 (to J.P.M.) and AI33292 and AI1055332 (to
D.R.B.); sequencing and founder virus analysis was performed with
federal funds from the National Cancer Institute, National Institutes of
Health, under Contract HHSN266200400088C. B.M. was supported by the
Alfred Benzon Foundation.
NR 43
TC 149
Z9 150
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 5
PY 2011
VL 108
IS 27
BP 11181
EP 11186
DI 10.1073/pnas.1103012108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 787LC
UT WOS:000292376700053
PM 21690411
ER
PT J
AU Josefsson, L
King, MS
Makitalo, B
Brannstrom, J
Shao, W
Maldarelli, F
Kearney, MF
Hu, WS
Chen, JB
Gaines, H
Mellors, JW
Albert, J
Coffin, JM
Palmer, SE
AF Josefsson, Lina
King, Martin S.
Makitalo, Barbro
Brannstrom, Johan
Shao, Wei
Maldarelli, Frank
Kearney, Mary F.
Hu, Wei-Shau
Chen, Jianbo
Gaines, Hans
Mellors, John W.
Albert, Jan
Coffin, John M.
Palmer, Sarah E.
TI Majority of CD4(+) T cells from peripheral blood of HIV-1-infected
individuals contain only one HIV DNA molecule
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DYNAMICS IN-VIVO; REVERSE-TRANSCRIPTASE;
INFECTED INDIVIDUALS; MONONUCLEAR-CELLS; TYPE-1 INFECTION;
RECOMBINATION; RESISTANCE; RNA; EVOLUTION
AB Neither the number of HIV-1 proviruses within individual infected cells in HIV-1-infected patients nor their genetic relatedness within individual infected cells and between cells and plasma virus are well defined. To address these issues we developed a technique to quantify and genetically characterize HIV-1 DNA from single infected cells in vivo. Analysis of peripheral blood CD4(+) T cells from nine patients revealed that the majority of infected cells contain only one copy of HIV-1 DNA, implying a limited potential for recombination in virus produced by these cells. The genetic similarity between HIV populations in CD4(+) T cells and plasma implies ongoing exchange between these compartments both early and late after infection.
C1 [Josefsson, Lina; Makitalo, Barbro; Brannstrom, Johan; Gaines, Hans; Palmer, Sarah E.] Swedish Inst Infect Dis Control, Dept Diagnost & Vaccinol, S-17182 Solna, Sweden.
[Josefsson, Lina; Albert, Jan; Palmer, Sarah E.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17182 Solna, Sweden.
[Josefsson, Lina; Maldarelli, Frank; Kearney, Mary F.; Hu, Wei-Shau; Chen, Jianbo; Coffin, John M.; Palmer, Sarah E.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[King, Martin S.] Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60069 USA.
[Shao, Wei] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Mellors, John W.] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA.
RP Josefsson, L (reprint author), Swedish Inst Infect Dis Control, Dept Diagnost & Vaccinol, S-17182 Solna, Sweden.
EM Lina.Josefsson@smi.se; john.coffin@tufts.edu
RI Chen, Jianbo/N-3737-2014
OI Chen, Jianbo/0000-0001-6491-6577
FU NIH; National Cancer Institute (Center for Cancer Research, NIH) the
Swedish Research Council; American Foundation for AIDS Research
[107170-44-RGRL]; F. M. Kirby Foundation
FX We acknowledge with gratitude the patients participating in this study,
G. Bratt and A. Thalme for clinical assistance with patients in Sweden,
Diane Rock for assistance with recruitment of the patients attending the
clinic at the National Institutes of Health (NIH), and M. Mild for
assistance in phylogenetic analysis. This study was supported by an NIH
Bench to Bedside Award (to F. M.) in the HIV Drug Resistance Program,
the Intramural Research Program of the National Cancer Institute (Center
for Cancer Research, NIH) the Swedish Research Council, and American
Foundation for AIDS Research Grant 107170-44-RGRL. J.M.C. was a research
professor of the American Cancer Society with support from the F. M.
Kirby Foundation.
NR 34
TC 94
Z9 94
U1 2
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 5
PY 2011
VL 108
IS 27
BP 11199
EP 11204
DI 10.1073/pnas.1107729108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 787LC
UT WOS:000292376700056
PM 21690402
ER
PT J
AU Wykes, MN
Kay, JG
Manderson, A
Liu, XQ
Brown, DL
Richard, DJ
Wipasa, J
Jiang, SHH
Jones, MK
Janse, CJ
Waters, AP
Pierce, SK
Miller, LH
Stow, JL
Good, MF
AF Wykes, Michelle N.
Kay, Jason G.
Manderson, Anthony
Liu, Xue Q.
Brown, Darren L.
Richard, Derek J.
Wipasa, Jiraprapa
Jiang, Suhua H.
Jones, Malcolm K.
Janse, Chris J.
Waters, Andrew P.
Pierce, Susan K.
Miller, Louis H.
Stow, Jennifer L.
Good, Michael F.
TI Rodent blood-stage Plasmodium survive in dendritic cells that infect
naive mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE immune evasion; rodent malaria
ID MALARIA PARASITE; QUARTAN MALARIA; MAMMALIAN HOST; SPOROZOITES; BERGHEI;
YOELII; MOUSE; MEROZOITES; PLATELETS; ANTIGEN
AB Plasmodium spp. parasites cause malaria in 300 to 500 million individuals each year. Disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. Infected individuals can also suffer relapses after several years, from Plasmodium vivax and Plasmodium ovale surviving in hepatocytes. Plasmodium falciparum and Plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood, suggesting that host cells other than erythrocytes (but not hepatocytes) may harbor these blood-stage parasites, thereby assisting their escape from host immunity. Using blood stage transgenic Plasmodium berghei-expressing GFP (PbGFP) to track parasites in host cells, we found that the parasite had a tropism for CD317(+) dendritic cells. Other studies using confocal microscopy, in vitro cultures, and cell transfer studies showed that blood-stage parasites could infect, survive, and replicate within CD317(+) dendritic cells, and that small numbers of these cells released parasites infectious for erythrocytes in vivo. These data have identified a unique survival strategy for blood-stage Plasmodium, which has significant implications for understanding the escape of Plasmodium spp. from immune-surveillance and for vaccine development.
C1 [Wykes, Michelle N.; Liu, Xue Q.; Richard, Derek J.; Jiang, Suhua H.; Jones, Malcolm K.; Good, Michael F.] Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Kay, Jason G.; Manderson, Anthony; Brown, Darren L.; Stow, Jennifer L.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
[Jones, Malcolm K.] Univ Queensland, Sch Vet Sci, Brisbane, Qld 4072, Australia.
[Wipasa, Jiraprapa] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50200, Thailand.
[Jiang, Suhua H.] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Immunol, Wuhan 430030, Hubei, Peoples R China.
[Jiang, Suhua H.] Shihezi Univ, Sch Med, Dept Pathogen Biol & Immunol, Shihezi City 832002, Xinjiang, Peoples R China.
[Janse, Chris J.] Leiden Univ, Med Ctr, Ctr Infect Dis, Dept Parasitol, NL-2333 ZA Leiden, Netherlands.
[Waters, Andrew P.] Univ Glasgow, Wellcome Ctr Mol Parasitol, Glasgow G12 8TA, Lanark, Scotland.
[Waters, Andrew P.] Univ Glasgow, Fac Biomed Life Sci, Glasgow Biomed Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
[Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Miller, Louis H.] NIAID, Malaria Cell Biol Sect, NIH, Rockville, MD 20852 USA.
RP Wykes, MN (reprint author), Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
EM michelle.wykes@qimr.edu.au; lmiller@niaid.nih.gov;
michael.good@griffith.edu.au
RI Waters, Andy/C-9377-2009; Wykes, Michelle/G-6272-2013; Stow,
Jennifer/I-4723-2013; Jones, Malcolm/A-1097-2009;
OI Waters, Andy/0000-0001-8900-2982; Wykes, Michelle/0000-0002-7956-0144;
Stow, Jennifer/0000-0002-5409-9101; Jones, Malcolm/0000-0002-0035-6141;
Richard, Derek/0000-0002-4839-8471
FU National Health and Medical Research Council (Australia)
FX We thank Drs. Denise Doolan, Christian Engwerda, and James McCarthy for
their critical reading of the manuscript; Drs. Alan Sher and Leanne
Tilley for their discussion of the data; Ms. Grace Chojnowski and Paula
Hall for their excellent cell sorting skills; and Ms. Virginia McPhun
for her technical assistance with some of the earlier developmental
assays. This study was supported by the National Health and Medical
Research Council (Australia).
NR 29
TC 33
Z9 35
U1 1
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 JUL 5
PY 2011
VL 108
IS 27
BP 11205
EP 11210
DI 10.1073/pnas.1108579108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 787LC
UT WOS:000292376700057
PM 21690346
ER
PT J
AU Wynn, TA
AF Wynn, Thomas A.
TI Integrating mechanisms of pulmonary fibrosis
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Review
ID TUMOR-NECROSIS-FACTOR; INDUCED LUNG INJURY; BRONCHIOLITIS OBLITERANS
SYNDROME; THYMIC STROMAL LYMPHOPOIETIN; MESENCHYMAL STEM-CELLS;
GROWTH-FACTOR-BETA; FACTOR-ALPHA; IL-13-INDUCED INFLAMMATION; NALP3
INFLAMMASOME; MURINE LUNG
AB Pulmonary fibrosis is a highly heterogeneous and lethal pathological process with limited therapeutic options. Although research on the pathogenesis of pulmonary fibrosis has frequently focused on the mechanisms that regulate the proliferation, activation, and differentiation of collagen-secreting myofibroblasts, recent studies have identified new pathogenic mechanisms that are critically involved in the initiation and progression of fibrosis in a variety of settings. A more detailed and integrated understanding of the cellular and molecular mechanisms of pulmonary fibrosis could help pave the way for effective therapeutics for this devastating and complex disease.
C1 [Wynn, Thomas A.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA.
[Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Wynn, TA (reprint author), NIAID, Program Barrier Immun & Repair, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twynn@niaid.nih.gov
RI Wynn, Thomas/C-2797-2011
FU National Institute of Allergy and Infectious Disease/National Institutes
of Health
FX I would like to sincerely thank the past and present members of my
laboratory for their guidance and support. The Wynn laboratory is
supported by the intramural research program of the National Institute
of Allergy and Infectious Disease/National Institutes of Health.
NR 146
TC 309
Z9 326
U1 3
U2 36
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUL 4
PY 2011
VL 208
IS 7
BP 1339
EP 1350
DI 10.1084/jem.20110551
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 791BZ
UT WOS:000292637000002
PM 21727191
ER
PT J
AU Nair, M
Prabhakaran, D
Narayan, KMV
Sinha, R
Lakshmy, R
Devasenapathy, N
Daniel, CR
Gupta, R
George, PS
Mathew, A
Tandon, N
Reddy, KS
AF Nair, Manisha
Prabhakaran, Dorairaj
Narayan, K. M. Venkat
Sinha, Rashmi
Lakshmy, Ramakrishnan
Devasenapathy, Niveditha
Daniel, Carrie R.
Gupta, Ruby
George, Preethi S.
Mathew, Aleyamma
Tandon, Nikhil
Reddy, K. Srinath
TI HbA(1c) values for defining diabetes and impaired fasting glucose in
Asian Indians
SO PRIMARY CARE DIABETES
LA English
DT Article
DE HbA(1c); Diabetes; "Asian Indians"
ID PLASMA-GLUCOSE; HIGH-RISK; GLYCOSYLATED HEMOGLOBIN; DIAGNOSTIC-CRITERIA;
GLYCATED HEMOGLOBIN; US POPULATION; A1C-BASED DIAGNOSIS; HBA1C;
MELLITUS; A1C
AB Aim: To determine the glycosylated haemoglobin (HbA(1c)) cut-points for diabetes and impaired fasting glucose (IFG) among Asian Indians.
Methods: Participants (n = 525) were a random sample selected from the India Health Study. Based on history and fasting plasma glucose (FPG), participants were classified into known diabetes, newly diagnosed diabetes (NDD), impaired fasting glucose (IFG) [ADA and WHO criteria] or normal fasting glucose (NFG). Receiver Operating Characteristic curves were used to identify the optimum sensitivity and specificity for defining HbA(1c), cut-points for NDD and IFG against the FPG criteria.
Results: There were 64 participants with a known history of diabetes. Of the remaining 461, IFG was present in 44.7% (ADA) and 18.2% (WHO), and 10.4% were NDD. Mean HbA(1c) were 5.4 (+/-0.04)% for NFG; 5.7 (+/-0.06)% among IFG-ADA, 5.8 (+/-0.09)% among IFG-WHO; 7.5 (+/-0.33)% for NDD and 8.4 (+/-0.32)% for known diabetes. Optimal HbA(1c) cut-point for NOD was 5.8% (sensitivity = 75%, specificity = 75.5%, AUC = 0.819). Cut-point for IFG (ADA) was 5.5% (sensitivity = 59.7%, specificity = 59.9%, AUC = 0.628) and for IFG (WHO) was 5.6% (sensitivity = 60.7%, specificity =65.1%, AUC = 0.671).
Conclusion: In this study population from north and south regions of India, the HbA(1c) cut-point that defines NDD (>= 5.8%) was much lower than that proposed by an international expert committee and the American Diabetes Association (>= 6.5%). A cut-point of >= 5.5% or >= 5.6% defined IFG, and was slightly lower than the >= 5.7% for high risk proposed, but accuracy was less than 70%. (C) 2011 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
C1 [Nair, Manisha] Publ Hlth Fdn India, Fogarty Int Ctr, New Delhi 122002, India.
[Nair, Manisha] Publ Hlth Fdn India, Ctr Excellence Ctr cArdiometab Risk Reduct S Asia, New Delhi 122002, India.
[Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India.
[Narayan, K. M. Venkat] Emory Univ, Atlanta, GA 30322 USA.
[Sinha, Rashmi; Daniel, Carrie R.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Lakshmy, Ramakrishnan; Gupta, Ruby] All India Inst Med Sci, Dept Cardiac Biochem, New Delhi, India.
[Devasenapathy, Niveditha] Indian Inst Publ Hlth, New Delhi, India.
[George, Preethi S.; Mathew, Aleyamma] Reg Canc Ctr, Thiruvananthapuram, Kerala, India.
[Tandon, Nikhil] All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India.
RP Nair, M (reprint author), Publ Hlth Fdn India, Fogarty Int Ctr, New Delhi 122002, India.
EM dr.manisha.das@gmail.com; dprabhakaran@ccdcindia.org; knaraya@emory.edu;
sinhar@exchange.nih.gov; lakshmy_ram@yahoo.com; niveditha@iiphd.org;
danielc3@mai1.nih.gov; g_ruby2123@yahoo.co.in; preethig@rcctvm.org;
amathew@rcctvm.org; nikhil_tandon@hotmail.com; ksrinath.reddy@phfi.org
RI Narayan, K.M. Venkat /J-9819-2012; Sinha, Rashmi/G-7446-2015;
OI Narayan, K.M. Venkat /0000-0001-8621-5405; Sinha,
Rashmi/0000-0002-2466-7462; Nair, Manisha/0000-0003-0660-5054;
Prabhakaran, Dorairaj/0000-0002-3172-834X
FU NIH
FX Funded by: NIH.
NR 48
TC 10
Z9 10
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1751-9918
J9 PRIM CARE DIABETES
JI Prim. Care Diabetes
PD JUL
PY 2011
VL 5
IS 2
BP 95
EP 102
DI 10.1016/j.pcd.2011.02.002
PG 8
WC Endocrinology & Metabolism; Primary Health Care
SC Endocrinology & Metabolism; General & Internal Medicine
GA 945MV
UT WOS:000304279500005
PM 21474403
ER
PT J
AU Ahuja, K
Bennett, F
Cohen, J
Edwards, R
Pritchard, H
Silver, A
Sirlin, J
Slee, J
Abse, D
Ashwood-Smith, MJ
Bavister, B
Bedford, JM
Beier, HM
Bronson, R
Cattanach, B
Daniel, JC
Dawes, EA
Ferguson-Smith, M
Gardner, R
Griffin, D
Hunter, RHF
Johnson, M
Jones, H
Lunenfeld, B
Mittwoch, U
Moor, R
Rankin, B
Schally, AV
Sharpe, DJ
Simpson, D
Yanagimachi, R
Ahuja, K
Alexandre, H
Bhargava, PM
Cohen, J
Dexter, A
Diedrich, K
Emperaire, JC
Findlay, A
Fishel, S
Fox, NL
Goddard, H
Gomel, V
Gore-Langton, RE
Gosden, R
Iritani, A
Koskimies, AI
MacDonald, G
Menezo, Y
Mettler, L
Monk, M
Mori, T
Mortimer, D
Papaioannou, VE
Racowsky, C
Surani, A
Trounson, A
Van Blerkom, J
Vincent, P
Walters, E
Webster, J
Williams, P
Aboulghar, M
Barri, PN
Benagiano, G
Blackwell, C
Bolton, VN
Brinsden, PR
Bustillo, M
Coulam, C
Chaouat, G
Crosignani, P
Gardner, D
Gianaroli, L
Hamberger, L
Hartshorne, G
Hollands, P
Howles, C
Illmensee, K
Jauniaux, E
Kini, D
Lee, S
Lees, M
Leese, H
Mathews, T
Moate, E
Nygren, K
Ockleford, C
Palermo, GD
Pandiyan, N
Rizk, B
Rosenwaks, Z
Sallam, H
Sathananthan, AH
Saunders, DM
Simpson, JL
Sunde, A
Tan, SL
Ulloa-Aguirre, A
Gosden, LV
Veiga, A
Albertini, DF
Alikani, M
Balaban, B
Thornhill, A
Beard, HK
Ben-Shlomo, I
Bennett, F
Borini, A
Carrell, D
De Jonge, C
Eichenlaub-Ritter, U
Fleming, S
Geber, S
Gerris, J
Golombok, S
Leather, DS
Nagy, ZP
Nielsen, HI
Oehninger, S
Olivennes, F
Patrizio, P
Paulson, RJ
de Fried, EP
Pool, TB
Risquez, F
Sauer, MV
Sciarra, JJ
Basuray, R
Boiso, I
Bose, CK
Cryan, B
Falconer, A
Hansis, C
Kahraman, S
Ko, MSH
Korsak, V
Loeffler, F
Ludwig, M
Magli, MC
Robertson, JA
Roche, LA
Thornhill, A
Wallberg-Henriksson, H
Woo, G
AF Ahuja, Kamal
Bennett, Fiona
Cohen, Jacques
Edwards, Ruth
Pritchard, Huw
Silver, Ann
Sirlin, Julio
Slee, John
Abse, Dannie
Ashwood-Smith, M. J.
Bavister, Barry
Bedford, J. Michael
Beier, Henning M.
Bronson, Richard
Cattanach, Bruce
Daniel, Joseph C.
Dawes, Edwin A.
Ferguson-Smith, Malcolm
Gardner, Richard
Griffin, Dave
Hunter, R. H. F.
Johnson, Martin
Jones, Howard
Lunenfeld, Bruno
Mittwoch, Ursula
Moor, Robert
Rankin, Barbara
Schally, Andrew V.
Sharpe, David J.
Simpson, David
Yanagimachi, Ryuzo 'Yana'
Ahuja, Kamal
Alexandre, Henri
Bhargava, Pushpa M.
Cohen, Jacques
Dexter, Alan
Diedrich, Klaus
Emperaire, Jean-Claude
Findlay, Alan
Fishel, Simon
Fox, Norma Lynn
Goddard, Hester
Gomel, Victor
Gore-Langton, Robert E.
Gosden, Roger
Iritani, A.
Koskimies, Aarne I.
MacDonald, Grace
Menezo, Yves
Mettler, Liselotte
Monk, Marilyn
Mori, Takahide
Mortimer, David
Papaioannou, Virginia E.
Racowsky, Catherine
Surani, Azim
Trounson, Alan
Van Blerkom, Jonathan
Vincent, Paul
Walters, Eurof
Webster, John
Williams, Peter
Aboulghar, M.
Barri, Pedro N.
Benagiano, Giuseppe
Blackwell, Caroline
Bolton, Virginia N.
Brinsden, Peter R.
Bustillo, Maria
Coulam, Carolyn
Chaouat, Gerard
Crosignani, Piergiorgio
Gardner, David
Gianaroli, Luca
Hamberger, Lars
Hartshorne, Geraldine
Hollands, Peter
Howles, Colin
Illmensee, Karl
Jauniaux, Eric
Kini, Dee
Lee, Sammy
Lees, Martin
Leese, Henry
Mathews, Thomas
Moate, Elaine
Nygren, Karl
Ockleford, Colin
Palermo, Gianpiero D.
Pandiyan, N.
Rizk, Botros
Rosenwaks, Zev
Sallam, Hassan
Sathananthan, A. Henry
Saunders, Douglas M.
Simpson, Joe Leigh
Sunde, Arne
Tan, Seang Lin
Ulloa-Aguirre, Alfredo
Gosden, Lucinda Veeck
Veiga, Anna
Albertini, David F.
Alikani, Mina
Balaban, Basak
Thornhill, Alan
Beard, Helen K.
Ben-Shlomo, Izhar
Bennett, Fiona
Borini, Andrea
Carrell, Douglas
De Jonge, Christopher
Eichenlaub-Ritter, Ursula
Fleming, Steven
Geber, Selmo
Gerris, Jan
Golombok, Susan
Leather, Dame Suzi
Nagy, Zsolt Peter
Nielsen, H. Ingolf
Oehninger, Sergio
Olivennes, Francois
Patrizio, Pasquale
Paulson, Richard J.
Polak de Fried, Ester
Pool, Thomas B. (Rusty)
Risquez, Francisco
Sauer, Mark V.
Sciarra, John J.
Basuray, Rita
Boiso, Irene
Bose, Chinmoy K.
Cryan, Bob
Falconer, Anthony
Hansis, Christoph
Kahraman, Semra
Ko, Minoru S. H.
Korsak, Vladislav
Loeffler, Frank
Ludwig, Michael
Magli, M. Cristina
Robertson, John A.
Roche, Lady Alexandra
Thornhill, A.
Wallberg-Henriksson, Harriet
Woo, George
CA IVF Canada
TI Salute to a giant ... Robert Geoffrey Edwards
SO REPRODUCTIVE BIOMEDICINE ONLINE
LA English
DT Biographical-Item
C1 [Pritchard, Huw] York Univ, Dept Chem, N York, ON M3J 1P3, Canada.
[Silver, Ann] Physiol Lab, Cambridge CB2 3EG, England.
[Slee, John] Bangor Univ, Bangor, Gwynedd, Wales.
[Slee, John] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Ashwood-Smith, M. J.] Univ Victoria, Victoria, BC, Canada.
[Bedford, J. Michael] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA.
[Bronson, Richard] SUNY Stony Brook, Med Ctr, Stony Brook, NY USA.
[Leese, Henry] Univ Hull, Hull York Med Sch, Kingston Upon Hull HU6 7RX, N Humberside, England.
[Hunter, R. H. F.] Univ Cambridge Sidney Sussex Coll, Cambridge, England.
[Lunenfeld, Bruno] Bar Ilan Univ, Ramat Gan, Israel.
[Mittwoch, Ursula] UCL, Dept Genet Evolut & Environm, London, England.
[Moor, Robert] Unit Reprod Physiol & Biochem, Cambridge, England.
[Rankin, Barbara; Goddard, Hester] Marshall Lab, Marshall, AL USA.
[Schally, Andrew V.] Univ Miami, Coral Gables, FL 33124 USA.
[Yanagimachi, Ryuzo 'Yana'] Univ Hawaii, Sch Med, Honolulu, HI 96822 USA.
[Ahuja, Kamal] London Womens Clin, London, England.
[Alexandre, Henri] Univ Libre Brussels, Brussels, Belgium.
[Alexandre, Henri] Univ Mons UMONS, Mons, Belgium.
[Cohen, Jacques] Tyho Galileo Res & Reprogenet Labs, Livingston, NJ USA.
[Diedrich, Klaus] Univ Lubeck, Lubeck, Germany.
[Emperaire, Jean-Claude] IVF Ctr Clin Jean Villar, Bordeaux Bruges, France.
[Findlay, Alan] Univ Cambridge Churchill Coll, Cambridge CB3 0DS, England.
[Fox, Norma Lynn] Human Genome Sci Inc, Clin Res, Rockville, MD USA.
[Gore-Langton, Robert E.] EMMES Corp, Rockville, MD USA.
[Iritani, A.; Mori, Takahide] Kyoto Univ, Kyoto 6068501, Japan.
[Koskimies, Aarne I.] Felicitas Clin, Helsinki, Finland.
[Monk, Marilyn] UCL, Inst Child Hlth, London WC1E 6BT, England.
[Mortimer, David] Oozoa Biomed Inc, Vancouver, BC, Canada.
[Racowsky, Catherine] Harvard Univ, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Sch Med, Boston, MA 02115 USA.
[Lees, Martin; Golombok, Susan] Univ Cambridge, Ctr Family Res, Cambridge CB2 1TN, England.
[Trounson, Alan] Calif Inst Regenerat Med, San Francisco, CA USA.
[Vincent, Paul] Wrigley Claydon Solicitors, Oldham, Lancs, England.
[Barri, Pedro N.] USP Inst Univ Dexeus, Dept Obstet Gynaecol & Reprod, Barcelona, Spain.
[Blackwell, Caroline] Duck End Farm, Reprod BioMed Online, Cambridge, England.
[Bolton, Virginia N.] Guys Hosp, Assisted Concept Unit, London SE1 9RT, England.
[Chaouat, Gerard] EMBIC, Paris, France.
[Crosignani, Piergiorgio] Maggiore Policlin Hosp, IRCCS Ca Granda Fdn, Milan, Italy.
[Gianaroli, Luca] SIS Me R SrL, ESHRE, Bologna, Italy.
[Hamberger, Lars] Gothenburg Univ, Gothenburg, Sweden.
[Hartshorne, Geraldine] Warwick Med Sch, Coventry, W Midlands, England.
[Howles, Colin] Merck Serono SA, Fertil & Endocrinol Global Business Unit, Reg Med Affairs, Geneva, Switzerland.
[Illmensee, Karl] Genesis Fertil Ctr, Patras, Greece.
[Jauniaux, Eric] Royal Free & Univ Coll London, UCL EGA Inst Womens Hlth, Acad Dept Obstet & Gynaecol, London, England.
[Ockleford, Colin] Univ Lancaster, Clin Anat Learning Ctr, Sch Hlth & Med, Div Med CME, Lancaster LA1 4YW, England.
[Palermo, Gianpiero D.] Cornell Inst Reprod Med, New York, NY USA.
[Pandiyan, N.] Chettinad Univ, Madras, Tamil Nadu, India.
[Pandiyan, N.] Chettinad Hosp & Res Inst, Madras, Tamil Nadu, India.
[Rizk, Botros] Univ S Alabama, Dept Obstet & Gynecol, Mobile, AL 36688 USA.
[Rosenwaks, Zev] Weill Cornell Med Coll, Ronald O Perelman & Claudia Cohen Ctr Reprod Med, New York, NY USA.
[Sathananthan, A. Henry] Monash Univ, Clayton, Vic 3800, Australia.
[Saunders, Douglas M.] Univ Sydney, Sydney, NSW 2006, Australia.
[Simpson, Joe Leigh] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33199 USA.
[Sunde, Arne] St Olavs Univ Hosp, Fertil Clin, Trondheim, Norway.
[Tan, Seang Lin] MUHC, McGill Reprod Ctr, Montreal, PQ, Canada.
[Tan, Seang Lin] Montreal Reprod Ctr, Montreal, PQ, Canada.
[Tan, Seang Lin] McGill Univ, Montreal, PQ, Canada.
[Veiga, Anna] Ctr Regenerat Med, Inst Univ Dexeus, Barcelona, Spain.
[Alikani, Mina] Tyho Galileo Res Labs, Livingston, NJ USA.
[Beard, Helen K.] ESHRE Journals Editorial Off, Childerley, Cambs, England.
[Ben-Shlomo, Izhar] Zefat Acad Coll, Safed, Israel.
[De Jonge, Christopher] Univ Minnesota, Reprod Med Ctr, Dept Ob Gyn & Womens Hlth, Minneapolis, MN 55455 USA.
[De Jonge, Christopher] Univ Minnesota, Reprod Med Ctr, Lab Operat, Minneapolis, MN 55455 USA.
[Eichenlaub-Ritter, Ursula] Univ Bielefeld, D-33615 Bielefeld, Germany.
[Gerris, Jan] Univ Hosp Ghent, Ctr Reprod Med, Dept Ob Gyn, Sector Man Woman & Child, Ghent, Belgium.
[Nielsen, H. Ingolf] Aarhus Univ, Aalborg Hosp, Dronninglund Fertil Ctr, DK-8000 Aarhus C, Denmark.
[Oehninger, Sergio] Eastern Virginia Med Sch, Jones Inst Reprod Med, Norfolk, VA 23501 USA.
[Patrizio, Pasquale] Yale Fertil Ctr, New Haven, CT USA.
[Paulson, Richard J.] Univ So Calif, Keck Sch Med, Div Reprod Endocrinol & Infertil, Los Angeles, CA 90033 USA.
[Polak de Fried, Ester] Univ Buenos Aires, CER Ctr Reprod Hlth, RA-1053 Buenos Aires, DF, Argentina.
[Risquez, Francisco] Ctr Med Docente Trinidad, Caracas, Venezuela.
[Sauer, Mark V.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Sciarra, John J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Basuray, Rita] Univ Kentucky, Lexington, KY USA.
[Boiso, Irene] Clin Sagrada Familia, Ctr Reprod Asistida, Barcelona, Spain.
[Bose, Chinmoy K.] Netaji Subhash Chandra Bose Canc Res Inst, Kolkata, India.
[Cryan, Bob] Univ Huddersfield, Huddersfield HD1 3DH, W Yorkshire, England.
[Falconer, Anthony] Royal Coll Obstet & Gynaecol, London, England.
[Hansis, Christoph] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10003 USA.
[Ko, Minoru S. H.] NIA, Dev Genom & Ageing Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Loeffler, Frank] St Marys Hosp, London, England.
[Loeffler, Frank] Queen Charlottes Matern Hosp, London, England.
[Ludwig, Michael] Endokrinologikum Hamburg, Hamburg, Germany.
[Magli, M. Cristina] SISMER, Bologna, Italy.
[Robertson, John A.] Univ Texas Austin, Sch Law, Austin, TX 78712 USA.
[Thornhill, A.] Bridge Genoma Ltd, London, England.
[Wallberg-Henriksson, Harriet] Karolinska Inst, S-10401 Stockholm, Sweden.
RI Ockleford, Colin/A-2921-2009; Tan, Seang Lin/I-7710-2012; Ko,
Minoru/B-7969-2009; Sauer, Markus/C-4378-2017
OI Ko, Minoru/0000-0002-3530-3015; Sauer, Markus/0000-0002-1692-3219
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1472-6483
EI 1472-6491
J9 REPROD BIOMED ONLINE
JI Reprod. Biomed. Online
PD JUL
PY 2011
VL 23
SU S
BP 1
EP 98
PG 98
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 929FY
UT WOS:000303047900001
ER
PT J
AU Konda, K
Celentano, D
Kegeles, S
Coates, T
Caceres, C
AF Konda, K.
Celentano, D.
Kegeles, S.
Coates, T.
Caceres, C.
CA NIMHCollaborative HIV STD Preventi
TI LATENT CLASS ANALYSIS OF SEXUAL RISK PATTERNS AMONG
HETEROSEXUALLY-IDENTIFIED, SOCIALLY MARGINALISED MEN IN URBAN, COASTAL
PERU
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Konda, K.; Coates, T.] Univ Calif Los Angeles, Lima, Peru.
[Celentano, D.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Kegeles, S.] UCSF, San Francisco, CA USA.
[NIMHCollaborative HIV STD Preventi] NIMH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2011
VL 87
SU 1
BP A237
EP A237
DI 10.1136/sextrans-2011-050108.321
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA 926ZQ
UT WOS:000302874201216
ER
PT J
AU Konda, K
Lescano, A
Celentano, D
Maiorana, A
Salazar, X
Rosasco, AM
Montano, S
Kochel, T
Hall, E
Coates, T
Caceres, C
Kegeles, S
AF Konda, K.
Lescano, A.
Celentano, D.
Maiorana, A.
Salazar, X.
Rosasco, A. M.
Montano, S.
Kochel, T.
Hall, E.
Coates, T.
Caceres, C.
Kegeles, S.
CA NIMH Collaborative HIV STD
TI IMPACT OF A COMMUNITY LEVEL, DIFFUSION BASED HIV/STI INTERVENTION ON
HETEROSEXUALLY-IDENTIFIED, SOCIALLY MARGINALISED MEN IN URBAN, COASTAL
PERU
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Meeting Abstract
C1 [Konda, K.; Coates, T.] Univ Calif Los Angeles, Lima, Peru.
[Lescano, A.; Montano, S.; Kochel, T.; Hall, E.] NAMRU 6, Callao, Peru.
[Celentano, D.] Johns Hopkins Univ, Baltimore, MD USA.
[Maiorana, A.; Kegeles, S.] UCSF, San Francisco, CA USA.
[Salazar, X.; Rosasco, A. M.; Caceres, C.] UPCH, Lima, Peru.
[NIMH Collaborative HIV STD] NIMH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUL
PY 2011
VL 87
SU 1
BP A214
EP A215
DI 10.1136/sextrans-2011-050108.269
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA 926ZQ
UT WOS:000302874201165
ER
PT J
AU Fawcett, J
AF Fawcett, Jan
TI THIS ISSUE: The Conundrum of Bipolar Depression
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
ID QUETIAPINE MONOTHERAPY; ANTIDEPRESSANT USE; DOUBLE-BLIND; STEP-BD;
DISORDER; EFFICACY
C1 [Fawcett, Jan] Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA.
[Fawcett, Jan] Rush Med Coll, Dept Psychiat, Chicago, IL 60612 USA.
[Fawcett, Jan] NIMH, Ctr Clin, Rockville, MD USA.
[Fawcett, Jan] Amer Psychiat Assoc, Practice Guidelines Comm Assessment & Management, Washington, DC 20005 USA.
[Fawcett, Jan] DSM V Mood Disorders Task Force, Arlington, VA USA.
NR 13
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD JUL
PY 2011
VL 41
IS 7
BP 333
EP 335
DI 10.3928/00485713-20110627-01
PG 3
WC Psychiatry
SC Psychiatry
GA 885HB
UT WOS:000299768500001
ER
PT J
AU Hopf, FW
Seif, T
Bonci, A
AF Hopf, F. Woodward
Seif, Taban
Bonci, Antonello
TI The SK channel as a novel target for treating alcohol use disorders
SO CHANNELS
LA English
DT Editorial Material
DE SK channel; nucleus accumbens; alcohol use disorder; action potential;
waveform
ID ACTIVATED POTASSIUM CHANNEL; NUCLEUS-ACCUMBENS NEURONS; CA2+-ACTIVATED
K+ CHANNELS; COCAINE WITHDRAWAL; IN-VITRO; CONDUCTANCE; PLASTICITY;
CURRENTS; REINFORCEMENT; EXCITABILITY
AB We recently described the SK-type potassium channel as a novel target for treatment of excessive alcohol intake.(1) SK channel function is reduced in the nucleus accumbens (NAcb) core in rats consuming alcohol under intermittent (IAA) but not continuous (CAA) access, and the FDA-approved SK activator chlorzoxazone reduces the excessive alcohol intake in IAA rats but not the more moderate intake in CAA rats. Here, we discuss the implications of these and related findings for SK as a treatment for alcohol use disorders. In addition, we report that many NAcb core electrophysiological parameters related to action potential waveform or basal parameters were not altered in alcohol-drinking rats. These results are in strong contrast to those reported for cocaine, where several NAcb ion channels show adaptations after cocaine exposure. These results suggest that alcohol intake is associated with only limited ion channel neuro-adaptations in the NAcb relative to cocaine, and support the hypothesis that SK represents a selective and potent intervention to reduce excessive alcohol intake.
C1 [Hopf, F. Woodward; Seif, Taban; Bonci, Antonello] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94143 USA.
[Hopf, F. Woodward; Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Bonci, Antonello] NIDA Intramural Program, Bethesda, MD USA.
RP Hopf, FW (reprint author), Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94143 USA.
EM woody@gallo.ucsf.edu
NR 34
TC 5
Z9 5
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6950
J9 CHANNELS
JI Channels
PD JUL-AUG
PY 2011
VL 5
IS 4
BP 289
EP 292
DI 10.4161/chan.5.4.16577
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 878NA
UT WOS:000299262600001
PM 21712648
ER
PT J
AU Botelho, MC
Machado, JC
Brindley, PJ
da Costa, JMC
AF Botelho, Monica Catarina
Machado, Jose Carlos
Brindley, Paul J.
Correia da Costa, Jose Manuel
TI Targeting molecular signaling pathways of Schistosoma haematobium
infection in bladder cancer
SO VIRULENCE
LA English
DT Review
DE Schistosoma haematobium; urinary schistosomiasis; squamous cell
carcinoma of the bladder; CHO cells; carcinogenesis-associated
phenotypes; animal models; Kras mutations; estrogenic DNA adducts
ID ESTROGEN-RECEPTOR-ALPHA; RURAL ZIMBABWEAN WOMEN; NUCLEIC-ACID ADDUCTS;
IN-VITRO; FIBROBLAST PROLIFERATION; TRANSCRIPTIONAL ACTIVITY; GENITAL
SCHISTOSOMIASIS; URINARY SCHISTOSOMIASIS; MURINE SCHISTOSOMIASIS;
MANSONI EGGS
AB Since 1911 epidemiological evidence indicates that S. haematobium is associated to squamous cell carcinoma of the bladder. However, the mechanisms of this interaction are not clearly defined. Using normal epithelial cells, S. haematobium parasite extracts were able to induce cancer-like phenotypes such as proliferation, apoptosis, migration, invasion and tumorigenesis. The parasite extracts on normal urothelium also presented carcinogenic and mutagenic ability. To further elucidate the biological effects of this parasite, new estrogenic molecules were identified in its extracts. These estrogens are also present in the sera of Schistosoma-infected patients, and they have the ability to repress ER transcriptional activity both in estrogen responsive MCF7 cells and normal urothelial HCV29 cells. This review will present some of the recent studies of mass spectrometry of S. haematobium extracts and sequence analysis of bladder tissue treated with the same extracts. Finally the molecular and cellular events that might be responsible for schistosomiasis-related bladder cancer will be discussed.
C1 [Botelho, Monica Catarina; Correia da Costa, Jose Manuel] Natl Inst Hlth, CIBP, Bethesda, MD 20892 USA.
[Botelho, Monica Catarina; Machado, Jose Carlos] Univ Porto, IPATIMUP Inst Pathol & Mol Immunol, P-4100 Oporto, Portugal.
[Machado, Jose Carlos] Univ Porto, FMUP Fac Med, P-4100 Oporto, Portugal.
[Correia da Costa, Jose Manuel] Univ Porto, CECA Ctr Study Anim Sci, P-4100 Oporto, Portugal.
[Brindley, Paul J.] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
RP Botelho, MC (reprint author), Natl Inst Hlth, CIBP, Bethesda, MD 20892 USA.
EM monicabotelho@hotmail.com
RI Machado, Jose Carlos/C-5907-2009; Botelho, Monica/E-7170-2014
OI Machado, Jose Carlos/0000-0003-4741-8415; Botelho,
Monica/0000-0003-0466-8465
NR 94
TC 25
Z9 25
U1 0
U2 11
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2150-5594
J9 VIRULENCE
JI Virulence
PD JUL-AUG
PY 2011
VL 2
IS 4
BP 267
EP 279
DI 10.4161/viru.2.4.16734
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 878LB
UT WOS:000299257400003
PM 21788729
ER
PT J
AU Killian, JK
Bilke, S
Davis, S
Walker, RL
Jaeger, E
Killian, MS
Waterfall, JJ
Bibikova, M
Fan, JB
Smith, WI
Meltzer, PS
AF Killian, J. Keith
Bilke, Sven
Davis, Sean
Walker, Robert L.
Jaeger, Erich
Killian, M. Scott
Waterfall, Joshua J.
Bibikova, Marina
Fan, Jian-Bing
Smith, William I., Jr.
Meltzer, Paul S.
TI A Methyl-Deviator Epigenotype of Estrogen Receptor-Positive Breast
Carcinoma Is Associated with Malignant Biology
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID DNA METHYLATION; CLINICAL-IMPLICATIONS; PROGNOSTIC VALUE; FOLLOW-UP;
CANCER; PATTERNS; SUBTYPE; ORIGIN; TAMOXIFEN; PROJECT
AB We broadly profiled DNA methylation in breast cancers (n = 351) and benign parenchyma (n = 47) for correspondence with disease phenotype, using FFPE diagnostic surgical pathology specimens. Exploratory analysis revealed a distinctive primary invasive carcinoma subclass featuring extreme global methylation deviation. Subsequently, we tested the correlation between methylation remodeling pervasiveness and malignant biological features. A methyl deviation index (MDI) was calculated for each lesion relative to terminal ductal-lobular unit baseline, and group comparisons revealed that high-grade and short-survival estrogen receptor-positive (ER) cancers manifest a significantly higher MDI than low-grade and long-survival ER(+) cancers. In contrast, ER(-) cancers display a significantly lower MDI, revealing a striking epigenomic distinction between cancer hormone receptor subtypes. Kaplan-Meier survival curves of MDI-based risk classes showed significant divergence between low- and high-risk groups. MDI showed superior prognostic performance to crude methylation levels, and MDI retained prognostic significance (P < 0.01) in Cox multivariate analysis, including clinical stage and pathological grade. Most MDI targets individually are significant markers of ER(+) cancer survival. Lymphoid and mesenchymal indexes were not substantially different between ER(+) and ER(-) groups and do not explain MDI dichotomy. However, the mesenchymal index was associated with ER(+) cancer survival, and a high lymphoid index was associated with medullary carcinoma. Finally, a comparison between metastases and primary tumors suggests methylation patterns are established early and maintained through disease progression for both ER + and ER- tumors. (Am J Pathol 2011, 179:55-65; DOI: 10.1016/j.ajpath.2011.03.022)
C1 [Killian, J. Keith; Bilke, Sven; Davis, Sean; Walker, Robert L.; Waterfall, Joshua J.; Meltzer, Paul S.] NCI, Genet Branch, Bethesda, MD 20892 USA.
[Jaeger, Erich; Bibikova, Marina; Fan, Jian-Bing] Illumina Inc, San Francisco, CA USA.
[Killian, M. Scott] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Smith, William I., Jr.] Suburban Hosp, Dept Pathol, Bethesda, MD USA.
RP Meltzer, PS (reprint author), NCI, Genet Branch, 37 Convent Dr,Room 6138, Bethesda, MD 20892 USA.
EM pmeltzer@mail.nih.gov
OI Davis, Sean/0000-0002-8991-6458
FU NIH
FX Supported primarily by NIH intramural funding.
NR 34
TC 9
Z9 9
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUL
PY 2011
VL 179
IS 1
BP 55
EP 65
DI 10.1016/j.ajpath.2011.03.022
PG 11
WC Pathology
SC Pathology
GA 865JL
UT WOS:000298307100007
PM 21641572
ER
PT J
AU Martin, P
Liu, YN
Pierce, R
Abou-Kheir, W
Casey, O
Seng, V
Camacho, D
Simpson, RM
Kelly, K
AF Martin, Philip
Liu, Yen-Nien
Pierce, Rachel
Abou-Kheir, Wassim
Casey, Orla
Seng, Victoria
Camacho, Daniel
Simpson, R. Mark
Kelly, Kathleen
TI Prostate Epithelial Pten/TP53 Loss Leads to Transformation of
Multipotential Progenitors and Epithelial to Mesenchymal Transition
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID INITIATING CELLS; STEM-CELL; IN-VIVO; CANCER; P53; SENESCENCE; DELETION;
DIFFERENTIATION; CARCINOMA; PATTERNS
AB Loss of PTEN and loss of TP53 are common genetic aberrations occurring in prostate cancer. PTEN and TP53 contribute to the regulation of self-renewal and differentiation in prostate progenitors, presumptive tumor initiating cells for prostate cancer. Here we characterize the transformed phenotypes resulting from deletion of the Pten and TP53 tumor suppressors in prostate epithelium. Using the PB-Cre4(+) Pten(fl/fl) TP53(fl/fl) model of prostate cancer, we describe the histological and metastatic properties of primary tumors, transplanted primary tumor cells, and clonal cell lines established from tumors. Adenocarcinoma was the major primary tumor type that developed, which progressed to lethal sarcomatoid carcinoma at approximately 6 months of age. In addition, basal carcinomas and prostatic urothelial carcinomas were observed. We show that tumor heterogeneity resulted, at least in part, from the transformation of multipotential progenitors. CK8+ luminal epithelial cells were capable of undergoing epithelial to mesenchymal transition in vivo to sarcomatoid carcinomas containing osseous metaplasia. Metastasis rarely was observed from primary tumors, but metastasis to lung and lymph nodes occurred frequently from orthotopic tumors initiated from a biphenotypic clonal cell line. Androgen deprivation influenced the differentiated phenotypes of metastases. These data show that one functional consequence of Pten/TP53 loss in prostate epithelium is lineage plasticity of transformed cells. (Am J Pathol 2011, 179:422-435; DOI: 10.1016/j.ajpath.2011.03.035)
C1 [Martin, Philip; Liu, Yen-Nien; Pierce, Rachel; Abou-Kheir, Wassim; Casey, Orla; Seng, Victoria; Camacho, Daniel; Kelly, Kathleen] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA.
[Simpson, R. Mark] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kelly, K (reprint author), Bldg 37,Room 1068, Bethesda, MD 20892 USA.
EM kellyka@mail.nih.gov
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 30
TC 25
Z9 26
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUL
PY 2011
VL 179
IS 1
BP 422
EP 435
DI 10.1016/j.ajpath.2011.03.035
PG 14
WC Pathology
SC Pathology
GA 865JL
UT WOS:000298307100040
PM 21703421
ER
PT J
AU Zeng, CY
Du, YP
Alberico, T
Seeberger, J
Sun, XP
Zou, S
AF Zeng, Chaoyang
Du, Yanping
Alberico, Thomas
Seeberger, Jeanne
Sun, Xiaoping
Zou, Sige
TI Gender-specific prandial response to dietary restriction and oxidative
stress in Drosophila melanogaster
SO FLY
LA English
DT Article
DE food intake; excretion; aging; dietary restriction; oxidative stress
ID CALORIC RESTRICTION; LIFE-SPAN; FEEDING-BEHAVIOR; AGE; RADIOPHOSPHORUS;
EXPRESSION; LONGEVITY; MORTALITY; INSIGHTS; DAMAGE
AB Drosophila melanogaster is ideal for studying lifespan modulated by dietary restriction (DR) and oxidative stress, and also for screening prolongevity compounds. It is critical to measure food intake in the aforementioned studies. Current methods, however, overlook the amount of the food excreted out of the flies as feces or deposited in eggs. Here we describe a feeding method using a radioactive tracer to measure gender-specific food intake, retention and excretion in response to DR and oxidative stress to account for all the ingested food. Flies were fed a full, restricted or paraquat-containing diet. The radioactivity values of the food in fly bodies, feces and eggs were measured separately after a 24-hr feeding. Food intake was calculated as the sum of these measurements. We found that most of the tracer in the ingested food was retained in the fly bodies and <8% of the tracer was excreted out of the flies as feces and eggs in the case of females during a 24-hr feeding. Under a DR condition, flies increased food intake in volume to compensate for the reduction of calorie content in the diet and also slightly increased excretion. Under an oxidative stress condition, flies reduced both food intake and excretion. Under all the tested dietary conditions, males ingested and excreted 3- to 5-fold less food than females. This study describes an accurate method to measure food intake and provides a basis to further investigate prandial response to DR and prolongevity interve ntions in invertebrates.
C1 [Alberico, Thomas; Seeberger, Jeanne; Sun, Xiaoping; Zou, Sige] NIA, Funct Genom Unit, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Zeng, Chaoyang; Du, Yanping] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53201 USA.
RP Zou, S (reprint author), NIA, Funct Genom Unit, Lab Expt Gerontol, Baltimore, MD 21224 USA.
EM zous@grc.nia.nih.gov
FU National Institute on Aging, NIH; Shaw Scientist Foundation of Milwaukee
FX We thank Dr. Donald Ingram, Jason Sinclair and Dr. Toshimitsu Komatsu
for discussion, Sharron Daly for assistance with the radioactive
measurements and Drs. Kevin Pearson and Min Zhu for critical reading of
the manuscript. This study was funded by the Intramural Research Program
of the National Institute on Aging, NIH, to Sige Zou and the Shaw
Scientist Foundation of Milwaukee to Chaoyang Zeng.
NR 42
TC 6
Z9 6
U1 1
U2 7
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6934
J9 FLY
JI Fly
PD JUL-SEP
PY 2011
VL 5
IS 3
BP 174
EP 180
DI 10.4161/fly.5.3.15572
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 863QX
UT WOS:000298183400002
PM 21471736
ER
PT J
AU Velayati, A
Knight, MA
Stubblefield, BK
Sidransky, E
Tayebi, N
AF Velayati, Arash
Knight, Melanie A.
Stubblefield, Barbara K.
Sidransky, Ellen
Tayebi, Nahid
TI Identification of Recombinant Alleles Using Quantitative Real-Time PCR
Implications for Gaucher Disease
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID GLUCOCEREBROSIDASE GENE; PSEUDOGENE; MUTATION; METAXIN; REGION; N370S
AB Pseudogenes, resulting from duplications of functional genes, contribute to the functional complexity of their parental genes. The glucocerebrosidase gene (GBA), located in a gene-rich region on chromosome 1q 21, is mutated in Gaucher disease. The presence of contiguous, highly homologous pseudogenes for both GBA and metaxin 1 at this locus increases the likelihood of DNA rearrangement. We describe a facile method to identify and analyze recombinant alleles in patients with Gaucher disease. Genomic DNA from 20 patients with recombinant GBA alleles and five controls was evaluated to identify DNA rearrangements or copy number variation using six probes specific for either the GBA gene or pseudogene. Quantitative real-time PCR was performed on genomic DNA, and Southern blot analyses using HincII together with sequencing confirmed the real-time results. Both GBA fusions and duplications could be detected. Different sites of crossover were identified, and alleles resulting from gene conversion could be distinguished from reciprocal recombinant alleles. Quantitative real-time PCR is a sensitive and rapid method to detect fusions and duplications in patients with recombinant GBA alleles. This technique is more sensitive, faster, and cheaper than Southern blot analysis, and can be used in diagnostic laboratories, and to detect other recombinant alleles within the genome. (J Mol Diagn 2011, 13:401-405; DOI: 10.1016/j.jmoldx.2011.02.005)
C1 [Velayati, Arash; Knight, Melanie A.; Stubblefield, Barbara K.; Sidransky, Ellen; Tayebi, Nahid] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Division of Intramural Research of the National Human Genome Research
Institute; National Institutes of Health
FX Supported by the Division of Intramural Research of the National Human
Genome Research Institute, and the National Institutes of Health.
NR 13
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD JUL
PY 2011
VL 13
IS 4
BP 401
EP 405
DI 10.1016/j.jmoldx.2011.02.005
PG 5
WC Pathology
SC Pathology
GA 865JF
UT WOS:000298306500007
PM 21704274
ER
PT J
AU Hosey, G
Ichiho, H
Satterfield, D
Dankwa-Mullan, I
Kuartei, S
Rhee, K
Belyeu-Camacho, T
Debrum, I
Demei, Y
Lippwe, K
Luces, PS
Roby, F
AF Hosey, Gwen
Ichiho, Henry
Satterfield, Dawn
Dankwa-Mullan, Irene
Kuartei, Stevenson
Rhee, Kyu
Belyeu-Camacho, Tayna
deBrum, Ione
Demei, Yorah
Lippwe, Kipier
Luces, Patrick Solidum
Roby, Faiese
TI Chronic Disease Surveillance Systems Within the US Associated Pacific
Island Jurisdictions
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
AB In recent years, illness and death due to chronic disease in the US Associated Pacific Islands (USAPI) jurisdictions have dramatically increased. Effective chronic disease surveillance can help monitor disease trends, evaluate public policy, prioritize resource allocation, and guide program planning, evaluation, and research. Although chronic disease surveillance is being conducted in the USAPI, no recently published capacity assessments for chronic disease surveillance are available. The objective of this study was to assess the quality of existing USAPI chronic disease data sources and identify jurisdictional capacity for chronic disease surveillance. The assessment included a chronic disease data source inventory, literature review, and review of surveillance documentation available from the web or through individual jurisdictions. We used the World Health Organization's Health Metric Network Framework to assess data source quality and to identify jurisdictional capacity. Results showed that USAPI data sources are generally aligned with widely accepted chronic disease surveillance indicators and use standardized data collection methodology to measure chronic disease behavioral risks, preventive practices, illness, and death. However, all jurisdictions need to strengthen chronic disease surveillance through continued assessment and expanded support for valid and reliable data collection, analysis and reporting, dissemination, and integration among population-based and institution-based data sources. For sustained improvement, we recommend investment and technical assistance in support of a chronic disease surveillance system that integrates population-based and institution-based data sources. An integrated strategy that bridges and links USAPI data sources can support evidence-based policy and population health interventions.
C1 [Ichiho, Henry] Pacific Diabet Educ Program, Honolulu, HI USA.
[Satterfield, Dawn] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Dankwa-Mullan, Irene] Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD USA.
[Kuartei, Stevenson] Minist Hlth, Koror, Palau.
[Rhee, Kyu] Hlth Resources & Serv Adm, Rockville, MD USA.
RP Hosey, G (reprint author), Ctr Dis Control & Prevent, 4150 Technol Way,Ste 210, Carson City, NV 89706 USA.
EM ghh0@cdc.gov
FU Nia Aitaoto and Dorraine Watts
FX We thank the following Pacific Island representatives who contributed to
this project: Tuiasina Salamo Laumoli, Dottie Siavii, and Pasa Turituri,
American Samoa; Joseph K. Villagomez, Rebecca Ann Covarrubias, Isidro
Ogarto, John Tagabuel, Commonwealth of the Northern Mariana Islands;
Vita A. Skilling, Marcus Samo, Shra Alik, and Brenda Hadley Eperiam,
Federated States of Micronesia; J. Peter Roberto, Roselie Zabala, and
Gil S. Suguitan, Guam; Amenta Matthew, Justina Langidrik, Donny Andrike,
and Godfrey Waidubu, Republic of the Marshall Islands; Augusta Rengiil,
Republic of Palau. We also recognize the contributions of Lawrence
Barker, Kaetz Beartusk, Michelle Carlberg, Gloria Colclough, Jack
Colbert, Ed Gregg, Ann Goding, Laura Kann, Juliette Lee, Veronica Lea,
Kristen McCall, Barbara Park, Karen Siener, Castine Verrill, Charles
Warren, and MaryBeth Welton, Centers for Disease Control and Prevention;
and Susan Tanner, End-Stage Renal Disease Network 17. Finally, we thank
Nia Aitaoto and Dorraine Watts for their support and encouragement
during this project.
NR 20
TC 3
Z9 3
U1 0
U2 1
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD JUL
PY 2011
VL 8
IS 4
AR A86
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 874OY
UT WOS:000298969100016
PM 21672410
ER
PT J
AU Beare, PA
Gilk, SD
Larson, CL
Hill, J
Stead, CM
Omsland, A
Cockrell, DC
Howe, D
Voth, DE
Heinzen, RA
AF Beare, Paul A.
Gilk, Stacey D.
Larson, Charles L.
Hill, Joshua
Stead, Christopher M.
Omsland, Anders
Cockrell, Diane C.
Howe, Dale
Voth, Daniel E.
Heinzen, Robert A.
TI Dot/Icm Type IVB Secretion System Requirements for Coxiella burnetii
Growth in Human Macrophages
SO MBIO
LA English
DT Article
ID LEGIONELLA-PNEUMOPHILA; HOST-CELL; Q-FEVER; PARASITOPHOROUS VACUOLES;
THP-1 CELLS; LEISHMANIA; PROTEIN; IDENTIFICATION; PHAGOLYSOSOME;
APOPTOSIS
AB Central to Q fever pathogenesis is replication of the causative agent, Coxiella burnetii, within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear phagocytes. C. burnetii modulates PV biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a Dot/Icm type IVB secretion system (T4BSS). In this study, we utilized a C. burnetii strain carrying IcmD inactivated by the Himar1 transposon to investigate the requirements for Dot/Icm function in C. burnetii parasitism of human THP-1 macrophage-like cells. The icmD::Tn mutant failed to secrete characterized T4BSS substrates, a defect that correlated with deficient replication, PV development, and apoptosis protection. Restoration of type IVB secretion and intracellular growth of the icmD:: Tn mutant required complementation with icmD, -J, and -B, indicating a polar effect of the transposon insertion on downstream dot/icm genes. Induction of icmDJB expression at 1 day postinfection resulted in C. burnetii replication and PV generation. Collectively, these data prove that T4BSS function is required for productive infection of human macrophages by C. burnetii. However, illustrating the metabolic flexibility of C. burnetti, the icmD:: Tn mutant could replicate intracellularly when sequestered in a PV generated by wild-type bacteria, where Dot/Icm function is provided in trans, and within a phenotypically similar PV generated by the protozoan parasite Leishmania amazonensis, where host cells are devoid of Dot/Icm T4BSS effector proteins.
IMPORTANCE Coxiella burnetii, the cause of human Q fever, is the only bacterial pathogen known to replicate in a vacuole resembling a phagolysosome. The organism manipulates host macrophages to promote the biogenesis of a vacuolar compartment permissive for growth. By analogy to the well-established cellular microbiology of Legionella pneumophila, the Dot/Icm type IVB secretion system of C. burnetii is implicated as a critical virulence factor in host cell modification that delivers proteins with effector functions directly into the host cell cytosol. Using new genetic tools, we verify that Dot/Icm function is essential for productive infection of human macrophages by C. burnetii. Interestingly, despite the production of homologous secretion systems, L. pneumophila and C. burnetii have strikingly different temporal requirements for Dot/Icm function during their respective infectious cycles.
C1 [Beare, Paul A.; Gilk, Stacey D.; Larson, Charles L.; Hill, Joshua; Stead, Christopher M.; Omsland, Anders; Cockrell, Diane C.; Howe, Dale; Heinzen, Robert A.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, Hamilton, MT 59840 USA.
[Voth, Daniel E.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA.
RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, Hamilton, MT 59840 USA.
EM rheinzen@niaid.nih.gov
FU National Institutes of Health (NIH), National Institute of Allergy and
Infectious Diseases (NIAID) [R01AI087669]
FX This work was supported by funding from the National Institutes of
Health (NIH), National Institute of Allergy and Infectious Diseases
(NIAID) grant R01AI087669 (D. E. V.), and the Intramural Research
Program of the NIH, NIAID (R.A.H.).
NR 50
TC 71
Z9 71
U1 1
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2011
VL 2
IS 4
AR e00175-11
DI 10.1128/mBio.00175-11
PG 10
WC Microbiology
SC Microbiology
GA 845SX
UT WOS:000296844000021
PM 21862628
ER
PT J
AU Csiszovszki, Z
Krishna, S
Orosz, L
Adhya, S
Semsey, S
AF Csiszovszki, Zsolt
Krishna, Sandeep
Orosz, Laszlo
Adhya, Sankar
Semsey, Szabolcs
TI Structure and Function of the D-Galactose Network in Enterobacteria
SO MBIO
LA English
DT Article
ID ESCHERICHIA-COLI; YERSINIA-PESTIS; REGULATORY NETWORKS; GAL
TRANSCRIPTION; GENE-EXPRESSION; LIPOPOLYSACCHARIDE; REPRESSOR; PROTEIN;
OPERON; DNA
AB Galactose is important for the survival and virulence of bacteria. In Escherichia coli, galactose is utilized by the Leloir pathway, which is controlled by a complex network. To shed light on the potential functions the galactose network could perform, we performed bioinformatical analysis of reference genome sequences belonging to the Enterobacteriaceae family. We found that several genomes have reduced numbers of components compared to the E. coli galactose system, suggesting that the network can be optimized for different environments. Typically, genes are removed by deletions; however, in Yersinia pestis, the galactose mutarotase (galM) gene is inactivated by a single-base-pair deletion. Lack of GalM activity indicates that the two anomers of D-galactose are used for different purposes, alpha-D-galactose as a carbon source and beta-D-galactose for induction of UDP-galactose synthesis for biosynthetic glycosylation. We demonstrate that activity of the galM gene can be restored by different single-base-pair insertions. During the evolution of Y. pestis to become a vector-transmitted systemic pathogen, many genes were converted to pseudogenes. It is not clear whether pseudogenes are present to maintain meiotrophism or are in the process of elimination. Our results suggest that the galM pseudogene has not been deleted because its reactivation may be beneficial in certain environments.
IMPORTANCE Evolution of bacteria to populate a new environment necessarily involves reengineering of their molecular network. Members of the Enterobacteriaceae family of bacteria have diverse lifestyles and can function in a wide range of environments. In this study we performed bioinformatical analysis of 34 reference genome sequences belonging to the Enterobacteriaceae family to gain insight into the natural diversity of the D-galactose utilization network. Our bioinformatical analysis shows that in several species, some genes of the network are completely missing or are inactivated by large deletions. The only exception is the galactose mutarotase (galM) gene of Yersinia pestis, which is converted to a pseudogene by a single-base-pair deletion. In this paper, we discuss the possible consequences of galM inactivation on network function. We suggest that galM was converted to a pseudogene rather than being deleted in evolution because its reactivation can be beneficial in certain environments.
C1 [Orosz, Laszlo; Semsey, Szabolcs] Eotvos Lorand Univ, Dept Genet, Budapest, Hungary.
[Csiszovszki, Zsolt; Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Krishna, Sandeep] NCBS, Bangalore, Karnataka, India.
[Semsey, Szabolcs] Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
RP Semsey, S (reprint author), Eotvos Lorand Univ, Dept Genet, Budapest, Hungary.
EM semsey@nbi.dk
RI Semsey, Szabolcs/L-6329-2013;
OI Semsey, Szabolcs/0000-0002-4522-5495
FU Hungarian Scientific Research Fund (OTKA) [PD75496]; Danish Council for
Independent ResearchpipeNatural Sciences; NIH, National Cancer
Institute, Center for Cancer Research, United States; Danish National
Research Foundation
FX This research was supported by the Hungarian Scientific Research Fund
(OTKA) grant PD75496 to S. S., by the Danish Council for Independent
Research vertical bar Natural Sciences, by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research, United States, and by the Danish National Research Foundation.
NR 43
TC 3
Z9 4
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2011
VL 2
IS 4
AR e00053-11
DI 10.1128/mBio.00053-11
PG 8
WC Microbiology
SC Microbiology
GA 845SX
UT WOS:000296844000003
PM 21712421
ER
PT J
AU Srikantan, S
Gorospe, M
AF Srikantan, Subramanya
Gorospe, Myriam
TI Altered glycobiology of stem cells linked to age-related osteoarthritis
SO AGING-US
LA English
DT Article
C1 [Srikantan, Subramanya; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
OI srikantan, subramanya/0000-0003-1810-6519
NR 5
TC 0
Z9 0
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JUL
PY 2011
VL 3
IS 7
BP 663
EP 664
PG 2
WC Cell Biology
SC Cell Biology
GA 845AU
UT WOS:000296796000001
PM 21808096
ER
PT J
AU Warwick, MT
AF Warwick, Margaret Turner
TI Clinical leadership and management in the NHS
SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE
LA English
DT Editorial Material
C1 [Warwick, Margaret Turner] Natl Heart & Lung Inst, Bethesda, MD USA.
[Warwick, Margaret Turner] Royal Brompton Hosp, Brompton, England.
[Warwick, Margaret Turner] Royal Coll Phys, Ottawa, ON, Canada.
[Warwick, Margaret Turner] Royal Devon & Exeter Healthcare Trust, Board Governors, Devon, England.
RP Warwick, MT (reprint author), Natl Heart & Lung Inst, Bethesda, MD USA.
EM m@turnerwarwick.eclipse.co.uk
NR 3
TC 1
Z9 1
U1 0
U2 2
PU ROYAL SOC MEDICINE PRESS LTD
PI LONDON
PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND
SN 0141-0768
J9 J ROY SOC MED
JI J. R. Soc. Med.
PD JUL
PY 2011
VL 104
IS 7
BP 308
EP 309
DI 10.1258/jrsm.2011.110105
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 839WL
UT WOS:000296400100010
ER
PT J
AU Wickner, RB
Edskes, HK
Kryndushkin, D
McGlinchey, R
Bateman, D
Kelly, A
AF Wickner, Reed B.
Edskes, Herman K.
Kryndushkin, Dmitry
McGlinchey, Ryan
Bateman, David
Kelly, Amy
TI Prion diseases of yeast: Amyloid structure and biology
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE Prion
ID HET-S PRION; BETA-SHEET STRUCTURE; SOLID-STATE NMR;
SACCHAROMYCES-CEREVISIAE; TRANSLATION TERMINATION; IN-VITRO;
HETEROKARYON INCOMPATIBILITY; ENVIRONMENTAL-STRESS; PODOSPORA-ANSERINA;
POLAR ZIPPERS
AB Prion "variants" or "strains" are prions with the identical protein sequence, but different characteristics of the prion infection: e. g. different incubation periods for scrapie strains or different phenotype intensities for yeast prion variants. We have shown that infectious amyloids of the yeast prions [PSI+], [URE3] and [PIN+] each have an in-register parallel beta-sheet architecture. Moreover, we have pointed out that this amyloid architecture can explain how one protein can faithfully transmit any of several conformations to new protein monomers. This explains how proteins can be genes. Published by Elsevier Ltd.
C1 [Wickner, Reed B.; Edskes, Herman K.; Kryndushkin, Dmitry; McGlinchey, Ryan; Bateman, David; Kelly, Amy] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
FU National Institute of Diabetes Digestive and Kidney Diseases
FX This work was supported by the Intramural Program of the National
Institute of Diabetes Digestive and Kidney Diseases.
NR 87
TC 19
Z9 19
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD JUL
PY 2011
VL 22
IS 5
BP 469
EP 475
DI 10.1016/j.semcdb.2011.02.021
PG 7
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 839JF
UT WOS:000296360800006
PM 21345375
ER
PT J
AU Lee, KA
Lee, SM
Yang, HJ
Park, CW
Mazaki-Tovi, S
Yoon, BH
Romero, R
AF Lee, Kyung A.
Lee, Seung Mi
Yang, Hye Jin
Park, Chan-Wook
Mazaki-Tovi, Shali
Yoon, Bo Hyun
Romero, Roberto
TI The frequency of meconium-stained amniotic fluid increases as a function
of the duration of labor
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Fetal bowel function; first stage of labor; pregnancy
ID PRETERM PREMATURE RUPTURE; ACID-BASE STATUS; IN-UTERO DEFECATION;
INTRAAMNIOTIC INFECTION/INFLAMMATION; ASPIRATION SYNDROME; NEONATAL
OUTCOMES; PROLONGED 2ND-STAGE; PRELABOR RUPTURE; GESTATIONAL-AGE; FETAL
MEMBRANES
AB Methods. aEuro integral The clinical characteristics of women who delivered term singleton live newborns between 2001 and 2006 were examined. The cases involving neonates with major congenital anomalies were excluded.
Results. aEuro integral(1) The frequency of MSAF in term pregnancies was 18.4%% (806/4376); (2) MSAF was found in only 2.8%% (28/1008) of women who delivered by elective cesarean, but in 23.1%% (778/3368) of women who delivered after the onset of labor (p aEuroS < aEuroS0.001); (3) The longer the duration of labor (first stage, second stage, or total), the higher the frequency of MSAF (p aEuroS < aEuroS0.001 for each); this remained significant after adjusting for other confounding variables such as parity, duration of rupture of membranes, gestational age at delivery, and mode of delivery (p aEuroS < aEuroS0.001 for each).
Conclusion. aEuro integral MSAF was found in only 2.8%% (28/1008) of women who delivered before the onset of labor, but in 23.1%% (778/3368) of women who delivered after the onset of labor. The longer the duration of labor, the higher the risk of MSAF in term singleton gestation.
C1 [Lee, Kyung A.; Lee, Seung Mi; Yang, Hye Jin; Park, Chan-Wook; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
[Mazaki-Tovi, Shali; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea.
EM yoonbh@snu.ac.kr
RI Yoon, Bo Hyun/H-6344-2011; Park, Chan-Wook/J-5498-2012
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported, in part, by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH, DHHS.
NR 58
TC 11
Z9 13
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD JUL
PY 2011
VL 24
IS 7
BP 880
EP 885
DI 10.3109/14767058.2010.531329
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 772FY
UT WOS:000291220900002
PM 21410421
ER
PT J
AU Schroeder, JL
Bakalar, M
Pohida, TJ
Balaban, RS
AF Schroeder, J. L.
Bakalar, M.
Pohida, T. J.
Balaban, R. S.
TI Rapid overlapping-volume acquisition and reconstruction (ROVAR):
automated 3D tiling for high-resolution, large field-of-view optical
microscopy
SO JOURNAL OF MICROSCOPY
LA English
DT Article
DE Automation; in vivo; multiphoton; stitching; volume; 3D
ID IN-VIVO; MULTIPHOTON
AB Micrometer-scale three-dimensional data from fluorescence microscopes oiler unique insight into cellular morphology and function by resolving subcellular locations of fluorescent dyes and proteins. To increase field-of-view size while using a high-resolution multiphoton microscope, we have created an automated system of rapidly acquiring overlapping image stacks from multiple fields-of-view along a nonplanar tissue surface. Each image stack is acquired only between the surface and the maximal penetrating depth. as determined by the image signal-to-background ratio. This results in the acquisition of the volume containing visible tissue along the tissue surface, excluding the empty volume above the tissue and the volume beyond the maximum imaging depth within the tissue. The automated collection of overlapping volumes is Followed by reconstruction that can efficiently generate a single three-dimensional volume of the tissue surface. This approach yields data spanning multiple millimetres at micrometre resolution that is faster while requiring less work from the microscope operator. The advantages of the system are demonstrated by acquisition of data from intact, unfixed organs without a coverglass both in vivo and in situ.
C1 [Schroeder, J. L.; Balaban, R. S.] NHLBI, Cardiac Energet Lab, Bethesda, MD USA.
[Bakalar, M.; Pohida, T. J.] NIH, CIT, Div Computat Biosci, Bethesda, MD USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, Bethesda, MD USA.
EM balabanr@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 12
TC 6
Z9 6
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-2720
J9 J MICROSC-OXFORD
JI J. Microsc..
PD JUL
PY 2011
VL 243
IS 1
BP 103
EP 110
DI 10.1111/j.1365-2818.2011.03490.x
PG 8
WC Microscopy
SC Microscopy
GA 788XT
UT WOS:000292478400010
PM 21348869
ER
PT J
AU Graves, RE
Freedy, JR
Aigbogun, NU
Lawson, WB
Mellman, TA
Alim, TN
AF Graves, Ruth Elaine
Freedy, John R.
Aigbogun, Notalelomwan U.
Lawson, William B.
Mellman, Thomas A.
Alim, Tanya N.
TI PTSD Treatment of African American Adults in Primary Care: The Gap
Between Current Practice and Evidence-Based Treatment Guidelines
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE posttraumatic stress disorder; African Americans; treatment; primary
care; mental health; collaborative care
ID POSTTRAUMATIC-STRESS-DISORDER; DISEASE MANAGEMENT PROGRAMS; NATIONAL
COMORBIDITY SURVEY; COLLABORATIVE CARE; ANXIETY DISORDERS; PHYSICAL
SYMPTOMS; MENTAL-DISORDERS; PANIC DISORDER; DEPRESSION; POPULATION
AB Background: Posttraumatic stress disorder (PTSD) is a common, potentially disabling, underdiagnosed, and undertreated illness. Primary care physicians assume a critical role in the diagnosis, treatment, and referral of African Americans with PTSD since mental health access is limited for this population. This study is an examination of PTSD treatment of African Americans in the primary care setting. Actual treatment provision is contrasted with existing evidence-based PTSD treatment guidelines.
Method: Researchers screened 738 consenting, mostly African American, adults in 4 academically affiliated primary care offices for both trauma exposure and mental health symptoms, including PTSD.
Results: Employing criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) (DSM-IV), investigators diagnosed 91 of the participants with current PTSD using the Structured Clinical Interview for DSM and the Clinician-Administered of PTSD Scale for DSM-IV. Treatment statistics include: 69.2% (n = 63) had never received treatment from a mental health provider; 18.6% (n = 17) were currently seeing a mental health practitioner; nearly half (47.9%, n = 24) of a subsample had never discussed traumatic event exposure or mental health symptoms with their primary care doctor; 32% (n = 29) were prescribed psychotropic medication and only 18.6% (n = 171 were participating in any form of psychotherapy. Concurrent psychiatric disorders were found in 46.2% (n = 42) of the participants with PTSD.
Conclusion: Most African American adult primary care patients with PTSD were either undiagnosed or undertreated in this inner-city setting. These results demonstrate a clear need to improve screening and treatment services. Both individual (provider and patient) and system-based changes will be required to meet the demonstrated clinical need.
C1 [Graves, Ruth Elaine] Howard Univ, Dept Community & Family Med, Washington, DC 20059 USA.
[Freedy, John R.] Med Univ S Carolina, Dept Family Med, Charleston, SC USA.
[Aigbogun, Notalelomwan U.] NCI, Frederick, MD 21701 USA.
RP Graves, RE (reprint author), Howard Univ Hosp, Psychiat Suite 5B,2041 Georgia Ave NW, Washington, DC 20060 USA.
EM RevElaineGraves@att.net
OI Lawson, William/0000-0002-9324-7090
FU National Institute of Mental Health [01-D1-007]; Howard University;
General Clinical Research Center from the National Institutes of Health
[2 MO 1 RR1024]
FX Funding for this study was made possible by a National Institute of
Mental Health contract (01-D1-007), a Howard University New Faculty
Research grant, and in part by a General Clinical Research Center grant
from the National Institutes of Health (2 MO 1 RR1024).
NR 60
TC 5
Z9 5
U1 1
U2 6
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD JUL
PY 2011
VL 103
IS 7
BP 585
EP 593
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 829SY
UT WOS:000295605800005
PM 21999033
ER
PT J
AU Wang, YM
Cheng, ZQ
ElAlieh, HZ
Nakamura, E
Nguyen, MT
Mackem, S
Clemens, TL
Bikle, DD
Chang, WH
AF Wang, Yongmei
Cheng, Zhiqiang
ElAlieh, Hashem Z.
Nakamura, Eiichiro
Nguyen, Minh-Thanh
Mackem, Susan
Clemens, Thomas L.
Bikle, Daniel D.
Chang, Wenhan
TI IGF-1R Signaling in Chondrocytes Modulates Growth Plate Development by
Interacting With the PTHrP/Ihh Pathway
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE IGF-1 RECEPTOR; CHONDROCYTE; GROWTH PLATE DEVELOPMENT; IHH; PTHRP
ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-FORMATION;
PTH-RELATED-PROTEIN; INDIAN-HEDGEHOG; FACTOR-I; HYPERTROPHIC
CHONDROCYTES; INDEPENDENT REGULATION; EXTRACELLULAR CALCIUM; SKELETAL
DEVELOPMENT; POSTNATAL-GROWTH
AB Systemic derangements and perinatal death of generalized insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) knockout mice preclude definitive assessment of IGF-1R actions in growth-plate (GP) chondrocytes. We generated cartilage-specific Igf1r knockout ((Cart)Igf1r(-/-)) mice to investigate local control of chondrocyte differentiation in the GP by this receptor. These mice died shortly after birth and showed disorganized chondrocyte columns, delayed ossification and vascular invasion, decreased cell proliferation, increased apoptosis, and increased expression of parathyroid hormone-related protein (Pthrp) RNA and protein in their GPs. The increased Pthrp expression in the knockout GPs likely was due to an increase in gene transcription, as determined by the increased activity of a LacZ reporter that was inserted downstream of the endogenous PTHrP promoter and bred into the knockout mice. To circumvent the early death of (Cart)Igf1r(-/-) mice and investigate the role of IGF-1R during postnatal growth, we made tamoxifen (Tam)-inducible, cartilage-specific Igf1r knockout ((TamCart)Igf1(-/-)) mice. At 2 weeks of age and 7 to 8 days after Tam injection, the (TamCart)Igf1(-/-) mice showed growth retardation with a disorganized GP, reduced chondrocyte proliferation, decreased type 2 collagen and Indian Hedgehog (Ihh) expression, but increased expression of PTHrP. Consistent with in vivo observations, in vitro knockout of the Igf1r gene by adenoviral expression of Cre recombinase suppressed cell proliferation, promoted apoptosis, and increased Pthrp expression. Our data indicate that the IGF-1R in chondrocytes controls cell growth, survival, and differentiation in embryonic and postnatal GPs in part by suppression of Pthrp expression. (C) 2011 American Society for Bone and Mineral Research.
C1 [Wang, Yongmei; Cheng, Zhiqiang; ElAlieh, Hashem Z.; Bikle, Daniel D.; Chang, Wenhan] Univ Calif San Francisco, Vet Affairs Med Ctr, Endocrine Unit, San Francisco, CA 94143 USA.
[Nakamura, Eiichiro; Nguyen, Minh-Thanh; Mackem, Susan] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Clemens, Thomas L.] Johns Hopkins Univ, Ctr Musculoskeletal Res, Dept Orthoped Surg, Baltimore, MD USA.
RP Chang, WH (reprint author), Vet Adm Med Ctr, Endocrine Unit 111N, 4150 Clement St, San Francisco, CA 94121 USA.
EM wenhan.chang@ucsf.edu
FU NIH [RO1-AG21353, R21-AR50662, RO1-AR050023, RO1 DK 54793]; Department
of Veterans Affairs Merit Review; Research Enhancement Award Program in
Bone Disease
FX This work was supported by NIH RO1-AG21353 (WC), R21-AR50662 (WC),
RO1-AR050023 (DB), and RO1 DK 54793 (DB); by the Department of Veterans
Affairs Merit Review (DB); and by the Research Enhancement Award Program
in Bone Disease (WC and DB).
NR 35
TC 34
Z9 36
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUL
PY 2011
VL 26
IS 7
BP 1437
EP 1446
DI 10.1002/jbmr.359
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 783DJ
UT WOS:000292061400007
PM 21312270
ER
PT J
AU Barnett, BP
Ruiz-Cabello, J
Hota, P
Ouwerkerk, R
Shamblott, MJ
Lauzon, C
Walczak, P
Gilson, WD
Chacko, VP
Kraitchman, DL
Arepally, A
Bulte, JWM
AF Barnett, Brad P.
Ruiz-Cabello, Jesus
Hota, Partha
Ouwerkerk, Ronald
Shamblott, Michael J.
Lauzon, Cal
Walczak, Piotr
Gilson, Wesley D.
Chacko, Vadappuram P.
Kraitchman, Dara L.
Arepally, Aravind
Bulte, Jeff W. M.
TI Use of perfluorocarbon nanoparticles for non-invasive multimodal cell
tracking of human pancreatic islets
SO CONTRAST MEDIA & MOLECULAR IMAGING
LA English
DT Article
DE cell tracking; molecular imaging; fluorine MRI; ultrasound imaging;
X-ray imaging; islet cell; diabetes
ID F-19 MAGNETIC-RESONANCE; STEM-CELLS; TARGETED DELIVERY; 1.5 TESLA;
TRANSPLANTATION; MRI; PERFLUOROCTYLBROMIDE; REJECTION; SYSTEM; MODEL
AB In vivo imaging of engraftment and immunorejection of transplanted islets is critical for further clinical development, with (1)H MR imaging of superparamagnetic iron oxide-labeled cells being the current premier modality. Using perfluorocarbon nanoparticles, we present here a strategy for non-invasive imaging of cells using other modalities. To this end, human cadaveric islets were labeled with rhodamine-perfluorooctylbromide (PFOB) nanoparticles, rhodamine-perfluoropolyether (PFPE) nanoparticles or Feridex (R) as control and tested in vitro for cell viability and c-peptide secretion for 1 week. (19)F MRI, computed tomography (CT) and ultrasound (US) imaging was performed on labeled cell phantoms and on cells following transplantation beneath the kidney capsule of mice and rabbits. PFOB and PFPE-labeling did not reduce human islet viability or glucose responsiveness as compared with unlabeled cells or SPIO-labeled cells. PFOB-and PFPE-labeled islets were effectively fluorinated for visualization by (19)F MRI. PFOB-labeled islets were acoustically reflective for detection by US imaging and became sufficiently brominated to become radiopaque allowing visualization with CT. Thus, perfluorocarbon nanoparticles are multimodal cellular contrast agents that may find applications in real-time targeted delivery and imaging of transplanted human islets or other cells in a clinically applicablemanner using MRI, US or CT imaging. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Dept Radiol, Inst Cell Engn,Cellular Imaging Sect, Baltimore, MD 21205 USA.
[Barnett, Brad P.; Ruiz-Cabello, Jesus; Hota, Partha; Walczak, Piotr; Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Vasc Biol Program, Baltimore, MD 21205 USA.
[Barnett, Brad P.; Ruiz-Cabello, Jesus; Hota, Partha; Lauzon, Cal; Walczak, Piotr; Gilson, Wesley D.; Chacko, Vadappuram P.; Kraitchman, Dara L.; Arepally, Aravind; Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Div MR Res, Baltimore, MD 21205 USA.
[Ruiz-Cabello, Jesus] Univ Complutense Madrid, Inst Estudios Biofunc, Madrid, Spain.
[Hota, Partha; Bulte, Jeff W. M.] Johns Hopkins Univ, Sch Med, Dept Chem & Biomol Engn, Baltimore, MD 21205 USA.
[Ouwerkerk, Ronald] NIDDK, NIH, Bethesda, MD USA.
[Shamblott, Michael J.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA.
[Shamblott, Michael J.; Lauzon, Cal] Johns Hopkins Univ, Sch Med, Hugo W Moser Kennedy Krieger Inst, Baltimore, MD 21205 USA.
RP Bulte, JWM (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, Inst Cell Engn,Cellular Imaging Sect, 217 Traylor,720 Rutland Ave, Baltimore, MD 21205 USA.
RI Walczak, Piotr/B-8707-2008; Bulte, Jeff/A-3240-2008; Ruiz-Cabello,
Jesus/A-9570-2012;
OI Bulte, Jeff/0000-0003-1202-1610; Ruiz-Cabello,
Jesus/0000-0001-8681-5056; Walczak, Piotr/0000-0002-3733-3322
FU NIBIB NIH HHS [R01 EB007825-02, R01 EB007825, R01 EB007825-03]
NR 42
TC 34
Z9 35
U1 1
U2 20
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1555-4309
J9 CONTRAST MEDIA MOL I
JI Contrast Media Mol. Imaging
PD JUL-AUG
PY 2011
VL 6
IS 4
BP 251
EP 259
DI 10.1002/cmmi.424
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 825QB
UT WOS:000295295100009
PM 21861285
ER
PT J
AU Minnicozzi, M
Sawyer, RT
Fenton, MJ
AF Minnicozzi, Michael
Sawyer, Richard T.
Fenton, Matthew J.
TI Innate immunity in allergic disease
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE innate immunity; allergy; asthma; atopic dermatitis; food allergy;
inflammation
ID THYMIC STROMAL LYMPHOPOIETIN; INTESTINAL EPITHELIAL-CELLS; TOLL-LIKE
RECEPTORS; PULMONARY DENDRITIC CELLS; CD4(+) T-CELLS; ANTIGEN-PRESENTING
CELLS; NOD-LIKE RECEPTORS; FC-EPSILON-RI; PATTERN-RECOGNITION RECEPTORS;
EPIDERMAL LANGERHANS CELLS
AB The innate immune system consists of multiple cell types that express germline-encoded pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Allergens are frequently found in forms and mixtures that contain PAMPs and DAMPs. The innate immune system is interposed between the external environment and the internal acquired immune system. It is also an integral part of the airways, gut, and skin. These tissues face continuous exposure to allergens, PAMPs, and DAMPs. Interaction of allergens with the innate immune system normally results in immune tolerance but, in the case of allergic disease, this interaction induces recurring and/or chronic inflammation as well as the loss of immunologic tolerance. Upon activation by allergens, the innate immune response commits the acquired immune response to a variety of outcomes mediated by distinct T-cell subsets, such as T-helper 2, regulatory T, or T-helper 17 cells. New studies highlighted in this review underscore the close relationship between allergens, the innate immune system, and the acquired immune system that promotes homeostasis versus allergic disease.
C1 [Minnicozzi, Michael; Sawyer, Richard T.; Fenton, Matthew J.] NIAID, Asthma Allergy & Inflammat Branch, Div Allergy Immunol & Transplantat, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
RP Fenton, MJ (reprint author), NIAID, Asthma Allergy & Inflammat Branch, Div Allergy Immunol & Transplantat, Dept Hlth & Human Serv,NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM fentonm@niaid.nih.gov
NR 274
TC 34
Z9 34
U1 2
U2 20
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD JUL
PY 2011
VL 242
SI SI
BP 106
EP 127
DI 10.1111/j.1600-065X.2011.01025.x
PG 22
WC Immunology
SC Immunology
GA 822AR
UT WOS:000295016200007
PM 21682741
ER
PT J
AU Srivastava, K
Srivastava, A
Sharma, KL
Mittal, B
AF Srivastava, Kshitij
Srivastava, Anvesha
Sharma, Kiran Lata
Mittal, Balraj
TI Candidate gene studies in gallbladder cancer: A systematic review and
meta-analysis
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Review
DE Gallbladder cancer; Polymorphism; Review; Cancer; Meta-analysis
ID BILIARY-TRACT CANCERS; NORTH INDIAN POPULATION; GALL-BLADDER CANCER;
DNA-REPAIR GENES; PRIMARY-CARCINOMA; DISEASE ASSOCIATIONS; REPRODUCTIVE
FACTORS; GALLSTONE DISEASE; INCREASED RISK; CHILEAN WOMEN
AB Gallbladder cancer (GBC) is the most frequent biliary tract malignancy. Wide variations in GBC incidence and familial and epidemiological data suggest involvement of a genetic component in its etiopathogenesis. A systematic review of genetic association studies in GBC was performed by applying a meta-analysis approach and systematically reviewing PubMed database using appropriate terms. Odds ratios (ORs) and 95% confidence intervals (CIs) were appropriately derived for each gene-disease association using fixed and random effect models. Meta-regression with population size and genotyping method was also performed. Study quality was assessed using a 10-point scoring system designed from published guidelines. Following a review of 44 published manuscripts and one unpublished report, 80 candidate gene variants and 173 polymorphisms were analyzed among 1046 cases and 2310 controls. Majority of studies were of intermediate quality. Four polymorphisms with >3 separate studies were included in the meta-analysis [OGG1 (rs1052133), TP53 (rs1042522), CYP1A1 (rs1048943) and GSTM1 null polymorphism]. The meta-analysis demonstrated no significant associations of any of the above polymorphisms with GBC susceptibility except TP53 (rs1042522) polymorphism. To conclude, existing candidate gene studies in GBC susceptibility have so far been insufficient to confirm any association. Future research should focus on a more comprehensive approach utilizing potential gene-gene, gene-environment interactions and high-risk haplotypes. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Srivastava, Anvesha; Sharma, Kiran Lata; Mittal, Balraj] Sanjay Gandhi Post Grad Inst Med Sci, Dept Genet, Lucknow 226014, Uttar Pradesh, India.
[Srivastava, Kshitij] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Mittal, B (reprint author), Sanjay Gandhi Post Grad Inst Med Sci, Dept Genet, Lucknow 226014, Uttar Pradesh, India.
EM balraj@sgpgi.ac.in
FU National Human Genome Research Institute; National Institutes of Health
(USA); Indian council of Medical Research (ICMR); DST; CSIR Government
of India
FX This research was supported [in part] by the Intramural Research Program
of the National Human Genome Research Institute, National Institutes of
Health (USA), Indian council of Medical Research (ICMR), DST and CSIR
Government of India.
NR 108
TC 43
Z9 45
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5742
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD JUL-OCT
PY 2011
VL 728
IS 1-2
BP 67
EP 79
DI 10.1016/j.mrrev.2011.06.002
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 821MX
UT WOS:000294980200006
PM 21708280
ER
PT J
AU Kamino, H
Moore, R
Negishi, M
AF Kamino, Hiroki
Moore, Rick
Negishi, Masahiko
TI Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma
cell lines
SO CANCER GENETICS
LA English
DT Article
DE CAR; cell growth; cell migration; liver cancer; nuclear receptor; TUBA8
ID NUCLEAR RECEPTORS; POSTTRANSLATIONAL MODIFICATIONS; RAT
HEPATOCARCINOGENESIS; TUMOR PROMOTION; TUBULIN; MICE; PATHOGENESIS;
MIGRATION; PROTEIN; STRAIN
AB Phenobarbital (PB), a nongenotoxic carcinogen, activates the nuclear constitutive active/androstane receptor (CAR), resulting in the transcriptional induction or repression of various hepatic genes. We previously demonstrated that liver tumors developed after chronic PB treatment only when CAR is present. To understand the molecular mechanism of tumor promotion, cDNA microarray analysis was performed. We identified tubulin alpha 8 (TU8A8) as one of the candidate genes that may be involved in liver tumor promotion. Tuba8 mRNA was induced with PB treatment in mouse livers before tumor development as well as in tumor tissues. Because the functions of TUBA8 are unknown in liver, we investigated the effects of TUBA8 gene expression on cell growth, proliferation, and cell migration. Sense or antisense cDNA for Tuba8 was stably transfected into Huh7 and HepG2 cells. Exogenous overexpression of Tuba8 inhibited cell growth and proliferation in Huh7 but not in HepG2 cells, while cell migration was increased in HepG2 cells but not Huh7 cells. These results indicate that TUBA8 can play a role in the regulation of cell growth, proliferation, and cell migration in a cell-specific manner in vitro, suggesting that TUBA8 may contribute to mouse liver tumorigenesis through these functions.
C1 [Kamino, Hiroki; Moore, Rick; Negishi, Masahiko] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
FU National Institutes of Health and National Institute of Environmental
Health Sciences [Z01ES1005-01]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health and National Institute of Environmental
Health Sciences (Z01ES1005-01). We acknowledge the efforts the staff of
the NIEHS DNA Sequencing Core, Flow Cytometry Center, and Fluorescence
Microscopy and Imaging Center. We especially thank all of our laboratory
members for valuable discussion.
NR 31
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Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2210-7762
J9 CANCER GENET-NY
JI Cancer Genet.
PD JUL
PY 2011
VL 204
IS 7
BP 382
EP 391
DI 10.1016/j.cancergen.2011.05.007
PG 10
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 819NX
UT WOS:000294834700004
PM 21872825
ER
PT J
AU Albrecht, M
Mukherjee, AL
Tierney, C
Morse, GD
Dykes, C
Klingman, KL
Demeter, LM
AF Albrecht, Mary
Mukherjee, A. Lisa
Tierney, Camlin
Morse, Gene D.
Dykes, Carrie
Klingman, Karin L.
Demeter, Lisa M.
TI A Randomized Clinical Trial Evaluating Therapeutic Drug Monitoring (TDM)
for Protease Inhibitor-Based Regimens in Antiretroviral-Experienced
HIV-Infected Individuals: Week 48 Results of the A5146 Study
SO HIV CLINICAL TRIALS
LA English
DT Article
DE antiretroviral therapy; clinical trials; HIV drug resistance;
pharmacokinetics; protease inhibitors; therapeutic drug monitoring
ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; HEAVILY
PRETREATED PATIENTS; VIROLOGICAL RESPONSE; LOPINAVIR-RITONAVIR;
HIV-1-INFECTED INDIVIDUALS; DARUNAVIR-RITONAVIR; QUOTIENT; AMPRENAVIR;
ATAZANAVIR
AB Background: We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease inhibitors (Pis) and dose escalation based upon a normalized inhibitory quotient (NI), which integrates PI trough concentration and drug resistance, could improve virologic outcome in PI-experienced patients with treatment failure. Secondary analyses through 48 weeks are presented. Methods: Eligible HIV-infected subjects with a screening viral load of >= 1000 copies/mL initiated a new PI-based regimen at entry and had NIQ performed at week 2. Subjects with an NIQ <= 1 were randomized at week 4 to a standard-of-care (SOC) arm or TDM arm featuring PI dose escalation. Results: One hundred and eighty-three subjects were randomized. There was no significant treatment difference in change from randomization to week 48 in HIV-1 RNA [P = .13, median (25th, 75th percentile log(10) copies/mL change): -0.03 (-0.74, 0.62) with TDM and 0.11 (-2.3, 0.82) with SOC]. In subgroup analysis, patients with 1:169 active PIs benefited from TDM compared to those with <0.69 active PIs (P = .05). Conclusions: While the TDM strategy of PI dose escalation did not improve virologic response at week 48 overall, in subgroup analysis, TDM favorably impacted virologic outcome in subjects taking PI-based regimens with moderate antiviral activity.
C1 [Albrecht, Mary] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Mukherjee, A. Lisa; Tierney, Camlin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Morse, Gene D.] SUNY Buffalo, Dept Pharm Practice, Buffalo, NY 14260 USA.
[Dykes, Carrie; Demeter, Lisa M.] Univ Rochester, Sch Med & Dent, Div Infect Dis, Rochester, NY USA.
[Klingman, Karin L.] NIH, Div Aids, Bethesda, MD 20892 USA.
RP Albrecht, M (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St, Boston, MA 02215 USA.
EM malbrech@bidmc.harvard.edu
FU National Institute of Allergy and Infectious Diseases [U01AI068636,
AI-25859, AI-25915, AI-27658, AI-27661, AI-32782, AI-34853, AI-38855,
AI-38858-09S1, AI-46370, AI-04637, AI-68634, AI-69415, AI-69418,
AI-69419, AI-69423, AI-69424, AI-69428, AI-69432, AI-69434, AI-69439,
AI-69447, AI-69450, AI-69452, AI-69467, AI-69470, AI-69471, AI-69472,
AI-69474, AI-69477, AI-69484, AI-69494, AI-69495, AI-69501, AI-69502,
AI-69511, AI-69513, AI-695332, AI-69556, P30-AI-050409, P30-AI-045008,
P30-AI-050410]; National Center for Research Resources [RR-0032,
RR-024156, RR 024160, RR-024992, RR-024996, RR-025747, RR-025780];
Virco; General Clinical Research Center Units
FX The project described was supported by award U01AI068636 from the
National Institute of Allergy and Infectious Diseases (AI-25859,
AI-25915, AI-27658, AI-27661, AI-32782, AI-34853, AI-38855,
AI-38858-09S1, AI-46370, AI-04637, AI-68634, AI-69415, AI-69418,
AI-69419, AI-69423, AI-69424, AI-69428, AI-69432, AI-69434, AI-69439,
AI-69447, AI-69450, AI-69452, AI-69467, AI-69470, AI-69471, AI-69472,
AI-69474, AI-69477, AI-69484, AI-69494, AI-69495, AI-69501, AI-69502,
AI-69511, AI-69513, AI-695332, AI-69556); P30-AI-050409, P30-AI-045008,
P30-AI-050410), and supported in part by General Clinical Research
Center Units funded by the National Center for Research Resources
(RR-0032, RR-024156, RR 024160, RR-024992, RR-024996, RR-025747,
RR-025780). Virco performed drug resistance testing and provided partial
financial support for drug concentration testing which was performed in
Dr. Morse's laboratory at SUNY Buffalo.
NR 50
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U1 0
U2 0
PU THOMAS LAND PUBLISHERS, INC
PI ST LOUIS
PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA
SN 1528-4336
J9 HIV CLIN TRIALS
JI HIV Clin. Trials
PD JUL-AUG
PY 2011
VL 12
IS 4
BP 201
EP 214
DI 10.1310/hct1204-201
PG 14
WC Infectious Diseases; Pharmacology & Pharmacy
SC Infectious Diseases; Pharmacology & Pharmacy
GA 820AU
UT WOS:000294878700003
PM 22044856
ER
PT J
AU Reznick, JS
AF Reznick, Jeffrey S.
TI Perspectives from the History of Medicine Division of the United States
National Library of Medicine, National Institutes of Health
SO MEDICAL HISTORY
LA English
DT Article
DE US National Library of Medicine (NLM); IndexCat; Directory of History of
Medicine Collections; Images; PubMed Central; Digital Collections;
Exhibition Programme; Turning the Pages; Profiles in Science; Medical
Heritage Library
C1 Natl Lib Med, Hist Med Div, NIH, Bethesda, MD 20894 USA.
RP Reznick, JS (reprint author), Natl Lib Med, Hist Med Div, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM jeffrey.reznick@nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 1
PU PROF SCI PUBL
PI LONDON
PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0025-7273
J9 MED HIST
JI Med. Hist.
PD JUL
PY 2011
VL 55
IS 3
SI SI
BP 413
EP 418
PG 6
WC Health Care Sciences & Services; History & Philosophy Of Science
SC Health Care Sciences & Services; History & Philosophy of Science
GA 807XH
UT WOS:000293935800024
PM 21792270
ER
PT J
AU Roney, CA
Xu, BY
Xie, JW
Yuan, SA
Wierwille, J
Chen, CW
Chen, Y
Griffiths, GL
Summers, RM
AF Roney, Celeste A.
Xu, Biying
Xie, Jianwu
Yuan, Shuai
Wierwille, Jeremiah
Chen, Chao-Wei
Chen, Yu
Griffiths, Gary L.
Summers, Ronald M.
TI Rh-I-UEA-1 Polymerized Liposomes Target and Image Adenomatous Polyps in
the APC(Min/+) Mouse Using Optical Colonography
SO MOLECULAR IMAGING
LA English
DT Article
ID COLORECTAL-CARCINOMA; COHERENCE TOMOGRAPHY; CT COLONOGRAPHY; BINDING
SITES; COLON-CANCER; MUCIN; EXPRESSION; MUCOSA; VIVO; MIXTURES
AB Mutated adenomatous polyposis coli (APC) genes predispose transformations to neoplasia, progressing to colorectal carcinoma. Early detection facilitates clinical management and therapy. Novel lectin-mediated polymerized targeted liposomes (Rh-I-UEA-1), with polyp specificity and incorporated imaging agents were fabricated to locate and image adenomatous polyps in APC(Min/+) mice. The biomarker alpha-L-fucose covalently joins the liposomal conjugated lectin Ulex europaeus agglutinin (UEA-1), via glycosidic linkage to the polyp mucin layer. Multispectral optical imaging (MSI) corroborated a global perspective of specific binding (rhodamine B 532 nm emission, 590-620 nm excitation) of targeted Rh-I-UEA-1 polymerized liposomes to polyps with 1.4-fold labeling efficiency. High-resolution coregistered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) reveal the spatial correlation of contrast distribution and tissue morphology. Freshly excised APC(Min) bowels were incubated with targeted liposomes (UEA-1 lectin), control liposomes (no lectin), or iohexol (Omnipaque) and imaged by the three techniques. Computed tomographic quantitative analyses did not confirm that targeted liposomes more strongly bound polyps than nontargeted liposomes or iohexol (Omnipaque) alone. OCT, with anatomic depth capabilities, along with the coregistered FMI, substantiated Rh-I-UEA-1 liposome binding along the mucinous polyp surface. UEA-1 lectin denotes alpha-L-fucose biomarker carbohydrate expression at the mucin glycoprotein layer; Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in APC(Min) mice.
C1 [Summers, Ronald M.] NHLBI, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin,NIH, Bethesda, MD 20892 USA.
NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA.
Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
RP Summers, RM (reprint author), NHLBI, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin,NIH, Bldg 10,Room 1C368X,MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU National Institutes of Health Clinical Center; National Heart, Lung, and
Blood Institute
FX Financial dislosure of authors: This research was supported by the
Intramural Research Programs of the National Institutes of Health
Clinical Center, and National Heart, Lung, and Blood Institute.
NR 31
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Z9 3
U1 3
U2 6
PU B C DECKER INC
PI HAMILTON
PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA
SN 1535-3508
J9 MOL IMAGING
JI Mol. Imaging
PD JUL-AUG
PY 2011
VL 10
IS 4
BP 305
EP 316
DI 10.2310/7290.2010.00054
PG 12
WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical
Imaging
SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical
Imaging
GA 815XF
UT WOS:000294562600009
PM 21521550
ER
PT J
AU Chalamalasetty, RB
Dunty, WC
Biris, KK
Ajima, R
Iacovino, M
Beisaw, A
Feigenbaum, L
Chapman, DL
Yoon, JK
Kyba, M
Yamaguchi, TP
AF Chalamalasetty, Ravindra B.
Dunty, William C., Jr.
Biris, Kristin K.
Ajima, Rieko
Iacovino, Michelina
Beisaw, Arica
Feigenbaum, Lionel
Chapman, Deborah L.
Yoon, Jeong Kyo
Kyba, Michael
Yamaguchi, Terry P.
TI The Wnt3a/beta-catenin target gene Mesogenin1 controls the segmentation
clock by activating a Notch signalling program
SO NATURE COMMUNICATIONS
LA English
DT Article
ID LUNATIC-FRINGE EXPRESSION; SOMITE BOUNDARY FORMATION; PARAXIAL MESODERM;
PRESOMITIC MESODERM; DYNAMIC EXPRESSION; MOUSE RIPPLY2; WNT;
SOMITOGENESIS; CATENIN; EMBRYOS
AB Segmentation is an organizing principle of body plans. The segmentation clock, a molecular oscillator best illustrated by the cyclic expression of Notch signalling genes, controls the periodic cleavage of somites from unsegmented presomitic mesoderm during vertebrate segmentation. Wnt3a controls the spatiotemporal expression of cyclic Notch genes; however, the underlying mechanisms remain obscure. Here we show by transcriptional profiling of Wnt3a(-/-) embryos that the bHLH transcription factor, Mesogenin1 (Msgn1), is a direct target gene of Wnt3a. To identify Msgn1 targets, we conducted genome-wide studies of Msgn1 activity in embryonic stem cells. We show that Msgn1 is a major transcriptional activator of a Notch signalling program and synergizes with Notch to trigger clock gene expression. Msgn1 also indirectly regulates cyclic genes in the Fgf and Wnt pathways. Thus, Msgn1 is a central component of a transcriptional cascade that translates a spatial Wnt3a gradient into a temporal pattern of clock gene expression.
C1 [Chalamalasetty, Ravindra B.; Dunty, William C., Jr.; Biris, Kristin K.; Ajima, Rieko; Beisaw, Arica; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Iacovino, Michelina; Kyba, Michael] Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN 55455 USA.
[Iacovino, Michelina; Kyba, Michael] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Frederick, MD 21702 USA.
[Chapman, Deborah L.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
[Yoon, Jeong Kyo] Maine Med Ctr, Ctr Mol Med, Res Inst, Scarborough, ME 04074 USA.
RP Yamaguchi, TP (reprint author), NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
EM yamagute@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Y. Saga, B. Herrmann, and R. Kageyama for providing reagents.
We are grateful to S. Mackem, A. Perantoni, M. Lewandoski, M. Anderson,
N. Adler, and M. Kennedy for providing comments on versions of this
manuscript. We are particularly indebted to J. Greear and R. Wolfe
(SAIC-Frederick) for excellent animal husbandry. This research was
supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 57
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U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2011
VL 2
AR 390
DI 10.1038/ncomms1381
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819DJ
UT WOS:000294805300017
PM 21750544
ER
PT J
AU Nery, FC
Armata, IA
Farley, JE
Cho, JA
Yaqub, U
Chen, P
da Hora, CC
Wang, QY
Tagaya, M
Klein, C
Tannous, B
Caldwell, KA
Caldwell, GA
Lencer, WI
Ye, YH
Breakefield, XO
AF Nery, Flavia C.
Armata, Ioanna A.
Farley, Jonathan E.
Cho, Jin A.
Yaqub, Uzma
Chen, Pan
da Hora, Cintia Carla
Wang, Qiuyan
Tagaya, Mitsuo
Klein, Christine
Tannous, Bakhos
Caldwell, Kim A.
Caldwell, Guy A.
Lencer, Wayne I.
Ye, Yihong
Breakefield, Xandra O.
TI TorsinA participates in endoplasmic reticulum-associated degradation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DYSTONIA-ASSOCIATED PROTEIN; VALOSIN-CONTAINING PROTEIN; ER-ASSOCIATED
DEGRADATION; DELTA-E-TORSINA; NUCLEAR-ENVELOPE; DYT1 DYSTONIA;
CHOLERA-TOXIN; RETRO-TRANSLOCATION; SECRETORY PATHWAY; MOUSE MODEL
AB TorsinA is an AAA+ ATPase located within the lumen of the endoplasmic reticulum and nuclear envelope, with a mutant form causing early onset torsion dystonia (DYT1). Here we report a new function for torsinA in endoplasmic reticulum-associated degradation (ERAD). Retro-translocation and proteosomal degradation of a mutant cystic fibrosis transmembrane conductance regulator (CFTR Delta F508) was inhibited by downregulation of torsinA or overexpression of mutant torsinA, and facilitated by increased torsinA. Retro-translocation of cholera toxin was also decreased by downregulation of torsinA. TorsinA associates with proteins implicated in ERAD, including Derlin-1, VIMP and p97. Further, torsinA reduces endoplasmic reticulum stress in nematodes overexpressing CFTR Delta F508, and fibroblasts from DYT1 dystonia patients are more sensitive than controls to endoplasmic reticulum stress and less able to degrade mutant CFTR. Therefore, compromised ERAD function in the cells of DYT1 patients may increase sensitivity to endoplasmic reticulum stress with consequent alterations in neuronal function contributing to the disease state.
C1 [Nery, Flavia C.; Armata, Ioanna A.; Farley, Jonathan E.; Yaqub, Uzma; da Hora, Cintia Carla; Tannous, Bakhos; Breakefield, Xandra O.] Harvard Univ, Sch Med, Ctr Neurosci, Dept Neurol, Boston, MA 02114 USA.
[Nery, Flavia C.; Armata, Ioanna A.; Farley, Jonathan E.; Yaqub, Uzma; da Hora, Cintia Carla; Tannous, Bakhos; Breakefield, Xandra O.] Harvard Univ, Sch Med, Ctr Mol Imaging Res, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nery, Flavia C.; Armata, Ioanna A.; Farley, Jonathan E.; Yaqub, Uzma; da Hora, Cintia Carla; Tannous, Bakhos; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA.
[Cho, Jin A.; Lencer, Wayne I.] Harvard Univ, Sch Med, Gastrointestinal Cell Biol & Harvard Digest Dis C, Childrens Hosp, Boston, MA 02115 USA.
[Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA.
[Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Dept Tuscaloosa, Tuscaloosa, AL 35487 USA.
[Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurol, Tuscaloosa, AL 35487 USA.
[Chen, Pan; Caldwell, Kim A.; Caldwell, Guy A.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Dept Neurobiol, Tuscaloosa, AL 35487 USA.
[Wang, Qiuyan; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Tagaya, Mitsuo] Tokyo Univ Pharm & Life Sci, Sch Sci, Tokyo 1920392, Japan.
[Klein, Christine] Med Univ Lubeck, Sect Clin & Mol Neurogenet, D-23538 Lubeck, Germany.
RP Breakefield, XO (reprint author), Harvard Univ, Sch Med, Ctr Neurosci, Dept Neurol, Boston, MA 02114 USA.
EM breakefield@hms.harvard.edu
FU NINDS [NS037409, P30NS045776]; Dystonia Medical Research Foundation;
NSF; QRxPharma; Volkswagen Foundation; Hermann and Lilly Schilling
Foundation; Crohn's & Colitis Foundation of America [3042];
[HD007466-11]; [DK083894]; [DK48106]; [DK0484424]
FX We thank Nathan Roberts (Dystonia Support Group of Alabama), Nathan
Spielberg, Igor Bagayev and Xuan Zhang for help with experiments;
Suzanne McDavitt for skilled editorial assistance; Trisha
Multhaupt-Buell for IRB submissions; Dr Phyllis Hanson (Washington
University) for torsinA constructs; Dr Pedro Gonzalez-Allegre
(University of Iowa) for torsinA antibodies; Drs Dinah Sah and Pei Ge
(Alnylam Pharmaceuticals) for siRNAs for torsinA; and the Imaging Core
of the Harvard Digestive Disease Center DK034854 (W.I.L.) for assistance
with confocal imaging. Adenovirus vectors were provided by the Vector
Core at the University of Pennsylvania School of Medicine; AAV vectors
were provided by Dr Miguel Sena-Esteves (UMass Memorial Medical.
Center.). This work was supported by: NINDS NS037409 (XOB); the Dystonia
Medical Research Foundation (F.N.); NINDS P30NS045776 and NSF CAREER
Award (K.A.C.); QRxPharma (K.A.C. and G.A.C.); Volkswagen Foundation.
and Hermann and Lilly Schilling Foundation. (C.K.); HD007466-11,
DK083894 and Crohn's & Colitis Foundation of America 3042 (J.A.C.); and
DK48106 and DK0484424 (W.I.L.).
NR 60
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2011
VL 2
AR 393
DI 10.1038/ncomms1383
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819DJ
UT WOS:000294805300020
PM 21750546
ER
PT J
AU Cuttica, MJ
Langenickel, T
Noguchi, A
Machado, RF
Gladwin, MT
Boehm, M
AF Cuttica, Michael J.
Langenickel, Thomas
Noguchi, Audrey
Machado, Roberto F.
Gladwin, Mark T.
Boehm, Manfred
TI Perivascular T-Cell Infiltration Leads to Sustained Pulmonary Artery
Remodeling after Endothelial Cell Damage
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE pulmonary vascular remodeling; inflammation; CD4(+) T cells;
Rag1(tm1Mom) mice
ID C-REACTIVE PROTEIN; MONOCYTE CHEMOATTRACTANT; VASCULAR-DISEASE;
HYPERTENSION; MONOCROTALINE; MICE; RATS; ATHEROSCLEROSIS; FIBROSIS;
FIBROBLASTS
AB Pulmonary hypertension is a vascular proliferative disease characterized by pulmonary artery remodeling because of dysregulated endothelial and smooth muscle cell proliferation. Although the role of inflammation in the development of the disease is not well-defined, plexogenic lesions in human disease are characterized by perivascular inflammation composed, in part, of T cells. We explored the role of T-cell infiltration on pulmonary vascular remodeling after endothelial cell damage. We induced endothelial cell damage using monocrotaline and isolated the role of T cells by using Rag1(tm1Mom) mice and performing adoptive T-cell transfer. We found that monocrotaline causes pulmonary vascular endothelial cell injury followed by a perivascular inflammatory response. The infiltration of inflammatory cells primarily involves CD4(+) T cells and leads to the progressive muscularization of small (< 30 mu m) arterioles. Pulmonary vascular proliferative changes were accompanied by progressive and persistent elevations in right ventricular pressure and right ventricular hypertrophy. Supporting the central role of CD4(+) T cells in the inflammatory response, Rag1(tm1Mom) (Rag12/2) mice, which are devoid of T and B cells, were protected from the development of vascular injury when exposed to monocrotaline. The introduction of T cells from control mice into Rag1(-/-) mice reproduced the vascular injury phenotype. These data indicate that after endothelial cell damage, CD4(+) T-cell infiltration participates in pulmonary vascular remodeling. This finding suggests that a CD4(+) T-cell immune response may contribute to the pathogenesis of inflammatory vascular lesions seen in some forms of pulmonary hypertension.
C1 [Cuttica, Michael J.] Northwestern Univ, Dept Pulm & Crit Care Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Langenickel, Thomas] Bristol Myers Squibb Co, Discovery Med & Clin Pharmacol, Princeton, NJ USA.
[Boehm, Manfred] NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA.
[Machado, Roberto F.] Univ Illinois, Sect Pulm Crit Care Sleep & Allergy, Chicago, IL USA.
[Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Dept Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
RP Boehm, M (reprint author), NHLBI, Translat Med Branch, NIH, 10 Ctr Dr,MSC1454,Bldg 10-CRC,Room 5 East 3132, Bethesda, MD 20892 USA.
EM boehmm@nhlbi.nih.gov
NR 45
TC 13
Z9 15
U1 0
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JUL
PY 2011
VL 45
IS 1
BP 62
EP 71
DI 10.1165/rcmb.2009-0365OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 808BL
UT WOS:000293948200007
PM 20813993
ER
PT J
AU Yang, XB
Walton, W
Cook, DN
Hua, XY
Tilley, S
Haskell, CA
Horuk, R
Blackstock, AW
Kirby, SL
AF Yang, Xuebin
Walton, William
Cook, Donald N.
Hua, Xiaoyang
Tilley, Stephen
Haskell, Christopher A.
Horuk, Richard
Blackstock, A. William
Kirby, Suzanne L.
TI The Chemokine, CCL3, and Its Receptor, CCR1, Mediate Thoracic
Radiation-Induced Pulmonary Fibrosis
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE chemokine; fibrosis; radiation; lung; inflammation
ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; INDUCED LUNG INJURY; RENAL
FIBROSIS; MULTIPLE-MYELOMA; HOST-DEFENSE; MICE; ANTAGONIST; DISEASE;
RECRUITMENT; MECHANISMS
AB Patients receiving thoracic radiation often develop pulmonary injury and fibrosis. Currently, there are no effective measures to prevent or treat these conditions. We tested whether blockade of the chemokine, CC chemokine ligand (CCL) 3, and its receptors, CC chemokine receptor (CCR) 1 and CCR5, can prevent radiation-induced lung inflammation and fibrosis. C57BL/6J mice received thoracic radiation, and the interaction of CCL3 with CCR1 or CCR5 was blocked using genetic techniques, or by pharmacologic intervention. Lung inflammation was assessed by histochemical staining of lung tissue and by flow cytometry. Fibrosis was measured by hydroxyproline assays and collagen staining, and lung function was studied by invasive procedures. Irradiated mice lacking CCL3 or its receptor, CCR1, did not develop the lung inflammation, fibrosis, and decline in lung function seen in irradiated wild-type mice. Pharmacologic treatment of wild-type mice with a small molecule inhibitor of CCR1 also prevented lung inflammation and fibrosis. By contrast, mice lacking CCR5 were not protected from radiation-induced injury and fibrosis. The selective interaction of CCL3 with its receptor, CCR1, is critical for radiation-induced lung inflammation and fibrosis, and these conditions can be largely prevented by a small molecule inhibitor of CCR1.
C1 [Yang, Xuebin; Walton, William; Kirby, Suzanne L.] Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA.
[Cook, Donald N.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
[Hua, Xiaoyang; Tilley, Stephen] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
[Haskell, Christopher A.] Bayer Healthcare Pharmaceut, Davis, CA USA.
[Horuk, Richard] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA.
[Blackstock, A. William] Wake Forest Univ, Dept Radiat Oncol, Winston Salem, NC 27109 USA.
RP Kirby, SL (reprint author), Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA.
EM skirby7001@gmail.com
FU National Institutes of Health [5R0 1CA098641-02, 5-U19-AI067798]
FX This work was supported by National Institutes of Health grants 5R0
1CA098641-02 and 5-U19-AI067798.
NR 46
TC 15
Z9 15
U1 0
U2 3
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JUL
PY 2011
VL 45
IS 1
BP 127
EP 135
DI 10.1165/rcmb.2010-0265OC
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 808BL
UT WOS:000293948200015
PM 20870892
ER
PT J
AU Russell, RM
AF Russell, Robert M.
TI A primer on determining the dietary requirements for folate
SO BIOFACTORS
LA English
DT Editorial Material
ID FOLIC-ACID; PROSTATE; TRIAL; RISK
C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Russell, RM (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0951-6433
J9 BIOFACTORS
JI Biofactors
PD JUL-AUG
PY 2011
VL 37
IS 4
SI SI
BP 251
EP 252
DI 10.1002/biof.167
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 816DE
UT WOS:000294578100001
PM 21674646
ER
PT J
AU Yetley, EA
AF Yetley, Elizabeth A.
TI Monitoring folate status in population-based surveys
SO BIOFACTORS
LA English
DT Review
DE folate status; National Health and Nutrition Examination Survey
ID SERUM 25-HYDROXYVITAMIN D; FOLIC-ACID; UNITED-STATES; BLOOD FOLATE;
VITAMIN-B-12 STATUS; FOOD FORTIFICATION; CANCER-RISK; INDICATORS;
SUPPLEMENTS; RADIOASSAY
AB Folate status assessments depend primarily on the measurement of biomarkers such as serum and red blood cell folate. Lessons learned from a large national monitoring system such as the National Health and Nutrition Examination Survey and a public health intervention such as the implementation of folic acid fortification in the United States have provided useful insights into the challenges of assessing folate status and possible solutions for addressing these challenges.
C1 [Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Yetley, EA (reprint author), 302 King James Ct, Upper Marlboro, MD 20774 USA.
EM beth@yetley.com
NR 28
TC 2
Z9 2
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-6433
J9 BIOFACTORS
JI Biofactors
PD JUL-AUG
PY 2011
VL 37
IS 4
SI SI
BP 285
EP 289
DI 10.1002/biof.176
PG 5
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 816DE
UT WOS:000294578100007
PM 21809406
ER
PT J
AU Palini, S
Zolla, L
De Stefani, S
Scala, V
D'Alessandro, A
Polli, V
Rocchi, P
Tiezzi, A
Pelosi, E
Dusi, L
Bulletti, C
AF Palini, S.
Zolla, L.
De Stefani, S.
Scala, V.
D'Alessandro, A.
Polli, V.
Rocchi, P.
Tiezzi, A.
Pelosi, E.
Dusi, L.
Bulletti, C.
TI Eomics in blastocoele
SO HUMAN REPRODUCTION
LA English
DT Meeting Abstract
CT 27th Annual Meeting of the
European-Society-of-Human-Reproduction-and-Embryology
CY JUL 03-06, 2011
CL Stockholm, SWEDEN
SP European Soc Human Reprod & Embryol
C1 [Zolla, L.; D'Alessandro, A.] Univ Tuscia, Viterbo, Italy.
[Pelosi, E.] NIA, Baltimore, MD USA.
[Dusi, L.] Med Ctr Palladio, Vicenza, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD JUL
PY 2011
VL 26
SU 1
BP I170
EP I170
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 814KO
UT WOS:000294450500424
ER
PT J
AU Falik-Zaccai, TC
Gunay-Aygun, M
Zivony-Elboum, Y
Gumruk, F
Geiger, D
Cetin, M
Khayat, M
Kleta, R
Kfir, N
Anikster, Y
Arcos-Bugos, M
Stanescu, H
Arat, M
Freiberg, A
Maric, I
Kehrel, BE
Jurk, K
Nurden, A
White, JG
Gahl, WA
AF Falik-Zaccai, T. C.
Gunay-Aygun, M.
Zivony-Elboum, Y.
Gumruk, F.
Geiger, D.
Cetin, M.
Khayat, M.
Kleta, R.
Kfir, N.
Anikster, Y.
Arcos-Bugos, M.
Stanescu, H.
Arat, M.
Freiberg, A.
Maric, I
Kehrel, B. E.
Jurk, K.
Nurden, A.
White, J. G.
Gahl, W. A.
TI Gray platelet syndrome: clinical features and genetic analysis
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 [Falik-Zaccai, T. C.] Technion Israel Inst Technol, Inst Human Genet, Western Galilee Hosp Nahariya, IL-32000 Haifa, Israel.
[Gunay-Aygun, M.; Kleta, R.; Anikster, Y.; Arcos-Bugos, M.; Stanescu, H.; Gahl, W. A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD USA.
[Zivony-Elboum, Y.; Khayat, M.; Kfir, N.] Western Galilee Hosp, Inst Human Genet, Nahariyya, Israel.
[Gumruk, F.; Cetin, M.] Hacettepe Univ, Childrens Hosp, Pediat Hematol Unit, Ankara, Turkey.
[Geiger, D.] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel.
[Arat, M.] Ankara Univ, Fac Med, Dept Hematol, TR-06100 Ankara, Turkey.
[Freiberg, A.] PennState Hershey Childrens Hosp, Div Pediat Hematol Oncol, Hershey, PA USA.
[Maric, I] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kehrel, B. E.; Jurk, K.] Univ Hosp Munster, Dept Anaesthesiol & Intens Care, Munster, Germany.
[Nurden, A.] Hop Xavier Arnozan, Ctr Reference Pathol Plaquettaires Plateforme Tec, Pessac, France.
[White, J. G.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 2
SI SI
BP 8
EP 8
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 800DU
UT WOS:000293340800030
ER
PT J
AU Haberichter, S
Schroeder, JA
Jacobi, PM
Gehrand, AL
Friedman, KD
DiMichele, D
Montgomery, RR
AF Haberichter, S.
Schroeder, J. A.
Jacobi, P. M.
Gehrand, A. L.
Friedman, K. D.
DiMichele, D.
Montgomery, R. R.
TI An L1278P von Willebrand factor (VWF) mutation identified in a type 1
VWD patient causes reduced VWF secretion and increased VWF clearance
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 [Haberichter, S.; Schroeder, J. A.; Jacobi, P. M.; Gehrand, A. L.; Friedman, K. D.] BloodCtr Wisconsin, Blood Res Inst, Kenosha, WI USA.
[DiMichele, D.] NHLBI, NIH, Bethesda, MD USA.
[Montgomery, R. R.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 2
SI SI
BP 55
EP 55
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 800DU
UT WOS:000293340800167
ER
PT J
AU Erten-Lyons, D
Wilmot, B
Anur, P
McWeeney, S
Westaway, SK
Silbert, L
Kramer, P
Kaye, J
AF Erten-Lyons, Deniz
Wilmot, Beth
Anur, Pavana
McWeeney, Shannon
Westaway, Shawn K.
Silbert, Lisa
Kramer, Patricia
Kaye, Jeffrey
CA Alzheimer's Dis Neuroimaging
TI Microcephaly Genes and Risk of Late-onset Alzheimer Disease
SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS
LA English
DT Article
DE Alzheimer disease; microcephaly genes; cognitive reserve
ID ONGOING ADAPTIVE EVOLUTION; BRAIN SIZE; MOLECULAR EVOLUTION; HEAD
CIRCUMFERENCE; MAJOR DETERMINANT; OLDEST-OLD; ASPM GENE; ASSOCIATION;
POPULATION; DEMENTIA
AB Brain development in the early stages of life has been suggested to be one of the factors that may influence an individual's risk of Alzheimer disease (AD) later in life. Four microcephaly genes, which regulate brain development in utero and have been suggested to play a role in the evolution of the human brain, were selected as candidate genes that may modulate the risk of AD. We examined the association between single nucleotide polymorphisms tagging common sequence variations in these genes and risk of AD in two case-control samples. We found that the G allele of rs2442607 in microcephalin 1 was associated with an increased risk of AD (under an additive genetic model, P = 0.01; odds ratio = 3.41; confidence interval, 1.77-6.57). However, this association was not replicated using another case-control sample research participants from the Alzheimer Disease Neuroimaging Initiative. We conclude that the common variations we measured in the 4 microcephaly genes do not affect the risk of AD or that their effect size is small.
C1 [Erten-Lyons, Deniz; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA.
[Erten-Lyons, Deniz; Westaway, Shawn K.; Silbert, Lisa; Kramer, Patricia; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Wilmot, Beth; Anur, Pavana; McWeeney, Shannon] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Portland, OR 97201 USA.
[Wilmot, Beth; McWeeney, Shannon] Oregon Hlth & Sci Univ, Div Bioinformat & Computat Biol, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
[McWeeney, Shannon] Oregon Hlth & Sci Univ, Dept Publ Hlth & Preventat Med, Div Biostat, Portland, OR 97201 USA.
RP Erten-Lyons, D (reprint author), NIA, Layton Aging & Alzheimers Dis Ctr, 3181 SW Sam Jackson Pk Rd,CR 131, Portland, OR 97239 USA.
EM ertenlyo@ohsu.edu
RI Scharre, Douglas/E-4030-2011;
OI Kaye, Jeffrey/0000-0002-9971-3478; McWeeney,
Shannon/0000-0001-8333-6607; Silbert, Lisa/0000-0002-4525-0068
FU Office of Research and Development, Department of Veterans Affairs,
National Institutes of Health [AG08017, MO1 RR000334, UL1 RR024140];
Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes
of Health) [U01 AG024904]; National Institute on Aging, the National
Institute of Biomedical Imaging and Bioengineering; Northern California
Institute for Research and Education; NIH [P30 AG010129, K01 AG030514];
Dana Foundation
FX Supported by Merit Review Grant and Research Career Development Award,
Office of Research and Development, Department of Veterans Affairs,
National Institutes of Health (AG08017, MO1 RR000334, UL1 RR024140),
Alzheimer Tax Check-off Grant. Data collection and sharing for this
project was funded by the Alzheimer's Disease Neuroimaging Initiative
(ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is
funded by the National Institute on Aging, the National Institute of
Biomedical Imaging and Bioengineering, and through generous
contributions from the following: Abbott; AstraZeneca AB; Bayer Schering
Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan
Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics;
Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co.,
Inc.; Novartis AG; Pfizer Inc.; F. Hoffman-La Roche; Schering-Plough;
Synarc, Inc.; and nonprofit partners the Alzheimer's Association and
Alzheimer's Drug Discovery Foundation, with participation from the US
Food and Drug Administration. Private sector contributions to ADNI are
facilitated by the Foundation for the National Institutes of Health
(www.fnih.org). The grantee organization is the Northern California
Institute for Research and Education, and the study is coordinated by
the Alzheimer's Disease Cooperative Study at the University of
California, San Diego. ADNI data are disseminated by the Laboratory for
Neuro Imaging at the University of California, Los Angeles. This
research was also supported by NIH grants P30 AG010129, K01 AG030514,
and the Dana Foundation.
NR 34
TC 0
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0893-0341
J9 ALZ DIS ASSOC DIS
JI Alzheimer Dis. Assoc. Dis.
PD JUL-SEP
PY 2011
VL 25
IS 3
BP 276
EP 282
DI 10.1097/WAD.0b013e31820a1d32
PG 7
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA 811JW
UT WOS:000294206600013
PM 21297427
ER
PT J
AU Cornwell, BR
Heller, R
Biggs, A
Pine, DS
Grillon, C
AF Cornwell, Brian R.
Heller, Randi
Biggs, Arter
Pine, Daniel S.
Grillon, Christian
TI Becoming the Center of Attention in Social Anxiety Disorder: Startle
Reactivity to a Virtual Audience During Speech Anticipation
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; PUBLIC SPEAKING TASK; CEREBRAL
BLOOD-FLOW; AMYGDALA ACTIVATION; VIETNAM VETERANS; ACOUSTIC STARTLE;
PHOBIA; COMORBIDITY; REALITY; FACES
AB Objective: A detailed understanding of how individuals diagnosed with social anxiety disorder (SAD) respond physiologically under social-evaluative threat is lacking. Our aim was to isolate the specific components of public speaking that trigger fear in vulnerable individuals and best discriminate between SAD and healthy individuals.
Method: Sixteen individuals diagnosed with SAD (DSM-IV-TR criteria) and 16 healthy individuals were enrolled in the study from December 2005 to March 2008. Subjects were asked to prepare and deliver a short speech in a virtual reality (VR) environment. The VR environment simulated standing center stage before a live audience and allowed us to gradually introduce social cues during speech anticipation. Startle eye-blink responses were elicited periodically by white noise bursts presented during anticipation, speech delivery, and recovery in VR, as well as outside VR during an initial habituation phase, and startle reactivity was measured by electromyography. Subjects rated their distress at 4 time-points in VR using a 0-10 scale, with anchors being "not distressed" to "highly distressed." State anxiety was measured before and after VR with the Spielberger State-Trait Anxiety Inventory.
Results: Individuals with SAD reported greater distress and state anxiety than healthy individuals across the entire procedure (P values < .005). Analyses of startle reactivity revealed a robust group difference during speech anticipation in VR, specifically as audience members directed their eye gaze and turned their attention toward participants (P < .05, Bonferroni-corrected).
Conclusions: The VR environment is sufficiently realistic to provoke fear and anxiety in individuals highly vulnerable to socially threatening situations. Individuals with SAD showed potentiated startle, indicative of a strong phasic fear response, specifically when they perceived themselves as occupying the focus of others' attention as speech time approached. Potentiated startle under social-evaluative threat indexes SAD-related fear of negative evaluation. J Clin Psychiatry 2011;72(7):942-948 (C) Copyright 2010 Physicians Postgraduate Press, Inc.
C1 [Cornwell, Brian R.; Heller, Randi; Biggs, Arter; Pine, Daniel S.; Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RP Cornwell, BR (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, I5K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM cornwellb@mail.nih.gov
FU National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 46
TC 17
Z9 18
U1 7
U2 20
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD JUL
PY 2011
VL 72
IS 7
BP 942
EP 948
DI 10.4088/JCP.09m05731blu
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 804UD
UT WOS:000293678600009
PM 21034683
ER
PT J
AU Lopez, JE
McCoy, BN
Krajacich, BJ
Schwan, TG
AF Lopez, Job E.
McCoy, Brandi N.
Krajacich, Benjamin J.
Schwan, Tom G.
TI Acquisition and Subsequent Transmission of Borrelia hermsii by the Soft
Tick Ornithodoros hermsi
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE relapsing fever spirochetes; Borrelia hermsii; Ornithodoros hermsi;
acquisition; transmission
ID RELAPSING FEVER; ANTIGENIC VARIATION; BURGDORFERI; ARGASIDAE; INFECTION;
DEFENSIN; IMMUNITY; MOUBATA; DISEASE; MIDGUT
AB Tick-borne relapsing fever is caused by spirochetes within the genus Borrelia. The hallmark of this disease is recurrent febrile episodes and high spirochete densities in mammalian blood resulting from immune evasion. Between episodes of spirochetemia when bacterial densities are low, it is unknown whether ticks can acquire the spirochetes, become colonized by the bacteria, and subsequently transmit the bacteria once they feed again. We addressed these questions by feeding ticks, Ornithodoros hermsi Wheeler (Acari: Argasidae), daily on an infected mouse during low and high levels of spirochete infections. This study demonstrates that spirochete acquisition by the tick vector can occur during low levels of mammalian infection and that once a spirochetemic threshold is attained within the blood, nearly 100% of ticks become colonized by Borrelia hermsii.
C1 [Lopez, Job E.; McCoy, Brandi N.; Krajacich, Benjamin J.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Lopez, JE (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM lopezjob@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank B. Joseph Hinnebusch and Ryan O. Rego for reviewing this
manuscript. This work was supported by the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 31
TC 7
Z9 7
U1 1
U2 4
PU ENTOMOLOGICAL SOC AMER
PI LANHAM
PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA
SN 0022-2585
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD JUL
PY 2011
VL 48
IS 4
BP 891
EP 895
DI 10.1603/ME10283
PG 5
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 810KJ
UT WOS:000294123900021
PM 21845950
ER
PT J
AU Cebrian-Torrejon, G
Spelman, K
Leblanc, K
Munoz-Durango, K
Gutierrez, ST
Ferreira, ME
de Arias, AR
Figadere, B
Fournet, A
Maciuk, A
Grellier, P
Cech, NB
Poupon, E
AF Cebrian-Torrejon, Gerardo
Spelman, Kevin
Leblanc, Karine
Munoz-Durango, Katalina
Gutierrez, Sandra Torijano
Ferreira, Maria Elena
de Arias, Antonieta Rojas
Figadere, Bruno
Fournet, Alain
Maciuk, Alexandre
Grellier, Philippe
Cech, Nadja B.
Poupon, Erwan
TI The antiplasmodium effects of a traditional South American remedy:
Zanthoxylum chiloperone var. angustifolium against chloroquine resistant
and chloroquine sensitive strains of Plasmodium falciparum
SO REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY
LA English
DT Article
DE alkylamides; avicennol; canthinone alkaloids; Heme-drug adducts;
Plasmodium falciparum; Zanthoxylum chiloperone
ID HIGH-THROUGHPUT SCREEN; CANTHIN-6-ONE ALKALOIDS; IN-VITRO; ANTIMALARIAL;
CONSTITUENTS; MALARIA; ASSAY; HEME; ALKYLAMIDES; ARTEMISININ
AB Zanthoxylum chiloperone var. angustifolium Engl., Rutaceae, is used in traditional medicine to treat fungal and protozoal infections in the central area of South America. Considering the increasing resistance of Plasmodium falciparum in malarial ridden areas, we explored the anti-plasmodial effects of three compounds isolated from Z. chiloperone. The pyranocoumarin trans-avicennol and the canthinone alkaloids, canthin-6-one and 5-methoxycanthin-6-one, were found to have IC50 on chloroquine/mefloquine resistant and sensitive strains of P. falciparum of 0.5-2.7, 2.0-5.3 and 5.1-10.4 mu g/mL, respectively. Moreover, the formation of heme adducts by these compounds is described by a novel alternative method based on MS-CID methods. The alkylamide sanshool was also identified, for first time in this plant, in the dichloromethanic and ethanolic extracts and the extracts were found to be notably non-toxic and displayed good anti-plasmodial effects.
C1 [Cebrian-Torrejon, Gerardo; Leblanc, Karine; Munoz-Durango, Katalina; Gutierrez, Sandra Torijano; Figadere, Bruno; Fournet, Alain; Maciuk, Alexandre; Poupon, Erwan] Univ Paris Sud, Fac Pharm, Lab Pharmacognosie, CNRS,UMR BioCIS 8076, F-92296 Chatenay Malabry, France.
[Spelman, Kevin] NIA, Bioanalyt Chem & Drug Discovery Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA.
[Ferreira, Maria Elena] Univ Nacl Asuncion, Inst Invest Ciencias Salud Asuncion, Dept Trop Med, San Lorenzo, Paraguay.
[de Arias, Antonieta Rojas] Ctr Desarrollo Invest Cient CEDIC FMB Diaz Gill M, Asuncion, Paraguay.
[Grellier, Philippe] Museum Natl Hist Nat, CNRS, Dept Reg Dev & Diversite Mol, FRE 3206, Paris, France.
[Cech, Nadja B.] Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27412 USA.
RP Fournet, A (reprint author), Univ Paris Sud, Fac Pharm, Lab Pharmacognosie, CNRS,UMR BioCIS 8076, 5 Rue Jean Baptiste Clement, F-92296 Chatenay Malabry, France.
EM alain.fournet@ird.fr
OI Munoz-Durango, Katalina/0000-0002-7905-1243
FU European Community
FX The authors thank the European Community for the financial support
(Marie Curie Early Stage Training Fellowship of the European Community's
Sixth Framework Programme: contract BioMedChem (for G. CT., K. S. and K.
MD.). Thanks are due to Mrs. A. Solgadi (SAMM) for MS experiments and
Dra Nashira Campos Vieira (University of Brasilia) for the portuguese
traduction.
NR 34
TC 4
Z9 4
U1 0
U2 13
PU SOC BRASILEIRA FARMACOGNOSIA
PI JOAO PESSOA
PA C/O PROF JOSE MARIA BARBOSA FILHO, UNIV FEDERAL PARAIBA, LAB TECNOLOGIA
FARMACEUTICA, JOAO PESSOA, 58051-970PB, BRAZIL
SN 0102-695X
J9 REV BRAS FARMACOGN
JI Rev. Bras. Farmacogn.-Braz. J. Pharmacogn.
PD JUL-AUG
PY 2011
VL 21
IS 4
BP 652
EP 661
DI 10.1590/S0102-695X2011005000104
PG 10
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 810KB
UT WOS:000294123100014
ER
PT J
AU Nelson, LM
AF Nelson, Lawrence M.
TI One World, One Woman: A Kyosei Approach to Primary Ovarian Insufficiency
PREFACE
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Editorial Material
ID WOMEN
C1 NICHHD, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Nelson, LM (reprint author), NICHHD, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
EM Lawrence_Nelson@nih.gov
FU Intramural NIH HHS [Z01 HD000633-17]
NR 10
TC 0
Z9 0
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD JUL
PY 2011
VL 29
IS 4
BP 279
EP 281
DI 10.1055/s-0031-1280913
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 810PQ
UT WOS:000294138600002
PM 21969263
ER
PT J
AU Sullivan, SD
Castrillon, DH
AF Sullivan, Shannon D.
Castrillon, Diego H.
TI Insights into Primary Ovarian Insufficiency through Genetically
Engineered Mouse Models
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE Primary ovarian insufficiency; premature ovarian failure; primordial
follicle activation; apoptosis; mouse model
ID ANTI-MULLERIAN HORMONE; FOLLICLE-STIMULATING-HORMONE; POLYCYCLIC
AROMATIC-HYDROCARBONS; GRANULOSA-CELL APOPTOSIS; BAX GENE-EXPRESSION;
C-KIT RECEPTOR; PRIMORDIAL FOLLICLES; OOCYTE GROWTH; LIFE-SPAN;
TRANSCRIPTION FACTOR
AB Primary ovarian insufficiency (POI), also known as premature ovarian failure, is a form of hypergonadotropic hypogonadism that causes infertility in similar to 1% of women <40 years of age. POI has important health consequences for affected patients; however, the mechanisms that cause ovarian dysfunction are poorly understood. Elucidating these mechanisms is paramount to developing better testing and treatment strategies for affected girls and women. For obvious reasons, studies looking directly at the human ovary are extremely limited. Recently, numerous genetically engineered mouse models have been developed to investigate the molecular mechanisms that may be involved in the pathogenesis of POI. Two potential mechanisms may be involved in the development of POI: (1) abnormalities in primordial follicle activation and (2) increased rates of apoptosis of oocytes. Each of these mechanisms may lead to early depletion of ovarian follicular reserve, and thus be a contributing factor in POI. This review addresses current knowledge of molecular mechanisms controlling primordial follicle activation and oocyte apoptosis, as evidenced from various genetic mouse models. Translation of these data into clinically effective treatments or even prevention strategies may improve fertility and quality of life for women with this form of reproductive dysfunction.
C1 [Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Sullivan, Shannon D.] NICHD, NIH, Washington, DC USA.
[Sullivan, Shannon D.] Washington Hosp Ctr, Washington, DC 20010 USA.
RP Castrillon, DH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pathol, Room NB6-452,6000 Harry Hines Blvd, Dallas, TX 75390 USA.
EM diego.castrillon@utsouthwestern.edu
FU National Institutes of Health [R01HD048690]; Eunice Kennedy Shriver
National Institute of Child Health & Human Development
FX Research in the Castrillon Laboratory was supported by grant No.
R01HD048690 from the National Institutes of Health and the Eunice
Kennedy Shriver National Institute of Child Health & Human Development.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institute of
Child Health and Human Development or the National Institutes of Health.
NR 97
TC 16
Z9 16
U1 1
U2 8
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD JUL
PY 2011
VL 29
IS 4
BP 283
EP 298
DI 10.1055/s-0031-1280914
PG 16
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 810PQ
UT WOS:000294138600003
PM 21972066
ER
PT J
AU Cheng, MH
Nelson, LM
AF Cheng, Mickie H.
Nelson, Lawrence M.
TI Mechanisms and Models of Immune Tolerance Breakdown in the Ovary
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE Primary ovarian insufficiency; ovarian autoimmunity; SCA-POI; APS1;
ovarian failure
ID IDIOPATHIC ADDISONS-DISEASE; EARLY EMBRYONIC-DEVELOPMENT; AIRE-DEFICIENT
MICE; AUTOIMMUNE OOPHORITIS; ZONA-PELLUCIDA; T-CELLS; ADRENAL
INSUFFICIENCY; STEROIDOGENIC ENZYMES; THYMECTOMIZED MICE; SELF-TOLERANCE
AB Ovarian autoimmunity is increasingly implicated in the etiology of primary ovarian insufficiency (POI), previously termed premature ovarian failure or premature menopause. Links to autoimmunity in human POI have long been noted due to the close association of POI with several autoimmune diseases and syndromes such as Addison's disease and Autoimmune polyglandular syndrome 1. However, diagnosis of autoimmune-mediated POI (aPOI) remains challenging because of the lack of sensitive or specific markers of disease. Autoimmunity can arise from the breakdown of immunological tolerance in several ways. How then may we discern what constitutes a relevant target and what represents a downstream phenomenon? The answer lies in the study of pathogenic mechanisms in translational models of disease. From examples in humans and mice, we see that ovarian autoimmunity likely arises from a limited number of antigens targeted in the ovary that are organ specific. These antigens may be conserved but not limited to those seen in animal models of autoimmune ovarian disease. Recent advances in these areas have begun to define the relevant antigens and mechanisms of immune tolerance breakdown in the ovary. Work in translational models continues to provide insight into mechanisms of disease pathogenesis that will allow more accurate diagnosis and, ultimately, improved interventions for women with aPOI.
C1 [Cheng, Mickie H.] Univ Calif San Francisco, Ctr Diabet, Dept Med, Div Endocrinol, San Francisco, CA 94143 USA.
[Nelson, Lawrence M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Cheng, MH (reprint author), Univ Calif San Francisco, Ctr Diabet, Dept Med, Div Endocrinol, 513 Parnassus Ave,HSW 1102 Box 0540, San Francisco, CA 94143 USA.
EM mickie.cheng@ucsf.edu
FU National Institute of Child Health and Human Development, National
Institutes of Health [K08HD058599]
FX Supported in part by the Intramural Research Program, National Institute
of Child Health and Human Development, National Institutes of Health.
LMN is a commissioned officer in the U.S. Public Health Service. MHC is
supported by the National Institute of Child Health and Human
Development, National Institutes of Health (K08HD058599).
NR 66
TC 3
Z9 3
U1 0
U2 4
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
EI 1526-4564
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD JUL
PY 2011
VL 29
IS 4
BP 308
EP 316
DI 10.1055/s-0031-1280916
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 810PQ
UT WOS:000294138600005
PM 21969265
ER
PT J
AU Sterling, EW
Nelson, LM
AF Sterling, Evelina Weidman
Nelson, Lawrence M.
TI From Victim to Survivor to Thriver: Helping Women with Primary Ovarian
Insufficiency Integrate Recovery, Self-Management, and Wellness
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE Primary ovarian insufficiency (POI); premature ovarian failure (POF);
integrative care; recovery; self-management
ID RANDOMIZED CONTROLLED-TRIAL; VITRO FERTILIZATION PREGNANCIES; UNDERLYING
COPING FLEXIBILITY; HORMONE REPLACEMENT THERAPY; BONE-MINERAL DENSITY;
POSTMENOPAUSAL WOMEN; NATURAL MENOPAUSE; YOUNG-WOMEN; PSYCHOSOCIAL
TRANSITION; VENOUS THROMBOEMBOLISM
AB Most women discover that they are infertile in a gradual manner after many failed attempts at conception. By contrast, most women with primary ovarian insufficiency (POI) uncover their infertility as part of an evaluation of other presenting complaints, frequently before attempts at conception have even been contemplated. The most common words women use to describe how they feel in the hours after getting the diagnosis of POI are "devastated," "shocked," and "confused." Clearly, the news propels some patients onto a difficult journey. POI is a serious and incurable chronic disease. The diagnosis is more than infertility and affects a woman's physical and emotional well-being. Management of the condition must address both. Patients face the acute shock of the diagnosis, associated stigma of infertility, grief from the death of dreams, anxiety from the disruption of life plans, confusion around the cause, symptoms of estrogen deficiency, worry over the associated potential medical sequelae such as reduced bone density and cardiovascular risk, and the uncertain future that all of these factors create. There is a need for an evidenced-based integrated program to assist women with POI in navigating the transition to acceptance of the diagnosis, ongoing management of the condition, and ongoing maintenance of wellness in the presence of the disorder. A health-centered approach can gradually replace the disease-centered approach and put patients in partnerships with professional health-care providers. Ideally, the journey transitions each patient from seeing herself as a victim, to a survivor, to a woman who is thriving.
C1 [Sterling, Evelina Weidman] Rachels Well, Marietta, GA 30068 USA.
[Nelson, Lawrence M.] NICHHD, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Sterling, EW (reprint author), Rachels Well, 4880 Lower Roswell Rd,Suite 165,610, Marietta, GA 30068 USA.
EM evelina@rachelswell.org
FU National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, MD
FX This work was supported in part by the Intramural Research Program,
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, MD. LMN is a commissioned officer in the
U.S. Public Health Service.
NR 99
TC 3
Z9 3
U1 3
U2 7
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
EI 1526-4564
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD JUL
PY 2011
VL 29
IS 4
BP 353
EP 361
DI 10.1055/s-0031-1280920
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 810PQ
UT WOS:000294138600009
PM 21969269
ER
PT J
AU Gordon, J
Kopp, JB
AF Gordon, Judit
Kopp, Jeffrey B.
TI Off the Beaten Renin-Angiotensin-Aldosterone System Pathway: New
Perspectives on Antiproteinuric Therapy
SO ADVANCES IN CHRONIC KIDNEY DISEASE
LA English
DT Article
DE Proteinuria; Albuminuria; Podocyte; Glomerulus; Diabetes; Novel
therapies
ID CHRONIC KIDNEY-DISEASE; IDIOPATHIC MEMBRANOUS NEPHROPATHY; EXPERIMENTAL
DIABETIC-NEPHROPATHY; CHILDHOOD IGA NEPHROPATHY; URINE PROTEIN
EXCRETION; PKC BETA INHIBITOR; APOPTOSIS IN-VITRO; PODOCYTE INJURY;
RENAL-FUNCTION; TGF-BETA
AB CKD is a major public health problem in the developed and the developing world. The degree of proteinuria associated with renal failure is a generally well accepted marker of disease severity. Agents with direct antiproteinuric effects are highly desirable therapeutic strategies for slowing, or even halting, progressive loss of kidney function. We review progress on therapies acting further downstream of the renin-angiotensin-aldosterone system pathway (e.g., transforming growth factor-beta antagonism, endothelin antagonism) and on those acting independent of the renin-angiotensin-aldosterone system pathway. In all, we discuss 26 therapeutic targets or compounds and 2 lifestyle changes (dietary modification and weight loss) that have been used clinically for diabetic or nondiabetic kidney disease. These therapies include endogenous molecules (estrogens, isotretinoin), biologic antagonists (monoclonal antibodies, soluble receptors), and small molecules. Where mechanistic data are available, these therapies have been shown to exert favorable effects on glomerular cell phenotype. In some cases, recent work has indicated surprising new molecular pathways for some therapies, such as direct effects on the podocyte by glucocorticoids, rituximab, and erythropoietin. It is hoped that recent advances in the basic science of kidney injury will prompt development of more effective pharmaceutical and biologic therapies for proteinuria. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.
C1 [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
Johns Hopkins Med Inst, Div Nephrol, Baltimore, MD 21205 USA.
RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM Jbkopp@nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU NIDDK
FX This work was supported by the NIDDK Intramural Research Program.
NR 127
TC 7
Z9 7
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1548-5595
J9 ADV CHRONIC KIDNEY D
JI Adv. Chronic Kidney Dis.
PD JUL
PY 2011
VL 18
IS 4
BP 300
EP 311
DI 10.1053/j.ackd.2011.06.002
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 805HK
UT WOS:000293717300011
PM 21782136
ER
PT J
AU Goodman, M
Squibb, K
Youngstrom, E
Anthony, LG
Kenworthy, L
Lipkin, PH
Mattison, DR
LaKind, JS
AF Goodman, Michael
Squibb, Katherine
Youngstrom, Eric
Anthony, Laura Gutermuth
Kenworthy, Lauren
Lipkin, Paul H.
Mattison, Donald R.
LaKind, Judy S.
TI Using systematic reviews and meta-analyses to support regulatory
decision making for neurotoxicants: lessons learned from a case study of
PCBs
SO CIENCIA & SAUDE COLETIVA
LA English
DT Review
DE Domain; Function testing; Meta-analysis; Neurodevelopment;
Neurotoxicants; PCBs; Risk assessment; Weight of evidence
ID POLYCHLORINATED-BIPHENYLS PCBS; PRENATAL EXPOSURE; DICHLORODIPHENYL
DICHLOROETHENE; DEVELOPMENTAL NEUROTOXICITY; CHEMICAL-EXPOSURE; MOTOR
DEVELOPMENT; PUBLICATION BIAS; CHILDREN; DIOXINS; CONTAMINANTS
AB We examined prospective cohort studies evaluating the relation between prenatal and neonatal exposure to polychlorinated biphenyls (PCBs) and neurodevelopment in children to assess the feasibility of conducting a meta-analysis to support decision making. We described studies in terms of exposure and end point categorization, statistical analysis, and reporting of results. We used this evaluation to assess the feasibility of grouping studies into reasonably uniform categories. The most consistently used tests included Brazelton's Neonatal Behavioral Assessment Scale, the neurologic optimality score in the neonatal period, the Bayley Scales of Infant Development at 5-8months of age, and the McCarthy Scales of Children's Abilities in 5-year-olds. Despite administering the same tests at similar ages, the studies were too dissimilar to allow a meaningful quantitative examination of outcomes across cohorts. These analyses indicate that our ability to conduct weight-of-evidence assessments of the epidemiologic literature on neurotoxicants may be limited, even in the presence of multiple studies, if the available study methods, data analysis, and reporting lack comparability.
C1 [LaKind, Judy S.] LaKind Associates LLC, Catonsville, MD 21228 USA.
[Goodman, Michael] Emory Univ, Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA.
[Squibb, Katherine] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Anthony, Laura Gutermuth; Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA.
[Youngstrom, Eric] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Youngstrom, Eric] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Anthony, Laura Gutermuth; Kenworthy, Lauren] George Washington Univ, Dept Pediat, Washington, DC 20052 USA.
[Anthony, Laura Gutermuth; Kenworthy, Lauren] George Washington Univ, Dept Psychiat, Washington, DC USA.
[Kenworthy, Lauren] George Washington Univ, Dept Neurol, Washington, DC USA.
[Lipkin, Paul H.] Kennedy Krieger Inst, Ctr Dev & Learning, Baltimore, MD USA.
[Lipkin, Paul H.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[LaKind, Judy S.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[LaKind, Judy S.] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA USA.
RP LaKind, JS (reprint author), LaKind Associates LLC, 106 Oakdale Ave, Catonsville, MD 21228 USA.
EM lakindassoc@comcast.net
RI Mattison, Donald/L-4661-2013
OI Mattison, Donald/0000-0001-5623-0874
NR 44
TC 0
Z9 0
U1 0
U2 4
PU ABRASCO
PI RIO DE JANEIRO
PA RUA HESPERIA, 16-PARTE MANGUINHOS, RIO DE JANEIRO, 21050-040, BRAZIL
SN 1413-8123
J9 CIENC SAUDE COLETIVA
JI Cienc. Saude Coletiva
PD JUL
PY 2011
VL 16
IS 7
BP 3207
EP 3220
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 801LV
UT WOS:000293441300020
PM 21808908
ER
PT J
AU Wing, RR
Lang, W
Wadden, TA
Safford, M
Knowler, WC
Bertoni, AG
Hill, JO
Brancati, FL
Peters, A
Wagenknecht, L
AF Wing, Rena R.
Lang, Wei
Wadden, Thomas A.
Safford, Monika
Knowler, William C.
Bertoni, Alain G.
Hill, James O.
Brancati, Frederick L.
Peters, Anne
Wagenknecht, Lynne
CA Look AHEAD Res Grp
TI Benefits of Modest Weight Loss in Improving Cardiovascular Risk Factors
in Overweight and Obese Individuals With Type 2 Diabetes
SO DIABETES CARE
LA English
DT Article
ID LIFE-STYLE INTERVENTION; LONG-TERM; LIPOPROTEINS; REDUCTION; DISEASE;
PLASMA; MAINTENANCE; MELLITUS; HEALTH; LIPIDS
AB OBJECTIVE-Overweight and obese individuals are encouraged to lose 5-10% of their body weight to improve cardiovascular disease (CVD) risk, but data supporting this recommendation are limited, particularly for individuals with type 2 diabetes.
RESEARCH DESIGN AND METHODS-We conducted an observational analysis of participants in the Look AHEAD (Action For Health in Diabetes) study (n = 5,145, 40.5% male, 37% from ethnic/racial minorities) and examined the association between the magnitude of weight loss and changes in CVD risk factors at 1 year and the odds of meeting predefined criteria for clinically significant improvements in risk factors in individuals with type 2 diabetes.
RESULTS-The magnitude of weight loss at 1 year was strongly (P < 0.0001) associated with improvements in glycemia, blood pressure, tryiglycerides, and HDL cholesterol but not with LDL cholesterol (P = 0.79). Compared with weight-stable participants, those who lost 5 to <10% ([means +/- SD] 7.25 +/- 2.1 kg) of their body weight had increased odds of achieving a 0.5% point reduction in HbA(1c) (odds ratio 3.52 [95% CI 2.81-4.40]), a 5-mmHg decrease in diastolic blood pressure (1.48 [1.20-1.82]), a 5-mmHg decrease in systolic blood pressure (1.56 [1.27-1.91]), a 5 mg/dL increase in HDL cholesterol (1.69 [1.37-2.07]), and a 40 mg/dL decrease in triglycerides (2.20 [1.71-2.83]). The odds of clinically significant improvements in most risk factors were even greater in those who lost 10-15% of their body weight.
CONCLUSIONS-Modest weight losses of 5 to <10% were associated with significant improvements in CVD risk factors at 1 year, but larger weight losses had greater benefits.
C1 [Wing, Rena R.] Miriam Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI 02906 USA.
[Lang, Wei] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Wadden, Thomas A.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Safford, Monika] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA.
[Knowler, William C.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Bertoni, Alain G.; Wagenknecht, Lynne] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Hill, James O.] Univ Colorado, Hlth Sci Ctr, Ctr Human Nutr, Denver, CO USA.
[Brancati, Frederick L.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Peters, Anne] Roybal Comprehens Hlth Ctr, Los Angeles, CA USA.
RP Wing, RR (reprint author), Miriam Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI 02906 USA.
EM rwing@lifespan.org
OI Peters, Anne/0000-0003-0520-0776
FU National Institute of Diabetes and Digestive and Kidney Diseases; NIH;
CDC
FX This trial was funded by the National Institute of Diabetes and
Digestive and Kidney Diseases, with cofunding from other institutes at
NIH and from CDC; all institutions were involved in design, conduct, and
reporting of results.
NR 24
TC 340
Z9 342
U1 2
U2 24
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2011
VL 34
IS 7
BP 1481
EP 1486
DI 10.2337/dc10-2415
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 799CN
UT WOS:000293261200007
PM 21593294
ER
PT J
AU Bainbridge, KE
Hoffman, HJ
Cowie, CC
AF Bainbridge, Kathleen E.
Hoffman, Howard J.
Cowie, Catherine C.
TI Risk Factors for Hearing Impairment Among US Adults With Diabetes
National Health and Nutrition Examination Survey 1999-2004
SO DIABETES CARE
LA English
DT Article
ID NOISE EXPOSURE HISTORY; UNITED-STATES; OLDER-ADULTS; MELLITUS;
PREVALENCE; NIDDM
AB OBJECTIVE-The objective of this study was to examine the risk factors of low/mid-frequency and high-frequency hearing impairment among a nationally representative sample of diabetic adults.
RESEARCH DESIGN AND METHODS-Data came from 536 participants, aged 20-69 years, with diagnosed or undiagnosed diabetes who completed audiometric testing during 1999 2004 in the National Health and Nutrition Examination Survey (NHANES). We defined hearing impairment as the pure-tone average >25 dB hearing level of pure-tone thresholds at low/mid-frequencies (500; 1,000; and 2,000 Hz) and high frequencies (3,000; 4,000; 6,000; and 8,000 Hz) and identified independent risk factors using logistic regression.
RESULTS-Controlling for age, race/ethnicity, and marital status, odds ratios for associations with low/mid-frequency hearing impairment were 2.20 (95% CI 1.28-3.79) for HDL <40 mg/dL and 3.55 (1.57-8.03) for poor health. Controlling for age, race/ethnicity, sex, and income-to-poverty ratio, odds ratios for associations with high-frequency hearing impairment were 4.39 (1.26-15.26) for history of coronary heart disease and 4.42 (1.26-15.45) for peripheral neuropathy.
CONCLUSIONS-Low HDL, coronary heart disease, peripheral neuropathy, and having poor health are potentially preventable correlates of hearing impairment for people with diabetes. Glycemic control, years since diagnosis, and type of glycemic medication were not associated with hearing impairment.
C1 [Bainbridge, Kathleen E.; Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, Bethesda, MD 20892 USA.
[Cowie, Catherine C.] NIDDKD, Diabet Epidemiol Program, Bethesda, MD 20892 USA.
RP Bainbridge, KE (reprint author), Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, Bethesda, MD 20892 USA.
EM bainbridgek@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
[HHSN267200700001G]
FX This work was financially supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (HHSN267200700001G).
NR 25
TC 25
Z9 29
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2011
VL 34
IS 7
BP 1540
EP 1545
DI 10.2337/dc10-2161
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 799CN
UT WOS:000293261200019
PM 21593298
ER
PT J
AU Bowers, K
Yeung, E
Williams, MA
Qi, L
Tobias, DK
Hu, FB
Zhang, CL
AF Bowers, Katherine
Yeung, Edwina
Williams, Michelle A.
Qi, Lu
Tobias, Deirdre K.
Hu, Frank B.
Zhang, Cuilin
TI A Prospective Study of Prepregnancy Dietary Iron Intake and Risk for
Gestational Diabetes Mellitus
SO DIABETES CARE
LA English
DT Article
ID PROSPECTIVE COHORT; PREGNANT-WOMEN; SERUM FERRITIN; DEFICIENCY; ANEMIA;
DETERMINANTS; STORES
AB OBJECTIVE-It is important to identify modifiable factors that may lower gestational diabetes mellitus (GDM) risk. Dietary iron is of particular interest given that iron is a strong prooxidant, and high body iron levels can damage pancreatic beta-cell function and impair glucose metabolism. The current study is to determine if prepregnancy dietary and supplemental iron intakes are associated with the risk of GDM.
RESEARCH DESIGN AND METHODS-A prospective study was conducted among 13,475 women who reported a singleton pregnancy between 1991 and 2001 in the Nurses' Health Study II. A total of 867 incident GDM cases were reported. Pooled logistic regression was used to estimate the relative risk (RR) of GDM by quintiles of iron intake controlling for dietary and nondietary risk factors.
RESULTS-Dietary heme iron intake was positively and significantly associated with GDM risk. After adjusting for age, BMI, and other risk factors, RRs (95% CIs) across increasing quintiles of heme iron were 1.0 (reference), 1.11 (0.87-1.43), 1.31 (1.03-1.68), 1.51 (1.17-1.93), and 1.58 (1.21-2.08), respectively (P for linear trend 0.0001). The multivariate adjusted RR for GDM associated with every 0.5-mg per day of increase in intake was 1.22 (1.10-1.36). No significant associations were observed between total dietary, nonheme, or supplemental iron intake and GDM risk.
CONCLUSIONS-These findings suggest that higher prepregnancy intake of dietary heme iron is associated with an increased GDM risk.
C1 [Bowers, Katherine; Yeung, Edwina; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20847 USA.
[Williams, Michelle A.] Swedish Med Ctr, Ctr Perinatal Studies, Seattle, WA USA.
[Williams, Michelle A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Qi, Lu; Tobias, Deirdre K.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; Hu, Frank B.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Qi, Lu; Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA.
[Tobias, Deirdre K.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20847 USA.
EM bowerska2@mail.nih.gov; zhangcu@mail.nih.gov
RI Yeung, Edwina/F-5992-2015; Bowers, Katherine/N-5226-2015
OI Yeung, Edwina/0000-0002-3851-2613;
FU National Institutes of Health (NIH) [CA50385, DK58845]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH
FX This study was funded by research grants CA50385 and DK58845 from the
National Institutes of Health (NIH). K.B., C.Z., and E.Y. were supported
by the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, NIH.
NR 26
TC 32
Z9 35
U1 1
U2 10
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2011
VL 34
IS 7
BP 1557
EP 1563
DI 10.2337/dc11-0134
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 799CN
UT WOS:000293261200022
PM 21709294
ER
PT J
AU Qiu, CF
Zhang, CL
Gelaye, B
Enquobahrie, DA
Frederick, IO
Williams, MA
AF Qiu, Chunfang
Zhang, Cuilin
Gelaye, Bizu
Enquobahrie, Daniel A.
Frederick, Ihunnaya O.
Williams, Michelle A.
TI Gestational Diabetes Mellitus in Relation to Maternal Dietary Heme Iron
and Nonheme Iron Intake
SO DIABETES CARE
LA English
DT Article
ID SERUM FERRITIN; WOMENS HEALTH; RISK; PREGNANCY; STORES
AB OBJECTIVE-Higher heme iron intake is associated with increased type 2 diabetes risk. However, no previous study has evaluated gestational diabetes mellitus (GDM) risk in relation to heme iron intake during pregnancy. We investigated associations of maternal preconceptional and early pregnancy heme and nonheme iron intake with subsequent GDM risk.
RESEARCH DESIGN AND METHODS-We conducted a prospective cohort study of 3,158 pregnant women. A food frequency questionnaire was used to assess maternal diet. Multivariable generalized linear regression models were used to derive estimates of relative risks (RRs) and 95% CIs.
RESULTS-Approximately 5.0% of the cohort developed GDM (n = 158). Heme iron intake was positively and significantly associated with GDM risk (P(trend) = 0.04). After adjusting for confounders, women reporting the highest heme iron intake levels (>= 1.52 vs. <0.48 mg per day) experienced a 3.31-fold increased GDM risk (95% CI 1.02-10.72). In fully adjusted models, we noted that a 1-mg per day increase in heme iron was associated with a 51% increased GDM risk (RR 1.51 [95% CI 0.99-2.36]). Nonheme iron was inversely, though not statistically significantly, associated with GDM risk, and the corresponding RRs were 1.00, 0.83, 0.62, and 0.61 across quartiles of nonheme iron intake (P(trend) = 0.08).
CONCLUSIONS-High levels of dietary heme iron intake during the preconceptional and early pregnancy period may be associated with increased GDM risk. Associations of GDM risk with dietary nonheme iron intake are less clear. Confirmation of these findings by future studies is warranted.
C1 [Qiu, Chunfang; Enquobahrie, Daniel A.; Frederick, Ihunnaya O.; Williams, Michelle A.] Swedish Med Ctr, Ctr Perinatal Studies, Seattle, WA 98107 USA.
[Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Gelaye, Bizu; Enquobahrie, Daniel A.; Williams, Michelle A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Qiu, CF (reprint author), Swedish Med Ctr, Ctr Perinatal Studies, Seattle, WA 98107 USA.
EM chun-fang.qiu@swedish.org
OI Gelaye, Bizu/0000-0001-7934-548X
FU National Institutes of Health [R01-HD-32562]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health
FX This research was supported by an award from the National Institutes of
Health (R01-HD-32562). C.Z. was supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health.
NR 25
TC 33
Z9 37
U1 3
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2011
VL 34
IS 7
BP 1564
EP 1569
DI 10.2337/dc11-0135
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 799CN
UT WOS:000293261200023
PM 21709295
ER
PT J
AU Tobias, DK
Hu, FB
Forman, JP
Chavarro, J
Zhang, CL
AF Tobias, Deirdre K.
Hu, Frank B.
Forman, John P.
Chavarro, Jorge
Zhang, Cuilin
TI Increased Risk of Hypertension After Gestational Diabetes Mellitus
Findings from a large prospective cohort study
SO DIABETES CARE
LA English
DT Article
ID GLUCOSE-INTOLERANCE; CARDIOVASCULAR RISK; YOUNG-WOMEN; PREGNANCY
AB OBJECTIVE-Whether a history of gestational diabetes mellitus (GDM) is associated with an increased risk of hypertension after the index pregnancy is not well established.
RESEARCH DESIGN AND METHODS-We investigated the association between GDM and subsequent risk of hypertension after the index pregnancy among 25,305 women who reported at least one singleton pregnancy between 1991 and 2007 in the Nurses' Health Study II.
RESULTS-During 16 years of follow-up, GDM developed in 1,414 women (5.6%) and hypertension developed in 3,138. A multivariable Cox proportional hazards model showed women with a history of GDM had a 26% increased risk of developing hypertension compared with those without a history of GDM (hazard ratio 1.26 [95% CI 1.11-1.431; P = 0.0004). These results were independent of pregnancy hypertension or subsequent type 2 diabetes.
CONCLUSIONS-These results indicate that women with GDM are at a significant increased risk of developing hypertension after the index pregnancy.
C1 [Tobias, Deirdre K.; Hu, Frank B.; Chavarro, Jorge] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Tobias, Deirdre K.; Hu, Frank B.; Chavarro, Jorge] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hu, Frank B.; Forman, John P.; Chavarro, Jorge] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hu, Frank B.; Forman, John P.; Chavarro, Jorge] Harvard Univ, Sch Med, Boston, MA USA.
[Forman, John P.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
[Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
RP Tobias, DK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
EM dbanel@hsph.harvard.edu; zhangcu@mail.nih.gov
FU Eunice Kennedy Shriver NICHD, National Institutes of Health (NIH); NIH
[CA-50385, DK-58845]; Eunice Kennedy Shriver NICHD
FX C.Z. was supported by the Intramural Research Program of the Eunice
Kennedy Shriver NICHD, National Institutes of Health (NIH). This study
was funded by NIH research grants CA-50385 and DK-58845 and the
Intramural Research Program of the Eunice Kennedy Shriver NICHD.
NR 11
TC 12
Z9 12
U1 0
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2011
VL 34
IS 7
BP 1582
EP 1584
DI 10.2337/dc11-0268
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 799CN
UT WOS:000293261200027
PM 21593289
ER
PT J
AU Dabelea, D
Pihoker, C
Talton, JW
D'Agostino, RB
Fujimoto, W
Klingensmith, GJ
Lawrence, JM
Linder, B
Marcovina, SM
Mayer-Davis, EJ
Imperatore, G
Dolan, LM
AF Dabelea, Dana
Pihoker, Catherine
Talton, Jennifer W.
D'Agostino, Ralph B., Jr.
Fujimoto, Wilfred
Klingensmith, Georgeanna J.
Lawrence, Jean M.
Linder, Barbara
Marcovina, Santica M.
Mayer-Davis, Elizabeth J.
Imperatore, Giuseppina
Dolan, Lawrence M.
CA SEARCH Diabet Youth Study
TI Etiological Approach to Characterization of Diabetes Type The SEARCH for
Diabetes in Youth Study
SO DIABETES CARE
LA English
DT Article
ID BETA-CELL FUNCTION; CHILDREN; MELLITUS; DIAGNOSIS; GENOTYPES;
CLASSIFICATION; INSULIN; AUTOIMMUNITY; ADOLESCENTS; ADULTS
AB OBJECTIVE-To describe an etiologic approach to classification of diabetes types in youth based on the 1997 American Diabetes Association (ADA) framework, using data from the SEARCH for Diabetes in Youth Study.
RESEARCH DESIGN AND METHODS-SEARCH conducted a comprehensive assessment of 2,291 subjects aged <20 years with recently diagnosed diabetes. Using autoimmunity (at least one of two diabetes autoantibodies) and insulin sensitivity (equation validated against hyperinsulinemic-euglycemic clamps) as the main etiologic markers, we described four categories along a bidimensional spectrum: autoimmune plus insulin-sensitive (IS), autoimmune plus insulin-resistant (IR), nonautoimmune plus IS, and nonautoimmune plus IR. We then explored how characteristics, including genetic susceptibility to autoimmunity (HLA genotypes), insulin deficiency, and clinical factors varied across these four categories.
RESULTS-Most subjects fell into either the autoimmune plus IS (54.5%) or nonautoimmune plus IR categories (15.9%) and had characteristics that align with traditional descriptions of type 1 or type 2 diabetes. The group classified as autoimmune plus IR (19.5%) had similar prevalence and titers of diabetes autoantibodies and similar distribution of HLA risk genotypes to those in the autoimmune plus IS group, suggesting that it includes individuals with type 1 diabetes who are obese. The group classified as nonautoimmune plus IS (10.1%) likely includes individuals with undetected autoimmunity but may also include those with monogenic diabetes and thus requires further testing.
CONCLUSIONS-The SEARCH study offers researchers and clinicians a practical application for the etiologic classification of diabetes type and at the same time identifies a group of youths who would benefit from further testing.
C1 [Dabelea, Dana] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA.
[Pihoker, Catherine] Univ Washington, Dept Washington, Seattle, WA 98195 USA.
[Talton, Jennifer W.; D'Agostino, Ralph B., Jr.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA.
[Fujimoto, Wilfred] Kuakini Med Ctr, Honolulu, HI USA.
[Klingensmith, Georgeanna J.] Univ Colorado Denver, Barbara Davis Ctr, Sch Med, Aurora, CO USA.
[Klingensmith, Georgeanna J.] Univ Colorado Denver, Dept Pediat, Sch Med, Aurora, CO USA.
[Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA.
[Linder, Barbara] NIDDK, NIH, Bethesda, MD USA.
[Marcovina, Santica M.] Univ Washington, Dept Med, Seattle, WA USA.
[Mayer-Davis, Elizabeth J.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Mayer-Davis, Elizabeth J.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Imperatore, Giuseppina] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Dolan, Lawrence M.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp, Cincinnati, OH USA.
RP Dabelea, D (reprint author), Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO 80045 USA.
EM dana.dabelea@ucdenver.edu
RI Dagostino Jr, Ralph/C-4060-2017
OI Dagostino Jr, Ralph/0000-0002-3550-8395
FU NCRR NIH HHS [UL1 RR025014]
NR 25
TC 67
Z9 69
U1 0
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2011
VL 34
IS 7
BP 1628
EP 1633
DI 10.2337/dc10-2324
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 799CN
UT WOS:000293261200036
PM 21636800
ER
PT J
AU O'Connor, PJ
Bodkin, NL
Fradkin, J
Glasgow, RE
Greenfield, S
Gregg, E
Kerr, EA
Pawlson, LG
Selby, JV
Sutherland, JE
Taylor, ML
Wysham, CH
AF O'Connor, Patrick J.
Bodkin, Noni L.
Fradkin, Judith
Glasgow, Russell E.
Greenfield, Sheldon
Gregg, Edward
Kerr, Eve A.
Pawlson, L. Gregory
Selby, Joseph V.
Sutherland, John E.
Taylor, Michael L.
Wysham, Carol H.
TI Diabetes Performance Measures: Current Status and Future Directions
SO DIABETES CARE
LA English
DT Article
ID QUALITY-OF-CARE; GLYCEMIC CONTROL; CLINICAL-QUALITY; CARDIOTHORACIC
SURGEONS; MEDICATION NONADHERENCE; UNINTENDED CONSEQUENCES; INTERMEDIATE
OUTCOMES; TRANSLATING RESEARCH; SURGICAL MORTALITY; COST-EFFECTIVENESS
C1 [O'Connor, Patrick J.] Hlth Partners Res Fdn, Minneapolis, MN 55440 USA.
[Bodkin, Noni L.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA.
[Fradkin, Judith] NIDDK, Bethesda, MD USA.
[Glasgow, Russell E.] NCI, Rockville, MD USA.
[Greenfield, Sheldon] Univ Calif Irvine, Irvine, CA USA.
[Gregg, Edward] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Kerr, Eve A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Pawlson, L. Gregory] Natl Comm Qual Assurance, Washington, DC USA.
[Selby, Joseph V.] Kaiser Permanente No Calif, Oakland, CA USA.
[Sutherland, John E.] NE Iowa Med Educ Fdn, Waterloo, IA USA.
[Taylor, Michael L.] Caterpillar Inc, Peoria, IL 61629 USA.
[Wysham, Carol H.] Univ Washington, Sch Med, Spokane, WA USA.
RP O'Connor, PJ (reprint author), Hlth Partners Res Fdn, Minneapolis, MN 55440 USA.
EM patrick.j.oconnor@healthpartners.com
RI Kerr, Eve/I-3330-2013
FU sanofi-aventis
FX The consensus development conference was supported by an unrestricted
grant from sanofi-aventis. The company had no input into the content of
the report. No other potential conflicts of interest relevant to this
article were reported.
NR 93
TC 51
Z9 51
U1 3
U2 12
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2011
VL 34
IS 7
BP 1651
EP 1659
DI 10.2337/dc11-0735
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 799CN
UT WOS:000293261200041
PM 21709298
ER
PT J
AU Aronow, WS
Fleg, JL
Pepine, CJ
Artinian, NT
Bakris, G
Brown, AS
Ferdinand, KC
Forciea, MA
Frishman, WH
Jaigobin, C
Kostis, JB
Mancia, G
Oparil, S
Ortiz, E
Reisin, E
Rich, MW
Schocken, DD
Weber, MA
Wesley, DJ
Harrington, RA
Bates, ER
Bhatt, DL
Bridges, CR
Eisenberg, MJ
Ferrari, VA
Fisher, JD
Gardner, TJ
Gentile, F
Gilson, MF
Hlatky, MA
Jacobs, AK
Kaul, S
Moliterno, DJ
Mukherjee, D
Rosenson, RS
Stein, JH
Weitz, HH
Wesley, DJ
AF Aronow, Wilbert S.
Fleg, Jerome L.
Pepine, Carl J.
Artinian, Nancy T.
Bakris, George
Brown, Alan S.
Ferdinand, Keith C.
Forciea, Mary Ann
Frishman, William H.
Jaigobin, Cheryl
Kostis, John B.
Mancia, Giuseppi
Oparil, Suzanne
Ortiz, Eduardo
Reisin, Efrain
Rich, Michael W.
Schocken, Douglas D.
Weber, Michael A.
Wesley, Deborah J.
Harrington, Robert A.
Bates, Eric R.
Bhatt, Deepak L.
Bridges, Charles R.
Eisenberg, Mark J.
Ferrari, Victor A.
Fisher, John D.
Gardner, Timothy J.
Gentile, Federico
Gilson, Michael F.
Hlatky, Mark A.
Jacobs, Alice K.
Kaul, Sanjay
Moliterno, David J.
Mukherjee, Debabrata
Rosenson, Robert S.
Stein, James H.
Weitz, Howard H.
Wesley, Deborah J.
TI ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly A
Report of the American College of Cardiology Foundation Task Force on
Clinical Expert Consensus Documents Developed in Collaboration With the
American Academy of Neurology, American Geriatrics Society, American
Society for Preventive Cardiology, American Society of Hypertension,
American Society of Nephrology, Association of Black Cardiologists, and
European Society of Hypertension
SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION
LA English
DT Article
DE ACCF/AHA Expert Consensus Documents; antihypertensive agents; elderly;
risk assessment; hypertension comorbidities; hypertension
pathophysiology; hypertension therapy
ID ISOLATED SYSTOLIC HYPERTENSION; RENAL-ARTERY STENOSIS; AMBULATORY
BLOOD-PRESSURE; LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED
CONTROLLED-TRIAL; CONVERTING-ENZYME-INHIBITORS;
CONGESTIVE-HEART-FAILURE; VERAPAMIL SR-TRANDOLAPRIL; RENIN-ANGIOTENSIN
SYSTEM; LIPID-LOWERING TREATMENT
C1 [Aronow, Wilbert S.; Pepine, Carl J.; Frishman, William H.] Amer Coll Cardiol Fdn, New York, NY 13206 USA.
[Fleg, Jerome L.; Ortiz, Eduardo] NHLBI, Bethesda, MD USA.
[Artinian, Nancy T.; Brown, Alan S.] Amer Heart Assoc, Dallas, TX USA.
[Ferdinand, Keith C.] Assoc Black Cardiologists, Atlanta, GA USA.
[Forciea, Mary Ann] Amer Coll Physicians, Philadelphia, PA USA.
[Jaigobin, Cheryl] Amer Acad Neurol, St Paul, MN USA.
[Mancia, Giuseppi] European Soc Hypertens, Iowa City, IA USA.
[Reisin, Efrain] Amer Soc Nephrol, Washington, DC 20005 USA.
[Rich, Michael W.] Amer Geriatr Soc, New York, NY USA.
[Schocken, Douglas D.] Amer Soc Prevent Cardiol, Jacksonville, FL 32216 USA.
[Weber, Michael A.] Amer Soc Hypertens, New York, NY USA.
[Wesley, Deborah J.] ACCF Task Force Clin Expert Consensus Documents, Detroit, MI USA.
RP Aronow, WS (reprint author), Amer Coll Cardiol Fdn, New York, NY 13206 USA.
NR 740
TC 52
Z9 58
U1 3
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-1711
J9 J AM SOC HYPERTENS
JI J. Am. Soc. Hypertens.
PD JUL-AUG
PY 2011
VL 5
IS 4
BP 259
EP 352
DI 10.1016/j.jash.2011.06.001
PG 94
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 807BF
UT WOS:000293866000007
PM 21771565
ER
PT J
AU D'Adamo, CR
Miller, RR
Hicks, GE
Orwig, DL
Hochberg, MC
Semba, RD
Yu-Yahiro, JA
Ferrucci, L
Magaziner, J
Shardell, MD
AF D'Adamo, Christopher R.
Miller, Ram R.
Hicks, Gregory E.
Orwig, Denise L.
Hochberg, Marc C.
Semba, Richard D.
Yu-Yahiro, Janet A.
Ferrucci, Luigi
Magaziner, Jay
Shardell, Michelle D.
TI Serum Vitamin E Concentrations and Recovery of Physical Function During
the Year After Hip Fracture
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Vitamin E; Physical function; Hip fracture; Nutrition; Micronutrients
ID OLDER WOMEN; GAMMA-TOCOPHEROL; CONTROLLED-TRIAL; PERFORMANCE;
SUPPLEMENTATION; INTERVENTION; COMMUNITY; INCHIANTI; OUTCOMES; SCALE
AB Background. Poor nutritional status after hip fracture is common and may contribute to physical function decline. Low serum concentrations of vitamin E have been associated with decline in physical function among older adults, but the role of vitamin E in physical recovery from hip fracture has never been explored.
Methods. Serum concentrations of alpha- and gamma-tocopherol, the two major forms of vitamin E, were measured in female hip fracture patients from the Baltimore Hip Studies cohort 4 at baseline and at 2-, 6-, and 12-month postfracture follow-up visits. Four physical function measures-Six-Minute Walk Distance, Lower Extremity Gain Scale, Short Form-36 Physical Functioning Domain, and Yale Physical Activity Survey-were assessed at 2, 6, and 12 months postfracture. Generalized estimating equations modeled the relationship between baseline and time-varying serum tocopherol concentrations and physical function after hip fracture.
Results. A total of 148 women aged 65 years and older were studied. After adjusting for covariates, baseline vitamin E concentrations were positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, and Yale Physical Activity Survey scores (p < .1) and faster improvement in Lower Extremity Gain Scale and Yale Physical Activity Survey scores (p < .008). Time-varying vitamin E was also positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, Yale Physical Activity Survey, and Short Form-36 Physical Functioning Domain (p < .03) and faster improvement in Six-Minute Walk Distance and Short Form-36 Physical Functioning Domain (p < .07).
Conclusions. Serum concentrations of both alpha- and gamma-tocopherol were associated with better physical function after hip fracture. Vitamin E may represent a potentially modifiable factor related to recovery of postfracture physical function.
C1 [D'Adamo, Christopher R.; Miller, Ram R.; Orwig, Denise L.; Magaziner, Jay; Shardell, Michelle D.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA.
[Hochberg, Marc C.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
[Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Yu-Yahiro, Janet A.] Union Mem Hosp, Dept Orthoped Res, Baltimore, MD USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
RP D'Adamo, CR (reprint author), 520 W Lombard St,E Hall, Baltimore, MD 21201 USA.
EM cdadamo@compmed.umm.edu
FU National Institute on Aging at the National Institutes of Health [R01
AG018668, R37 AG09901, T32 AG00262, K23 AG027746, P60 AG12583, P30
AG028747]
FX This work was supported by the National Institute on Aging at the
National Institutes of Health (R01 AG018668, R37 AG09901, T32 AG00262,
K23 AG027746, P60 AG12583, and P30 AG028747).
NR 40
TC 6
Z9 6
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2011
VL 66
IS 7
BP 784
EP 793
DI 10.1093/gerona/glr057
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 806KZ
UT WOS:000293807900007
PM 21486921
ER
PT J
AU Semba, RD
Cappola, AR
Sun, K
Bandinelli, S
Dalal, M
Crasto, C
Guralnik, JM
Ferrucci, L
AF Semba, Richard D.
Cappola, Anne R.
Sun, Kai
Bandinelli, Stefania
Dalal, Mansi
Crasto, Candace
Guralnik, Jack M.
Ferrucci, Luigi
TI Plasma Klotho and Mortality Risk in Older Community-Dwelling Adults
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Aging; Klotho; Longevity; Mortality
ID CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; BONE-MINERAL
DENSITY; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL
WOMEN; FUNCTIONAL VARIANT; GENE POLYMORPHISMS; OXIDATIVE STRESS; HORMONE
KLOTHO
AB Background. The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans.
Methods. We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy.
Results. During 6 years of follow-up, 194(24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho (<575 pg/mL) had an increased risk of death compared with participants in the highest tertile of plasma klotho (>763 pg/mL; hazards ratio 1.78, 95% confidence interval 1.20-2.63).
Conclusions. In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans.
C1 [Semba, Richard D.; Sun, Kai; Dalal, Mansi; Crasto, Candace] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Cappola, Anne R.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Bandinelli, Stefania] Azienda Sanit, Florence, Italy.
[Guralnik, Jack M.] NIA, Epidemiol & Demog Sect, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Semba, RD (reprint author), Smith Bldg,M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
FU National Institute on Aging (NIA) [R01 AG027012, 263 MD 9164, 263 MD
821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Italian Ministry of
Health [ICS110.1/RF97.71]; NIA, National Institutes of Health,
Baltimore, Maryland
FX This work was supported by the National Institute on Aging (NIA) (R01
AG027012), the Italian Ministry of Health (ICS110.1/RF97.71), and NIA
contracts 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, and
N01-AG-5-0002, the Intramural Research Program of NIA, National
Institutes of Health, Baltimore, Maryland.
NR 35
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2011
VL 66
IS 7
BP 794
EP 800
DI 10.1093/gerona/glr058
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 806KZ
UT WOS:000293807900008
PM 21474560
ER
PT J
AU Rossi, AP
Watson, NL
Newman, AB
Harris, TB
Kritchevsky, SB
Bauer, DC
Satterfield, S
Goodpaster, BH
Zamboni, M
AF Rossi, Andrea P.
Watson, Nora L.
Newman, Anne B.
Harris, Tamara B.
Kritchevsky, Stephen B.
Bauer, Douglas C.
Satterfield, Suzanne
Goodpaster, Bret H.
Zamboni, Mauro
TI Effects of Body Composition and Adipose Tissue Distribution on
Respiratory Function in Elderly Men and Women: The Health, Aging, and
Body Composition Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Aging; Lung function; Body composition
ID FAT-FREE MASS; X-RAY ABSORPTIOMETRY; SKELETAL-MUSCLE MASS;
PULMONARY-FUNCTION; LUNG-FUNCTION; WEIGHT CHANGE; PHYSICAL-DISABILITY;
MORTALITY; AGE; OBESITY
AB Background. Previous cross-sectional studies demonstrate positive associations of fat-free mass and negative associations of centrally distributed fat deposits with respiratory function in older adults. Few studies have evaluated whether greater losses of muscle and increases in fat are associated with more rapid decline in respiratory function in aging.
Methods. Nine hundred and fifty-seven men and 1,024 women aged, respectively. 73.6 +/- 2.8 years and 73.2 +/- 2.8 years at baseline were followed for 5 years. Body weight, waist circumference, bone mineral density, fat-free mass, fat mass and fat mass percentage as measured by DXA, abdominal subcutaneous and visceral adipose tissue, thigh muscle area, thigh intermuscular fat by CT and forced expiratory volume in 1 second (FEV1) and forced vital capacity (PVC) were evaluated at baseline and after 5-years follow-up.
Results. Cross-sectional analyses showed that height and thigh muscle area were positively and visceral adipose tissue negatively related to FEV1 and FVC. Increase in fat mass over five years was associated with concurrent FEV1 and FVC decline. In analyses stratified by weight-change categories, men and women who gained weight (vs stable/lost weight) had more rapid declines in FEV1 and PVC.
Conclusion. In this well-functioning cohort, less muscle and greater abdominal fat were each associated with poorer lung spirometry cross-sectionally, whereas increase in fat mass over 5 years was associated with concurrent FEV1 and FVC decline. Weight gain and accompanying fat deposition may accelerate age-related declines in respiratory function.
C1 [Rossi, Andrea P.; Zamboni, Mauro] Univ Verona, Div Geriatr Med, Dept Med, I-37126 Verona, Italy.
[Watson, Nora L.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Harris, Tamara B.] NIA, Geriatr Epidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Goodpaster, Bret H.] Univ Pittsburgh, Div Endocrinol & Metab, Dept Med, Pittsburgh, PA 15260 USA.
RP Rossi, AP (reprint author), Univ Verona, Osped Maggiore, Cattedra Geriatria, Piazzale Stefani 1, I-37126 Verona, Italy.
EM andrea.rossi@hotmail.it
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; ZAMBONI, Mauro/0000-0001-6961-9483;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institutes of Health, National Institute on Aging
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging
(N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106).
NR 30
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U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2011
VL 66
IS 7
BP 801
EP 808
DI 10.1093/gerona/glr059
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 806KZ
UT WOS:000293807900009
PM 21498841
ER
PT J
AU Beck, A
Crain, AL
Solberg, LI
Unutzer, J
Glasgow, RE
Maciosek, MV
Whitebird, R
AF Beck, Arne
Crain, A. Lauren
Solberg, Leif I.
Unuetzer, Juergen
Glasgow, Russell E.
Maciosek, Michael V.
Whitebird, Robin
TI Severity of Depression and Magnitude of Productivity Loss
SO ANNALS OF FAMILY MEDICINE
LA English
DT Article
DE Depression, severity; work impairment; primary care; practice-based
research
ID RANDOMIZED CONTROLLED-TRIAL; WORK PRODUCTIVITY; PRIMARY-CARE; ACTIVITY
IMPAIRMENT; VALIDITY; PERFORMANCE; SYMPTOMS; PHQ-9; METAANALYSIS;
IMPROVEMENT
AB PURPOSE Depression is associated with lowered work functioning, including absences, impaired productivity, and decreased job retention. Few studies have examined depression symptoms across a continuum of severity in relationship to the magnitude of work impairment in a large and heterogeneous patient population, however. We assessed the relationship between depression symptom severity and productivity loss among patients initiating treatment for depression.
METHODS Data were obtained from patients participating in the DIAMOND (Depression Improvement Across Minnesota: Offering a New Direction) initiative, a statewide quality improvement collaborative to provide enhanced depression care. Patients newly started on antidepressants were surveyed with the Patient Health Questionnaire 9-item screen (PHQ-9), a measure of depression symptom severity; the Work Productivity and Activity Impairment (WPAI) questionnaire, a measure of loss in productivity; and items on health status and demographics.
RESULTS We analyzed data from the 771 patients who reported being currently employed. General linear models adjusting for demographics and health status showed a significant linear, monotonic relationship between depression symptom severity and productivity loss: with every 1-point increase in PHQ-9 score, patients experienced an additional mean productivity loss of 1.65% (P < .001). Even minor levels of depression symptoms were associated with decrements in work function. Full-time vs part-time employment status and self-reported fair or poor health vs excellent, very good, or good health were also associated with a loss of productivity (P < .001 and P = .045, respectively).
CONCLUSIONS This study shows a relationship between the severity of depression symptoms and work function, and suggests that even minor levels of depression are associated with a loss of productivity. Employers may find it beneficial to invest in effective treatments for depressed employees across the continuum of depression severity.
C1 [Beck, Arne] Kaiser Permanente, Inst Hlth Res, Denver, CO 80237 USA.
[Beck, Arne] Univ Colorado, Hlth Sci Ctr, Dept Family Med, Denver, CO USA.
[Crain, A. Lauren; Solberg, Leif I.; Maciosek, Michael V.; Whitebird, Robin] HealthPartners Res Fdn, Minneapolis, MN USA.
[Unuetzer, Juergen] Univ Washington, Seattle, WA 98195 USA.
[Glasgow, Russell E.] NCI, Washington, DC USA.
RP Beck, A (reprint author), Kaiser Permanente, Inst Hlth Res, POB 378066, Denver, CO 80237 USA.
EM arne.beck@kp.org
FU National Institute of Mental Health [5R01MH080692]
FX This research was funded by grant 5R01MH080692 from the National
Institute of Mental Health.
NR 28
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U1 5
U2 15
PU ANNALS FAMILY MEDICINE
PI LEAWOOD
PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA
SN 1544-1709
J9 ANN FAM MED
JI Ann. Fam. Med.
PD JUL-AUG
PY 2011
VL 9
IS 4
BP 305
EP 311
DI 10.1370/afm.1260
PG 7
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 797ED
UT WOS:000293106400005
PM 21747101
ER
PT J
AU Williams, DE
Lynch, JE
Doshi, V
Singh, GD
Hargens, AR
AF Williams, David E.
Lynch, John E.
Doshi, Vidhi
Singh, G. Dave
Hargens, Alan R.
TI Bruxism and Temporal Bone Hypermobility in Patients with Multiple
Sclerosis
SO CRANIO-THE JOURNAL OF CRANIOMANDIBULAR PRACTICE
LA English
DT Article
ID INTRACRANIAL-PRESSURE; CRANIAL BONE; VITAMIN-D; FLEXURE
AB In this study, the authors investigated the link between jaw clenching/bruxism and temporal bone movement associated with multiple sclerosis (MS). Twenty-one subjects participated in this study (10 patients with MS and 11 controls). To quantify the change in intracranial dimension between the endocranial surfaces of the temporal bones during jaw clenching, an ultrasonic pulsed phase locked loop (PPLL) device was used. A sustained jaw clenching force of 100 lbs was used to measure the mean change in acoustic pathlength (Delta L) as the measure of intracranial distance. In the control subjects the mean Delta L was 0.27 mm +/- 0.24. In subjects with MS the mean Delta L was 1.71 mm +/- 1.18 (p<0.001). The increase in magnitude of bi-temporal bone intracranial expansion was approximately six times greater in subjects with MS compared to controls. Therefore, jaw clenching/bruxism is associated with more marked displacement of the temporal bones and expansion of the cranial cavity in patients with MS than in control subjects.
C1 [Singh, G. Dave] BioModeling Solut LLC, Cornell Oaks Corp Ctr, Beaverton, OR 97006 USA.
[Lynch, John E.] Lunas Med Prod Grp, Blacksburg, VA USA.
[Singh, G. Dave] NIH Funded Program Craniofacial Res, Bethesda, MD USA.
[Hargens, Alan R.] Univ Calif San Diego, Orthopaed Clin Physiol Lab, San Diego, CA 92103 USA.
[Hargens, Alan R.] NASA, Washington, DC 20546 USA.
[Hargens, Alan R.] Stanford Univ, Stanford, CA 94305 USA.
RP Singh, GD (reprint author), BioModeling Solut LLC, Cornell Oaks Corp Ctr, 15455 NW Greenbrier Pkwy,Commons Bldg,Suite 250, Beaverton, OR 97006 USA.
EM drsingh@drdavesingh.com
FU Stryker Corp., Kalamazoo, MI
FX This research was supported by a research grant from Stryker Corp.,
Kalamazoo, MI. The authors would like to thank G.W. Ellison, UCSD
Department of Neurosciences, San Diego, CA, and B.R. Macias, Department
of Health and Kinesiology, Texas A&M University, for technical
assistance.
NR 29
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U1 1
U2 4
PU CHROMA INC
PI CHATTANOOGA
PA PO BOX 8887, CHATTANOOGA, TN 37414 USA
SN 0886-9634
J9 CRANIO
JI Cranio-J. Craniomandib. Pract.
PD JUL
PY 2011
VL 29
IS 3
BP 178
EP 186
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 803XE
UT WOS:000293614800005
PM 22586826
ER
PT J
AU Sheffield, AM
Gubbels, SP
Hildebrand, MS
Newton, SS
Chiorini, JA
Di Pasquale, G
Smith, RJH
AF Sheffield, Abraham M.
Gubbels, Samuel P.
Hildebrand, Michael S.
Newton, Stephen S.
Chiorini, John A.
Di Pasquale, Giovanni
Smith, Richard J. H.
TI Viral vector tropism for supporting cells in the developing murine
cochlea
SO HEARING RESEARCH
LA English
DT Article
ID MEDIATED GENE-TRANSFER; MAMMALIAN INNER-EAR; ADENOASSOCIATED VIRUS
TYPE-2; GUINEA-PIG COCHLEA; HEARING-LOSS; IN-VIVO; HAIR-CELLS; CONNEXIN
26; SENSORINEURAL DEAFNESS; TRANSGENE EXPRESSION
AB Gene-based therapeutics are being developed as novel treatments for genetic hearing loss. One roadblock to effective gene therapy is the identification of vectors which will safely deliver therapeutics to targeted cells. The cellular heterogeneity that exists within the cochlea makes viral tropism a vital consideration for effective inner ear gene therapy. There are compelling reasons to identify a viral vector with tropism for organ of Corti supporting cells. Supporting cells are the primary expression site of connexin 26 gap junction proteins that are mutated in the most common form of congenital genetic deafness (DFNB1). Supporting cells are also primary targets for inducing hair cell regeneration. Since many genetic forms of deafness are congenital it is necessary to administer gene transfer-based therapeutics prior to the onset of significant hearing loss. We have used transuterine microinjection of the fetal murine otocyst to investigate viral tropism in the developing inner ear. For the first time we have characterized viral tropism for supporting cells following in utero delivery to their progenitors. We report the inner ear tropism and potential ototoxicity of three previously untested vectors: early-generation adenovirus (Ad5.CMV.GFP), advanced-generation adenovirus (Adf.11D) and bovine adeno-associated virus (BAAV.CMV.GFP). Adenovirus showed robust tropism for organ of Corti supporting cells throughout the cochlea but induced increased ABR thresholds indicating ototoxicity. BAAV also showed tropism for organ of Corti supporting cells, with preferential transduction toward the cochlear apex. Additionally, BAAV readily transduced spiral ganglion neurons. Importantly, the BAAV-injected ears exhibited normal hearing at 5 weeks of age when compared to non-injected ears. Our results support the use of BAAV for safe and efficient targeting of supporting cell progenitors in the developing murine inner ear. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Sheffield, Abraham M.; Hildebrand, Michael S.; Newton, Stephen S.; Smith, Richard J. H.] Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA.
[Gubbels, Samuel P.] Univ Wisconsin, Dept Surg, Div Otolaryngol, Madison, WI USA.
[Chiorini, John A.; Di Pasquale, Giovanni] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Smith, RJH (reprint author), Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA.
EM richard-smith@uiowa.edu
OI Hildebrand, Michael/0000-0003-2739-0515
FU NIH - NIDCD [DC003544]; Royal National Institute for Deaf People (RJHS);
NIH-NCRR-CTSA [1UL1RR025011]
FX We would like to acknowledge Dr. Douglas Brough (GenVec Inc.,
Gaithersburg, MD, USA) for providing the Adf.11D vector as well as
valuable discussion; The University of Iowa Gene Transfer Vector Core
for preparation of Ad5.CMV.GFP; Dr. Marlan Hansen (U. of Iowa, Iowa
City, IA, USA) for assistance with images and cochlear dissections;
Penny Harding (U. of Iowa, Iowa City, IA, USA) for cryosectioning
cochleae. No researchers involved in this study report a conflict of
interest. This research was supported in part by grants from the NIH -
NIDCD (DC003544) and The Royal National Institute for Deaf People
(RJHS). SPG is supported by NIH-NCRR-CTSA 1UL1RR025011 (PI-Marc K.
Drezner, MD).
NR 61
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U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD JUL
PY 2011
VL 277
IS 1-2
BP 28
EP 36
DI 10.1016/j.heares.2011.03.016
PG 9
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 805KZ
UT WOS:000293726600004
PM 21530627
ER
PT J
AU Olulade, O
Hu, S
Gonzalez-Castillo, J
Tamer, GG
Luh, WM
Ulmer, JL
Talavage, TM
AF Olulade, O.
Hu, S.
Gonzalez-Castillo, J.
Tamer, G. G., Jr.
Luh, W. -M.
Ulmer, J. L.
Talavage, T. M.
TI Assessment of temporal state-dependent interactions between auditory
fMRI responses to desired and undesired acoustic sources
SO HEARING RESEARCH
LA English
DT Article
ID EVENT-RELATED FMRI; FUNCTIONAL MRI; HEMODYNAMIC-RESPONSES; BOLD
RESPONSE; HUMAN BRAIN; VOLUME MEASUREMENT; CORTICAL AREAS; GRADIENT
NOISE; SCANNER NOISE; CORTEX
AB A confounding factor in auditory functional magnetic resonance imaging (fMRI) experiments is the presence of the acoustic noise inherently associated with the echo planar imaging acquisition technique. Previous studies have demonstrated that this noise can induce unwanted neuronal responses that can mask stimulus-induced responses. Similarly, activation accumulated over multiple stimuli has been demonstrated to elevate the baseline, thus reducing the dynamic range available for subsequent responses. To best evaluate responses to auditory stimuli, it is necessary to account for the presence of all recent acoustic stimulation, beginning with an understanding of the attenuating effects brought about by interaction between and among induced unwanted neuronal responses, and responses to desired auditory stimuli. This study focuses on the characterization of the duration of this temporal memory and qualitative assessment of the associated response attenuation. Two experimental parameters - inter-stimulus interval (ISI) and repetition time (TR) - were varied during an fMRI experiment in which participants were asked to passively attend to an auditory stimulus. Results present evidence of a state-dependent interaction between induced responses. As expected, attenuating effects of these interactions become less significant as TR and ISI increase and in contrast to previous work, persist up to 18s after a stimulus presentation. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Olulade, O.; Talavage, T. M.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
[Olulade, O.] Georgetown Univ, Med Ctr, Ctr Study Learning, Washington, DC 20007 USA.
[Hu, S.] USA, Res Lab, Adelphi, MD USA.
[Gonzalez-Castillo, J.; Tamer, G. G., Jr.; Talavage, T. M.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA.
[Luh, W. -M.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
[Ulmer, J. L.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA.
RP Olulade, O (reprint author), Purdue Univ, Sch Elect & Comp Engn, EE Bldg,465 Northwestern Ave, W Lafayette, IN 47907 USA.
EM oao24@georgetown.edu; shuowen.hu@us.army.mil;
javier.gonzalez-castillo@nih.gov; gtamer@purdue.edu; luhw@mail.nih.gov;
julmer@mcw.edu; tmt@ecn.purdue.edu
RI Gonzalez-Castillo, Javier/B-6903-2012;
OI Gonzalez-Castillo, Javier/0000-0002-6520-5125
FU NIH [R01EB003990]; National Institute of Mental Health
FX The authors wish to thank Dr. Robert W. Prost and Cathy S. Marszalkowski
for their assistance in the execution of this project. This research was
supported in part by NIH grant R01EB003990 and the Intramural Research
Program of the National Institute of Mental Health.
NR 57
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD JUL
PY 2011
VL 277
IS 1-2
BP 67
EP 77
DI 10.1016/j.heares.2011.03.008
PG 11
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 805KZ
UT WOS:000293726600009
PM 21426929
ER
PT J
AU Rahman, MM
Antani, SK
Thoma, GR
AF Rahman, Md Mahmudur
Antani, Sameer K.
Thoma, George R.
TI A Learning-Based Similarity Fusion and Filtering Approach for Biomedical
Image Retrieval Using SVM Classification and Relevance Feedback
SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE
LA English
DT Article
DE Classification; classifier combination; content-based image retrieval
(CBIR); medical imaging; relevance feedback (RF); similarity fusion
ID MEDICAL APPLICATIONS; CLASSIFIERS
AB This paper presents a classification-driven biomedical image retrieval framework based on image filtering and similarity fusion by employing supervised learning techniques. In this framework, the probabilistic outputs of a multiclass support vector machine (SVM) classifier as category prediction of query and database images are exploited at first to filter out irrelevant images, thereby reducing the search space for similarity matching. Images are classified at a global level according to their modalities based on different low-level, concept, and keypoint-based features. It is difficult to find a unique feature to compare images effectively for all types of queries. Hence, a query-specific adaptive linear combination of similarity matching approach is proposed by relying on the image classification and feedback information from users. Based on the prediction of a query image category, individual pre-computed weights of different features are adjusted online. The prediction of the classifier may be inaccurate in some cases and a user might have a different semantic interpretation about retrieved images. Hence, the weights are finally determined by considering both precision and rank order information of each individual feature representation by considering top retrieved relevant images as judged by the users. As a result, the system can adapt itself to individual searches to produce query-specific results. Experiment is performed in a diverse collection of 5 000 biomedical images of different modalities, body parts, and orientations. It demonstrates the efficiency (about half computation time compared to search on entire collection) and effectiveness (about 10%-15% improvement in precision at each recall level) of the retrieval approach.
C1 [Rahman, Md Mahmudur; Antani, Sameer K.; Thoma, George R.] NIH, US Natl Lib Med, Bethesda, MD 20892 USA.
RP Rahman, MM (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM rahmanmm@mail.nih.gov; santani@mail.nih.gov; gthoma@mail.nih.gov
OI Antani, Sameer/0000-0002-0040-1387
FU National Institutes of Health (NIH); National Library of Medicine (NLM);
Lister Hill National Center for Biomedical Communications (LHNCBC)
FX Manuscript received August 23, 2010; revised December 23, 2010; accepted
March 30, 2011. Date of publication June 16, 2011; date of current
version July 15, 2011. This research was supported by the Intramural
Research Program of the National Institutes of Health (NIH), National
Library of Medicine (NLM), and Lister Hill National Center for
Biomedical Communications (LHNCBC).
NR 33
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U1 0
U2 13
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1089-7771
J9 IEEE T INF TECHNOL B
JI IEEE T. Inf. Technol. Biomed.
PD JUL
PY 2011
VL 15
IS 4
BP 640
EP 646
DI 10.1109/TITB.2011.2151258
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA 804NK
UT WOS:000293660300018
PM 21690019
ER
PT J
AU Ssebugenyi, I
Kizza, A
Mpoza, B
Aluma, G
Boaz, I
Newell, K
Laeyendecker, O
Shott, JP
Serwadda, D
Reynolds, SJ
AF Ssebugenyi, I.
Kizza, A.
Mpoza, B.
Aluma, G.
Boaz, I.
Newell, K.
Laeyendecker, O.
Shott, J. P.
Serwadda, D.
Reynolds, S. J.
TI Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR
Monitor v1.5 HIV-1 assays on plasma specimens from Rakai, Uganda
SO INTERNATIONAL JOURNAL OF STD & AIDS
LA English
DT Article
DE HIV-1; viral load; antiretroviral treatment; monitoring;
resource-limited; realtime polymerase chain reaction
ID ANTIRETROVIRAL TREATMENT FAILURE; COBAS-TAQMAN; SOUTH-AFRICA; GROUP-O;
PERFORMANCE; VIRUS; CRITERIA; SUBTYPES; RNA
AB The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART >= six months and 147 from ART-naive patients. The Roche assay detected >= 400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results >= 400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA >= 400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA >= 400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA >= 400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P < 0.0001; mean difference, 0.05). The limits of agreement were -0.97 and 1.07 log(10) copies/mL (mean +/- 2 SD). The Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity.
C1 [Ssebugenyi, I.; Kizza, A.; Mpoza, B.; Aluma, G.; Boaz, I.] Rakai Hlth Sci Program, Kalisizo, Rakai, Uganda.
[Newell, K.; Shott, J. P.] NCI, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Newell, K.; Laeyendecker, O.; Shott, J. P.; Reynolds, S. J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Laeyendecker, O.; Reynolds, S. J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Serwadda, D.] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Reynolds, SJ (reprint author), US Embassy Kampala, POB 7007, Kampala, Uganda.
EM sjr@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD;
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX The authors would like to thank Abbott Molecular Inc for providing the
instruments, assay reagents and supplies to support this study. The
study was supported through the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD. This project has been funded in
whole or in part with federal funds from the National Cancer Institute,
National Institutes of Health, under contract HHSN261200800001E.
NR 12
TC 6
Z9 6
U1 0
U2 0
PU ROYAL SOC MEDICINE PRESS LTD
PI LONDON
PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND
SN 0956-4624
J9 INT J STD AIDS
JI Int. J. STD AIDS
PD JUL
PY 2011
VL 22
IS 7
BP 373
EP 375
DI 10.1258/ijsa.2009.009526
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 797AX
UT WOS:000293095700004
PM 21729954
ER
PT J
AU Sica, A
Melillo, G
Varesio, L
AF Sica, Antonio
Melillo, Giovanni
Varesio, Luigi
TI Hypoxia: a double-edged sword of immunity
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Review
DE Hypoxia; Innate immunity; Adaptive immunity
ID NF-KAPPA-B; INDUCIBLE FACTOR-1-ALPHA; TUMOR PROGRESSION; DENDRITIC
CELLS; OXYGEN HOMEOSTASIS; ENDOTHELIAL-CELLS; SUPPRESSOR-CELLS;
EPITHELIAL-CELLS; GENE-EXPRESSION; INNATE IMMUNITY
AB Hypoxia is a condition of low oxygen tension that characterizes virtually every site of inflammation, tissue damage, and neoplasia. Hypoxic environment attracts infiltrating immune cells that move against oxygen gradients and respond to these demanding conditions by switching to anaerobic metabolism to maintain their energy requirements. Several lines of evidence suggest that oxygen deprivation causes opposite effects on the innate or adaptive immune responses. We will review the evidence that the hypoxic environment promotes the recruitment, activation, and survival of innate immune cells while inhibiting the adaptive immunity through downregulation of effector lymphocyte functions. This divergent regulation of the innate and adaptive immunity appears to reflect evolutionary mechanisms aimed to both guarantee tissue homeostasis and provide safeguard mechanisms against autoimmunity. Selective inhibition of hypoxic signaling pathways in myeloid versus lymphoid cells may open new therapeutic opportunities in diseases characterized by low oxygen tension.
C1 [Sica, Antonio] IRCCS, Ist Clin Humanitas, I-20089 Milan, Italy.
[Sica, Antonio] Univ Piemonte, DISCAFF, I-28100 Novara, Italy.
[Melillo, Giovanni] NCI, Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Varesio, Luigi] G Gaslini Inst Children, Mol Biol Lab, Genoa, Italy.
RP Sica, A (reprint author), IRCCS, Ist Clin Humanitas, Italy Via Manzoni 56, I-20089 Milan, Italy.
EM antonio.sica@humanitas.it
RI varesio, luigi/J-8261-2016
OI varesio, luigi/0000-0001-5659-2218
FU Associazione Italiana Ricerca sul Cancro (AIRC), Italy; Fondazione
Berlucchi, Italy; European Commission; Ministero Universita Ricerca
(MUR), Italy; Associazione Italiana Glicogenosi; Fondazione Italiana per
la lotta al neuroblastoma; Ministero della Salute; Regione Piemonte
[331]
FX This work was supported by Associazione Italiana Ricerca sul Cancro
(AIRC), Italy; Fondazione Berlucchi, Italy; European Commission (project
Mugen); Ministero Universita Ricerca (MUR), Italy; Associazione Italiana
Glicogenosi; Fondazione Italiana per la lotta al neuroblastoma; and
Ministero della Salute and by Regione Piemonte (project number 331,
August 8th, 2009).
NR 97
TC 28
Z9 30
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD JUL
PY 2011
VL 89
IS 7
BP 657
EP 665
DI 10.1007/s00109-011-0724-8
PG 9
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 804FG
UT WOS:000293639100004
PM 21336851
ER
PT J
AU Grefsheim, SF
LaBeause, JH
Satterthwaite, RK
AF Grefsheim, Suzanne F.
LaBeause, Jan H.
Satterthwaite, Rebecca K.
TI Jocelyn Anne Rankin, PhD, FMLA, 1946-2010 OBITUARY
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Biographical-Item
C1 [Grefsheim, Suzanne F.] NIH, Div Lib Serv, Off Res Serv, Bethesda, MD 20892 USA.
[LaBeause, Jan H.] Mercer Univ, Sch Med, Med Lib, Macon, GA 31207 USA.
[LaBeause, Jan H.] Mercer Univ, Sch Med, Peyton T Anderson Learning Resources Ctr, Macon, GA 31207 USA.
[Satterthwaite, Rebecca K.] Ctr Dis Control & Prevent, TechSoft Grp, Atlanta, GA 30333 USA.
RP Grefsheim, SF (reprint author), NIH, Div Lib Serv, Off Res Serv, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM grefshes@mail.nih.gov; labeause_j@mercer.edu; bus8@cdc.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD JUL
PY 2011
VL 99
IS 3
BP 183
EP 184
DI 10.3163/1536-5050.99.3.002
PG 2
WC Information Science & Library Science
SC Information Science & Library Science
GA 801ND
UT WOS:000293445700002
PM 21874675
ER
PT J
AU Cooper, ID
AF Cooper, I. Diane
TI Is the informationist a new role? A logic model analysis
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Editorial Material
ID MEDICAL LIBRARIAN
C1 NIH, NIH Lib, Bethesda, MD 20892 USA.
RP Cooper, ID (reprint author), NIH, NIH Lib, 10 Ctr Dr,Room 1L09H,MSC 1150, Bethesda, MD 20892 USA.
EM cooperd@mail.nih.gov
RI Cooper, Diane/G-5826-2011
NR 13
TC 2
Z9 3
U1 2
U2 9
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD JUL
PY 2011
VL 99
IS 3
BP 189
EP 192
DI 10.3163/1536-5050.99.3.004
PG 4
WC Information Science & Library Science
SC Information Science & Library Science
GA 801ND
UT WOS:000293445700004
PM 21753909
ER
PT J
AU Ananias, HJK
Yu, ZL
Dierckx, RA
van der Wiele, C
Helfrich, W
Wang, F
Tan, YJ
Chen, XY
de Jong, IJ
Elsinga, PH
AF Ananias, Hildo J. K.
Yu, Zilin
Dierckx, Rudi A.
van der Wiele, Christophe
Helfrich, Wijnand
Wang, Fan
Tan, Yongjun
Chen, Xiaoyuan
de Jong, Igle J.
Elsinga, Philip H.
TI (99m)Technetium-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) as a Targeted
Imaging Agent with MicroSPECT in a PC-3 Prostate Cancer Xenograft Model
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE bombesin; prostate; cancer; imaging; SPECT; microSPECT; GRPR; GRP
ID GASTRIN-RELEASING-PEPTIDE; RADIOLABELED BOMBESIN ANALOGS; PELVIC
LYMPH-NODES; RECEPTOR ANTAGONIST; POSITIVE TUMORS; BONE METASTASES;
IN-VITRO; GRP; RADIOPHARMACEUTICALS; DIAGNOSIS
AB The peptide bombesin (BN) and derivates thereof show high binding affinity for the gastrin-releasing peptide receptor (GRPR), which is highly expressed in primary and metastasized prostate cancer. We have synthesized a new BN-based radiopharmaceutical (99m)technetium-HYNIC(tricine/TPPTS)-Aca-BN(7-14) (Tc-99m-HABN) and evaluated its GRPR targeting properties in vitro and in a xenograft tumor model for human prostate cancer in athymic mice. Tc-99m-HABN was synthesized, and its lipophilicity and stability were investigated. The IC50, internalization and efflux properties were determined in vitro using the GRPR expressing human prostate cancer cell line PC-3. Tc-99m-HABN biodistribution and microSPECT imaging were performed in PC-3 tumor-bearing athymic mice. Tc-99m-HABN was prepared with high labeling yield (>90%), hip radiochemical purity (>95%) and a specific activity of similar to 19.8 MBq/nmol. The partition coefficient log D value was -1.60 +/- 0.06. Tc-99m-HABN proved to be stable in human serum for 6 h. The IC50 of HYNIC-Aca-BN(7-14) was 12.81 +/- 0.14 nM. Incubation of PC-3 cells with Tc-99m-HABN demonstrated rapid cellular internalization and a long intracellular retention time. When mice were injected with Tc-99m-HABN, the activity was predominantly cleared via the kidneys. Uptake in the tumor was 2.24 +/- 0.64% ID/g after 30 min, with a steady decrease during the 4 h study period. In vivo experiments with a blocking agent showed GRPR mediated uptake. Tc-99m-HABN microSPECT imaging resulted in clear delineation of the tumor. Tc-99m-HABN is a novel BN-based radiopharmaceutical that proved to be suitable for targeted imaging of prostate cancer with microSPECT using the human prostate cancer cell line PC-3 in a xenograft mouse model.
C1 [Ananias, Hildo J. K.; de Jong, Igle J.] Univ Groningen, Univ Med Ctr Groningen, Dept Urol, NL-9713 AV Groningen, Netherlands.
[Yu, Zilin; Dierckx, Rudi A.; Elsinga, Philip H.] Univ Groningen, Univ Med Ctr Groningen, Dept Nucl Med & Mol Imaging, NL-9713 AV Groningen, Netherlands.
[van der Wiele, Christophe] Ghent Univ Hosp, Dept Nucl Med, B-9000 Ghent, Belgium.
[Helfrich, Wijnand] Univ Groningen, Univ Med Ctr Groningen, Surg Res Lab, NL-9713 AV Groningen, Netherlands.
[Wang, Fan] Peking Univ, Med Isotopes Res Ctr, Beijing, Peoples R China.
[Tan, Yongjun; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
RP Ananias, HJK (reprint author), Hanzeplein 1, NL-9712 RB Groningen, Netherlands.
EM h.j.k.ananias@uro.umcg.nl
FU Dutch Cancer Society [KWF 2008-4243]; Dutch Urology Foundation; Jan
Kornelis de Cock Stichting [08-02]
FX We thank Jurgen Sijbesma for his assistance with the animal experiments
and Chao Wu for his assistance with the micro-SPECT imaging and image
reconstruction. This work was supported by grants of the Dutch Cancer
Society (KWF 2008-4243), the Dutch Urology Foundation 1973 (Stichting
Urologie 1973) and the Jan Kornelis de Cock Stichting (J.K. de Cock
Stichting 08-02).
NR 53
TC 18
Z9 18
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUL-AUG
PY 2011
VL 8
IS 4
SI SI
BP 1165
EP 1173
DI 10.1021/mp200014h
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 799SW
UT WOS:000293307400019
PM 21699202
ER
PT J
AU Zhou, Y
Kim, YS
Yan, X
Jacobson, O
Chen, XY
Liu, S
AF Zhou, Yang
Kim, Young-Seung
Yan, Xin
Jacobson, Orit
Chen, Xiaoyuan
Liu, Shuang
TI Cu-64-Labeled Lissamine Rhodamine B: A Promising PET Radiotracer
Targeting Tumor Mitochondria
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE Cu-64 PET radiotracers; mitochondrial potential; tumor imaging
ID IN-VIVO; IMAGING AGENTS; TRIPHENYLPHOSPHONIUM CATIONS; LIPOPHILIC
CATIONS; PEG(4) LINKERS; BRAIN-TUMOR; RGD PEPTIDE; CELLS; PROBE;
DERIVATIVES
AB Enhanced mitochondrial potential in carcinoma cells is an important characteristic of cancer. It is of great current interest to develop a radiotracer that is sensitive to mitochondrial potential changes at the early stage of tumor growth. In this report, we present the synthesis and evaluation of Cu-64-labeled Lissamine rhodamine B (LRB), Cu-64(DOTA-LRB) (DOTA-LRB = 2-(6-(diethylamino)-3-(diethyliminio)-3H-xanthen-9-yl)-5-(N-(2-(2-(4,7,10-tris(carb oxym ethyl)- 1,4,7,10-tetraazacyclo-dodecan-1-yl)acetamido)ethyl)sulfamoyl)benzenesulfonate) as a new radiotracer for imaging tumors in athymic nude mice bearing U87MG human glioma xenografts by positron emission tomography (PET). We also explored its localization mechanism using Cu(DOTA-LRB) as the fluorescent probe in both the U87MG human glioma cell line and the cultured primary U87MG glioma cells. It was found that Cu-64(DOTA-LRB) had the highest tumor uptake (6.54 +/- 1.50, 6.91 +/- 1.26, 5.68 +/- 1.13, 7.58 +/- 1.96, and 5.14 +/- 1.50%ID/g at 0.5, 1, 2, 4, and 24 h postinjection, respectively) among many Cu-64-labeled organic cations evaluated in the same animal model. The cellular staining study indicated that Cu(DOTA-LRB) was able to localize in mitochondria of U87MG glioma cells due to the enhanced negative rnitochondrial potential. This statement is completely supported by the results from decoupling experiment with carbonylcyanide-m-chlorophenylhydrazone (CCCP). MicroPET data showed that the U87MG glioma tumors were clearly visualized as early as 30 min postinjection with Cu-64 (DOTA-LRB). Cu-64(DOTA-LRB) remained stable during renal excretion, but underwent extensive degradation during hepatobiliary excretion. On the basis of the results from this study, it was concluded that Cu-64(DOTA-LRB) represents a new class of promising PET radiotracers for noninvasive imaging of the MDR-negative tumors.
C1 [Zhou, Yang; Kim, Young-Seung; Yan, Xin; Liu, Shuang] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA.
[Jacobson, Orit; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD USA.
RP Liu, S (reprint author), Purdue Univ, Sch Hlth Sci, 550 Stadium Mall Dr, W Lafayette, IN 47907 USA.
EM liu100@purdue.edu
FU Purdue University; National Cancer Institute (NCI) [R01 CA115883]
FX This work is supported, in part, by Purdue University and Research Grant
R01 CA115883 from the National Cancer Institute (NCI).
NR 61
TC 13
Z9 13
U1 1
U2 18
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUL-AUG
PY 2011
VL 8
IS 4
SI SI
BP 1198
EP 1208
DI 10.1021/mp200025m
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 799SW
UT WOS:000293307400022
PM 21545131
ER
PT J
AU Navath, RS
Menjoge, AR
Dai, H
Romero, R
Kannan, S
Kannan, RM
AF Navath, Raghavendra S.
Menjoge, Anupa R.
Dai, Hui
Romero, Roberto
Kannan, Sujatha
Kannan, Rangararnanujam M.
TI Injectable PAMAM Dendrimer-PEG Hydrogels for the Treatment of Genital
Infections: Formulation and in Vitro and in Vivo Evaluation
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE injectable hydrogels; biodegradable hydrogel; sustained release of
amoxicillin; pregnant guinea pig model; pregnancy; treatment of genital
infections; formulation; in vitro and in vivo evaluation
ID SEXUALLY-TRANSMITTED INFECTIONS; REPRODUCTIVE-TRACT SECRETIONS;
DRUG-DELIVERY APPLICATIONS; GUINEA-PIG MODEL; POLYAMIDOAMINE DENDRIMER;
MECHANISTIC INVESTIGATIONS; POLY(ETHYLENE GLYCOL); BACTERIAL VAGINOSIS;
CHORIOAMNIONITIS; RELEASE
AB Local intravaginal drug therapy is preferred for treatment of ascending genital infections during pregnancy. In the present study, an in situ forming biodegradable hydrogel for sustained release of amoxicillin in the cervicovaginal region is described. A generation 4 poly(amidoamine) [G4-(NH(2))(64)] dendrimer with peripheral thiopyridyl terminations is crosslinked with 8-arm polyethylene glycol (PEG) bearing thiol terminations. The hydrogels were formulated and tested in vivo in a pregnant guinea pig model for volume, retention times, biodegradation, tolerability and transport across fetal membrane. The physicochemical characterization of the hydrogels was carried out using differential calorimetry, SEM, and confocal imaging. The hydrogels offer antibacterial activity arising from sustained release of amoxicillin from gels. The in vivo studies in guinea pig showed that 100-200 mu L, of gel sufficiently covered the cervicovaginal region with a residence time of at least 72 h and gel was primarily retained in the maternal tissues without crossing the fetal membranes into the fetus. The dendrimer gels were stable up to 72 h, and the in vivo biodegradation of gel occurred after 72 h; this correlated well with the in vitro degradation pattern. The pH of the vagina was not altered upon application of the gel, and none of the animals aborted up to 72 h after application of gel. The histological evaluation of the cervical tissues showed absence of edema in the epithelial cell layer, no sloughing of the epithelial or superficial mucous layer, and absence of necrosis and infiltration of inflammatory cells in the submucosal layers, confirming that tissues were tolerant to the gel. The immunohistofluorescence images showed the localization of the gel components on the superficial mucified epithelial layer. The cross-linking density and swelling of hydrogels was impacted by the polymer content, and the 10% hydrogels exhibited the highest cross-link density. The in vitro drug release studies carried out using Franz diffusion cells showed that amoxicillin release from 6 and 10% gels was sustained for 240 h as compared to 3% gels. As the polymer concentration increased to 10%, the release pattern from gels approached diffusion controlled mechanism with diffusional exponent n = 0.49. In conclusion, the biodegradable in situ forming hydrogels of the present study offer a therapeutic option to provide sustained localized delivery of amoxillin intracervically to the pregnant woman for the treatment of ascending genital infections.
C1 [Navath, Raghavendra S.; Menjoge, Anupa R.; Kannan, Rangararnanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA.
[Navath, Raghavendra S.; Menjoge, Anupa R.; Kannan, Rangararnanujam M.] Wayne State Univ, Dept Biomed Engn, Detroit, MI 48202 USA.
[Navath, Raghavendra S.; Menjoge, Anupa R.; Dai, Hui; Romero, Roberto; Kannan, Sujatha; Kannan, Rangararnanujam M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI 48201 USA.
[Navath, Raghavendra S.; Menjoge, Anupa R.; Dai, Hui; Romero, Roberto; Kannan, Sujatha; Kannan, Rangararnanujam M.] Dept Hlth & Human Serv, Detroit, MI 48201 USA.
[Dai, Hui; Kannan, Sujatha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Crit Care Med, Detroit, MI 48201 USA.
RP Kannan, RM (reprint author), Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA.
EM rkannan.wsu@gmail.com
FU Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH/DHHS)
FX This research was supported by the Division of Intramural Research,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH/DHHS). We would like to thank Dr. Mihai
Manitiu for his help with SEM images, Dr. Bing Wang for help with animal
experiments and Dr. C. J. Kim for the histopathological evaluations of
the tissues.
NR 65
TC 42
Z9 42
U1 2
U2 84
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUL-AUG
PY 2011
VL 8
IS 4
SI SI
BP 1209
EP 1223
DI 10.1021/mp200027z
PG 15
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 799SW
UT WOS:000293307400023
PM 21615144
ER
PT J
AU Shukla, S
Skoumbourdis, AP
Walsh, MJ
Hartz, AMS
Fung, KL
Wu, CP
Gottesman, MM
Bauer, B
Thomas, CJ
Ambudkar, SV
AF Shukla, Suneet
Skoumbourdis, Amanda P.
Walsh, Martin J.
Hartz, Anika M. S.
Fung, King Leung
Wu, Chung-Pu
Gottesman, Michael M.
Bauer, Bjoern
Thomas, Craig J.
Ambudkar, Suresh V.
TI Synthesis and Characterization of a BODIPY Conjugate of the BCR-ABL
Kinase Inhibitor Tasigna (Nilotinib): Evidence for Transport of Tasigna
and Its Fluorescent Derivative by ABC Drug Transporters
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE ABC transporter; ABCG2; BCR-ABL kinase; multidrug resistance;
P-glycoprotein; Tasigna
ID CHRONIC MYELOID-LEUKEMIA; BLOOD-BRAIN-BARRIER; CHRONIC MYELOGENOUS
LEUKEMIA; REVERSES MULTIDRUG-RESISTANCE; HIGH-AFFINITY INTERACTION;
HEMATOPOIETIC STEM-CELLS; HUMAN P-GLYCOPROTEIN; IMATINIB MESYLATE;
TYROSINE KINASE; IN-VIVO
AB Tasigna (Nilotinib) is a BCR-ABL kinase inhibitor recently approved by the Food and Drug Administration, which is indicated for the treatment of drug-resistant chronic myelogenous leukemia (CML). The efflux of tyrosine kinase inhibitors by ATP-binding cassette (ABC) drug transporters, which actively pump these drugs out of cells utilizing ATP as an energy source, has been linked to the development of drug resistance in CML patients. We report here the synthesis and characterization of a fluorescent derivative of Tasigna to study its interaction with two major ABC transporters, P-glycoprotein (Pgp) and ABCG2, in in vitro and ex vivo assays. A fluorescent derivative of Tasigna, BODIPY FL Tasigna, inhibited the BCR-ABL kinase activity in K562 cells and was also effluxed by Pgp- and ABCG2-expressing cells in both cultured cells and rat brain capillaries expressing Pgp and ABCG2. In addition, [H-3]-Tasigna was found to be transported by Pgp-expressing polarized LLC-PK1 cells in a transepithelial transport assay. Consistent with these results, both Tasigna and BODIPY FL Tasigna were less effective at inhibiting the phosphorylation of Crkl (a substrate of BCR-ABL kinase) in Pgp- and ABCG2-expressing K562 cells due to their reduced intracellular concentration. Taken together, these data provide evidence that BODIPY FL Tasigna is transported by Pgp and ABCG2, and Tasigna is transported by Pgp. Further, we propose that BODIPY FL Tasigna can potentially be used as a probe for functional analysis of Pgp and ABCG2 in cancer cells and in other preclinical studies.
C1 [Shukla, Suneet; Fung, King Leung; Wu, Chung-Pu; Gottesman, Michael M.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Skoumbourdis, Amanda P.; Walsh, Martin J.; Thomas, Craig J.] NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
[Hartz, Anika M. S.] Univ Minnesota, Sch Med, Dept Biochem & Mol Biochem, Duluth, MN 55812 USA.
[Hartz, Anika M. S.] Univ Minnesota, Coll Pharm, Dept Pharmaceut Sci, Duluth, MN 55812 USA.
RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ambudkar@helix.nih.gov
RI shukla, suneet/B-4626-2012
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. We thank Dr.
Krishnamachary Nandigama for providing Pgp-expressing High-five insect
cell crude membranes, Anne Ramsey for help in kinase assays, and George
Leiman for editorial assistance.
NR 53
TC 20
Z9 20
U1 2
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUL-AUG
PY 2011
VL 8
IS 4
SI SI
BP 1292
EP 1302
DI 10.1021/mp2001022
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 799SW
UT WOS:000293307400031
PM 21630681
ER
PT J
AU Djamshidian, A
O'Sullivan, SS
Wittmann, BC
Lees, AJ
Averbeck, BB
AF Djamshidian, Atbin
O'Sullivan, Sean S.
Wittmann, Bianca C.
Lees, Andrew J.
Averbeck, Bruno B.
TI Novelty seeking behaviour in Parkinson's disease
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Impulsive compulsive behaviour; Parkinson's disease; Novelty seeking;
Learning; Dopamine
ID STRIATAL DOPAMINE RELEASE; IMPULSE-CONTROL; COMPULSIVE BEHAVIORS;
DRUG-USE; MECHANISMS; DISORDERS; COCAINE; HUMANS; MEMORY; RISK
AB Novelty seeking can be a positive trait leading to creativity and innovation, but it is also related to increased risk of damaging addictive behaviour. We have assessed novelty seeking with a three armed bandit task, in which novel stimuli were occasionally introduced, replacing choice options from which the participants had been choosing. This allowed us to assess whether or not they would be prone to selecting novel stimuli. We tested 25 non impulsive patients with Parkinson's disease (PD) and 27 PD patients with impulsive compulsive behaviours (ICBs). Both patient groups were examined "on" and "off" dopaminergic medication in a counterbalanced order and their behaviour was compared with 24 healthy controls. We found that PD patients with ICBs were significantly more prone to choose novel options than either non impulsive PD patients or controls, regardless of medication status. Our findings suggest that attraction to novelty is a personality trait in all PD patients with ICBs which is independent of medication status. Published by Elsevier Ltd.
C1 [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Lees, Andrew J.] Univ London, Dept Mol Neurosci, London, England.
[Djamshidian, Atbin; O'Sullivan, Sean S.; Lees, Andrew J.] Univ London, Reta Lila Weston Inst Neurol Studies, London, England.
[Wittmann, Bianca C.] Univ Giessen, Dept Psychol, Giessen, Germany.
[Averbeck, Bruno B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA.
EM bruno.averbeck@nih.gov
RI O'Sullivan, Sean/C-9333-2012; Lees, Andrew/A-6605-2009;
OI O'Sullivan, Sean/0000-0002-0583-7956; Djamshidian,
Atbin/0000-0001-7174-6000; Wittmann, Bianca/0000-0002-2583-3311
FU NIH, NIMH
FX The authors wish to thank the patients and families who participated in
the study. This research was supported in part by the Intramural
Research Program of the NIH, NIMH.
NR 42
TC 25
Z9 25
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD JUL
PY 2011
VL 49
IS 9
BP 2483
EP 2488
DI 10.1016/j.neuropsychologia.2011.04.026
PG 6
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 803WA
UT WOS:000293611600022
PM 21565210
ER
PT J
AU McCann, TE
Kosaka, N
Turkbey, B
Mitsunaga, M
Choyke, PL
Kobayashi, H
AF McCann, Thomas E.
Kosaka, Nobuyuki
Turkbey, Baris
Mitsunaga, Makoto
Choyke, Peter L.
Kobayashi, Hisataka
TI Molecular imaging of tumor invasion and metastases: the role of MRI
SO NMR IN BIOMEDICINE
LA English
DT Review
DE cancer; invasion; metastasis; molecular imaging; MRI; PET; optical
imaging
ID SUPERPARAMAGNETIC IRON-OXIDE; CELL-PENETRATING PEPTIDES; MAGNETIC
RESONANCE LYMPHANGIOGRAPHY; MATRIX-METALLOPROTEINASE ACTIVITY; OPTICAL
PROTEOLYTIC BEACONS; LYMPH-NODE METASTASES; WHOLE-BODY MRI; IN-VIVO;
CONTRAST AGENT; BONE METASTASES
AB The processes of tumor invasion and metastasis have been well characterized at the molecular level, and numerous biomarkers of tumor aggressiveness have been discovered. Molecular imaging offers the opportunity to depict specific cell markers relevant to tumor aggressiveness. Here, we describe the role of MRI in identifying tumor invasiveness and metastasis with reference to other methods. Target-specific molecular imaging probes for tumor invasiveness have been developed for positron emission tomography and optical imaging, but progress in MRI has been slower. For example, proteases associated with tumor invasion, such as specific matrix metalloproteinases or cathepsins, can be targeted in vivo using optical and positron emission tomography methods, but have not yet been successful with MRI. In addition, we describe the use of MRI to detect metastases. Novel MR contrast agents based on iron oxide and dendrimer nanomaterials allow for better characterization of tumor metastases. Organ-specific MR contrast agents are used to identify metastatic disease in the liver. Finally, diffusion-weighted whole-body MRI is discussed as an alternative offered by MRI that does not require the use of molecular probes to screen distant metastases. Published in 2010 by John Wiley & Sons, Ltd.
C1 [McCann, Thomas E.; Kosaka, Nobuyuki; Turkbey, Baris; Mitsunaga, Makoto; 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, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA.
FU National Institutes of Health (NIH); Pfizer Inc.; Center for Cancer
Research, NCI/NIH
FX This research year was made possible through the Clinical Research
Training Program, a public-private partnership supported jointly by the
National Institutes of Health (NIH) and Pfizer Inc. (via a grant to the
Foundation for NIH from Pfizer Inc.). This research was supported by the
Intramural Research Program of the Center for Cancer Research, NCI/NIH.
NR 52
TC 13
Z9 13
U1 1
U2 17
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD JUL
PY 2011
VL 24
IS 6
SI SI
BP 561
EP 568
DI 10.1002/nbm.1590
PG 8
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 806LE
UT WOS:000293808500002
PM 21793070
ER
PT J
AU Ching, W
Luhmann, M
AF Ching, Willie
Luhmann, Melissa
TI Neuro-Oncologic Physical Therapy for the Older Person
SO TOPICS IN GERIATRIC REHABILITATION
LA English
DT Article
DE brain metastases; brain tumor; neuro-oncology; physical therapy;
rehabilitation; spinal cord tumor
ID SPINAL-CORD COMPRESSION; BRAIN METASTASES; RADIATION-THERAPY;
CANCER-PATIENTS; REHABILITATION; TUMORS; FATIGUE; GLIOBLASTOMA;
INSTRUMENT; GUIDELINES
AB Because of the uncertainty of the course of diagnoses, patients with neuro-oncological malignancies present challenges to the physical therapist. At times, the presentation of impairments and disabilities of these patients with neuro-oncological diagnoses do not necessarily coincide with the involved area of the brain or spinal cord. It is our intention to provide guidance to the physical therapist who will be working with these patients with neuro-oncological diagnoses, in hopes that their encounters will be more productive and meaningful. This article describes a brief overview of common central nervous system malignancies, its medical treatment, as well as possible complications and adverse effects that would need to be considered in rehabilitating these patients. Special consideration is given to the elderly patients with neuro-oncological diagnoses. Pertinent physical therapy assessments and interventions are discussed.
C1 [Ching, Willie; Luhmann, Melissa] NIH, Dept Hlth & Human Serv, Mark O Hatfield Clin Res Ctr, Rehabil Med Dept,Phys Therapy Sect, Bethesda, MD 20892 USA.
RP Ching, W (reprint author), NIH, Dept Hlth & Human Serv, Mark O Hatfield Clin Res Ctr, Rehabil Med Dept,Phys Therapy Sect, Bethesda, MD 20892 USA.
EM chingw@mail.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 56
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0882-7524
EI 1550-2414
J9 TOP GERIATR REHABIL
JI Top. Geriatr. Rehabil.
PD JUL-SEP
PY 2011
VL 27
IS 3
BP 184
EP 192
DI 10.1097/TGR.0b013e3182198f25
PG 9
WC Gerontology; Rehabilitation
SC Geriatrics & Gerontology; Rehabilitation
GA 802IQ
UT WOS:000293503600005
PM 22049262
ER
PT J
AU Stout, NL
Levy, E
Pfalzer, L
AF Stout, Nicole L.
Levy, Ellen
Pfalzer, Lucinda
TI Upper Quadrant Impairments Associated With Cancer Treatment
SO TOPICS IN GERIATRIC REHABILITATION
LA English
DT Article
DE cancer rehabilitation; upper quadrant dysfunction
ID LYMPH-NODE BIOPSY; QUALITY-OF-LIFE; MODIFIED RADICAL-MASTECTOMY;
ACCESSORY NERVE PALSY; PRIMARY BREAST-CANCER; AXILLARY WEB SYNDROME;
SHOULDER COMPLAINTS; NECK DISSECTIONS; EARLY-DIAGNOSIS; ARM MORBIDITY
AB Cancer treatments commonly compromise a patient's functional mobility. Cancers of the upper body affect use of the upper extremities and incite many impairments of the upper quadrant. Cancer treatments including surgery, chemotherapy, and radiation each have unique side effects and adverse effects that directly and indirectly impact the upper quadrant. Impairments can occur early, during, or immediately after cancer treatment; or late, long after the patient has completed treatment. It is imperative in physical therapy practice that clinicians are knowledgeable about the cancer disease process, cancer treatment, and its short- and long-term effects. This article highlights cancer treatment modalities and their side effects, summarizes the presenting signs and symptoms of upper extremity impairments that the physical therapist should recognize as cancer-related in the Review of Systems, and highlights many upper extremity impairments commonly associated with cancer treatment.
C1 [Stout, Nicole L.] Natl Naval Med Ctr, Breast Care Ctr, Bethesda, MD 20889 USA.
[Levy, Ellen] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Pfalzer, Lucinda] Univ Michigan, Dept Phys Therapy, Flint, MI 48503 USA.
RP Stout, NL (reprint author), Natl Naval Med Ctr, Breast Care Ctr, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM nicole.stout@med.navy.mil
NR 93
TC 0
Z9 0
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0882-7524
J9 TOP GERIATR REHABIL
JI Top. Geriatr. Rehabil.
PD JUL-SEP
PY 2011
VL 27
IS 3
BP 222
EP 233
DI 10.1097/TGR.0b013e31821990fb
PG 12
WC Gerontology; Rehabilitation
SC Geriatrics & Gerontology; Rehabilitation
GA 802IQ
UT WOS:000293503600009
ER
PT J
AU Croarkin, E
Huang, MH
AF Croarkin, Earllaine
Huang, Min-Hui
TI Screening Balance Deficits in Older Individuals Diagnosed With Cancer
SO TOPICS IN GERIATRIC REHABILITATION
LA English
DT Article
DE balance; cancer; falls
ID ANDROGEN-DEPRIVATION THERAPY; PARANEOPLASTIC CEREBELLAR DEGENERATION;
RECEIVING RADIATION-THERAPY; BODY-COMPOSITION CHANGES; DWELLING
ELDERLY-PEOPLE; CENTRAL-NERVOUS-SYSTEM; BREAST-CANCER; PROSTATE-CANCER;
RISK-FACTORS; FALL RISK
AB Nearly one-third of older adults experience a fall every year. Balance and gait deficits are among the most important risk factors of falls. Cancer and associated interventions used to cure it challenge systems responsible for maintaining balance control. Older individuals diagnosed with cancer are more likely to develop impairments and disability and are at a slightly higher risk of falls. An improved understanding of age-related changes in balance control and increased knowledge of screening tools that identify those at risk for falls can help lower fall risk.
C1 [Croarkin, Earllaine] NIH, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20896 USA.
[Huang, Min-Hui] Univ Michigan, Phys Therapy Dept, Sch Hlth Profess & Studies, Flint, MI 48503 USA.
RP Croarkin, E (reprint author), NIH, Mark O Hatfield Clin Res Ctr, 10 Ctr Dr MSC 1604, Bethesda, MD 20896 USA.
EM earllaine_croarkin@nih.gov
NR 104
TC 0
Z9 0
U1 6
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0882-7524
J9 TOP GERIATR REHABIL
JI Top. Geriatr. Rehabil.
PD JUL-SEP
PY 2011
VL 27
IS 3
BP 244
EP 251
DI 10.1097/TGR.0b013e318219915a
PG 8
WC Gerontology; Rehabilitation
SC Geriatrics & Gerontology; Rehabilitation
GA 802IQ
UT WOS:000293503600011
ER
PT J
AU Gaitan, MI
Shea, CD
Evangelou, IE
Stone, RD
Fenton, KM
Bielekova, B
Massacesi, L
Reich, DS
AF Gaitan, Maria I.
Shea, Colin D.
Evangelou, Iordanis E.
Stone, Roger D.
Fenton, Kaylan M.
Bielekova, Bibiana
Massacesi, Luca
Reich, Daniel S.
TI Evolution of the Blood-Brain Barrier in Newly Forming Multiple Sclerosis
Lesions
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID GADOLINIUM-ENHANCING LESIONS; MRI; PERFUSION; RING; DTPA; DEMYELINATION;
PERMEABILITY; INFLAMMATION; ENHANCEMENT; PATHOLOGY
AB Objective: Multiple sclerosis (MS) lesions develop around small, inflamed veins. New lesions enhance with gadolinium on magnetic resonance imaging (MRI), reflecting disruption of the blood-brain barrier (BBB). Single time point results from pathology and standard MRI cannot capture the spatiotemporal expansion of lesions. We investigated the development and expansion of new MS lesions, focusing on the dynamics of BBB permeability.
Methods: We performed dynamic contrast-enhanced (DCE) MRI in relapsing-remitting MS. We obtained data over 65 minutes, during and after gadolinium injection. We labeled spatiotemporal enhancement dynamics as centrifugal when initially central enhancement expanded outward and centripetal when initially peripheral enhancement gradually filled the center.
Results: We detected 34 enhancing lesions in 200 DCE-MRI scans. In 65%, enhancement first appeared as a closed ring; in 18%, as a nodule; and in 18%, as an open ring. Lesions with initially nodular enhancement were smaller than those initially enhancing as rings (p < 0.0001). All initially nodular lesions enhanced centrifugally, whereas initially ringlike lesions enhanced centripetally, becoming nodular if small (82%) or nearly nodular if larger (18%). Open-ring lesions were periventricular or juxtacortical and enhanced centripetally. Centrifugally enhancing lesions evolved into centripetally enhancing lesions over several days.
Interpretation: The rapid change of enhancement dynamics from centrifugal to centripetal reflects the outward growth of MS lesions around their central vein and suggests that factors mediating lesion growth and tissue repair derive from different locations at different times. We propose a model of new lesion growth that unites our imaging observations with existing pathology data. ANN NEUROL 2011;70:22-29
C1 [Gaitan, Maria I.; Shea, Colin D.; Evangelou, Iordanis E.; Stone, Roger D.; Fenton, Kaylan M.; Bielekova, Bibiana; Massacesi, Luca; Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Massacesi, Luca] Univ Florence, Dept Neurol & Psychiat Sci, Florence, Italy.
RP Reich, DS (reprint author), 10 Ctr Dr MSC 1400,Bldg 10,Room 5C103, Bethesda, MD 20892 USA.
EM reichds@ninds.nih.gov
RI Reich, Daniel/E-5701-2010;
OI Reich, Daniel/0000-0002-2628-4334; Massacesi, Luca/0000-0001-5083-372X
FU National Institute of Neurological Disorders and Stroke
FX The Intramural Research Program of the National Institute of
Neurological Disorders and Stroke supported this work.
NR 40
TC 61
Z9 62
U1 0
U2 6
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 JUL
PY 2011
VL 70
IS 1
BP 22
EP 29
DI 10.1002/ana.22472
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 800CN
UT WOS:000293336600006
PM 21710622
ER
PT J
AU Hottinger, AF
Iwamoto, FM
Karimi, S
Riedel, E
Dantis, J
Park, J
Panageas, KS
Lassman, AB
Abrey, LE
Fleisher, M
Holland, EC
DeAngelis, LM
Hormigo, A
AF Hottinger, Andreas F.
Iwamoto, Fabio M.
Karimi, Sasan
Riedel, Elyn
Dantis, Jocelynn
Park, Joseph
Panageas, Katherine S.
Lassman, Andrew B.
Abrey, Lauren E.
Fleisher, Martin
Holland, Eric C.
DeAngelis, Lisa M.
Hormigo, Adilia
TI YKL-40 and MMP-9 as Serum Markers for Patients with Primary Central
Nervous System Lymphoma
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID CHITINASE PROTEIN FAMILY; HUMAN CARTILAGE GP-39; PRIMARY CNS LYMPHOMA;
MATRIX METALLOPROTEINASES; GENE-EXPRESSION; SURVIVAL;
MATRIX-METALLOPROTEINASE-9; BIOMARKER; ADHESION; GLIOMAS
AB Objective: To evaluate YKL-40 and MMP-9 proteins as tumor biomarkers in serum samples from patients with primary central nervous system lymphoma (PCNSL).
Methods: In this prospective longitudinal study, serum samples from consecutive patients with histologically confirmed PCNSL were collected concurrently with magnetic resonance imaging (MRI) scans at multiple time points and were analyzed for levels of YKL-40 and MMP-9 by enzyme-linked immunosorbent assay. Marker levels were correlated to disease status and survival.
Results: Forty-five patients with PCNSL were accrued. Median follow-up for survivors was 25 months, and 21 (47%) died during the study. A total of 230 serum samples were collected, and 93% had corresponding MRI scans. PCNSL patients without evidence of radiographic disease (29 patients, 131 samples) had significantly lower levels of serum YKL-40 and MMP-9 than patients with active tumor (n = 34 patients, 84 samples; p = 0.03 and 0.01, respectively). There was a significant inverse correlation between survival and doubling of the YKL-40 level (hazard ratio, 1.7; p = 0.01).
Interpretation: In patients with PCNSL, serum levels of YKL-40 and MMP-9 are associated with radiographic disease status. Longitudinal increase in serum levels of YKL-40, but not MMP-9, predicts survival in patients with PCNSL. ANN NEUROL 2011;70:163-169
C1 [Hottinger, Andreas F.; Iwamoto, Fabio M.; Dantis, Jocelynn; Park, Joseph; Lassman, Andrew B.; Abrey, Lauren E.; Holland, Eric C.; DeAngelis, Lisa M.; Hormigo, Adilia] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[Hottinger, Andreas F.; Iwamoto, Fabio M.; Karimi, Sasan; Lassman, Andrew B.; Abrey, Lauren E.; Holland, Eric C.; DeAngelis, Lisa M.; Hormigo, Adilia] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA.
[Hottinger, Andreas F.] Univ Hosp Geneva, Dept Oncol, Geneva, Switzerland.
[Iwamoto, Fabio M.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
[Karimi, Sasan] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[Riedel, Elyn; Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol Biostat, New York, NY 10021 USA.
[Fleisher, Martin] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA.
[Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA.
[Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA.
RP Hormigo, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA.
EM hormigoa@mskcc.org
FU Society for Memorial Sloan-Kettering Cancer Center
FX Supported by the Society for Memorial Sloan-Kettering Cancer Center
(A.H.).
NR 39
TC 17
Z9 17
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD JUL
PY 2011
VL 70
IS 1
BP 163
EP 169
DI 10.1002/ana.22360
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 800CN
UT WOS:000293336600020
PM 21391238
ER
PT J
AU Pratt, MM
John, K
MacLean, AB
Afework, S
Phillips, DH
Poirier, MC
AF Pratt, M. Margaret
John, Kaarthik
MacLean, Allan B.
Afework, Senait
Phillips, David H.
Poirier, Miriam C.
TI Polycyclic Aromatic Hydrocarbon (PAH) Exposure and DNA Adduct
Semi-Quantitation in Archived Human Tissues
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Review
DE DNA damage; human tissues; immunohistochemistry; immunoassay; PAH-DNA
adducts; semi-quantitation; molecular epidemiology
ID WHITE BLOOD-CELLS; SISTER-CHROMATID EXCHANGE; CELLULAR IMAGING-SYSTEM;
HUMAN CANCER-RISK; BREAST-CANCER; IMMUNOHISTOCHEMICAL DETECTION;
COLORECTAL ADENOMA; UROTHELIAL CELLS; ANIMAL-MODELS; BIOMARKERS
AB Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products), considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies.
C1 [Pratt, M. Margaret; John, Kaarthik; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, Bethesda, MD 20892 USA.
[MacLean, Allan B.; Afework, Senait] Royal Free Hosp Hampstead, Dept Obstet & Gynaecol, London NW3 2QG, England.
[Phillips, David H.] Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England.
RP Pratt, MM (reprint author), NCI, Carcinogen DNA Interact Sect, Bldg 37,Rm 4032 NIH,37 Convent Dr, Bethesda, MD 20892 USA.
EM m2pratt@yahoo.com; kaarthikj@gmail.com; a.maclean@ucl.ac.uk;
senuch@yahoo.com; d.phillips@qub.ac.uk; poirierm@exchange.nih.gov
OI Phillips, David/0000-0001-8509-3485
FU Center for Cancer Research, National Cancer Institute, NIH
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH. We wish to thank
all of our colleagues who contributed to these studies, including: Hilde
E. Van Gijssel, Philip R. Taylor, Sanford M. Dawsey, Philip E. Castle,
Francis L. Martin, David M. DeMarini, Radim J. Sram, David K.
Manchester, Paul Sirajuddin, Ofelia A. Olivero, Rao L. Divi, Laura J.
Schild-Hay, Mark J. Roth, and Steven Hewitt.
NR 49
TC 31
Z9 33
U1 1
U2 44
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD JUL
PY 2011
VL 8
IS 7
BP 2675
EP 2691
DI 10.3390/ijerph8072675
PG 17
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 796QS
UT WOS:000293067300007
PM 21845152
ER
PT J
AU Kraft, AD
Harry, GJ
AF Kraft, Andrew D.
Harry, G. Jean
TI Features of Microglia and Neuroinflammation Relevant to Environmental
Exposure and Neurotoxicity
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Review
DE neuroinflammation; microglia; neurotoxicity; neurodegeneration;
cytokines; environmental exposure
ID CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; DIESEL EXHAUST PARTICLES;
TOLL-LIKE RECEPTORS; NITRIC-OXIDE SYNTHASE; MANGANESE-INDUCED
PARKINSONISM; FOCAL CEREBRAL-ISCHEMIA; NECROSIS-FACTOR-ALPHA;
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OXIDATIVE STRESS CONTRIBUTES
AB Microglia are resident cells of the brain involved in regulatory processes critical for development, maintenance of the neural environment, injury and repair. They belong to the monocytic-macrophage lineage and serve as brain immune cells to orchestrate innate immune responses; however, they are distinct from other tissue macrophages due to their relatively quiescent phenotype and tight regulation by the CNS microenvironment. Microglia actively survey the surrounding parenchyma and respond rapidly to changes such that any disruption to neural architecture or function can contribute to the loss in regulation of the microglia phenotype. In many models of neurodegeneration and neurotoxicity, early events of synaptic degeneration and neuronal loss are accompanied by an inflammatory response including activation of microglia, perivascular monocytes, and recruitment of leukocytes. In culture, microglia have been shown to be capable of releasing several potentially cytotoxic substances, such as reactive oxygen intermediates, nitric oxide, proteases, arachidonic acid derivatives, excitatory amino acids, and cytokines; however, they also produce various neurotrophic factors and quench damage from free radicals and excitotoxins. As the primary source for pro-inflammatory cytokines, microglia are implicated as pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Neuroinflammation should be considered as a balanced network of processes whereby subtle modifications can shift the cells toward disparate outcomes. For any evaluation of neuroinflammation and microglial responses, within the framework of neurotoxicity or degeneration, one key question in determining the consequence of neuroinflammation is whether the response is an initiating event or the consequence of tissue damage. As examples of environmental exposure-related neuroinflammation in the literature, we provide an evaluation of data on manganese and diesel exhaust particles.
C1 [Harry, G. Jean] NIEHS, Neurotoxicol Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Kraft, Andrew D.] US EPA, Oak Ridge Inst Sci & Educ Res Participant, Natl Ctr Environm Assessment, Off Res & Dev, Arlington, VA 22202 USA.
RP Harry, GJ (reprint author), NIEHS, Neurotoxicol Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
EM kraft.andrew@epamail.epa.gov; harry@niehs.nih.gov
FU Division of Intramural Research, National Institute of Environmental
Health Sciences, National Institutes of Health, Department of Health and
Human Services [1Z01ES101623 and ES021164]; U.S. Department of Energy;
EPA
FX This research was supported by the Division of Intramural Research,
National Institute of Environmental Health Sciences, National Institutes
of Health, Department of Health and Human Services #1Z01ES101623 and
ES021164, and in part by an appointment to the Research Participation
Program for the U. S. Environmental Protection Agency, Office of
Research and Development, administered by the Oak Ridge Institute for
Science and Education through an interagency agreement between the U.S.
Department of Energy and EPA. The views expressed in this article are
those of the authors and they do not represent the NIH or U. S. EPA
policy and guidance.
NR 282
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U1 3
U2 24
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD JUL
PY 2011
VL 8
IS 7
BP 2980
EP 3018
DI 10.3390/ijerph8072980
PG 39
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 796QS
UT WOS:000293067300025
PM 21845170
ER
PT J
AU Klein, AP
Duggal, P
Lee, KE
Cheng, CY
Klein, R
Bailey-Wilson, JE
Klein, BEK
AF Klein, Alison P.
Duggal, Priya
Lee, Kristine E.
Cheng, Ching-Yu
Klein, Ronald
Bailey-Wilson, Joan E.
Klein, Barbara E. K.
TI Linkage Analysis of Quantitative Refraction and Refractive Errors in the
Beaver Dam Eye Study
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID HIGH MYOPIA MAPS; GENOME-WIDE ASSOCIATION; HIGH-GRADE MYOPIA; OCULAR
REFRACTION; SUSCEPTIBILITY LOCUS; SCAN; POPULATION; FAMILIES; TRAITS;
IDENTIFICATION
AB PURPOSE. Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed.
METHODS. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed.
RESULTS. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 X 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 X 10(-3) and 1.48 X 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 X 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 X 10-3), a region previously linked to high myopia.
CONCLUSIONS. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11. (Invest Ophthalmol Vis Sci. 2011; 52:5220-5225) DOI: 10.1167/iovs.10-7096
C1 [Klein, Alison P.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA.
[Klein, Alison P.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Klein, Alison P.; Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Lee, Kristine E.; Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI USA.
[Cheng, Ching-Yu; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
RP Klein, AP (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 1550 Orleans St, Baltimore, MD 21231 USA.
EM aklein1@jhmi.edu
RI Cheng, Ching-Yu/K-7017-2013;
OI Cheng, Ching-Yu/0000-0003-0655-885X; Bailey-Wilson,
Joan/0000-0002-9153-2920; Klein, Ronald/0000-0002-4428-6237
FU National Eye Institute [EY06594, EY015286]; Research to Prevent
Blindness; National Human Genome Research Institute; National Center for
Research Resources [RR03655]; National Institutes of Health
[HHSN268200782096C]
FX Supported by National Eye Institute Grants EY06594 (RK, BEKK) and
EY015286 (BEKK) from the National Eye Institute; grants from Research to
Prevent Blindness (RK, BEKK); and the Intramural Research Program of the
National Human Genome Research Institute. Some of the results of this
paper were obtained by using the software program S. A. G. E., which is
supported by U.S. Public Health Service Resource Grant RR03655 from the
National Center for Research Resources. Genotyping services were
provided by the Center for Inherited Disease Research (CIDR). CIDR is
funded through a federal contract from the National Institutes of Health
to The Johns Hopkins University, Contract HHSN268200782096C. APK has
full access to the data and takes responsibility for the integrity of
the data and the data analysis
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PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2011
VL 52
IS 8
BP 5220
EP 5225
DI 10.1167/iovs.10-7096
PG 6
WC Ophthalmology
SC Ophthalmology
GA 800QC
UT WOS:000293377400028
PM 21571680
ER
PT J
AU Chen, JJ
Smaoui, N
Hammer, MBH
Jiao, XD
Riazuddin, SA
Harper, S
Katsanis, N
Riazuddin, S
Chaabouni, H
Berson, EL
Hejtmancik, JF
AF Chen, Jianjun
Smaoui, Nizar
Hammer, Monia Ben Hamed
Jiao, Xiaodong
Riazuddin, S. Amer
Harper, Shyana
Katsanis, Nicholas
Riazuddin, Sheikh
Chaabouni, Habiba
Berson, Eliot L.
Hejtmancik, J. Fielding
TI Molecular Analysis of Bardet-Biedl Syndrome Families: Report of 21 Novel
Mutations in 10 Genes
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BBS GENES; POPULATION; DISEASE; IDENTIFICATION; COMPLEX; LOCUS;
INHERITANCE; PROTEINS; OBESITY
AB PURPOSE. Bardet-Biedl syndrome (BBS) is genetically heterogeneous with 15 BBS genes currently identified, accounting for approximately 70% of cases. The aim of our study was to define further the spectrum of BBS mutations in a cohort of 44 European-derived American, 8 Tunisian, 1 Arabic, and 2 Pakistani families (55 families in total) with BBS.
METHODS. A total of 142 exons of the first 12 BBS-causing genes were screened by dideoxy sequencing. Cases in which no mutations were found were then screened for BBS13, BBS14, BBS15, RPGRIP1L, CC2D2A, NPHP3, TMEM67, and INPP5E.
RESULTS. Forty-three mutations, including 8 frameshift mutations, 10 nonsense mutations, 4 splice site mutations, 1 deletion, and 20 potentially or probably pathogenic missense variations, were identified in 46 of the 55 families studied (84%). Of these, 21 (2 frameshift mutations, 4 nonsense mutations, 4 splice site mutations, 1 deletion, and 10 missense variations) were novel. The molecular genetic findings raised the possibility of triallelic inheritance in 7 Caucasian families, 1 Arabian family, and 1 Tunisian patient. No mutations were detected for BBS4, BBS11, BBS13, BBS14, BBS15, RPGRIP1L, CC2D2A, NPHP3, TMEM67, or INPP5E.
CONCLUSIONS. This mutational analysis extends the spectrum of known BBS mutations. Identification of 21 novel mutations highlights the genetic heterogeneity of this disorder. Differences in European and Tunisian patients, including the high frequency of the M390R mutation in Europeans, emphasize the population specificity of BBS mutations with potential diagnostic implications. The existence of some BBS cases without mutations in any currently identified BBS genes suggests further genetic heterogeneity. (Invest Ophthalmol Vis Sci. 2011; 52:5317-5324) DOI: 10.1167/iovs.11-7554
C1 [Chen, Jianjun; Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Rockville, MD 20852 USA.
[Smaoui, Nizar; Hammer, Monia Ben Hamed] NEI, DNA Diagnost Lab, NIH, Rockville, MD 20852 USA.
[Riazuddin, S. Amer; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Harper, Shyana; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA.
[Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC USA.
[Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC USA.
[Riazuddin, Sheikh] Allama Iqbal Med Coll, Allama Iqbal Med Res Ctr, Lahore, Pakistan.
[Chaabouni, Habiba] Hop Charles Nicolle, Serv Malad Congenitales & Hereditaires, Tunis, Tunisia.
RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 5635 Fishers Lane, Rockville, MD 20852 USA.
EM f3h@helix.nih.gov
RI Katsanis, Nicholas/E-1837-2012;
OI Katsanis, Nicholas/0000-0002-2480-0171
FU Foundation Fighting Blindness
FX Supported in part by a Center Grant from the Foundation Fighting
Blindness (ELB).
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PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2011
VL 52
IS 8
BP 5317
EP 5324
DI 10.1167/iovs.11-7554
PG 8
WC Ophthalmology
SC Ophthalmology
GA 800QC
UT WOS:000293377400041
PM 21642631
ER
PT J
AU Ma, ZW
Yao, WL
Theendakara, V
Chan, CC
Wawrousek, E
Hejtmancik, JF
AF Ma, Zhiwei
Yao, Wenliang
Theendakara, Veena
Chan, Chi-Chao
Wawrousek, Eric
Hejtmancik, J. Fielding
TI Overexpression of Human gamma C-crystallin 5 bp Duplication Disrupts
Lens Morphology in Transgenic Mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BETA-B1-CRYSTALLIN PROMOTER; CATARACT; MOUSE; MUTATIONS; GENE;
SUPERFAMILY; PROTEINS; CHICKEN; MUTANT
AB PURPOSE. To delineate the molecular mechanisms underlying autosomal dominant congenital cataracts caused by a 5 bp duplication in human CRYGC.
METHODS. c. 119_123dup (CRYGC5bpd) and wild-type human gamma C-crystallin (CRYGC) were expressed in transgenic mouse lenses by the chicken beta B1-crystallin promoter. Lenses were characterized histologically, by real-time PCR, SDS-PAGE, and Western blot. pET and Tet-on expression systems were used to express human CRYGC and CRYGC5bpd proteins in Escherichia coliand HeLa cells, respectively.
RESULTS. Transgenic expression of CRYGC5bpd mutant gamma C-crystallin results in nuclear cataracts in which lens fiber cells begin to show variable degrees of degeneration and vacuolization by postnatal day 21. By 6 weeks of age all CRYGC5bpd lenses exhibit abnormalities of varying severity, comprising large vacuoles in cortical fiber cells, swelling and disorganization of fiber cells, and defective fiber cell migration and elongation. Levels of CRYGC5bpd mRNA are 3.7- and 14.1-fold higher than endogenous Crygc mRNA in postnatal day 1 and 6-week CRYGC5bpd mice lens, respectively. Crygc, Crygb, Crybb2, and Crybb3 mRNA levels are decreased in CRYGC5bpd mice compared with wild-type and CRYGC mice. Both wild-type and mutant human gamma C crystallin are uniformly distributed in the cytosol of HeLa cells, but CRYGC5bpd is degraded when expressed in E. coli BL21(DE3).
CONCLUSIONS. Transgenic expression of mutant CRYGC5bpd gamma-crystallin at near-physiological levels causes lens opacities and fiber cell defects, confirming the pathogenicity of this mutation. These results further suggest that HCG5pbd gamma-crystallin causes cataracts through a direct toxic or developmental effect on lens cells causing damaged microstructure rather than through formation of HMW aggregates with resultant light scattering. (Invest Ophthalmol Vis Sci. 2011; 52:5369-5375) DOI: 10.1167/iovs.11-7168
C1 [Ma, Zhiwei; Yao, Wenliang; Theendakara, Veena; Hejtmancik, J. Fielding] NEI, OGVFB, NIH, Rockville, MD 20852 USA.
[Wawrousek, Eric] NEI, Lab Mol & Dev Biol, NIH, Rockville, MD 20852 USA.
[Yao, Wenliang] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Theendakara, Veena] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
RP Hejtmancik, JF (reprint author), NEI, OGVFB, NIH, 5635 Fishers Lane,Room 1127, Rockville, MD 20852 USA.
EM f3h@helix.nih.gov
FU National Eye Institute
FX Supported by the National Eye Institute Intramural Program.
NR 20
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U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2011
VL 52
IS 8
BP 5369
EP 5375
DI 10.1167/iovs.11-7168
PG 7
WC Ophthalmology
SC Ophthalmology
GA 800QC
UT WOS:000293377400047
PM 21436266
ER
PT J
AU West, SK
Stare, D
Mkocha, H
Munoz, B
Gaydos, C
Quinn, TC
AF West, Sheila K.
Stare, Dianne
Mkocha, Harran
Munoz, Beatriz
Gaydos, Charlotte
Quinn, Thomas C.
TI Do Infants Increase the Risk of Re-emergent Infection in Households
after Mass Drug Administration for Trachoma?
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID AZITHROMYCIN
AB PURPOSE. Mass treatment with azithromycin for trachoma endemic communities typically excludes infants under age 6 months, whose parents are provided with tubes of tetracycline to administer daily over 4 to 6 weeks. The authors sought to determine whether infants aged < 6 months are a source of re-emergent infection in their families after mass treatment in trachoma-endemic communities.
METHODS. In a longitudinal study of all children aged less than 10 years in four communities, the authors identified 91 infants aged < 6 months living in 86 of 1241 households. All children aged < ten years in all households were examined for trachoma and ocular infection with C. trachomatis at baseline, and 6 months after mass drug administration.
RESULTS. The prevalence of infection at baseline in the infants was 5.9%. At 6 months post mass drug administration, the rate of infection among children older than 6 months and less than 10 years who resided in households with infants was 6.0% compared with 11.1% in children in households without infants (P = 0.18). After adjustment for age, sex, baseline infection status, and treatment, residing in a household with an infant was not associated with infection at 6 months (odds ratio [95% confidence interval] 0.50 [0.20-1.22]).
CONCLUSIONS. This prospective study did not find evidence that living in a household with an infant increased the risk of infection 6 months post mass drug administration in other children residing in the household. (Invest Ophthalmol Vis Sci. 2011;52:6040-6042) DOI:10.1167/iovs.11-7372
C1 [West, Sheila K.; Stare, Dianne; Munoz, Beatriz] Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21287 USA.
[Gaydos, Charlotte; Quinn, Thomas C.] Johns Hopkins Univ, Dept Infect Dis, Baltimore, MD 21287 USA.
[Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania.
[Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
RP West, SK (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, 600 N Wolfe St,Wilmer Room 129, Baltimore, MD 21287 USA.
EM shwest@jhmi.edu
FU Bill and Melinda Gates Foundation; Research to Prevent Blindness;
Division of Intramural Research, NIAID
FX Supported by the Bill and Melinda Gates Foundation. Pfizer provided
azithromycin to Tanzania as part of their donation program. SKW received
a Senior Scientific Investigator award from Research to Prevent
Blindness. TCQ was supported by the Division of Intramural Research,
NIAID.
NR 7
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U1 0
U2 1
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUL
PY 2011
VL 52
IS 8
BP 6040
EP 6042
DI 10.1167/iovs.11-7372
PG 3
WC Ophthalmology
SC Ophthalmology
GA 800QC
UT WOS:000293377400132
PM 21680866
ER
PT J
AU Waryah, AM
Ahmed, ZM
Binder, MA
Choo, DI
Sisk, RA
Shahzad, M
Khan, SN
Friedman, TB
Riazuddin, S
Riazuddin, S
AF Waryah, Ali M.
Ahmed, Zubair M.
Binder, Munir A.
Choo, Daniel I.
Sisk, Robert A.
Shahzad, Mohsin
Khan, Shaheen N.
Friedman, Thomas B.
Riazuddin, Sheikh
Riazuddin, Saima
TI Molecular and clinical studies of X-linked deafness among Pakistani
families
SO JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE DFN3; gushers; hearing loss; NDP; Norrie disease; POU3F4
ID NORRIE-DISEASE GENE; EXUDATIVE VITREORETINOPATHY; HEARING-LOSS;
PRENATAL-DIAGNOSIS; MISSENSE MUTATIONS; POU3F4 MUTATIONS; CHINESE
FAMILY; DFN3 PATIENTS; CHROMOSOME; PHENOTYPE
AB There are 68 sex-linked syndromes that include hearing loss as one feature and five sex-linked nonsyndromic deafness loci listed in the OMIM database. The possibility of additional such sex-linked loci was explored by ascertaining three unrelated Pakistani families (PKDF536, PKDF1132 and PKDF740) segregating X-linked recessive deafness. Sequence analysis of POU3F4 (DFN3) in affected members of families PKDF536 and PKDF1132 revealed two novel nonsense mutations, p. Q136X and p. W114X, respectively. Family PKDF740 is segregating congenital blindness, mild-to-profound progressive hearing loss that is characteristic of Norrie disease (MIM# 310600). Sequence analysis of NDP among affected members of this family revealed a novel single nucleotide deletion c. 49delG causing a frameshift and premature truncation (p. V17fsX1) of the encoded protein. These mutations were not found in 150 normal DNA samples. Identification of pathogenic alleles causing X-linked recessive deafness will improve molecular diagnosis, genetic counseling and molecular epidemiology of hearing loss among Pakistanis. Journal of Human Genetics (2011) 56, 534-540; doi: 10.1038/jhg.2011.55; published online 2 June 2011
C1 [Waryah, Ali M.; Binder, Munir A.; Shahzad, Mohsin; Khan, Shaheen N.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Ahmed, Zubair M.; Choo, Daniel I.; Riazuddin, Saima] Cincinnati Children Hosp Res Fdn, Mol Genet Lab, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH USA.
[Ahmed, Zubair M.; Choo, Daniel I.; Riazuddin, Saima] Univ Cincinnati, Coll Med, Dept Otolaryngol, Cincinnati, OH USA.
[Ahmed, Zubair M.; Sisk, Robert A.; Riazuddin, Saima] Cincinnati Childrens Hosp Res Fdn, Div Pediat Ophthalmol, Cincinnati, OH USA.
[Ahmed, Zubair M.; Sisk, Robert A.; Riazuddin, Saima] Univ Cincinnati, Coll Med, Dept Ophthalmol, Cincinnati, OH USA.
[Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD USA.
[Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
RP Riazuddin, S (reprint author), Cincinnati Childrens Hosp Med Ctr, Mol Genet Lab, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH 45229 USA.
EM saima.riazuddin@cchmc.org; saima.riazuddin@cchmc.org
RI Nasim Khan, Shaheen/F-2135-2015
FU Cincinnati Children's Hospital Research Foundation (CCHMC); National
Institute on Deafness and Other Communication Disorders (NIDCD/NIH)
[R00-DC009287-03, Z01-DC00039-14]; RPB; Higher Education Commission;
EMRO/WHO-COMSTECH; Ministry of Science and Technology (MoST);
International Center for Genetic Engineering and Biotechnology, Trieste,
Italy [CRP/PAK08-01, 08/009]
FX We are grateful to the families who made this research possible. This
work was supported by Cincinnati Children's Hospital Research Foundation
(CCHMC) intramural research funds to Sheikh Riazuddin and ZMA, the
National Institute on Deafness and Other Communication Disorders
(NIDCD/NIH) research Grant R00-DC009287-03, a Career Development Award
from RPB to ZMA. Work in Pakistan was supported by the Higher Education
Commission to Sheikh Riazuddin, Islamabad; EMRO/WHO-COMSTECH and
Ministry of Science and Technology (MoST) to Sheikh Riazuddin,
Islamabad; the International Center for Genetic Engineering and
Biotechnology, Trieste, Italy under project CRP/PAK08-01 Contract no.
08/009 to Sheikh Riazuddin. Part of this study carried out in the USA
was supported by intramural funds from the NIDCD/NIH (Z01-DC00039-14) to
TBF.
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U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1434-5161
J9 J HUM GENET
JI J. Hum. Genet.
PD JUL
PY 2011
VL 56
IS 7
BP 534
EP 540
DI 10.1038/jhg.2011.55
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 796PE
UT WOS:000293063200011
PM 21633365
ER
PT J
AU Chimowitz, MI
Lynn, MJ
Turan, TN
Fiorella, D
Lane, BF
Janis, S
Derdeyn, CP
AF Chimowitz, Marc I.
Lynn, Michael J.
Turan, Tanya N.
Fiorella, David
Lane, Bethany F.
Janis, Scott
Derdeyn, Colin P.
CA SAMMPRIS Investigators
TI Design of the Stenting and Aggressive Medical Management for Preventing
Recurrent Stroke in Intracranial Stenosis Trial
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Atherosclerosis; intracranial; stenosis; stroke
ID TRANSIENT ISCHEMIC ATTACK; CORONARY-ARTERY-DISEASE; ATHEROSCLEROTIC
DISEASE; CARDIOVASCULAR-DISEASE; RANDOMIZED-TRIAL; CLINICAL-TRIALS;
WINGSPAN STENT; CT ANGIOGRAPHY; BLOOD-PRESSURE; DOUBLE-BLIND
AB Background: Patients with recent transient ischemic attack (TIA) or stroke caused by 70% to 99% stenosis of a major intracranial artery are at high risk of recurrent stroke on usual medical management, suggesting the need for alternative therapies for this disease. Methods: The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial is an ongoing, randomized, multicenter, 2-arm trial that will determine whether intracranial angioplasty and stenting adds benefit to aggressive medical management alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of 2 years in patients with recent TIA or stroke caused by 70% to 99% stenosis of a major intracranial artery. Aggressive medical management in both arms consists of aspirin 325 mg per day, clopidogrel 75 mg per day for 90 days after enrollment, intensive risk factor management primarily targeting systolic blood pressure <140 mm Hg (<130 mm Hg in diabetics) and low density cholesterol <70 mg/dL, and a lifetsyle modification program. The sample size required to detect a 35% reduction in the rate of the primary endpoint from angioplasty and stenting based on the log-rank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and 5% crossover from the medical to the stenting arm is 382 patients per group. Results: Enrollment began in November 2008 and 451 patients have been enrolled as of March 31, 2011. Conclusions: This is the first randomized stroke prevention trial to compare angioplasty and stenting with medical therapy in patients with intracranial arterial stenosis and to incorporate intensive management of multiple risk factors and a lifestyle modification program in the study design. Hopefully, the results of the trial will lead to more effective therapy for this high-risk disease.
C1 [Chimowitz, Marc I.] Med Univ S Carolina, Stroke Program, Dept Neurosci, Stroke Ctr, Charleston, SC 29425 USA.
[Lynn, Michael J.; Lane, Bethany F.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA.
[Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Cerebrovasc Ctr, Stony Brook, NY 11794 USA.
[Janis, Scott] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA.
RP Chimowitz, MI (reprint author), Med Univ S Carolina, Stroke Program, Dept Neurosci, Stroke Ctr, 19 Hagood Ave,Harborview Off Tower,Ste 501, Charleston, SC 29425 USA.
EM mchimow@musc.edu
OI Turan, Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683
FU US Public Health Service National Institute of Neurological Disorders
and Stroke (NINDS) [U01 NS058728]
FX Funded by a research grant (U01 NS058728) from the US Public Health
Service National Institute of Neurological Disorders and Stroke (NINDS).
Other support is provided in the acknowledgment section.
NR 40
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Z9 62
U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD JUL-AUG
PY 2011
VL 20
IS 4
BP 357
EP 368
DI 10.1016/j.jstrokecerebrovasdis.2011.05.001
PG 12
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 803TD
UT WOS:000293603300013
PM 21729789
ER
PT J
AU Forger, DB
Paydarfar, D
Clay, JR
AF Forger, Daniel B.
Paydarfar, David
Clay, John R.
TI Optimal Stimulus Shapes for Neuronal Excitation
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID DEEP BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS; COMPUTATIONAL MODEL; INPUTS
AB An important problem in neuronal computation is to discern how features of stimuli control the timing of action potentials. One aspect of this problem is to determine how an action potential, or spike, can be elicited with the least energy cost, e. g., a minimal amount of applied current. Here we show in the Hodgkin & Huxley model of the action potential and in experiments on squid giant axons that: 1) spike generation in a neuron can be highly discriminatory for stimulus shape and 2) the optimal stimulus shape is dependent upon inputs to the neuron. We show how polarity and time course of postsynaptic currents determine which of these optimal stimulus shapes best excites the neuron. These results are obtained mathematically using the calculus of variations and experimentally using a stochastic search methodology. Our findings reveal a surprising complexity of computation at the single cell level that may be relevant for understanding optimization of signaling in neurons and neuronal networks.
C1 [Forger, Daniel B.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[Forger, Daniel B.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Forger, Daniel B.; Paydarfar, David; Clay, John R.] Marine Biol Lab, Woods Hole, MA 02543 USA.
[Paydarfar, David] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Paydarfar, David] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Paydarfar, David] Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA USA.
[Clay, John R.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Forger, DB (reprint author), Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
EM forger@umich.edu
RI Forger, Daniel/C-5552-2015
OI Forger, Daniel/0000-0001-7581-4031
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health, Bethesda, MD [20892]; NIH [R01 HL718884]
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health, Bethesda, MD 20892 and NIH grant R01 HL718884 to
DP. DBF is an AFOSR Young Investigator (FA 9550-08-01-0076). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 18
TC 10
Z9 10
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD JUL
PY 2011
VL 7
IS 7
AR e1002089
DI 10.1371/journal.pcbi.1002089
PG 9
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 800BS
UT WOS:000293333200004
PM 21760759
ER
PT J
AU Lemaitre, RN
Tanaka, T
Tang, WH
Manichaikul, A
Foy, M
Kabagambe, EK
Nettleton, JA
King, IB
Weng, LC
Bhattacharya, S
Bandinelli, S
Bis, JC
Rich, SS
Jacobs, DR
Cherubini, A
McKnight, B
Liang, S
Gu, XJ
Rice, K
Laurie, CC
Lumley, T
Browning, BL
Psaty, BM
Chen, YDI
Friedlander, Y
Djousse, L
Wu, JHY
Siscovick, DS
Uitterlinden, AG
Arnett, DK
Ferrucci, L
Fornage, M
Tsai, MY
Mozaffarian, D
Steffen, LM
AF Lemaitre, Rozenn N.
Tanaka, Toshiko
Tang, Weihong
Manichaikul, Ani
Foy, Millennia
Kabagambe, Edmond K.
Nettleton, Jennifer A.
King, Irena B.
Weng, Lu-Chen
Bhattacharya, Sayanti
Bandinelli, Stefania
Bis, Joshua C.
Rich, Stephen S.
Jacobs, David R., Jr.
Cherubini, Antonio
McKnight, Barbara
Liang, Shuang
Gu, Xiangjun
Rice, Kenneth
Laurie, Cathy C.
Lumley, Thomas
Browning, Brian L.
Psaty, Bruce M.
Chen, Yii-Der I.
Friedlander, Yechiel
Djousse, Luc
Wu, Jason H. Y.
Siscovick, David S.
Uitterlinden, Andre G.
Arnett, Donna K.
Ferrucci, Luigi
Fornage, Myriam
Tsai, Michael Y.
Mozaffarian, Dariush
Steffen, Lyn M.
TI Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A
Meta-Analysis of Genome-Wide Association Studies from the CHARGE
Consortium
SO PLOS GENETICS
LA English
DT Article
ID ALPHA-LINOLENIC ACID; ISCHEMIC-HEART-DISEASE; DOCOSAHEXAENOIC ACID;
EICOSAPENTAENOIC ACID; DEPRESSIVE SYMPTOMATOLOGY; MYOCARDIAL-INFARCTION;
DIETARY-INTAKE; RISK-FACTOR; FISH-OIL; VARIANTS
AB Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from a-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p=3x10(-64)) and lower levels of eicosapentaenoic acid (EPA, p=5x10(-58)) and docosapentaenoic acid (DPA, p=4x10(-154)). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p=2x10(-12)) and DPA (p=1x10(-43)) and lower docosahexaenoic acid (DHA, p=1x10(-15)). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p=1x10(-8)). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.
C1 [Lemaitre, Rozenn N.; Bis, Joshua C.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Tang, Weihong; Weng, Lu-Chen; Jacobs, David R., Jr.; Steffen, Lyn M.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Div Biostat & Epidemiol, Charlottesville, VA USA.
[Foy, Millennia; Gu, Xiangjun; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Kabagambe, Edmond K.; Arnett, Donna K.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[Nettleton, Jennifer A.; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
[King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Bhattacharya, Sayanti] Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
[Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, Dept Clin & Expt Med, I-06100 Perugia, Italy.
[McKnight, Barbara; Rice, Kenneth; Laurie, Cathy C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Liang, Shuang; Tsai, Michael Y.] Univ Minnesota, Lab Med & Pathol, Minneapolis, MN USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Browning, Brian L.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Chen, Yii-Der I.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA.
[Friedlander, Yechiel] Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Sch Publ Hlth, Epidemiol Unit, Jerusalem, Israel.
[Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA.
[Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA.
[Wu, Jason H. Y.; Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA.
[Wu, Jason H. Y.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Siscovick, David S.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Mozaffarian, Dariush] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA.
RP Lemaitre, RN (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
EM rozenl@u.washington.edu
RI Manichaikul, Ani/B-7726-2009; Browning, Brian/A-1178-2010; Rice,
Kenneth/A-4150-2013; Djousse, Luc/F-5033-2017;
OI Browning, Brian/0000-0001-6454-6633; Rice, Kenneth/0000-0001-5779-4495;
Djousse, Luc/0000-0002-9902-3047; Kabagambe, Edmond/0000-0002-8993-3186;
Manichaikul, Ani/0000-0002-5998-795X; Cherubini,
Antonio/0000-0003-0261-9897
FU National Heart, Lung, and Blood Institute (NHLBI); National Human Genome
Research Institute [HSN268200625226C, U01-HG-004729, U01-HG-004446,
U01-HG-004424]; National Institutes of Health; NIH Roadmap for Medical
Research; National Institute of Neurological Disorders and Stroke
[HL075366, HL080295, HL087652, HL105756, HL085251]; National Institute
on Aging [AG-023269, AG-15928, AG-20098, AG-027058]; National Center for
Research Resources [M01RR00425]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; Italian Ministry of Health
[ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263
MD 821336]; National Institute on Aging, National Institutes of Health,
Baltimore, Maryland; MESA; National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases
[5K01DK082729-02]; [UL1RR025005]; [R01HL071051]; [R01HL071205];
[R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL071258];
[R01HL071259]
FX The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HSN268200625226C. Infrastructure was partly supported by Grant Number
UL1RR025005, a component of the National Institutes of Health and NIH
Roadmap for Medical Research. The Cardiovascular Health Study research
reported in this article was supported by the National Heart, Lung, and
Blood Institute contract N01-HC-85079 through N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and
grants HL075366, HL080295, HL087652, HL105756, and HL085251 with
additional contribution from the National Institute of Neurological
Disorders and Stroke. Additional support from the National Institute on
Aging was provided through AG-023269, AG-15928, AG-20098, and AG-027058.
DNA handling and genotyping was supported in part by the National Center
for Research Resources grant M01RR00425 to the Cedars-Sinai General
Clinical Research Center Genotyping core and the National Institute of
Diabetes and Digestive and Kidney Diseases grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. The Coronary
Artery Risk Development in Young Adults (CARDIA) study is funded by
contracts N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049,
N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, and N01-HC-45204
from the National Heart, Lung, and Blood Institute to the CARDIA
investigators. Genotyping of the CARDIA participants was supported by
grants U01-HG-004729, U01-HG-004446, and U01-HG-004424 from the National
Human Genome Research Institute and R01-HL-084099 from the National
Heart, Lung, and Blood Institute to MF. The InCHIANTI Study baseline
(1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by
the Italian Ministry of Health and in part by the U.S. National
Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336) and was
supported in part by the Intramural research program of the National
Institute on Aging, National Institutes of Health, Baltimore, Maryland.
The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SHARe were
supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156
from the National Heart, Lung, and Blood Institute. Funding for MESA
SHARe genotyping was provided by NHLBI Contract N02HL64278. MESA Family
is conducted and supported in collaboration with MESA investigators;
support is provided by grants and contracts R01HL071051, R01HL071205,
R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259. The
authors thank the other investigators, the staff, and the participants
of the MESA study for their valuable contributions. A full list of
participating MESA investigators and institutions can be found at
http://www.mesa-nhlbi.org. JA Nettleton is supported by a K01 from the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases (5K01DK082729-02). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 51
TC 105
Z9 107
U1 1
U2 22
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2011
VL 7
IS 7
AR e1002193
DI 10.1371/journal.pgen.1002193
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 800DB
UT WOS:000293338600041
PM 21829377
ER
PT J
AU Meyer, KB
Maia, AT
O'Reilly, M
Ghoussaini, M
Prathalingam, R
Porter-Gill, P
Ambs, S
Prokunina-Olsson, L
Carroll, J
Ponder, BAJ
AF Meyer, Kerstin B.
Maia, Ana-Teresa
O'Reilly, Martin
Ghoussaini, Maya
Prathalingam, Radhika
Porter-Gill, Patricia
Ambs, Stefan
Prokunina-Olsson, Ludmila
Carroll, Jason
Ponder, Bruce A. J.
TI A Functional Variant at a Prostate Cancer Predisposition Locus at 8q24
Is Associated with PVT1 Expression
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; TRANSCRIPTION FACTOR YY1; LONG-RANGE
INTERACTION; BREAST-CANCER; C-MYC; SUSCEPTIBILITY LOCI;
COLORECTAL-CANCER; CHROMOSOME 8Q24; SNP RS6983267; MULTIPLE LOCI
AB Genetic mapping studies have identified multiple cancer susceptibility regions at chromosome 8q24, upstream of the MYC oncogene. MYC has been widely presumed as the regulated target gene, but definitive evidence functionally linking these cancer regions with MYC has been difficult to obtain. Here we examined candidate functional variants of a haplotype block at 8q24 encompassing the two independent risk alleles for prostate and breast cancer, rs620861 and rs13281615. We used the mapping of DNase I hypersensitive sites as a tool to prioritise regions for further functional analysis. This approach identified rs378854, which is in complete linkage disequilibrium (LD) with rs620861, as a novel functional prostate cancer-specific genetic variant. We demonstrate that the risk allele (G) of rs378854 reduces binding of the transcription factor YY1 in vitro. This factor is known to repress global transcription in prostate cancer and is a candidate tumour suppressor. Additional experiments showed that the YY1 binding site is occupied in vivo in prostate cancer, but not breast cancer cells, consistent with the observed cancer-specific effects of this single nucleotide polymorphism (SNP). Using chromatin conformation capture (3C) experiments, we found that the region surrounding rs378854 interacts with the MYC and PVT1 promoters. Moreover, expression of the PVT1 oncogene in normal prostate tissue increased with the presence of the risk allele of rs378854, while expression of MYC was not affected. In conclusion, we identified a new functional prostate cancer risk variant at the 8q24 locus, rs378854 allele G, that reduces binding of the YY1 protein and is associated with increased expression of PVT1 located 0.5 Mb downstream.
C1 [Meyer, Kerstin B.; Maia, Ana-Teresa; O'Reilly, Martin; Prathalingam, Radhika; Carroll, Jason; Ponder, Bruce A. J.] Canc Res UK Cambridge Res Inst, Cambridge, England.
[Maia, Ana-Teresa; Ghoussaini, Maya; Carroll, Jason; Ponder, Bruce A. J.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Porter-Gill, Patricia; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Meyer, KB (reprint author), Canc Res UK Cambridge Res Inst, Cambridge, England.
EM kerstin.meyer@cancer.org.uk
RI Maia, Ana-Teresa/F-4404-2012;
OI Maia, Ana-Teresa/0000-0002-0454-9207; Prokunina-Olsson,
Ludmila/0000-0002-9622-2091
FU Cancer Research UK; Division of Cancer Epidemiology and Genetics and
Centre for Cancer Research, National Cancer Institute, National
Institutes of Health, United States of America
FX This work was funded by Cancer Research UK
(http://www.cancerresearchuk.org/) and by the Intramural Research
Program, Division of Cancer Epidemiology and Genetics and Centre for
Cancer Research, National Cancer Institute, National Institutes of
Health, United States of America (http://www.nih.gov/). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 42
TC 56
Z9 61
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2011
VL 7
IS 7
AR e1002165
DI 10.1371/journal.pgen.1002165
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 800DB
UT WOS:000293338600015
PM 21814516
ER
PT J
AU Sanna, S
Li, BS
Mulas, A
Sidore, C
Kang, HM
Jackson, AU
Piras, MG
Usala, G
Maninchedda, G
Sassu, A
Serra, F
Palmas, MA
Wood, WH
Njolstad, I
Laakso, M
Hveem, K
Tuomilehto, J
Lakka, TA
Rauramaa, R
Boehnke, M
Cucca, F
Uda, M
Schlessinger, D
Nagaraja, R
Abecasis, GR
AF Sanna, Serena
Li, Bingshan
Mulas, Antonella
Sidore, Carlo
Kang, Hyun M.
Jackson, Anne U.
Piras, Maria Grazia
Usala, Gianluca
Maninchedda, Giuseppe
Sassu, Alessandro
Serra, Fabrizio
Palmas, Maria Antonietta
Wood, William H., III
Njolstad, Inger
Laakso, Markku
Hveem, Kristian
Tuomilehto, Jaakko
Lakka, Timo A.
Rauramaa, Rainer
Boehnke, Michael
Cucca, Francesco
Uda, Manuela
Schlessinger, David
Nagaraja, Ramaiah
Abecasis, Goncalo R.
TI Fine Mapping of Five Loci Associated with Low-Density Lipoprotein
Cholesterol Detects Variants That Double the Explained Heritability
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E POLYMORPHISM;
CORONARY-ARTERY-DISEASE; SEQUENCE VARIATIONS; RARE VARIANTS;
HEART-DISEASE; RISK; GENE; POPULATION; PCSK9
AB Complex trait genome-wide association studies (GWAS) provide an efficient strategy for evaluating large numbers of common variants in large numbers of individuals and for identifying trait-associated variants. Nevertheless, GWAS often leave much of the trait heritability unexplained. We hypothesized that some of this unexplained heritability might be due to common and rare variants that reside in GWAS identified loci but lack appropriate proxies in modern genotyping arrays. To assess this hypothesis, we re-examined 7 genes (APOE, APOC1, APOC2, SORT1, LDLR, APOB, and PCSK9) in 5 loci associated with low-density lipoprotein cholesterol (LDL-C) in multiple GWAS. For each gene, we first catalogued genetic variation by re-sequencing 256 Sardinian individuals with extreme LDL-C values. Next, we genotyped variants identified by us and by the 1000 Genomes Project (totaling 3,277 SNPs) in 5,524 volunteers. We found that in one locus (PCSK9) the GWAS signal could be explained by a previously described low-frequency variant and that in three loci (PCSK9, APOE, and LDLR) there were additional variants independently associated with LDL-C, including a novel and rare LDLR variant that seems specific to Sardinians. Overall, this more detailed assessment of SNP variation in these loci increased estimates of the heritability of LDL-C accounted for by these genes from 3.1% to 6.5%. All association signals and the heritability estimates were successfully confirmed in a sample of similar to 10,000 Finnish and Norwegian individuals. Our results thus suggest that focusing on variants accessible via GWAS can lead to clear underestimates of the trait heritability explained by a set of loci. Further, our results suggest that, as prelude to large-scale sequencing efforts, targeted re-sequencing efforts paired with large-scale genotyping will increase estimates of complex trait heritability explained by known loci.
C1 [Sanna, Serena; Mulas, Antonella; Sidore, Carlo; Piras, Maria Grazia; Usala, Gianluca; Cucca, Francesco; Uda, Manuela] CNR, Ist Ric Genet & Biomed, Monserrato, Italy.
[Li, Bingshan; Sidore, Carlo; Kang, Hyun M.; Jackson, Anne U.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Sidore, Carlo; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Maninchedda, Giuseppe; Sassu, Alessandro; Serra, Fabrizio; Palmas, Maria Antonietta] Shardna Life Sci, Pula, Italy.
[Wood, William H., III] NIA, Gene Express & Genom Unit, Res Resources Branch, Baltimore, MD 21224 USA.
[Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Hveem, Kristian] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, N-7034 Trondheim, Norway.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
[Lakka, Timo A.] Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland.
[Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland.
[Schlessinger, David; Nagaraja, Ramaiah] NIA, Genet Lab, Baltimore, MD 21224 USA.
RP Sanna, S (reprint author), CNR, Ist Ric Genet & Biomed, Monserrato, Italy.
EM serena.sanna@inn.cnr.it; goncalo@umich.edu
RI Li, Bingshan/H-1944-2011; Abecasis, Goncalo/B-7840-2010;
OI Mulas, Antonella/0000-0002-6856-1483; Sidore, Carlo/0000-0001-7504-7477;
piras, maria grazia/0000-0001-9004-0900; sanna,
serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825;
Lakka, Timo/0000-0002-9199-2871
FU NIA [NO1-AG-1-2109]; National Institute on Aging [263-MA-410953];
National Institutes of Health [HG002651, HG005581, HL084729]; Fondazione
San Raffaele del Monte Tabor; municipal administrations; [DK062370]
FX This work was supported by contract NO1-AG-1-2109, from the NIA, to the
SardiNIA ("ProgeNIA") team and the Intramural Research Program of the
National Institute on Aging (263-MA-410953), and by the National
Institutes of Health (HG002651, HG005581, HL084729). The efforts of MB,
JT, and AUJ were supported in part by research grant DK062370. SharDNA
was supported by the Fondazione San Raffaele del Monte Tabor. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; We are grateful
to all the volunteers who generously participated in this study;
Monsignore Piseddu, Bishop of Ogliastra, and the mayors and citizens of
the Sardinian towns of Lanusei, Ilbono, Arzana, and Elini for their
continuous support. We also thank Debbie Nickerson and the University of
Washington Genome Sequencing Center, for providing sequencing data, and
Francis S. Collins and Karen L. Mohlke, for sharing the Finnish and
Norwegian results. The SharDNA investigators are thankful to the
populations of the ten Ogliastra villages for their volunteerism, the
municipal administrations for their support, and Raffaela Lener,
Massimiliano Cosso and Ignazio Piras for their collaboration.
NR 37
TC 88
Z9 88
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2011
VL 7
IS 7
AR e1002198
DI 10.1371/journal.pgen.1002198
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 800DB
UT WOS:000293338600045
PM 21829380
ER
PT J
AU Macon, MB
Villanueva, LR
Tatum-Gibbs, K
Zehr, RD
Strynar, MJ
Stanko, JP
White, SS
Helfant, L
Fenton, SE
AF Macon, Madisa B.
Villanueva, LaTonya R.
Tatum-Gibbs, Katoria
Zehr, Robert D.
Strynar, Mark J.
Stanko, Jason P.
White, Sally S.
Helfant, Laurence
Fenton, Suzanne E.
TI Prenatal Perfluorooctanoic Acid Exposure in CD-1 Mice: Low-Dose
Developmental Effects and Internal Dosimetry
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE perfluorooctanoic acid; mammary gland; development; prenatal; dosimetry
ID MAMMARY-GLAND DEVELOPMENT; NATIONAL BIRTH COHORT; SULFONATE PFOS;
PERFLUORINATED CHEMICALS; PEROXISOME PROLIFERATOR; PERFLUOROALKYL ACIDS;
SERUM CONCENTRATIONS; NEONATAL EXPOSURE; LACTATING MICE; COMPOUNDS PFCS
AB Perfluorooctanoic acid (PFOA) is an environmental contaminant that causes adverse developmental effects in laboratory animals. To investigate the low-dose effects of PFOA on offspring, timed-pregnant CD-1 mice were gavage dosed with PFOA for all or half of gestation. In the full-gestation study, mice were administered 0, 0.3, 1.0, and 3.0 mg PFOA/kg body weight (BW)/day from gestation days (GD) 1-17. In the late-gestation study, mice were administered 0, 0.01, 0.1, and 1.0 mg PFOA/kg BW/day from GD 10-17. Exposure to PFOA significantly (p < 0.05) increased offspring relative liver weights in all treatment groups in the full-gestation study and in the 1.0 mg PFOA/kg group in the late-gestation study. In both studies, the offspring of all PFOA-treated dams exhibited significantly stunted mammary epithelial growth as assessed by developmental scoring. At postnatal day 21, mammary glands from the 1.0 mg/kg GD 10-17 group had significantly less longitudinal epithelial growth and fewer terminal end buds compared with controls (p < 0.05). Evaluation of internal dosimetry in offspring revealed that PFOA concentrations remained elevated in liver and serum for up to 6 weeks and that brain concentrations were low and undetectable after 4 weeks. These data indicate that PFOA-induced effects on mammary tissue (1) occur at lower doses than effects on liver weight in CD-1 mice, an observation that may be strain specific, and (2) persist until 12 weeks of age following full-gestational exposure. Due to the low-dose sensitivity of mammary glands to PFOA in CD-1 mice, a no observable adverse effect level for mammary developmental delays was not identified in these studies.
C1 [Macon, Madisa B.; Tatum-Gibbs, Katoria] Univ N Carolina, Sch Med, Curriculum Toxicol, Chapel Hill, NC 27599 USA.
[Macon, Madisa B.; Stanko, Jason P.; White, Sally S.; Fenton, Suzanne E.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27711 USA.
[Villanueva, LaTonya R.] N Carolina Cent Univ, Dept Chem, Durham, NC 27709 USA.
[Villanueva, LaTonya R.; Tatum-Gibbs, Katoria] US EPA, Dev Toxicol Branch, Tox Assessment Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Zehr, Robert D.; Strynar, Mark J.; Helfant, Laurence] US EPA, Methods Dev & Applicat Branch, Human Exposure & Atmospher Sci Div, Natl Exposure Res Lab,Off Res & Dev, Res Triangle Pk, NC 27711 USA.
RP Fenton, SE (reprint author), POB 12233,Bldg 101,Mail Drop E1-08, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
FU U.S. Environmental Protection Agency; National Institute of
Environmental Health Sciences; University of North Carolina Curriculum
in Toxicology [5-T32 ES07126-26]
FX U.S. Environmental Protection Agency; National Institute of
Environmental Health Sciences; University of North Carolina Curriculum
in Toxicology Training Grant (5-T32 ES07126-26) to M.B.M.
NR 58
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U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JUL
PY 2011
VL 122
IS 1
BP 134
EP 145
DI 10.1093/toxsci/kfr076
PG 12
WC Toxicology
SC Toxicology
GA 800CT
UT WOS:000293337500014
PM 21482639
ER
PT J
AU Lacerda, SHD
Semberova, J
Holada, K
Simakova, O
Hudson, SD
Simak, J
AF Lacerda, Silvia H. De Paoli
Semberova, Jana
Holada, Karel
Simakova, Olga
Hudson, Steven D.
Simak, Jan
TI Carbon Nanotubes Activate Store-Operated Calcium Entry in Human Blood
Platelets
SO ACS NANO
LA English
DT Article
DE platelet activation; intracellular calcium; carbon nanotubes; fullerene;
nanotoxicity; thrombosis
ID MEMBRANES; AGGREGATION; CHOLESTEROL; SIMULATION; THROMBOSIS; BILAYER;
SURFACE; LENGTH
AB Carbon nanotubes (CNTs) are known to potentiate arterial thrombosis in animal models, which raises serious safety Issues concerning environmental or occupational exposure to CNTs and their use in various biomedical applications. We have shown previously that different CNTs, but not fullerene (nC60), induce the aggregation of human blood platelets. To date, however, a mechanism of potentially thrombogenic CNT-induced platelet activation has not been elucidated. Here we show that pristine multiwalled CNTs (MWCNTs) penetrate platelet plasma membrane without any discernible damage but interact with the dense tubular system (DTS) causing depletion of platelet intracellular Ca(2+) stores. This process is accompanied by the clustering of stromal interaction molecule 1 (STIM1) colocalized with Orai1, indicating the activation of store-operated Ca(2+) entry (SOCE). Our findings reveal the molecular mechanism of CNT-induced platelet activation which is critical in the evaluation of the biocompatibility of carbon nanomaterials with blood.
C1 [Lacerda, Silvia H. De Paoli; Semberova, Jana; Simak, Jan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Holada, Karel] Charles Univ Prague, Fac Med 1, Prague, Czech Republic.
[Semberova, Jana] Charles Univ Prague, Fac Med 3, Prague, Czech Republic.
[Simakova, Olga] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Hudson, Steven D.] NIST, Gaithersburg, MD 20899 USA.
RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
EM jan.simak@fda.hhs.gov
FU Ministry of Education, Youth and Sport of the Czech Republic [MSM
0021620806]
FX We thank G. Sando, Malvern Instruments, Columbia, MD, for the flow
particle image analysis of nanomaterial suspensions, M. Krumwiede,
University of Minnesota, Minneapolis, MN, for the valuable consultations
on the DAB-osmium labeling, and L. Diduch, National Institute of
Standards and Technology, Gaithersburg, MD, for image processing. K.
Holada was supported by Grant MSM 0021620806 of the Ministry of
Education, Youth and Sport of the Czech Republic.
NR 32
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U2 23
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD JUL
PY 2011
VL 5
IS 7
BP 5808
EP 5813
DI 10.1021/nn2015369
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 796ES
UT WOS:000293035200059
PM 21639133
ER
PT J
AU Courtney, PK
AF Courtney, Paul K.
TI Data Liquidity in Health Information Systems
SO CANCER JOURNAL
LA English
DT Review
DE Medical informatics; knowledge management; electronic health records;
personal health record
AB In 2001, the Institute of Medicine report Crossing the Quality Chasm and the National Committee on Vital and Health Statistics report Information for Health were released, and they provided the context for the development of information systems used to support health-supporting processes. Both had as their goals, implicit or explicit, to ensure the right data are provided to the right person at the right time, which is one definition of "data liquidity.'' This concept has had some traction in recent years as a shorthand way to express a system property for health information technology, but there is not a well-defined characterization of what properties of a system or of its components give it better or worse data liquidity. This article looks at some recent work that help to identify those properties and perhaps can help to ground the concept with metrics that are assessable.
C1 [Courtney, Paul K.] NCI, Clin Res Directorate, CMRP, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Courtney, PK (reprint author), NCI, 6116 Execut Blvd,MSC 8317, Rockville, MD 20852 USA.
EM paul.courtney@nih.gov
RI Courtney, Paul/C-9906-2009;
OI Courtney, Paul/0000-0001-6377-6103
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services nor does mention of trade names, commercial products,
or organizations imply endorsement by the U.S. Government.
NR 12
TC 5
Z9 5
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2011
VL 17
IS 4
BP 219
EP 221
DI 10.1097/PPO.0b013e3182270c83
PG 3
WC Oncology
SC Oncology
GA 799DZ
UT WOS:000293265100005
PM 21799328
ER
PT J
AU Hesse, BW
Suls, JM
AF Hesse, Bradford W.
Suls, Jerry M.
TI Informatics-Enabled Behavioral Medicine in Oncology
SO CANCER JOURNAL
LA English
DT Review
DE Behavioral medicine; biomedical informatics; health communication
ID QUALITY CANCER CARE; HEALTH INFORMATION; MEANINGFUL-USE;
RANDOMIZED-TRIAL; DECISION-MAKING; PALLIATIVE CARE; SPECIALTY CARE;
BREAST-CANCER; TECHNOLOGY; SURVIVORS
AB For the practicing physician, the behavioral implications of preventing, diagnosing, and treating cancer are many and varied. Fortunately, an enhanced capacity in informatics may help create a redesigned ecosystem in which applying evidence-based principles from behavioral medicine will become a routine part of care. Innovation to support this evolution will be spurred by the "meaningful use'' criteria stipulated by the Health Information Technology for Economic and Clinical Health Act of 2009 and by focused research and development efforts within the broader health information ecosystem. The implications for how to better integrate evidence-based principles in behavioral medicine into oncology care through both spheres of development are discussed within the framework of the cancer control continuum. The promise of using the data collected through these tools to accelerate discovery in psycho-oncology is also discussed. If nurtured appropriately, these developments should help accelerate successes against cancer by altering the behavioral milieu.
C1 [Hesse, Bradford W.] NCI, NIH, Bethesda, MD 20892 USA.
[Suls, Jerry M.] Univ Iowa, Iowa City, IA USA.
RP Hesse, BW (reprint author), NCI, NIH, 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 106
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U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2011
VL 17
IS 4
BP 222
EP 230
DI 10.1097/PPO.0b013e318227c811
PG 9
WC Oncology
SC Oncology
GA 799DZ
UT WOS:000293265100006
PM 21799329
ER
PT J
AU Basch, EM
Reeve, BB
Mitchell, SA
Clauser, SB
Minasian, L
Sit, L
Chilukuri, R
Baumgartner, P
Rogak, L
Blauel, E
Abernethy, AP
Bruner, D
AF Basch, Ethan M.
Reeve, Bryce B.
Mitchell, Sandra A.
Clauser, Stephen B.
Minasian, Lori
Sit, Laura
Chilukuri, Ram
Baumgartner, Paul
Rogak, Lauren
Blauel, Emily
Abernethy, Amy P.
Bruner, Deborah
TI Electronic Toxicity Monitoring and Patient-Reported Outcomes
SO CANCER JOURNAL
LA English
DT Review
DE symptom; adverse event; patient-reported outcome; PRO; toxicity;
tolerability; CTCAE; PRO-CTCAE
ID SYMPTOMS
AB Understanding the potential profile of adverse events associated with cancer treatment is essential in balancing safety versus benefits. Multiple stakeholders make use of this information for decision making, including patients, clinicians, researchers, regulators, and payors. Currently, adverse events are reported by clinical research staff, yet evidence suggests that this may contribute to underreporting of symptom events. Direct patient reporting via electronic interfaces offers a promising mechanism to enhance the efficiency and precision of our current approach and may complement clinician reports of adverse events. The National Cancer Institute has contracted to develop and test an item bank and software system for directly eliciting adverse symptom event information from patients in cancer clinical research, called the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events. The validity, usability, and scalability of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events prototype are currently being examined in academic and community-based settings.
C1 [Basch, Ethan M.; Sit, Laura; Rogak, Lauren; Blauel, Emily] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Reeve, Bryce B.] Univ N Carolina, Chapel Hill, NC USA.
[Mitchell, Sandra A.; Clauser, Stephen B.; Minasian, Lori] NCI, Bethesda, MD 20892 USA.
[Chilukuri, Ram; Baumgartner, Paul] SemanticBits LLC, Reston, VA USA.
[Abernethy, Amy P.] Duke Univ, Ctr Canc, Durham, NC USA.
[Bruner, Deborah] Univ Penn, Philadelphia, PA 19104 USA.
RP Basch, EM (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
EM basche@mskcc.org
FU National Cancer Institute [HHSN261201000043C, HHSN261201000063C];
Pfizer; Lilly; BMS; Helsinn; Amgen; Kanglaite; Alexion; Biovex
FX Development of the PRO-CTCAE was supported by the National Cancer
Institute (HHSN261201000043C and HHSN261201000063C). P.B. and R.C. are
employed by SemanticBits LLC. A.P.A's institution has received grants
from the following: Pfizer, Lilly, BMS, Helsinn, Amgen, Kanglaite,
Alexion, Biovex, and A.P.A. has also received honorarium from Heisinn,
Proventys, and Amgen.
NR 16
TC 25
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U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD JUL-AUG
PY 2011
VL 17
IS 4
BP 231
EP 234
DI 10.1097/PPO.0b013e31822c28b3
PG 4
WC Oncology
SC Oncology
GA 799DZ
UT WOS:000293265100007
PM 21799330
ER
PT J
AU Polkampally, PR
Matta, JR
McAreavey, D
Bakalov, V
Bondy, CA
Gharib, AM
AF Polkampally, Pritam R.
Matta, Jatin R.
McAreavey, Dorothea
Bakalov, Vladimir
Bondy, Carolyn A.
Gharib, Ahmed M.
TI Aneurysmal Dilatation of Medium Caliber Arteries in Turner Syndrome
SO CONGENITAL HEART DISEASE
LA English
DT Editorial Material
DE Aneurysm; Coronary Artery; Turners Syndrome; CT Angiogram
ID MORTALITY
AB Turner syndrome is the most common chromosomal abnormality in female subjects, affecting 1 in 2000 live births. The condition is associated with a generalized vasculopathy as well as congenital cardiac and other defects. We report aneurysmal dilation of medium caliber arteries involving the celiac axis and coronary vessels in two women with Turner syndrome.
C1 [Polkampally, Pritam R.; Matta, Jatin R.; Gharib, Ahmed M.] NIDDK, Bethesda, MD USA.
[McAreavey, Dorothea] Ctr Clin, Bethesda, MD USA.
[Bakalov, Vladimir; Bondy, Carolyn A.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Gharib, AM (reprint author), 10 Ctr Dr,CRC Room 3-5340, Bethesda, MD 20892 USA.
EM agharib@niddk.nih.gov
RI Gharib, Ahmed/O-2629-2016
OI Gharib, Ahmed/0000-0002-2476-481X
FU Intramural NIH HHS [Z99 DK999999]
NR 5
TC 4
Z9 4
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1747-079X
J9 CONGENIT HEART DIS
JI Congenit. Heart Dis.
PD JUL-AUG
PY 2011
VL 6
IS 4
BP 382
EP 383
DI 10.1111/j.1747-0803.2011.00485.x
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 795NW
UT WOS:000292981900014
PM 21463486
ER
PT J
AU Hamano, R
Huang, JQ
Yoshimura, T
Oppenheim, JJ
Chen, X
AF Hamano, Ryoko
Huang, Jiaqiang
Yoshimura, Teizo
Oppenheim, Joost J.
Chen, Xin
TI TNF optimally activatives regulatory T cells by inducing TNF receptor
superfamily members TNFR2, 4-1BB and OX40
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Co-stimulation; Immune regulation; TNF; Tregs
ID DENDRITIC CELLS; CUTTING EDGE; EXPANSION; SUPPRESSION; LOCALIZATION;
CHEMOTHERAPY; MECHANISMS; EXPRESSION; INDUCTION; TOLERANCE
AB TNF is a pleiotropic cytokine with intriguing biphasic pro-inflammatory and anti-inflammatory effects. Our previous studies demonstrated that TNF up-regulated FoxP3 expression and activated and expanded CD4(+)FoxP3(+) regulatory T cells (Tregs) via TNFR2. Furthermore, TNFR2-expressing Tregs exhibited maximal suppressive activity. In this study, we show that TNF, in concert with IL-2, preferentially up-regulated mRNA and surface expression of TNFR2, 4-1BB and OX40 on Tregs. Agonistic antibodies against 4-1BB and OX40 also induced the proliferation of suppressive Tregs. Thus, TNF amplifies its stimulatory effect on Tregs by inducing TNF receptor superfamily (TNFRSF) members. In addition, administration of neutralizing anti-TNF Ab blocked LPS-induced expansion of splenic Tregs and up-regulation of TNFR2, OX40 and 4-1BB receptors on Tregs in vivo, indicating that the expansion of Tregs expressing these co-stimulatory TNFRSF members in response to LPS is mediated by TNF. Altogether, our novel data indicate that TNF preferentially up-regulates TNFR2 on Tregs, and this is amplified by the stimulation of 4-1BB and OX40, resulting in the optimal activation of Tregs and augmented attenuation of excessive inflammatory responses.
C1 [Chen, Xin] SAIC Frederick Inc, BSP, Mol Immunoregulat Lab, CIP,NCI Frederick,Ctr Canc Res, Frederick, MD 21702 USA.
[Huang, Jiaqiang] QIAGEN Co, SABiosci Corp, Frederick, MD USA.
[Chen, Xin] SAIC Frederick Inc, NCI Frederick, Basic Sci Program, Frederick, MD 21702 USA.
[Hamano, Ryoko] Kanazawa Univ, Grad Sch Med, Dept Internal Med, Div Rheumatol, Kanazawa, Ishikawa, Japan.
RP Chen, X (reprint author), SAIC Frederick Inc, BSP, Mol Immunoregulat Lab, CIP,NCI Frederick,Ctr Canc Res, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA.
EM chenxin@mail.nih.gov
RI Chen, Xin/I-6601-2015
OI Chen, Xin/0000-0002-2628-4027
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research; Japan Society for the Promotion of Science
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. This Research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. R. H. is supported by International Training
Program of Japan Society for the Promotion of Science. 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. The authors thank Dr. Teresa Born and Dr. John E Sims
at Amgen Inc. for providing anti-mouse TNF antibody and isotype control
Mu IgG, and Dr O. M. Zack Howard, Dr. Hong Lou, Dr Hongchuan Li and Dr
Gonzalo M. de la Rosa for help in this study.
NR 32
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U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUL
PY 2011
VL 41
IS 7
BP 2010
EP 2020
DI 10.1002/eji.201041205
PG 11
WC Immunology
SC Immunology
GA 797ME
UT WOS:000293131200022
PM 21491419
ER
PT J
AU Largent, EA
Joffe, S
Miller, FG
AF Largent, Emily A.
Joffe, Steven
Miller, Franklin G.
TI Can RESEARCH and CARE Be Ethically Integrated?
SO HASTINGS CENTER REPORT
LA English
DT Article
ID CLINICAL-TRIALS
C1 [Largent, Emily A.] Harvard Univ, PhD Program Hlth Policy, Cambridge, MA 02138 USA.
[Joffe, Steven] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA.
[Miller, Franklin G.] Natl Inst Hlth, Dept Bioeth, Bethesda, MD 20892 USA.
[Joffe, Steven] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Largent, EA (reprint author), Harvard Univ, PhD Program Hlth Policy, Cambridge, MA 02138 USA.
OI Joffe, Steven/0000-0002-0667-7384
FU Greenwall Foundation
FX Steven Joffe's work was supported by a faculty scholar award from the
Greenwall Foundation.
NR 25
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U1 0
U2 3
PU HASTINGS CENTER
PI BRIARCLIFF MANOR
PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA
SN 0093-0334
J9 HASTINGS CENT REP
JI Hastings Cent. Rep.
PD JUL-AUG
PY 2011
VL 41
IS 4
BP 37
EP 46
PG 10
WC Ethics; Health Care Sciences & Services; Medical Ethics; Social
Sciences, Biomedical
SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical
Ethics; Biomedical Social Sciences
GA 797WB
UT WOS:000293159700019
PM 21845922
ER
PT J
AU McDermott, MM
Liu, K
Carroll, TJ
Tian, L
Ferrucci, L
Li, DB
Carr, J
Guralnik, JM
Kibbe, M
Pearce, WH
Yuan, C
McCarthy, W
Kramer, CM
Tao, HM
Liao, YH
Clark, ET
Xu, DX
Berry, J
Orozco, J
Sharma, L
Criqui, MH
AF McDermott, Mary M.
Liu, Kiang
Carroll, Timothy J.
Tian, Lu
Ferrucci, Luigi
Li, Debiao
Carr, James
Guralnik, Jack M.
Kibbe, Melina
Pearce, William H.
Yuan, Chun
McCarthy, Walter
Kramer, Christopher M.
Tao, Huimin
Liao, Yihua
Clark, Elizabeth Talley
Xu, Dongxiang
Berry, Jarett
Orozco, Jennifer
Sharma, Leena
Criqui, Michael H.
TI Superficial Femoral Artery Plaque and Functional Performance in
Peripheral Arterial Disease Walking and Leg Circulation Study (WALCS
III)
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE atherosclerotic plaque intermittent claudication; peripheral arterial
disease; physical functioning
ID ANKLE-BRACHIAL INDEX; INTERMITTENT CLAUDICATION; MAGNETIC-RESONANCE;
MORTALITY; CLASSIFICATION; OSTEOARTHRITIS; ASSOCIATION; CRITERIA
AB OBJECTIVES We studied associations of magnetic resonance imaging measurements of plaque area and relative percent lumen reduction in the proximal superficial femoral artery with functional performance among participants with peripheral arterial disease.
BACKGROUND The clinical significance of directly imaged plaque characteristics in lower extremity arteries is not well established.
METHODS A total of 454 participants with an ankle brachial index <1.00 underwent magnetic resonance cross-sectional imaging of the proximal superficial femoral artery and completed a 6-min walk test, measurement of 4-m walking velocity at usual and fastest pace, and measurement of physical activity with a vertical accelerometer.
RESULTS Adjusting for age, sex, race, body mass index, smoking, statin use, comorbidities, and other covariates, higher mean plaque area (1st quintile [least plaque]: 394 m, 2nd quintile: 360 m, 3rd quintile: 359 m, 4th quintile: 329 m, 5th quintile [greatest plaque]: 311 m; p trend <0.001) and smaller mean percent lumen area (1st quintile [greatest plaque]: 319 m, 2nd quintile: 330 m, 3rd quintile: 364 m, 4th quintile: 350 m, 5th quintile: 390 m; p trend <0.001) were associated with shorter distance achieved in the 6-min walk test. Greater mean plaque area was also associated with slower usual-paced walking velocity (p trend = 0.006) and slower fastest-paced 4-m walking velocity (p trend = 0.003). Associations of mean plaque area and mean lumen area with 6-min walk distance remained statistically significant even after additional adjustment for the ankle brachial index and leg symptoms.
CONCLUSIONS Among participants with peripheral arterial disease, greater plaque burden and smaller lumen area in the proximal superficial femoral artery are associated independently with poorer functional performance, even after adjusting for the ankle brachial index and leg symptoms. (J Am Coll Cardiol Img 2011;4:730-9) (C) 2011 by the American College of Cardiology Foundation
C1 [McDermott, Mary M.; Sharma, Leena] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[McDermott, Mary M.; Liu, Kiang; Tao, Huimin; Liao, Yihua] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Li, Debiao; Carr, James] Northwestern Univ, Dept Radiol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kibbe, Melina] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA.
[Pearce, William H.] Northwestern Univ, Div Vasc Surg, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kibbe, Melina; Pearce, William H.] Jesse Brown Vet Affairs Med Ctr, Surg Serv, Chicago, IL USA.
[McCarthy, Walter] Rush Univ, Med Ctr, Univ Cardiovasc Surg, Chicago, IL 60612 USA.
[Orozco, Jennifer] Rush Univ, Med Ctr, Dept Vasc Surg, Chicago, IL 60612 USA.
[Clark, Elizabeth Talley] Mt Sinai Hosp, Dept Surg, Chicago, IL USA.
[Carroll, Timothy J.] Northwestern Univ, Dept Biomed Engn & Radiol, Evanston, IL USA.
[Tian, Lu] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Yuan, Chun] Univ Washington, Dept Radiol Elect Engn & Bioengn, Seattle, WA 98195 USA.
[Xu, Dongxiang] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA.
[Kramer, Christopher M.] Univ Virginia Hlth Syst, Dept Radiol & Med, Charlottesville, VA USA.
[Berry, Jarett] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA.
RP McDermott, MM (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
RI Li, Debiao/B-7622-2009; Carroll, Timothy/B-6934-2009
FU National Heart, Lung, and Blood Institute [R01-HL083064]; National
Institute on Aging; Jesse Brown VA Medical Center; VP Diagnostics;
Philips Healthcare; Siemens Healthcare
FX From the *Department of Medicine, Northwestern University Feinberg
School of Medicine, Chicago, Illinois; dagger Department of Preventive
Medicine, Northwestern University Feinberg School of Medicine, Chicago,
Illinois; double dagger Department of Radiology, Northwestern University
Feinberg School of Medicine, Chicago, Illinois; Department of Surgery,
Northwestern University Feinberg School of Medicine, Chicago, Illinois;
parallel to Division of Vascular Surgery, Northwestern University
Feinberg School of Medicine, Chicago, Illinois; Surgical Services, Jesse
Brown Veterans Affairs Medical Center, Chicago, Illinois; #University
Cardiovascular Surgeons, Rush University Medical Center, Chicago,
Illinois; **Department of Vascular Surgery, Rush University Medical
Center, Chicago, Illinois; dagger dagger Department of Surgery, Mount
Sinai Hospital, Chicago, Illinois; double dagger double dagger
Department of Biomedical Engineering and Radiology, Northwestern
University, Evanston, Illinois; Department of Health Research and
Policy, Stanford University School of Medicine, Stanford, California;
parallel to parallel to Department of Family and Preventive Medicine,
University of California at San Diego, San Diego, California;
Longitudinal Studies Section, Clinical Research Branch, National
Institute on Aging, Bethesda, Maryland; ##Department of Epidemiology and
Public Health, University of Maryland School of Medicine, Baltimore,
Maryland; ***Department of Radiology, Electrical Engineering, and
Bioengineering, University of Washington, Seattle, Washington; dagger
dagger dagger Department of Radiology, University of Washington School
of Medicine, Seattle, Washington; double dagger double dagger double
dagger Department of Radiology and Medicine, University of Virginia
Health System, Charlottesville, Virginia; and the Department of
Medicine, University of Texas Southwestern Medical Center, Dallas,
Texas. Dr. Li is currently affiliated with the Department of Radiology
and Bioengineering, Cedars Sinai Medical Center, Los Angeles,
California. Supported by funding from the National Heart, Lung, and
Blood Institute (R01-HL083064), by the Intramural Research Program of
the National Institute on Aging, and by the Jesse Brown VA Medical
Center. Dr. Yuan receives research support from VP Diagnostics and from
Philips Healthcare. Dr. Kramer receives research support from Siemens
Healthcare. Dr. Xu is a technical consultant for VP Diagnostics and
owner of Imaging Biomarker Solutions. All other authors have reported
that they have no relationships to disclose. Eike Nagel, MD, PhD, served
as Guest Editor for this article.
NR 22
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD JUL
PY 2011
VL 4
IS 7
BP 730
EP 739
DI 10.1016/j.jcmg.2011.04.009
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 798CQ
UT WOS:000293180100007
PM 21757163
ER
PT J
AU Thorgeirsson, S
AF Thorgeirsson, S.
TI Genomic Decoding of Liver Cancer: Mechanistic and Clinical Implications
SO JOURNAL OF PATHOLOGY
LA English
DT Meeting Abstract
CT 6th Joint Meeting of the British Division of the
International-Academy-of-Pathology-and-the-Pathological-Society-of-Great
-Britain-and-Ireland
CY MAY 10-13, 2011
CL Univ Ghent, Dept Pathol, Onderbergen, BELGIUM
SP Int Acad Pathol, Pathol Soc Great Britain & Ireland
HO Univ Ghent, Dept Pathol
C1 [Thorgeirsson, S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD JUL
PY 2011
VL 224
SU 2
BP S14
EP S14
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 799GZ
UT WOS:000293275800049
ER
PT J
AU O'Seaghdha, CM
Fox, CS
AF O'Seaghdha, Conall M.
Fox, Caroline S.
TI The Fourth Dimension: Associations of Change in Albuminuria over Time
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID RECLASSIFICATION; MICROALBUMINURIA; MARKER
C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Framingham Offspring Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA.
[O'Seaghdha, Conall M.] Harvard Univ, Sch Med, Div Renal, Boston, MA USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Div Endocrinol, Boston, MA USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
NR 11
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U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL
PY 2011
VL 22
IS 7
BP 1186
EP 1188
DI 10.1681/ASN.2011050488
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 798KA
UT WOS:000293203400005
PM 21680650
ER
PT J
AU Matsusaka, T
Sandgren, E
Shintani, A
Kon, V
Pastan, I
Fogo, AB
Ichikawa, I
AF Matsusaka, Taiji
Sandgren, Eric
Shintani, Ayumi
Kon, Valentina
Pastan, Ira
Fogo, Agnes B.
Ichikawa, Iekuni
TI Podocyte Injury Damages Other Podocytes
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; GLOMERULAR SCLEROSIS; RENAL-DISEASE;
EXTREME ABLATION; NEPHROTIC RATS; KIDNEY-DISEASE; PROTEINURIA;
HYPERTROPHY; CELL; PODOCYTOPATHIES
AB Loss of podocytes promotes glomerulosclerosis, but whether this results from a continued primary insult or a secondary mechanism triggered by the initial loss of podocytes is unknown. We generated chimeric mice in which only a subpopulation of podocytes expressed hCD25, which is the receptor for the immunotoxin LMB2. In addition, genetic labeling of hCD25-negative cells with human placental alkaline phosphatase allowed the study of these two distinct podocyte populations. Administration of LMB2 did not cause podocyte injury in hCD25-negative control mice. In contrast, LMB2 severely damaged or sloughed off the subpopulation of hCD25-positive podocytes within the chimeric glomeruli. Moreover, hCD25-negative podocytes, which were immune to the initial toxin injury, developed injury as early as 4 d after LMB2 injection, evidenced by foot process effacement, upregulation of desmin, and downregulation of nephrin, podocin, and podocalyxin. Furthermore, the magnitude of secondary injury correlated with the magnitude of primary injury, supporting the concept of an amplified cascade of podocyte injury. In conclusion, podocyte damage can propagate injury by triggering secondary damage of "remnant" intact podocytes, even when the primary insult is short-lived. This transmission of podocyte injury may form a vicious cycle leading to accelerated podocyte deterioration and glomerulosclerosis.
C1 [Kon, Valentina; Fogo, Agnes B.; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Kanagawa 2591100, Japan.
[Ichikawa, Iekuni] Tokai Univ, Sch Med, Dept Bioeth, Kanagawa 2591100, Japan.
[Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Kanagawa 2591100, Japan.
[Sandgren, Eric] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA.
[Shintani, Ayumi] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37232 USA.
[Fogo, Agnes B.; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA.
[Fogo, Agnes B.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ichikawa, I (reprint author), Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
EM iekuni.ichikawa@gmail.com
FU National Institutes of Health [DK37868, DK44757]; Japan Society for the
Promotion of Science; MEXT; HAITEKU; National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Daiichi Sankyo
Co., Ltd.; Chugai Pharmaceutical Co., Ltd.
FX This study was supported by National Institutes of Health grants DK37868
and DK44757, the Research for the Future Program and Grant-in-Aid for
Scientific Research of Japan Society for the Promotion of Science, MEXT,
HAITEKU, and in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research. Parts of this study were presented in abstract form at the
annual meetings of the American Society of Nephrology in 2003 and 2004.
We thank Mr. Yutaka Ishikawa, Mr. Akira Akatsuka, Ms. Shiho Imai, Ms.
Naoko Sasaoka, Ms. Suguri Niwa, and Ms. Chic Sakurai for technical
assistance, and Dr. Hidetake Kurihara for providing anti-podocalyxin
antibody and rat podocyte cell line.; Iekuni Ichikawa received research
funds from Daiichi Sankyo Co., Ltd. Taiji Matsusaka received a research
fund from Chugai Pharmaceutical Co., Ltd.
NR 47
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U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL
PY 2011
VL 22
IS 7
BP 1275
EP 1285
DI 10.1681/ASN.2010090963
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 798KA
UT WOS:000293203400015
PM 21719786
ER
PT J
AU McCaskill-Stevens, W
Abrams, JS
AF McCaskill-Stevens, Worta
Abrams, Jeffrey S.
TI Comorbidities in the Aging Breast Cancer Population: Are Current
Assessments Leading to Improved Outcomes?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID COMPREHENSIVE GERIATRIC ASSESSMENT
C1 [McCaskill-Stevens, Worta] NCI, Canc Prevent Div, EPN, Bethesda, MD 20892 USA.
[Abrams, Jeffrey S.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP McCaskill-Stevens, W (reprint author), NCI, Canc Prevent Div, EPN, Rm 2017,6130 Execut Blvd,MSC-7340, Bethesda, MD 20892 USA.
EM wm57h@nih.gov
NR 6
TC 5
Z9 5
U1 0
U2 1
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 JUL
PY 2011
VL 103
IS 14
BP 1072
EP 1073
DI 10.1093/jnci/djr239
PG 2
WC Oncology
SC Oncology
GA 796BB
UT WOS:000293024100001
PM 21719778
ER
PT J
AU Rubinstein, L
LeBlanc, M
Smith, MA
AF Rubinstein, Lawrence
LeBlanc, Michael
Smith, Malcolm A.
TI More Randomization in Phase II Trials: Necessary but not Sufficient
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID RENAL-CELL CARCINOMA; ACUTE PROMYELOCYTIC LEUKEMIA; METASTATIC
BREAST-CANCER; SURROGATE END-POINTS; COLORECTAL-CANCER; CHEMOTHERAPY
PLUS; CLINICAL-TRIALS; PROGRESSION-FREE; BEVACIZUMAB; SURVIVAL
C1 [Rubinstein, Lawrence] NCI, NIH, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[LeBlanc, Michael] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Rubinstein, L (reprint author), NCI, NIH, Biometr Res Branch, Div Canc Treatment & Diag, Execut Plaza N,Rm 8130,MSC-7434, Bethesda, MD 20892 USA.
EM rubinsteinl@ctep.nci.nih.gov
FU NCI NIH HHS [R01 CA090998]
NR 41
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Z9 7
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JUL
PY 2011
VL 103
IS 14
BP 1075
EP 1077
DI 10.1093/jnci/djr238
PG 3
WC Oncology
SC Oncology
GA 796BB
UT WOS:000293024100003
PM 21709273
ER
PT J
AU Freedman, LS
Schatzkin, A
Midthune, D
Kipnis, V
AF Freedman, Laurence S.
Schatzkin, Arthur
Midthune, Douglas
Kipnis, Victor
TI Dealing With Dietary Measurement Error in Nutritional Cohort Studies
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID DOUBLY LABELED WATER; BREAST-CANCER; NATIONAL-INSTITUTES; POOLED
ANALYSIS; 24-HOUR RECALL; RELATIVE RISK; FAT; HEALTH; BIOMARKER;
QUESTIONNAIRE
AB Dietary measurement error creates serious challenges to reliably discovering new diet-disease associations in nutritional cohort studies. Such error causes substantial underestimation of relative risks and reduction of statistical power for detecting associations. On the basis of data from the Observing Protein and Energy Nutrition Study, we recommend the following approaches to deal with these problems. Regarding data analysis of cohort studies using food-frequency questionnaires, we recommend 1) using energy adjustment for relative risk estimation; 2) reporting estimates adjusted for measurement error along with the usual relative risk estimates, whenever possible (this requires data from a relevant, preferably internal, validation study in which participants report intakes using both the main instrument and a more detailed reference instrument such as a 24-hour recall or multiple-day food record); 3) performing statistical adjustment of relative risks, based on such validation data, if they exist, using univariate (only for energy-adjusted intakes such as densities or residuals) or multivariate regression calibration. We note that whereas unadjusted relative risk estimates are biased toward the null value, statistical significance tests of unadjusted relative risk estimates are approximately valid. Regarding study design, we recommend increasing the sample size to remedy loss of power; however, it is important to understand that this will often be an incomplete solution because the attenuated signal may be too small to distinguish from unmeasured confounding in the model relating disease to reported intake. Future work should be devoted to alleviating the problem of signal attenuation, possibly through the use of improved self-report instruments or by combining dietary biomarkers with self-report instruments.
C1 [Midthune, Douglas; Kipnis, Victor] US Natl Canc Inst, Biometry Res Grp, Canc Prevent Div, Bethesda, MD USA.
[Schatzkin, Arthur] US Natl Canc Inst, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Freedman, Laurence S.] Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, Tel Hashomer, Israel.
RP Kipnis, V (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, 6130 Execut Blvd,EPN-3131,MSC 7354, Bethesda, MD 20892 USA.
EM kipnisv@mail.nih.gov
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U2 30
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 JUL
PY 2011
VL 103
IS 14
BP 1086
EP 1092
DI 10.1093/jnci/djr189
PG 7
WC Oncology
SC Oncology
GA 796BB
UT WOS:000293024100007
PM 21653922
ER
PT J
AU Pine, SR
Mechanic, LE
Enewold, L
Chaturvedi, AK
Katki, HA
Zheng, YL
Bowman, ED
Engels, EA
Caporaso, NE
Harris, CC
AF Pine, Sharon R.
Mechanic, Leah E.
Enewold, Lindsey
Chaturvedi, Anil K.
Katki, Hormuzd A.
Zheng, Yun-Ling
Bowman, Elise D.
Engels, Eric A.
Caporaso, Neil E.
Harris, Curtis C.
TI Increased Levels of Circulating Interleukin 6, Interleukin 8, C-Reactive
Protein, and Risk of Lung Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SERUM-LEVELS; AFRICAN-AMERICANS; CARCINOMA-CELLS; SURVIVAL;
INFLAMMATION; PROGRESSION; EXPRESSION; POPULATION; SENESCENCE; PROGNOSIS
AB Background Previous studies that were based primarily on small numbers of patients suggested that certain circulating proinflammatory cytokines may be associated with lung cancer; however, large independent studies are lacking.
Methods Associations between serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels and lung cancer were analyzed among 270 case patients and 296 control subjects participating in the National Cancer Institute-Maryland (NCI-MD) case-control study.
Results were validated in 532 case patients and 595 control subjects in a nested case-control study within the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Association with C-reactive protein (CRP), a systemic inflammation biomarker, was also analyzed. Associations between biomarkers and lung cancer were estimated using logistic regression models adjusted for smoking, stage, histology, age, and sex. The 10-year standardized absolute risks of lung cancer were estimated using a weighted Cox regression model. Results Serum IL-6 and IL-8 levels in the highest quartile were associated with lung cancer in the NCI-MD study (IL-6, odds ratio [OR] = 3.29, 95% confidence interval [CI] = 1.88 to 5.77; IL-8, OR = 2.06, 95% CI = 1.19 to 3.57) and with lung cancer risk in the PLCO study (IL-6, OR = 1.48, 95% CI = 1.04 to 2.10; IL-8, OR = 1.57, 95% CI = 1.10 to 2.24), compared with the lowest quartile. In the PLCO study, increased IL-6 levels were only associated with lung cancer diagnosed within 2 years of blood collection, whereas increased IL-8 levels were associated with lung cancer diagnosed more than 2 years after blood collection (OR = 1.57, 95% CI = 1.15 to 2.13). The 10-year standardized absolute risks of lung cancer in the PLCO study were highest among current smokers with high IL-8 and CRP levels (absolute risk = 8.01%, 95% CI = 5.77% to 11.05%).
Conclusions Although increased levels of both serum IL-6 and IL-8 are associated with lung cancer, only IL-8 levels are associated with lung cancer risk several years before diagnosis. Combination of IL-8 and CRP are more robust biomarkers than either marker alone in predicting subsequent lung cancer. J Natl Cancer Inst 2011;103:1112-1122
C1 [Pine, Sharon R.; Mechanic, Leah E.; Bowman, Elise D.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Pine, Sharon R.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Div Med Oncol,Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Mechanic, Leah E.] NCI, Epidemiol & Genet Res Program, Host Susceptibil Factors Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Enewold, Lindsey] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Enewold, Lindsey] Walter Reed Army Med Ctr, US Mil Canc Inst, Washington, DC 20307 USA.
[Chaturvedi, Anil K.; Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Rockville, MD USA.
[Katki, Hormuzd A.] NCI, Biostat Branch, Rockville, MD USA.
[Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Rockville, MD USA.
[Chaturvedi, Anil K.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Zheng, Yun-Ling] Georgetown Univ, Lombardi Comprehens Canc Ctr, Biomarkers Epidemiol Program, Washington, DC USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Rm 3068A,MSC 4258, Bethesda, MD 20892 USA.
EM curtis_harris@nih.gov
RI Katki, Hormuzd/B-4003-2015; Chaturvedi, Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research.
NR 42
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U1 2
U2 14
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 JUL
PY 2011
VL 103
IS 14
BP 1112
EP 1122
DI 10.1093/jnci/djr216
PG 11
WC Oncology
SC Oncology
GA 796BB
UT WOS:000293024100010
PM 21685357
ER
PT J
AU Murphy, G
Kamangar, F
Dawsey, SM
Stanczyk, FZ
Weinstein, SJ
Taylor, PR
Virtamo, J
Abnet, CC
Albanes, D
Freedman, ND
AF Murphy, Gwen
Kamangar, Farin
Dawsey, Sanford M.
Stanczyk, Frank Z.
Weinstein, Stephanie J.
Taylor, Philip R.
Virtamo, Jarmo
Abnet, Christian C.
Albanes, Demetrius
Freedman, Neal D.
TI The Relationship Between Serum Ghrelin and the Risk of Gastric and
Esophagogastric Junctional Adenocarcinomas
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; DIETARY ASSESSMENT INSTRUMENTS;
PEPSINOGEN-I; PROSTATE-CANCER; STOMACH-CANCER; CELL-LINES; EXPRESSION;
REPRODUCIBILITY; CARCINOGENESIS; QUESTIONNAIRE
AB Background Cancers of the upper gastrointestinal tract remain a substantial cause of morbidity and mortality worldwide. Ghrelin is a hormone produced in the oxyntic glands of the stomach, and under conditions of chronic inflammation and atrophy, serum ghrelin concentrations decrease. However, the relationship between ghrelin and the risk of gastric and esophagogastric junctional cancers has not been investigated.
Methods We conducted a nested case-control study within the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to examine the relationship between serum ghrelin concentration and the risk of gastric non cardia adenocarcinoma (GNCA) and esophagogastric junctional adenocarcinoma (EGJA). Data from 261 GNCA patients, 98 EGJA patients, and 441 control subjects were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression with adjustment for potential confounders. Lag analysis was also performed to investigate the temporal nature of the associations between baseline serum pepsinogen I and ghrelin in GNCA and EGJA patients. All statistical tests were two-sided.
Results Lower concentrations of serum ghrelin were statistically significantly associated with an increased risk of both GNCA (adjusted OR = 1.75, 95% CI = 1.49 to 2.04; P < .001) and EGJA (adjusted OR = 1.56, 95% CI = 1.28 to 1.89, P < .001). A multivariable model found that the risk of both GNCA and EGJA were statistically significantly increased for those individuals in the lowest quartile of serum ghrelin levels compared with those in the highest quartile (OR of GNCA = 5.63, 95% CI = 3.16 to 10.03; OR of EGJA = 4.90, 95% CI = 2.11 to 11.35). The statistical significance of these associations remained even after restricting the analysis to those patients who developed cancer more than 10 years after baseline serum ghrelin measurements.
Conclusion Low baseline concentrations of serum ghrelin were associated with a statistically significant increase in the risk of GNCA and EGJA, suggesting a potential role for gastric hormones in carcinogenesis. J Natl Cancer Inst 2011;103:1123-1129
C1 [Murphy, Gwen] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA.
[Stanczyk, Frank Z.] Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA.
[Stanczyk, Frank Z.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Murphy, G (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 3034, Rockville, MD 20892 USA.
EM murphygw@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015; Murphy,
Gwen/G-7443-2015; Freedman, Neal/B-9741-2015
OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services;
National Cancer Institute; US Public Health Service contracts
[N01-CN-45165, N01-RC-45035, N01-RC-37004]
FX This work was supported by the Intramural Research Program, Division of
Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services. The
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by
funding provided by the Intramural Research Program of the National
Cancer Institute and US Public Health Service contracts (N01-CN-45165,
N01-RC-45035, and N01-RC-37004).
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U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JUL
PY 2011
VL 103
IS 14
BP 1123
EP 1129
DI 10.1093/jnci/djr194
PG 7
WC Oncology
SC Oncology
GA 796BB
UT WOS:000293024100011
PM 21693726
ER
PT J
AU Di Michele, DM
AF Di Michele, D. M.
TI Immune tolerance induction in haemophilia: evidence and the way forward
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Review
DE gene transfer; haemophilia A; haemophilia B; immune modulation; immune
tolerance; inhibitors
ID RECOMBINANT FACTOR-VIII; HIGH-RESPONDING INHIBITORS;
VON-WILLEBRAND-FACTOR; HIGH-TITER INHIBITORS; FACTOR-IX INHIBITORS;
REGULATORY T-CELLS; PREVIOUSLY UNTREATED PATIENTS; A PATIENTS;
GENE-TRANSFER; SINGLE INSTITUTION
AB Given the inhibitor-associated morbidity resulting from limited effective treatment options, antibody eradication is the ultimate goal of inhibitor management. The only clinically proven strategy for achieving antigen-specific tolerance to factor VIII is immune tolerance induction (ITI). First reported over 30 years ago, much of our current knowledge about ITI in haemophilia A and B was derived from small cohort studies and retrospective national and international ITI registries. More recently, prospective randomised ITI trials have been designed and initiated to answer outstanding questions related to the optimisation of current therapeutic strategy in haemophilia A. However, due to the low incidence of inhibitor development in haemophilia B compared to haemophilia A, there are few comparable data from which to develop a useful evidence-based approach to the prevention and eradication of FIX inhibitors. The lack of an effective strategy is particularly problematic given the even greater morbidity associated with the almost unique occurrence of allergic and anaphylactic reactions that often herald FIX antibody development, and further complicates attempts to eradicate FIX inhibitors. Ultimately, successful inhibitor prevention and eradication strategies for both diseases will emerge from the clinical translation of our evolving knowledge of immune stimulation and tolerance. This paper will discuss our current understanding of immune tolerance outcome and outcome predictors for haemophilia A and B; it will also review the current consensus recommendations for ITI, as well as the emerging scientific body of immunological knowledge that may significantly impact the therapeutic and preventative strategies of the future.
C1 NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
RP Di Michele, DM (reprint author), NHLBI, Div Blood Dis & Resources, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM dimicheledm@nhlbi.nih.gov
NR 98
TC 25
Z9 25
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 1
SI SI
BP 216
EP 225
DI 10.1111/j.1538-7836.2011.04349.x
PG 10
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 796BG
UT WOS:000293024600024
PM 21781258
ER
PT J
AU Johnson, AD
AF Johnson, A. D.
TI The genetics of common variation affecting platelet development,
function and pharmaceutical targeting
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Review
DE aggregation; genome; GWAS; platelet; polymorphism; SNP
ID QUANTITATIVE TRAIT LOCI; GENOME-WIDE ASSOCIATION;
CORONARY-ARTERY-DISEASE; SINGLE NUCLEOTIDE POLYMORPHISMS;
MYOCARDIAL-INFARCTION; DEPENDENT INHIBITION; RECEPTOR EXPRESSION;
ISOLATED POPULATION; INHERITED TRAITS; CYP2C19 GENOTYPE
AB Common variant effects on human platelet function and response to anti-platelet treatment have traditionally been studied using candidate gene approaches involving a limited number of variants and genes. These studies have often been undertaken in clinically defined cohorts. More recently, studies have applied genome-wide scans in larger population samples than prior candidate studies, in some cases scanning relatively healthy individuals. These studies demonstrate synergy with some prior candidate gene findings (e. g., GP6, ADRA2A) but also uncover novel loci involved in platelet function. Here, I summarise findings on common genetic variation influencing platelet development, function and therapeutics. Taken together, candidate gene and genome-wide studies begin to account for common variation in platelet function and provide information that may ultimately be useful in pharmacogenetic applications in the clinic. More than 50 loci have been identified with consistent associations with platelet phenotypes in >= 2 populations. Several variants are under further study in clinical trials relating to anti-platelet therapies. In order to have useful clinical applications, variants must have large effects on a modifiable outcome. Regardless of clinical applications, studies of common genetic influences, even of small effect, offer additional insights into platelet biology including the importance of intracellular signalling and novel receptors. Understanding of common platelet-related genetics remains behind parallel fields (e. g., lipids, blood pressure) due to challenges in phenotype ascertainment. Further work is necessary to discover and characterise loci for platelet function, and to assess whether these loci contribute to disease aetiologies or response to therapeutics.
C1 [Johnson, A. D.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
RP Johnson, AD (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM johnsonad2@nhlbi.nih.gov
RI Johnson, Andrew/G-6520-2013
FU National Institutes of Health
FX A. Johnson was supported by a National Institutes of Health Intramural
Research Training Fellowship.
NR 116
TC 14
Z9 14
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 1
SI SI
BP 246
EP 257
DI 10.1111/j.1538-7836.2011.04359.x
PG 12
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 796BG
UT WOS:000293024600027
PM 21781261
ER
PT J
AU Kapogiannis, D
Mooshagian, E
Campion, P
Grafman, J
Zimmermann, TJ
Ladt, KC
Wassermann, EM
AF Kapogiannis, Dimitrios
Mooshagian, Eric
Campion, Paul
Grafman, Jordan
Zimmermann, Trelawny J.
Ladt, Kelsey C.
Wassermann, Eric M.
TI Reward Processing Abnormalities in Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE transcranial magnetic stimulation; dopamine; gambling; motor cortex
ID HUMAN MOTOR CORTEX; IMPULSE CONTROL DISORDERS; SOMATIC MARKER
HYPOTHESIS; PREFRONTAL CORTEX; INTRACORTICAL INHIBITION;
TOURETTE-SYNDROME; DOPAMINE; EXCITABILITY; ASSOCIATION; AGONIST
AB The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid-A-mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age-matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk-taking behavior on the Iowa Gambling Task. However, pramipexole increased risk-taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk-taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endo-phenotype for risk-taking behavior in patients on agonist treatment. (C) 2011 Movement Disorder Society
C1 [Kapogiannis, Dimitrios; Mooshagian, Eric; Campion, Paul; Zimmermann, Trelawny J.; Ladt, Kelsey C.; Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA.
[Kapogiannis, Dimitrios] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Mooshagian, Eric] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Henry M Jackson Fdn, Rockville, MD USA.
[Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
RP Wassermann, EM (reprint author), 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA.
EM wassermanne@ninds.nih.gov
OI Grafman, Jordan H./0000-0001-8645-4457; Campion,
Paul/0000-0002-9569-5321
FU National Institute of Neurological Disorders and Stroke; National
Institute on Aging, National Institutes of Health; Center for
Neuroscience and Regenerative Medicine at the Uniformed Service
University of the Health Sciences, via the Henry Jackson foundation
FX Nothing to report. Funding for this work came exclusively from the
Clinical Neuroscience Program of the National Institute of Neurological
Disorders and Stroke and the Intramural Research Program of the National
Institute on Aging (to Dr. Kapogiannis), National Institutes of Health,
and the Center for Neuroscience and Regenerative Medicine at the
Uniformed Service University of the Health Sciences, via the Henry
Jackson foundation (to Dr. Mooshagian).
NR 40
TC 18
Z9 20
U1 3
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUL
PY 2011
VL 26
IS 8
BP 1451
EP 1457
DI 10.1002/mds.23701
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 800CB
UT WOS:000293334800015
PM 21538525
ER
PT J
AU Yeh, SH
Yang, WB
Gean, PW
Hsu, CY
Tseng, JT
Su, TP
Chang, W
Hung, JJ
AF Yeh, Shiu Hwa
Yang, Wen Bin
Gean, Po Wu
Hsu, Chung Yi
Tseng, Joseph T.
Su, Tsung Ping
Chang, Wen
Hung, Jan Jong
TI Translational and transcriptional control of Sp1 against ischaemia
through a hydrogen peroxide-activated internal ribosomal entry site
pathway
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID FOCAL CEREBRAL-ISCHEMIA; GENE-TRANSCRIPTION; SP-FAMILY; HYPOXIA;
PROMOTER; DISEASE; STRESS; PROTECTION; INDUCTION; NEURONS
AB The exact mechanism underlying increases in Sp1 and the physiological consequences thereafter remains unknown. In rat primary cortical neurons, oxygen-glucose deprivation (OGD) causes an increase in H(2)O(2) as well as Sp1 in early ischaemia but apparently does not change mRNA level or Sp1 stability. We hereby identified a longer 5'-UTR in Sp1 mRNA that contains an internal ribosome entry site (IRES) that regulates rapid and efficient translation of existing mRNAs. By using polysomal fragmentation and bicistronic luciferase assays, we found that H(2)O(2) activates IRES-dependent translation. Thus, H(2)O(2) or tempol, a superoxide dismutase-mimetic, increases Sp1 levels in OGD-treated neurons. Further, early-expressed Sp1 binds to Sp1 promoter to cause a late rise in Sp1 in a feed-forward manner. Short hairpin RNA against Sp1 exacerbates OGD-induced apoptosis in primary neurons. While Sp1 levels increase in the cortex in a rat model of stroke, inhibition of Sp1 binding leads to enhanced apoptosis and cortical injury. These results demonstrate that neurons can use H(2)O(2) as a signalling molecule to quickly induce Sp1 translation through an IRES-dependent translation pathway that, in cooperation with a late rise in Sp1 via feed-forward transcriptional activation, protects neurons against ischaemic damage.
C1 [Yeh, Shiu Hwa; Gean, Po Wu; Chang, Wen; Hung, Jan Jong] Natl Cheng Kung Univ, Dept Pharmacol, Coll Biosci & Biotechnol, Tainan 701, Taiwan.
[Yang, Wen Bin; Hsu, Chung Yi; Tseng, Joseph T.; Chang, Wen; Hung, Jan Jong] Natl Cheng Kung Univ, Inst Bioinformat & Biosignal Transduct, Coll Biosci & Biotechnol, Tainan 701, Taiwan.
[Gean, Po Wu; Tseng, Joseph T.; Chang, Wen; Hung, Jan Jong] Natl Cheng Kung Univ, Ctr Gene Regulat & Signal Transduct, Tainan 701, Taiwan.
[Su, Tsung Ping] Natl Inst Drug Abuse, Dept Hlth & Human Serv, NIH, Baltimore, MD USA.
RP Chang, W (reprint author), Natl Cheng Kung Univ, Dept Pharmacol, Coll Biosci & Biotechnol, Tainan 701, Taiwan.
EM wcchang@mail.ncku.edu.tw; petehung@mail.ncku.edu.tw
RI HUNG, Jan-Jong/G-7872-2011
OI Yang, Wen-Bin/0000-0002-6497-4176;
FU National Cheng-Kung University, National Science Council, Taiwan [NSC
97-2320-B-006-016-MY3, NSC 97-2311-B-006-002-MY3]; National Institute on
Drug Abuse, National Institutes of Health, Department of Health and
Human Services, USA; NSC, Taiwan
FX The National Cheng-Kung University project of the Program for Promoting
Academic Excellence and Developing World Class Research Centers,
National Science Council, Taiwan (NSC 97-2320-B-006-016-MY3 and NSC
97-2311-B-006-002-MY3); Intramural Research Program, National Institute
on Drug Abuse, National Institutes of Health, Department of Health and
Human Services, USA. Funding for open access charge: NSC, Taiwan.
NR 36
TC 18
Z9 18
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2011
VL 39
IS 13
BP 5412
EP 5423
DI 10.1093/nar/gkr161
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 795ZV
UT WOS:000293020000016
PM 21441538
ER
PT J
AU Hardin, AH
Sarkar, SK
Seol, Y
Liou, GF
Osheroff, N
Neuman, KC
AF Hardin, Ashley H.
Sarkar, Susanta K.
Seol, Yeonee
Liou, Grace F.
Osheroff, Neil
Neuman, Keir C.
TI Direct measurement of DNA bending by type IIA topoisomerases:
implications for non-equilibrium topology simplification
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SCANNING FORCE MICROSCOPY; LOCAL JUXTAPOSITION GEOMETRY;
ESCHERICHIA-COLI; STRUCTURAL BASIS; CONFORMATIONAL-ANALYSIS; PLASMID
PBR322; MECHANISM; IV; SPECIFICITY; CLEAVAGE
AB Type IIA topoisomerases modify DNA topology by passing one segment of duplex DNA (transfer or T-segment) through a transient double-strand break in a second segment of DNA (gate or G-segment) in an ATP-dependent reaction. Type IIA topoisomerases decatenate, unknot and relax supercoiled DNA to levels below equilibrium, resulting in global topology simplification. The mechanism underlying this non-equilibrium topology simplification remains speculative. The bend angle model postulates that non-equilibrium topology simplification scales with the bend angle imposed on the G-segment DNA by the binding of a type IIA topoisomerase. To test this bend angle model, we used atomic force microscopy and single-molecule Forster resonance energy transfer to measure the extent of bending imposed on DNA by three type IIA topoisomerases that span the range of topology simplification activity. We found that Escherichia coli topoisomerase IV, yeast topoisomerase II and human topoisomerase II alpha each bend DNA to a similar degree. These data suggest that DNA bending is not the sole determinant of non-equilibrium topology simplification. Rather, they suggest a fundamental and conserved role for DNA bending in the enzymatic cycle of type IIA topoisomerases.
C1 [Hardin, Ashley H.; Sarkar, Susanta K.; Seol, Yeonee; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Hardin, Ashley H.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
[Liou, Grace F.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Osheroff, Neil] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA.
[Osheroff, Neil] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA.
RP Neuman, KC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM neumankc@mail.nih.gov
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU National Heart, Lung, and Blood Institute; National Institute of
Diabetes and Digestive and Kidney Diseases at the National Institutes of
Health; National Institutes of Health [GM033944]
FX This research was supported by the Intramural Research Programs of the
National Heart, Lung, and Blood Institute and the National Institute of
Diabetes and Digestive and Kidney Diseases at the National Institutes of
Health and by a National Institutes of Health extramural grant (GM033944
to N.O.).
NR 65
TC 31
Z9 31
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2011
VL 39
IS 13
BP 5729
EP 5743
DI 10.1093/nar/gkr109
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 795ZV
UT WOS:000293020000041
PM 21421557
ER
PT J
AU Lu, J
Kerns, RT
Peddada, SD
Bushel, PR
AF Lu, Jun
Kerns, Robnet T.
Peddada, Shyamal D.
Bushel, Pierre R.
TI Principal component analysis-based filtering improves detection for
Affymetrix gene expression arrays
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PREFERRED ANALYSIS-METHODS; MICROARRAY DATA-ANALYSIS; FALSE DISCOVERY
RATE; PROBE LEVEL DATA; SIGNATURES; DATASET; POWER
AB Gene expression array technology has reached the stage of being routinely used to study clinical samples in search of diagnostic and prognostic biomarkers. Due to the nature of array experiments, which examine the expression of tens of thousands of genes simultaneously, the number of null hypotheses is large. Hence, multiple testing correction is often necessary to control the number of false positives. However, multiple testing correction can lead to low statistical power in detecting genes that are truly differentially expressed. Filtering out non-informative genes allows for reduction in the number of null hypotheses. While several filtering methods have been suggested, the appropriate way to perform filtering is still debatable. We propose a new filtering strategy for Affymetrix GeneChips (R), based on principal component analysis of probe-level gene expression data. Using a wholly defined spike-in data set and one from a diabetes study, we show that filtering by the proportion of variation accounted for by the first principal component (PVAC) provides increased sensitivity in detecting truly differentially expressed genes while controlling false discoveries. We demonstrate that PVAC exhibits equal or better performance than several widely used filtering methods. Furthermore, a data-driven approach that guides the selection of the filtering threshold value is also proposed.
C1 [Lu, Jun; Kerns, Robnet T.; Bushel, Pierre R.] NIEHS, Microarray & Genome Informat Grp, Res Triangle Pk, NC 27709 USA.
[Lu, Jun; Kerns, Robnet T.] SRA Int Inc, Res Triangle Pk, NC 27709 USA.
[Peddada, Shyamal D.; Bushel, Pierre R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Bushel, PR (reprint author), NIEHS, Microarray & Genome Informat Grp, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bushel@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012
FU National Institutes of Health (NIH); National Institute of Environmental
Health Sciences (NIEHS) [Z01 ES102345-04, Z01 ES101744-04]; NIEHS-NIH
FX This research was supported, in part by, the Intramural Research Program
of the National Institutes of Health (NIH) and National Institute of
Environmental Health Sciences (NIEHS) (Z01 ES102345-04 and Z01
ES101744-04). Funding for open access charge: NIEHS-NIH.
NR 32
TC 4
Z9 4
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2011
VL 39
IS 13
AR e86
DI 10.1093/nar/gkr241
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 795ZV
UT WOS:000293020000003
PM 21525126
ER
PT J
AU Guigon, CJ
Kim, DW
Willingham, MC
Cheng, SY
AF Guigon, C. J.
Kim, D. W.
Willingham, M. C.
Cheng, S-y
TI Mutation of thyroid hormone receptor-beta in mice predisposes to the
development of mammary tumors
SO ONCOGENE
LA English
DT Article
DE thyroid hormone receptor; breast cancer; mammary tumors; Pten; mouse
models
ID BREAST-CANCER RISK; C-ERBA-BETA; TRANSGENIC MICE;
HEPATOCELLULAR-CARCINOMA; POSTMENOPAUSAL WOMEN; NUCLEAR RECEPTORS;
LIGAND-BINDING; MOUSE MODEL; V-ERBA; GENE
AB Correlative data suggest that thyroid hormone receptor-beta (TR beta) mutations could increase the risk of mammary tumor development, but unequivocal evidence is still lacking. To explore the role of TR beta mutants in vivo in breast tumor development and progression, we took advantage of a knock-in mouse model harboring a mutation in the Thrb gene encoding TR beta (Thrb(PV) mouse). Although in adult nulliparous females, a single ThrbPV allele did not contribute to mammary gland abnormalities, the presence of two ThrbPV alleles led to mammary hyperplasia in similar to 36% Thrb(PV/PV) mice. The ThrbPV mutation further markedly augmented the risk of mammary hyperplasia in a mouse model with high susceptibility to mammary tumors (Pten(+/-) mouse), as demonstrated by the occurrence of mammary hyperplasia in similar to 60% of Thrb(PV/+) Pten(+/-) and similar to 77% of Thrb(PV/PV) Pten(+/-) mice versus similar to 33% of Thrb(+/+) Pten(+/-) mice. The Thrb(PV) mutation increased the activity of signal transducer and activator of transcription (STAT5) to increase cell proliferation and the expression of the STAT5 target gene encoding beta-casein in the mammary gland. We next sought to understand the molecular mechanism underlying STAT5 overactivation by TR beta PV. Cell-based studies with a breast cancer cell line (T47D cells) showed that thyroid hormone (T3) repressed STAT5 signaling in TR beta-expressing cells through decreasing STAT5-mediated transcription activity and target gene expression, whereas sustained STAT5 signaling was observed in TR beta PV-expressing cells. Collectively, these findings show for the first time that a TR beta mutation promotes the development of mammary hyperplasia via aberrant activation of STAT5, thereby conferring a fertile genetic ground for tumorigenesis. Oncogene (2011) 30, 3381-3390; doi:10.1038/onc.2011.50; published online 14 March 2011
C1 [Guigon, C. J.; Kim, D. W.; Cheng, S-y] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Willingham, M. C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX We thank Dr L Fozzatti for her help in mouse dissection, Dr C Lu for
taking mouse body pictures, and Drs B Vonderhaar and E Ginsburg for
providing T47D cells and helpful technical advice. This research was
supported by the Intramural Research Program of Center for Cancer
Research, National Cancer Institute, National Institutes of Health.
NR 65
TC 18
Z9 19
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUL
PY 2011
VL 30
IS 30
BP 3381
EP 3390
DI 10.1038/onc.2011.50
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 798NO
UT WOS:000293215700008
PM 21399657
ER
PT J
AU Church, DM
Schneider, VA
Graves, T
Auger, K
Cunningham, F
Bouk, N
Chen, HC
Agarwala, R
McLaren, WM
Ritchie, GRS
Albracht, D
Kremitzki, M
Rock, S
Kotkiewicz, H
Kremitzki, C
Wollam, A
Trani, L
Fulton, L
Fulton, R
Matthews, L
Whitehead, S
Chow, W
Torrance, J
Dunn, M
Harden, G
Threadgold, G
Wood, J
Collins, J
Heath, P
Griffiths, G
Pelan, S
Grafham, D
Eichler, EE
Weinstock, G
Mardis, ER
Wilson, RK
Howe, K
Flicek, P
Hubbard, T
AF Church, Deanna M.
Schneider, Valerie A.
Graves, Tina
Auger, Katherine
Cunningham, Fiona
Bouk, Nathan
Chen, Hsiu-Chuan
Agarwala, Richa
McLaren, William M.
Ritchie, Graham R. S.
Albracht, Derek
Kremitzki, Milinn
Rock, Susan
Kotkiewicz, Holland
Kremitzki, Colin
Wollam, Aye
Trani, Lee
Fulton, Lucinda
Fulton, Robert
Matthews, Lucy
Whitehead, Siobhan
Chow, Will
Torrance, James
Dunn, Matthew
Harden, Glenn
Threadgold, Glen
Wood, Jonathan
Collins, Joanna
Heath, Paul
Griffiths, Guy
Pelan, Sarah
Grafham, Darren
Eichler, Evan E.
Weinstock, George
Mardis, Elaine R.
Wilson, Richard K.
Howe, Kerstin
Flicek, Paul
Hubbard, Tim
TI Modernizing Reference Genome Assemblies
SO PLOS BIOLOGY
LA English
DT Editorial Material
ID COPY-NUMBER VARIATION; STRUCTURAL VARIATION; SEQUENCE; DRAFT; MAP
C1 [Church, Deanna M.; Schneider, Valerie A.; Bouk, Nathan; Chen, Hsiu-Chuan; Agarwala, Richa] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Graves, Tina; Albracht, Derek; Kremitzki, Milinn; Rock, Susan; Kotkiewicz, Holland; Kremitzki, Colin; Wollam, Aye; Trani, Lee; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO USA.
[Auger, Katherine; Matthews, Lucy; Whitehead, Siobhan; Chow, Will; Torrance, James; Dunn, Matthew; Harden, Glenn; Threadgold, Glen; Wood, Jonathan; Collins, Joanna; Heath, Paul; Griffiths, Guy; Pelan, Sarah; Grafham, Darren; Howe, Kerstin; Hubbard, Tim] Wellcome Trust Sanger Inst, Cambridge, England.
[Cunningham, Fiona; McLaren, William M.; Ritchie, Graham R. S.; Flicek, Paul] European Bioinformat Inst, Cambridge, England.
[Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA.
[Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA USA.
RP Church, DM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM church@ncbi.nlm.nih.gov
RI Hubbard, Tim/C-2567-2008;
OI Hubbard, Tim/0000-0002-1767-9318; Ritchie, Graham/0000-0002-6456-9736;
Cunningham, Fiona/0000-0002-7445-2419; Howe,
Kerstin/0000-0003-2237-513X; Chow, William/0000-0002-9056-201X; Flicek,
Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116
FU Wellcome Trust [095908, 077198]
NR 23
TC 94
Z9 94
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1544-9173
J9 PLOS BIOL
JI PLoS. Biol.
PD JUL
PY 2011
VL 9
IS 7
AR e1001091
DI 10.1371/journal.pbio.1001091
PG 5
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 798OQ
UT WOS:000293219800002
PM 21750661
ER
PT J
AU Zhang, H
Zhang, G
Gonzalez, FJ
Park, SM
Cai, DS
AF Zhang, Hai
Zhang, Guo
Gonzalez, Frank J.
Park, Sung-min
Cai, Dongsheng
TI Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic
Glucose Sensing and Energy Balance Regulation
SO PLOS BIOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; TERMINAL TRANSACTIVATION DOMAIN; MITOCHONDRIAL
COMPLEX-III; NERVOUS-SYSTEM CONTROL; BETA/NF-KAPPA-B; FOOD-INTAKE;
BODY-WEIGHT; LEPTIN RESISTANCE; MAMMALIAN TARGET; HOMEOSTASIS
AB Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2 alpha in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2 alpha degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2 alpha protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance.
C1 [Zhang, Hai; Zhang, Guo; Cai, Dongsheng] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA.
[Zhang, Hai; Cai, Dongsheng] Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA.
[Zhang, Hai] Univ Wisconsin, Cellular & Mol Biol Program, Madison, WI USA.
[Gonzalez, Frank J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Park, Sung-min] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10467 USA.
[Cai, Dongsheng] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA.
RP Zhang, H (reprint author), Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA.
EM dongsheng.cai@einstein.yu.edu
RI Zhang, Guo/C-8005-2013; Zhang, Guo/Q-8513-2016
OI Zhang, Guo/0000-0002-3880-6996
FU US National Institutes of Health [RO1 DK078750, RO1 AG 031774]
FX This study was supported by US National Institutes of Health grants RO1
DK078750 and RO1 AG 031774. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 68
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U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1544-9173
J9 PLOS BIOL
JI PLoS. Biol.
PD JUL
PY 2011
VL 9
IS 7
AR e1001112
DI 10.1371/journal.pbio.1001112
PG 16
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 798OQ
UT WOS:000293219800016
PM 21814490
ER
PT J
AU Goldstein, E
Cobey, S
Takahashi, S
Miller, JC
Lipsitch, M
AF Goldstein, Edward
Cobey, Sarah
Takahashi, Saki
Miller, Joel C.
Lipsitch, Marc
TI Predicting the Epidemic Sizes of Influenza A/H1N1, A/H3N2, and B: A
Statistical Method
SO PLOS MEDICINE
LA English
DT Article
ID VIRUS; VACCINATION; INFECTION; EVOLUTION
AB Background: The epidemic sizes of influenza A/H3N2, A/H1N1, and B infections vary from year to year in the United States. We use publicly available US Centers for Disease Control (CDC) influenza surveillance data between 1997 and 2009 to study the temporal dynamics of influenza over this period.
Methods and Findings: Regional outpatient surveillance data on influenza-like illness (ILI) and virologic surveillance data were combined to define a weekly proxy for the incidence of each strain in the United States. All strains exhibited a negative association between their cumulative incidence proxy (CIP) for the whole season (from calendar week 40 of each year to calendar week 20 of the next year) and the CIP of the other two strains (the complementary CIP) from the start of the season up to calendar week 2 (or 3, 4, or 5) of the next year. We introduce a method to predict a particular strain's CIP for the whole season by following the incidence of each strain from the start of the season until either the CIP of the chosen strain or its complementary CIP exceed certain thresholds. The method yielded accurate predictions, which generally occurred within a few weeks of the peak of incidence of the chosen strain, sometimes after that peak. For the largest seasons in the data, which were dominated by A/H3N2, prediction of A/H3N2 incidence always occurred at least several weeks in advance of the peak.
Conclusion: Early circulation of one influenza strain is associated with a reduced total incidence of the other strains, consistent with the presence of interference between subtypes. Routine ILI and virologic surveillance data can be combined using this new method to predict the relative size of each influenza strain's epidemic by following the change in incidence of a given strain in the context of the incidence of cocirculating strains.
C1 [Goldstein, Edward; Cobey, Sarah; Miller, Joel C.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Takahashi, Saki] Harvard Univ, Dept Appl Math, Cambridge, MA 02138 USA.
[Miller, Joel C.] US Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Goldstein, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
EM egoldste@hsph.harvard.edu
RI Miller, Joel/C-4229-2015;
OI Miller, Joel/0000-0003-4426-0405; Lipsitch, Marc/0000-0003-1504-9213
FU US National Institutes of Health [1 U54 GM088558]; Science & Technology
Directorate; Department of Homeland Security; Fogarty International
Center, US National Institutes of Health; Harvard College;
Avian/Pandemic Flu Registry; Roche; Pfizer/Wyeth; Novartis Vaccines and
Diagnostics
FX This work was supported in part by the US National Institutes of Health
Models of Infectious Disease Agent Study program through cooperative
agreement 1 U54 GM088558 (ML, EG, SC); by the RAPIDD program of the
Science & Technology Directorate, Department of Homeland Security, and
the Fogarty International Center, US National Institutes of Health
(JCM); and by the Harvard College Research Program (ST). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute of General
Medical Sciences or the National Institutes of Health. No funding bodies
had any role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.; Marc Lipsitch is on the PLoS
Medicine Editorial Board. ML discloses consulting income from the
Avian/Pandemic Flu Registry (Outcome Sciences, funded in part by Roche)
and from Pfizer/Wyeth and from Novartis Vaccines and Diagnostics. The
other authors declare no competing interests.
NR 13
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD JUL
PY 2011
VL 8
IS 7
AR e1001051
DI 10.1371/journal.pmed.1001051
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 797ZQ
UT WOS:000293169700002
PM 21750666
ER
PT J
AU Schowalter, RM
Pastrana, DV
Buck, CB
AF Schowalter, Rachel M.
Pastrana, Diana V.
Buck, Christopher B.
TI Glycosaminoglycans and Sialylated Glycans Sequentially Facilitate Merkel
Cell Polyomavirus Infectious Entry
SO PLOS PATHOGENS
LA English
DT Article
ID HEPARAN-SULFATE; BK-VIRUS; PAPILLOMAVIRUS CAPSIDS; SIALIC ACIDS;
GANGLIOSIDES; BINDING; RECEPTORS; CARCINOMA; HEMAGGLUTINATION;
BIOSYNTHESIS
AB Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus.
C1 [Schowalter, Rachel M.; Pastrana, Diana V.; Buck, Christopher B.] NCI, Tumor Virus Mol Biol Sect, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Schowalter, RM (reprint author), NCI, Tumor Virus Mol Biol Sect, Cellular Oncol Lab, Bethesda, MD 20892 USA.
EM buckc@mail.nih.gov
OI Buck, Christopher/0000-0003-3165-8094
FU NIH; Center for Cancer Research, NCI
FX This research was funded by the Intramural Research Program of the NIH,
with support from the Center for Cancer Research, NCI. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 67
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U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUL
PY 2011
VL 7
IS 7
AR e1002161
DI 10.1371/journal.ppat.1002161
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 800DG
UT WOS:000293339300044
PM 21829355
ER
PT J
AU Cooney, MA
Louis, GMB
Hediger, ML
Vexler, A
Kostyniak, PJ
AF Cooney, Maureen A.
Louis, Germaine M. Buck
Hediger, Mary L.
Vexler, Albert
Kostyniak, Paul J.
TI Organochlorine pesticides and endometriosis (vol 30, pg 365, 2010)
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Correction
C1 [Cooney, Maureen A.; Louis, Germaine M. Buck; Hediger, Mary L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Vexler, Albert] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA.
[Kostyniak, Paul J.] SUNY Buffalo, Dept Pharmacol & Toxicol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA.
RP Cooney, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Rm 7B05, Rockville, MD 20852 USA.
EM cooneyma@mail.nih.gov; louisf@mail.nih.gov; hedigerm@mail.nih.gov;
avexler@buffalo.edu; pjkost@buffalo.edu
NR 1
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD JUL
PY 2011
VL 32
IS 1
BP 145
EP 145
DI 10.1016/j.reprotox.2011.03.006
PG 1
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 799YO
UT WOS:000293323200021
ER
PT J
AU Stanko, JP
Enoch, RR
Rayner, JL
Davis, CC
Wolf, DC
Malarkey, DE
Fenton, SE
AF Stanko, Jason P.
Enoch, Rolondo R.
Rayner, Jennifer L.
Davis, Christine C.
Wolf, Douglas C.
Malarkey, David E.
Fenton, Suzanne E.
TI Effects of prenatal exposure to a low dose atrazine metabolite mixture
on pubertal timing and prostate development of male Long-Evans rats (vol
30, pg 540, 2010)
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Correction
C1 [Stanko, Jason P.; Fenton, Suzanne E.] US EPA, Reprod Toxicol Div, ORD NHEERL, Res Triangle Pk, NC 27711 USA.
[Davis, Christine C.] US EPA, Hlth & Environm Impacts Div, OAR OAQPS, Res Triangle Pk, NC 27711 USA.
[Wolf, Douglas C.] US EPA, ORD, Res Triangle Pk, NC 27711 USA.
[Enoch, Rolondo R.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA.
[Rayner, Jennifer L.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
[Malarkey, David E.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Fenton, SE (reprint author), NIEHS, NIH, NTP, CMPB, 111 TW Alexander Dr,MD E1-08, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD JUL
PY 2011
VL 32
IS 1
BP 146
EP 147
DI 10.1016/j.reprotox.2011.03.007
PG 2
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 799YO
UT WOS:000293323200022
ER
PT J
AU Weniger, MA
Wiestner, A
AF Weniger, Marc A.
Wiestner, Adrian
TI Molecular Targeted Approaches in Mantle Cell Lymphoma
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID PROTEASOME INHIBITOR BORTEZOMIB; HISTONE DEACETYLASE INHIBITORS; CHRONIC
LYMPHOCYTIC-LEUKEMIA; DEPENDENT KINASE INHIBITOR; SINGLE-AGENT
TEMSIROLIMUS; PHASE-1 DOSE-ESCALATION; MULTIPLE-MYELOMA CELLS;
CANCER-CELLS; CYCLIN D1; CLINICAL-TRIALS
AB Mantle cell lymphoma (MCL) is a malignancy of mature B cells characterized by the translocation t(11;14) that leads to aberrant expression of cyclin D1. Response to first-line chemotherapy is good, but most patients relapse, resulting in a median survival of 5 to 7 years. The important PI3K/AKT/mTOR pathway can be targeted with small molecules. mTOR inhibitors have clinical activity and temsirolimus has been approved in Europe. Second-generation mTOR inhibitors and the PI3K inhibitor CAL-101 offer additional means to target the pathway. Promising results with the BTK inhibitor PCI-32765 suggest that B-cell receptor signaling could play a role. For unknown reasons, MCL appears to be particularly sensitive to disruption of protein homeostasis. The proteasome inhibitor bortezomib achieves responses in up to 50% of relapsed patients. Much work has been done in elucidating the mechanism of its cytotoxicity, its incorporation into combination therapies, and the development of second-generation proteasome inhibitors. Deacetylase and HSP90 inhibitors are also promising classes of drugs that can synergize with proteasome inhibitors. Finally, BH3 mimetics are emerging as tools to sensitize tumor cells to chemotherapy. Participation in clinical trials offers patients an immediate chance to benefit from these advances and is essential to maintain the momentum of progress. Semin Hematol 48:214-226. Published by Elsevier Inc.
C1 [Weniger, Marc A.; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Weniger, MA (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wiestnea@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL005076-05]
NR 100
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U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JUL
PY 2011
VL 48
IS 3
BP 214
EP 226
DI 10.1053/j.seminhematol.2011.05.001
PG 13
WC Hematology
SC Hematology
GA 799YI
UT WOS:000293322400010
PM 21782064
ER
PT J
AU Lee, NR
Fidler, DJ
Blakeley-Smith, A
Daunhauer, L
Robinson, C
Hepburn, SL
AF Lee, Nancy Raitano
Fidler, Deborah J.
Blakeley-Smith, Audrey
Daunhauer, Lisa
Robinson, Cordelia
Hepburn, Susan L.
TI Caregiver Report of Executive Functioning in a Population-Based Sample
of Young Children With Down Syndrome
SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES
LA English
DT Article
ID AUTISM SPECTRUM DISORDERS; WORKING-MEMORY DEFICITS; PREFRONTAL CORTEX;
ADOLESCENTS; DISSOCIATION; DISABILITIES; INDIVIDUALS; BEHAVIOR; RATINGS;
DISEASE
AB The current study describes everyday executive function (EF) profiles in young children with Down syndrome. Caregivers of children with Down syndrome (n = 26; chronological ages = 4-10 years; mental ages = 2-4 years) completed the Behavior Rating Inventory of Executive Function Preschool (BRIEF-P; G. A. Gioia, K. A. Espy, & P. K. Isquith, 2003), a caregiver report measure of everyday/functional EF skills in multiple domains. On the BRIEF-P, elevations were noted on a global EF composite as well as the Working Memory and Plan/Organize scales in particular (relative to norms developed for typically developing children of a similar mental age). These results suggest a specific pattern of EF weaknesses in young children with Down syndrome, consistent with the extant literature that has focused primarily on older individuals who have been tested using laboratory EF tasks.
C1 [Lee, Nancy Raitano; Blakeley-Smith, Audrey; Robinson, Cordelia] Univ Colorado, Sch Med, Boulder, CO 80309 USA.
[Fidler, Deborah J.; Daunhauer, Lisa] Colorado State Univ, Ft Collins, CO 80523 USA.
[Hepburn, Susan L.] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA.
RP Lee, NR (reprint author), NIMH, NIH, Unit Brain Imaging, Child Psychiat Branch, Bldg 10,Room 4C110 MSC 1367,10 Ctr Dr, Bethesda, MD 20892 USA.
EM lnancy@mail.nih.gov
RI Lee, Nancy Raitano/F-2565-2011; Lee, Nancy/M-7492-2016;
OI Lee, Nancy/0000-0002-6663-0713; Hepburn, Susan/0000-0002-8545-3804
FU NICHD NIH HHS [L30 HD048361, U19 HD035468]
NR 49
TC 20
Z9 20
U1 2
U2 19
PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES
PI WASHINGTON
PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA
SN 1944-7515
J9 AJIDD-AM J INTELLECT
JI AJIDD-Am. J. Intellect. Dev. Disabil.
PD JUL
PY 2011
VL 116
IS 4
BP 290
EP 304
DI 10.1352/1944-7558-116.4.290
PG 15
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 794ZO
UT WOS:000292941500004
PM 21740257
ER
PT J
AU Andreeva, VA
Cockburn, MG
Yaroch, AL
Unger, JB
Rueda, R
Reynolds, KD
AF Andreeva, Valentina A.
Cockburn, Myles G.
Yaroch, Amy L.
Unger, Jennifer B.
Rueda, Robert
Reynolds, Kim D.
TI Preliminary Evidence for Mediation of the Association Between
Acculturation and Sun-Safe Behaviors
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID NATIONAL TRENDS SURVEY; SKIN-CANCER; UNITED-STATES; RISK BEHAVIORS; US
POPULATION; HEALTH; PROTECTION; MELANOMA; ADULTS; PREVENTION
AB Objectives: To identify and test mediators of the relationship between acculturation and sun-safe behaviors among Latinos in the United States. We hypothesized that the effect of acculturation on use of sunscreen, shade, and sun-protective clothing would be mediated by perceived health status, educational level, access to health care, and contact with social networks regarding health matters.
Design: The 2005 Health Information National Trends Survey, implemented by the National Cancer Institute.
Setting: Nationwide survey.
Participants: A probability-based sample of the US civilian, noninstitutionalized adult population, comprising 496 Latino respondents.
Main Outcome Measures: Use of sunscreen, shade, and sun-protective clothing when outdoors on sunny days, assessed by self-report on frequency scales.
Results: The positive association between acculturation and sunscreen use and the negative association between acculturation and use of sun-protective clothing were mediated by educational level (P <.05 for both). Perceived health status and contact with social networks regarding health matters were supported as mediators for sunscreen use only (P <.05). Health care access was not supported as a mediator for any of the outcomes.
Conclusions: Structural equation models revealed distinct direct and indirect paths between acculturation and each sun-safe practice. Our findings emphasize behavior-specific mediated associations and could inform sun safety programming for Latinos with low and high levels of acculturation. The models support educational level, contact with social networks regarding health matters, and perceived health status as mediators primarily for sunscreen use. Future research should test different mediators for use of shade or sun-protective clothing.
C1 [Andreeva, Valentina A.] Univ Paris 08, Nutr Epidemiol Res Unit, F-93017 Bobigny, France.
[Andreeva, Valentina A.; Cockburn, Myles G.; Unger, Jennifer B.; Reynolds, Kim D.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Rueda, Robert] Univ So Calif, Rossier Sch Educ, Dept Educ Psychol, Los Angeles, CA USA.
[Yaroch, Amy L.] NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Yaroch, Amy L.] Gretchen Swanson Ctr Nutr, Omaha, NE USA.
[Reynolds, Kim D.] Claremont Grad Univ, Sch Community & Global Hlth, San Dimas, CA USA.
RP Andreeva, VA (reprint author), Univ Paris 08, Nutr Epidemiol Res Unit, 74 Rue Marcel Cachin, F-93017 Bobigny, France.
EM v.andreeva@uren.smbh.univ-paris13.fr
FU Department of Preventive Medicine, Keck School of Medicine, University
of Southern California; Centers for Disease Control and Prevention
[U55/CCU921930-02]; National Institute of Environmental Health Sciences
[5P30 ES07048]; National Cancer Institute [R01 CA121052, CA100285]
FX Dr Andreeva was supported by a doctoral dissertation fellowship at the
Department of Preventive Medicine, Keck School of Medicine, University
of Southern California. Dr Cockburn was supported in part by grant
U55/CCU921930-02 from the Centers for Disease Control and Prevention,
grant 5P30 ES07048 from the National Institute of Environmental Health
Sciences, and grant R01 CA121052 from the National Cancer Institute. Dr
Reynolds was supported by grant CA100285 from the National Cancer
Institute.
NR 55
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U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD JUL
PY 2011
VL 147
IS 7
BP 814
EP 819
PG 6
WC Dermatology
SC Dermatology
GA 793RL
UT WOS:000292840700007
PM 21768480
ER
PT J
AU Szentpetery, Z
Szakacs, G
Bojjireddy, N
Tai, AW
Balla, T
AF Szentpetery, Zsofia
Szakacs, Gergely
Bojjireddy, Naveen
Tai, Andrew W.
Balla, Tamas
TI Genetic and functional studies of phosphatidyl-inositol 4-kinase type
III alpha
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article
DE Phosphoinositide; PI 4-kinase; Chromosome 22; K562 leukemia cells;
Golgi; Endoplasmic reticulum
ID 22Q11 DELETION SYNDROME; SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE;
GOLGI-COMPLEX; CLONING; YEAST; LEUKEMIA; REVEALS; FAMILY; STT4
AB Phosphatidylinositol 4-kinase type IIIa (PI4KIII alpha) is one of four mammalian PI 4-kinases that catalyzes the first committed step in polyphosphoinositide synthesis. PI4KIII alpha has been linked to regulation of ER exit sites and to the synthesis of plasma membrane phosphoinositides and recent studies have also revealed its importance in replication of the Hepatitis C virus in liver. Two isoforms of the mammalian PI4KIII alpha have been described and annotated in GenBank: a larger, similar to 230 kDa (isoform 2) and a shorter splice variant containing only the similar to 97 kDa C-terminus that includes the catalytic domain (isoform 1). However, Northern analysis of human tissues and cancer cells showed only a single transcript of similar to 7.5 kb with the exception of the proerythroleukemia line K562, which contained significantly higher level of the 7.5 kb transcript along with smaller ones of 2.4, 3.5 and 4.2 kb size. Bioinformatic analysis also confirmed the high copy number of PI4KIII alpha transcript in K562 cells along with several genes located in the same region in Chr22, including two pseudogenes that cover most exons coding for isoform 1, consistent with chromosome amplification. A panel of polyclonal antibodies raised against peptides within the C-terminal half of PI4KIII alpha failed to detect the shorter isoform 1 either in COS-7 cells or K562 cells. Moreover, expression of a cDNA encoding isoform 1 yielded a protein of similar to 97 kDa that showed no catalytic activity and failed to rescue hepatitis C virus replication. These data draw attention to PI4KIII alpha as one of the genes found in Chr22q11, a region affected by chromosomal instability, but do not substantiate the existence of a functionally relevant short form of PI4KIII alpha. Published by Elsevier B.V.
C1 [Szentpetery, Zsofia; Bojjireddy, Naveen; Balla, Tamas] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Szakacs, Gergely] Hungarian Acad Sci, Inst Enzymol, Budapest, Hungary.
[Tai, Andrew W.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Tai, Andrew W.] Ann Arbor Vet Adm Hlth Syst, Ann Arbor, MI USA.
RP Balla, T (reprint author), NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
RI Szakacs, Gergely/A-2580-2009;
OI Szakacs, Gergely/0000-0002-9311-7827; Balla, Tamas/0000-0002-9077-3335
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health [AI083785]; American
Gastroenterological Association Foundation
FX This research was supported in part by the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development (to T.B.) and grant AI083785 (to A.W.T.) of the
National Institutes of Health (T.B.) as well as by the American
Gastroenterological Association Foundation (to A.W.T.).
NR 44
TC 11
Z9 11
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD JUL-AUG
PY 2011
VL 1811
IS 7-8
BP 476
EP 483
DI 10.1016/j.bbalip.2011.04.013
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 794ZM
UT WOS:000292941300007
PM 21601653
ER
PT J
AU Gao, F
Kim, HW
Igarashi, M
Kiesewetter, D
Chang, L
Ma, KZ
Rapoport, SI
AF Gao, Fei
Kim, Hyung-Wook
Igarashi, Miki
Kiesewetter, Dale
Chang, Lisa
Ma, Kaizong
Rapoport, Stanley I.
TI Liver conversion of docosahexaenoic and arachidonic acids from their
18-carbon precursors in rats on a DHA-free but alpha-LNA-containing n-3
PUFA adequate diet (Retracted article. See vol. 1851, pg. 238, 2015)
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Article; Retracted Publication
DE Conversion; Arachidonic; Docosahexaenoic; Diet; Liver; Turnover
ID POLYUNSATURATED FATTY-ACIDS; LINOLENIC ACID; BRAIN PHOSPHOLIPIDS;
ADULT-RATS; IN-VIVO; METABOLISM; DEPRIVATION; DESATURATION; VEGETARIANS;
DEFICIENT
AB The long-chain polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA. 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6), are critical for health. These PUFAs can be synthesized in liver from their plant-derived precursors, a-linolenic acid (alpha-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6). Vegetarians and vegans may have suboptimal long-chain n-3 PUFA status, and the extent of the conversion of alpha-LNA to EPA and DHA by the liver is debatable. We quantified liver conversion of DHA and other n-3 PUFAs from alpha-LNA in rats fed a DHA-free but alpha-LNA (n-3 PUFA) adequate diet, and compared results to conversion of LA to AA. [U-C-13]LA or [U-13C] alpha-LNA was infused intravenously for 2 h at a constant rate into unanesthetized rats fed a DHA-free alpha-LNA adequate diet, and published equations were used to calculate kinetic parameters. The conversion coefficient k* of DHA from alpha-LNA was much higher than for AA from LA (97.2 x 10(-3) vs. 10.6 x 10(-3) min(-1)), suggesting that liver elongation-desaturation is more selective for n-3 PUFA biosynthesis on a per molecule basis. The net daily secretion rate of DHA, 20.3 mu mol/day, exceeded the reported brain DHA consumption rate by 50-fold, suggesting that the liver can maintain brain DHA metabolism with an adequate dietary supply solely of alpha-LNA. This infusion method could be used in vegetarians or vegans to determine minimal daily requirements of EPA and DHA in humans. Published by Elsevier B.V.
C1 [Gao, Fei; Kim, Hyung-Wook; Igarashi, Miki; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Kiesewetter, Dale] Natl Inst Biomed Imaging & Bioengn, Positron Emiss Tomog Radiochem Grp, NIH, Bethesda, MD 20892 USA.
RP Gao, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Room 1S126, Bethesda, MD 20892 USA.
EM gaof@mail.nih.gov
FU National Institute on Aging, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health. The authors
thank Dr. Ameer Taha for the comments on the manuscript and the National
Institutes of Health Fellows Editorial Board for editorial assistance.
NR 48
TC 12
Z9 12
U1 2
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD JUL-AUG
PY 2011
VL 1811
IS 7-8
BP 484
EP 489
DI 10.1016/j.bbalip.2011.05.008
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 794ZM
UT WOS:000292941300008
PM 21651989
ER
PT J
AU Kitamura, A
Matsushita, K
Takiguchi, Y
Shimada, H
Tada, Y
Yamanaka, M
Hiroshima, K
Tagawa, M
Tomonaga, T
Matsubara, H
Inoue, M
Hasegawa, M
Sato, Y
Levens, D
Tatsumi, K
Nomura, F
AF Kitamura, Atsushi
Matsushita, Kazuyuki
Takiguchi, Yuichi
Shimada, Hideaki
Tada, Yuji
Yamanaka, Makako
Hiroshima, Kenzo
Tagawa, Masatoshi
Tomonaga, Takeshi
Matsubara, Hisahiro
Inoue, Makoto
Hasegawa, Mamoru
Sato, Yasunori
Levens, David
Tatsumi, Koichiro
Nomura, Fumio
TI Synergistic effect of non-transmissible Sendai virus vector encoding the
c-myc suppressor FUSE-binding protein-interacting repressor plus
cisplatin in the treatment of malignant pleural mesothelioma
SO CANCER SCIENCE
LA English
DT Article
ID GENE-THERAPY; PHOSPHORYLATION; TRANSCRIPTION; EFFICACY; SYSTEM; CANCER;
REPAIR; CELLS; TFIIH
AB Human malignant pleural mesothelioma (HMPM) is highly resistant to conventional therapy, and therefore novel therapies are required. We previously reported that overexpression of the FUSE-binding protein-interacting repressor (FIR), a c-myc transcriptional repressor, induces apoptosis via c-Myc suppression, and is thus a suitable cancer therapy. In the current preclinical trial, a fusion gene deleted non-transmissible Sendai virus vector encoding FIR (SeV/Delta F/FIR) was prepared and its cytotoxic activity against an orthotopic xenograft model of HMPM, in combination with cisplatin, was assessed. SeV/Delta F/FIR and a fusion gene deleted non-transmissible Sendai virus vector encoding green fluorescent protein (SeV/Delta F/GFP) were prepared. The transduction efficiency of these agents in terms of dose-dependent cytotoxicity and/or apoptosis induction was then assessed in a few HMPM cells. Combination therapy with SeV/Delta F/FIR plus cisplatin was evaluated in vitro and in a mouse model. SeV/Delta F/FIR significantly reduced cell viability in three HMPM cell lines but was less effective in non-tumor immortalized mesothelial cells. SeV/Delta F/FIR cytotoxicity was partly due to apoptosis induction via c-Myc suppression. In addition, SeV/Delta F/FIR showed synergistic antitumor effects in combination with cisplatin, as was revealed by isobologram analysis in MSTO-211H. Moreover, combination therapy with SeV/Delta F/FIR plus cisplatin demonstrated significant tumor reduction and improvement in survival rate in an animal model. Combination therapy with SeV/Delta F/FIR plus cisplatin has therapeutic potential against HMPM. SeV/Delta F/FIR plus cisplatin will be an attractive modality against HMPM in the future. (Cancer Sci 2011; 102: 1366-1373)
C1 [Kitamura, Atsushi; Matsushita, Kazuyuki; Nomura, Fumio] Chiba Univ, Dept Mol Diag, Grad Sch Med, Chiba, Japan.
[Kitamura, Atsushi; Tada, Yuji; Yamanaka, Makako; Tatsumi, Koichiro] Chiba Univ, Dept Respirol, Grad Sch Med, Chiba, Japan.
[Takiguchi, Yuichi] Chiba Univ, Dept Chemotherapy, Grad Sch Med, Chiba, Japan.
[Shimada, Hideaki] Toho Univ, Dept Surg, Sch Med, Tokyo, Japan.
[Hiroshima, Kenzo] Tokyo Womens Med Univ, Yachiyo Med Ctr, Dept Pathol, Yachiyo, Japan.
[Tagawa, Masatoshi] Chiba Canc Ctr, Div Pathol & Cell Therapy, Chiba 2608717, Japan.
[Tomonaga, Takeshi] Natl Inst Biomed Innovat, Proteome Res Ctr, Proteome Res Project, Ibaraki, Japan.
[Matsubara, Hisahiro] Chiba Univ, Dept Frontier Surg, Grad Sch Med, Chiba, Japan.
[Inoue, Makoto; Hasegawa, Mamoru] DNAVEC Corp, Tsukuba, Ibaraki, Japan.
[Sato, Yasunori] Chiba Univ Hosp, Clin Res Ctr, Chiba, Japan.
[Levens, David] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Matsushita, K (reprint author), Chiba Univ, Dept Mol Diag, Grad Sch Med, Chiba, Japan.
EM kmatsu@faculty.chiba-u.jp
RI Levens, David/C-9216-2009;
OI Levens, David/0000-0002-7616-922X; Matsushita,
Kazuyuki/0000-0001-6742-0761
NR 29
TC 9
Z9 9
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD JUL
PY 2011
VL 102
IS 7
BP 1366
EP 1373
DI 10.1111/j.1349-7006.2011.01931.x
PG 8
WC Oncology
SC Oncology
GA 793ZN
UT WOS:000292863100018
PM 21435101
ER
PT J
AU Aletras, AH
Tilak, GS
Hsu, LY
Arai, AE
AF Aletras, Anthony H.
Tilak, Gauri S.
Hsu, Li-Yueh
Arai, Andrew E.
TI Heterogeneity of Intramural Function in Hypertrophic Cardiomyopathy
Mechanistic Insights From MRI Late Gadolinium Enhancement and
High-Resolution Displacement Encoding With Stimulated Echoes Strain Maps
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE hypertrophic cardiomyopathy; MRI; DENSE; displacement encoding with
stimulated echoes; myocardial function; strain; late gadolinium
enhancement
ID CARDIOVASCULAR MAGNETIC-RESONANCE; DELAYED CONTRAST ENHANCEMENT;
MYOCARDIAL FIBROSIS; REGIONAL HETEROGENEITY; QUANTITATIVE-ANALYSIS;
CONTRACTILE FUNCTION; SYMPTOMATIC PATIENTS; HYPERTENSIVE HEARTS;
VENTRICULAR SEPTUM; SUDDEN-DEATH
AB Background-In hypertrophic cardiomyopathy (HCM), myocardial abnormalities are commonly heterogeneous. Two patterns of late gadolinium enhancement (LGE) have been reported: a bright "confluent" and an intermediate intensity abnormality termed "diffuse," each representing different degrees of myocardial scarring. We used MRI to study the relation between intramural cardiac function and the extent of fibrosis in HCM. The aim of this study was to determine whether excess collagen or myocardial scarring, as determined by LGE MRI, are the primary mechanisms leading to heterogeneous regional contractile function in patients with HCM.
Methods and Results-Intramural left ventricular strain, transmural left ventricular function, and regions of myocardial fibrosis/scarring were imaged in 22 patients with HCM, using displacement encoding with stimulated echoes (DENSE), cine MRI, and LGE. DENSE systolic strain maps were qualitatively and quantitatively compared with LGE images. Intramural systolic strain by DENSE was significantly depressed within areas of confluent and diffuse LGE but also in the core of the most hypertrophic nonenhanced segment (all P<0.001 versus nonhypertrophied segments). DENSE demonstrated an unexpected inner rim of largely preserved contractile function and a noncontracting outer wall within hypertrophic segments in 91% of patients.
Conclusions-LGE predicted some but not all of the heterogeneity of intramural contractile abnormalities. This indicates that myocardial scarring or excess interstitial collagen deposition does not fully explain the observed contractile heterogeneity in HCM. Thus, myofibril disarray or other nonfibrotic processes affect systolic function in a large number of patients with HCM. (Circ Cardiovasc Imaging. 2011;4:425-434.)
C1 [Aletras, Anthony H.; Tilak, Gauri S.; Hsu, Li-Yueh; Arai, Andrew E.] NHLBI, Cardiovasc & Pulm Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Aletras, Anthony H.] Univ Cent Greece, Dept Comp Sci & Biomed Informat, Lamia, Greece.
RP Arai, AE (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Dept Hlth & Human Serv, Bldg 10,B1D-461,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM AraiA@nhlbi.nih.gov
OI Aletras, Anthony/0000-0002-3786-3817
FU National Heart, Lung and Blood Institute [Z01 HL004607-08 CE]
FX This work was supported by the Intramural Research Program of the
National Heart, Lung and Blood Institute, Z01 HL004607-08 CE.
NR 48
TC 15
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD JUL
PY 2011
VL 4
IS 4
BP 425
EP 434
DI 10.1161/CIRCIMAGING.110.958751
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 794BV
UT WOS:000292871000012
PM 21576279
ER
PT J
AU Freiberg, MS
Chang, CCH
Skanderson, M
McGinnis, K
Kuller, LH
Kraemer, KL
Rimland, D
Goetz, MB
Butt, AA
Barradas, MCR
Gibert, C
Leaf, D
Brown, ST
Samet, J
Kazis, L
Bryant, K
Justice, AC
AF Freiberg, Matthew S.
Chang, Chung-Chou H.
Skanderson, Melissa
McGinnis, Kathleen
Kuller, Lewis H.
Kraemer, Kevin L.
Rimland, David
Goetz, Matthew B.
Butt, Adeel A.
Barradas, Maria C. Rodriguez
Gibert, Cynthia
Leaf, David
Brown, Sheldon T.
Samet, Jeffrey
Kazis, Lewis
Bryant, Kendall
Justice, Amy C.
CA Vet Aging Cohort Study
TI The Risk of Incident Coronary Heart Disease Among Veterans With and
Without HIV and Hepatitis C
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE viruses; coronary disease; mortality; comorbidity
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYOCARDIAL-INFARCTION; MICROBIAL
TRANSLOCATION; CARDIOVASCULAR-DISEASE; INFECTED INDIVIDUALS;
ARTERY-DISEASE; ASSOCIATION; SEROPOSITIVITY; ATHEROSCLEROSIS; PREVALENCE
AB Background-Whether hepatitis C virus (HCV) confers additional coronary heart disease (CHD) risk among human immunodeficiency virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured.
Methods and Results-We analyzed data on 8579 participants (28% HIV+, 9% HIV + HCV+) from the Veterans Aging Cohort Study Virtual Cohort who participated in the 1999 Large Health Study of Veteran Enrollees. We analyzed data collected on HIV and HCV status, risk factors for and the incidence of CHD, and mortality from January 2000 to July 2007. We compared models to assess CHD risk when death was treated as a censoring event and as a competing risk. During the median 7.3 years of follow-up, there were 194 CHD events and 1186 deaths. Compared with HIV - HCV - Veterans, HIV + HCV + Veterans had a significantly higher risk of CHD regardless of whether death was adjusted for as a censoring event (adjusted hazard ratio, 2.03; 95% confidence interval, 1.28 to 3.21) or a competing risk (adjusted HR, 2.45; 95% confidence interval, 1.83 to 3.27 respectively). Compared with HIV - HCV - Veterans, HIV + HCV + Veterans also had a significantly higher adjusted risk of CHD regardless of whether death was treated as a censored event (adjusted hazard ratio, 1.93; 95% confidence interval, 1.02 to 3.62) or a competing risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.03 to 2.07).
Conclusions-HIV + HCV + Veterans have an increased risk of CHD compared with HIV + HCV - and HIV - HCV - Veterans. (Circ Cardiovasc Qual Outcomes. 2011;4:425-432.)
C1 [Freiberg, Matthew S.; Chang, Chung-Chou H.; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA.
[Freiberg, Matthew S.; Chang, Chung-Chou H.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Skanderson, Melissa; McGinnis, Kathleen; Justice, Amy C.] W Haven Vet Adm Med Ctr, VA Connecticut Hlth Care Syst, West Haven, CT USA.
[Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA.
[Rimland, David] Atlanta Vet Adm Med Ctr, Atlanta, GA USA.
[Goetz, Matthew B.; Leaf, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Goetz, Matthew B.; Leaf, David] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA.
[Butt, Adeel A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
[Barradas, Maria C. Rodriguez] Baylor Coll Med, Houston, TX 77030 USA.
[Barradas, Maria C. Rodriguez] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA.
[Gibert, Cynthia] George Washington Univ, Sch Med, Washington, DC USA.
[Gibert, Cynthia] Washington DC Vet Adm Med Ctr, Washington, DC USA.
[Brown, Sheldon T.] James J Peters VA Bronx, New York, NY USA.
[Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA.
[Samet, Jeffrey] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Bryant, Kendall] NIAAA, Bethesda, MD USA.
[Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
RP Freiberg, MS (reprint author), Univ Pittsburgh, Sch Med, 230 McKee Pl, Pittsburgh, PA 15213 USA.
EM freibergms@upmc.edu
OI Kazis, Lewis/0000-0003-1800-5849; Samet, Jeffrey/0000-0002-0897-3400;
Goetz, Matthew/0000-0003-4542-992X
FU National Institute on Alcohol Abuse and Alcoholism [2U10 AA 13566, K23
AA015914]; National Heart, Lung, and Blood Institute [1RO1HL095136-03]
FX This study was supported by the National Institute on Alcohol Abuse and
Alcoholism (2U10 AA 13566 and K23 AA015914) and the National Heart,
Lung, and Blood Institute (1RO1HL095136-03).
NR 33
TC 54
Z9 56
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2011
VL 4
IS 4
BP 425
EP 432
DI 10.1161/CIRCOUTCOMES.110.957415
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 794CH
UT WOS:000292872500009
PM 21712519
ER
PT J
AU Gadgeel, SM
Ivy, P
Chen, W
Mauer, J
Smith, D
LoRusso, P
AF Gadgeel, Shirish M.
Ivy, Percy
Chen, Wei
Mauer, Joan
Smith, Daryn
LoRusso, Patricia
TI Analysis of Lung Cancer Patients Enrolled in CTEP (Cancer Therapy
Evaluation Program)-Sponsored Phase I Trials
SO CLINICAL LUNG CANCER
LA English
DT Article
DE Clinical Trials; CTEP; Non small-cell; Phase I; Small-cell
ID III TRIAL; ONCOLOGY TRIALS; CLINICAL-TRIALS; CHEMOTHERAPY; DOCETAXEL;
TOPOTECAN; BENEFITS; RISKS; PARTICIPANTS; PERCEPTIONS
AB Introduction: A recent review of phase I trials suggests that participation in these trials can be associated with clinical benefit and the rate of drug-related deaths is low. We conducted an analysis of the Cancer Therapy Evaluation Program (CTEP)-sponsored phase I trials to assess the outcomes of lung cancer patients enrolled in phase I trials. Materials and Methods: Data from all CTEP-sponsored adult phase I trials conducted between 1997 and 2008 were analyzed. An analysis of demographics, rates of toxicities, and clinical benefit rate among patients with non small-cell lung cancer (NSCLC), small-cell lung cancer (SCLC), and other cancers was conducted. Results: Of the 3560 patients enrolled in 136 phase I trials, 301 (8.5%) had NSCLC and 40 (1.1%) had SCLC. The median age of lung cancer patients, at 60 years, was significantly higher than patients with other cancers. The rest of the demographics were similar among the groups. The rate of Grade 3-5 toxicities was higher among NSCLC patients (54% versus 46%). The toxicity-related death rate was <= 1% among all groups. The clinical benefit rate and median duration in study of approximately 2 months were similar among all groups of patients. Conclusion: An analysis of the CTEP-sponsored phase I trials shows that lung cancer patients enrolled in these trials have a similar incidence of toxicity-related deaths and a similar probability of clinical benefit as patients with other cancers. These data suggest that patients with progressive lung cancer following approved therapies should be considered for phase I trials.
C1 [Gadgeel, Shirish M.] Wayne State Univ, Karmanos Canc Ctr, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Ivy, Percy; Mauer, Joan] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Gadgeel, SM (reprint author), Wayne State Univ, Karmanos Canc Ctr, Karmanos Canc Inst, 4100 John R St,4 HWCRC, Detroit, MI 48201 USA.
EM gadgeels@karmanos.org
NR 24
TC 3
Z9 3
U1 0
U2 1
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1525-7304
J9 CLIN LUNG CANCER
JI Clin. Lung Cancer
PD JUL
PY 2011
VL 12
IS 4
BP 218
EP 223
DI 10.1016/j.cllc.2011.03.022
PG 6
WC Oncology
SC Oncology
GA 795PJ
UT WOS:000292985800003
PM 21726820
ER
PT J
AU Kristinsson, SY
Minter, AR
Korde, N
Tan, E
Landgren, O
AF Kristinsson, Sigurdur Y.
Minter, Alex R.
Korde, Neha
Tan, Esther
Landgren, Ola
TI Bone disease in multiple myeloma and precursor disease: novel diagnostic
approaches and implications on clinical management
SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
LA English
DT Review
DE bisphosphonates; bone disease; fractures; MGUS; multiple myeloma;
radiology; smoldering multiple myeloma
ID CARBOXY-TERMINAL TELOPEPTIDE; UNDETERMINED SIGNIFICANCE MGUS; REDUCES
SKELETAL EVENTS; B LIGAND RANKL; MONOCLONAL GAMMOPATHY; ZOLEDRONIC ACID;
RECEPTOR ACTIVATOR; RANDOMIZED-TRIAL; FRACTURE RISK; WORKING GROUP
AB The manifestations of bone involvement in patients with multiple myeloma (MM) can have devastating clinical effects and increase mortality. Recent studies demonstrate that patients with the precursor conditions smoldering MM (SMM) and monoclonal gammopathy of undetermined significance (MGUS) show evidence of bone disease and increased risk of fractures. The understanding of the pathogenesis of bone disease in MM has expanded in recent years. The traditional skeletal survey will probably be replaced by newer and more sensitive imaging techniques, which may have a prognostic impact and change our definition of MGUS and SMM. Bisphosphonates are recommended to prevent skeletal events in patients with MM, and have also been studied in SMM and MGUS. This article summarizes the current knowledge of bone disease in plasma cell disorders, and discusses the current standard and future role of novel imaging techniques, as well as the evidence and current guidelines for bisphosphonates in MM, SMM and MGUS.
C1 [Kristinsson, Sigurdur Y.] Karolinska Univ, Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
[Minter, Alex R.; Korde, Neha; Tan, Esther; Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Korde, Neha] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Kristinsson, SY (reprint author), Karolinska Univ, Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
EM sigurdur.kristinsson@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU National Cancer Institute, National Institutes of Health, Bethesda, MD,
USA
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Bethesda, MD,
USA. The authors have no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript apart from those disclosed.
NR 101
TC 8
Z9 12
U1 0
U2 4
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7159
J9 EXPERT REV MOL DIAGN
JI Expert Rev. Mol. Diagn.
PD JUL
PY 2011
VL 11
IS 6
BP 593
EP 603
DI 10.1586/ERM.11.44
PG 11
WC Pathology
SC Pathology
GA 794PH
UT WOS:000292912200010
PM 21745013
ER
PT J
AU Carson, V
Iannotti, RJ
Pickett, W
Janssen, I
AF Carson, Valerie
Iannotti, Ronald J.
Pickett, William
Janssen, Ian
TI Urban and rural differences in sedentary behavior among American and
Canadian youth
SO HEALTH & PLACE
LA English
DT Article
DE Urban-rural health; Sedentary behavior; Youth; Mediation
ID PHYSICAL-ACTIVITY; SCHOOL-CHILDREN; UNITED-STATES; SCREEN TIME;
ADOLESCENTS; HEALTH; ENVIRONMENT; PERCEPTION; MEDIATION; PATTERNS
AB We examined relationships between urban-rural status and three screen time behaviors (television, computer, video games), and the potential mediating effect of parent and peer support on these relationships. Findings are based on American (n=8563) and Canadian (n=8990) youth in grades 6-10 from the 2005/06 Health Behavior in School-Aged Children Survey. Weekly hours of individual screen time behaviors were calculated. Urban-rural status was defined using the Beale coding system. Parent and peer support variables were derived from principal component analysis. In comparison to the referent group (non-metro adjacent), American youth in the most rural areas were more likely to be high television users and less likely to be high computer users. Conversely, Canadian youth in medium and large metropolitan areas were less likely to be high television users and more likely to be high computer users. Parent and peer support did not strongly mediate the relationships between urban-rural status and screen time. These findings suggest that interventions aiming to reduce screen time may be most effective if they consider residential location and the specific screen time behavior. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Carson, Valerie; Janssen, Ian] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON K7L 3N6, Canada.
[Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD 20892 USA.
[Pickett, William; Janssen, Ian] Queens Univ, Dept Community Hlth & Epidemiol, Kingston, ON K7L 3N6, Canada.
[Pickett, William] Kingston Gen Hosp, Dept Emergency Med, Kingston, ON K7L 3N6, Canada.
RP Janssen, I (reprint author), Queens Univ, Sch Kinesiol & Hlth Studies, 28 Div St, Kingston, ON K7L 3N6, Canada.
EM ian.janssen@queensu.ca
RI Janssen, Ian/B-7700-2009
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Canadian Institutes of Health Research [2004MOP 84478,
2004MOP-CHI-128223-C]; Heart and Stroke Foundation of Canada; Public
Health Agency of Canada [HT089-05205/001/SS]; CIHR-Frederick Banting and
Charles Best Doctoral Award; Canada Research Chair; Ontario Ministry of
Research and Innovation
FX The American study was supported by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development. The Canadian study was supported by research agreements
with the Canadian Institutes of Health Research (operating Grants:
2004MOP 84478 and 2004MOP-CHI-128223-C), the Heart and Stroke Foundation
of Canada, and the Public Health Agency of Canada (Contract:
HT089-05205/001/SS), the latter of which funds the Canadian version of
the World Health Organization Health Behaviour in School-Aged Children
Survey (WHO-HBSC). The WHO-HBSC is a WHO/Euro collaborative study.
International Coordinator of the 2005-2006 study: Candace Currie,
University of Edinburgh, Scotland: Data Bank Manager: Oddrun Samdal,
University of Bergen. Norway. VC was supported by a CIHR-Frederick
Banting and Charles Best Doctoral Award. IJ was supported by a Canada
Research Chair and an Early Research Award from the Ontario Ministry of
Research and Innovation.
NR 47
TC 5
Z9 5
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8292
J9 HEALTH PLACE
JI Health Place
PD JUL
PY 2011
VL 17
IS 4
BP 920
EP 928
DI 10.1016/j.healthplace.2011.04.007
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 792ZH
UT WOS:000292788400008
PM 21565545
ER
PT J
AU Tanpure, RP
Nguyen, BL
Strecker, TE
Aguirre, S
Sharma, S
Chaplin, DJ
Siim, BG
Hamel, E
Lippert, JW
Pettit, GR
Trawick, ML
Pinney, KG
AF Tanpure, Rajendra P.
Nguyen, Benson L.
Strecker, Tracy E.
Aguirre, Savannah
Sharma, Suman
Chaplin, David J.
Siim, Bronwyn G.
Hamel, Ernest
Lippert, John W., III
Pettit, George R.
Trawick, Mary Lynn
Pinney, Kevin G.
TI Regioselective Synthesis of Water-Soluble Monophosphate Derivatives of
Combretastatin A-1
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID VASCULAR DISRUPTING AGENTS; ANTINEOPLASTIC AGENTS; PHOSPHATE PRODRUG; A4
PHOSPHATE; CELL-GROWTH; TUMOR; TUBULIN; POTENT; INHIBITORS; THERAPY
AB The natural products combretastatin A-4 (CA4) and combretastatin A-1 (CA1) are potent cancer vascular disrupting agents and inhibitors of tubulin assembly (IC50 = 1-2 mu M). The phosphorylated prodrugs CA4P and CA1P are undergoing human clinical trials against cancer. CA1 is unique due to its incorporation of a vicinal phenol, which has afforded the opportunity to prepare both diphosphate and regioisomeric monophosphate derivatives. Here, we describe the first synthetic routes suitable for the regiospecific preparation of the CA1-monophosphates CA1MPA (8a/b) and CA1MPB (4a/b). The essential regio chemistry necessary to distinguish between the two vicinal phenolic groups was accomplished with a tosyl protecting group strategy. Each of the four monophosphate analogues (including Z and E isomers) demonstrated in vitro cytotoxicity against selected human cancer cell lines comparable to their corresponding diphosphate congeners. Furthermore, Z-CA1MPA (8a) and Z-CA1MPB (4a) were inactive as inhibitors of tubulin assembly (Ic(50) > 40 mu M), as anticipated in this pure protein assay.
C1 [Tanpure, Rajendra P.; Nguyen, Benson L.; Strecker, Tracy E.; Aguirre, Savannah; Trawick, Mary Lynn; Pinney, Kevin G.] Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA.
[Sharma, Suman; Chaplin, David J.; Siim, Bronwyn G.] OXiGENE Inc, San Francisco, CA 94080 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Pettit, George R.] Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA.
[Pettit, George R.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
RP Pinney, KG (reprint author), Baylor Univ, Dept Chem & Biochem, 1 Bear Pl 97348, Waco, TX 76798 USA.
EM Kevin_Pinney@baylor.edu
OI Pinney, Kevin/0000-0003-1262-8631; Sharma, Sanjeev
Kumar/0000-0002-3273-0708
FU OXiGENE, Inc.; Welch Foundation [AA-1278]; Division of Cancer Treatment
Diagnosis, NCI, DHHS [R01 CA90441-01, SR01 CA090441-07-08]; NSF
[CHE-0420802]; National Cancer Institute [5R01CA140674]
FX The authors are grateful to OXiGENE, Inc. (grants to K.G.P. and M.L.T.),
and the Welch Foundation (grant no. AA-1278 to K.G.P.), and one of us
(G.R.P.) is grateful for grants R01 CA90441-01 and SR01 CA090441-07-08
from The Division of Cancer Treatment Diagnosis, NCI, DHHS, for their
financial support of this project, and to the NSF for funding the Varian
500 MHz NMR spectrometer (grant no. CHE-0420802). In addition, portions
of this project were partially supported by Award Number 5R01CA140674
(to K.G.P. and M.L.T.) from the National Cancer Institute. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute or the
National Institutes of Health. The authors also thank Dr. A. Ramirez
(Mass Spectrometry Core Facility, Baylor University) for mass
spectroscopic analysis, Dr. C. Moehnke for assistance with NMR studies,
and Dr. J. Karban and Dr. M. Nemec (Director) for use of the shared
Molecular Biosciences Center at Baylor University.
NR 39
TC 7
Z9 8
U1 1
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD JUL
PY 2011
VL 74
IS 7
BP 1568
EP 1574
DI 10.1021/np200104t
PG 7
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 796FB
UT WOS:000293036100003
PM 21718055
ER
PT J
AU Zuck, KM
Shipley, S
Newman, DJ
AF Zuck, Karina M.
Shipley, Suzanne
Newman, David J.
TI Induced Production of N-Formyl Alkaloids from Aspergillus fumigatus by
Co-culture with Streptomyces peucetius
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID EUPENICILLIUM-SHEARII; MELANOCIN-C; XANTHOCILLIN; FUNGUS; METABOLITES;
FERMENTATION
AB Co-culture of the fungus Aspergillus fumigatus with the bacteria Streptomyces peucetius led to the induction of production of formyl xanthocillin analogues. This mixed fermentation yielded two new metabolites, fumiformamide (1) and N,N'-((1Z,3Z)-1,4-bis(4-methoxyphenyl)buta-1,3-diene-2,3-diyl)diformamide (2), together with two known N-formyl derivatives and the xanthocillin analogue BU-4704. The structures were determined by spectroscopic methods and by comparison with literature. Cytotoxic activity of all the analogues was tested on the NCI-60 cell line screen, and compound 2 exhibited significant activity against several cell lines. The analogues did not show antimicrobial activity.
C1 [Zuck, Karina M.; Shipley, Suzanne] SAIC Frederick Inc, Frederick, MD 21702 USA.
[Newman, David J.] NCI, Nat Prod Branch, Frederick, MD 21702 USA.
RP Zuck, KM (reprint author), SAIC Frederick Inc, POB B, Frederick, MD 21702 USA.
EM zuckk@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Division of Cancer Treatment and Diagnosis of the
National Cancer Institute
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported [in part] by the Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute. We gratefully acknowledge S. Staffone, C.
Manning, and K. Santullo for help with extraction and fractionation of
the extracts, Q Van and K. Gustafson for running NMR experiments, L.
Cartner and C. Saucedo for assistance with the IR and UV-vis
spectrophotometers, and J. Whitt, J. Britt, and L. Bowles for the
60-cell-line NCI screening.
NR 25
TC 31
Z9 31
U1 3
U2 38
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD JUL
PY 2011
VL 74
IS 7
BP 1653
EP 1657
DI 10.1021/np200255f
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 796FB
UT WOS:000293036100016
PM 21667925
ER
PT J
AU Morley, JE
Abbatecola, AM
Argiles, JM
Baracos, V
Bauer, J
Bhasin, S
Cederholm, T
Coats, AJS
Cummings, SR
Evans, WJ
Fearon, K
Ferrucci, L
Fielding, RA
Guralnik, JM
Harris, TB
Inui, A
Kalantar-Zadeh, K
Kirwan, BA
Mantovani, G
Muscaritoli, M
Newman, AB
Rossi-Fanelli, F
Rosano, GMC
Roubenoff, R
Schambelan, M
Sokol, GH
Storer, TW
Vellas, B
von Haehling, S
Yeh, SS
Anker, SD
AF Morley, John E.
Abbatecola, Angela Marie
Argiles, Josep M.
Baracos, Vickie
Bauer, Juergen
Bhasin, Shalender
Cederholm, Tommy
Coats, Andrew J. Stewart
Cummings, Steven R.
Evans, William J.
Fearon, Kenneth
Ferrucci, Luigi
Fielding, Roger A.
Guralnik, Jack M.
Harris, Tamara B.
Inui, Akio
Kalantar-Zadeh, Kamyar
Kirwan, Bridget-Anne
Mantovani, Giovanni
Muscaritoli, Maurizio
Newman, Anne B.
Rossi-Fanelli, Filippo
Rosano, Giuseppe M. C.
Roubenoff, Ronenn
Schambelan, Morris
Sokol, Gerald H.
Storer, Thomas W.
Vellas, Bruno
von Haehling, Stephan
Yeh, Shing-Shing
Anker, Stefan D.
CA Soc Sarcopenia Cachexia Wasting
TI Sarcopenia With Limited Mobility: An International Consensus
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
ID 6-MINUTE WALK DISTANCE; SKELETAL-MUSCLE STRENGTH; CROSS-SECTIONAL AREA;
IANA TASK-FORCE; OLDER-ADULTS; BODY-COMPOSITION; PHYSICAL FUNCTION; GAIT
SPEED; NEUROMUSCULAR ACTIVATION; PULMONARY-HYPERTENSION
AB A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that "Sarcopenia, le, reduced muscle mass, with limited mobility" should be considered an important clinical entity and that most older persons should be screened for this condition. "Sarcopenia with limited mobility" is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s. (J Am Med Dir Assoc 2011; 12: 403-409)
C1 [Morley, John E.] St Louis Univ, Sch Med, Div Geriatr Med, St Louis, MO 63104 USA.
[Morley, John E.] VA Med Ctr, GRECC, St Louis, MO USA.
[Abbatecola, Angela Marie] INRCA, Sci Direct, Ancona, Italy.
[Argiles, Josep M.] Univ Barcelona, Dept Biochem, Barcelona, Spain.
[Baracos, Vickie] Univ Alberta, Dept Oncol, Edmonton, AB T6G 2M7, Canada.
[Bauer, Juergen] Geriatr Ctr Oldenberg, Oldenburg, Germany.
[Bauer, Juergen] Univ Erlangen Nurnberg, Dept Geriatr Med, Nurnberg, Germany.
[Bhasin, Shalender; Storer, Thomas W.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Cederholm, Tommy] Univ Uppsala Hosp, Uppsala, Sweden.
[Coats, Andrew J. Stewart] Univ E Anglia, Norwich NR4 7TJ, Norfolk, England.
[Cummings, Steven R.] Univ Calif San Francisco, San Francisco Coordinating Ctr, San Francisco, CA 94143 USA.
[Cummings, Steven R.; Schambelan, Morris] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Cummings, Steven R.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Evans, William J.] GlaxoSmithKline Inc, Muscle Metab Discovery Performance Unit, Durham, NC USA.
[Evans, William J.] Duke Univ, Dept Med, Durham, NC USA.
[Evans, William J.] Duke Univ, Dept Geriatr, Durham, NC USA.
[Fearon, Kenneth] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Fearon, Kenneth] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland.
[Ferrucci, Luigi; Guralnik, Jack M.; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA.
[Fielding, Roger A.] Tufts Univ, Sch Med, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA.
[Inui, Akio] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Psychosomat Internal Med, Kagoshima 890, Japan.
[Kalantar-Zadeh, Kamyar] David Geffen UCLA Sch Med, Harold Simmons Ctr, Div Nephrol, Torrance, CA USA.
[Kalantar-Zadeh, Kamyar] David Geffen UCLA Sch Med, Harold Simmons Ctr, Div Nephrol, Los Angeles, CA USA.
[Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Los Angeles, CA USA.
[Kirwan, Bridget-Anne] SOCAR Res, Nyon, Switzerland.
[Mantovani, Giovanni] Univ Cagliari, Sch Med, Dept Med Oncol, Cagliari, Italy.
[Muscaritoli, Maurizio] Univ Roma La Sapienza, Internal Med & Clin Nutr Management Unit, Rome, Italy.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Pittsburgh, PA USA.
[Rossi-Fanelli, Filippo] Univ Rome, Rome, Italy.
[Rosano, Giuseppe M. C.] IRCCS, Med Sci Ctr Clin & Expt Med, San Raffael, Italy.
[Roubenoff, Ronenn] Novartis Inst Biomed Res, Boston, MA USA.
[Roubenoff, Ronenn] Tufts Med Ctr, Dept Med, Boston, MA USA.
[Schambelan, Morris] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA.
[Sokol, Gerald H.] Tampa Gen Hosp, Moffitt Canc Ctr, Tampa, FL 33606 USA.
[Sokol, Gerald H.] US FDA, Tampa, FL USA.
[Vellas, Bruno] Toulouse Univ Hosp, Toulouse, France.
[von Haehling, Stephan] Charite, Dept Cardiol, Berlin, Germany.
[Yeh, Shing-Shing] Stony Brook Univ Hosp, Northport VAMC & Med, Stony Brook, NY USA.
[Anker, Stefan D.] Charite Campus Virchow Klinikum, Dept Cardiol, Berlin, Germany.
RP Morley, JE (reprint author), St Louis Univ, Sch Med, Div Geriatr Med, 1402 S Grand Blvd,M238, St Louis, MO 63104 USA.
EM morley@slu.edu
RI morley, john/F-9177-2011; Newman, Anne/C-6408-2013; Rossi Fanelli,
Filippo/E-9587-2011;
OI morley, john/0000-0001-6444-2965; Newman, Anne/0000-0002-0106-1150;
Rossi Fanelli, Filippo/0000-0002-8674-1672; Kirwan,
Bridget-Anne/0000-0002-3814-3598; Baracos, Vickie/0000-0002-9609-1001;
Kalantar-Zadeh, Kamyar/0000-0002-8666-0725
FU Intramural NIH HHS [Z01 AG000015-49]
NR 93
TC 263
Z9 266
U1 14
U2 47
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD JUL
PY 2011
VL 12
IS 6
BP 403
EP 409
DI 10.1016/j.jamda.2011.04.014
PG 7
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 795SS
UT WOS:000292996700005
PM 21640657
ER
PT J
AU McGowan, PM
Simedrea, C
Ribot, EJ
Foster, PJ
Palmieri, D
Steeg, PS
Allan, AL
Chambers, AF
AF McGowan, Patricia M.
Simedrea, Carmen
Ribot, Emeline J.
Foster, Paula J.
Palmieri, Diane
Steeg, Patricia S.
Allan, Alison L.
Chambers, Ann F.
TI Notch1 Inhibition Alters the CD44(hi)/CD24(lo) Population and Reduces
the Formation of Brain Metastases from Breast Cancer
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID ALDEHYDE DEHYDROGENASE-ACTIVITY; MAMMARY STEM-CELLS; INITIATING CELLS;
OVARIAN-CANCER; IN-VITRO; EXPRESSION; ACTIVATION; SURVIVAL; GENES; MODEL
AB Brain metastasis from breast cancer is an increasingly important clinical problem. Here we assessed the role of CD44(hi)/CD24(lo) cells and pathways that regulate them, in an experimental model of brain metastasis. Notch signaling (mediated by gamma-secretase) has been shown to contribute to maintenance of the cancer stem cell (CSC) phenotype. Cells sorted for a reduced stem-like phenotype had a reduced ability to form brain metastases compared with unsorted or CD44(hi)/CD24(lo) cells (P < 0.05; Kruskal-Wallis). To assess the effect of gamma-secretase inhibition, cells were cultured with DAPT and the CD44/CD24 phenotypes quantified. 231-BR cells with a CD44(hi)/CD24(lo) phenotype was reduced by about 15% in cells treated with DAPT compared with DMSO-treated or untreated cells (P = 0.001, ANOVA). In vivo, mice treated with DAPT developed significantly fewer micro- and macrometastases compared with vehicle treated or untreated mice (P = 0.011, Kruskal-Wallis). Notch1 knockdown reduced the expression of CD44(hi)/CD24(lo) phenotype by about 20%. In vitro, Notch1 shRNA resulted in a reduction in cellular growth at 24, 48, and 72 hours time points (P = 0.033, P = 0.002, and P = 0.009, ANOVA) and about 60% reduction in Matrigel invasion was observed (P < 0.001, ANOVA). Cells transfected with shNotch1 formed significantly fewer macrometastases and micrometastases compared with scrambled shRNA or untransfected cells (P < 0.001; Kruskal-Wallis). These data suggest that the CSC phenotype contributes to the development of brain metastases from breast cancer, and this may arise in part from increased Notch activity. Mol Cancer Res; 9(7); 834-44. (C)2011 AACR.
C1 [McGowan, Patricia M.; Simedrea, Carmen; Foster, Paula J.; Chambers, Ann F.] Univ Western Ontario, Dept Med Biophys, London, ON, Canada.
[Allan, Alison L.; Chambers, Ann F.] Univ Western Ontario, Dept Oncol, London, ON, Canada.
[Allan, Alison L.] Univ Western Ontario, Dept Anat & Cell Biol, London, ON, Canada.
[Ribot, Emeline J.; Foster, Paula J.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada.
[Palmieri, Diane; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP McGowan, PM (reprint author), St Vincents Univ Hosp, Educ & Res Ctr, Elm Pk, Dublin 4, Ireland.
EM patricia.mcgowan@ucd.ie
RI Foster, Paula/M-2201-2013; Palmieri, Diane/B-4258-2015; Chambers,
Ann/L-6285-2015;
OI Foster, Paula/0000-0002-4868-3395; Chambers, Ann/0000-0002-9509-5123;
McGowan, Patricia/0000-0003-3936-2503
FU US Department of Defense [W81XWH-06-2-0033]; Translational Breast Cancer
Research Training Program at the London Regional Cancer Program; Ontario
Institute of Cancer Research [08NOV-230]; Canadian Institutes of Health
Research; Canada Research Chairs Program
FX This research was supported by grant #W81XWH-06-2-0033 US Department of
Defense Breast Cancer Research Program (A.F. Chambers, P.J. Foster, and
P.S. Steeg). P.M. McGowan was the recipient of a Postdoctoral Fellowship
from the Translational Breast Cancer Research Training Program at the
London Regional Cancer Program. A.L. Allan is supported by research
funding from the Ontario Institute of Cancer Research (#08NOV-230) and a
Canadian Institutes of Health Research New Investigator Award. A.F.
Chambers is Canada Research Chair in Oncology, supported by the Canada
Research Chairs Program.
NR 58
TC 56
Z9 58
U1 0
U2 15
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD JUL
PY 2011
VL 9
IS 7
BP 834
EP 844
DI 10.1158/1541-7786.MCR-10-0457
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 794DG
UT WOS:000292875000003
PM 21665937
ER
PT J
AU Putney, JW
AF Putney, James W.
TI The Physiological Function of Store-operated Calcium Entry
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Calcium channels; Store-operated channels; Calcium signaling; Ion
channels; Orai; STIM; Calcium oscillations
ID INTRACELLULAR CA2+ STORES; PAROTID ACINAR-CELLS; SMOOTH-MUSCLE-CELLS;
RECEPTOR POTENTIAL CHANNELS; ACTIVATES CRAC CHANNELS; EMBRYONIC
KIDNEY-CELLS; TYROSINE KINASE SYK; PLASMA-MEMBRANE;
ENDOPLASMIC-RETICULUM; CATION CHANNELS
AB Store-operated Ca(2+) entry is a process whereby the depletion of intracellular Ca(2+) stores signals the opening of plasma membrane Ca(2+) channels. It has long been thought that the main function of store-operated Ca(2+) entry was the replenishment of intracellular Ca(2+) stores following their discharge during intracellular Ca(2+) signaling. Recent results, however, suggest that the primary function of these channels may be to provide direct Ca(2+) signals to recipients localized to spatially restricted areas close to the sites of Ca(2+) entry in order to initiate specific signaling pathways.
C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Putney, JW (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM putney@niehs.nih.gov
FU National Institutes of Health, NIEHS
FX Drs. Stephen Shears and David Armstrong read the manuscript and provided
helpful comments. Work from the author's laboratory discussed in this
review was supported by the Intramural Program of the National
Institutes of Health, NIEHS.
NR 114
TC 36
Z9 37
U1 0
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUL
PY 2011
VL 36
IS 7
SI SI
BP 1157
EP 1165
DI 10.1007/s11064-010-0383-0
PG 9
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 794NU
UT WOS:000292907700003
PM 21234676
ER
PT J
AU Yang, DK
Shcheynikov, N
Muallem, S
AF Yang, Dongki
Shcheynikov, Nikolay
Muallem, Shmuel
TI IRBIT: It Is Everywhere
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE IRBIT; IP3 receptors; NBCe1-B; CFTR; NHE3; Fip1
ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; TRANSMEMBRANE CONDUCTANCE
REGULATOR; HCO3-SALVAGE MECHANISMS; NA+/H+ EXCHANGER NHE3; BINDING
PROTEIN; IP3 RECEPTOR; PANCREATIC-DUCT; MEMBRANE LOCALIZATION;
NA+-HCO3-COTRANSPORT; FUNCTIONAL EXPRESSION
AB IRBIT (IP(3)Rs binding protein released with IP3) is a protein originally identified by the Mikoshiba group as an inhibitor of IP3 receptors function. Subsequently it was found to have multiple functions and regulate the activity of diverse proteins, including regulation of HCO3- transporters to coordinate epithelial HCO3- secretion and to determine localization of the Fip1 subunit of the CPSF complex to regulate mRNA processing. This review highlights the remarkably divers functions of IRBIT that are likely only a fraction of all the potential functions of this protein.
C1 [Yang, Dongki; Shcheynikov, Nikolay; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Muallem, S (reprint author), NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA.
EM shmuel.muallem@nih.gov
FU NIDCR NIH HHS [R01 DE012309, R01 DE012309-14]
NR 64
TC 13
Z9 13
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUL
PY 2011
VL 36
IS 7
SI SI
BP 1166
EP 1174
DI 10.1007/s11064-010-0353-6
PG 9
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 794NU
UT WOS:000292907700004
PM 21152975
ER
PT J
AU Ambudkar, IS
AF Ambudkar, Indu S.
TI Dissection of Calcium Signaling Events in Exocrine Secretion
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Calcium homeostasis; Calcium influx; Ion channels; Fluid secretion;
Salivary gland cells; Physiology; Knockout-mouse models
ID PROTEIN-COUPLED-RECEPTORS; STORE-OPERATED CHANNELS; SALIVARY-GLAND
CELLS; PAROTID ACINAR-CELLS; TRPC CHANNELS; MOLECULAR-BASIS; CRAC
CHANNEL; CA2+ INFLUX; ORAI1; STIM1
AB The secretion of fluid and electrolytes by salivary gland acinar cells requires the coordinated regulation of multiple ion channel and transporter proteins, signaling components, and water transport. Importantly, neurotransmitter stimulated increase in the cytosolic free [Ca(2+)] ([Ca(2+)](i)) is critical for the regulation of salivary gland secretion as it regulates several major ion fluxes that together establish the sustained osmotic gradient to drive fluid secretion. The mechanisms that act to modulate these increases in [Ca(2+)] i are therefore central to the process of salivary fluid secretion. Such modulation involves membrane receptors for neurotransmitters, as well as mechanisms that mediate intracellular Ca(2+) release, and Ca(2+) entry, as well as those that maintain cellular Ca(2+) homeostasis. Together, these mechanisms determine the spatial and temporal aspects of the [Ca(2+)] i signals that regulate fluid secretion. Molecular cloning of these transporters and channels as well as development of mice lacking these proteins has established the physiological significance of key components that are involved in regulating [Ca(2+)] i in salivary glands. This review will discuss these important studies and the findings which have led to resolution of the Ca(2+) signaling mechanisms that determine salivary gland fluid secretion.
C1 Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N 113, Bethesda, MD 20892 USA.
EM indu.ambudkar@nih.gov
FU Intramural NIH HHS [ZIA DE000438-26]
NR 51
TC 22
Z9 22
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUL
PY 2011
VL 36
IS 7
SI SI
BP 1212
EP 1221
DI 10.1007/s11064-011-0465-7
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 794NU
UT WOS:000292907700008
PM 21534000
ER
PT J
AU He, XJ
Takahashi, S
Suzuki, H
Hashikawa, T
Kulkarni, AB
Mikoshiba, K
Ohshima, T
AF He, Xiaojuan
Takahashi, Satoru
Suzuki, Hiromi
Hashikawa, Tsutomu
Kulkarni, Ashok B.
Mikoshiba, Katsuhiko
Ohshima, Toshio
TI Hypomyelination Phenotype Caused by Impaired Differentiation of
Oligodendrocytes in Emx1-cre Mediated Cdk5 Conditional Knockout Mice
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Cyclin-dependent kinase 5; Oligodendrocyte differentiation;
Hypomyelination; Conditional knockout mice
ID CYCLIN-DEPENDENT KINASE-5; CENTRAL-NERVOUS-SYSTEM; SHAKING RAT KAWASAKI;
TRANSCRIPTIONAL CONTROL; NEURONAL MIGRATION; CEREBRAL-CORTEX; P35;
EXPRESSION; DISRUPTION; PATTERNS
AB Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in neuronal migration and differentiation, and in axonal elongation. Although many studies have been conducted to analyze neuronal functions of Cdk5, its kinase activity has also been reported during oligodendrocyte differentiation, which suggests Cdk5 may play an important role in oligodendrocytes. Here, we describe a hypomyelination phenotype observed in Emx1-cre mediated Cdk5 conditional knockout (cKO) mice (Emx1-cKO), in which the Cdk5 gene was deleted in neurons, astrocytes and oligodendrocyte -lineage cells. In contrast, the Cdk5 gene in CaMKII cKO mice was deleted only in neurons. Because the development of mature oligodendrocytes from oligodendrocyte precursor cells is a complex process, we performed in situ hybridization using markers for the oligodendrocyte precursor cell and for the differentiated oligodendrocyte. Our results indicate that hypomyelination in Emx1-cKO is due to the impaired differentiation of oligodendrocytes, rather than to the proliferation or migration of their precursors. The present study confirmed the in vivo role of Cdk5 in oligodendrocyte differentiation.
C1 [He, Xiaojuan; Ohshima, Toshio] Waseda Univ, Dept Life Sci & Med Biosci, Shinjuku Ku, Tokyo 1628480, Japan.
[Takahashi, Satoru] Asahikawa Med Coll, Dept Pediat, Asahikawa, Hokkaido 0788510, Japan.
[Suzuki, Hiromi; Mikoshiba, Katsuhiko] RIKEN, Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama 3510198, Japan.
[Hashikawa, Tsutomu] RIKEN, Brain Sci Inst, Support Unit Neuromorphol Anal, Wako, Saitama 3510198, Japan.
[Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Ohshima, T (reprint author), Waseda Univ, Dept Life Sci & Med Biosci, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
EM ohshima@waseda.jp
RI Mikoshiba, Katsuhiko/N-7943-2015
FU Intramural NIH HHS [Z01 DE000664-12]
NR 41
TC 7
Z9 9
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUL
PY 2011
VL 36
IS 7
SI SI
BP 1293
EP 1303
DI 10.1007/s11064-010-0391-0
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 794NU
UT WOS:000292907700017
PM 21210220
ER
PT J
AU Gan, CP
Zain, RB
Abraham, MT
Patel, V
Gutkind, JS
Cheong, SC
Chong, CE
Hamid, S
Teo, SH
AF Gan, C. P.
Zain, R. Binti
Abraham, M. T.
Patel, V.
Gutkind, J. S.
Cheong, S. C.
Chong, Chan Eng
Hamid, Sharifah
Teo, Soo Hwang
TI Expression of GNA12 and its role in oral cancer
SO ORAL ONCOLOGY
LA English
DT Meeting Abstract
CT 3rd World Congress of the International-Academy-of-Oral-Oncology
CY JUL 14-17, 2011
CL Singapore, SINGAPORE
SP Int Acad Oral Oncol
C1 [Gan, C. P.; Cheong, S. C.; Chong, Chan Eng; Hamid, Sharifah; Teo, Soo Hwang] Canc Res Initiat Fdn CARIF, Oral Canc Res Team, Subang Jaya, Selangor, Malaysia.
[Gan, C. P.; Zain, R. Binti] Univ Malaya, Fac Dent, Dept Oral Pathol Oral Med & Periodontol, Kuala Lumpur, Malaysia.
[Zain, R. Binti] Univ Malaya, Oral Canc Res & Coordinating Ctr OCRCC, Kuala Lumpur, Malaysia.
[Abraham, M. T.] Tengku Ampuan Rahimah Hosp, Dept Oral & Maxillofacial Surg, Klang, Selangor, Malaysia.
[Patel, V.; Gutkind, J. S.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Cheong, S. C.] Univ Malaya, Dept Oral & Maxillofacial Surg, Fac Dent, Kuala Lumpur, Malaysia.
RI Zain, Rosnah/B-8054-2010; Gutkind, J. Silvio/A-1053-2009; Management
Center, Dental Research/C-2478-2013
NR 0
TC 2
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD JUL
PY 2011
VL 47
SU 1
BP S114
EP S115
DI 10.1016/j.oraloncology.2011.06.369
PG 2
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 793IX
UT WOS:000292815100335
ER
PT J
AU Gutkind, JS
AF Gutkind, J. Silvio
TI Emerging animal models for the functional genomics analysis of the oral
cancer oncogenome
SO ORAL ONCOLOGY
LA English
DT Meeting Abstract
CT 3rd World Congress of the International-Academy-of-Oral-Oncology
CY JUL 14-17, 2011
CL Singapore, SINGAPORE
SP Int Acad Oral Oncol
C1 [Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RI Gutkind, J. Silvio/A-1053-2009
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD JUL
PY 2011
VL 47
SU 1
BP S13
EP S14
DI 10.1016/j.oraloncology.2011.06.061
PG 2
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 793IX
UT WOS:000292815100035
ER
PT J
AU Spelman, K
Depoix, D
McCray, M
Mouray, E
Grellier, P
AF Spelman, Kevin
Depoix, Delphine
McCray, Megan
Mouray, Elisabeth
Grellier, Philippe
TI The Traditional Medicine Spilanthes acmella, and the Alkylamides
Spilanthol and Undeca-2E-ene-8,10-diynoic Acid Isobutylamide,
Demonstrate In Vitro and In Vivo Antimalarial Activity
SO PHYTOTHERAPY RESEARCH
LA English
DT Article
DE Plasmodium falciparum; alkylamides; deca-2E,6Z,8E-trienoic acid
isobutylamide; malaria; traditional medicine; phytotherapy
AB Spilanthes spp. are used as traditional herbal medicines in Africa and India to treat malaria. Yet, to date, there are no data on the active constituents or the most effective extraction methods for this indication. The isolated alkylamides, spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, found in S. acmella Murr., were shown to have IC(50)s of 16.5 mu g/mL and 41.4 mu g/mL on Plasmodium falciparum strain PFB and IC(50)s of 5.8 mu g/mL and 16.3 mu g/mL for the chloroquine resistant P. falciparum K1 strain, respectively. Further investigations revealed that at relatively low concentrations, spilanthol and the water extract of S. acmella reduced the parasitemia 59% and 53% in mice infected with P. yoelii yoelii 17XNL at 5 mg/kg and 50 mg/kg, respectively. Unexpectedly, the 95% ethanol extract of S. acmella was less effective (36% reduction in parasitemia) at 50 mg/kg. These results provide the first evidence supporting S. acmella against malaria and demonstrating active constituents in S. acmella against P. falciparum. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Spelman, Kevin] NIA, NIH, Clin Invest Lab, Baltimore, MD 21224 USA.
[McCray, Megan] Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27412 USA.
[Depoix, Delphine; Mouray, Elisabeth; Grellier, Philippe] Museum Natl Hist Nat, CNRS, FRE 3206, Dept Regulat Dev & Divers Mol, Paris, France.
RP Spelman, K (reprint author), NIA, NIH, Clin Invest Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM phytochemks@gmail.com
FU National Center for Complementary and Alternative Medicine (NCCAM) at
the National Institutes of Health [1R15AT001466-01]; Marie Curie
Foundation at the Museum National d'Histoire Naturelle, Paris;
Laboratoire of Pharmacognosy, Universite Paris [11]; National Science
Foundation [0420292]
FX This publication was made possible by grant number 1R15AT001466-01 from
the National Center for Complementary and Alternative Medicine (NCCAM)
at the National Institutes of Health and the Marie Curie Foundation
which provided an early stage training fellowship for KS at the Museum
National d'Histoire Naturelle, Paris and the Laboratoire of
Pharmacognosy, Universite Paris 11. Additional support was provided by
the National Science Foundation under grant number 0420292. Special
thanks to Nadja Cech for providing the spilanthol and S. acmella
extracts.
NR 11
TC 11
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U1 3
U2 40
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0951-418X
J9 PHYTOTHER RES
JI Phytother. Res.
PD JUL
PY 2011
VL 25
IS 7
BP 1098
EP 1101
DI 10.1002/ptr.3395
PG 4
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 796DW
UT WOS:000293031400021
PM 22692989
ER
PT J
AU Silvera, SAN
Mayne, ST
Risch, HA
Gammon, MD
Vaughan, T
Chow, WH
Dubin, JA
Dubrow, R
Schoenberg, J
Stanford, JL
West, AB
Rotterdam, H
Blot, WJ
AF Silvera, Stephanie A. Navarro
Mayne, Susan T.
Risch, Harvey A.
Gammon, Marilie D.
Vaughan, Thomas
Chow, Wong-Ho
Dubin, Joel A.
Dubrow, Robert
Schoenberg, Janet
Stanford, Janet L.
West, A. Brian
Rotterdam, Heidrun
Blot, William J.
TI Principal Component Analysis of Dietary and Lifestyle Patterns in
Relation to Risk of Subtypes of Esophageal and Gastric Cancer
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Esophageal Adenocarcinoma; Gastric Cardia Adenocarcinoma; Esophageal
Squamous Cell Carcinoma; Diet; Principal Components
ID BODY-MASS INDEX; SQUAMOUS-CELL CARCINOMA; GASTROESOPHAGEAL-REFLUX
DISEASE; GUIDELINES-FOR-AMERICANS; MAJOR CHRONIC DISEASE;
BARRETTS-ESOPHAGUS; RISING INCIDENCE; NUTRIENT INTAKE; ADENOCARCINOMA;
CARDIA
AB PURPOSE: To carry out pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers.
METHODS: We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GC:A), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression.
RESULTS: PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing gastroesophageal reflux disease (GERD)/body mass index (BMI) score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA.
CONCLUSIONS: PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, whereas fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC. Ann Epidemiol 2011;21:543-550. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Silvera, Stephanie A. Navarro] Montclair State Univ, Dept Hlth & Nutr Sci, Montclair, NJ 07043 USA.
[Mayne, Susan T.; Risch, Harvey A.; Dubrow, Robert] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA.
[West, A. Brian] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Vaughan, Thomas; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Vaughan, Thomas; Stanford, Janet L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Schoenberg, Janet] New Jersey Dept Hlth & Senior Serv, Canc Epidemiol Serv, Trenton, NJ USA.
[Rotterdam, Heidrun] Columbia Univ, Dept Pathol, New York, NY USA.
[Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Blot, William J.] Vanderbilt Univ, Nashville, TN USA.
[Dubin, Joel A.] Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada.
[Dubin, Joel A.] Univ Waterloo, Dept Hlth Studies & Gerontol, Waterloo, ON N2L 3G1, Canada.
RP Silvera, SAN (reprint author), Montclair State Univ, Dept Hlth & Nutr Sci, 1 Normal Ave, Montclair, NJ 07043 USA.
EM silveras@mail.montclair.edu
FU United States Public Health Service [U01-CA57983, U01-CA57949,
U01-CA57923, P30ES10126]; National Cancer Institute, Division of Cancer
Epidemiology and Genetics; National Institutes of Health; Department of
Health and Human Services [N02-CP40501, N01-CN05230]
FX We thank the following: study managers Ms. Sarah Greene and Ms. Linda
Lannom (Westat), data management Ms. Shelley Niwa (Westar), and field
supervisors Mrs. Patricia Owen (Connecticut), Mr. Tom English (New
Jersey), and Ms. Berta Nicol-Blades (Washington) for data collection and
processing; Dr. Alan Kristal for assistance in designing and processing
the dietary questionnaires; the Yale Cancer Center Rapid Case
Ascertainment Shared Resource, the 178 hospitals in Connecticut, New
Jersey, and Washington for their participation in the study; and the
study participants. This research was supported [in part] by United
States Public Health Service (U01-CA57983, U01-CA57949, U01-CA57923,
P30ES10126), the National Cancer Institute, Division of Cancer
Epidemiology and Genetics, the Intramural Research Program of the
National Institutes of Health, and the Department of Health and Human
Services (N02-CP40501, N01-CN05230).
NR 53
TC 30
Z9 31
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JUL
PY 2011
VL 21
IS 7
BP 543
EP 550
DI 10.1016/j.annepidem.2010.11.019
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 779GW
UT WOS:000291767100009
ER
PT J
AU Soderholm, JF
Bird, SL
Kalab, P
Sampathkumar, Y
Hasegawa, K
Uehara-Bingen, M
Weis, K
Heald, R
AF Soderholm, Jonathan F.
Bird, Stephen L.
Kalab, Petr
Sampathkumar, Yasaswini
Hasegawa, Keisuke
Uehara-Bingen, Michael
Weis, Karsten
Heald, Rebecca
TI Importazole, a Small Molecule Inhibitor of the Transport Receptor
Importin-beta
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID NUCLEAR-PROTEIN IMPORT; DIFFERENTIAL SCANNING FLUOROMETRY; RAN-GTP; EGG
EXTRACTS; IN-VITRO; COMPLEX; EXPORT; MOTOR; CRM1; IDENTIFICATION
AB During interphase, the transport receptor importin-beta carries cargoes into the nucleus, where,RanGTP releases them. A similar mechanism operates in mitosis to generate a gradient of active spindle assembly factors around mitotic chromosomes. Importin-beta and RanGTP have been implicated in additional cellular processes, but the precise, roles of the Ran/importin-beta pathway throughout the cell cycle remain poorly understood. We implemented a FRET-based, high-throughput small molecule screen for compounds that interfere with the interaction between RanGTP and importin-beta and identified importazole, a 2,4-diaminoquinazoline. Importazole specifically blocks importin-beta-mediated nuclear import both in-Xenopus egg extracts and cultured cells, without disrupting transportin-mediated nuclear import or CRM1-mediated nuclear export. When added during mitosis, importazole impairs the release of an importin-beta cargo FRET probe and causes both predicted and novel defects in spindle assembly. Together, these results indicate that importazole specifically inhibits the function of importin-beta, likely by altering its interaction with RanGTP. Importazole is a valuable tool to evaluate the function of the importin-beta/RanGTP pathway at specific stages during the cell cycle.
C1 [Soderholm, Jonathan F.; Bird, Stephen L.; Kalab, Petr; Sampathkumar, Yasaswini; Weis, Karsten; Heald, Rebecca] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Kalab, Petr; Hasegawa, Keisuke] NCI, NIH, Bethesda, MD 20892 USA.
[Uehara-Bingen, Michael] Univ Calif San Francisco, Small Mol Discovery Ctr, San Francisco, CA 94158 USA.
RP Weis, K (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, MC 3200 LSA, Berkeley, CA 94720 USA.
EM kweis@berkeley.edu; bheald@berkeley.edu
RI Weis, Karsten/F-5719-2011; Kalab, Petr/B-2478-2009
OI Weis, Karsten/0000-0001-7224-925X;
FU National Institutes of Health [R01 GM065232, R21 NS53592]; Cancer
Research Coordinating Committee; Center for Cancer Research, NCI,
National Institutes of Health
FX The authors thank Brian Wolff Janice Williams, Brian Feng, and James
Wells at the Small Molecule Discovery Center at UCSF for help with the
screen, Elisa Dultz for live cell imaging of imporatzole effects, Karin
Reif for NFAT cDNA, David Halpin for biotin-labeled RCC1, and Lili Wang
at the Broad Institute for developing the thermal shift assay to probe
binding of importazole to importin-beta. This work was supported by the
National Institutes of Health (R01 GM065232 and R21 NS53592, K.W. and
RH.), the Cancer Research Coordinating Committee (S.L.B.), and the
Intramural Research Program of the Center for Cancer Research, NCI,
National Institutes of Health (P.K. and K.H.).
NR 43
TC 56
Z9 58
U1 2
U2 8
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 JUL
PY 2011
VL 6
IS 7
BP 700
EP 708
DI 10.1021/cb2000296
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 793VB
UT WOS:000292850900005
PM 21469738
ER
PT J
AU Ruder, EH
Laiyemo, AO
Graubard, BI
Hollenbeck, AR
Schatzkin, A
Cross, AJ
AF Ruder, Elizabeth H.
Laiyemo, Adeyinka O.
Graubard, Barry I.
Hollenbeck, Albert R.
Schatzkin, Arthur
Cross, Amanda J.
TI Non-Steroidal Anti-Inflammatory Drugs and Colorectal Cancer Risk in a
Large, Prospective Cohort
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID LOW-DOSE ASPIRIN; FAMILIAL ADENOMATOUS POLYPOSIS; SERVICES-TASK-FORCE;
PRIMARY PREVENTION; WOMENS HEALTH; FOLLOW-UP; COLON; INFLAMMATION;
EXPRESSION; PARADIGM
AB OBJECTIVES: Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with colorectal cancer; however, the association within colorectal subsites or among higher risk individuals is understudied. We investigated NSAID use and colorectal adenocarcinoma by subsite, and among individuals with a family history of colon cancer in the National Institutes of Health-AARP Diet and Health Study.
METHODS: Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer incidence among 301,240 men and women (mean age 62.8 years); including 26,994 individuals with a first-degree relative with a history of colon cancer. We accrued 3,894 colorectal cancer cases during 10 years of follow-up; 372 cases had a first-degree relative with colon cancer.
RESULTS: Both aspirin and non-aspirin NSAID use reduced colorectal cancer risk (HR for users compared with non-users = 0.91, 95% CI: 0.85, 0.98; HR = 0.82, 95% CI: 0.77, 0.87, respectively). Daily aspirin use reduced the risk of cancer in the distal colon (HR = 0.84, 95% CI: 0.71, 0.99) and rectum (HR = 0.76, 95% CI: 0.64, 0.90); daily non-aspirin NSAID use reduced the risk of both proximal (HR = 0.65, 95% CI: 0.54, 0.78) and distal colon cancer (HR = 0.69, 95% CI: 0.55, 0.87), but not rectal cancer. Among participants with a first-degree relative with colon cancer, daily use of aspirin was associated with a decreased risk of rectal cancer (HR = 0.38, 95% CI: 0.19, 0.78), and daily use of non-aspirin NSAIDs was associated with a decreased risk of colon cancer (HR = 0.49, 95% CI: 0.29, 0.82). No protective benefit for daily aspirin use and colon cancer or daily non-aspirin NSAID use and rectal cancer was observed in this higher risk subgroup, although power was limited by small case numbers.
CONCLUSIONS: NSAID use was associated with a reduced colorectal cancer risk; the magnitude of this association differed between aspirin and non-aspirin NSAIDs. Daily aspirin and non-aspirin NSAID use by individuals with a family history of colon cancer significantly reduced the risk of rectal and colon cancer, respectively.
C1 [Ruder, Elizabeth H.; Graubard, Barry I.; Schatzkin, Arthur; Cross, Amanda J.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD 20852 USA.
[Ruder, Elizabeth H.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH,US Dept HHS, Rockville, MD 20852 USA.
[Laiyemo, Adeyinka O.] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Ruder, EH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 6120 Executive Blvd, Rockville, MD 20852 USA.
EM rudereh@mail.nih.gov
FU National Institutes of Health, National Cancer Institute; Florida
Department of Health (FDOH)
FX This research was supported (in part) by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute. Cancer
incidence data from the Atlanta metropolitan area were collected by the
Georgia Center for Cancer Statistics, Department of Epidemiology,
Rollins School of Public Health, Emory University; those from California
by the California Department of Health Services, Cancer Surveillance
Section; and those from the Detroit metropolitan area by the Michigan
Cancer Surveillance Program, Community Health Administration, State of
Michigan. The Florida cancer incidence data used in this report were
collected by the Florida Cancer Data System (FCDC) under contract with
the Florida Department of Health (FDOH). The views expressed herein are
solely those of the authors and do not necessarily reflect those of the
FCDC or FDOH. Cancer incidence data from Louisiana were collected by the
Louisiana Tumor Registry, Louisiana State University Medical Center in
New Orleans; those from New Jersey by the New Jersey State Cancer
Registry, Cancer Epidemiology Services, New Jersey State Department of
Health and Senior Services; and those from North Carolina by the North
Carolina Central Cancer Registry. Cancer incidence data from
Pennsylvania were supplied by the Division of Health Statistics and
Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania.
The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations or conclusions. Cancer
incidence data from Arizona were collected by the Arizona Cancer
Registry, Division of Public Health Services, Arizona Department of
Health Services, and those from Texas were collected by the Texas Cancer
Registry, Cancer Epidemiology and Surveillance Branch, Texas Department
of State Health Services. We are indebted to the participants in the
National Institutes of Health-AARP Diet and Health Study for their
outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace
Morrissey from Westat for study outcomes ascertainment and management
and Leslie Carroll at Information Management Services for data support
and analysis.
NR 43
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Z9 60
U1 4
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD JUL
PY 2011
VL 106
IS 7
BP 1340
EP 1350
DI 10.1038/ajg.2011.38
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 789JG
UT WOS:000292511100020
PM 21407185
ER
PT J
AU Kalisch, BJ
Tschannen, D
Lee, H
Friese, CR
AF Kalisch, Beatrice J.
Tschannen, Dana
Lee, Hyunhwa
Friese, Christopher R.
TI Hospital Variation in Missed Nursing Care
SO AMERICAN JOURNAL OF MEDICAL QUALITY
LA English
DT Article
DE nursing; safety; quality; errors of omission
ID EARLY MOBILIZATION; PATIENT OUTCOMES; STAFFING LEVELS; ERRORS;
MEDICATION; AMBULATION; MORTALITY; WORKLOAD; QUALITY; NURSES
AB Quality of nursing care across hospitals is variable, and this variation can result in poor patient outcomes. One aspect of quality nursing care is the amount of necessary care that is omitted. This article reports on the extent and type of nursing care missed and the reasons for missed care. The MISSCARE Survey was administered to nursing staff (n = 4086) who provide direct patient care in 10 acute care hospitals. Missed nursing care patterns as well as reasons for missing care (labor resources, material resources, and communication) were common across all hospitals. Job title (ie, registered nurse vs nursing assistant), shift worked, absenteeism, perceived staffing adequacy, and patient work loads were significantly associated with missed care. The data from this study can inform quality improvement efforts to reduce missed nursing care and promote favorable patient outcomes.
C1 [Kalisch, Beatrice J.; Tschannen, Dana; Friese, Christopher R.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA.
[Lee, Hyunhwa] NINR, NIH, Bethesda, MD 20892 USA.
RP Kalisch, BJ (reprint author), Univ Michigan, Sch Nursing, 400 N Ingalls 4170, Ann Arbor, MI 48109 USA.
EM bkalisch@umich.edu
RI Friese, Christopher/D-2097-2013
OI Friese, Christopher/0000-0002-2281-2056
FU Blue Cross Blue Shield Foundation of Michigan; R00 Pathway to
Independence award [NR010750]
FX The authors disclosed receipt of the following financial support for the
research and/or authorship of this article: This research was supported
by a research grant from the Blue Cross Blue Shield Foundation of
Michigan. In addition, Dr Friese is supported by a R00 Pathway to
Independence award NR010750.
NR 37
TC 45
Z9 48
U1 1
U2 14
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1062-8606
J9 AM J MED QUAL
JI Am. J. Med. Qual.
PD JUL-AUG
PY 2011
VL 26
IS 4
BP 291
EP 299
DI 10.1177/1062860610395929
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 792ME
UT WOS:000292748900006
PM 21642601
ER
PT J
AU Neubauer, B
Machura, K
Schnermann, J
Wagner, C
AF Neubauer, Bjoern
Machura, Katharina
Schnermann, Juergen
Wagner, Charlotte
TI Renin expression in large renal vessels during fetal development depends
on functional beta(1)/beta(2)-adrenergic receptors
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE sympathetic nervous system; renal development; cAMP signaling; ACE
inhibition
ID RAT JUXTAGLOMERULAR CELLS; MESSENGER-RNA EXPRESSION; BETA-2-ADRENERGIC
RECEPTORS; GENE-EXPRESSION; ACE-INHIBITION; KIDNEY CORTEX; MICE;
INNERVATION; MOUSE; APPARATUS
AB Neubauer B, Machura K, Schnermann J, Wagner C. Renin expression in large renal vessels during fetal development depends on functional beta(1)/beta(2)-adrenergic receptors. Am J Physiol Renal Physiol 301: F71-F77, 2011. First published March 9, 2011; doi: 10.1152/ajprenal.00443.2010.-During nephrogenesis, renin expression shifts from large renal arteries toward smaller vessels in a defined spatiotemporal pattern, finally becoming restricted to the juxtaglomerular position. Chronic stimulation in adult kidneys leads to a recruitment of renin expression in the upstream vasculature. The mechanisms that control this characteristic switch-on and switch-off in the immature and adult kidney are not well-understood. Previous studies in mice with juxtaglomerular cell-specific deletion of the adenylyl cyclase-stimulatory G protein Gs alpha suggested that signaling along the cAMP pathway plays an essential role for renin expression during nephrogenesis and in the adult kidney. To identify the Gs alpha-dependent receptor that might be involved in activating this pathway, the present studies were performed to compare renin expression in wild types with that in mice with targeted deletions of beta(1) and beta(2)-adrenoceptors. The sympathetic nervous system is an important regulator of the renin system in the adult kidney so that activation of beta-adrenenoceptors may also participate in the activation of renin expression along the developing arterial tree and in upstream vasculature in adulthood. Compared with wild-types, renin expression was found to be significantly lower at all developmental stages in the kidneys of beta(1)/beta(2)Adr(-/-) mice. Three-dimensional analysis showed reduced renin expression in all segments of the vascular tree in mutants and a virtual absence of renin expression in the large arcuate arteries. Adult mutant kidneys showed the typical upstream renin expression after chronic stimulation. Tyrosine hydroxylase staining in fetal and postnatal kidneys revealed that sympathetic innervation of renin-producing cells occurs early in fetal development. Our data indicate that genetic disruption of beta-adrenergic receptors reduces basal renin expression along the developing preglomerular tree and in adult kidneys. Furthermore, beta-adrenergic receptor input is critical for the expression of renin in large renal vessels during early fetal development.
C1 [Neubauer, Bjoern; Machura, Katharina; Wagner, Charlotte] Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany.
[Schnermann, Juergen] Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA.
RP Wagner, C (reprint author), Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany.
EM charlotte.schmid@vkl.uni-regensburg.de
FU Deutsche Forschungsgemeinschaft [SFB 699, WA 2-1]
FX This study was financially supported by the Deutsche
Forschungsgemeinschaft (SFB 699, WA 2-1).
NR 37
TC 9
Z9 9
U1 1
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JUL
PY 2011
VL 301
IS 1
BP F71
EP F77
DI 10.1152/ajprenal.00443.2010
PG 7
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 791CY
UT WOS:000292641000013
PM 21389089
ER
PT J
AU Stodkilde, L
Norregaard, R
Fenton, RA
Wang, GX
Knepper, MA
Frokiaer, J
AF Stodkilde, Lene
Norregaard, Rikke
Fenton, Robert A.
Wang, Guixian
Knepper, Mark A.
Frokiaer, Jorgen
TI Bilateral ureteral obstruction induces early downregulation and
redistribution of AQP2 and phosphorylated AQP2
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE water transport; membrane protein; degradation; urine-concentrating
capacity
ID AQUAPORIN-2 WATER CHANNEL; COLLECTING DUCT; PLASMA-MEMBRANE; VASOPRESSIN
TREATMENT; EPITHELIAL-CELLS; V2 RECEPTOR; ENDOCYTOSIS; KIDNEY;
UBIQUITINATION; ACCUMULATION
AB Stodkilde L, Norregaard R, Fenton RA, Wang G, Knepper MA, Frokiaer J. Bilateral ureteral obstruction induces early downregulation and redistribution of AQP2 and phosphorylated AQP2. Am J Physiol Renal Physiol 301: F226-F235, 2011. First published April 27, 2011; doi:10.1152/ajprenal.00664.2010.-Bilateral ureteral obstruction (BUO) is characterized by impairment of urine flow from the kidneys and altered expression of specific membrane proteins in the kidney involved in regulation of renal water and salt transport. Importantly, 24-h BUO reduces the abundance of the collecting duct water channel aquaporin-2 (AQP2) and AQP2 phosphorylated at serine 256 (AQP2pS256). To investigate the mechanism behind downregulation of AQP2 in BUO, rats were subjected to BUO and examined after 2, 6, 12, and 24 h. Q-PCR and immunoblotting showed significantly decreased AQP2 mRNA expression after 2-h BUO and decreased abundance of total AQP2 after 12 and 24 h. In parallel, immunohistochemistry showed weaker labeling of AQP2 at the apical surface of inner medullary collecting ducts (IMCD) compared with controls. The abundance of AQP2pS256 was significantly reduced from 6-h BUO and was confirmed by immunohistochemistry. Importantly, immunoblotting showed reduced abundance of AQP2pS261 after 12- and 24-h BUO mimicking total AQP2. Immunohistochemistry demonstrated early changed intracellular localization of AQP2pS261 in BUO, and colocalization studies showed redistribution from the apical membrane to early endosomes and lysosomes. In conclusion, BUO induces a very early regulation of AQP2 both at the level of abundance and on cellular localization. AQP2 and AQP2 phosphorylated at ser261 redistribute to more intracellular localizations and colocalize with the early endosomal marker EEA1 and the lysosomal marker cathepsin D, suggesting that early downregulation of AQP2 could in part be caused by degradation of AQP2 through a lysosomal degradation pathway.
C1 [Stodkilde, Lene; Norregaard, Rikke; Fenton, Robert A.; Wang, Guixian; Frokiaer, Jorgen] Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark.
[Stodkilde, Lene; Norregaard, Rikke; Wang, Guixian; Frokiaer, Jorgen] Univ Aarhus, Inst Clin Med, Aarhus, Denmark.
[Fenton, Robert A.] Univ Aarhus, Inst Anat, Aarhus, Denmark.
[Knepper, Mark A.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Frokiaer, J (reprint author), Aarhus Univ, Hosp Skejby, Water & Salt Res Ctr, Inst Clin Med, DK-8200 Aarhus, Denmark.
EM JF@KI.AU.DK
OI Frokiaer, Jorgen/0000-0002-6206-8065
FU Danish National Research Foundation (Danmarks Grundforskningsfond);
Faculty of Health Sciences, University of Aarhus; Marie Curie
Intra-European Fellowship; A. P. Moller Foundation for the Advancement
of Medical Science; Aase and Ejnar Danielsen Foundation; Beckett
Foundation; National Heart, Lung, and Blood Institute (National
Institutes of Health) [ZO1-HL-001285]
FX The Water and Salt Research Center at the University of Aarhus is
established and supported by the Danish National Research Foundation
(Danmarks Grundforskningsfond). L. Stodkilde is partly supported by the
Faculty of Health Sciences, University of Aarhus. R. A. Fenton is
supported by a Marie Curie Intra-European Fellowship. Additional funding
was provided by the A. P. Moller Foundation for the Advancement of
Medical Science, Aase and Ejnar Danielsen Foundation, and the Beckett
Foundation. Funding to M. A. Knepper was provided by the Intramural
Budget of the National Heart, Lung, and Blood Institute (National
Institutes of Health Project ZO1-HL-001285).
NR 43
TC 6
Z9 7
U1 1
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JUL
PY 2011
VL 301
IS 1
BP F226
EP F235
DI 10.1152/ajprenal.00664.2010
PG 10
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 791CY
UT WOS:000292641000030
PM 21525134
ER
PT J
AU Li, H
Bradbury, JA
Dackor, RT
Edin, ML
Graves, JP
DeGraff, LM
Wang, PM
Bortner, CD
Maruoka, S
Lih, FB
Cook, DN
Tomer, KB
Jetten, AM
Zeldin, DC
AF Li, Hong
Bradbury, J. Alyce
Dackor, Ryan T.
Edin, Matthew L.
Graves, Joan P.
DeGraff, Laura M.
Wang, Ping Ming
Bortner, Carl D.
Maruoka, Shuichiro
Lih, Fred B.
Cook, Donald N.
Tomer, Kenneth B.
Jetten, Anton M.
Zeldin, Darryl C.
TI Cyclooxygenase-2 Regulates Th17 Cell Differentiation during Allergic
Lung Inflammation
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE Th17 cell; COX-2; asthma; prostaglandins; IL-17
ID PROSTAGLANDIN E-2 PRODUCTION; RAT ALVEOLAR MACROPHAGES; HUMAN
SYNOVIAL-CELLS; ROR-GAMMA-T; INDUCIBLE CYCLOOXYGENASE; STIMULATES
COLLAGENASE; PROSTACYCLIN RECEPTOR; ASTHMATIC AIRWAYS; DENDRITIC CELLS;
T-H-17 CELLS
AB Rationale: Th17 cells comprise a distinct lineage of proinflammatory T helper cells that are major contributors to allergic responses. It is unknown whether cyclooxygenase (COX)-derived eicosanoids regulate Th17 cells during allergic lung inflammation.
Objectives: To determine the role of COX metabolites in regulating Th17 cell differentiation and function during allergic lung inflammation.
Methods: COX-1(-/-), COX-2(-/-), and wild-type mice were studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of Th17 differentiation using flow cytometry, cytokine assays, confocal microscopy, real-time polymerase chain reaction, and immunoblotting. In addition, the role of specific eicosanoids and their receptors was examined using synthetic prostaglandins (PGs), selective inhibitors, and siRNA knockdown.
Measurements and Main Results: Th17 cell differentiation in lung, lymph nodes, and bronchoalveolar lavage fluid was significantly lower in COX-2(-/-) mice after ovalbumin sensitization and exposure in vivo. In vitro studies revealed significantly impaired Th17 cell differentiation of COX-2(-/-) naive CD4(+) T cells with decreased Stat3 phosphorylation and ROR gamma t expression. Synthetic PGF(2 alpha) and PGI(2) enhanced Th17 cell differentiation of COX-2(-/-) CD4(+) T cells in vitro. The selective COX-2 inhibitor, NS-398, and PGF(2 alpha) receptor and PGI(2) receptor siRNA knockdown significantly decreased Th17 cell differentiation in vitro. Administration of synthetic PGs restored accumulation of Th17 cells in lungs of allergic COX-2(-/-) mice in vivo.
Conclusions: COX-2 is a critical regulator of Th17 cell differentiation during allergic lung inflammation via autocrine signaling of PGI(2) and PGF(2 alpha) through their respective cell surface receptors.
C1 [Zeldin, Darryl C.] NIEHS, Div Intramural Res, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Bortner, Carl D.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Lih, Fred B.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,Room A222, Res Triangle Pk, NC 27709 USA.
EM zeldin@niehs.nih.gov
RI Tomer, Kenneth/E-8018-2013;
OI Jetten, Anton/0000-0003-0954-4445; Edin, Matthew/0000-0002-7042-500X
FU Division of Intramural Research, National Institutes of Health/National
Institute of Environmental Health Sciences [Z01 ES025043, Z01 ES050167]
FX Supported by the Division of Intramural Research, National Institutes of
Health/National Institute of Environmental Health Sciences (Z01 ES025043
and Z01 ES050167).
NR 49
TC 24
Z9 29
U1 0
U2 11
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 JUL 1
PY 2011
VL 184
IS 1
BP 37
EP 49
PG 13
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 792RL
UT WOS:000292766700009
PM 21474648
ER
PT J
AU Senbagavalli, P
Anuradha, R
Ramanathan, VD
Kumaraswami, V
Nutman, TB
Babu, S
AF Senbagavalli, Prakash
Anuradha, Rajamanickam
Ramanathan, Vadakkuppattu D.
Kumaraswami, Vasanthapuram
Nutman, Thomas B.
Babu, Subash
TI Heightened Measures of Immune Complex and Complement Function and Immune
Complex-Mediated Granulocyte Activation in Human Lymphatic Filariasis
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID BLOOD MONONUCLEAR-CELLS; FC-GAMMA-RIIA; BANCROFTIAN FILARIASIS;
WUCHERERIA-BANCROFTI; CYTOKINE PRODUCTION; BRUGIA-MALAYI; SOUTH-INDIA;
INFECTION; ANTIGEN; MICROFILARIAE
AB The presence of circulating immune complexes (CICs) is a characteristic feature of human lymphatic filariasis. However, the role of CICs in modulating granulocyte function and complement functional activity in filarial infection is unknown. The levels of CICs in association with complement activation in clinically asymptomatic, filarial-infected patients (INF); filarial-infected patients with overt lymphatic pathologic changes (CPDT); and uninfected controls (EN) were examined. Significantly increased levels of CICs and enhanced functional efficiency of the classical and mannose-binding lectin pathways of the complement system was observed in INF compared with CPDT and EN. Polyethylene glycol precipitated CICs from INF and CPDT induced significantly increased granulocyte activation compared with those from EN, determined by the increased production of neutrophil granular proteins and a variety of pro-inflammatory cytokines. Thus, CIC-mediated enhanced granulocyte activation and modulation of complement function are important features of filarial infection and disease.
C1 NIH, Int Ctr Excellence Res, Madras, Tamil Nadu, India.
NIH, Parasit Dis Lab, NIAID, Bethesda, MD 20892 USA.
SAIC Frederick Inc, NCI, Frederick, MD USA.
RP Babu, S (reprint author), SAIC Frederick Inc, NIAID, Clin Monitoring Res Program, Int Ctr Excellence Res,TB Res Ctr, Madras, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 43
TC 4
Z9 4
U1 0
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 JUL
PY 2011
VL 85
IS 1
BP 89
EP 96
DI 10.4269/ajtmh.2011.11-0086
PG 8
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 788GK
UT WOS:000292433200017
PM 21734131
ER
PT J
AU Karamchandani-Patel, G
Hanson, EP
Saltzman, R
Kimball, CE
Sorensen, RU
Orange, JS
AF Karamchandani-Patel, Gital
Hanson, Eric P.
Saltzman, Rushani
Kimball, C. Eve
Sorensen, Ricardo U.
Orange, Jordan S.
TI Congenital alterations of NEMO glutamic acid 223 result in hypohidrotic
ectodermal dysplasia and immunodeficiency with normal serum IgG levels
SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
LA English
DT Article
ID KAPPA-B; MUTATIONS
AB Background: Hypomorphic mutations in the nuclear factor-kappa B (NF-kappa B) essential modulator (NEMO) gene result in a variable syndrome of somatic and immunologic abnormalities. Clinically relevant genotype-phenotype associations are essential to understanding this complex disease.
Objective: To study 2 unrelated boys with novel NEMO mutations altering codon 223 for similarity in phenotype in consideration of potential genotype-phenotype associations.
Methods: Clinical and laboratory features, including cell counts, immunoglobulin quantity and quality, natural killer cell cytotoxicity, and Toll-like and tumor necrosis factor receptor signaling, were evaluated. Because both mutations affected NEMO codon 223 and were novel, consideration was given to new potential genotype-phenotype associations.
Results: Both patients were diagnosed as having hypohidrotic ectodermal dysplasia and had severe or recurrent infections. One had recurrent sinopulmonary infections and the other necrotizing soft tissue methicillin-resistant Staphylococcus aureus infection and Streptococcus anginosus subdural empyema with bacteremia. NEMO gene sequence demonstrated a 3-nucleotide deletion (c.667_669delGAG) in one patient and a substitution (667G>A) in the other. These findings predict either the deletion of NEMO glutamic acid 223 or it being replaced with lysine, respectively. Both patients had normal serum IgG levels but poor specific antibodies. Natural killer cell cytotoxicity and Toll-like and tumor necrosis factor receptor signaling were also impaired. Serious bacterial infection did not occur in both patients after immunoglobulin replacement therapy.
Conclusions: Two different novel mutations affecting NEMO glutamic acid 223 resulted in clinically relevant similar phenotypes, providing further evidence to support genotype-phenotype correlations in this disease. They suggest NEMO residue 223 is required for ectodermal development and immunity and is apparently dispensable for quantitative IgG production but may be required for specific antibody production.
C1 [Saltzman, Rushani] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Karamchandani-Patel, Gital; Sorensen, Ricardo U.; Orange, Jordan S.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Hanson, Eric P.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD USA.
[Kimball, C. Eve] All Children Pediat Partners, Reading, PA USA.
[Orange, Jordan S.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Orange, JS (reprint author), Childrens Hosp Philadelphia, 3615 Civ Ctr Blvd ARC 907A, Philadelphia, PA 19104 USA.
EM Orange@mail.med.upenn.edu
OI orange, jordan/0000-0001-7117-7725
FU National Institutes of Health [NIH-AI-079731]; Jeffrey Modell Foundation
FX This work was supported by National Institutes of Health grant
NIH-AI-079731 to Dr Orange and the Jeffrey Modell Foundation (Dr Orange
and Dr Sorensen).
NR 10
TC 4
Z9 4
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1081-1206
J9 ANN ALLERG ASTHMA IM
JI Ann. Allergy Asthma Immunol.
PD JUL
PY 2011
VL 107
IS 1
BP 50
EP 56
DI 10.1016/j.anai.2011.03.009
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA 792AG
UT WOS:000292712300009
PM 21704885
ER
PT J
AU Deshpande, N
Metter, EJ
Ferrucci, L
AF Deshpande, Nandini
Metter, E. Jeffrey
Ferrucci, Luigi
TI Sensorimotor and Psychosocial Correlates of Adaptive Locomotor
Performance in Older Adults
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Adaptive behavior; Gait; Locomotion; Rehabilitation; Walking
ID WALKING INCHIANTI TOOLKIT; COMMUNITY MOBILITY; GAIT PATTERNS; AGE;
DISABILITY; PREDICTOR; STRENGTH; BALANCE
AB Deshpande N, Metter EJ, Ferrucci L. Sensorimotor and psychosocial correlates of adaptive locomotor performance in older adults. Arch Phys Med Rehabil 2011;92: 1074-9.
Objective: To identify sensorimotor and psychosocial factors independently associated with an inability to perform adaptive walking tasks in older adults.
Design: Cross-sectional cohort study.
Setting: Population-based older cohort. Participants: Community-living elderly (N=720; age >= 65y) who could walk 7m at self-selected normal speed.
Interventions: Not applicable.
Main Outcome Measures: Walking performance was assessed in 4 walking tests: fast walking, obstacle crossing, narrow-based walking, and walking while talking. Possible correlates of the inability to perform the walking test included knee extensor strength, lower limb coordination, Cumulative Somatosensory Impairment Index (CSII), visual acuity and contrast sensitivity, cognition, depression, personal mastery, social support, and years of education.
Results: The results of binary logistic regression analyses, adjusted for demographics and self-selected normal speed, demonstrated that poor knee extensor strength was associated with an inability to perform tasks demanding an increase in walking speed (fast walking and obstacle crossing). Both poor lower limb coordination and higher CSII were significantly associated with failure in tests that demanded precise control over foot placement (obstacle crossing and narrow-based walking). Higher CSII was associated with failure in all tests except in the walking while talking. In contrast, poor cognition was associated with an inability to perform walking while talking. Poor personal mastery was the only variable that was associated with failure in all walking tests.
Conclusions: The results demonstrated a systematic and coherent pattern in these associations and indicated possible sensorimotor and psychological parameters that should be specifically investigated and should be intervened if a patient reports a difficulty/inability in walking in certain situations.
C1 [Deshpande, Nandini] Queens Univ, Sch Rehabil Therapy, Kingston, ON K7L 3N6, Canada.
[Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Deshpande, N (reprint author), Queens Univ, Sch Rehabil Therapy, 31 George St, Kingston, ON K7L 3N6, Canada.
EM nandinijd@yahoo.com
FU Italian Ministry of Health [ICS 110.1\RS97.71]; National Institute on
Aging [N01-AG-916413, N01-AG-821336, N01-AG-5-0002, R01 AG027012];
National Institute on Aging, National Institutes of Health
FX The InCHIANTI study was supported as a "targeted project" (ICS
110.1\RS97.71) by the Italian Ministry of Health and in part, by the
National Institute on Aging (contract nos. N01-AG-916413, N01-AG-821336,
N01-AG-5-0002; grant no. R01 AG027012) and the Intramural Research
Program, National Institute on Aging, National Institutes of Health.
NR 34
TC 4
Z9 4
U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD JUL
PY 2011
VL 92
IS 7
BP 1074
EP 1079
DI 10.1016/j.apmr.2011.02.006
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 790UU
UT WOS:000292615900008
PM 21704787
ER
PT J
AU Rodriguez-Canales, J
Eberle, FC
Jaffe, ES
Emmert-Buck, MR
AF Rodriguez-Canales, Jaime
Eberle, Franziska C.
Jaffe, Elaine S.
Emmert-Buck, Michael R.
TI Why is it crucial to reintegrate pathology into cancer research?
SO BIOESSAYS
LA English
DT Article
DE cancer research; molecular biology; pathology; systems biology;
translational research
ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION; HODGKINS LYMPHOMA;
TISSUE SPECIMENS; TUMOR MICROENVIRONMENT; LUNG ADENOCARCINOMA; SYSTEMS
PATHOLOGY; PROSTATE-CANCER; MEDICINE; REDUCTIONISM
AB The integration of pathology with molecular biology is vital if we are to enhance the translational value of cancer research. Pathology represents a bridge between medicine and basic biology, it remains the gold standard for cancer diagnosis, and it plays an important role in discovery studies. In the past, pathology and cancer research were closely associated; however, the molecular biology revolution has shifted the focus of investigators toward the molecular alterations of tumors. The reductionist approach taken in molecular studies is producing great insight into the inner workings of neoplasia, but it can also minimize the importance of histopathology and of understanding the disease as a whole. In turn, pathologists can underestimate the role of molecular studies in developing new ancillary techniques for clinical diagnosis. A multidisciplinary approach that integrates pathology and molecular biology within a translational research system is needed. This process will require overcoming cultural barriers and can be achieved through education, a more effective incorporation of pathology into biological research, and conversely an integration of biological research into the pathology laboratory.
C1 [Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.] NCI, Laser Capture Microdissect Core & Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Eberle, Franziska C.; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Eberle, Franziska C.] Univ Tubingen, Dept Dermatol, Tubingen, Germany.
RP Rodriguez-Canales, J (reprint author), NCI, Laser Capture Microdissect Core & Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM rodrigja@mail.nih.gov; buckm@mail.nih.gov
OI Rodriguez-Canales, Jaime/0000-0002-0885-2377; Jaffe,
Elaine/0000-0003-4632-0301
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health (NIH)
FX We thank Kamran Ghoreschi for his assistance with Fig. 2, and Jodie M.
Fleming for providing the histological slide of a xenograft from human
breast ductal carcinoma (Fig. 1B). This work was supported in part by
the intramural program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health (NIH). M. R. E.-B. is an
inventor on all NIH patents covering laser-capture microdissection
technology and receives royalty payments through the NIH technology
transfer program.
NR 68
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PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0265-9247
J9 BIOESSAYS
JI Bioessays
PD JUL
PY 2011
VL 33
IS 7
BP 490
EP 498
DI 10.1002/bies.201100017
PG 9
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 791ZO
UT WOS:000292710500003
PM 21590787
ER
PT J
AU Rosenberg, PS
Anderson, WF
AF Rosenberg, Philip S.
Anderson, William F.
TI Age-Period-Cohort Models in Cancer Surveillance Research: Ready for
Prime Time?
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Editorial Material
ID CHRONIC DISEASE RATES; FEMALE BREAST-CANCER; UNITED-STATES; ETIOLOGIC
HETEROGENEITY; INTERPRETING TRENDS; EUROPEAN COUNTRIES; TEMPORAL
VARIATION; TESTICULAR CANCER; MORTALITY-RATES; LEXIS DIAGRAM
AB Standard descriptive methods for the analysis of cancer surveillance data include canonical plots based on the lexis diagram, directly age-standardized rates (ASR), estimated annual percentage change (EAPC), and joinpoint regression. The age-period-cohort (APC) model has been used less often. Here, we argue that it merits much broader use. First, we describe close connections between estimable functions of the model parameters and standard quantities such as the ASR, EAPC, and joinpoints. Estimable functions have the added value of being fully adjusted for period and cohort effects, and generally more precise. Second, the APC model provides the descriptive epidemiologist with powerful new tools, including rigorous statistical methods for comparative analyses, and the ability to project the future burden of cancer. We illustrate these principles by using invasive female breast cancer incidence in the United States, but these concepts apply equally well to other cancer sites for incidence or mortality. Cancer Epidemiol Biomarkers Prev; 20(7); 1263-8. (C)2011 AACR.
C1 [Rosenberg, Philip S.; Anderson, William F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Anderson, WF (reprint author), NCI, Rockville, MD 20852 USA.
EM wanderso@mail.nih.gov
FU Intramural NIH HHS [ZIA CP010183-08, Z01 CP010183-05]
NR 58
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U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2011
VL 20
IS 7
BP 1263
EP 1268
DI 10.1158/1055-9965.EPI-11-0421
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 789FK
UT WOS:000292499700001
PM 21610223
ER
PT J
AU Breen, EC
Hussain, SK
Magpantay, L
Jacobson, LP
Detels, R
Rabkin, CS
Kaslow, RA
Variakojis, D
Bream, JH
Rinaldo, CR
Ambinder, RF
Martinez-Maza, O
AF Breen, Elizabeth Crabb
Hussain, Shehnaz K.
Magpantay, Larry
Jacobson, Lisa P.
Detels, Roger
Rabkin, Charles S.
Kaslow, Richard A.
Variakojis, Daina
Bream, Jay H.
Rinaldo, Charles R.
Ambinder, Richard F.
Martinez-Maza, Otoniel
TI B-Cell Stimulatory Cytokines and Markers of Immune Activation Are
Elevated Several Years Prior to the Diagnosis of Systemic
AIDS-Associated Non-Hodgkin B-Cell Lymphoma
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY;
EPSTEIN-BARR-VIRUS; INDUCED CYTIDINE DEAMINASE; HIV-1 INFECTION; SOMATIC
HYPERMUTATION; SOLUBLE CD30; SERUM-LEVELS; MOLECULAR PATHOGENESIS;
INTERLEUKIN-6
AB Background: The risk of developing non-Hodgkin lymphoma (NHL) is greatly increased in HIV infection. The aim of this study was to determine whether elevated serum levels of molecules associated with B-cell activation precede the diagnosis of AIDS-associated NHL (AIDS-NHL).
Methods: Serum levels of B-cell activation-associated molecules, interleukin (IL)6, IL10, soluble CD23 (sCD23), sCD27, sCD30, C-reactive protein (CRP), and immunoglobulin E were determined in 179 NHL cases and HIV+ controls in the Multicenter AIDS Cohort Study, collected at up to 3 time points per subject, 0 to 5 years prior to AIDS-NHL diagnosis.
Results: Serum IL6, IL10, CRP, sCD23, sCD27, and sCD30 levels were all significantly elevated in the AIDS-NHL group, when compared with HIV+ controls or with AIDS controls, after adjusting for CD4 T-cell number. Elevated serum levels of B-cell activation-associated molecules were seen to be associated with the development of systemic [non-CNS (central nervous system)] NHL, but not with the development of primary CNS lymphoma.
Conclusions: Levels of certain B-cell stimulatory cytokines and molecules associated with immune activation are elevated for several years preceding the diagnosis of systemic AIDS-NHL. This observation is consistent with the hypothesis that chronic B-cell activation contributes to the development of these hematologic malignancies.
Impact: Marked differences in serum levels of several molecules are seen for several years prediagnosis in those who eventually develop AIDS-NHL. Some of these molecules may serve as candidate biomarkers and provide valuable information to better define the etiology of NHL. Cancer Epidemiol Biomarkers Prev; 20(7); 1303-14. (C)2011 AACR.
C1 [Breen, Elizabeth Crabb] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Breen, Elizabeth Crabb; Magpantay, Larry; Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA.
[Hussain, Shehnaz K.; Magpantay, Larry; Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Magpantay, Larry; Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
[Magpantay, Larry; Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Hussain, Shehnaz K.; Detels, Roger; Martinez-Maza, Otoniel] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
[Jacobson, Lisa P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Bream, Jay H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Ambinder, Richard F.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA.
[Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Kaslow, Richard A.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[Kaslow, Richard A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Kaslow, Richard A.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Kaslow, Richard A.] Univ Alabama, Dept Genet, Birmingham, AL USA.
[Variakojis, Daina] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA.
[Rinaldo, Charles R.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
RP Breen, EC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Room 3160A,Box 957076, Los Angeles, CA 90095 USA.
EM ebreen@mednet.ucla.edu
RI Martinez-Maza, Otoniel/B-2667-2009; Ambinder, Richard/G-1607-2011
OI Martinez-Maza, Otoniel/0000-0003-1364-0675;
FU Leukemia and Lymphoma Society [6155-03]; National Institutes of Health
[R01-CA57152, R01-CA73475, K07-CA140360]; Specialized Program of
Research Excellence (SPORE) in Lymphoma [P50-CA96888]; UCLA Older
Americans Independence Center (OAIC); OAIC Inflammatory Biology Core
[P30-AG028748]; National Cancer Institute; National Institute of Allergy
and Infectious Diseases; National Cancer Institute [UO1-AI-35042,
UL1-RR025005, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041]
FX This work was supported by grants from the Leukemia and Lymphoma Society
(6155-03) and the National Institutes of Health (R01-CA57152,
R01-CA73475, and K07-CA140360), including the Specialized Program of
Research Excellence (SPORE) in Lymphoma (P50-CA96888), the UCLA Older
Americans Independence Center (OAIC) and the OAIC Inflammatory Biology
Core (P30-AG028748), and the Intramural Research Program, National
Cancer Institute. The MACS is funded by the National Institute of
Allergy and Infectious Diseases, with additional supplemental funding
from the National Cancer Institute [UO1-AI-35042, UL1-RR025005 (GCRC),
UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041]. Some of
this work was carried out in the facilities of the UCLA AIDS Institute,
which were supported in part by funds from the James B. Pendleton
Charitable Trust and the McCarthy Family Foundation.
NR 81
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2011
VL 20
IS 7
BP 1303
EP 1314
DI 10.1158/1055-9965.EPI-11-0037
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 789FK
UT WOS:000292499700006
PM 21527584
ER
PT J
AU Schiffman, M
Glass, AG
Wentzensen, N
Rush, BB
Castle, PE
Scott, DR
Buckland, J
Sherman, ME
Rydzak, G
Kirk, P
Lorincz, AT
Wacholder, S
Burk, RD
AF Schiffman, Mark
Glass, Andrew G.
Wentzensen, Nicolas
Rush, Brenda B.
Castle, Philip E.
Scott, David R.
Buckland, Julie
Sherman, Mark E.
Rydzak, Greg
Kirk, Peter
Lorincz, Attila T.
Wacholder, Sholom
Burk, Robert D.
TI A Long-term Prospective Study of Type-Specific Human Papillomavirus
Infection and Risk of Cervical Neoplasia Among 20,000 Women in the
Portland Kaiser Cohort Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CYTOLOGICALLY NORMAL WOMEN; INTRAEPITHELIAL NEOPLASIA; FOLLOW-UP;
ABSOLUTE RISK; CANCER; HPV; DNA; ABNORMALITIES; PERSISTENCE
AB Background: Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (>= CIN3). Adding HPV testing to cytology is recommended for women >= 30 but long-term prospective studies of HPV testing are rare.
Methods: Beginning in 1989-1990, similar to 20,000 women in a prepaid health maintenance organization (median age 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan-Meier estimates of cumulative probability for >= CIN3, up to 18 years of follow-up.
Results: We observed 47 cases of invasive cervical cancer during the study period, and 156 cases of CIN3. Predictive values and Kaplan-Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against >= CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8-15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2-6.6). The risk for >= CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7).
Conclusion and Impact: The data from this cohort study show the long-term predictive value of HPV testing, particularly in women >= 30, and a possible role for distinguishing particularly carcinogenic types like HPV16. Cancer Epidemiol Biomarkers Prev; 20(7); 1398-409. (C)2011 AACR.
C1 [Schiffman, Mark; Wentzensen, Nicolas; Castle, Philip E.; Sherman, Mark E.; Kirk, Peter; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Glass, Andrew G.; Rush, Brenda B.; Scott, David R.] Kaiser Permanente, Portland, OR USA.
[Buckland, Julie; Rydzak, Greg] Informat Management Serv Inc, Silver Spring, MD USA.
[Lorincz, Attila T.] Wolfson Inst Prevent Med, London, England.
[Burk, Robert D.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
FU National Institutes of Health; National Cancer Institute [CA78527]
FX The Portland Cohort Study and NCI investigators were funded by the
Intramural Research Program of the National Institutes of Health. HPV
DNA testing by Dr. Burk was supported by National Cancer Institute grant
CA78527 and used the facilities available through the Einstein Cancer
Research Center. The earliest rounds of HPV PCR testing at Cetus (now
Roche) and the Hybrid Capture testing at Digene Corporation (now Qiagen)
were donated by these companies, representing a very small percentage
(<<1%) of the total project costs.
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2011
VL 20
IS 7
BP 1398
EP 1409
DI 10.1158/1055-9965.EPI-11-0206
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 789FK
UT WOS:000292499700016
PM 21602310
ER
PT J
AU Jiao, L
Taylor, PR
Weinstein, SJ
Graubard, BI
Virtamo, J
Albanes, D
Stolzenberg-Solomon, RZ
AF Jiao, Li
Taylor, Philip R.
Weinstein, Stephanie J.
Graubard, Barry I.
Virtamo, Jarmo
Albanes, Demetrius
Stolzenberg-Solomon, Rachael Z.
TI Advanced Glycation End Products, Soluble Receptor for Advanced Glycation
End Products, and Risk of Colorectal Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; SERUM-LEVELS; DIABETIC-PATIENTS; FORM SRAGE;
RAGE; ENDPRODUCTS; INFLAMMATION; ACTIVATION; PROTEIN; AGE
AB Background: Advanced glycation end products (AGE) accumulate in human tissue proteins during aging, particularly under hyperglycemia conditions. AGEs induce oxidative stress and inflammation via the receptor for AGEs (RAGE) and soluble RAGE (sRAGE) can neutralize the effects mediated by RAGE-ligand engagement.
Methods: We examined the association between N(epsilon)-(carboxymethyl) lysine (CML), a prominent AGE, and sRAGE and colorectal cancer risk in a prospective case-cohort study nested within a cancer prevention trial among 29,133 Finnish male smokers. Among study subjects who were alive without cancer 5 years after baseline (1985-1988), we identified 483 incident colorectal cancer cases and randomly sampled 485 subcohort participants as the comparison group with the follow-up to April 2006. Baseline serum levels of CML-AGE, sRAGE, glucose and insulin were determined. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% CI.
Results: Comparing highest with lowest quintile of sRAGE, the RR for incident colorectal cancer was 0.65 (95% CI, 0.39-1.07; P(trend) = 0.03), adjusting for age, years of smoking, body mass index, and CML-AGE. Further adjustment for serum glucose strengthened the association (RR = 0.52; 95% CI, 0.30-0.89; P(trend =) 0.009). Highest quintile of CML-AGE was not associated with an increased risk of colorectal cancer (multivariate RR = 1.20; 95% CI, 0.64-2.26).
Conclusions: Higher prediagnostic levels of serum sRAGE were associated with lower risk of colorectal cancer in male smokers.
Impact: This is the first epidemiologic study to implicate the receptor for AGEs in colorectal cancer development. Cancer Epidemiol Biomarkers Prev; 20(7); 1430-8. (C)2011 AACR.
C1 [Jiao, Li; Taylor, Philip R.; Weinstein, Stephanie J.; Graubard, Barry I.; Albanes, Demetrius; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Jiao, L (reprint author), Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, 2002 Holcombe Blvd,MS 152, Houston, TX 77030 USA.
EM jiao@bcm.edu
RI Albanes, Demetrius/B-9749-2015
FU National Cancer Institute; Division of Cancer Epidemiology and Genetics
of the National Cancer Institute at the NIH; U.S. Public Health Service
from the National Cancer Institute, U.S. Department of Health and Human
Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HSN261201000006C]
FX This work was supported by funding from the Intramural Research Program
of the National Cancer Institute (P. R. Taylor, S.J. Weinstein, B. I.
Graubard, D. Albanes, R.Z. Stolzenberg-Solomon) and an Intramural
Research Award (L. Jiao) in the Division of Cancer Epidemiology and
Genetics of the National Cancer Institute at the NIH. The
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by
U.S. Public Health Service contracts (N01-CN-45165, N01-RC-45035,
N01-RC-37004, and HSN261201000006C) from the National Cancer Institute,
U.S. Department of Health and Human Services.
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PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2011
VL 20
IS 7
BP 1430
EP 1438
DI 10.1158/1055-9965.EPI-11-0066
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 789FK
UT WOS:000292499700019
PM 21527578
ER
PT J
AU Yuan, P
Liang, KW
Ma, BY
Zheng, N
Nussinov, R
Huang, J
AF Yuan, Peng
Liang, Kaiwei
Ma, Buyong
Zheng, Nan
Nussinov, Ruth
Huang, Jian
TI Multiple-Targeting and Conformational Selection in the Estrogen
Receptor: Computation and Experiment
SO CHEMICAL BIOLOGY & DRUG DESIGN
LA English
DT Article
DE conformational ensemble; conformational selection; docking;
phytoestrogen; SERMs; two-state theory
ID LIGAND-BINDING DOMAIN; ER-BETA LIGANDS; BREAST-CANCER CELLS; PROTEIN
DOCKING; ALPHA; PHYTOESTROGENS; SUBTYPE; DESIGN; ANTAGONISM; PREDICTION
AB Conformational selection is a primary mechanism in biomolecular recognition. The conformational ensemble may determine the ability of a drug to compete with a native ligand for a receptor target. Traditional docking procedures which use one or few protein structures are limited and may not be able to represent a complex competition among closely related protein receptors in agonist and antagonist ensembles. Here, we test a protocol aimed at selecting a drug candidate based on its ability to synergistically bind to distinct conformational states. We demonstrate, for the case of estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta), that the functional outcome of ligand binding can be inferred from its ability to simultaneously bind both ER alpha and ER beta in agonist and antagonist conformations as calculated docking scores. Combining a conformational selection method with an experimental reporter gene system in yeast, we propose that several phytoestrogens can be novel estrogen receptor beta selective agonists. Our work proposes a computational protocol to select estrogen receptor subtype selective agonists. Compared with other models, present method gives the best prediction in ligands' function.
C1 [Yuan, Peng; Liang, Kaiwei; Zheng, Nan; Huang, Jian] Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Hubei, Peoples R China.
[Ma, Buyong; Nussinov, Ruth] NCI, SAIC Frederick, Ctr Canc Res Nanobiol Program, Ft Detrick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Huang, J (reprint author), Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Hubei, Peoples R China.
EM jianhuang@whu.edu.cn
RI Ma, Buyong/F-9491-2011; Yuan, Peng/P-3244-2016
OI Ma, Buyong/0000-0002-7383-719X; Yuan, Peng/0000-0003-4051-4447
FU National Basic Science Foundation for Talent Education [J0630648];
National Natural Science Foundation of China [30670647, 30970914];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX We are grateful to Dr Dan Noonan for generously providing yeast strains
and plasmids. This work was supported by the National Basic Science
Foundation for Talent Education (J0630648) and National Natural Science
Foundation of China (30670647 and 30970914). This project has been
funded in whole or in part with Federal funds from the National Cancer
Institute, National Institutes of Health, under contract number
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported (in part) by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 69
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U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1747-0277
J9 CHEM BIOL DRUG DES
JI Chem. Biol. Drug Des.
PD JUL
PY 2011
VL 78
IS 1
BP 137
EP 149
DI 10.1111/j.1747-0285.2011.01119.x
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 791VR
UT WOS:000292695900014
PM 21443691
ER
PT J
AU Uchida, N
Bonifacino, A
Krouse, AE
Metzger, ME
Csako, G
Lee-Stroka, A
Fasano, RM
Leitman, SF
Mattapallil, JJ
Hsieh, MM
Tisdale, JF
Donahue, RE
AF Uchida, Naoya
Bonifacino, Aylin
Krouse, Allen E.
Metzger, Mark E.
Csako, Gyorgy
Lee-Stroka, Agnes
Fasano, Ross M.
Leitman, Susan F.
Mattapallil, Joseph J.
Hsieh, Matthew M.
Tisdale, John F.
Donahue, Robert E.
TI Accelerated lymphocyte reconstitution and long-term recovery after
transplantation of lentiviral-transduced rhesus CD34(+) cells mobilized
by G-CSF and plerixafor
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; SIMIAN IMMUNODEFICIENCY VIRUS; CD4 T-CELLS;
NONHUMAN-PRIMATES; BONE-MARROW; PERIPHERAL-BLOOD; VECTOR; EXPRESSION;
INFECTION; GENE
AB Objective. Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34(+) cells in rhesus macaques. We sought to evaluate whether these CD34(+) cells can stably reconstitute blood cells with lentiviral gene marking.
Materials and Methods. We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34(+) cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization.
Results. G-CSF and plerixafor mobilization resulted in CD34(+) cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) expression was greater in G-CSF and plerixafor-mobilized CD34(+) cells when compared to G-CSF alone. Animals transplanted with G-CSF and plerixafor-mobilized cells showed engraftment of all lineages, similar to animals who received G-CSF and stem cell factor mobilized grafts. Lymphocyte engraftment was accelerated in animals receiving the G-CSF and plerixaformobilized CD34(+) cells. One animal in the G-CSF and plerixafor group developed cold agglutinin-associated skin rash during the first 3 months of rapid lymphocyte recovery. One year after transplantation, all animals had 2% to 10% transgene expression in all blood cell lineages.
Conclusions. G-CSF and plerixafor-mobilized CD34(+) cells accelerate lymphocyte engraftment and contain hematopoietic stein cell capable of reconstituting multilineage blood cells. These findings indicate important differences to consider in plerixafor-based hematopoietic stem cell mobilization protocols in rhesus macaques. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
C1 [Bonifacino, Aylin; Krouse, Allen E.; Metzger, Mark E.; Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Rockville, MD 20892 USA.
[Uchida, Naoya; Hsieh, Matthew M.; Tisdale, John F.] NIDDKD, Mol & Clin Hematol Branch, NHLBI, NIH, Rockville, MD USA.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Lee-Stroka, Agnes; Fasano, Ross M.; Leitman, Susan F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
RP Donahue, RE (reprint author), NHLBI, Hematol Branch, NIH, 5 Res Court,Bldg 5RC,1B06,MSC 3315, Rockville, MD 20892 USA.
EM donahuer@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute; National Institute of
Diabetes, Digestive, and Kidney Diseases; Clinical Center at the
National Institutes of Health; National Institutes of Allergy and
Infectious Diseases [AI07812]; National Institute of Dental and
Craniofacial Research [DE018339, DE019397]
FX This work was supported by the intramural research programs of the
National Heart, Lung, and Blood Institute, the National Institute of
Diabetes, Digestive, and Kidney Diseases, and the Clinical Center at the
National Institutes of Health, and in part by grants, AI07812 from
National Institutes of Allergy and Infectious Diseases and DE018339 and
DE019397 from the National Institute of Dental and Craniofacial Research
to J.J.M. We thank the staff at 5 Research Court for their excellent
care and handling of the rhesus macaques. We particularly would like to
thank Earl West for being the first to identify the development of the
cold agglutinin in RQ7375 and Dr. Chyi-Chia Richard Lee of the
Dermatopathology & Surgical Pathology of the National Cancer Institute
for interpreting the skin biopsy. We would also like to thank William
DeGraff and Dr. Jim Mitchell of the Radiation Biology Branch, NCI for
the use of the Eldorado Cobalt-60 irradiator, and Dr. Derek Persons of
the St Jude Children's Research Hospital for providing us viral vectors
and sharing data.
NR 24
TC 14
Z9 15
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD JUL
PY 2011
VL 39
IS 7
BP 795
EP 805
DI 10.1016/j.exphem.2011.04.002
PG 11
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 790WZ
UT WOS:000292622800008
PM 21549175
ER
PT J
AU Wiench, M
Miranda, TB
Hager, GL
AF Wiench, Malgorzata
Miranda, Tina B.
Hager, Gordon L.
TI Control of nuclear receptor function by local chromatin structure
SO FEBS JOURNAL
LA English
DT Review
DE chromatin remodeling; DNA methylation; DNase I hypersensitivity;
enhancer; histone modifications; nuclear receptors; nucleosome
positioning; promoter
ID MAMMARY-TUMOR VIRUS; DNASEI HYPERSENSITIVE SITES; TRANSCRIPTION FACTOR
ACCESS; STEROID-HORMONE RECEPTORS; NUCLEOSOME CORE PARTICLE;
LIGAND-SPECIFIC DYNAMICS; LONG TERMINAL REPEAT; GLUCOCORTICOID-RECEPTOR;
ESTROGEN-RECEPTOR; HUMAN GENOME
AB Steroid hormone receptors regulate gene transcription in a highly tissue-specific manner. The local chromatin structure underlying promoters and hormone response elements is a major component involved in controlling these highly restricted expression patterns. Chromatin remodeling complexes, as well as histone and DNA modifying enzymes, are directed to gene-specific regions and create permissive or repressive chromatin environments. These structures further enable proper communication between transcription factors, co-regulators and basic transcription machinery. The regulatory elements active at target genes can be either constitutively accessible to receptors or subject to rapid receptor-dependent modification. The chromatin states responsible for these processes are in turn determined during development and differentiation. Thus access of regulatory factors to elements in chromatin provides a major level of cell selective regulation.
C1 [Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; NIGMS
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. T.B. Miranda
is funded in part by the NIGMS Pharmacology Research Associate
Fellowship.
NR 188
TC 21
Z9 21
U1 2
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JUL
PY 2011
VL 278
IS 13
BP 2211
EP 2230
DI 10.1111/j.1742-4658.2011.08126.x
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 789PJ
UT WOS:000292527500003
PM 21501385
ER
PT J
AU Cardesa-Salzmann, TM
Colomo, L
Gutierrez, G
Chan, WC
Weisenburger, D
Climent, F
Gonzalez-Barca, E
Mercadal, S
Arenillas, L
Serrano, S
Tubbs, R
Delabie, J
Gascoyne, RD
Connors, JM
Mate, JL
Rimsza, L
Braziel, R
Rosenwald, A
Lenz, G
Wright, G
Jaffe, ES
Staudt, L
Jares, P
Lopez-Guillermo, A
Campo, E
AF Cardesa-Salzmann, Teresa M.
Colomo, Luis
Gutierrez, Gonzalo
Chan, Wing C.
Weisenburger, Dennis
Climent, Fina
Gonzalez-Barca, Eva
Mercadal, Santiago
Arenillas, Leonor
Serrano, Sergio
Tubbs, Ray
Delabie, Jan
Gascoyne, Randy D.
Connors, Joseph M.
Mate, Jose L.
Rimsza, Lisa
Braziel, Rita
Rosenwald, Andreas
Lenz, Georg
Wright, George
Jaffe, Elaine S.
Staudt, Louis
Jares, Pedro
Lopez-Guillermo, Armando
Campo, Elias
TI High microvessel density determines a poor outcome in patients with
diffuse large B-cell lymphoma treated with rituximab plus chemotherapy
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE rituximab; aggressive non-Hodgkin's lymphoma; kidney; central nervous
system
ID NF-KAPPA-B; PROGNOSTIC-SIGNIFICANCE; FOLLICULAR LYMPHOMA; GENE
SIGNATURES; VEGF-A; SURVIVAL; ANGIOGENESIS; EXPRESSION;
IMMUNOCHEMOTHERAPY; MUTATIONS
AB Background
Diffuse large B-cell lymphoma is a clinically and molecularly heterogeneous disease. Gene expression profiling studies have shown that the tumor microenvironment affects survival and that the angiogenesis-related signature is prognostically unfavorable. The contribution of histopathological microvessel density to survival in diffuse large B-cell lymphomas treated with immunochemotherapy remains unknown. The purpose of this study is to assess the prognostic impact of histopathological microvessel density in two independent series of patients with diffuse large B-cell lymphoma treated with immunochemotherapy.
Design and Methods
One hundred and forty-seven patients from the Leukemia Lymphoma Molecular Profiling Project (training series) and 118 patients from the Catalan Lymphoma-Study group-GELCAB (validation cohort) were included in the study. Microvessels were immunostained with CD31 and quantified with a computerized image analysis system. The stromal scores previously defined in 110 Leukemia Lymphoma Molecular Profiling Project cases were used to analyze correlations with microvessel density data.
Results
Microvessel density significantly correlated with the stromal score (r = 0.3209; P < 0.001). Patients with high microvessel density showed significantly poorer overall survival than those with low microvessel density both in the training series (4-year OS 54% vs. 78%; P = 0.004) and in the validation cohort (57% vs. 81%; P = 0.006). In multivariate analysis, in both groups high microvessel density was a statistically significant unfavorable prognostic factor independent of international prognostic index [training series: international prognostic index (relative risk 2.7; P = 0.003); microvessel density (relative risk 1.96; P = 0.002); validation cohort: international prognostic index (relative risk 4.74; P < 0.001); microvessel density (relative risk 2.4; P = 0.016)].
Conclusions
These findings highlight the impact of angiogenesis in the outcome of patients with diffuse large B-cell lymphoma and the interest of evaluating antiangiogenic drugs in clinical trials.
C1 [Cardesa-Salzmann, Teresa M.; Colomo, Luis; Gutierrez, Gonzalo; Jares, Pedro; Lopez-Guillermo, Armando; Campo, Elias] Univ Barcelona, Hosp Clin, Barcelona, Spain.
[Chan, Wing C.; Weisenburger, Dennis] Univ Nebraska Med Ctr, Omaha, NE USA.
[Climent, Fina] Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain.
[Gonzalez-Barca, Eva; Mercadal, Santiago] Hosp Duran i Reynals, Inst Catala Oncol, Lhospitalet De Llobregat, Spain.
[Arenillas, Leonor; Serrano, Sergio] Hosp del Mar, Barcelona, Spain.
[Tubbs, Ray] Cleveland Clin, Cleveland, OH 44106 USA.
[Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway.
[Gascoyne, Randy D.; Connors, Joseph M.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Mate, Jose L.] Hosp Germans Trias, Badalona, Spain.
[Rimsza, Lisa] Univ Arizona, Ctr Canc, Tucson, AZ USA.
[Braziel, Rita] Oregon Hlth & Sci Univ, Portland, OR USA.
[Rosenwald, Andreas] Univ Wurzburg, Wurzburg, Germany.
[Lenz, Georg] Mol Krebsforschungszentrum MKFZ Charite Univ Med, Berlin, Germany.
[Wright, George; Jaffe, Elaine S.; Staudt, Louis] NCI, NIH, Bethesda, MD 20892 USA.
RP Lopez-Guillermo, A (reprint author), Hosp Clin Barcelona, Dept Hematol, Calle Villarroel 170, E-08036 Barcelona, Spain.
EM alopezg@clinic.ub.es
RI Lenz, Georg/I-6844-2012; Colomo, Luis/A-2259-2016;
OI Campo, elias/0000-0001-9850-9793; Colomo, Luis/0000-0001-5236-5085;
Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301;
Arenillas, Leonor/0000-0002-8176-7179
FU Ministry of Education and Science of Spain [SAF 2008 03630-O, FIS PI
070409]; Red Tematica de Investigacion Cooperativa en Cancer RTICC
[U.2006-RET2039-O]
FX this work was supported by a grant from the Ministry of Education and
Science of Spain (SAF 2008 03630-O (EC), FIS PI 070409 (ALG) and by the
Red Tematica de Investigacion Cooperativa en Cancer RTICC
U.2006-RET2039-O (EC)
NR 30
TC 28
Z9 31
U1 0
U2 1
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUL
PY 2011
VL 96
IS 7
BP 996
EP 1001
DI 10.3324/haematol.2010.037408
PG 6
WC Hematology
SC Hematology
GA 792FX
UT WOS:000292727200009
PM 21546504
ER
PT J
AU Wu, JW
Wang, SP
Alvarez, F
Casavant, S
Gauthier, N
Abed, L
Soni, KG
Yang, GS
Mitchell, GA
AF Wu, Jiang Wei
Wang, Shu Pei
Alvarez, Fernando
Casavant, Stephanie
Gauthier, Nicolas
Abed, Lynda
Soni, Krishnakant G.
Yang, Gongshe
Mitchell, Grant A.
TI Deficiency of Liver Adipose Triglyceride Lipase in Mice Causes
Progressive Hepatic Steatosis
SO HEPATOLOGY
LA English
DT Article
ID HORMONE-SENSITIVE LIPASE; FATTY LIVER; INSULIN-RESISTANCE; NONALCOHOLIC
STEATOHEPATITIS; HEPATOCELLULAR-CARCINOMA; MURINE STEATOHEPATITIS;
METABOLIC SYNDROME; ENERGY-METABOLISM; DISEASE; TISSUE
AB Accumulation of cytoplasmic triacylglycerol (TG) underlies hepatic steatosis, a major cause of cirrhosis. The pathways of cytoplasmic TG metabolism are not well known in hepatocytes, but evidence suggests an important role in lipolysis for adipose triglyceride lipase (ATGL). We created mice with liver-specific inactivation of Pnpla2, the ATGL gene. These ATGLLKO mice had severe progressive periportal macrovesicular and pericentral microvesicular hepatic steatosis (73, 150, and 226 mu mol TG/g liver at 4, 8, and 12 months, respectively). However, plasma levels of glucose, TG, and cholesterol were similar to those of controls. Fasting 3-hydroxybutyrate level was normal, but in thin sections of liver, beta oxidation of palmitate was decreased by one-third in ATGLLKO mice compared with controls. Tests of very low-density lipoprotein production, glucose, and insulin tolerance and gluconeogenesis from pyruvate were normal. Plasma alanine aminotransferase levels were elevated in ATGLLKO mice, but histological estimates of inflammation and fibrosis and messenger RNA (mRNA) levels of tumor necrosis factor-a and interleukin-6 were similar to or lower than those in controls. ATGLLKO cholangiocytes also showed cytoplasmic lipid droplets, demonstrating that ATGL is also a major lipase in cholangiocytes. There was a 50-fold reduction of hepatic diacylglycerol acyltransferase 2 mRNA level and a 2.7-fold increase of lipolysosomes in hepatocytes (P < 0.001), suggesting reduced TG synthesis and increased lysosomal degradation of TG as potential compensatory mechanisms. Conclusion: Compared with the hepatic steatosis of obesity and diabetes, steatosis in ATGL deficiency is well tolerated metabolically. ATGLLKO mice will be useful for studying the pathophysiology of hepatic steatosis. (HEPATOLOGY 2011;54:122-132)
C1 [Wu, Jiang Wei; Yang, Gongshe] NW A&F Univ, Coll Anim Sci & Technol, Lab Anim Fat Deposit & Muscle Dev, Yangling, Shaanxi, Peoples R China.
[Wu, Jiang Wei; Wang, Shu Pei; Casavant, Stephanie; Gauthier, Nicolas; Mitchell, Grant A.] Univ Montreal, Div Med Genet, Dept Pediat, Montreal, PQ H3T 1C5, Canada.
[Alvarez, Fernando] Univ Montreal, Div Gastroenterol Hepatol & Nutr, Dept Pediat, Montreal, PQ H3T 1C5, Canada.
[Abed, Lynda] Univ Montreal, CHU St Justine, Dept Pathol, Montreal, PQ H3T 1C5, Canada.
[Soni, Krishnakant G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA.
RP Yang, GS (reprint author), NW A&F Univ, Coll Anim Sci & Technol, Lab Anim Fat Deposit & Muscle Dev, Yangling, Shaanxi, Peoples R China.
EM gsyang999@hotmail.com; grant.mitchell@recherche-ste.justine.qc.ca
FU Canadian Institutes of Health Research [221920]
FX Supported by Canadian Institutes of Health Research Operating Grant
221920 (to G. A. M.).
NR 39
TC 78
Z9 81
U1 1
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2011
VL 54
IS 1
BP 122
EP 132
DI 10.1002/hep.24338
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 788JH
UT WOS:000292440700017
PM 21465509
ER
PT J
AU Park, O
Wang, H
Weng, HL
Feigenbaum, L
Li, H
Yin, S
Ki, SH
Yoo, SH
Dooley, S
Wang, FS
Young, HA
Gao, B
AF Park, Ogyi
Wang, Hua
Weng, Honglei
Feigenbaum, Lionel
Li, Hai
Yin, Shi
Ki, Sung Hwan
Yoo, Seong Ho
Dooley, Steven
Wang, Fu-Sheng
Young, Howard A.
Gao, Bin
TI In Vivo Consequences of Liver-Specific Interleukin-22 Expression in
Mice: Implications for Human Liver Disease Progression
SO HEPATOLOGY
LA English
DT Article
ID HEPATITIS-C; MOUSE MODEL; IL-22; INFLAMMATION; HEPATOCYTES; CELLS;
STAT3; ACTIVATION; PSORIASIS; CYTOKINES
AB Interleukin-22 (IL-22), which acts as either a proinflammatory or anti-inflammatory cytokine in various disease models, is markedly up-regulated in chronic liver diseases, including hepatitis B and C. In this report, we demonstrate a strong correlation between IL-22 expression in the liver with active, inflammatory human liver disease. To clarify the role of IL-22 up-regulation in the pathogenesis of liver diseases, liver-specific IL-22 transgenic (IL-22TG) mice, under the control of albumin promoter, were developed. Despite elevated IL-22 serum levels ranging from 4,000 to 7,000 pg/mL, IL-22TG mice developed normally without obvious adverse phenotypes or evidence of chronic inflammation (except for slightly thicker epidermis and minor inflammation of the skin) compared with wild-type mice. Interestingly, IL-22TG mice were completely resistant to concanavalin A induced T cell hepatitis with minimal effect on liver inflammation and had accelerated liver regeneration after partial hepatectomy. Although they did not spontaneously develop liver tumors, IL-22TG mice were more susceptible to diethylnitrosamine-induced liver cancer. Microarray analyses revealed that a variety of antioxidant, mitogenic, acute phase genes were up-regulated in the livers of IL-22TG mice compared with those from wild-type mice. Conclusion: These findings indicate that localized production of IL-22 in the liver promotes hepatocyte survival and proliferation but primes the liver to be more susceptible to tumor development without significantly affecting liver inflammation. (HEPATOLOGY 2011;54:252-261)
C1 [Park, Ogyi; Wang, Hua; Yin, Shi; Ki, Sung Hwan; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Yoo, Seong Ho] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Weng, Honglei; Dooley, Steven] Univ Heidelberg, Med Clin, Med Fac Mannheim, D-6800 Mannheim, Germany.
[Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
[Young, Howard A.] NCI, Expt Immunol Lab, Canc Inflammat Program, NIH, Frederick, MD 21701 USA.
[Li, Hai] Shanghai Jiao Tong Univ, Dept Gastroenterol, Renji Hosp, Shanghai 200030, Peoples R China.
[Wang, Fu-Sheng] Beijing 302 Hosp, Res Ctr Biol Therapy, Beijing, Peoples R China.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism; National Cancer
Institute; German Federal Ministry for Education and Research (BMBF)
FX Supported by the intramural program of the National Institute on Alcohol
Abuse and Alcoholism (B.G.) and the National Cancer Institute (H.A.Y),
and by the German Federal Ministry for Education and Research (BMBF)
grants "Virtual Liver" and "Cell Therapy" (H.W., S.D.).
NR 27
TC 85
Z9 96
U1 2
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2011
VL 54
IS 1
BP 252
EP 261
DI 10.1002/hep.24339
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 788JH
UT WOS:000292440700029
PM 21465510
ER
PT J
AU Horiguchi, N
Gao, B
AF Horiguchi, Norio
Gao, Bin
TI Inflammation Does Not Always Kill Hepatocytes During Liver Damage Reply
SO HEPATOLOGY
LA English
DT Letter
ID SIGNAL TRANSDUCER; TRANSCRIPTION 3; MACROPHAGES; ACTIVATOR; INJURY; MICE
C1 [Horiguchi, Norio; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
[Horiguchi, Norio] Gunma Univ, Dept Med & Mol Sci, Grad Sch Med, Gunma, Japan.
RP Horiguchi, N (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
NR 5
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2011
VL 54
IS 1
BP 367
EP 367
DI 10.1002/hep.24383
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 788JH
UT WOS:000292440700039
ER
PT J
AU Brunt, EM
Kleiner, DE
Behling, C
Contos, MJ
Cummings, OW
Ferrell, LD
Torbenson, MS
Yeh, M
AF Brunt, Elizabeth M.
Kleiner, David E.
Behling, Cynthia
Contos, Melissa J.
Cummings, Oscar W.
Ferrell, Linda D.
Torbenson, Michael S.
Yeh, Matthew
TI Misuse of Scoring Systems
SO HEPATOLOGY
LA English
DT Letter
ID FATTY LIVER-DISEASE
C1 [Brunt, Elizabeth M.] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63130 USA.
[Kleiner, David E.] NCI, Dept Labs, NIH, Bethesda, MD 20892 USA.
[Contos, Melissa J.] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA USA.
[Behling, Cynthia] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA.
[Cummings, Oscar W.] Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA.
[Ferrell, Linda D.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
[Torbenson, Michael S.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA.
[Yeh, Matthew] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
RP Brunt, EM (reprint author), Washington Univ, Dept Pathol & Immunol, St Louis, MO 63130 USA.
OI Kleiner, David/0000-0003-3442-4453
NR 5
TC 14
Z9 14
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2011
VL 54
IS 1
BP 369
EP 370
DI 10.1002/hep.24347
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 788JH
UT WOS:000292440700042
PM 21488072
ER
PT J
AU Lok, AS
Everhart, JE
AF Lok, Anna S.
Everhart, James E.
TI Occult Hepatitis B Virus Infection and Hepatocellular Carcinoma
Development in Patients with Chronic Hepatitis C Reply
SO HEPATOLOGY
LA English
DT Letter
C1 [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Everhart, James E.] NIDDK, NIH, Bethesda, MD USA.
RP Lok, AS (reprint author), Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2011
VL 54
IS 1
BP 374
EP 374
DI 10.1002/hep.24410
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 788JH
UT WOS:000292440700048
ER
PT J
AU Guo, XC
Johnson, RC
O'Brien, SJ
AF Guo, Xiuchan
Johnson, Randall C.
O'Brien, Stephen J.
TI Association Between Human Leukocyte Antigen DP Gene Polymorphisms and
Chronic Hepatitis B in a Chinese Population Reply
SO HEPATOLOGY
LA English
DT Letter
ID GENOME-WIDE ASSOCIATION
C1 [Guo, Xiuchan] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Inst Viral Dis Control & Prevent, Beijing, Peoples R China.
[Johnson, Randall C.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
RP Guo, XC (reprint author), Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Inst Viral Dis Control & Prevent, Beijing, Peoples R China.
NR 3
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2011
VL 54
IS 1
BP 375
EP 376
DI 10.1002/hep.24448
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 788JH
UT WOS:000292440700050
ER
PT J
AU Kim, KH
Ryan, MJ
Estep, JE
Miniard, BM
Rudge, TL
Peggins, JO
Broadt, TL
Wang, MH
Preuss, MA
Siegal, GP
Hemminki, A
Harris, RD
Aurigemma, R
Curiel, DT
Alvarez, RD
AF Kim, Kenneth H.
Ryan, Michael J.
Estep, James E.
Miniard, Brock M.
Rudge, Thomas L.
Peggins, James O.
Broadt, Trevor L.
Wang, Minghui
Preuss, Meredith A.
Siegal, Gene P.
Hemminki, Akseli
Harris, Raymond D.
Aurigemma, Rosemarie
Curiel, David T.
Alvarez, Ronald D.
TI A New Generation of Serotype Chimeric Infectivity-Enhanced Conditionally
Replicative Adenovirals: The Safety Profile of Ad5/3-Delta 24 in Advance
of a Phase I Clinical Trial in Ovarian Cancer Patients
SO HUMAN GENE THERAPY
LA English
DT Article
ID GENE-TRANSFER EFFICIENCY; ONCOLYTIC ADENOVIRUS; ORTHOTOPIC MODELS;
EFFICACY; VECTORS; THERAPY; TROPISM
AB Conditionally replicative adenoviral (CRAd) virotherapy represents a promising therapeutic approach for cancer. We have demonstrated that a serotype chimeric adenoviral 5/3 fiber-knob modification achieves enhanced ovarian cancer infectivity, conditional replication, and oncolytic activity. This study evaluated the safety of intraperitoneal (IP) Ad5/3-Delta 24 in advance of a phase I clinical trial in gynecologic cancers. Syrian hamster cohorts were treated with IP Ad5/3-Delta 24 or control buffer for 3 consecutive days and euthanized on study days 8, 17, 57, and 89. Blood and tissue samples were harvested from each animal. For biodistribution studies, presence and quantitation of viral levels within samples were determined via quantitative polymerase chain reaction. For safety studies, animals were assessed for adverse vector-related tissue or laboratory effects. In the biodistribution study, low levels of Ad5/3-Delta 24 DNA were noted outside of the abdominal cavity. Viral DNA levels in tissues obtained from the peritoneal cavity peaked at day 8 and declined thereafter. In the safety study, no specific histopathologic changes were attributable to virus administration. Hematologic findings noted in the 1 x 10(11) viral particles (vp)/dose group on Days 4 and/or 8 were indicative of an Ad5/3-Delta 24-specific generalized inflammatory response; these findings resolved by day 56. The no observable adverse effect level was determined to be 1 x 10(10) vp/dose. This study elucidates the safety profile of IP administration of the serotype chimeric infectivity-enhanced CRAd, Ad5/3-Delta 24, and provides guidance for a planned phase I trial for patients with recurrent gynecologic cancers.
C1 [Kim, Kenneth H.; Alvarez, Ronald D.] Univ Alabama, Div Gynecol Oncol, Birmingham, AL 35249 USA.
[Ryan, Michael J.; Estep, James E.; Miniard, Brock M.; Rudge, Thomas L.] Battelle Biomed Res Ctr, W Jefferson, OH 43162 USA.
[Peggins, James O.] NCI, Toxicol & Pharmacol Branch, Frederick, MD 21702 USA.
[Broadt, Trevor L.] NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Wang, Minghui; Preuss, Meredith A.; Curiel, David T.] Univ Alabama, Div Human Gene Therapy, Birmingham, AL 35249 USA.
[Siegal, Gene P.] Univ Alabama, Dept Pathol, Birmingham, AL 35249 USA.
[Hemminki, Akseli] Univ Helsinki, Finnish Inst Mol Med, Canc Gene Therapy Grp, Mol Canc Biol Program,Transplantat Lab,Haartman I, Helsinki, Finland.
[Hemminki, Akseli] Univ Helsinki, Cent Hosp, HUSLAB, Helsinki, Finland.
[Harris, Raymond D.] NCI, Virol Res & Dev Lab, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Aurigemma, Rosemarie] NCI, Biol Resources Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Alvarez, RD (reprint author), Univ Alabama, Div Gynecol Oncol, 176F RM 10250,619 19th St, Birmingham, AL 35249 USA.
EM ronald.alvarez@ccc.uab.edu
FU National Institutes of Health (NIH) [5R01CA121187]; National Cancer
Institute, NIH [N01-CO-12400]; Division of Cancer Treatment and
Diagnosis of the National Cancer Institute [N01-CM-42200]
FX This work was supported by National Institutes of Health (NIH) grant
5R01CA121187 and has been funded in whole or in part with federal funds
from the National Cancer Institute, NIH, under Contract No.
N01-CO-12400. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. government.; This research
was supported in part by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute under Contract No. N01-CM-42200.
NR 23
TC 10
Z9 10
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JUL
PY 2011
VL 22
IS 7
BP 821
EP 828
DI 10.1089/hum.2010.180
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 792IT
UT WOS:000292737600007
PM 21171861
ER
PT J
AU Pinheiro, A
Lanning, D
Alves, PC
Mage, RG
Knight, KL
van der Loo, W
Esteves, PJ
AF Pinheiro, Ana
Lanning, Dennis
Alves, Paulo C.
Mage, Rose G.
Knight, Katherine L.
van der Loo, Wessel
Esteves, Pedro J.
TI Molecular bases of genetic diversity and evolution of the immunoglobulin
heavy chain variable region (IGHV) gene locus in leporids
SO IMMUNOGENETICS
LA English
DT Review
DE Leporids; Rabbit; IGHV; Evolution; Immunoglobulin repertoire
ID RABBIT ORYCTOLAGUS-CUNICULUS; AMINO-ACID-SEQUENCE; ALLOTYPE-SUPPRESSED
RABBITS; E ALLELIC POLYMORPHISM; H-MUTANT RABBITS; LIGHT-CHAIN; B-LOCUS;
ANTIBODY REPERTOIRE; VH-GENE; NATURAL-POPULATIONS
AB The rabbit has long been a model for studies of the immune system. Work using rabbits contributed both to the battle against infectious diseases such as rabies and syphilis, and to our knowledge, of antibodies' structure, function, and regulated expression. With the description of rabbit Ig allotypes, the discovery of different gene segments encoding immunoglobulins became possible. This challenged the "one gene-one protein" dogma. The observation that rabbit allotypic specificities of the variable regions were present on IgM and IgG molecules also led to the hypothesis of Ig class switching. Rabbit allotypes contributed to the documentation of phenomena such as allelic exclusion and imbalance in production of allelic gene products. During the last 30 years, the rabbit Ig allotypes revealed a number of unique features, setting them apart from mice, humans, and other mammals. Here, we review the most relevant findings concerning the rabbit IGHV. Among these are the preferential usage of one VH gene in VDJ rearrangements, the existence of trans-species polymorphism in the IGHV locus revealed by serology and confirmed by sequencing IGHV genes in Lepus, the unusually large genetic distances between allelic lineages and the fact that the antibody repertoire is diversified in this species only after birth. The whole genome sequence of a rabbit, plus re-sequencing of additional strains and related genera, will allow further evolutionary investigations of antibody variation. Continued research will help define the roles that genetic, allelic, and population diversity at antibody loci may play in host-parasite interactions.
C1 [Pinheiro, Ana; Alves, Paulo C.; van der Loo, Wessel; Esteves, Pedro J.] Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, P-4485661 Vairao, Portugal.
[Pinheiro, Ana; Alves, Paulo C.] Univ Porto, Dept Biol, Fac Ciencias, P-4169007 Oporto, Portugal.
[Lanning, Dennis; Knight, Katherine L.] Loyola Univ Chicago, Stritch Sch Med, Dept Microbiol & Immunol, Maywood, IL 60153 USA.
[Mage, Rose G.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Esteves, Pedro J.] CESPU, IPSN, Ctr Invest Tecnol Saude, P-4585116 Gandra, Portugal.
RP Esteves, PJ (reprint author), Univ Porto, Ctr Invest Biodiversidade & Recursos Genet, Campus Agrario Vairao, P-4485661 Vairao, Portugal.
EM pjesteves@mail.icav.up.pt
RI ALVES, Paulo Celio/B-5448-2009; Pinheiro, Ana/A-9902-2011; Esteves,
Pedro/A-7537-2010;
OI ALVES, Paulo Celio/0000-0003-4797-0939; Pinheiro,
Ana/0000-0002-9047-954X; Esteves, Pedro/0000-0002-6055-8298; van der
Loo, Wessel/0000-0003-1833-7122
FU Foundation for Science and Technology-Portugal [SFRH/BD/71252/2010,
SFRH/BPD/27021/2006]; NIAID, NIH
FX This work was supported by grants of Foundation for Science and
Technology-Portugal to A.P. and P.J.E. (SFRH/BD/71252/2010 and
SFRH/BPD/27021/2006), respectively, and the intramural program of the
NIAID, NIH (R.G.M.).
NR 115
TC 19
Z9 19
U1 0
U2 17
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0093-7711
J9 IMMUNOGENETICS
JI Immunogenetics
PD JUL
PY 2011
VL 63
IS 7
BP 397
EP 408
DI 10.1007/s00251-011-0533-9
PG 12
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 789ZS
UT WOS:000292558900001
PM 21594770
ER
PT J
AU Greten, TF
Manns, MP
Korangy, F
AF Greten, Tim F.
Manns, Michael P.
Korangy, Firouzeh
TI Myeloid derived suppressor cells in human diseases
SO INTERNATIONAL IMMUNOPHARMACOLOGY
LA English
DT Review
DE Myeloid derived suppressor cells; Human; Tumor immunology
ID COLONY-STIMULATING FACTOR; NATURAL-KILLER-CELLS; REGULATORY T-CELLS;
CANCER-PATIENTS; HEPATOCELLULAR-CARCINOMA; DENDRITIC CELLS;
IMMUNOSUPPRESSIVE ACTIVITY; ACTIVATED GRANULOCYTES; IMMUNE DYSFUNCTION;
ANTITUMOR IMMUNITY
AB Myeloid derived suppressor cells (MDSC) have been described as a heterogeneous cell population with potent immune suppressor function in mice. Limited data are available on MDSC in human diseases. Interpretation of these data is complicated by the fact that different markers have been used to analyze human MDSC subtypes in various clinical settings. Human MDSC are CD11b(+), CD33(+), HLA-DRneg/low and can be divided into granulocytic CD14(-) and monocytic CD14(+) subtypes. Interleukin 4R alpha, VEGFR, CD15 and CD66b have been suggested to be more specific markers for human MDSC, however these markers can only be found on some MDSC subsets. Until today the best marker for human MDSC remains their suppressor function, which can be either direct or indirect through the induction of regulatory T cells. Immune suppressor activity has been associated with high arginase 1 and iNOS activity as well as ROS production by MDSC. Not only in murine models, but even more importantly in patients with cancer, different drugs have been shown to either reverse the immune suppressor function of MDSC or directly target these cells. Systemic treatment with all-transretinoic acid has been shown to mature human MDSC and reverse their immune suppressor function. Alternatively, MDSC can be targeted by treatment with the multi-targeted receptor tyrosine kinase inhibitor sunitinib. This review will provide a comprehensive summary of the recent literature on human MDSC. (c) 2011 Published by Elsevier B.V.
C1 [Greten, Tim F.; Korangy, Firouzeh] NCI, NIH, Med Oncol Branch, Bethesda, MD 20892 USA.
[Manns, Michael P.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.
RP Greten, TF (reprint author), NCI, NIH, Med Oncol Branch, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
FU Helmholtz Association within the Helmholtz Alliance on Immunotherapy of
Cancer; Center for Cancer Research, National Cancer Institute (NCI),
National Institutes of Health
FX The authors' work was supported by the Initiative and Networking Fund of
the Helmholtz Association within the Helmholtz Alliance on Immunotherapy
of Cancer (M.P.M.) and in part by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute (NCI), National
Institutes of Health (T.F.G.)
NR 70
TC 179
Z9 193
U1 4
U2 37
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-5769
J9 INT IMMUNOPHARMACOL
JI Int. Immunopharmacol.
PD JUL
PY 2011
VL 11
IS 7
SI SI
BP 802
EP 807
DI 10.1016/j.intimp.2011.01.003
PG 6
WC Immunology; Pharmacology & Pharmacy
SC Immunology; Pharmacology & Pharmacy
GA 791IX
UT WOS:000292660000006
PM 21237299
ER
PT J
AU Chan, T
Wiltrout, RH
Weiss, JM
AF Chan, Tim
Wiltrout, Robert H.
Weiss, Jonathan M.
TI Immunotherapeutic modulation of the suppressive liver and tumor
microenvironments
SO INTERNATIONAL IMMUNOPHARMACOLOGY
LA English
DT Review
DE Tumor-associated macrophages; Myeloid derived suppressor cells;
Regulatory dendritic cells; Regulatory T cells; Tumor immunotherapy;
Liver microenvironment
ID REGULATORY T-CELLS; PLASMACYTOID DENDRITIC CELLS; L-ARGININE METABOLISM;
COLONY-STIMULATING FACTOR; INNATE IMMUNE-RESPONSES;
NATURAL-KILLER-CELLS; IN-VIVO; HEPATOCELLULAR-CARCINOMA; MYELOID CELLS;
KUPFFER CELLS
AB The liver is an immunologically unique organ, consisting of resident hematopoietic and parenchymal cells which often contribute to a relatively tolerant microenvironment It is also becoming increasingly clear that tumor-induced immunosuppression occurs via many of the same cellular mechanisms which contribute to the tolerogenic liver microenvironment. Myeloid cells, consisting of dendritic cells (DC), macrophages and myeloid derived suppressor cells (MDSC), have been implicated in providing a tolerogenic liver environment and immune dysfunction within the tumor microenvironment which can favor tumor progression. As we increase our understanding of the biological mechanisms involved for each phenotypic and/or functionally distinct leukocyte subset, immunotherapeutic strategies can be developed to overcome the inherent barriers to the development of improved strategies for the treatment of liver disease and tumors. In this review, we discuss the principal myeloid cell-based contributions to immunosuppression that are shared between the liver and tumor microenvironments. We further highlight immune-based strategies shown to modulate immunoregulatory cells within each microenvironment and enhance anti-tumor responses. Published by Elsevier B.V.
RP Weiss, JM (reprint author), NCI Frederick Bldg 560,Room 31-18, Frederick, MD 21702 USA.
EM weissj@ncifcrf.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 173
TC 14
Z9 15
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-5769
J9 INT IMMUNOPHARMACOL
JI Int. Immunopharmacol.
PD JUL
PY 2011
VL 11
IS 7
SI SI
BP 879
EP 889
DI 10.1016/j.intimp.2010.12.024
PG 11
WC Immunology; Pharmacology & Pharmacy
SC Immunology; Pharmacology & Pharmacy
GA 791IX
UT WOS:000292660000016
PM 21241810
ER
PT J
AU Lee-Young, RS
Ayala, JE
Fueger, PT
Mayes, WH
Kang, L
Wasserman, DH
AF Lee-Young, R. S.
Ayala, J. E.
Fueger, P. T.
Mayes, W. H.
Kang, L.
Wasserman, D. H.
TI Obesity impairs skeletal muscle AMPK signaling during exercise: role of
AMPK alpha 2 in the regulation of exercise capacity in vivo
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE muscle glucose uptake; exercise tolerance; exercise training; diet
ID ACTIVATED PROTEIN-KINASE; INSULIN-RESISTANCE; GLUCOSE-UPTAKE;
NITRIC-OXIDE; MOUSE; CONTRACTION; TRANSPORT; GLUT4; MICE
AB Objective: Skeletal muscle AMP-activated protein kinase (AMPK)alpha 2 activity is impaired in obese, insulin-resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state.
Design: C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPK alpha 2 subunit in skeletal muscle (alpha 2-KD) were fed chow or high-fat (HF) diets from 3 to 16 weeks of age. At 15 weeks, mice performed an exercise stress test to determine exercise capacity. In WT mice, muscle glucose uptake and skeletal muscle AMPK alpha 2 activity was assessed in chronically catheterized mice (carotid artery/jugular vein) at 16 weeks. In a separate study, HF-fed WT and alpha 2-KD mice performed 5 weeks of exercise training (from 15 to 20 weeks of age) to test whether AMPK alpha 2 is necessary to restore work tolerance.
Results: HF-fed WT mice had reduced exercise tolerance during an exercise stress test, and an attenuation in muscle glucose uptake and AMPK alpha 2 activity during a single bout of exercise (P<0.05 versus chow). In chow-fed alpha 2-KD mice, running speed and time were impaired similar to 45 and similar to 55%, respectively (P<0.05 versus WT chow); HF feeding further reduced running time similar to 25% (P<0.05 versus alpha 2-KD chow). In response to 5 weeks of exercise training, HF-fed WT and alpha 2-KD mice increased maximum running speed similar to 35% (P<0.05 versus pre-training) and maintained body weight at pre-training levels, whereas body weight increased in untrained HF WT and alpha 2-KD mice. Exercise training restored running speed to levels seen in healthy, chow-fed mice.
Conclusion: HF feeding impairs AMPK alpha 2 activity in skeletal muscle during exercise in vivo. Although this defect directly contributes to reduced exercise capacity, findings in HF-fed alpha 2-KD mice show that AMPK alpha 2-independent mechanisms are also involved. Importantly, alpha 2-KD mice on a HF-fed diet adapt to regular exercise by increasing exercise tolerance, demonstrating that this adaptation is independent of skeletal muscle AMPK alpha 2 activity. International Journal of Obesity (2011) 35, 982-989; doi: 10.1038/ijo.2010.220; published online 16 November 2010
C1 [Lee-Young, R. S.; Ayala, J. E.; Fueger, P. T.; Mayes, W. H.; Kang, L.; Wasserman, D. H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Ayala, J. E.; Wasserman, D. H.] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA.
RP Lee-Young, RS (reprint author), Baker IDI Heart & Diabet Inst, Cellular & Mol Metab Lab, Div Metab & Obes, Melbourne, Vic 3004, Australia.
EM robert.lee-young@bakeridi.edu
RI Fueger, Patrick/G-8956-2013
FU National Institutes of Health [U24 DK-59637, R01 DK-54902]; American
Diabetes Association
FX This work was supported by National Institutes of Health Grants U24
DK-59637 and R01 DK-54902 (to DHW). RS Lee-Young was supported by a
Mentor-Based Fellowship from the American Diabetes Association.
NR 22
TC 16
Z9 17
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD JUL
PY 2011
VL 35
IS 7
BP 982
EP 989
DI 10.1038/ijo.2010.220
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 791DB
UT WOS:000292641300012
PM 21079619
ER
PT J
AU Tammemagi, CM
Pinsky, PF
Caporaso, NE
Kvale, PA
Hocking, WG
Church, TR
Riley, TL
Commins, J
Oken, MM
Berg, CD
Prorok, PC
AF Tammemagi, C. Martin
Pinsky, Paul F.
Caporaso, Neil E.
Kvale, Paul A.
Hocking, William G.
Church, Timothy R.
Riley, Thomas L.
Commins, John
Oken, Martin M.
Berg, Christine D.
Prorok, Philip C.
TI Lung Cancer Risk Prediction: Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial Models and Validation
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BODY-MASS INDEX; OXIDATIVE DNA-DAMAGE; CHRONIC INFLAMMATION;
SUSCEPTIBILITY LOCUS; AFRICAN-AMERICANS; SMOKERS; SMOKING; COHORT;
DISEASE; WOMEN
AB Introduction Identification of individuals at high risk for lung cancer should be of value to individuals, patients, clinicians, and researchers. Existing prediction models have only modest capabilities to classify persons at risk accurately.
Methods Prospective data from 70 962 control subjects in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) were used in models for the general population (model 1) and for a subcohort of ever-smokers (N = 38 254) (model 2). Both models included age, socioeconomic status (education), body mass index, family history of lung cancer, chronic obstructive pulmonary disease, recent chest x-ray, smoking status (never, former, or current), pack-years smoked, and smoking duration. Model 2 also included smoking quit-time (time in years since ever-smokers permanently quit smoking). External validation was performed with 44 223 PLCO intervention arm participants who completed a supplemental questionnaire and were subsequently followed. Known available risk factors were included in logistic regression models. Bootstrap optimism-corrected estimates of predictive performance were calculated (internal validation). Nonlinear relationships for age, pack-years smoked, smoking duration, and quit-time were modeled using restricted cubic splines. All reported P values are two-sided.
Results During follow-up (median 9.2 years) of the control arm subjects, 1040 lung cancers occurred. During follow-up of the external validation sample (median 3.0 years), 213 lung cancers occurred. For models 1 and 2, bootstrap optimism-corrected receiver operator characteristic area under the curves were 0.857 and 0.805, and calibration slopes (model-predicted probabilities vs observed probabilities) were 0.987 and 0.979, respectively. In the external validation sample, models 1 and 2 had area under the curves of 0.841 and 0.784, respectively. These models had high discrimination in women, men, whites, and nonwhites.
Conclusion The PLCO lung cancer risk models demonstrate high discrimination and calibration.
C1 [Tammemagi, C. Martin] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada.
[Berg, Christine D.] NIH, Early Detect Res Grp, Canc Prevent Div, Natl Canc Inst, Bethesda, MD 20892 USA.
[Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kvale, Paul A.] Henry Ford Hlth Syst, Div Pulm & Crit Care Med, Detroit, MI USA.
[Hocking, William G.] Marshfield Clin Fdn Med Res & Educ, Dept Hematol Oncol, Marshfield, WI USA.
[Church, Timothy R.] Univ Minnesota, Dept Environm Hlth Sci, Minneapolis, MN USA.
[Riley, Thomas L.; Commins, John] Informat Management Serv Inc, Rockville, MD USA.
[Oken, Martin M.] N Mem Hlth Care, Hubert H Humphrey Canc Ctr, Robbinsdale, MN USA.
[Prorok, Philip C.] NIH, Biometry Res Grp, Canc Prevent Div, Natl Canc Inst, Bethesda, MD 20892 USA.
RP Tammemagi, CM (reprint author), Brock Univ, Dept Community Hlth Sci, 500 Glenridge Ave, St Catharines, ON L2S 3A1, Canada.
EM martin.tammemagi@brocku.ca
RI Berg , Christine/K-1047-2014;
OI Hocking, William/0000-0002-0690-3759; Church, Timothy
R./0000-0003-3292-5035
FU Division of Cancer Prevention, National Cancer Institute, National
Institute of Health, Department of Health and Human Services; National
Cancer Institute's Prostate, Lung, Colorectal, and Ovarian Cancer
Screening Trial
FX This research was supported by contracts from the Division of Cancer
Prevention, National Cancer Institute, National Institute of Health,
Department of Health and Human Services. The funders did not have any
involvement in the design of this ancillary study; the collection,
analysis, and interpretation of the data; the writing of the manuscript;
or the decision to submit the manuscript for publication.; This report
describes an ancillary study in the National Cancer Institute's
Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which is
a federally funded registered clinical trial (ClinicalTrials.gov
Identifier: NCT00002540). The authors thank the Screening Center
investigators and staff of the Prostate, Lung, Colorectal, and Ovarian
(PLCO) Cancer Screening Trial. Most importantly, we acknowledge the
study participants for their contributions to making this study
possible. We thank Professor Frank E. Harrell, Jr, for helpful guidance
regarding risk prediction modeling and interpretation. Dr C. Martin
Tammemagi's involvement in the PLCO has been through his affiliation
with Henry Ford Health System in Detroit, Michigan.
NR 66
TC 101
Z9 104
U1 0
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD JUL
PY 2011
VL 103
IS 13
BP 1058
EP 1068
DI 10.1093/jnci/djr173
PG 11
WC Oncology
SC Oncology
GA 790BF
UT WOS:000292562800012
PM 21606442
ER
PT J
AU Sastry, M
Xu, L
Georgiev, IS
Bewley, CA
Nabel, GJ
Kwong, PD
AF Sastry, Mallika
Xu, Ling
Georgiev, Ivelin S.
Bewley, Carole A.
Nabel, Gary J.
Kwong, Peter D.
TI Mammalian production of an isotopically enriched outer domain of the
HIV-1 gp120 glycoprotein for NMR spectroscopy
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Adenovirus vector; Eukaryotic expression; HIV-1 envelope; Isotope
enrichment; N-linked glycosylation
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ESCHERICHIA-COLI; RESONANCE ASSIGNMENTS;
RECOMBINANT PROTEINS; STRUCTURAL BASIS; HUMAN CD2; IN-VITRO; ADENOVIRUS;
VECTORS; CELLS
AB NMR spectroscopic characterization of the structure or the dynamics of proteins generally requires the production of samples isotopically enriched in (15)N, (13)C, or (2)H. The bacterial expression systems currently in use to obtain isotopic enrichment, however, cannot produce a number of eukaryotic proteins, especially those that require post-translational modifications such as N-linked glycosylation for proper folding or activity. Here, we report the use of an adenovirus vector-based mammalian expression system to produce isotopically enriched (15)N or (15)N/(13)C samples of an outer domain variant of the HIV-1 gp120 envelope glycoprotein with 15 sites of N-linked glycosylation. Yields for the (15)N- and (15)N/(13)C-labeled gp120s after affinity chromatography were 45 and 44 mg/l, respectively, with an average of over 80% isotope incorporation. Recognition of the labeled gp120 by cognate antibodies that recognize complex epitopes showed affinities comparable to the unlabeled protein. NMR spectra, including (1)H-(15)N and (1)H-(13)C HSQCs, (15)N-edited NOESY-HSQC, and 3D HNCO, were of high quality, with signal-to-noise consistent with an efficient level of isotope incorporation, and with chemical shift dispersion indicative of a well-folded protein. The exceptional protein yields, good isotope incorporation, and ability to obtain well-folded post-translationally modified proteins make this mammalian system attractive for the production of isotopically enriched eukaryotic proteins for NMR spectroscopy.
C1 [Sastry, Mallika; Xu, Ling; Georgiev, Ivelin S.; Nabel, Gary J.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
FU NIH (NIAID); NIH (NIDDK)
FX We thank the NMR staff at the New York Structural Biology Consortium for
assistance with instrumentation. We also thank Mary Ann Gawinowicz of
the Protein Core Facility at Columbia University for N terminal
sequencing and mass spectrometry, L. Shapiro for editorial assistance
with the manuscript, and T. Waybright and T. Veenstra at the NCI for
assistance with mass spectral data acquisition. We also thank the
members of the structural biology and structural bioinformatics core
sections at the Vaccine Research Center for insightful comments and
discussions. Support for this work was provided by the Intramural
Program of the NIH (NIAID and NIDDK).
NR 47
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U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD JUL
PY 2011
VL 50
IS 3
BP 197
EP 207
DI 10.1007/s10858-011-9506-4
PG 11
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 791HV
UT WOS:000292656700002
PM 21667299
ER
PT J
AU Hu, KN
Qiang, W
Tycko, R
AF Hu, Kan-Nian
Qiang, Wei
Tycko, Robert
TI A general Monte Carlo/simulated annealing algorithm for resonance
assignment in NMR of uniformly labeled biopolymers
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Sequential assignment; Solid state NMR; Magic-angle spinning;
Multidimensional spectroscopy
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; IMMUNOGLOBULIN BINDING
DOMAIN; SPECTRIN SH3 DOMAIN; HUMAN PRION PROTEIN; ANGLE-SPINNING NMR;
HET-S PRION; AMYLOID FIBRILS; SIDE-CHAIN; BACKBONE RESONANCES
AB We describe a general computational approach to site-specific resonance assignments in multidimensional NMR studies of uniformly (15)N,(13)C-labeled biopolymers, based on a simple Monte Carlo/simulated annealing (MCSA) algorithm contained in the program MCASSIGN2. Input to MCASSIGN2 includes lists of multidimensional signals in the NMR spectra with their possible residue-type assignments (which need not be unique), the biopolymer sequence, and a table that describes the connections that relate one signal list to another. As output, MCASSIGN2 produces a high-scoring sequential assignment of the multidimensional signals, using a score function that rewards good connections (i.e., agreement between relevant sets of chemical shifts in different signal lists) and penalizes bad connections, unassigned signals, and assignment gaps. Examination of a set of high-scoring assignments from a large number of independent runs allows one to determine whether a unique assignment exists for the entire sequence or parts thereof. We demonstrate the MCSA algorithm using two-dimensional (2D) and three-dimensional (3D) solid state NMR spectra of several model protein samples (alpha-spectrin SH3 domain and protein G/B1 microcrystals, HET-s(218-289) fibrils), obtained with magic-angle spinning and standard polarization transfer techniques. The MCSA algorithm and MCASSIGN2 program can accommodate arbitrary combinations of NMR spectra with arbitrary dimensionality, and can therefore be applied in many areas of solid state and solution NMR.
C1 [Hu, Kan-Nian; Qiang, Wei; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
RI Qiang, Wei/I-1053-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases within
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases within
the National Institutes of Health. Computational facilities of the Helix
Systems at the National Institutes of Health were used in this work.
NR 36
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U1 0
U2 20
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD JUL
PY 2011
VL 50
IS 3
BP 267
EP 276
DI 10.1007/s10858-011-9517-1
PG 10
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 791HV
UT WOS:000292656700009
PM 21710190
ER
PT J
AU Johnson, RL
Hwang, JY
Arnold, LA
Huang, RL
Wichterman, J
Augustinaite, I
Austin, CP
Inglese, J
Guy, RK
Huang, WW
AF Johnson, Ronald L.
Hwang, Jong Yeon
Arnold, Leggy A.
Huang, Ruili
Wichterman, Jennifer
Augustinaite, Indre
Austin, Christopher P.
Inglese, James
Guy, R. Kiplin
Huang, Wenwei
TI A Quantitative High-Throughput Screen Identifies Novel Inhibitors of the
Interaction of Thyroid Receptor beta with a Peptide of Steroid Receptor
Coactivator 2
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE thyroid receptor; small molecule; HTS; coactivator; protein-protein
interaction
ID NUCLEAR HORMONE RECEPTORS; CO-REPRESSOR; SRC FAMILY; BINDING;
SUPERFAMILY; ANISOTROPY; LIBRARIES; ASSAY
AB The thyroid hormone receptors (TR) are members of the nuclear hormone receptor (NHR) superfamily that regulate development, growth, and metabolism. Upon ligand binding, TR releases bound corepressors and recruits coactivators to modulate target gene expression. Steroid receptor coactivator 2 (SRC2) is an important coregulator that interacts with TR beta to activate gene transcription. To identify novel inhibitors of the TR beta and SRC2 interaction, the authors performed a quantitative high-throughput screen (qHTS) of a TR beta-SRC2 fluorescence polarization assay against more than 290 000 small molecules. The qHTS assayed compounds at 6 concentrations up to 92 mu M to generate titration-response curves and determine the potency and efficacy of all compounds. The qHTS data set enabled the characterization of actives for structure-activity relationships as well as for potential artifacts such as fluorescence interference. Selected qHTS actives were tested in the screening assay using fluoroprobes labeled with Texas Red or fluorescein. The retest identified 19 series and 4 singletons as active in both assays with 40% or greater efficacy, free of compound interference, and not toxic to mammalian cells. Selected compounds were tested as independent samples, and a methylsulfonylnitrobenzoate series inhibited the TR beta-SRC2 interaction with 5 mu M IC(50). This series represents a new class of thyroid hormone receptor-coactivator modulators. (Journal of Biomolecular Screening 2011; 16: 618-627)
C1 [Johnson, Ronald L.; Huang, Ruili; Wichterman, Jennifer; Austin, Christopher P.; Inglese, James; Huang, Wenwei] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Hwang, Jong Yeon; Arnold, Leggy A.; Augustinaite, Indre; Guy, R. Kiplin] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA.
RP Johnson, RL (reprint author), NHGRI, Chem Genom Ctr, NIH, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM rjohnso2@mail.nih.gov
RI Guy, Rodney/J-7107-2013
OI Guy, Rodney/0000-0002-9638-2060
FU National Institutes of Health [DK58080]; NIH Roadmap for Medical
Research; National Human Genome Research Institute, National Institutes
of Health; American Lebanese Syrian Associated Charities; St. Jude
Children's Research Hospital
FX We thank Sam Michael for automation assistance, Paul Shinn and Danielle
Van Leer for compound management, Bill Leister, Chris LeClair, and
Jeremy Smith for analytical chemistry, Rajarshi Guha for informatics,
and Ryan MacArthur for preparation of three dimensional plots. This work
was supported by the National Institutes of Health (grant number
DK58080); the NIH Roadmap for Medical Research; the Intramural Research
Program of the National Human Genome Research Institute, National
Institutes of Health; the American Lebanese Syrian Associated Charities;
and St. Jude Children's Research Hospital.
NR 35
TC 7
Z9 7
U1 1
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JUL
PY 2011
VL 16
IS 6
BP 618
EP 627
DI 10.1177/1087057111402199
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 790DW
UT WOS:000292569700005
PM 21482722
ER
PT J
AU Greenhouse, B
Ho, B
Hubbard, A
Njama-Meya, D
Narum, DL
Lanar, DE
Dutta, S
Rosenthal, PJ
Dorsey, G
John, CC
AF Greenhouse, Bryan
Ho, Benjamin
Hubbard, Alan
Njama-Meya, Denise
Narum, David L.
Lanar, David E.
Dutta, Sheetij
Rosenthal, Philip J.
Dorsey, Grant
John, Chandy C.
TI Antibodies to Plasmodium falciparum Antigens Predict a Higher Risk of
Malaria But Protection From Symptoms Once Parasitemic
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID LIVER-STAGE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1; CLINICAL MALARIA;
HIGHLAND AREA; CIRCUMSPOROZOITE PROTEIN; VACCINE CANDIDATES;
ESCHERICHIA-COLI; UGANDAN CHILDREN; WESTERN KENYA; TRANSMISSION
AB Background. Associations between antibody responses to Plasmodium falciparum antigens and protection against symptomatic malaria have been difficult to ascertain, in part because antibodies are potential markers of both exposure to P. falciparum and protection against disease.
Methods. We measured IgG responses to P. falciparum circumsporozoite protein, liver-stage antigen 1, apical-membrane antigen 1 (AMA-1), and merozoite surface proteins (MSP) 1 and 3, in children in Kampala, Uganda, and measured incidence of malaria before and after antibody measurement.
Results. Stronger responses to all 5 antigens were associated with an increased risk of clinical malaria (P < .01) because of confounding with prior exposure to P. falciparum. However, with use of another assessment, risk of clinical malaria once parasitemic, stronger responses to AMA-1, MSP-1, and MSP-3 were associated with protection (odds ratios, 0.34, 0.36, and 0.31, respectively, per 10-fold increase; P < .01). Analyses assessing antibodies in combination suggested that any protective effect of antibodies was overestimated by associations between individual responses and protection.
Conclusions. Using the risk of symptomatic malaria once parasitemic as an outcome may improve detection of associations between immune responses and protection from disease. Immunoepidemiology studies designed to detect mechanisms of immune protection should integrate prior exposure into the analysis and evaluate multiple immune responses.
C1 [Greenhouse, Bryan; Rosenthal, Philip J.; Dorsey, Grant] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Hubbard, Alan] Univ Calif Berkeley, Div Biostat, Berkeley, CA 94720 USA.
[Ho, Benjamin; John, Chandy C.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Njama-Meya, Denise] Makerere Univ, Kampala, Uganda.
[Narum, David L.] NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA.
[Lanar, David E.; Dutta, Sheetij] Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD USA.
RP Greenhouse, B (reprint author), Univ Calif San Francisco, Dept Med, Box 0811, San Francisco, CA 94143 USA.
EM bgreenhouse@medsfgh.ucsf.edu
OI Greenhouse, Bryan/0000-0003-0287-9111
FU National Institute of Allergy and Infectious Disease (NIAID) [AI052142,
AI056270]; Doris Duke Charitable Foundation [2004047]; National
Institutes of Health, NIAID, Laboratory of Malaria Immunology and
Vaccinology
FX This work was supported by the National Institute of Allergy and
Infectious Disease (NIAID) (AI052142, AI056270) and the Doris Duke
Charitable Foundation (2004047). This work was funded in part by the
Intramural Research Program of the National Institutes of Health, NIAID,
Laboratory of Malaria Immunology and Vaccinology.
NR 50
TC 37
Z9 37
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 JUL 1
PY 2011
VL 204
IS 1
BP 19
EP 26
DI 10.1093/infdis/jir223
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790AV
UT WOS:000292561800005
PM 21628654
ER
PT J
AU Wentzensen, N
Rodriguez, AC
Viscidi, R
Herrero, R
Hildesheim, A
Ghosh, A
Morales, J
Wacholder, S
Guillen, D
Alfaro, M
Safaeian, M
Burk, RD
Schiffman, M
AF Wentzensen, Nicolas
Cecilia Rodriguez, Ana
Viscidi, Raphael
Herrero, Rolando
Hildesheim, Allan
Ghosh, Arpita
Morales, Jorge
Wacholder, Sholom
Guillen, Diego
Alfaro, Mario
Safaeian, Mahboobeh
Burk, Robert D.
Schiffman, Mark
TI A Competitive Serological Assay Shows Naturally Acquired Immunity to
Human Papillomavirus Infections in the Guanacaste Natural History Study
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID POPULATION-BASED COHORT; COSTA-RICA; TYPE-16; WOMEN; ANTIBODIES;
SEROPREVALENCE; NEUTRALIZATION; GARDASIL(R); RESPONSES; CANCER
AB Background. A competitive Luminex Immunoassay (cLIA) has been developed to measure neutralizing antibodies against human papillomavirus (HPV) types 6, 11, 16 and 18.
Methods. In a cohort of 974 women from the Guanacaste Natural History Study, we studied the relationship of baseline cLIA and virus-like particle (VLP) enzyme-linked immunosorbent assay (ELISA) (HPV16 and HPV18 only) seropositivity to measures of HPV exposure, HPV DNA positivity, number of sexual partners, cytology findings, and age. We then studied immunity against subsequent infection with HPV6, 11, 16, 18 and related types over a 7-year period.
Results. cLIA seroprevalence varied with previous exposure; the prevalence of cLIA results positive for HPV16 and HPV18 was lower than the prevalence of positive VLP ELISA responses. cLIA and VLP ELISA positivity predicted protection from subsequent infections with concordant types. The combined odds ratio for HPV16 and HPV18 cLIA positivity was 0.41 (95% confidence interval [CI], 0.21-0.80), and the combined odds ratio for the HPV16 and HPV18 VLP ELISA positivity was 0.65 (95% CI, 0.46-0.93). Of individual types, statistical significance was only reached for HPV16 cLIA positivity (odds ratio, 0.44; 95% CI, 0.15-0.94).
Conclusions. Both assays showed an association between positive results and significant protection from subsequent infections for HPV16 and HPV18 combined. cLIA seroprevalence was lower than VLP ELISA, suggesting that the assay detects a subset of antibodies following natural infection that are specifically linked to immunity against subsequent HPV infection.
C1 [Wentzensen, Nicolas; Hildesheim, Allan; Ghosh, Arpita; Wacholder, Sholom; Safaeian, Mahboobeh; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Viscidi, Raphael] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 5024, Rockville, MD 20852 USA.
EM wentzenn@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU NIH; National Cancer Institute
FX The Intramural Research Program of the NIH and the National Cancer
Institute.
NR 21
TC 32
Z9 32
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 JUL 1
PY 2011
VL 204
IS 1
BP 94
EP 102
DI 10.1093/infdis/jir209
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790AV
UT WOS:000292561800014
PM 21628663
ER
PT J
AU Chun, TW
Murray, D
Justement, JS
Hallahan, CW
Moir, S
Kovacs, C
Fauci, AS
AF Chun, Tae-Wook
Murray, Danielle
Justement, J. Shawn
Hallahan, Claire W.
Moir, Susan
Kovacs, Colin
Fauci, Anthony S.
TI Relationship Between Residual Plasma Viremia and the Size of HIV
Proviral DNA Reservoirs in Infected Individuals Receiving Effective
Antiretroviral Therapy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID INTENSIFICATION; GUT; REPLICATION; ACTIVATION; BURDEN
AB Residual plasma viremia (<50 copies/mL) persists in certain human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART); however, the relationship between the degree of residual plasma viremia, the size of HIV reservoirs, and the level of immune activation has not been delineated. Here, we demonstrate that residual plasma viremia correlates with the size of the CD4(+) T cell viral reservoir, but not with markers of immune activation, suggesting that reactivation of the latent viral reservoir may not be the sole source of residual plasma viremia. Novel therapeutic strategies aimed at targeting the source of residual viremia may be necessary to achieve viral eradication.
C1 [Chun, Tae-Wook; Murray, Danielle; Justement, J. Shawn; Moir, Susan; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Hallahan, Claire W.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Kovacs, Colin] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada.
RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A32,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twchun@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX The Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 15
TC 91
Z9 92
U1 1
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 JUL 1
PY 2011
VL 204
IS 1
BP 135
EP 138
DI 10.1093/infdis/jir208
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790AV
UT WOS:000292561800018
PM 21628667
ER
PT J
AU Lai, LL
Kwa, S
Kozlowski, PA
Montefiori, DC
Ferrari, G
Johnson, WE
Hirsch, V
Villinger, F
Chennareddi, L
Earl, PL
Moss, B
Amara, RR
Robinson, HL
AF Lai, Lilin
Kwa, SueFen
Kozlowski, Pamela A.
Montefiori, David C.
Ferrari, Guido
Johnson, Welkin E.
Hirsch, Vanessa
Villinger, Francois
Chennareddi, Lakshmi
Earl, Patricia L.
Moss, Bernard
Amara, Rama Rao
Robinson, Harriet L.
TI Prevention of Infection by a Granulocyte-Macrophage Colony-Stimulating
Factor Co-Expressing DNA/Modified Vaccinia Ankara Simian
Immunodeficiency Virus Vaccine
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID T-HELPER-CELL; MYELOID SUPPRESSOR-CELLS; TRACT DENDRITIC CELLS; GM-CSF
DNA; RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; CONTROL REPLICATION;
CONJUGATE VACCINES; HUMORAL IMMUNITY; TYPE-1 INFECTION
AB A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immunodeficiency virus (HIV) infections and a similar genetic distance from the SIV239 vaccine as intraclade HIV isolates. The heterologous prime-boost vaccine regimen used recombinant DNA for priming and recombinant modified vaccinia Ankara for boosting. Co-expression of GM-CSF in the DNA prime enhanced the avidity of elicited immunoglobulin G for SIV envelope glycoproteins, the titers of neutralizing antibody for easy-to-neutralize SIV isolates, and antibody-dependent cellular cytotoxicity. Impressively, the co-expressed GM-CSF increased vaccine-induced prevention of infection from 25% in the non-GM-CSF co-expressing vaccine group to 71% in the GM-CSF co-expressing vaccine group. The prevention of infection showed a strong correlation with the avidity of the elicited Env-specific antibody for the Env of the SIVsmE660 challenge virus (r = 0.9; P < .0001).
C1 [Robinson, Harriet L.] GeoVax Inc, GeoVax Labs, Smyrna, GA 30080 USA.
[Lai, Lilin; Kwa, SueFen; Villinger, Francois; Chennareddi, Lakshmi; Amara, Rama Rao] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Amara, Rama Rao] Emory Univ, Dept Microbiol & Immunol, Vaccine Res Ctr, Atlanta, GA 30322 USA.
[Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, Gene Therapy Program, New Orleans, LA USA.
[Montefiori, David C.; Ferrari, Guido] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27710 USA.
[Johnson, Welkin E.] Harvard Univ, New England Natl Primate Res Ctr, Southborough, MA USA.
[Hirsch, Vanessa; Earl, Patricia L.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Robinson, HL (reprint author), GeoVax Inc, GeoVax Labs, 1900 Lake Pk Dr,Ste 380, Smyrna, GA 30080 USA.
EM hrobinson@geovax.com
RI Ferrari, Guido/A-6088-2015
FU Integrated Preclinical/Clinical AIDS Vaccine Development program project
[5U19 AI074073]; NIH [AI30034, AI083118]; Emory University [CFAR P30
AI050409]; NCRR/NIH [P30 RR00165, 30 RR00168]
FX This research was supported by an Integrated Preclinical/Clinical AIDS
Vaccine Development program project 5U19 AI074073 (HLR), NIH grants
AI30034 (DCM) and AI083118 (WEJ), the Emory University CFAR P30 AI050409
and by NCRR/NIH base grants P30 RR00165(YNPRC) and P30 RR00168 (NEPRC)
NR 50
TC 60
Z9 60
U1 0
U2 3
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 JUL 1
PY 2011
VL 204
IS 1
BP 164
EP 173
DI 10.1093/infdis/jir199
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 790AV
UT WOS:000292561800022
PM 21628671
ER
PT J
AU Schwaninger, AE
Meyer, MR
Huestis, MA
Maurer, HH
AF Schwaninger, Andrea E.
Meyer, Markus R.
Huestis, Marilyn A.
Maurer, Hans H.
TI Development and validation of LC-HRMS and GC-NICI-MS methods for
stereoselective determination of MDMA and its phase I and II metabolites
in human urine
SO JOURNAL OF MASS SPECTROMETRY
LA English
DT Article
DE stereoselective method; MDMA; phase I metabolites; phase II metabolites;
urine
ID CHROMATOGRAPHY-MASS-SPECTROMETRY; DESIGNER DRUGS; MAIN METABOLITES;
3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; ENANTIOSELECTIVE MEASUREMENT;
STEREOCHEMICAL ANALYSIS; CLINICAL TOXICOLOGY; MDEA ENANTIOMERS;
AMPHETAMINE; MDA
AB 3,4-Methylenedioxymethamphetamine (MDMA) is a racemic drug of abuse and its R- and S-enantiomers are known to differ in their dose-response curve. The S-enantiomer was shown to be eliminated at a higher rate than the R-enantiomer most likely explained by stereoselective metabolism that was observed in various in vitro experiments. The aim of this work was the development and validation of methods for evaluating the stereoselective elimination of phase I and particularly phase II metabolites of MDMA in human urine. Urine samples were divided into three different methods. Method A allowed stereoselective determination of the 4-hydroxy-3-methoxymethamphetamine (HMMA) glucuronides and only achiral determination of the intact sulfate conjugates of HMMA and 3,4-dihydroxymethamphetamine (DHMA) after C18 solid-phase extraction by liquid chromatography-high-resolution mass spectrometry with electrospray ionization. Method B allowed the determination of the enantiomer ratios of DHMA and HMMA sulfate conjugates after selective enzymatic cleavage and chiral analysis of the corresponding deconjugated metabolites after chiral derivatization with S-heptafluorobutyrylprolyl chloride using gas chromatography-mass spectrometry with negative-ion chemical ionization. Method C allowed the chiral determination of MDMA and its unconjugated metabolites using method B without sulfate cleavage. The validation process including specificity, recovery, matrix effects, process efficiency, accuracy and precision, stabilities and limits of quantification and detection showed that all methods were selective, sensitive, accurate and precise for all tested analytes. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Schwaninger, Andrea E.; Meyer, Markus R.; Maurer, Hans H.] Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, Dept Expt & Clin Toxicol, D-66421 Homburg, Saar, Germany.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Maurer, HH (reprint author), Univ Saarland, Inst Expt & Clin Pharmacol & Toxicol, Dept Expt & Clin Toxicol, D-66421 Homburg, Saar, Germany.
EM hans.maurer@uks.eu
RI Meyer, Markus/B-9293-2009;
OI Steuer, Andrea Eva/0000-0001-8983-2353
FU Medical Faculty, Saarland University, Homburg
FX The authors would like to thank their colleagues Jessika Hunsicker,
Daniela Remane, Carsten Schroder, Gabriele Ulrich and Armin A. Weber,
and ThermoFisher Scientific for their helpful support. This work was
financially supported by HOMFOR 2010, the research fund of the Medical
Faculty, Saarland University, Homburg.
NR 38
TC 20
Z9 20
U1 1
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1076-5174
J9 J MASS SPECTROM
JI J. Mass Spectrom.
PD JUL
PY 2011
VL 46
IS 7
BP 603
EP 614
DI 10.1002/jms.1929
PG 12
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 790OK
UT WOS:000292598700001
PM 21656610
ER
PT J
AU Xu, Y
Okuda, M
Hser, YI
Hasin, D
Liu, SM
Grant, BF
Blanco, C
AF Xu, Yang
Okuda, Mayumi
Hser, Yih-Ing
Hasin, Deborah
Liu, Shang-Min
Grant, Bridget F.
Blanco, Carlos
TI Twelve-month prevalence of psychiatric disorders and treatment-seeking
among Asian Americans/Pacific Islanders in the United States: Results
from the National Epidemiological Survey on Alcohol and Related
Conditions
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Epidemiology; Psychiatric disorders; Asian American; Pacific Islanders;
Mental health; Treatment utilization
ID MENTAL-HEALTH-SERVICES; COMORBIDITY SURVEY REPLICATION; ETHNIC-MINORITY
GROUPS; DSM-IV DISORDERS; LOS-ANGELES; HELP-SEEKING; DEPRESSION;
AMERICAN; GENDER; PROGRAMS
AB To compare the 12-month prevalence of psychiatric disorders in Asian Americans/Pacific Islanders in contrast to non-Hispanic whites; and further compare persistence and treatment-seeking rates for psychiatric disorders among Asian American/Pacific Islanders and non-Hispanic whites, analyses from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, Wave 1 (n = 43,093) were conducted for the subsample of 1332 Asian Americans/Pacific Islanders (596 men and 736 women) and 24.507 non-Hispanic whites (10,845 men and 13,662 women). The past 12-month prevalence for any psychiatric disorder was significantly lower in Asian American/Pacific Islander males and females than non-Hispanic white males and females. Asian American/Pacific Islander males were less likely than non-Hispanic white males to have any mood, anxiety, substance use, and personality disorders, whereas the prevalence of mood disorders among Asian American/Pacific Islander females did not differ from those of non-Hispanic white females. In some cases, such as drug use disorders, both male and female Asian Americans/Pacific Islanders were more likely to have more persistent disorders than non-Hispanic whites. Compared to non-Hispanic white females, Asian American/Pacific Islander females had lower rates of treatment-seeking for any mood/anxiety disorders. Although less prevalent than among non-Hispanic whites, psychiatric disorders are not uncommon among Asian Americans/Pacific Islanders. The lower treatment-seeking rates for mood/anxiety disorders in Asian American/Pacific Islander females underscore the unmet needs for psychiatric service among this population. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Hasin, Deborah; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY 10032 USA.
[Xu, Yang; Okuda, Mayumi; Hasin, Deborah; Liu, Shang-Min; Blanco, Carlos] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hser, Yih-Ing] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90025 USA.
[Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
RP Blanco, C (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr,Unit 69, New York, NY 10032 USA.
EM cb255@columbia.edu
RI Blanco, Carlos/I-4906-2013; Okuda, Mayumi/L-6210-2013; Xu,
Yang/B-5543-2016
OI Blanco, Carlos/0000-0001-6187-3057; Okuda, Mayumi/0000-0002-3479-5599;
FU Pfizer; GlaxoSmithKline; NIH [DA019606, DA020783, DA023200, DA023973,
MH076051, P30DA016383, K05DA0176648]; American Foundation for Suicide
Prevention; New York State Psychiatric Institute; [AA014223-03]
FX Dr. Blanco has received research support from Pfizer and
GlaxoSmithKline. Drs. Xu, Okuda, Hser, Grant, and Hasin and Ms. Liu
report no competing interests.; Funding for this study was provided by
NIH grants DA019606, DA020783, DA023200, DA023973 and MH076051 (Dr.
Blanco), NIH grants P30DA016383 and K05DA0176648 (Dr. Hser), a grant
from the American Foundation for Suicide Prevention (Dr. Blanco),
AA014223-03 (Dr. Hasin), and the New York State Psychiatric Institute
(Drs. Blanco, Hasin).
NR 64
TC 11
Z9 11
U1 3
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD JUL
PY 2011
VL 45
IS 7
BP 910
EP 918
DI 10.1016/j.jpsychires.2010.12.009
PG 9
WC Psychiatry
SC Psychiatry
GA 791LY
UT WOS:000292667900008
PM 21238989
ER
PT J
AU Beesdo-Baum, K
Winkel, S
Pine, DS
Hoyer, J
Hofler, M
Lieb, R
Wittchen, HU
AF Beesdo-Baum, Katja
Winkel, Susanne
Pine, Daniel S.
Hoyer, Juergen
Hoefler, Michael
Lieb, Roselind
Wittchen, Hans-Ulrich
TI The diagnostic threshold of generalized anxiety disorder in the
community: A developmental perspective
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE DSM-5; Diagnostic criteria; Classification; Epidemiology; Community
study
ID DSM-III-R; COMORBIDITY SURVEY REPLICATION; MAJOR DEPRESSION;
MENTAL-DISORDERS; DURATION REQUIREMENT; SYMPTOM CRITERION; YOUNG-ADULTS;
RISK-FACTORS; SELF-REPORT; IV
AB Discussion surrounds the question as to whether criteria for generalized anxiety disorder (GAD) should change, particularly in youth. This study examines the effects of possible criteria changes on GAD prevalence and clinical correlates. DSM-IV GAD was assessed using the M-CIDI in a community sample of adolescents and young adults. Diagnostic thresholds were modified in two age spans (9-20 and 21-34 years) using a person-by-year data file (N = 38,534 cases). Relaxing the duration or excessiveness criteria led to the most pronounced changes in GAD prevalence, while relaxing frequency, uncontrollability, or associated-symptom criteria had smaller effects. A lower duration requirement increased rates more in older than younger age spans. Opposite effects occurred for changes in associated-symptoms or clinical-significance criteria. Broader GAD definitions identified cases in both age spans that appeared mostly milder than DSM-IV cases but that still differed from non-GAD cases in various clinical factors and validators. Developmental aspects require stronger consideration in future diagnostic systems. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Beesdo-Baum, Katja; Winkel, Susanne; Hoyer, Juergen; Hoefler, Michael; Wittchen, Hans-Ulrich] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01187 Dresden, Germany.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Lieb, Roselind] Univ Basel, Inst Psychol, Div Clin Psychol & Epidemiol, CH-4003 Basel, Switzerland.
[Lieb, Roselind; Wittchen, Hans-Ulrich] Max Planck Inst Psychiat, D-80804 Munich, Germany.
RP Beesdo-Baum, K (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Chemnitzer St 46, D-01187 Dresden, Germany.
EM beesdo@psychologie.tu-dresden.de
RI Beesdo-Baum, Katja/A-5793-2012; Wittchen, Hans-Ulrich/A-8507-2014;
Hoyer, Juergen/D-3619-2011;
OI Hoyer, Juergen/0000-0002-1697-6732; Wittchen,
Hans-Ulrich/0000-0002-6311-7711
FU German Federal Ministry of Education and Research (BMBF) [01EB9405/6,
01EB 9901/6, EB01016200, 01EB0140, 01EB0440]; Deutsche
Forschungsgemeinschaft (DFG) [LA1148/1-1, WI2246/1-1, WI 709/7-1, WI
709/8-1]
FX This work is part of the Early Developmental Stages of Psychopathology
(EDSP) Study which was funded by the German Federal Ministry of
Education and Research (BMBF) project no. 01EB9405/6, 01EB 9901/6,
EB01016200, 01EB0140, and 01EB0440. Part of the field work and analyses
were also additionally supported by grants of the Deutsche
Forschungsgemeinschaft (DFG) LA1148/1-1, WI2246/1-1, WI 709/7-1, and WI
709/8-1. The funding sources had no further role in study design, in the
collection, analysis and interpretation of data, in the writing of the
report, and in the decision to submit the paper for publication.
NR 62
TC 14
Z9 14
U1 6
U2 27
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD JUL
PY 2011
VL 45
IS 7
BP 962
EP 972
DI 10.1016/j.jpsychires.2010.12.007
PG 11
WC Psychiatry
SC Psychiatry
GA 791LY
UT WOS:000292667900015
PM 21227450
ER
PT J
AU Denisco, RC
Kenna, GA
O'Neil, MG
Kulich, RJ
Moore, PA
Kane, WT
Mehta, NR
Hersh, EV
Katz, NP
AF Denisco, Richard C.
Kenna, George A.
O'Neil, Michael G.
Kulich, Ronald J.
Moore, Paul A.
Kane, William T.
Mehta, Noshir R.
Hersh, Elliot V.
Katz, Nathaniel P.
TI Prevention of prescription opioid abuse The role of the dentist
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
DE Opioids; abuse; diversion; addiction; misuse; substance abuse; pain;
dentists
ID PAIN MEDICATION; SCHOOL-DISTRICT; NONMEDICAL USE; DENTAL PAIN;
DRUG-ABUSE; MANAGEMENT; IBUPROFEN; SURGERY; PATIENT
AB Background. Opioids are analgesics that have potential for misuse, abuse or addiction. Up to an estimated 23 percent of prescribed doses are used nonmedically. As prescribers of 12 percent of immediate-release (IR) opioids in the United States, dentists can minimize the potential for misuse or abuse.
Methods. The authors participated in a two-day meeting in March 2010 cohosted by Tufts Health Care Institute Program on Opioid Risk Management, Boston, and Tufts University School of Dental Medicine, Boston. The purpose of the meeting was to synthesize available opioid abuse literature and data from a 2010 survey regarding West Virginia dentists' analgesic prescribing practices, identify dentists' roles in prescribing opioids that are used nonmedically, highlight practices that dentists can implement and identify research gaps.
Results. Dentists can play a role in minimizing opioid abuse through patient education, careful patient assessment and referral for substance abuse treatment when indicated, and using tools such as prescription monitoring programs. Research is needed to determine the optimal number of doses needed to treat dental-related pain.
Conclusions. Dentists cannot assume that their prescribing of opioids does not affect the opioid abuse problem in the United States. The authors suggest that dentists, along with other prescribers, take steps to identify problems and minimize prescription opioid abuse through greater prescriber and patient education; use of peer-reviewed recommendations for analgesia; and, when indicated, the tailoring of the appropriate and legitimate prescribing of opioids to adequately treat pain.
Practice Implications. The authors encourage dentists to incorporate practical safeguards when prescribing opioids, consistently educate patients about how to secure unused opioids properly, screen patients for substance use disorders and develop a referral network for the treatment of substance use disorders.
C1 [Kenna, George A.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Denisco, Richard C.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, Rockville, MD USA.
[Kenna, George A.; Katz, Nathaniel P.] Tufts Hlth Care Inst Program Opioid Risk Manageme, Boston, MA USA.
[O'Neil, Michael G.] Univ Charleston, Sch Pharm, Ctr Excellence Educ & Prevent Drug Divers & Subst, Charleston, WV USA.
[Kulich, Ronald J.] Massachusetts Gen Hosp, Ctr Pain Med, Boston, MA 02114 USA.
[Kulich, Ronald J.] Harvard Univ, Sch Med, Boston, MA USA.
[Moore, Paul A.] Univ Pittsburgh, Sch Dent Med, Dept Dent Anesthesiol, Pittsburgh, PA 15260 USA.
[Kane, William T.] Missouri Dent Assoc Well Being Program, Jefferson City, MO USA.
[Mehta, Noshir R.] Tufts Univ, Sch Dent Med, Dept Gen Dent, Boston, MA 02111 USA.
[Mehta, Noshir R.] Tufts Univ, Sch Dent Med, Craniofacial Pain Ctr, Boston, MA 02111 USA.
[Hersh, Elliot V.] Univ Penn, Sch Dent Med, Div Pharmacol & Therapeut, Philadelphia, PA 19104 USA.
[Katz, Nathaniel P.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Katz, Nathaniel P.] Analges Solut, Natick, MA USA.
RP Kenna, GA (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02912 USA.
EM George_Kenna@Brown.edu
FU Endo Pharmaceuticals, Newark, Del.; Grunenthal, Aachen, Germany; King
Pharmaceuticals [now part of Pfizer, New York City]; Dominion
Diagnostics, North Kingstown, R.I.; Covdien, Dublin; Purdue Pharma,
Stamford, Conn.
FX The authors thank Amy Rosenstein, Rosemarie Curran, Rosalie Phillips and
Sarah Haile from the Tufts Health Care Institute for their
administrative support. In addition, the authors thank the supporters of
the Tufts Health Care Institute Program on Opioid Risk Management (Endo
Pharmaceuticals, Newark, Del.; Grunenthal, Aachen, Germany; King
Pharmaceuticals [now part of Pfizer, New York City]; Dominion
Diagnostics, North Kingstown, R.I.; Covdien, Dublin; and Purdue Pharma,
Stamford, Conn.) for their financial support of The Role of Dentists in
Preventing Opioid Abuse Meeting in March 2010, as well as Angela Casey
for her assistance in writing this article.
NR 80
TC 25
Z9 28
U1 0
U2 7
PU AMER DENTAL ASSOC
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD JUL
PY 2011
VL 142
IS 7
BP 800
EP 810
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 790HM
UT WOS:000292579100011
PM 21719802
ER
PT J
AU Shea, MK
Houston, DK
Tooze, JA
Davis, CC
Johnson, MA
Hausman, DB
Cauley, JA
Bauer, DC
Tylavsky, F
Harris, TB
Kritchevsky, SB
AF Shea, M. Kyla
Houston, Denise K.
Tooze, Janet A.
Davis, Cralen C.
Johnson, Mary Ann
Hausman, Dorothy B.
Cauley, Jane A.
Bauer, Douglas C.
Tylavsky, Frances
Harris, Tamara B.
Kritchevsky, Stephen B.
CA Hlth Aging Body Composition Study
TI Correlates and Prevalence of Insufficient 25-Hydroxyvitamin D Status in
Black and White Older Adults: The Health, Aging and Body Composition
Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE vitamin D; insufficiency; race; prevalence; determinants
ID VITAMIN-D INSUFFICIENCY; NUTRITION EXAMINATION SURVEY;
RANDOMIZED-CONTROLLED-TRIAL; 3RD NATIONAL-HEALTH; SERUM
25-HYDROXYVITAMIN-D; D DEFICIENCY; AFRICAN-AMERICANS; PLASMA
25-HYDROXYVITAMIN-D; ELDERLY POPULATION; HYPOVITAMINOSIS-D
AB OBJECTIVES: To determine the prevalence and correlates of vitamin D insufficiency in black and white older adults.
DESIGN: Cross-sectional.
SETTING: Health, Aging and Body Composition Study.
PARTICIPANTS: Nine hundred seventy-seven black and 1,604 white adults aged 70 to 81.
MEASUREMENTS: Logistic regression and classification and regression tree analysis were used to identify correlates of vitamin D insufficiency (25-hydroxyvitamin D (25(OH)D) <30 ng/mL) separately in blacks and whites.
RESULTS: The prevalence of 25(OH)D insufficiency was 84% in blacks and 57% in whites. Seventy-six percent of blacks and 56% of whites did not take a multivitamin; those who did not take a multivitamin were more likely to be vitamin D insufficient (odds ratio (OR) = 5.17 (95% confidence interval (CI) = 3.47-7.70) for blacks; OR = 2.56, 95% CI = 2.05-3.19 for white). Additional risk factors for vitamin D insufficiency were vitamin D-containing supplement use, female sex, and obesity in blacks; and winter season, low dietary vitamin D intake, obesity, type 2 diabetes mellitus, and female sex in whites.
CONCLUSION: Vitamin D insufficiency was more prevalent in blacks than whites. Not consuming a multivitamin increased the odds of vitamin D insufficiency in blacks and whites. Knowledge of additional risk factors such as dietary intake and comorbid conditions may help identify older adults who are likely to be vitamin D insufficient. J Am Geriatr Soc 59: 1165-1174, 2011.
C1 [Shea, M. Kyla] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Dept Internal Med,Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA.
[Johnson, Mary Ann; Hausman, Dorothy B.] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA.
[Cauley, Jane A.] Univ Pittsburgh, Div Epidemiol, Pittsburgh, PA USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Tylavsky, Frances] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Harris, Tamara B.] NIA, Bethesda, MD 20892 USA.
RP Shea, MK (reprint author), Wake Forest Univ, Sch Med, Sticht Ctr Aging, Dept Internal Med,Sect Gerontol & Geriatr Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM kshea@wfubmc.edu
OI Kritchevsky, Stephen/0000-0003-3336-6781; Cauley, Jane
A/0000-0003-0752-4408
FU Novartis; National Institute on Aging (NIA) [N01-AG-6-2101,
N01-AG-6-2103, N01-AG-6-2106, R01-AG029364]; Wake Forest University
Claude D. Pepper Older Americans Independence Center [P30-AG21332];
National Institutes of Health, NIA
FX DKH receives speaker honoraria from Abbott Nutrition Health Institute.
JAC receives grant support from Novartis (to study Zoledronic acid
treatment).; Health ABC was funded by the National Institute on Aging
(NIA; N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106). This work was
also supported by the NIA (R01-AG029364), the Wake Forest University
Claude D. Pepper Older Americans Independence Center (P30-AG21332), and
the Intramural Research Program of the National Institutes of Health,
NIA.
NR 48
TC 26
Z9 26
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUL
PY 2011
VL 59
IS 7
BP 1165
EP 1174
DI 10.1111/j.1532-5415.2011.03476.x
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 791VT
UT WOS:000292696100001
PM 21668915
ER
PT J
AU Sack, U
Walther, W
Scudiero, D
Selby, M
Kobelt, D
Lemm, M
Fichtner, I
Schlag, PM
Shoemaker, RH
Stein, U
AF Sack, Ulrike
Walther, Wolfgang
Scudiero, Dominic
Selby, Mike
Kobelt, Dennis
Lemm, Margit
Fichtner, Iduna
Schlag, Peter M.
Shoemaker, Robert H.
Stein, Ulrike
TI Novel Effect of Antihelminthic Niclosamide on S100A4-Mediated Metastatic
Progression in Colon Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
AB Background Metastasis formation in colon cancer severely reduces the survival rate in patients. S100A4, a calcium-binding protein, is implicated in promoting metastasis formation in colon cancer.
Methods To identify a transcription inhibitor of S100A4, high-throughput screening of 1280 pharmacologically active compounds was performed using a human colon cancer cell line expressing a S100A4 promoter-driven luciferase (LUC) reporter gene construct (HCT116-S1004p-LUC). Niclosamide, an antihelminthic agent, was identified as a potential candidate. Colon cancer cell lines (HCT116, SW620, LS174T, SW480, and DLD-1) were treated with 1 mu M niclosamide to analyze the effect on S100A4 mRNA and protein expression by quantitative reverse transcription-polymerase chain reaction and immunoblot assays, and effects on cell migration, invasion, proliferation, and colony formation were also assessed in vitro. The effect of niclosamide on liver metastasis was assessed in a xenograft mouse model of human colon cancer (n = 8 mice) by in vivo imaging. The long-term effect of niclosamide on metastasis formation after discontinued treatment was quantified by scoring, and overall survival (n = 12 mice) was analyzed by Kaplan-Meier method after discontinuation of treatment. All statistical tests were two-sided.
Results Reduced S100A4 mRNA and protein expression, and inhibited cell migration, invasion, proliferation, and colony formation were observed in niclosamide-treated colon cancer cells in vitro. In vivo imaging of niclosamide-treated mice showed reduced liver metastasis compared with solvent-treated control mice (n = 4 mice per group). Compared with the control group, discontinuation of treatment for 26 days showed reduced liver metastasis formation in mice (n = 6 mice per group) (control vs discontinuous treatment, mean metastasis score = 100% vs 34.9%, mean difference = 65.1%; 95% confidence interval [CI] = 18.4% to 111.9%, P<.01) and increased overall survival (n = 6 mice per group; control vs discontinuous treatment, median survival = 24 vs 46.5 days, ratio = 0.52, 95% CI = 0.19 to 0.84, P=.001).
Conclusion Niclosamide inhibits S100A4-induced metastasis formation in a mouse model of colon cancer and has therapeutic potential.
C1 [Walther, Wolfgang; Stein, Ulrike] Charite, Expt & Clin Res Ctr, Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
[Scudiero, Dominic; Selby, Mike; Shoemaker, Robert H.] Natl Canc Inst Frederick, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
[Schlag, Peter M.] Charite, Charite Comprehens Canc Ctr, D-13125 Berlin, Germany.
RP Sack, U (reprint author), Charite, Expt & Clin Res Ctr, Max Delbruck Ctr Mol Med, Robert Rossle St 10, D-13125 Berlin, Germany.
EM ustein@mdc-berlin.de
FU German Research Association [STE 671/8-1]; Alexander von Humboldt
Foundation; Max-Delbruck-Center for Molecular Medicine Helmholtz
Association
FX German Research Association (STE 671/8-1 to USt and PMS), the Alexander
von Humboldt Foundation (to USt and WW), and the Max-Delbruck-Center for
Molecular Medicine Helmholtz Association fellowship (to USa).
NR 40
TC 67
Z9 69
U1 1
U2 16
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 JUL
PY 2011
VL 103
IS 13
BP 1018
EP 1036
DI 10.1093/jnci/djr190
PG 19
WC Oncology
SC Oncology
GA 790BF
UT WOS:000292562800009
PM 21685359
ER
PT J
AU Petracci, E
Decarli, A
Schairer, C
Pfeiffer, RM
Pee, D
Masala, G
Palli, D
Gail, MH
AF Petracci, Elisabetta
Decarli, Adriano
Schairer, Catherine
Pfeiffer, Ruth M.
Pee, David
Masala, Giovanna
Palli, Domenico
Gail, Mitchell H.
TI Risk Factor Modification and Projections of Absolute Breast Cancer Risk
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
AB Background Although modifiable risk factors have been included in previous models that estimate or project breast cancer risk, there remains a need to estimate the effects of changes in modifiable risk factors on the absolute risk of breast cancer.
Methods Using data from a case-control study of women in Italy (2569 case patients and 2588 control subjects studied from June 1, 1991, to April 1, 1994) and incidence and mortality data from the Florence Registries, we developed a model to predict the absolute risk of breast cancer that included five non-modifiable risk factors (reproductive characteristics, education, occupational activity, family history, and biopsy history) and three modifiable risk factors (alcohol consumption, leisure physical activity, and body mass index). The model was validated using independent data, and the percent risk reduction was calculated in high-risk subgroups identified by use of the Lorenz curve.
Results The model was reasonably well calibrated (ratio of expected to observed cancers = 1.10, 95% confidence interval [CI] = 0.96 to 1.26), but the discriminatory accuracy was modest. The absolute risk reduction from exposure modifications was nearly proportional to the risk before modifying the risk factors and increased with age and risk projection time span. Mean 20-year reductions in absolute risk among women aged 65 years were 1.6% (95% CI = 0.9% to 2.3%) in the entire population, 3.2% (95% CI = 1.8% to 4.8%) among women with a positive family history of breast cancer, and 4.1% (95% CI = 2.5% to 6.8%) among women who accounted for the highest 10% of the total population risk, as determined from the Lorenz curve.
Conclusions These data give perspective on the potential reductions in absolute breast cancer risk from preventative strategies based on lifestyle changes. Our methods are also useful for calculating sample sizes required for trials to test lifestyle interventions.
C1 [Petracci, Elisabetta; Schairer, Catherine; Pfeiffer, Ruth M.; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Decarli, Adriano] Univ Milan, Dept Occupat Hlth, Branch Med Stat & Biometry, Milan, Italy.
[Decarli, Adriano] Fdn IRCSS Ist Nazl Tumori, Milan, Italy.
[Masala, Giovanna; Palli, Domenico] ISPO Canc Prevent & Res Inst, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Pee, David] Informat Management Serv Inc, Rockville, MD USA.
RP Petracci, E (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Plaza S,EPS 8049, Bethesda, MD 20892 USA.
EM elisa-betta.petracci@gmail.com; gailm@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011; Petracci, Elisabetta/K-1520-2016; Decarli,
Adriano/C-3129-2017;
OI Masala, Giovanna/0000-0002-5758-9069; Petracci,
Elisabetta/0000-0001-9456-3514; Decarli, Adriano/0000-0003-1451-8292;
PALLI, Domenico/0000-0002-5558-2437
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; Associazione Italiana per la Ricerca sul
Cancro [AIRC IG 10415]
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health and the Associazione Italiana per la
Ricerca sul Cancro (AIRC IG 10415 to A.D.).
NR 37
TC 28
Z9 28
U1 2
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JUL
PY 2011
VL 103
IS 13
BP 1037
EP 1048
DI 10.1093/jnci/djr172
PG 12
WC Oncology
SC Oncology
GA 790BF
UT WOS:000292562800010
PM 21705679
ER
PT J
AU Rizzo, G
Abuhamad, AZ
Benacerraf, BR
Chaoui, R
Corral, E
D' Addario, V
Espinoza, J
Lee, W
Alberto, LTM
Pooh, R
Sepulveda, W
Sinkovskaya, E
Vinals, F
Volpe, P
Pietrolucci, ME
Arduini, D
AF Rizzo, Giuseppe
Abuhamad, Alfred Z.
Benacerraf, Beryl R.
Chaoui, Rabih
Corral, Edgardo
D' Addario, Vincenzo
Espinoza, Jimmy
Lee, Wesley
Merce Alberto, Luis T.
Pooh, Ritsuko
Sepulveda, Waldo
Sinkovskaya, Elena
Vinals, Fernando
Volpe, Paolo
Pietrolucci, Maria Elena
Arduini, Domenico
TI Collaborative Study on 3-Dimensional Sonography for the Prenatal
Diagnosis of Central Nervous System Defects
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
DE congenital central nervous system defects; fetal neurosonography;
prenatal diagnosis; 3-dimensional sonography
ID FETAL-BRAIN; CORPUS-CALLOSUM; INTERNET LINK; NEUROSONOGRAPHY; ANOMALIES;
ROUTINE; VOLUMES; ECHOCARDIOGRAPHY; STANDARDIZATION; VISUALIZATION
AB Objectives-Prenatal diagnosis of central nervous system (CNS) anomalies by 2-dimensional sonography is challenging because of difficulties in obtaining complete visualization of the fetal brain during routine examinations, which is necessary for identification of its axial, coronal, and sagittal planes. Three-dimensional (3D) sonography has been introduced as a tool for studying the fetal CNS because of its ability to facilitate examinations of the fetal brain. The objective of this study was to determine inter-center agreement in diagnosing CNS defects by review of 3D volume data sets.
Methods-This study included 11 centers with expertise in 3D fetal neurosonography. A total of 217 fetuses with and without confirmed CNS defects were scanned after 18 weeks' gestation, and their volume data sets were uploaded onto a centralized file transfer protocol server and later analyzed by all of the centers. Intercenter agreement was determined using a kappa statistic for multiple raters.
Results-All volumes were made anonymous and sent to the centers for blinded analysis with the exception of the data sets they had themselves previously uploaded. For identification of fetuses with CNS defects, the sensitivity, specificity, positive and negative predictive values, and false-positive and -negative rates were 93.3%, 96.5%, 96.5%, 93.3%, 3.5%, and 6.7%, respectively. No differences were found in the efficacy of the diagnostic indices according to either the route of acquisition (transabdominal or transvaginal) or the gestational age at diagnosis (18-24 or >24 weeks). Intercenter agreement was excellent (kappa = 0.92; 95% confidence interval, 0.88-0.97).
Conclusions-Among centers with technical expertise, remote review of 3D sonographic volumes of the fetal CNS resulted in an accurate and reliable method for diagnosis of fetal brain malformations.
C1 [Rizzo, Giuseppe; Pietrolucci, Maria Elena; Arduini, Domenico] Univ Roma Tor Vergata, Dept Obstet & Gynecol, I-00186 Rome, Italy.
[Abuhamad, Alfred Z.; Sinkovskaya, Elena] Eastern Virginia Med Sch, Div Maternal Fetal Med, Dept Obstet & Gynecol, Norfolk, VA 23501 USA.
[Benacerraf, Beryl R.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA.
[Chaoui, Rabih] Prenatal Diag & Human Genet, Berlin, Germany.
[Corral, Edgardo; Sepulveda, Waldo] Univ Santiago Chile, San Jose Hosp, Maternal Fetal Med Unit, Dept Obstet & Gynecol, Santiago, Chile.
[D' Addario, Vincenzo] Univ Med Sch, Dept Gynecol Obstet & Neonatol, Bari, Italy.
[Espinoza, Jimmy; Lee, Wesley] William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48072 USA.
[Espinoza, Jimmy; Lee, Wesley] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
[Merce Alberto, Luis T.] Natl Ctr Ultrasonog Gynecol & Obstet, Madrid, Spain.
[Pooh, Ritsuko] CRIFM Clin Res Inst Fetal Med, Osaka, Japan.
[Vinals, Fernando] Clin Sanatorio Aleman, Ctr AGB Ultrasonog, Concepcion, Chile.
[Volpe, Paolo] Azienda Sanit Locale Bari, Di Venere & Sarcone Hosp, Fetal Med Unit, Bari, Italy.
RP Rizzo, G (reprint author), Univ Roma Tor Vergata, Dept Obstet & Gynecol, Fatebenefratelli S Giovanni Calabita Hosp, Isola Tiberina 89, I-00186 Rome, Italy.
EM giuseppe.rizzo@uniroma2.it
OI RIZZO, Giuseppe/0000-0002-5525-4353
NR 23
TC 13
Z9 13
U1 0
U2 2
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
USA
SN 0278-4297
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD JUL
PY 2011
VL 30
IS 7
BP 1003
EP 1008
PG 6
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 788HF
UT WOS:000292435300017
PM 21705734
ER
PT J
AU Katki, HA
Kinney, WK
Fetterman, B
Lorey, T
Poitras, NE
Cheung, L
Demuth, F
Schiffman, M
Wacholder, S
Castle, PE
AF Katki, Hormuzd A.
Kinney, Walter K.
Fetterman, Barbara
Lorey, Thomas
Poitras, Nancy E.
Cheung, Li
Demuth, Franklin
Schiffman, Mark
Wacholder, Sholom
Castle, Philip E.
TI Cervical cancer risk for women undergoing concurrent testing for human
papillomavirus and cervical cytology: a population-based study in
routine clinical practice
SO LANCET ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; INTRAEPITHELIAL NEOPLASIA; CONVENTIONAL
CYTOLOGY; SCREENING-TESTS; FOLLOW-UP; DNA; HPV; METAANALYSIS;
MANAGEMENT; PERSISTENCE
AB Background Concurrent testing for human papillomavirus (HPV) and cervical cytology (co-testing) is an approved alternative to cytology alone in women aged 30 years and older. We aimed to assess the safety in routine clinical practice of 3-year screening intervals for women testing negative for HPV with normal cytology and to assess if co-testing can identify women at high risk of cervical cancer or cervical intraepithelial neoplasia grade 3 (CIN3) or worse over 5 years.
Methods We assessed the 5-year cumulative incidence, starting in 2003-05, of cervical cancer and CIN3 or worse for 331 818 women aged 30 years and older who enrolled in co-testing at Kaiser Permanente Northern California (Berkeley, CA, USA) and had adequate enrolment co-test results. Follow-up continued until Dec 31, 2009. We defined cumulative incidence to include prevalence at enrolment and incidence after enrolment. Prevalence at enrolment was defined as the ratio of women diagnosed with each outcome on the biopsy visit immediately after their enrolment screening visit to the total enrolled women. At screening visits only HPV test and Pap smear samples were collected, and at biopsy visits colposcopically directed biopsies were taken. To estimate post-enrolment incidence, we used Weibull survival models.
Findings In 315 061 women negative by HPV testing, the 5-year cumulative incidence of cancer was 3.8 per 100 000 women per year, slightly higher than for the 306 969 who were both negative by HPV and Pap testing (3.2 per 100 000), and half the cancer risk of the 319 177 who were negative by Pap testing (7.5 per 100 000). 313 465 (99.5%) women negative by HPV testing had either normal cytology or equivocal abnormalities. Abnormal cytology greatly increased cumulative incidence of CIN3 or worse over 5 years for the 16 757 positive by HPV testing (12.1% vs 5.9%; p<0.0001). By contrast, although statistically significant, abnormal cytology did not increase 5-year risk of CIN3 or worse for women negative by HPV testing to a substantial level (0.86% vs 0.16%; p=0.004). 12 208 (73%) of the women positive by HPV testing had no cytological abnormality, and these women had 258 (35%) of 747 CIN3 or worse, 25 (29%) of 87 cancers, and 17 (63%) of 27 adenocarcinomas.
Interpretation For women aged 30 years and older in routine clinical practice who are negative by co-testing (both HPV and cytology), 3-year screening intervals were safe because a single negative test for HPV was sufficient to reassure against cervical cancer over 5 years. Incorporating HPV testing with cytology also resulted in earlier identification of women at high risk of cervical cancer, especially adenocarcinoma. Testing for HPV without adjunctive cytology might be sufficiently sensitive for primary screening for cervical cancer.
C1 [Katki, Hormuzd A.; Schiffman, Mark; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20882 USA.
[Kinney, Walter K.] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA.
[Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy E.] Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA.
[Cheung, Li; Demuth, Franklin] Informat Management Serv Inc, Silver Spring, MD USA.
[Castle, Philip E.] Amer Soc Clin Pathologists, Washington, DC USA.
RP Katki, HA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,Room 8014,EPS MSC 7244, Bethesda, MD 20882 USA.
EM katkih@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015;
OI Cheung, Li/0000-0003-1625-4331
FU NIH/National Cancer Institute; American Cancer Society (WKK); Women's
Health Research Institute at Kaiser Permanente Northern California; US
National Cancer Institute/NIH/DHHS; American Cancer Society
FX This research was supported, in part, by the Intramural Research Program
of the NIH/National Cancer Institute, and by the American Cancer Society
(WKK). The authors acknowledge the support of the Women's Health
Research Institute at Kaiser Permanente Northern California. We thank
David Check (US National Cancer Institute) for help in preparing the
figures. We thank J Thomas Cox (University of California, Santa Barbara)
for assisting with the chart review to verify all reported cervical
cancers.; Funding Intramural Research Program of the US National Cancer
Institute/NIH/DHHS, and the American Cancer Society.
NR 49
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U1 3
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUL
PY 2011
VL 12
IS 7
BP 663
EP 672
DI 10.1016/S1470-2045(11)70145-0
PG 10
WC Oncology
SC Oncology
GA 791CU
UT WOS:000292640200018
PM 21684207
ER
PT J
AU Fowke, JH
Gao, YT
Chow, WH
Cai, QY
Shu, XO
Li, HL
Ji, BT
Rothman, N
Yang, G
Chung, FL
Zheng, W
AF Fowke, Jay H.
Gao, Yu-Tang
Chow, Wong-Ho
Cai, Qiuyin
Shu, Xiao-Ou
Li, Hong-lan
Ji, Bu-Tian
Rothman, Nat
Yang, Gong
Chung, Fung-Lung
Zheng, Wei
TI Urinary isothiocyanate levels and lung cancer risk among non-smoking
women: A prospective investigation
SO LUNG CANCER
LA English
DT Article
DE Isothiocyanate; Lung neoplasm; Diet; Genetic susceptibility; Women
ID OXIDATIVE DNA-DAMAGE; CRUCIFEROUS VEGETABLES; DIETARY ISOTHIOCYANATES;
WATERCRESS CONSUMPTION; BRUSSELS-SPROUTS; NEVER SMOKERS; CELLS;
INDOLE-3-CARBINOL; POLYMORPHISMS; GLUTATHIONE
AB Background: Aside from tobacco carcinogen metabolism, isothiocyanates (ITC) from cruciferous vegetables may induce apoptosis or steroid metabolism to reduce lung cancer risk. To separate the effect of these divergent mechanisms of action, we investigated the association between urinary ITC levels and lung cancer risk among non-smoking women.
Methods: We conducted a nested case-control within the Shanghai Women's Health Study. Subjects included 209 incident lung cancer cases who never used tobacco, and 787 individually matched nonsmoking controls. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) summarizing the association between urinary ITC levels and lung cancer. Secondary analyses stratified the ITC-lung cancer analyses by menopausal status, exposure to environmental tobacco smoke, and GSTM1 and GSTT1 genotypes.
Results: Urinary ITC levels were not significantly associated with lower lung cancer risk among nonsmoking women, regardless of exposure to environmental tobacco smoke or menopausal status. Furthermore, this association was not modified by GSTT1 genotype. However, an inverse association was suggested among women with a GSTM1-positive genotype (Q1: OR = 1.0 (reference); Q2: OR = 0.35 (0.14, 0.89); Q3: OR = 0.47 (0.20, 1.10); Q4: OR = 0.63 (0.35, 1.54), p-trend = 0.38). In contrast, lung cancer risk was positively associated with urinary ITC levels among women with the GSTM1-null genotype (Q1: OR = 1.0 (reference); Q2: OR = 1.67 (0.80, 3.50); Q3: OR = 1.54 (0.71, 3.33); Q4: OR = 2.22 (1.05, 4.67), p-trend = 0.06).
Conclusion: Urinary ITC levels were not associated overall with lower lung cancer risk among non-smoking women, but secondary analyses suggested an interaction between urinary ITC levels, GSTM1 genotype, and lung cancer risk. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Fowke, Jay H.; Cai, Qiuyin; Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.
[Gao, Yu-Tang; Li, Hong-lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Chow, Wong-Ho; Ji, Bu-Tian; Rothman, Nat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Chung, Fung-Lung] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Fowke, JH (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, 2525 W End Ave,6th Floor,Suite 600, Nashville, TN 37203 USA.
EM jay.fowke@vanderbilt.edu
FU USPHS [R37 CA70867]
FX Funding provided by USPHS Grant R37 CA70867.
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U1 0
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD JUL
PY 2011
VL 73
IS 1
BP 18
EP 24
DI 10.1016/j.lungcan.2010.10.024
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 788KH
UT WOS:000292443300003
PM 21122939
ER
PT J
AU Kuntz, KM
Lansdorp-Vogelaar, I
Rutter, CM
Knudsen, AB
van Ballegooijen, M
Savarino, JE
Feuer, EJ
Zauber, AG
AF Kuntz, Karen M.
Lansdorp-Vogelaar, Iris
Rutter, Carolyn M.
Knudsen, Amy B.
van Ballegooijen, Marjolein
Savarino, James E.
Feuer, Eric J.
Zauber, Ann G.
TI A Systematic Comparison of Microsimulation Models of Colorectal Cancer:
The Role of Assumptions about Adenoma Progression
SO MEDICAL DECISION MAKING
LA English
DT Article
DE microsimulation; colorectal cancer; screening
ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; COST-EFFECTIVENESS
ANALYSIS; SERVICES TASK-FORCE; LARGE-INTESTINE; LARGE-BOWEL; CLINICAL
GUIDELINES; MEDICARE POPULATION; POLYPS; AUTOPSY
AB Background. As the complexity of microsimulation models increases, concerns about model transparency are heightened. Methods. The authors conducted model "experiments" to explore the impact of variations in "deep" model parameters using 3 colorectal cancer (CRC) models. All natural history models were calibrated to match observed data on adenoma prevalence and cancer incidence but varied in their underlying specification of the adenocarcinoma process. The authors projected CRC incidence among individuals with an underlying adenoma or preclinical cancer v. those without any underlying condition and examined the impact of removing adenomas. They calculated the percentage of simulated CRC cases arising from adenomas that developed within 10 or 20 years prior to cancer diagnosis and estimated dwell time-defined as the time from the development of an adenoma to symptom-detected cancer in the absence of screening among individuals with a CRC diagnosis. Results. The 20-year CRC incidence among 55-year-old individuals with an adenoma or preclinical cancer was 7 to 75 times greater than in the condition-free group. The removal of all adenomas among the subgroup with an underlying adenoma or cancer resulted in a reduction of 30% to 89% in cumulative incidence. Among CRCs diagnosed at age 65 years, the proportion arising from adenomas formed within 10 years ranged between 4% and 67%. The mean dwell time varied from 10.6 to 25.8 years. Conclusions. Models that all match observed data on adenoma prevalence and cancer incidence can produce quite different dwell times and very different answers with respect to the effectiveness of interventions. When conducting applied analyses to inform policy, using multiple models provides a sensitivity analysis on key (unobserved) "deep" model parameters and can provide guidance about specific areas in need of additional research and validation.
C1 [Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN 55455 USA.
[Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
[Rutter, Carolyn M.; Savarino, James E.] Grp Hlth Res Inst, Ctr Hlth Studies, Seattle, WA USA.
[Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
RP Kuntz, KM (reprint author), Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, MMC 729,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM kmkuntz@umn.edu
FU National Cancer Institute [U01-CA-088204, U01-CA-097426, U01-CA-097427,
U01-CA-115953]
FX Received 15 January 2009 from the Division of Health Policy and
Management, School of Public Health, University of Minnesota,
Minneapolis (KMK); Department of Public Health, Erasmus MC, Rotterdam,
the Netherlands (IL-V, MvB); Center for Health Studies, Group Health
Research Institute, Seattle, Washington (CMR, JES); Institute for
Technology Assessment, Massachusetts General Hospital, Boston (ABK);
Division of Cancer Control and Population Sciences, National Cancer
Institute, Bethesda, Maryland (EJF); and Department of Epidemiology and
Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
(AGZ). This research was supported by the National Cancer Institute
(U01-CA-088204, U01-CA-097426, U01-CA-097427, and U01-CA-115953).
Revision accepted for publication 5 April 2011.
NR 48
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U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD JUL-AUG
PY 2011
VL 31
IS 4
BP 530
EP 539
DI 10.1177/0272989X11408730
PG 10
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 792HL
UT WOS:000292732800004
PM 21673186
ER
PT J
AU van Ballegooijen, M
Rutter, CM
Knudsen, AB
Zauber, AG
Savarino, JE
Lansdorp-Vogelaar, I
Boer, R
Feuer, EJ
Habbema, JDF
Kuntz, KM
AF van Ballegooijen, Marjolein
Rutter, Carolyn M.
Knudsen, Amy B.
Zauber, Ann G.
Savarino, James E.
Lansdorp-Vogelaar, Iris
Boer, Rob
Feuer, Eric J.
Habbema, J. Dik F.
Kuntz, Karen M.
TI Clarifying Differences in Natural History between Models of Screening:
The Case of Colorectal Cancer
SO MEDICAL DECISION MAKING
LA English
DT Article
DE microsimulation; natural history; colorectal cancer; screening models;
standard model output
ID SOCIETY-TASK-FORCE; COST-EFFECTIVENESS; DECISION-ANALYSIS; COLONOGRAPHY;
SURVEILLANCE; STRATEGIES
AB Background. Microsimulation models are important decision support tools for screening. However, their complexity makes them difficult to understand and limits realization of their full potential. Therefore, it is important to develop documentation that clarifies their structure and assumptions. The authors demonstrate this problem and explore a solution for natural history using 3 independently developed colorectal cancer screening models. Methods. The authors first project effectiveness and cost-effectiveness of colonoscopy screening for the 3 models (CRC-SPIN, SimCRC, and MISCAN). Next, they provide a conventional presentation of each model, including information on structure and parameter values. Finally, they report the simulated reduction in clinical cancer incidence following a one-time complete removal of adenomas and preclinical cancers for each model. They call this new measure the maximum clinical incidence reduction (MCLIR). Results. Projected effectiveness varies widely across models. For example, estimated mortality reduction for colonoscopy screening every 10 years from age 50 to 80 years, with surveillance in adenoma patients, ranges from 65% to 92%. Given only conventional information, it is difficult to explain these differences, largely because differences in structure make parameter values incomparable. In contrast, the MCLIR clearly shows the impact of model differences on the key feature of natural history, the dwell time of preclinical disease. Dwell times vary from 8 to 25 years across models and help explain differences in projected screening effectiveness. Conclusions. The authors propose a new measure, the MCLIR, which summarizes the implications for predicted screening effectiveness of differences in natural history assumptions. Including the MCLIR in the standard description of a screening model would improve the transparency of these models.
C1 [van Ballegooijen, Marjolein; Lansdorp-Vogelaar, Iris; Boer, Rob; Habbema, J. Dik F.] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands.
[Rutter, Carolyn M.; Savarino, James E.] Grp Hlth Res Inst, Seattle, WA USA.
[Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Washington, DC USA.
[Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA.
RP van Ballegooijen, M (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM m.vanballegooijen@erasmusmc.nl
RI Boer, Rob/E-6473-2015
OI Boer, Rob/0000-0003-0680-001X
FU National Institutes of Health/National Cancer Institute [U01-CA-088204,
U01-CA-097427, U01-CA-097426, U01-CA-115953]
FX Received 18 July 2010 from the Department of Public Health, Erasmus MC,
Rotterdam, the Netherlands (MvB, IL-V, RB, JDFH); Group Health Research
Institute, Seattle, Washington (CMR, JES); Institute for Technology
Assessment, Massachusetts General Hospital, Boston (ABK); Department of
Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center,
New York, New York (AGZ); Division of Cancer Control and Population
Sciences, National Cancer Institute, Washington, DC (EJF); and Division
of Health Policy and Management, School of Public Health, University of
Minnesota, Minneapolis (KMK). This work was supported by the National
Institutes of Health/National Cancer Institute (U01-CA-088204,
U01-CA-097427, U01-CA-097426, and U01-CA-115953). Revision accepted for
publication 4 April 2011.
NR 24
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U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD JUL-AUG
PY 2011
VL 31
IS 4
BP 540
EP 549
DI 10.1177/0272989X11408915
PG 10
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 792HL
UT WOS:000292732800005
PM 21673187
ER
PT J
AU Shogan, PJ
Folio, L
AF Shogan, Paul J.
Folio, Les
TI Situs Inversus Totalis
SO MILITARY MEDICINE
LA English
DT Article
ID CONGENITAL HEART-DISEASE; VISCEROATRIAL SITUS; ADULTS
AB We present a case of situs inversus totalis. A 22-month-old infant presented with cyanosis, double-inlet left ventricle, severe pulmonary stenosis, and concern for underlying visceroatrial abnormalities. Chest (Fig. 1) and abdominal (Fig. 2) radiographs were obtained. Abdominal sonography was performed to clarify the presence of splenic tissue and further define the relationships of the inferior vena cava and abdominal aorta (Figs. 3-7). This case demonstrates typical radiographic and sonographic findings of situs inversus totalis and shows the utility of sonography.
C1 [Shogan, Paul J.] Walter Reed Army Med Ctr, Dept Radiol, Natl Capital Consortium, Washington, DC 20307 USA.
[Shogan, Paul J.] Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA.
[Folio, Les] NIH, Bethesda, MD 20892 USA.
RP Shogan, PJ (reprint author), Walter Reed Army Med Ctr, Dept Radiol, Natl Capital Consortium, Washington, DC 20307 USA.
NR 7
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U1 0
U2 0
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
J9 MIL MED
JI Milit. Med.
PD JUL
PY 2011
VL 176
IS 7
BP 840
EP 843
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 792XO
UT WOS:000292783900018
PM 22128729
ER
PT J
AU Yap, MN
Bernstein, HD
AF Yap, Mee-Ngan
Bernstein, Harris D.
TI The translational regulatory function of SecM requires the precise
timing of membrane targeting
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID SIGNAL RECOGNITION PARTICLE; ESCHERICHIA-COLI; PROTEIN-TRANSLOCATION;
DEPENDENT TRANSLOCATION; CYTOPLASMIC MEMBRANE; NASCENT POLYPEPTIDE;
TRIGGER FACTOR; A-SITE; EXPORT; SECRETION
AB In Escherichia coli, secA expression is regulated at the translational level by an upstream gene (secM) that encodes a presecretory protein. SecM contains a C-terminal sequence motif that induces a transient translation arrest. Inhibition of SecM membrane targeting prolongs the translation arrest and increases SecA synthesis by concomitantly altering the structure of the secM-secA mRNA. Here we show that the SecM signal peptide plays an essential role in this regulatory process by acting as a molecular timer that co-ordinates membrane targeting with the synthesis of the arrest motif. We found that signal peptide mutations that alter targeting kinetics and insertions or deletions that change the distance between the SecM signal peptide and the arrest motif perturb the balance between the onset and release of arrest that is required to regulate SecA synthesis. Furthermore, we found that the strength of the interaction between the ribosome and the SecM arrest motif is calibrated to ensure the release of arrest upon membrane targeting. Our results strongly suggest that several distinctive features of the SecM protein evolved as a consequence of constraints imposed by the ribosome and the Sec machinery.
C1 [Yap, Mee-Ngan; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases; NIH
[GM094212]
FX We thank Yihong Ye for critical reading of the manuscript. We also thank
Wanyoike Kang'ethe, Don Oliver and P. C. Tai for providing antisera.
This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and by
an NIH K99/R00 award (GM094212) to M.-N.Y.
NR 48
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U1 3
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD JUL
PY 2011
VL 81
IS 2
BP 540
EP 553
DI 10.1111/j.1365-2958.2011.07713.x
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 790CX
UT WOS:000292567200019
PM 21635582
ER
PT J
AU Beylin, D
Chrisman, CJ
Weingarten, M
AF Beylin, David
Chrisman, Cara J.
Weingarten, Michael
TI Granting you success
SO NATURE BIOTECHNOLOGY
LA English
DT Editorial Material
C1 [Beylin, David; Chrisman, Cara J.; Weingarten, Michael] NCI, Small Business Innovat Res Dev Ctr, Bethesda, MD 20892 USA.
RP Beylin, D (reprint author), NCI, Small Business Innovat Res Dev Ctr, Bethesda, MD 20892 USA.
EM ncisbir@mail.nih.gov
NR 0
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U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUL
PY 2011
VL 29
IS 7
BP 567
EP 570
DI 10.1038/bioe.2011.5
PG 4
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 790NM
UT WOS:000292595200008
PM 21874663
ER
PT J
AU Klesges, RC
Ebbert, JO
Morgan, GD
Sherrill-Mittleman, D
Asfar, T
Talcott, WG
DeBon, M
AF Klesges, Robert C.
Ebbert, Jon O.
Morgan, Glen D.
Sherrill-Mittleman, Deborah
Asfar, Taghrid
Talcott, Wayne G.
DeBon, Margaret
TI Impact of Differing Definitions of Dual Tobacco Use: Implications for
Studying Dual Use and a Call for Operational Definitions
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID SMOKELESS-TOBACCO; NORTHERN SWEDEN; NICOTINE DEPENDENCE;
CIGARETTE-SMOKING; CANCER MORTALITY; POLYTOBACCO USE; RISK BEHAVIORS;
HARM REDUCTION; CONCURRENT USE; SNUFF USE
AB Concomitant use of two forms of tobacco is an increasing public health concern, yet there is little consensus regarding a consistent definition of so-called "dual use." We defined dual use as cigarette and smokeless tobacco (ST) consumption with either product used daily or nondaily.
We analyzed a cohort of 36,013 Air Force recruits. We categorized dual tobacco use across 2 dimensions, type of tobacco products (cigarettes, ST, or others), and the frequency of use (daily vs. nondaily). We determined how varying the definition impacted the prevalence estimates and evaluated the prevalence estimate based on our recommended definition of dual use. Multivariate logistic regression analysis was used to evaluate the risk profile of dual users of ST and cigarettes versus mono users of ST and mono users of cigarettes.
Varying definitions of dual use vary prevalence estimates 50-fold (0.5%-25.3%). Including only ST and cigarettes narrows the prevalence estimate to less than 4-fold (2.0%-9.7%). Dual users are more likely to be young Caucasian males, with lower education, and from families with relatively higher incomes. Compared with mono users, dual users of cigarettes and ST have a distinct pattern of risk profiles.
Depending on the definition of dual use, markedly different prevalence and risk profiles are observed. Dual users of ST and cigarettes are a unique group of tobacco users. We propose a common definition of dual use to advance our understanding of this unique group.
C1 [Klesges, Robert C.; Talcott, Wayne G.; DeBon, Margaret] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38105 USA.
[Klesges, Robert C.; Sherrill-Mittleman, Deborah; Asfar, Taghrid] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
[Ebbert, Jon O.] Mayo Clin, Div Primary Care Internal Med, Rochester, MN USA.
[Morgan, Glen D.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Klesges, RC (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, 66 N Pauline,Suite 633, Memphis, TN 38105 USA.
EM bob.klesges@stjude.org
FU National Cancer Institute [CA127964]; National Heart, Lung, and Blood
Institute [HL053478]
FX This work was supported by research grants (CA127964) from the National
Cancer Institute and from the National Heart, Lung, and Blood Institute
(HL053478).
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD JUL
PY 2011
VL 13
IS 7
BP 523
EP 531
DI 10.1093/ntr/ntr032
PG 9
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 790CI
UT WOS:000292565700003
PM 21436298
ER
PT J
AU Eddy, J
Vallur, AC
Varma, S
Liu, HF
Reinhold, WC
Pommier, Y
Maizels, N
AF Eddy, Johanna
Vallur, Aarthy C.
Varma, Sudir
Liu, Hongfang
Reinhold, William C.
Pommier, Yves
Maizels, Nancy
TI G4 motifs correlate with promoter-proximal transcriptional pausing in
human genes
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA-POLYMERASE-II; TOPOISOMERASE-I; G-QUADRUPLEX; BINDING SPECIFICITY;
GENOMIC INSTABILITY; ESCHERICHIA-COLI; EUKARYOTIC CELLS; 1ST INTRON;
DNA; SEQUENCE
AB The RNA Pol II transcription complex pauses just downstream of the promoter in a significant fraction of human genes. The local features of genomic structure that contribute to pausing have not been defined. Here, we show that genes that pause are more G-rich within the region flanking the transcription start site (TSS) than RefSeq genes or non-paused genes. We show that enrichment of binding motifs for common transcription factors, such as SP1, may account for G-richness upstream but not downstream of the TSS. We further show that pausing correlates with the presence of a GrIn1 element, an element bearing one or more G4 motifs at the 5'-end of the first intron, on the non-template DNA strand. These results suggest potential roles for dynamic G4 DNA and G4 RNA structures in cis-regulation of pausing, and thus genome-wide regulation of gene expression, in human cells.
C1 [Eddy, Johanna; Maizels, Nancy] NCI, Mol & Cellular Biol Grad Program, NIH, Bethesda, MD 20892 USA.
[Vallur, Aarthy C.; Maizels, Nancy] NCI, Dept Immunol, NIH, Bethesda, MD 20892 USA.
[Varma, Sudir; Liu, Hongfang; Reinhold, William C.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Hongfang] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Seattle, WA 98195 USA.
[Maizels, Nancy] Univ Washington, Dept Biochem, Sch Med, Seattle, WA 98195 USA.
RP Maizels, N (reprint author), Univ Washington, Dept Immunol, Sch Med, Box 357650, Seattle, WA 98195 USA.
EM maizels@u.washington.edu
RI Varma, Sudhir/N-8763-2014
OI Varma, Sudhir/0000-0002-4096-4782
FU US National Cancer Institute [P01 CA77852]; Basic and Cancer Immunology
Training Grant [CA009537]; US National Institutes of Health [R01
GM41712]; NIH [R01 GM65988]; Cancer Research Institute; National Cancer
Institute, Center for Cancer Research [Z01 BC 006150-19LMP]
FX US National Cancer Institute (P01 CA77852 to N.M.); Basic and Cancer
Immunology Training Grant (CA009537 to J.E.); US National Institutes of
Health (R01 GM41712 and NIH R01 GM65988 to N.M.); Cancer Research
Institute Tumor Immunology Predoctoral Training Grant (to J.E.);
Intramural Research Program of the National Cancer Institute, Center for
Cancer Research support (Z01 BC 006150-19LMP to Y.P. and W.C.R.).
Funding for open access charge: P01 NCI CA77852.
NR 47
TC 38
Z9 39
U1 1
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2011
VL 39
IS 12
BP 4975
EP 4983
DI 10.1093/nar/gkr079
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 790CA
UT WOS:000292564900014
PM 21371997
ER
PT J
AU Reyes, A
He, J
Mao, CC
Bailey, LJ
Di Re, M
Sembongi, H
Kazak, L
Dzionek, K
Holmes, JB
Cluett, TJ
Harbour, ME
Fearnley, IM
Crouch, RJ
Conti, MA
Adelstein, RS
Walker, JE
Holt, IJ
AF Reyes, A.
He, J.
Mao, C. C.
Bailey, L. J.
Di Re, M.
Sembongi, H.
Kazak, L.
Dzionek, K.
Holmes, J. B.
Cluett, T. J.
Harbour, M. E.
Fearnley, I. M.
Crouch, R. J.
Conti, M. A.
Adelstein, R. S.
Walker, J. E.
Holt, I. J.
TI Actin and myosin contribute to mammalian mitochondrial DNA maintenance
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID II-B; NUCLEOIDS; PROTEIN; MEMBRANE; ORGANIZATION; CYTOSKELETON; CELLS;
IDENTIFICATION; LOCALIZATION; MACHINERY
AB Mitochondrial DNA maintenance and segregation are dependent on the actin cytoskeleton in budding yeast. We found two cytoskeletal proteins among six proteins tightly associated with rat liver mitochondrial DNA: non-muscle myosin heavy chain IIA and beta-actin. In human cells, transient gene silencing of MYH9 (encoding non-muscle myosin heavy chain IIA), or the closely related MYH10 gene (encoding non-muscle myosin heavy chain IIB), altered the topology and increased the copy number of mitochondrial DNA; and the latter effect was enhanced when both genes were targeted simultaneously. In contrast, genetic ablation of non-muscle myosin IIB was associated with a 60% decrease in mitochondrial DNA copy number in mouse embryonic fibroblasts, compared to control cells. Gene silencing of beta-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some beta-actin and non-muscle myosin heavy chain IIA reside within human mitochondria and confirm that they are associated with mitochondrial DNA. Collectively, these results strongly implicate the actomyosin cytoskeleton in mammalian mitochondrial DNA maintenance.
C1 [Reyes, A.; He, J.; Mao, C. C.; Bailey, L. J.; Di Re, M.; Sembongi, H.; Kazak, L.; Dzionek, K.; Holmes, J. B.; Cluett, T. J.; Fearnley, I. M.; Walker, J. E.; Holt, I. J.] MRC, Mitochondrial Biol Unit, Cambridge, England.
[Holmes, J. B.; Crouch, R. J.] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Harbour, M. E.] Cambridge Inst Med Res, Cambridge, England.
[Conti, M. A.; Adelstein, R. S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Holt, IJ (reprint author), MRC, Mitochondrial Biol Unit, Cambridge, England.
EM holt@mrc-mbu.cam.ac.uk
OI Adelstein, Robert/0000-0002-8683-2144
FU Medical Research Council; European Union; Eunice Kennedy Shriver
National Institute of Child Health and Human Development and National
Heart; Chang Gung Memorial Hospital, Lin-Kou, Taiwan [CMRPG360491-2,
380651, NSC 97-2321-B-182A-002-MY2]
FX Medical Research Council; the European Union; the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development and National Heart; Lung and Blood Institute;
National Institutes of Health and grants [CMRPG360491-2, 380651, NSC
97-2321-B-182A-002-MY2] from the Chang Gung Memorial Hospital, Lin-Kou,
Taiwan (to C.C.M.). Funding for open access charge: Medical Research
Council.
NR 32
TC 34
Z9 37
U1 2
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2011
VL 39
IS 12
BP 5098
EP 5108
DI 10.1093/nar/gkr052
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 790CA
UT WOS:000292564900023
PM 21398640
ER
PT J
AU Kang, HS
Okamoto, K
Takeda, Y
Beak, JY
Gerrish, K
Bortner, CD
DeGraff, LM
Wada, T
Xie, W
Jetten, AM
AF Kang, Hong Soon
Okamoto, Kyoko
Takeda, Yukimasa
Beak, Ju Youn
Gerrish, Kevin
Bortner, Carl D.
DeGraff, Laura M.
Wada, Taira
Xie, Wen
Jetten, Anton M.
TI Transcriptional profiling reveals a role for ROR alpha in regulating
gene expression in obesity-associated inflammation and hepatic steatosis
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE staggerer mice; obesity; metabolic syndrome; macrophage;
insulin-resistance; diabetes; retinoid-related orphan receptors
ID ORPHAN NUCLEAR RECEPTOR; DIET-INDUCED OBESITY; INDUCED LUNG
INFLAMMATION; ADIPOSE-TISSUE; DEFICIENT MICE; INSULIN SENSITIVITY;
ENERGY-EXPENDITURE; RETINOIC ACID; ADIPOCYTE DIFFERENTIATION; MACROPHAGE
ACCUMULATION
AB Retinoid-related orphan receptor (ROR)alpha 4 is the major ROR alpha isoform expressed in adipose tissues and liver. In this study we demonstrate that ROR alpha-deficient staggerer mice (ROR alpha(sg/sg)) fed with a high-fat diet (HFD) exhibited reduced adiposity and hepatic triglyceride levels compared with wild-type (WT) littermates and were resistant to the development of hepatic steatosis, adipose-associated inflammation, and insulin resistance. Gene expression profiling showed that many genes involved in triglyceride synthesis and storage, including Cidec, Cidea, and Mogat1, were expressed at much lower levels in liver of ROR alpha(sg/sg) mice. In contrast, overexpression of ROR alpha in mouse hepatoma Hepa1-6 cells significantly increased the expression of genes that were repressed in ROR alpha(sg/sg) liver, including Sult1b1, Adfp, Cidea, and ApoA4. ChIP and promoter analysis suggested that several of these genes were regulated directly by ROR alpha. In addition to reduced lipid accumulation, inflammation was greatly diminished in white adipose tissue (WAT) of ROR alpha(sg/sg) mice fed with an HFD. The infiltration of macrophages and the expression of many immune response and proinflammatory genes, including those encoding various chemo/cytokines, Toll-like receptors, and TNF signaling proteins, were significantly reduced in ROR alpha(sg/sg) WAT. Moreover, ROR alpha(sg/sg) mice fed with an HFD were protected from the development of insulin resistance. ROR alpha(sg/sg) mice consumed more oxygen and produced more carbon dioxide, suggesting increased energy expenditure in this genotype. Our study indicates that ROR alpha plays a critical role in the regulation of several aspects of metabolic syndrome. Therefore, ROR alpha may provide a novel therapeutic target in the management of obesity and associated metabolic diseases.
C1 [Kang, Hong Soon; Okamoto, Kyoko; Takeda, Yukimasa; Beak, Ju Youn; DeGraff, Laura M.; Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Gerrish, Kevin] NIEHS, Microarray Grp, NIH, Res Triangle Pk, NC 27709 USA.
[Bortner, Carl D.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Wada, Taira; Xie, Wen] Univ Pittsburgh, Ctr Pharmacogenet, Pittsburgh, PA USA.
[Wada, Taira; Xie, Wen] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA.
RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
RI Xie, Wen/M-1768-2016;
OI Jetten, Anton/0000-0003-0954-4445
FU NIEHS [Z01-ES-101586]
FX This research was supported by the Intramural Research Program of the
NIEHS (Z01-ES-101586).
NR 62
TC 29
Z9 30
U1 1
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD JUL
PY 2011
VL 43
IS 13
BP 818
EP 828
DI 10.1152/physiolgenomics.00206.2010
PG 11
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 792IF
UT WOS:000292735600004
PM 21540300
ER
PT J
AU Jeppesen, DK
Bohr, VA
Stevnsner, T
AF Jeppesen, Dennis Kjolhede
Bohr, Vilhelm A.
Stevnsner, Tinna
TI DNA repair deficiency in neurodegeneration
SO PROGRESS IN NEUROBIOLOGY
LA English
DT Review
DE DNA repair; Genomic instability; Reactive oxygen species;
Neurodegeneration; Aging; Mitochondria; Cockayne syndrome; Alzheimer's
disease; Parkinson's disease; Werner syndrome
ID BASE-EXCISION-REPAIR; STRAND BREAK REPAIR; WERNER-SYNDROME PROTEIN;
SYNDROME GROUP-B; RNA-POLYMERASE-II; AMYOTROPHIC-LATERAL-SCLEROSIS; CELL
NUCLEAR ANTIGEN; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE BRAIN;
SUBSTANTIA-NIGRA NEURONS
AB Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby causing Huntington's disease. Single-strand breaks are common DNA lesions and are associated with the neurodegenerative diseases, ataxia-oculomotor apraxia-1 and spinocerebellar ataxia with axonal neuropathy-1. DNA double-strand breaks are toxic lesions and two main pathways exist for their repair: homologous recombination and non-homologous end-joining. Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage may be linked with the age-associated neurodegenerative disorders Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Mutation in the WRN protein leads to the premature aging disease Werner syndrome, a disorder that features neurodegeneration. In this article we review the evidence linking deficiencies in the DNA repair pathways with neurodegeneration. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Jeppesen, Dennis Kjolhede; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark.
[Jeppesen, Dennis Kjolhede; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Stevnsner, T (reprint author), Univ Aarhus, Dept Mol Biol, Danish Ctr Mol Gerontol, CF Moellers Alle 3,Build 1130, DK-8000 Aarhus C, Denmark.
EM tvs@mb.au.dk
FU Danish Cancer Society; The Velux Foundation
FX D.K. Jeppesen was supported by the Danish Cancer Society and part of
this work was supported by a grant from The Velux Foundation to the
Danish Aging Research Center.
NR 459
TC 119
Z9 128
U1 5
U2 34
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0301-0082
J9 PROG NEUROBIOL
JI Prog. Neurobiol.
PD JUL
PY 2011
VL 94
IS 2
BP 166
EP 200
DI 10.1016/j.pneurobio.2011.04.013
PG 35
WC Neurosciences
SC Neurosciences & Neurology
GA 791OL
UT WOS:000292674400006
PM 21550379
ER
PT J
AU Mitchell, JB
AF Mitchell, James B.
TI Chasing Free Radicals in Cells and Tissues AWARD
SO RADIATION RESEARCH
LA English
DT Editorial Material
ID SEMIAUTOMATED COLORIMETRIC ASSAY; OXYGEN ENHANCEMENT RATIO; GLUTATHIONE
DEPLETION; PHOTODYNAMIC THERAPY; LUNG-CANCER; BUTHIONINE SULFOXIMINE;
NITROXIDE COMPOUNDS; CONTRAST AGENTS; CYTO-TOXICITY; REDOX STATUS
C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
NR 39
TC 0
Z9 0
U1 0
U2 0
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD JUL
PY 2011
VL 176
IS 1
BP 1
EP 7
DI 10.1667/RR2626.1
PG 7
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 788JT
UT WOS:000292441900001
PM 21545292
ER
PT J
AU DiCarlo, AL
Poncz, M
Cassatt, DR
Shah, JR
Czarniecki, CW
Maidment, BW
AF DiCarlo, Andrea L.
Poncz, Mortimer
Cassatt, David R.
Shah, Jui R.
Czarniecki, Christine W.
Maidment, Bert W.
TI Development and Licensure of Medical Countermeasures for Platelet
Regeneration after Radiation Exposure
SO RADIATION RESEARCH
LA English
DT Editorial Material
ID BODY IRRADIATION; IN-VIVO; THROMBOPOIETIN; MICE; THROMBOCYTOPENIA;
PANCYTOPENIA; ANTIBODIES; SURVIVAL; GROWTH; MODELS
C1 [DiCarlo, Andrea L.; Cassatt, David R.; Shah, Jui R.; Czarniecki, Christine W.; Maidment, Bert W.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Poncz, Mortimer] Childrens Hosp Philadelphia, Div Pediat Hematol, Philadelphia, PA 19104 USA.
RP DiCarlo, AL (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 5301, Bethesda, MD 20892 USA.
EM cohena@niaid.nih.gov
NR 23
TC 6
Z9 6
U1 0
U2 0
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD JUL
PY 2011
VL 176
IS 1
BP 134
EP 137
DI 10.1667/RR2610.1
PG 4
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 788JT
UT WOS:000292441900014
PM 21545289
ER
PT J
AU Ramkumar, HL
Brooks, BP
Cao, XG
Tamura, D
DiGiovanna, JJ
Kraemer, KH
Chan, CC
AF Ramkumar, Hema L.
Brooks, Brian P.
Cao, Xiaoguang
Tamura, Deborah
DiGiovanna, John J.
Kraemer, Kenneth H.
Chan, Chi-Chao
TI Ophthalmic Manifestations and Histopathology of Xeroderma Pigmentosum:
Two Clinicopathological Cases and a Review of the Literature
SO SURVEY OF OPHTHALMOLOGY
LA English
DT Review
DE ciliary body hamartoma; ocular pathology; optic atrophy xeroderma
pigmentosum; pigmentary retinal degeneration
ID SQUAMOUS-CELL CARCINOMA; DNA-REPAIR DEFICIENCY; OCULAR MANIFESTATIONS;
NEUROLOGICAL DISEASE; COCKAYNES SYNDROME; SKIN-CANCER;
ULTRAVIOLET-RADIATION; MALIGNANT-MELANOMA; BLACK-FAMILY; CONJUNCTIVAL
AB Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the ultraviolet (UV) exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. We report the clinical history and ocular pathology of two white women who had xeroderma pigmentosum with neurological degeneration: Case 1 (died at age 44 years) and Case 2 (died at age 45 years). Case 1, with mutations in the XPA gene, had more than 180 basal cell carcinomas of her skin and eyelids and died from complications of neurodegeneration. Case 2, with mutations in the XPD gene, was sun-protected and had three skin cancers. She died from complications of neurodegeneration and pneumonia. Both patients had bilateral pinguecula, corneal pannus, and exposure keratopathy. Case 1 had bilateral optic atrophy, and Case 2 had bilateral peripheral retinal pigmentary degeneration. Both patients developed retinal gliosis. The ophthalmic manifestations and pathology of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neurodegeneration of the retina. (Surv Ophthalmol 56:348-361, 2011. Published by Elsevier Inc.)
C1 [Ramkumar, Hema L.; Cao, Xiaoguang; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ramkumar, Hema L.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Ramkumar, Hema L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Brooks, Brian P.] NEI, Unit Pediat Dev & Genet Ophthalmol, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Cao, Xiaoguang] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China.
[Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
OI Ramkumar, Hema/0000-0002-1452-0694
FU Howard Hughes Medical Institute; National Eye Institute; Center for
Cancer Research of the National Cancer Institute, National Institutes of
Health
FX The authors report no proprietary or commercial interest in any product
mentioned or concept discussed in this article. Publication of this
research was supported by the Howard Hughes Medical Institute, the
Intramural Research Programs of the National Eye Institute, and the
Center for Cancer Research of the National Cancer Institute, National
Institutes of Health.
NR 97
TC 17
Z9 17
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6257
EI 1879-3304
J9 SURV OPHTHALMOL
JI Surv. Ophthalmol.
PD JUL-AUG
PY 2011
VL 56
IS 4
BP 348
EP 361
DI 10.1016/j.survophthal.2011.03.001
PG 14
WC Ophthalmology
SC Ophthalmology
GA 790KD
UT WOS:000292586000005
PM 21684361
ER
PT J
AU Rein, A
Datta, SAK
Jones, CP
Musier-Forsyth, K
AF Rein, Alan
Datta, Siddhartha A. K.
Jones, Christopher P.
Musier-Forsyth, Karin
TI Diverse interactions of retroviral Gag proteins with RNAs
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA-VIRUS;
HIV-1 NUCLEOCAPSID PROTEIN; ACID CHAPERONE ACTIVITY; PRIMER
BINDING-SITE; ASSEMBLY IN-VITRO; REVERSE TRANSCRIPTION; GENOMIC RNA;
VIRAL-RNA
AB Retrovirus particles are constructed from a single virus-encoded protein, termed Gag. Given that assembly is an essential step in the viral replication cycle, it is a potential target for antiviral therapy. However, such an approach has not yet been exploited because of the lack of fundamental knowledge concerning the structures and interactions responsible for assembly. Assembling an infectious particle entails a remarkably diverse array of interactions, both specific and nonspecific, between Gag proteins and RNAs. These interactions are essential for the construction of the particle, for packaging of the viral RNA into the particle, and for placement of the primer for viral DNA synthesis. Recent results have provided some new insights into each of these interactions. In the case of HIV-1 Gag, it is clear that more than one domain of the protein contributes to Gag RNA interaction.
C1 [Rein, Alan; Datta, Siddhartha A. K.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Dept Chem, Ctr Retroviral Res, Columbus, OH 43210 USA.
[Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Dept Biochem, Ctr Retroviral Res, Columbus, OH 43210 USA.
[Jones, Christopher P.; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM reina@mail.nih.gov
OI Datta, Siddhartha/0000-0002-4098-7490
FU NIH, National Cancer Institute, Center for Cancer Research; NIH [R01
GM065056, T32 GM008512]
FX This work was supported in part by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research, and by
NIH Grant R01 GM065056 (to K.M.-F.). C.P.J. was supported by NIH
Training Grant T32 GM008512. We thank Kevin Weeks for Figure 3.
NR 85
TC 45
Z9 45
U1 0
U2 8
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD JUL
PY 2011
VL 36
IS 7
BP 373
EP 380
DI 10.1016/j.tibs.2011.04.001
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 792DO
UT WOS:000292720900004
PM 21550256
ER
PT J
AU Molina, KM
Kiely, M
AF Molina, Kristine M.
Kiely, Michele
TI Understanding Depressive Symptoms among High-Risk, Pregnant,
African-American Women
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID INTIMATE PARTNER VIOLENCE; MOOD REGULATION EXPECTANCIES; STRESSFUL LIFE
EVENTS; SUBSTANCE USE; HEALTH BEHAVIORS; SOCIAL SUPPORT; CHECKLIST HSCL;
PREVALENCE; POSTPARTUM; DISTRESS
AB Purpose: Depression has been shown to be a risk factor of poor pregnancy outcomes among African-American women. The goal of this study was to examine both risk and protective factors of depressive symptoms among urban, high-risk African-American, pregnant women.
Methods: Data were drawn from a larger randomized controlled trial, Health Outcomes of Pregnancy Education that was a part of the National Institutes of Health-DC Initiative to Reduce Infant Mortality in Minority Populations in the District of Columbia. For purposes of the present study, a sample of African-American pregnant women (n = 1,044) were recruited from six urban prenatal care clinics. Baseline depressive symptoms were assessed using the Hopkins Symptom Checklist-Depression Scale.
Results: Forty-four. percent of women were confirmed as moderately to severely depressed at baseline. In multivariate linear regression analysis among the total sample, maternal age, intimate partner violence, illicit drug and alcohol use during pregnancy, and reproductive history (no live birth/only loss; no live birth/no loss) were associated with increased depressive symptoms. Being very happy about the pregnancy, having emotional support from others, and reporting more positive expectancies about the ability to regulate negative moods were associated with decreased depressive symptoms.
Conclusion: Results highlight the importance of attending to the context of high-risk, African-American, pregnant women, paying attention to both risk and protective factors of poor psychological well-being. Implications for future research in this area are discussed. Copyright (C) 2011 by the Jacobs Institute of Women's Health. Published by Elsevier Inc.
C1 [Molina, Kristine M.] Univ Michigan, Dept Psychol, Joint PhD Program Personal Social Contexts Psycho, Ann Arbor, MI 48109 USA.
[Molina, Kristine M.] Univ Michigan, Womens Studies Dept, Ann Arbor, MI 48109 USA.
[Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
RP Molina, KM (reprint author), Univ Michigan, Dept Psychol, Joint PhD Program Personal Social Contexts Psycho, 530 Church St,East Hall, Ann Arbor, MI 48109 USA.
EM kmolida@umich.edu; kielym@mail.nih.gov
FU NICHD NIH HHS [5U18HD31206, 3U18HD030445, U18 HD036104, U18 HD030445,
3U18HD03919, 3U18HD030447, 5U18HD036104, U18 HD030447, U18 HD031206]
NR 50
TC 4
Z9 5
U1 5
U2 15
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 JUL-AUG
PY 2011
VL 21
IS 4
BP 293
EP 303
DI 10.1016/j.whi.2011.01.008
PG 11
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA 792XZ
UT WOS:000292785000007
PM 21565525
ER
PT J
AU Kim, SE
Bahta, M
Lountos, GT
Ulrich, RG
Burke, TR
Waugh, DS
AF Kim, Sung-Eun
Bahta, Medhanit
Lountos, George T.
Ulrich, Robert G.
Burke, Terrence R., Jr.
Waugh, David S.
TI Isothiazolidinone (IZD) as a phosphoryl mimetic in inhibitors of the
Yersinia pestis protein tyrosine phosphatase YopH
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID PROMISCUOUS INHIBITORS; BIDENTATE INHIBITORS; CRYSTAL-STRUCTURES; 1B
INHIBITORS; DESIGN; PHOSPHOTYROSINE; MECHANISM; LIBRARY; MODEL;
CRYSTALLOGRAPHY
AB Isothiazolidinone (IZD) heterocycles can act as effective components of protein tyrosine phosphatase (PTP) inhibitors by simultaneously replicating the binding interactions of both a phosphoryl group and a highly conserved water molecule, as exemplified by the structures of several PTP1B-inhibitor complexes. In the first unambiguous demonstration of IZD interactions with a PTP other than PTP1B, it is shown by X-ray crystallography that the IZD motif binds within the catalytic site of the Yersinia pestis PTP YopH by similarly displacing a highly conserved water molecule. It is also shown that IZD-based bidentate ligands can inhibit YopH in a nonpromiscuous fashion at low micromolar concentrations. Hence, the IZD moiety may represent a useful starting point for the development of YopH inhibitors.
C1 [Kim, Sung-Eun; Bahta, Medhanit; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Lountos, George T.; Waugh, David S.] NCI, Ctr Macromol Crystallog, Frederick, MD 21702 USA.
[Ulrich, Robert G.] USA, Lab Mol Immunol, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), NCI, Biol Chem Lab, POB B, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov; waughd@mail.nih.gov
RI Burke, Terrence/N-2601-2014; Lountos, George/B-3983-2015
FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer
Institute, National Institutes of Health; Joint Science and Technology
Office of the Department of Defense
FX Appreciation is expressed to Afroz Sultana (LMI) for technical support
and to Joseph Tropea and Scott Cherry (MCL) for purification of YopH.
Electrospray mass-spectrometry experiments were conducted on the LC/ESMS
instrument maintained by the Biophysics Resource in the Structural
Biophysics Laboratory, Center for Cancer Research, National Cancer
Institute at Frederick. This 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 and the Joint Science and Technology Office of the Department of
Defense. 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 49
TC 13
Z9 13
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD JUL
PY 2011
VL 67
BP 639
EP 645
DI 10.1107/S0907444911018610
PN 7
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 788RD
UT WOS:000292461200006
PM 21697602
ER
PT J
AU Armani, M
Tangrea, MA
Shapiro, B
Emmert-Buck, MR
Smela, E
AF Armani, Michael
Tangrea, Michael A.
Shapiro, Benjamin
Emmert-Buck, Michael R.
Smela, Elisabeth
TI Quantifying mRNA levels across tissue sections with 2D-RT-qPCR
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Tissue lysis; RNA purification; Gene expression mapping; Tissue section;
PCR
ID BRAIN GENE-EXPRESSION; IN-SITU HYBRIDIZATION; POLYMERASE-CHAIN-REACTION;
BREAST-CANCER; RT-PCR; DNA; AMPLIFICATION; PURIFICATION; PROCESSOR;
MOUSE
AB Measurement of mRNA levels across tissue samples facilitates an understanding of how genes function and what their roles are in disease. Quantifying low-abundance mRNA requires a workflowthat preserves spatial information, isolates RNA, and performs reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR). This is complex because these steps are typically performed in three separate platforms. In the present study, we describe two-dimensional RT-qPCR (2D-RT-qPCR), a method that quantifies RNA across tissues sections in a single integrated platform. The method uses the grid format of a multi-well plate to macrodissect tissue sections and preserve the spatial location of the RNA; this also eliminates the need for physical homogenization of the tissue. A new lysis and nucleic acid purification protocol is performed in the same multi-well plate, followed by RT-qPCR. The feasibility 2D-RT-qPCR was demonstrated on a variety of tissue types. Potential applications of the technology as a high-throughput tissue analysis platform are discussed.
C1 [Smela, Elisabeth] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA.
[Armani, Michael; Shapiro, Benjamin] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Armani, Michael; Tangrea, Michael A.; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA.
RP Smela, E (reprint author), Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA.
EM buckm@mail.nih.gov; smela@umd.edu
RI Shapiro, Benjamin/H-6176-2011; Smela, Elisabeth/B-9911-2011
OI Smela, Elisabeth/0000-0003-3921-2265
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work was supported in part by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research.
NR 38
TC 1
Z9 1
U1 0
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JUL
PY 2011
VL 400
IS 10
BP 3383
EP 3393
DI 10.1007/s00216-011-5062-8
PG 11
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 789IE
UT WOS:000292508200021
PM 21559756
ER
PT J
AU Sampson, JN
Kidd, KK
Kidd, JR
Zhao, HY
AF Sampson, Joshua N.
Kidd, Kenneth K.
Kidd, Judith R.
Zhao, Hongyu
TI Selecting SNPs to Identify Ancestry
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Ancestry; ethnicity; SNPs; error rate; allele frequency; genotype; AIM;
bootstrap; FOSSIL
ID HUMAN-POPULATION STRUCTURE; GENETIC ASSOCIATION; PHYLOGENETIC TREES;
CROSS-VALIDATION; MARKERS; ORIGIN; STRATIFICATION; DIVERSITY; INFERENCE;
PANELS
AB An individual's genotypes at a group of single-nucleotide polymorphisms (SNPs) can be used to predict that individual's ethnicity or ancestry. In medical studies, knowledge of a subject's ancestry can minimize possible confounding, and in forensic applications, such knowledge can help direct investigations. Our goal is to select a small subset of SNPs, from the millions already identified in the human genome, that can predict ancestry with a minimal error rate. The general form for this variable selection procedure is to estimate the expected error rates for sets of SNPs using a training dataset and consider those sets with the lowest error rates given their size. The quality of the estimate for the error rate determines the quality of the resulting SNPs. As the apparent error rate performs poorly when either the number of SNPs or the number of populations is large; we propose a new estimate, the Improved Bayesian Estimate. We demonstrate that selection procedures based on this estimate produce small sets of SNPs that can accurately predict ancestry. We also provide a list of the 100 optimal SNPs for identifying ancestry.
C1 [Sampson, Joshua N.] NCI, Bethesda, MD 20892 USA.
[Kidd, Kenneth K.; Kidd, Judith R.; Zhao, Hongyu] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Zhao, Hongyu] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
RP Sampson, JN (reprint author), 6120 Execut Blvd,8038, Bethesda, MD 20892 USA.
EM joshua.sampson@nih.gov
FU NIJ [2007-DN-BX-K197, 2010-DN-BX-K225]; National Institute of Justice,
Office of Justice Programs, US Department of Justice
FX This work was supported, in part, by NIJ grants 2007-DN-BX-K197 and
2010-DN-BX-K225 to KKK awarded by the National Institute of Justice,
Office of Justice Programs, US Department of Justice. Points of view in
this document are those of the authors and do not necessarily represent
the official position or policies of the US Department of Justice.
NR 31
TC 2
Z9 2
U1 1
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD JUL
PY 2011
VL 75
BP 539
EP 553
DI 10.1111/j.1469-1809.2011.00656.x
PN 4
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 787FA
UT WOS:000292360800010
PM 21668909
ER
PT J
AU Friesen, MC
Coble, JB
Katki, HA
Ji, BT
Xue, SZ
Lu, W
Stewart, PA
AF Friesen, Melissa C.
Coble, Joseph B.
Katki, Hormuzd A.
Ji, Bu-Tian
Xue, Shouzheng
Lu, Wei
Stewart, Patricia A.
TI Validity and Reliability of Exposure Assessors' Ratings of Exposure
Intensity by Type of Occupational Questionnaire and Type of Rater
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE dust; exposure assessment; foundry industry; population-based studies;
professional judgment; reliability; textile industry; validity
ID INTERRATER AGREEMENT; VALIDATION; CARCINOGENS; INDUSTRY
AB Methods: Subjects from three foundries (n = 72) and three textile plants (n = 74) in Shanghai, China, completed an occupational history (OH) and an industry-specific questionnaire (IQ). Six total dust measurements were collected per subject and were used to calculate a subject-specific measurement mean, which was used as the gold standard. Six raters independently ranked the intensity of each subject's current job on an ordinal scale (1-4) based on the OH alone and on the OH and IQ together. Aggregate ratings were calculated for the group, for industrial hygienists, and for occupational physicians. We calculated intra-class correlation coefficients (ICCs) to evaluate the reliability of the raters. We calculated the correlation between the subject-specific measurement means and the ratings to evaluate the raters' validity. Analyses were stratified by industry, type of questionnaire, and type of rater. We also examined the agreement between the ratings by exposure category, where the subject-specific measurement means were categorized into two and four categories.
Results: The reliability and validity measures were higher for the aggregate ratings than for the ratings from the individual raters. The group's performance was maximized with three raters. Both the reliability and validity measures were higher for the foundry industry than for the textile industry. The ICCs were consistently lower in the OH/IQ round than in the OH round in both industries. In contrast, the correlations with the measurement means were higher in the OH/IQ round than in the OH round for the foundry industry (group rating, OH/IQ: Spearman rho = 0.77; OH: rho = 0.64). No pattern by questionnaire type was observed for the textile industry (group rating, Spearman rho = 0.50, both assessment rounds). For both industries, the agreement by exposure category was higher when the task was reduced to discriminating between two versus four exposure categories.
Conclusions: Assessments based on professional judgment may reduce misclassification by using two or three raters, by using questionnaires that systematically collect task information, and by defining intensity categories that are distinguishable by the raters. However, few studies have the resources to use multiple raters and these additional efforts may not be adequate for obtaining valid subjective ratings. Thus, improving exposure assessment approaches for studies that rely on professional judgment remain an important research need.
C1 [Friesen, Melissa C.; Coble, Joseph B.; Katki, Hormuzd A.; Ji, Bu-Tian; Xue, Shouzheng; Stewart, Patricia A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lu, Wei] Shanghai Municipal Ctr Dis Control, Shanghai, Peoples R China.
RP Friesen, MC (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015; Friesen, Melissa/A-5362-2009
FU National Cancer Institute
FX Intramural Research Program at the National Cancer Institute.
NR 30
TC 10
Z9 10
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD JUL
PY 2011
VL 55
IS 6
BP 601
EP 611
DI 10.1093/annhyg/mer019
PG 11
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA 789XX
UT WOS:000292553900007
PM 21511891
ER
PT J
AU Hines, CJ
Deddens, JA
Coble, J
Kamel, F
Alavanja, MCR
AF Hines, Cynthia J.
Deddens, James A.
Coble, Joseph
Kamel, Freya
Alavanja, Michael C. R.
TI Determinants of Captan Air and Dermal Exposures among Orchard Pesticide
Applicators in the Agricultural Health Study
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE agriculture; captan; dermal exposure-pesticides; determinants of
exposure; exposure assessment-mixed models; orchards; pesticide
exposure; variance components
ID FARM APPLICATORS; ALGORITHM; FAMILIES; WORKERS; FRANCE
AB Methods: External exposure metrics included personal air, hand rinse, and dermal patch samples collected from each applicator on 2 days in 2002-2003. A 24-h urine sample was also collected. Exposure determinants were identified for each external metric using multiple linear regression models via the NLMIXED procedure in SAS. The AHS algorithm was adjusted, consistent with the identified determinants. Mixed-effect models were used to evaluate the correlation between the adjusted and unadjusted algorithm and urinary captan metabolite levels.
Results: Consistent determinants of captan exposure were a measure of application size (kilogram of captan sprayed or application method), wearing chemical-resistant (CR) gloves and/or a coverall/suit, repairing spray equipment, and product formulation. Application by airblast was associated with a 4- to 5-fold increase in exposure as compared to hand spray. Exposure reduction to the hands, right thigh, and left forearm from wearing CR gloves averaged similar to 80%, to the right and left thighs and right forearm from wearing a coverall/suit by similar to 70%. Applicators using wettable powder formulations had significantly higher air, thigh, and forearm exposures than those using liquid formulations. Application method weights in the AHS algorithm were adjusted to nine for airblast and two for hand spray; protective equipment reduction factors were adjusted to 0.2 (CR gloves), 0.3 (coverall/suit), and 0.1 (both).
Conclusions: Adjustment of application method, CR glove, and coverall weights in the AHS algorithm based on our exposure determinant findings substantially improved the correlation between the AHS algorithm and urinary metabolite levels.
C1 [Hines, Cynthia J.; Deddens, James A.] NIOSH, Cincinnati, OH 45226 USA.
[Deddens, James A.] Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA.
[Coble, Joseph; Alavanja, Michael C. R.] NCI, Rockville, MD 20892 USA.
[Kamel, Freya] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Hines, CJ (reprint author), NIOSH, 4676 Columbia Pkwy,R-14, Cincinnati, OH 45226 USA.
EM chines@cdc.gov
OI Kamel, Freya/0000-0001-5052-6615
FU National Institute for Occupational Safety and Health; National
Institutes of Health, National Cancer Institute [Z01-CP010119]; National
Institute of Environmental Health Sciences [Z01-ES049030]
FX This work has been supported in part by the Intramural research program
of the National Institute for Occupational Safety and Health; National
Institutes of Health, National Cancer Institute (Z01-CP010119); National
Institute of Environmental Health Sciences (Z01-ES049030).
NR 27
TC 9
Z9 10
U1 1
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD JUL
PY 2011
VL 55
IS 6
BP 620
EP 633
DI 10.1093/annhyg/mer008
PG 14
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA 789XX
UT WOS:000292553900009
PM 21427168
ER
PT J
AU Sutton, M
Mills, JL
Molloy, AM
Troendle, JF
Brody, LC
Conley, M
Mc Donnell, R
Scott, JM
Kirke, PN
AF Sutton, Marie
Mills, James L.
Molloy, Anne M.
Troendle, James F.
Brody, Lawrence C.
Conley, Mary
Mc Donnell, Robert
Scott, John M.
Kirke, Peadar N.
TI Maternal Folate, Vitamin B12 and Homocysteine Levels in Pregnancies
Affected by Congenital Malformations Other Than Neural Tube Defects
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
ID FOLIC-ACID FORTIFICATION; PERICONCEPTIONAL MULTIVITAMIN USE; OROFACIAL
CLEFTS; BIRTH-DEFECTS; MICROBIOLOGICAL ASSAY; CLINICAL GENETICS;
HEART-DEFECTS; ORAL CLEFTS; RISK; SUPPLEMENTATION
C1 [Sutton, Marie] Hlth Res Board, Evidence Ctr, Child Hlth Epidemiol Unit, Dublin 2, Ireland.
[Mills, James L.; Troendle, James F.; Conley, Mary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Molloy, Anne M.] Trinity Coll Dublin, Sch Med, Dublin, Ireland.
[Troendle, James F.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA.
[Mc Donnell, Robert] Dr Steevens Hosp, Hlth Informat Unit, Dept Publ Hlth, Hlth Serv, Dublin, Ireland.
[Scott, John M.] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland.
RP Sutton, M (reprint author), Hlth Res Board, Evidence Ctr, Child Hlth Epidemiol Unit, 3rd Floor,Knockmaun House,42-47 Lower Mt St, Dublin 2, Ireland.
EM msutton@hrb.ie
OI Molloy, Anne/0000-0002-1688-9049
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Health Research Board of Ireland
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the Health Research Board of Ireland.
NR 33
TC 5
Z9 5
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD JUL
PY 2011
VL 91
IS 7
BP 610
EP 615
DI 10.1002/bdra.20817
PG 6
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 790PY
UT WOS:000292602900003
PM 21591245
ER
PT J
AU Athar, M
Kopelovich, L
AF Athar, Mohammad
Kopelovich, Levy
TI Rapamycin and mTORC1 Inhibition in the Mouse: Skin Cancer Prevention
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID MAMMALIAN TARGET; MOTIF PHOSPHORYLATION; CELL-GROWTH; MODEL; AKT;
CARCINOGENESIS; TUMORIGENESIS; MICE; ACTIVATION; EVEROLIMUS
AB Therapeutic and preventive effects of rapamycin include reduced risk of nonmelanoma skin cancer (NMSC). In this issue of the journal (beginning on page 1011), Checkley and colleagues report that rapamycin inhibits mTOR complex 1 in murine epidermis, thereby inhibiting tumor promotion mediated by tetradecanoyl phorbol-13 acetate in association with a strong anti-inflammatory effect. Rapamycin is an immunosuppressive drug for preventing graft rejection in organ transplant recipients and reduces the risk of NMSC and Kaposi's sarcoma in this population, albeit by mechanisms distinct from immunosuppression. Important future directions include identifying molecular predictors of rapamycin/ rapalog sensitivity or resistance (potentially, for example, PI3K pathway alterations and KRAS mutations) and combined nonrapalog, mTOR-targeting approaches, all of which should increase efficacy and minimize toxicity. Cancer Prev Res; 4(7); 957-61. (C)2011 AACR.
C1 [Athar, Mohammad] Univ Alabama Birmingham, Dept Dermatol, Skin Dis Res Ctr, Birmingham, AL 35294 USA.
[Athar, Mohammad] Univ Alabama Birmingham, UAB Comprehens Canc Ctr, Birmingham, AL 35294 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Kopelovich, L (reprint author), NCI, NIH, DCP, Execut Plaza N,Suite 2114,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM kopelovl@mail.nih.gov
FU NCI NIH HHS [R01 CA138998, N01 CN043301, 1R01CA138998, N01-CN-43300, R01
CA138998-02]; NIAMS NIH HHS [P30 AR050948, P30 AR050948-07,
P30AR050948]; NIEHS NIH HHS [R21ES017494, R01 ES015323-05, R21 ES017494,
R21 ES017494-02, R01 ES015323]
NR 58
TC 13
Z9 13
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 JUL
PY 2011
VL 4
IS 7
BP 957
EP 961
DI 10.1158/1940-6207.CAPR-11-0266
PG 5
WC Oncology
SC Oncology
GA 788MN
UT WOS:000292449200003
PM 21733819
ER
PT J
AU Mao, JT
Roth, MD
Fishbein, MC
Aberle, DR
Zhang, ZF
Rao, JY
Tashkin, DP
Goodglick, L
Holmes, EC
Cameron, RB
Dubinett, SM
Elashoff, R
Szabo, E
Elashoff, D
AF Mao, Jenny T.
Roth, Michael D.
Fishbein, Michael C.
Aberle, Denise R.
Zhang, Zuo-Feng
Rao, Jian Yu
Tashkin, Donald P.
Goodglick, Lee
Holmes, E. Carmack
Cameron, Robert B.
Dubinett, Steven M.
Elashoff, Robert
Szabo, Eva
Elashoff, David
TI Lung Cancer Chemoprevention with Celecoxib in Former Smokers
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID C-REACTIVE PROTEIN; BRONCHIAL EPITHELIUM; CYCLOOXYGENASE-2 INHIBITORS;
ACTIVE SMOKERS; HIGH-RISK; TRIAL; PREVENTION; INTERLEUKIN-10;
MACROPHAGES; BUDESONIDE
AB Ample studies suggest that the cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway plays a pivotal role in carcinogenesis and that COX-2 inhibition may help prevent lung cancer. Therefore, we conducted a randomized, double-blind, placebo-controlled trial of the COX-2-selective inhibitor celecoxib (400 mg bid for 6 months) in former-smokers (age >= 45, >= 30 pack-years of smoking, >= 1 year of sustained abstinence from smoking). We assessed the impact of celecoxib on cellular and molecular events associated with lung cancer pathogenesis; the primary endpoint was bronchial Ki-67 labeling index (Ki-67 LI) after 6 months of treatment. Of 137 randomized subjects, 101 completed both baseline and 6-month bronchoscopies and were evaluable for the primary endpoint analysis. The beneficial effect on Ki-67 LI was greater in the celecoxib arm (versus placebo) in a mixed-effects analysis (P = 0.0006), and celecoxib significantly decreased Ki-67 LI by an average of 34%, whereas placebo increased Ki-67 LI by an average of 3.8% (P = 0.04; t test). In participants who crossed over to the other study arm at 6 months (all of whom had received 6 months of celecoxib at the end of a 12 months treatment period), the decreases in Ki-67 LI correlated with a reduction and/or resolution of lung nodules on computed tomography. Celecoxib significantly reduced plasma c-reactive protein and interleukin-6 mRNA and protein and increased 15(S)-hydroxy-eicosatetraenoic acid levels in bronchoalveolar lavage (BAL) samples. The baseline ratio of COX-2 to 15-hydroxyprostaglandin dehydrogenase mRNA in BAL cells was a significant predictive marker of Ki-67 response to celecoxib (P = 0.002). Our collective findings support the continued investigation of celecoxib for lung cancer chemoprevention in former smokers at a low risk of cardiovascular disease. Cancer Prev Res; 4(7); 984-93. (C)2011 AACR.
C1 [Mao, Jenny T.] Univ New Mexico, New Mexico VA Hlth Care Syst, Pulm & Crit Care Sect, Albuquerque, NM 87108 USA.
[Mao, Jenny T.; Roth, Michael D.; Tashkin, Donald P.; Dubinett, Steven M.] Univ Calif Los Angeles, Sch Publ Hlth, Div Pulm & Crit Care Med, Los Angeles, CA 90024 USA.
[Fishbein, Michael C.; Rao, Jian Yu; Goodglick, Lee; Dubinett, Steven M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA.
[Aberle, Denise R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Radiol, Los Angeles, CA 90024 USA.
[Holmes, E. Carmack; Cameron, Robert B.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Surg, Los Angeles, CA 90024 USA.
[Elashoff, Robert; Elashoff, David] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Elashoff, David] Univ Calif Los Angeles, Sch Publ Hlth, Dept Med, David Geffen Sch Med UCLA, Los Angeles, CA 90024 USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Szabo, Eva] NCI, Canc Prevent Div, Rockville, MD USA.
RP Mao, JT (reprint author), Univ New Mexico, New Mexico VA Hlth Care Syst, Pulm & Crit Care Sect, Albuquerque, NM 87108 USA.
EM jenny.mao@va.gov
OI Aberle, Denise/0000-0002-8858-3401
FU National Cancer Institute [U01CA096134]; Early Detection Research
Network NCI [CA-86366]; Pfizer Inc.
FX This work was supported by a grant from the National Cancer Institute
(JTM, U01CA096134), and in part by the Early Detection Research Network
NCI (LG, CA-86366). Pfizer Inc. provided support for study drugs and
plasma celecoxib measurements.
NR 40
TC 38
Z9 38
U1 1
U2 4
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 JUL
PY 2011
VL 4
IS 7
BP 984
EP 993
DI 10.1158/1940-6207.CAPR-11-0078
PG 10
WC Oncology
SC Oncology
GA 788MN
UT WOS:000292449200006
PM 21733822
ER
PT J
AU Morris, PG
Hudis, CA
Giri, D
Morrow, M
Falcone, DJ
Zhou, XK
Du, BH
Brogi, E
Crawford, CB
Kopelovich, L
Subbaramaiah, K
Dannenberg, AJ
AF Morris, Patrick G.
Hudis, Clifford A.
Giri, Dilip
Morrow, Monica
Falcone, Domenick J.
Zhou, Xi Kathy
Du, Baoheng
Brogi, Edi
Crawford, Carolyn B.
Kopelovich, Levy
Subbaramaiah, Kotha
Dannenberg, Andrew J.
TI Inflammation and Increased Aromatase Expression Occur in the Breast
Tissue of Obese Women with Breast Cancer
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID BODY-MASS INDEX; TUMOR-NECROSIS-FACTOR; ADIPOSE-TISSUE;
INSULIN-RESISTANCE; MACROPHAGE INFILTRATION; PROSPECTIVE COHORT;
PHYSICAL-ACTIVITY; GENE-EXPRESSION; WEIGHT-LOSS; PROGNOSIS
AB Obesity is a risk factor for the development of hormone receptor-positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. In humans, obesity causes subclinical inflammation in visceral and subcutaneous adipose tissue, characterized by necrotic adipocytes surrounded by macrophages forming crown-like structures (CLS). Recently, we found increased numbers of CLS, activation of the NF-kappa B transcription factor, and elevated aromatase levels and activity in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity -> inflammation axis is important for the development and progression of breast cancer. Here, our main objective was to determine if the findings in mouse models of obesity translated to women. Breast tissue was obtained from 30 women who underwent breast surgery. CLS of the breast (CLS-B) was found in nearly 50% (14 of 30) of patient samples. The severity of breast inflammation, defined as the CLS-B index, correlated with both body mass index (P < 0.001) and adipocyte size (P = 0.01). Increased NF-kappa B binding activity and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women. Collectively, our results suggest that the obesity -> inflammation -> aromatase axis is present in the breast tissue of most overweight and obese women. The presence of CLS-B may be a biomarker of increased breast cancer risk or poor prognosis. Cancer Prev Res; 4(7); 1021-9. (C)2011 AACR.
C1 [Morris, Patrick G.; Hudis, Clifford A.; Crawford, Carolyn B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Giri, Dilip; Brogi, Edi] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Morrow, Monica] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
[Falcone, Domenick J.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA.
[Zhou, Xi Kathy] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
[Du, Baoheng; Subbaramaiah, Kotha; Dannenberg, Andrew J.] Weill Cornell Med Coll, Weill Cornell Canc Ctr, Dept Med, New York, NY USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Dannenberg, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 525 E 68th St,Room F-206, New York, NY 10065 USA.
EM ksubba@med.cornell.edu; ajdannen@med.cornell.edu
FU NCI [N01-CN-43302]; Breast Cancer Research Foundation;
Botwinick-Wolfensohn Foundation; Kochavi Breast Cancer Prevention Fund
FX This work was supported by NCI N01-CN-43302 (to A.J. Dannenberg), the
Breast Cancer Research Foundation (to A.J. Dannenberg, C.A. Hudis), the
Botwinick-Wolfensohn Foundation (in memory of Mr. and Mrs. Benjamin
Botwinick; to A.J. Dannenberg), and the Kochavi Breast Cancer Prevention
Fund (to C.A. Hudis).
NR 40
TC 146
Z9 147
U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUL
PY 2011
VL 4
IS 7
BP 1021
EP 1029
DI 10.1158/1940-6207.CAPR-11-0110
PG 9
WC Oncology
SC Oncology
GA 788MN
UT WOS:000292449200010
PM 21622727
ER
PT J
AU Mackenzie, GG
Ouyang, N
Xie, G
Vrankova, K
Huang, LQ
Sun, Y
Komninou, D
Kopelovich, L
Rigas, B
AF Mackenzie, Gerardo G.
Ouyang, Nengtai
Xie, Gang
Vrankova, Kvetoslava
Huang, Liqun
Sun, Yu
Komninou, Despina
Kopelovich, Levy
Rigas, Basil
TI Phospho-Sulindac (OXT-328) Combined with Difluoromethylornithine
Prevents Colon Cancer in Mice
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID INDUCED CELL-DEATH; THIOREDOXIN SYSTEM; ANTIINFLAMMATORY DRUGS;
OXIDATIVE STRESS; KAPPA-B; CHEMOPREVENTION; INHIBITION; POLYAMINES;
TUMOR; ASPIRIN
AB The nonsteroidal anti-inflammatory drug (NSAID) sulindac and the ornithine decarboxylase (ODC) antagonist difluoromethylornithine (DFMO), individually and together, are effective inhibitors of colon carcinogenesis. However, chronic use of sulindac is associated with significant side effects. We evaluated the chemopreventive efficacy of phospho-sulindac (P-S, OXT-328), an apparently safe derivative of sulindac, together with DFMO, in HT-29 human colon cancer xenografts. Nude mice were divided into four groups as follows: group 1 received vehicle (corn oil); group 2 received P-S (100 mg/kg/d) by oral gavage; group 3 received DFMO (2% in drinking water); and group 4 received P-S (100 mg/kg/d) by gavage plus DFMO (2% in drinking water; P-S/DFMO). Eighteen days after implantation, compared with controls, tumor volume was inhibited 65.9% by P-S, 52.9% by DFMO, and 70.9% by P-S/DFMO (P < 0.01 for all). P-S/DFMO reduced cell proliferation 27.1% and increased apoptosis 38.9% compared with controls (P < 0.05 for both). Compared with controls, P-S reduced the levels of thioredoxin-1 (Trx-1) and thioredoxin reductase (TrxR), whereas DFMO reduced polyamine content (putrescine and spermidine) and TrxR levels. Importantly, P-S/DFMO decreased putrescine and spermidine levels and the expression of Trx-1, TrxR, and cyclooxygenase (COX) 2. Of these molecular targets, TrxR most consistently correlated with tumor growth. Study results show that P-S/DFMO is an efficacious drug combination for colon cancer prevention and also show the safety of P-S, which may overcome the limiting side effects of conventional sulindac. P-S/DFMO has an intricate mechanism of action extending beyond polyamines and including the thioredoxin system, an emerging regulator of chemoprevention. P-S/DFMO merits further evaluation. Cancer Prev Res; 4(7); 1052-60. (C)2011 AACR.
C1 [Rigas, Basil] SUNY Stony Brook, Canc Prevent Div, Dept Med, HSC, Stony Brook, NY 11794 USA.
[Komninou, Despina] Medicon Pharmaceut Inc, New York, NY USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Rigas, B (reprint author), SUNY Stony Brook, Canc Prevent Div, Dept Med, HSC, T17-080, Stony Brook, NY 11794 USA.
EM basil.rigas@stonybrook.edu
FU NIH [R01-CA139453, R01CA13945402, 1N01CN43302WA22]
FX The work was supported by NIH grants R01-CA139453, R01CA13945402, and
1N01CN43302WA22.
NR 30
TC 22
Z9 23
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUL
PY 2011
VL 4
IS 7
BP 1052
EP 1060
DI 10.1158/1940-6207.CAPR-11-0067
PG 9
WC Oncology
SC Oncology
GA 788MN
UT WOS:000292449200013
PM 21464038
ER
PT J
AU Rosenberg, SA
Yang, JC
Sherry, RM
Kammula, US
Hughes, MS
Phan, GQ
Citrin, DE
Restifo, NP
Robbins, PF
Wunderlich, JR
Morton, KE
Laurencot, CM
Steinberg, SM
White, DE
Dudley, ME
AF Rosenberg, Steven A.
Yang, James C.
Sherry, Richard M.
Kammula, Udai S.
Hughes, Marybeth S.
Phan, Giao Q.
Citrin, Deborah E.
Restifo, Nicholas P.
Robbins, Paul F.
Wunderlich, John R.
Morton, Kathleen E.
Laurencot, Carolyn M.
Steinberg, Seth M.
White, Donald E.
Dudley, Mark E.
TI Durable Complete Responses in Heavily Pretreated Patients with
Metastatic Melanoma Using T-Cell Transfer Immunotherapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; CANCER REGRESSION; TRANSFER THERAPY;
ADOPTIVE TRANSFER; RECOMBINANT INTERLEUKIN-2; NASOPHARYNGEAL CARCINOMA;
TRANSPLANT PATIENTS; MALIGNANT-MELANOMA; AUTOLOGOUS TUMOR; BONE-MARROW
AB Purpose: Most treatments for patients with metastatic melanoma have a low rate of complete regression and thus overall survival in these patients is poor. We investigated the ability of adoptive cell transfer utilizing autologous tumor-infiltrating lymphocytes (TIL) to mediate durable complete regressions in heavily pretreated patients with metastatic melanoma.
Experimental Design: Ninety-three patients with measurable metastatic melanoma were treated with the adoptive transfer of autologous TILs administered in conjunction with interleukin-2 following a lymphodepleting preparative regimen on three sequential clinical trials. Ninety-five percent of these patients had progressive disease following a prior systemic treatment. Median potential follow-up was 62 months.
Results: Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) in the 3 trials using lymphodepleting preparative regimens (chemotherapy alone or with 2 or 12 Gy irradiation) were 49%, 52%, and 72%, respectively. Twenty of the 93 patients (22%) achieved a complete tumor regression, and 19 have ongoing complete regressions beyond 3 years. The actuarial 3- and 5-year survival rates for the entire group were 36% and 29%, respectively, but for the 20 complete responders were 100% and 93%. The likelihood of achieving a complete response was similar regardless of prior therapy. Factors associated with objective response included longer telomeres of the infused cells, the number of CD8(+)CD27(+) cells infused, and the persistence of the infused cells in the circulation at 1 month (all P(2) < 0.001).
Conclusions: Cell transfer therapy with autologous TILs can mediate durable complete responses in patients with metastatic melanoma and has similar efficacy irrespective of prior treatment. Clin Cancer Res; 17(13); 4550-7. (C) 2011 AACR.
C1 [Rosenberg, Steven A.; Yang, James C.; Sherry, Richard M.; Kammula, Udai S.; Hughes, Marybeth S.; Phan, Giao Q.; Restifo, Nicholas P.; Robbins, Paul F.; Wunderlich, John R.; Morton, Kathleen E.; Laurencot, Carolyn M.; White, Donald E.; Dudley, Mark E.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Citrin, Deborah E.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC-10,10 Ctr Dr,Room 3-3940, Bethesda, MD 20892 USA.
EM sar@nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural NIH HHS [Z01 SC003811-33]
NR 42
TC 628
Z9 651
U1 4
U2 59
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 JUL 1
PY 2011
VL 17
IS 13
BP 4550
EP 4557
DI 10.1158/1078-0432.CCR-11-0116
PG 8
WC Oncology
SC Oncology
GA 788LO
UT WOS:000292446600036
PM 21498393
ER
PT J
AU Pasricha, PJ
Colvin, R
Yates, K
Hasler, WL
Abell, TL
Unalp-Arida, A
Nguyen, L
Farrugia, G
Koch, KL
Parkman, HP
Snape, WJ
Lee, L
Tonascia, J
Hamilton, F
AF Pasricha, Pankaj J.
Colvin, Ryan
Yates, Katherine
Hasler, William L.
Abell, Thomas L.
Uenalp-Arida, Aynur
Nguyen, Linda
Farrugia, Gianrico
Koch, Kenneth L.
Parkman, Henry P.
Snape, William J.
Lee, Linda
Tonascia, James
Hamilton, Frank
TI Characteristics of Patients With Chronic Unexplained Nausea and Vomiting
and Normal Gastric Emptying
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE GCSI; Digestion; PAGI-SYM; PAGI-QOL
ID CARDINAL SYMPTOM INDEX; ELECTRICAL-STIMULATION; DYSPEPTIC SYMPTOMS;
PROXIMAL STOMACH; PANCREAS-KIDNEY; GASTROPARESIS; VALIDATION;
PREVALENCE; PREDICTORS; DISORDERS
AB BACKGROUND & AIMS: Chronic nausea and vomiting with normal gastric emptying is a poorly understood syndrome; we analyzed its characteristics. METHODS: We collected and analyzed data from 425 patients with chronic nausea and vomiting, enrolled at 6 centers by the Gastroparesis Clinical Research Consortium in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry. RESULTS: Among the patients, 319 (75%) had delayed emptying, defined by the results of a standardized, low-fat meal, and 106 had normal gastric emptying. Patients with or without delayed emptying did not differ in age, sex, or race, although those with normal gastric emptying were less likely to be diabetic. Symptom severity indexes were similar between groups for nausea, retching, vomiting, stomach fullness, inability to complete a meal, feeling excessively full after meals, loss of appetite, bloating, and visibly larger stomach. There were no differences in health care utilization, quality of life indexes, depression, or trait anxiety scores. However, state anxiety scores were slightly higher among patients with delayed gastric emptying. Total gastroparesis cardinal symptom index scores were not correlated with gastric retention after 2 or 4 hours in either group. Patients with the syndrome were not adequately captured by the stand-alone criteria for the Rome III diagnoses of chronic idiopathic nausea and functional vomiting. With rare exceptions, the diagnosis remained stable after a 48-week follow-up period. CONCLUSIONS: Patients with nausea and vomiting with normal gastric emptying represent a significant medical problem and are, for the most part, indistinguishable from those with gastroparesis. This syndrome is not categorized in the medical literature-it might be a separate clinical entity.
C1 [Pasricha, Pankaj J.] Stanford Univ, Sch Med, Div Gastroenterol & Hepatol, Palo Alto, CA 94305 USA.
[Colvin, Ryan; Yates, Katherine; Uenalp-Arida, Aynur; Lee, Linda; Tonascia, James] Johns Hopkins Univ, Baltimore, MD USA.
[Hasler, William L.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Abell, Thomas L.] Univ Mississippi, Jackson, MS 39216 USA.
[Farrugia, Gianrico] Mayo Clin, Rochester, MN USA.
[Koch, Kenneth L.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Parkman, Henry P.] Temple Univ, Philadelphia, PA 19122 USA.
[Snape, William J.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Hamilton, Frank] NIDDK, Bethesda, MD USA.
RP Pasricha, PJ (reprint author), Stanford Univ, Sch Med, Div Gastroenterol & Hepatol, 300 Pasteur Dr,Room M211,Alway Bldg, Palo Alto, CA 94305 USA.
EM Pasricha@stanford.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[U01DK073983, U01DK073975, U01DK073985, U01DK074007, U01DK073974,
U01DK074008]
FX The Gastroparesis Clinical Research Consortium (GpCRC) is supported by
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) (grants U01DK073983, U01DK073975, U01DK073985, U01DK074007,
U01DK073974, and U01DK074008).
NR 28
TC 56
Z9 56
U1 0
U2 3
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 JUL
PY 2011
VL 9
IS 7
BP 567
EP U89
DI 10.1016/j.cgh.2011.03.003
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 788TS
UT WOS:000292467900015
PM 21397732
ER
PT J
AU Abu Dayyeh, BK
Yang, M
Fuchs, BC
Karl, DL
Yamada, S
Sninsky, JJ
O'Brien, TR
Dienstag, JL
Tanabe, KK
Chung, RT
AF Abu Dayyeh, Barham K.
Yang, May
Fuchs, Bryan C.
Karl, Daniel L.
Yamada, Suguru
Sninsky, John J.
O'Brien, Thomas R.
Dienstag, Jules L.
Tanabe, Kenneth K.
Chung, Raymond T.
CA HALT-C Trial Grp
TI A Functional Polymorphism in the Epidermal Growth Factor Gene Is
Associated With Risk for Hepatocellular Carcinoma
SO GASTROENTEROLOGY
LA English
DT Article
DE Liver Disease; Cancer; Tumor; Prognosis; HCV
ID SERUM ALPHA-FETOPROTEIN; CHRONIC LIVER-DISEASE; CHRONIC HEPATITIS-C; EGF
POLYMORPHISM; CIRRHOTIC LIVER; EXPRESSION; RECEPTOR; REGENERATION;
DIAGNOSIS; MICE
AB BACKGROUND & AIMS: A single nucleotide polymorphism 61*G (rs4444903) in the epidermal growth factor (EGF) gene has been associated, in 2 case-control studies, with hepatocellular carcinoma (HCC). We tested associations between demographic, clinical, and genetic data and development of HCC, and developed a simple predictive model in a cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: Black and white subjects from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial (n = 816) were followed up prospectively for development of a definite or presumed case of HCC for a median time period of 6.1 years. We used the Cox proportional hazards regression model to determine the hazard ratio for risk of HCC and to develop prediction models. RESULTS: Subjects with EGF genotype G/G had a higher adjusted risk for HCC than those with genotype A/A (hazard ratio, 2.10; 95% confidence interval, 1.05-4.23; P = .03). After adjusting for EGF genotype, blacks had no increased risk of HCC risk compared with whites. Higher serum levels of EGF were observed among subjects with at least one G allele (P = .08); the subset of subjects with EGF G/G genotype and above-median serum levels of EGF had the highest risk of HCC. We developed a simple prediction model that included the EGF genotype to identify patients at low, intermediate, and high risk for HCC; 6-year cumulative HCC incidences were 2.3%, 10.4%, and 26%, respectively. CONCLUSIONS: We associated the EGF genotype G/G with increased risk for HCC; differences in its frequency among black and white subjects might account for differences in HCC incidence between these groups. We developed a model that incorporates EGF genotype and demographic and clinical variables to identify patients at low, intermediate, and high risk for HCC.
C1 [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
[Fuchs, Bryan C.; Karl, Daniel L.; Yamada, Suguru; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Abu Dayyeh, Barham K.; Dienstag, Jules L.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02114 USA.
[Fuchs, Bryan C.; Karl, Daniel L.; Yamada, Suguru; Tanabe, Kenneth K.] Harvard Univ, Dept Surg, Sch Med, Boston, MA 02114 USA.
[Yang, May] New England Res Inst, Watertown, MA 02172 USA.
[Sninsky, John J.] Celera Corp, Alameda, CA USA.
[O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Warren 1007C,55 Fruit St, Boston, MA 02114 USA.
EM rtchung@partners.org
FU Hoffmann-La Roche, Inc (now Genentech); Schering-Plough (now Merck);
Novartis; Romark; National Institutes of Health [DK078772]; Vertex
Pharmaceuticals; National Cancer Institute [5 K01 CA140861-02]; National
Institute of Diabetes & Digestive & Kidney Diseases; National Institute
of Allergy and Infectious Diseases; National Cancer Institute; National
Center for Minority Health and Health Disparities; General Clinical
Research Center; National Center for Research Resources, National
Institutes of Health; Celera Corporation; National Institutes of Health
FX These authors disclose the following: Raymond Chung receives research
support from Hoffmann-La Roche, Inc (now Genentech), Schering-Plough
(now Merck), Novartis, and Romark; is a consultant for Merck, Pfizer,
and Gilead; and is supported by National Institutes of Health grant
number DK078772. John Sninsky is an employee and has equity interest in
Celera Corporation. Jules Dienstag receives research support from Vertex
Pharmaceuticals; serves on the data monitoring committee for
Schering-Plough Research Institute, Human Genome Sciences, and
Medtronic; is on the Ad hoc Hepatitis Advisory Board for
Boehringer-Ingelheim; Antiviral Advisory Board for Gilead Sciences; is
an ad hoc consultant (with stock options) for Achillion; is on the
Clinical Advisory Board (with stock options) for Nucleonics; and is on
the Scientific Advisory Board (with stock options) for Metabasis.
Kenneth Tanabe received honoraria for a scientific lecture on January 1,
2008, from Vertex. Bryan Fuchs is supported by a K award from the
National Cancer Institute (5 K01 CA140861-02). The remaining authors
disclose no conflicts.; This study was supported by the National
Institute of Diabetes & Digestive & Kidney Diseases. Additional support
was provided by the National Institute of Allergy and Infectious
Diseases, the National Cancer Institute, the National Center for
Minority Health and Health Disparities, and by General Clinical Research
Center and Clinical and Translational Science Center grants from the
National Center for Research Resources, National Institutes of Health.
Additional funding to conduct this study was supplied by Hoffmann-La
Roche, Inc (now Genentech), and Celera Corporation through Cooperative
Research and Development Agreements with the National Institutes of
Health.
NR 40
TC 61
Z9 62
U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUL
PY 2011
VL 141
IS 1
BP 141
EP 149
DI 10.1053/j.gastro.2011.03.045
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 786IX
UT WOS:000292299700035
PM 21440548
ER
PT J
AU Hong, LE
Yang, X
Wonodi, I
Hodgkinson, CA
Goldman, D
Stine, OC
Stein, ES
Thaker, GK
AF Hong, L. E.
Yang, X.
Wonodi, I.
Hodgkinson, C. A.
Goldman, D.
Stine, O. C.
Stein, E. S.
Thaker, G. K.
TI A CHRNA5 allele related to nicotine addiction and schizophrenia
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE alpha 5; comorbidity; nAChR; nicotine addiction; schizophrenia; smoking
ID RECEPTOR SUBUNIT GENE; BIPOLAR DISORDER; HEAVY SMOKING; LUNG-CANCER;
SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; CANDIDATE GENES; ASSOCIATION;
DEPENDENCE; RISK
AB Schizophrenia and nicotine addiction are both highly heritable phenotypes. Because individuals with schizophrenia have a higher rate of smoking than those in the general population, one could hypothesize that genes associated with smoking might be overrepresented in schizophrenia and thus help explain their increased smoking incidence. Although a number of genes have been proposed to explain the increased smoking risk in schizophrenia, none of them have been consistently linked to smoking and schizophrenia, and thus difficult to explain the increased smoking in schizophrenia. A functional smoking-related nicotinic acetylcholine receptor alpha 5 subunit gene (CHRNA5) nonsynonymous single nucleotide polymorphism (SNP) rs16969968 (Asp398Asn) has recently been discovered and replicated. As such, we tested whether this variant contributes to smoking in schizophrenia in a sample of 313 schizophrenia patients and 525 controls. The Asp398Asn risk allele is significantly associated with smoking severity independently in schizophrenia patient smokers (P = 0.001) and control smokers (P = 0.029). Furthermore, the same risk allele is significantly associated with schizophrenia in both Caucasian (P = 0.022) and African-American (P = 0.006) nonsmoker schizophrenia patients compared with control nonsmokers. Intriguingly, this SNP was not significantly associated with smoking status (smokers vs. nonsmokers) in either schizophrenia patients or controls. Therefore, our study identifies a genetic variant that is simultaneously linked to smoking and schizophrenia in the same cohort, but whether this SNP contributes to the increased smoking prevalence in schizophrenia patients requires additional studies.
C1 [Hong, L. E.; Yang, X.; Wonodi, I.; Thaker, G. K.] Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Sch Med, Baltimore, MD 21228 USA.
[Hodgkinson, C. A.; Goldman, D.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
[Stine, O. C.] Univ Maryland, Genom Core Facil, GCRC, Sch Med, Baltimore, MD 21228 USA.
[Stein, E. S.] NIDA, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD USA.
RP Hong, LE (reprint author), Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Sch Med, POB 21247, Baltimore, MD 21228 USA.
EM ehong@mprc.umaryland.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU NIDA; NIAAA; National Institutes of Health [DA027680, MH085646,
MH077852]; Maryland Cigarette Restitution Fund Program
FX Support was received from the NIDA and NIAAA Intramural Research
Programs, National Institutes of Health grants DA027680, MH085646,
MH077852 and the Maryland Cigarette Restitution Fund Program.
NR 43
TC 20
Z9 20
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD JUL
PY 2011
VL 10
IS 5
BP 530
EP 535
DI 10.1111/j.1601-183X.2011.00689.x
PG 6
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 788PM
UT WOS:000292456900003
PM 21418140
ER
PT J
AU Kirkland, PA
Reidy, M
Masison, DC
AF Kirkland, P. Aaron
Reidy, Michael
Masison, Daniel C.
TI Functions of Yeast Hsp40 Chaperone Sis1p Dispensable for Prion
Propagation but Important for Prion Curing and Protection From Prion
Toxicity
SO GENETICS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; GUANIDINE-HYDROCHLORIDE; PSI+ PRION; SHUTTLE
VECTORS; ATPASE ACTIVITY; CO-CHAPERONES; DNAJ PROTEIN; IN-VIVO; HSP70;
HSP104
AB Replication of amyloid-based yeast prions [PSI(+)], [URE3], and [PIN(+)] depends on the protein disaggregation machinery that includes Hsp104, Hsp70, and Hsp40 molecular chaperones. Yet, overexpressing Hsp104 cures cells of [PSI(+)] prions. An Hsp70 mutant (Ssa1-21p) antagonizes propagation of [PSI(+)] in a manner resembling elevated Hsp104. The major cytosolic Hsp40 Sis1p is the only Hsp40 required for replication of these prions, but its role in [PSI(+)] curing is unknown. Here we find that all nonessential functional regions of Sis1p are dispensable for [PSI(+)] propagation, suggesting that other Hsp40's might provide Hsp40 functions required for [PSI(+)] replication. Conversely, several Sis1p functions were important for promoting antiprion effects of both Ssa1-21p and Hsp104, which implies a link between the antiprion effects of these chaperones and suggests that Sis1p is a specific Hsp40 important for [PSI(+)] curing. These contrasting findings suggest that the functions of Hsp104 that are important for propagation and elimination of [PSI(+)] are either distinct or specified by different Hsp40's. This work also uncovered a growth inhibition caused by [PSI(+)] when certain functions of Sis1p were absent, suggesting that Sis1p protects cells from cytotoxicity caused by [PSI(+)] prions.
C1 [Kirkland, P. Aaron; Reidy, Michael; Masison, Daniel C.] NIH, Lab Biochem & Genet, NIDDK, Bethesda, MD 20892 USA.
RP Masison, DC (reprint author), NIH, Lab Biochem & Genet, NIDDK, Bldg 8,Room 225,8 Ctr Dr, Bethesda, MD 20892 USA.
EM masisond@helix.nih.gov
OI Reidy, Michael/0000-0002-9290-7595
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, MD
FX We thank Giman Jung and Guo-Chiuan Hung for plasmid construction, Deepak
Sharma for assistance in manuscript preparation, and Elizabeth Craig
(University of Wisconsin, Madison) for generously providing several SIS1
plasmid constructs and antibodies. This work was supported by the
intramural program of the National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health, Bethesda, MD.
NR 53
TC 24
Z9 26
U1 1
U2 7
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD JUL
PY 2011
VL 188
IS 3
BP 565
EP 577
DI 10.1534/genetics.111.129460
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 789TJ
UT WOS:000292538900008
PM 21555396
ER
PT J
AU Stottmann, RW
Moran, JL
Turbe-Doan, A
Driver, E
Kelley, M
Beier, DR
AF Stottmann, R. W.
Moran, J. L.
Turbe-Doan, A.
Driver, E.
Kelley, M.
Beier, D. R.
TI Focusing Forward Genetics: A Tripartite ENU Screen for
Neurodevelopmental Mutations in the Mouse
SO GENETICS
LA English
DT Article
ID PLANAR CELL POLARITY; NEURAL-TUBE DEFECTS; CORTICAL DEVELOPMENT;
CASPASE-3-DEFICIENT MICE; LUNG DEVELOPMENT; CASPASE 3; MUTANT; PROTEIN;
IDENTIFICATION; MUTAGENESIS
AB The control of growth, patterning, and differentiation of the mammalian forebrain has a large genetic component, and many human disease loci associated with cortical malformations have been identified. To further understand the genes involved in controlling neural development, we have performed a forward genetic screen in the mouse (Mus musculus) using ENU mutagenesis. We report the results from our ENU screen in which we biased our ascertainment toward mutations affecting neurodevelopment. Our screen had three components: a careful morphological and histological examination of forebrain structure, the inclusion of a retinoic acid response element-lacZ reporter transgene to highlight patterning of the brain, and the use of a genetically sensitizing locus, Lis1/Pafah1b1, to predispose animals to neurodevelopmental defects. We recovered and mapped eight monogenic mutations, seven of which affect neurodevelopment. We have evidence for a causal gene in four of the eight mutations. We describe in detail two of these: a mutation in the planar cell polarity gene scribbled homolog (Drosophila) (Scrib) and a mutation in caspase-3 (Casp3). We find that refining ENU mutagenesis in these ways is an efficient experimental approach and that investigation of the developing mammalian nervous system using forward genetic experiments is highly productive.
C1 [Stottmann, R. W.; Moran, J. L.; Turbe-Doan, A.; Beier, D. R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet Dept Med, Boston, MA 02115 USA.
[Driver, E.; Kelley, M.] Natl Inst Deafness & Other Communicat Disorders, Dev Neurosci Sect, Bethesda, MD 20892 USA.
RP Beier, DR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet Dept Med, Ave Louis Pasteur, Boston, MA 02115 USA.
EM beier@receptor.med.harvard.edu
OI Moran, Jennifer/0000-0002-5664-4716; Driver,
Elizabeth/0000-0002-5618-1053
FU National Institutes of Health [R01HD0306404, R01MH081187, F32HD053198]
FX We thank A. Tilt, H. Qiu, S. Hines, A. Bolton, and S. Nicholson for
assistance in screening and mapping; M. Lun, Y. Yun, and M. Prysak for
assistance with animal husbandry; and J. Min for assistance with
caspase-3 immunohistochemistry. We thank U. Drager (University of
Massachusetts Medical School) for the RARE-lacZ mouse line, Lisa
Good-rich (Harvard Medical School) for the looptail mice, and A.
Wynshaw-Boris (University of California at San Francisco) for the Lis1
mouse. Funding for this project is from the National Institutes of
Health (grants R01HD0306404 and R01MH081187 to D. R. B. and grant
F32HD053198 to R.W.S.).
NR 44
TC 18
Z9 18
U1 0
U2 2
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD JUL
PY 2011
VL 188
IS 3
BP 615
EP 624
DI 10.1534/genetics.111.126862
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 789TJ
UT WOS:000292538900012
PM 21515572
ER
PT J
AU Masciari, S
Dewanwala, A
Stoffel, EM
Lauwers, GY
Zheng, H
Achatz, MI
Riegert-Johnson, D
Foretova, L
Silva, EM
Digianni, L
Verselis, SJ
Schneider, K
Li, FP
Fraumeni, J
Garber, JE
Syngal, S
AF Masciari, Serena
Dewanwala, Akriti
Stoffel, Elena M.
Lauwers, Gregory Y.
Zheng, Hui
Achatz, Maria Isabel
Riegert-Johnson, Douglas
Foretova, Lenka
Silva, Edaise M.
Digianni, Lisa
Verselis, Sigitas J.
Schneider, Katherine
Li, Frederick P.
Fraumeni, Joseph
Garber, Judy E.
Syngal, Sapna
TI Gastric cancer in individuals with Li-Fraumeni syndrome
SO GENETICS IN MEDICINE
LA English
DT Article
DE Li Fraumeni syndrome; gastric cancer; hereditary gastric cancer
syndromes; germline mutations; TP53
ID FAMILIAL ADENOMATOUS POLYPOSIS; BRCA1 MUTATION CARRIERS; P53 GERMLINE
MUTATIONS; E-CADHERIN GENE; BREAST-CANCER; COLORECTAL-CANCER;
CHILDHOOD-CANCER; DIFFUSE; TP53; RISK
AB Purpose: Li-Fraumeni syndrome is a rare hereditary cancer syndrome associated with germline mutations in the TP53 gene. Although sarcomas, brain tumors, leukemias, breast and adrenal cortical carcinomas are typically recognized as Li-Fraumeni syndrome-associated tumors, the occurrence of gastrointestinal neoplasms has not been fully evaluated. In this analysis, we investigated the frequency and characteristics of gastric cancer in Li-Fraumeni syndrome. Methods: Pedigrees and medical records of 62 TP53 mutation-positive families were retrospectively reviewed from the Dana-Farber/National Cancer Institute Li-Fraumeni syndrome registry. We identified subjects with gastric cancer documented either by pathology report or death certificate and performed pathology review of the available specimens. Results: Among 62 TP53 mutation-positive families, there were 429 cancer-affected individuals. Gastric cancer was the diagnosis in the lineages of 21 (4.9%) subjects from 14 families (22.6%). The mean and median ages at gastric cancer diagnosis were 43 and 36 years, respectively (range: 24-74 years), significantly younger compared with the median age at diagnosis in the general population based on Surveillance Epidemiology and End Results data (71 years). Five (8.1%) families reported two or more cases of gastric cancer, and six (9.7%) families had cases of both colorectal and gastric cancers. No association was seen between phenotype and type/location of the TP53 mutations. Pathology review of the available tumors revealed both intestinal and diffuse histologies. Conclusions: Early-onset gastric cancer seems to be a component of Li-Fraumeni syndrome, suggesting the need for early and regular endoscopic screening in individuals with germline TP53 mutations, particularly among those with a family history of gastric cancer. Genet Med 2011:13(7):651-657.
C1 [Masciari, Serena; Dewanwala, Akriti; Stoffel, Elena M.; Digianni, Lisa; Schneider, Katherine; Li, Frederick P.; Garber, Judy E.; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA.
[Stoffel, Elena M.; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Zheng, Hui] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA.
[Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Achatz, Maria Isabel] Hosp AC Camargo Fund Antonio Prudente, Dept Oncogenet, Sao Paulo, Brazil.
[Achatz, Maria Isabel] Natl Inst Sci & Technol Oncogen, Sao Paulo, Brazil.
[Riegert-Johnson, Douglas] Mayo Clin, Coll Med, Div Gastroenterol & Hepatol, Jacksonville, FL 32224 USA.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Silva, Edaise M.] Hosp AC Camargo Fund Antonio Prudente, Dept Anat Pathol, Sao Paulo, Brazil.
[Verselis, Sigitas J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Fraumeni, Joseph] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St,SM 209, Boston, MA 02115 USA.
EM ssyngal@partners.org
RI Achatz, Maria Isabel /C-5751-2013; Oncogenomica, Inct/H-9999-2013
OI Achatz, Maria Isabel /0000-0001-6894-1219;
FU Charles A. King Trust; Bank of America (Boston, MA); Humane Society of
the Commonwealth of Massachusetts; US National Cancer Institute [K24 CA
113433]; Harvard Catalyst/The Harvard Clinical and Translational Science
Center [UL1 RR 025758]; STARR Foundation; [MZ0 MOU 2005]
FX This work was supported by Charles A. King Trust, Bank of America
Fellowship, Co-Trustee (Boston, MA) and The Humane Society of the
Commonwealth of Massachusetts Postdoctoral Research Fellowship (S.M.),
the US National Cancer Institute Grant K24 CA 113433 (S.S.), Scholars in
Clinical Science Program of Harvard Catalyst/The Harvard Clinical and
Translational Science Center (Award no. UL1 RR 025758 and financial
contributions from Harvard University and its affiliated academic health
care centers), and supported, in part, by the STARR Foundation. Genetic
testing in CR (L.F.) was supported by Grant MZ0 MOU 2005. The authors
are grateful to the Li-Fraumeni patients and families who kindly
consented over the years to be part of the DFCI/NCI LFS registry.
NR 51
TC 39
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U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD JUL
PY 2011
VL 13
IS 7
BP 651
EP 657
DI 10.1097/GIM.0b013e31821628b6
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 789TC
UT WOS:000292538200008
PM 21552135
ER
PT J
AU Chen, JC
AF Chen, Jichun
TI Hematopoietic stem cell development, aging and functional failure
SO INTERNATIONAL JOURNAL OF HEMATOLOGY
LA English
DT Article
DE Hematopoietic stem cells; Ontogeny; Niche; Senescence; Bone marrow
failure
ID BONE-MARROW FAILURE; TELOMERASE REVERSE-TRANSCRIPTASE; ACQUIRED
APLASTIC-ANEMIA; UMBILICAL-CORD BLOOD; SLAM FAMILY RECEPTORS; COLONY
FORMING CELLS; FETAL LIVER; PROGENITOR CELLS; MOUSE MODEL;
DYSKERATOSIS-CONGENITA
AB Hematopoietic stem cells (HSCs) are found in yolk sac, fetal liver, umbilical cord blood, placenta, and amniotic fluid during mammalian embryonic development. In adults, HSCs reside in marrow cavity of long bones where they self-renew and differentiate to replenish short-lived mature blood cells. HSCs exist in very low frequencies within specific "niches" where they interact with the surrounding environment through molecular associations. Overall HSC function can last much longer than a normal lifetime, but HSCs do show functional senescence with characteristic features of decreased self-renewal, reduced clonal stability, reduced homing and engraftment, and biased lineage commitment. The progressive shortening of telomeres with increasing age, especially under conditions with specific mutations in the telomerase gene complex, could predispose patients to HSC dysfunction and bone marrow failure diseases. Continuous investigation into HSC biology should facilitate the utilization of HSCs as a therapeutic modality and helps to prevent HSC malfunction.
C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Chen, JC (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Clin Res Ctr Room 3E-5132,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chenji@nhlbi.nih.gov
FU NIH
FX This work was supported by NIH intramural research funds.
NR 109
TC 6
Z9 7
U1 0
U2 3
PU SPRINGER TOKYO
PI TOKYO
PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN
SN 0925-5710
J9 INT J HEMATOL
JI Int. J. Hematol.
PD JUL
PY 2011
VL 94
IS 1
BP 3
EP 10
DI 10.1007/s12185-011-0856-1
PG 8
WC Hematology
SC Hematology
GA 789JX
UT WOS:000292512900002
PM 21523336
ER
PT J
AU Goveas, JS
Espeland, MA
Hogan, P
Dotson, V
Tarima, S
Coker, LH
Ockene, J
Brunner, R
Woods, NF
Wassertheil-Smoller, S
Kotchen, JM
Resnick, S
AF Goveas, Joseph S.
Espeland, Mark A.
Hogan, Patricia
Dotson, Vonetta
Tarima, Sergey
Coker, Laura H.
Ockene, Judith
Brunner, Robert
Woods, Nancy F.
Wassertheil-Smoller, Sylvia
Kotchen, Jane M.
Resnick, Susan
TI Depressive symptoms, brain volumes and subclinical cerebrovascular
disease in postmenopausal women: The Women's Health Initiative MRI Study
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Late-life depression; Regional brain volumes; Subclinical
cerebrovasailar disease; Structural magnetic resonance imaging
ID MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; WHITE-MATTER
HYPERINTENSITIES; CONJUGATED EQUINE ESTROGENS; RECURRENT MAJOR
DEPRESSION; GERIATRIC DEPRESSION; MAGNETIC-RESONANCE; HIPPOCAMPAL
VOLUME; ALZHEIMER-DISEASE; WHIMS-MRI
AB Objective: Late-life depressive symptoms (DS) increase the risk of incident mild cognitive impairment and probable dementia in the elderly. Our objectives were to examine the relationship between elevated DS and regional brain volumes including frontal lobe subregions, hippocampus and amygdala, and to determine whether elevated DS were associated with increased subclinical cerebrovascular disease in postmenopausal women.
Methods: DS were assessed an average of 8 years prior to structural brain MRI in 1372 women. The 8-item Burnam regression algorithm was used to define DS with a cut-point of 0.009. Adjusting for potential confounders, mean differences in total brain, frontal lobe subregions, hippocampus and amygdala volumes and total ischemic lesion volumes in the basal ganglia and the cerebral white and gray matter outside the basal ganglia were compared between women with and without DS.
Results: Depressed women had lower baseline global cognition and were more likely to have prior hormone therapy history. After full adjustment, DS at baseline were associated with smaller superior and middle frontal gyral volumes. Hippocampal and amygdala volumes, and ischemic lesion volumes were similar in depressed and non-depressed women.
Limitations: Depression was not assessed based on semi-structured interview, and MRI scans were obtained cross-sectionally rather than longitudinally. Longitudinal MRI assessments will be necessary to define the temporal relationships between DS and frontal lobe volumes.
Conclusions: Elevated DS were associated with lower volumes in certain frontal lobe subregions but not in the medial temporal lobe structures. Our findings support the role of frontal lobe structures in late-life DS among women. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA.
[Espeland, Mark A.; Hogan, Patricia; Coker, Laura H.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth, Winston Salem, NC USA.
[Dotson, Vonetta] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA.
[Tarima, Sergey; Kotchen, Jane M.] Med Coll Wisconsin, Dept Populat Hlth, Milwaukee, WI 53226 USA.
[Ockene, Judith] Univ Massachusetts, Dept Prevent & Behav Med, Amherst, MA 01003 USA.
[Brunner, Robert] Univ Nevada, Sch Med, Dept Family & Community Med, Reno, NV 89557 USA.
[Woods, Nancy F.] Univ Washington, Seattle, WA 98195 USA.
[Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Resnick, Susan] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Goveas, JS (reprint author), Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA.
EM jgoveas@mcw.edu
RI Dotson, Vonetta/K-6090-2015;
OI Dotson, Vonetta/0000-0002-3043-3320
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, U.S. Department of Health and Human Services [N01WH22110, 24152,
32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, 44221]; Wyeth Pharmaceuticals; National Institute on
Aging, NIH
FX The Women's Health Initiative (WHI) program is funded by the National
Heart, Lung, and Blood Institute, National Institutes of Health, U.S.
Department of Health and Human Services through contracts N01WH22110,
24152, 32100-2,
32105-6,32108-9,32111-13,32115,32118-32119,32122,42107-26,42129-32, and
44221. The active study drug and placebo were supplied by Wyeth-Ayerst
Research Laboratories, Philadelphia, Pennsylvania.; The Women's Health
Initiative Memory Study was funded in part by Wyeth Pharmaceuticals as
an ancillary study to the WHI. Wyeth Pharmaceuticals did not participate
in the design and conduct of the studies, in the collection, analysis
and interpretation of the data, or in preparation, review or approval of
this manuscript. Dr. Susan M. Resnick is funded by the Intramural
Research Program, National Institute on Aging, NIH.
NR 62
TC 24
Z9 25
U1 2
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JUL
PY 2011
VL 132
IS 1-2
BP 275
EP 284
DI 10.1016/j.jad.2011.01.020
PG 10
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 788IK
UT WOS:000292438400037
PM 21349587
ER
PT J
AU Cooper, SD
Fletcher, BL
Silinski, MAR
Brown, SS
Lodge, JW
Fernando, RA
Collins, BJ
AF Cooper, Stephen D.
Fletcher, Brenda L.
Silinski, Melanie A. Rehder
Brown, Sherri S.
Lodge, Jon W.
Fernando, Reshan A.
Collins, Bradley J.
TI Determination of L-Ephedrine, Pseudoephedrine, and Caffeine in Rat
Plasma by Liquid Chromatography-Tandem Mass Spectrometry
SO JOURNAL OF ANALYTICAL TOXICOLOGY
LA English
DT Article
ID DIETARY-SUPPLEMENTS; PHARMACOLOGY; COMBINATION; ALKALOIDS
C1 [Cooper, Stephen D.; Fletcher, Brenda L.; Silinski, Melanie A. Rehder; Brown, Sherri S.; 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.
RP Cooper, SD (reprint author), RTI Int, POB 12194, Res Triangle Pk, NC 27709 USA.
FU National Institute of Environmental Health Sciences [N01-ES-65554]
FX This project has been funded in whole or in part with federal funds from
the National Institute of Environmental Health Sciences under Contract
No. N01-ES-65554. The authors thank Dr. Brian F. Thomas of RTI
International and Dr. Cynthia S. Smith of NIEHS/NTP for reviewing this
work.
NR 14
TC 5
Z9 5
U1 0
U2 5
PU PRESTON PUBL INC
PI NILES
PA 6600 W TOUHY AVE, NILES, IL 60714-4588 USA
SN 0146-4760
J9 J ANAL TOXICOL
JI J. Anal. Toxicol.
PD JUL-AUG
PY 2011
VL 35
IS 6
BP 341
EP 348
PG 8
WC Chemistry, Analytical; Toxicology
SC Chemistry; Toxicology
GA 787HV
UT WOS:000292368100003
PM 21740690
ER
PT J
AU Boyce, AM
Gafni, RI
AF Boyce, Alison M.
Gafni, Rachel I.
TI Approach to the Child with Fractures
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID X-RAY ABSORPTIOMETRY; PEDIATRIC OFFICIAL POSITIONS; BONE-MINERAL
DENSITY; BISPHOSPHONATE-INDUCED OSTEOPETROSIS; INTRAVENOUS PAMIDRONATE
THERAPY; OSTEOGENESIS-IMPERFECTA; CEREBRAL-PALSY; PHYSICAL-ACTIVITY;
ORAL ALENDRONATE; CLINICAL-TRIAL
AB Evaluation of the child with fractures is challenging, as no clear guidelines exist to distinguish traumatic from pathological fractures. Although most fractures in childhood are benign, recurrent fractures may be associated with a wide variety of primary skeletal diseases as well as secondary causes, necessitating a careful history and physical exam to guide the evaluation. There is no "goldstandard" for the evaluation and treatment of children with fractures and low bone mineral density (BMD); therefore, the diagnosis of osteoporosis in a pediatric patient should be made using a combination of clinical and radiographic features. Interpretation of bone densitometry in growing patients presents a unique set of challenges because areal BMD measured by dual-energy x-ray absorptiometry depends on multiple dynamic variables. Interpretation of pediatric dual-energy x-ray absorptiometry should be based on Z-scores (SD scores compared to age, sex, and ethnicity-matched controls), using normative databases specific to the brand of densitometer and the patient population. Given the skeleton's ability to recover from low BMD through modeling and remodeling, optimizing management of underlying conditions leading to bone fragility is the initial step. Conservative measures including calcium and vitamin D supplementation and weight-bearing physical activity are important interventions that should not be overlooked. The use of bisphosphonates in children and adolescents is controversial due to lack of long-term efficacy and safety data and should be limited to clinical trials and compassionate therapy in children with significantly compromised quality of life. Close monitoring is required, and further study is necessary to assess their long-term safety and efficacy in children. (J Clin Endocrinol Metab 96: 1943-1952, 2011)
C1 [Gafni, Rachel I.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Boyce, Alison M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Gafni, RI (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 30,Room 228,30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA.
EM gafnir@mail.nih.gov
NR 76
TC 17
Z9 17
U1 1
U2 5
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2011
VL 96
IS 7
BP 1943
EP 1952
DI 10.1210/jc.2010-2546
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 788OO
UT WOS:000292454500026
PM 21734001
ER
PT J
AU Lindsay, JR
Oldfield, EH
Stratakis, CA
Nieman, LK
AF Lindsay, John R.
Oldfield, Edward H.
Stratakis, Constantine A.
Nieman, Lynnette K.
TI The Postoperative Basal Cortisol and CRH Tests for Prediction of
Long-Term Remission from Cushing's Disease after Transsphenoidal Surgery
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE-SUPPRESSION TEST;
PITUITARY SURGERY; DIFFERENTIAL-DIAGNOSIS; STIMULATION TEST;
RISK-FACTORS; CURE; RECURRENCE; RADIOIMMUNOASSAY; MANAGEMENT
AB Context: Selective adenomectomy via transsphenoidal surgery induces remission of Cushing's disease (CD) in most patients. Although an undetectable postoperative serum cortisol (< 2 mu g/dl) has been advocated as an index of remission, there is no consensus on predictors of recurrence.
Objective: We hypothesized that patients with subnormal cortisol (2-4.9 mu g/dl) might achieve long-term remission and that postoperative responses to CRH might predict recurrence.
Design, Setting, and Participants: We prospectively studied CD patients with initial remission after adenomectomy or hemihypophysectomy (n = 14). Long-term recurrence (n = 39) or remission (n = 293) was assigned by laboratory results, glucocorticoid dependence, or patient survey at a mean of 10.6 yr after surgery.
Intervention and Main Outcome Measures: Postoperatively, morning cortisol was measured on d 3-5, and cortisol and ACTH responses to ovine CRH were assessed around d 10.
Results: Follow-up duration was median 11 yr (range 1-22.8 yr). Fewer patients achieved a cortisol nadir below 2 mu g/dl (87%) than below 5 mu g/dl (98%), yet recurrence rates were similar (< 2 mu g/dl, 9.5%; < 5 mu g/dl, 10.4%; 2-4.9 mu g/dl, 20%; not significant). CRH-stimulated cortisol (P < 0.002) and ACTH(P = 0.04) values were higher for the recurrence than the remission group. However, no basal or stimulated ACTH or serum or urine cortisol cutoff value predicted all who later recurred.
Conclusions: A postoperative cortisol below 2 mu g/dl predicts long-term remission after transsphenoidal surgery in CD. Remission in those with intermediate d 3-5 postoperative cortisol values (2-4.9 mu g/dl) suggests that these patients do not require immediate reoperation. However, because no single cortisol cutoff value excludes all patients with recurrence, all require long-term clinical follow-up. (J Clin Endocrinol Metab 96: 2057-2064, 2011)
C1 [Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Training Program, Bethesda, MD 20892 USA.
[Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Lindsay, John R.] Western Hlth & Social Care Trust, Altnagelvin Area Hosp, Derry BT4, Londonderry, North Ireland.
RP Nieman, LK (reprint author), Bldg 10 CRC,Room 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM niemanl@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Neurologic Disorders and Stroke,
National Institutes of Health
FX The intramural programs of the Eunice Kennedy Shriver National Institute
of Child Health and Human Development and the National Institute of
Neurologic Disorders and Stroke, National Institutes of Health,
supported this work.
NR 34
TC 40
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U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2011
VL 96
IS 7
BP 2057
EP 2064
DI 10.1210/jc.2011-0456
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 788OO
UT WOS:000292454500042
PM 21508126
ER
PT J
AU Baron, S
Finbloom, J
Horowitz, J
Bekisz, J
Morrow, A
Zhao, TM
Fey, S
Schmeisser, H
Balinsky, C
Miyake, K
Clark, C
Zoon, K
AF Baron, Samuel
Finbloom, Joel
Horowitz, Julie
Bekisz, Joseph
Morrow, Angel
Zhao, Tongmao
Fey, Samuel
Schmeisser, Hana
Balinsky, Corey
Miyake, Kotaro
Clark, Christopher
Zoon, Kathryn
TI Near Eradication of Clinically Relevant Concentrations of Human Tumor
Cells by Interferon-Activated Monocytes In Vitro
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID TUMORICIDAL ACTIVITY; BREAST-CARCINOMA; BLOOD MONOCYTES; DENDRITIC
CELLS; CANCER-PATIENTS; THERAPY; INFILTRATION; ALPHA; RECRUITMENT;
MECHANISMS
AB We have previously reported that low concentrations of interferon (IFN)-activated monocytes exert near-eradicative cytocidal activity against low concentrations of several human tumor cells in vitro. In the present study, we examined 7 human tumor cell lines and 3 diploid lines in the presence or absence of 10 ng/mL IFN alpha 2a and monocytes. The results confirmed strong cytocidal activity against 4 of 7 tumor lines but none against 3 diploid lines. To model larger in vivo tumors, we increased the target cell concentration and determined the concentration of IFN alpha 2a and monocytes, required for cell death. We found that increasing the tumor cell concentration from 10- to 100-fold (10(5) cells/well) required an increase in the concentration of IFNs by over 100-fold and monocytes by 10-fold. High concentrations of monocytes could sometimes kill tumor or diploid cells in the absence of IFN. We may conclude that killing of high concentrations of tumor or diploid cells required high concentrations of monocytes that could sometimes kill in the absence of IFN. Thus, high concentrations of tumor cells required high concentrations of IFN and monocytes to cause near eradication of tumor cells. These findings may have clinical implications.
C1 [Baron, Samuel; Finbloom, Joel; Horowitz, Julie; Bekisz, Joseph; Morrow, Angel; Zhao, Tongmao; Fey, Samuel; Schmeisser, Hana; Balinsky, Corey; Miyake, Kotaro; Clark, Christopher; Zoon, Kathryn] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
[Baron, Samuel] Univ Texas Med Branch, Galveston, TX USA.
RP Zoon, K (reprint author), NIAID, Cytokine Biol Sect, NIH, Bldg 33,Room 33-2N09G-2,33 North Dr, Bethesda, MD 20892 USA.
EM kzoon@niaid.nih.gov
FU NIAID, NIH
FX This work was supported by the Intramural Research Program of the NIAID,
NIH.
NR 34
TC 7
Z9 7
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD JUL
PY 2011
VL 31
IS 7
BP 569
EP 573
DI 10.1089/jir.2010.0153
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 788LW
UT WOS:000292447400007
PM 21323569
ER
PT J
AU Ribot, EJ
Martinez-Santiesteban, FM
Simedrea, C
Steeg, PS
Chambers, AF
Rutt, BK
Foster, PJ
AF Ribot, Emeline J.
Martinez-Santiesteban, Francisco M.
Simedrea, Carmen
Steeg, Patricia S.
Chambers, Ann F.
Rutt, Brian K.
Foster, Paula J.
TI In Vivo Single Scan Detection of Both Iron-Labeled Cells and Breast
Cancer Metastases in the Mouse Brain Using Balanced Steady-State Free
Precession Imaging at 1.5 T
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE MRI; b-SSFP; iron; cancer; metastasis; brain
ID CENTRAL-NERVOUS-SYSTEM; CELLULAR MRI; OXIDE PARTICLES; SSFP; RESOLUTION;
INJURY; MODEL
AB Purpose: To simultaneously detect iron-labeled cancer cells and brain tumors in vivo in one scan, the balanced steady-state free precession (b-SSFP) imaging sequence was optimized at 1.5 T on mice developing brain metastases subsequent to the injection of micron-sized iron oxide particle-labeled human breast cancer cells.
Materials and Methods: b-SSFP sequence parameters (repetition time, flip angle, and receiver bandwidth) were varied and the signal-to-noise ratio, contrast between the brain and tumors, and the number of detected iron-labeled cells were evaluated.
Results: Optimal b-SSFP images were acquired with a 26 msec repetition time, 35 degrees flip angle, and bandwidth of +/- 21 kHz. b-SSFP images were compared with T(2)-weighted 2D fast spin echo (FSE) and 3D spoiled gradient recalled echo (SPGR) images. The mean tumor-brain contrast-to-noise ratio and the ability to detect iron-labeled cells were the highest in the b-SSFP images.
Conclusion: A single b-SSFP scan can be used to visualize both iron-labeled cells and brain metastases.
C1 [Ribot, Emeline J.; Martinez-Santiesteban, Francisco M.; Foster, Paula J.] Univ Western Ontario, Imaging Res Labs, Robarts Res Inst, London, ON N6A 5K8, Canada.
[Simedrea, Carmen; Chambers, Ann F.] London Reg Canc Program, London, ON, Canada.
[Steeg, Patricia S.] NCI, Womens Cancers Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chambers, Ann F.; Foster, Paula J.] Univ Western Ontario, Dept Med Biophys, London, ON N6A 5K8, Canada.
[Rutt, Brian K.] Stanford Univ, Dept Radiol, Richard M Lucas Ctr Imaging, Stanford, CA 94305 USA.
RP Foster, PJ (reprint author), Univ Western Ontario, Imaging Res Labs, Robarts Res Inst, 100 Perth Dr,Rm 1200B, London, ON N6A 5K8, Canada.
EM pfos-ter@imaging.robarts.ca
RI Foster, Paula/M-2201-2013; Chambers, Ann/L-6285-2015
OI Foster, Paula/0000-0002-4868-3395; Chambers, Ann/0000-0002-9509-5123
FU US Department of Defense [W81XWH-06-2-0033]; London Regional Cancer
Program; Canada Research Chair in Oncology; National Cancer Institute
FX Contract grant sponsor: US Department of Defense Breast Cancer Research
Program; Contract grant number: W81XWH-06-2-0033 (to P.S.S., A.F.C.,
P.J.F.); Contract grant sponsors: Translational Breast Cancer Fellowship
from the London Regional Cancer Program (to E.J.R.); Canada Research
Chairs Program (Canada Research Chair in Oncology to A.F.C.); Intramural
Program of the National Cancer Institute (to P.S.S.).
NR 22
TC 10
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUL
PY 2011
VL 34
IS 1
BP 231
EP 238
DI 10.1002/jmri.22593
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 788CA
UT WOS:000292421800029
PM 21698713
ER
PT J
AU Patterson, GH
AF Patterson, G. H.
TI Highlights of the optical highlighter fluorescent proteins
SO JOURNAL OF MICROSCOPY
LA English
DT Review
DE Fluorescence microscopy; photoactivation; photoconversion;
photoswitching
ID CORRELATION SPECTROSCOPY; GENERATION; NANOSCOPY; DYNAMICS; BRIGHT;
PHOTOCONVERSION; CONVERSION; MUTANTS; CELLS
AB The development of super-resolution microscopy techniques using molecular localization, such as photoactivated localization microscopy, fluorescence photoactivated localization microscopy, stochastic optical reconstruction microscopy, photoactivated localization microscopy with independent running acquisition and many others, has heightened interest in molecules that will be grouped here into a category referred to as 'optical highlighter' fluorescent proteins. This review will survey many of the advances in development of fluorescent proteins for optically highlighting sub-populations of fluorescently labelled molecules.
C1 Natl Inst Biomed Imaging & Bioengn, Biophoton Sect, NIH, Bethesda, MD 20892 USA.
RP Patterson, GH (reprint author), Natl Inst Biomed Imaging & Bioengn, Biophoton Sect, NIH, Bldg 13,Room 3E33,13 S Drive, Bethesda, MD 20892 USA.
EM pattersg@mail.nih.gov
FU National Institutes of Health; National Institute of Biomedical Imaging
and Bioengineering
FX I thank Yan Fu for critical reading of this manuscript. This work was
supported by the intramural Research Program of the National Institutes
of Health, including the National Institute of Biomedical Imaging and
Bioengineering.
NR 33
TC 22
Z9 22
U1 0
U2 19
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-2720
J9 J MICROSC-OXFORD
JI J. Microsc..
PD JUL
PY 2011
VL 243
IS 1
BP 1
EP 7
DI 10.1111/j.1365-2818.2011.03505.x
PG 7
WC Microscopy
SC Microscopy
GA 788XT
UT WOS:000292478400001
PM 21623791
ER
PT J
AU Coutellier, L
Logemann, A
Rusnak, M
Usdin, TB
AF Coutellier, L.
Logemann, A.
Rusnak, M.
Usdin, T. B.
TI Maternal Absence of the Parathyroid Hormone 2 Receptor Affects Postnatal
Pup Development
SO JOURNAL OF NEUROENDOCRINOLOGY
LA English
DT Article
DE lactation; TIP39/PTH2-R system; prolactin; pup development
ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; DOPAMINERGIC NEURONAL-ACTIVITY;
THYROTROPIN-RELEASING-HORMONE; TUBEROINFUNDIBULAR PEPTIDE; 39 RESIDUES;
FEMALE RATS; PROLACTIN SECRETION; LACTATION; BEHAVIOR; PREGNANCY
AB During the lactation period, mothers have a variety of adaptive changes in brain physiology and behaviour that allow them to properly raise their pups. The exact circuitries and mechanisms responsible for these changes are not fully understood. Recent evidence suggests that the neuropeptide tuberoinfundibular peptide of 39 residues (TIP39) and its receptor, the parathyroid hormone 2 receptor (PTH2-R), contribute to these mechanisms. To further investigate this idea, we evaluated the growth rate of pups from dams with a genetically inactivated PTH2-R (PTH2-R-KO), as well as maternal behavioural and neuroendocrine parameters. We observed that PTH2R-KO-reared pups had a slowed growth rate. This was associated with a reduced volume of milk yielded by PTH2-R-KO dams after 30-min suckling compared to wild-type (WT) dams when pups were returned after 5 h of separation. Our data suggest a reduced sensitivity of PTH2-R-KO dams to pup stimulation. We also observed a significant reduction in suckling-induced c-Fos expression in the paraventricular hypothalamic nucleus and signs of lower prolactin levels in the PTH2-R-KO dams. Our data suggest that the reduced growth rate of PTH2-R-KO-reared pups was likely the result of alterations in the milk-production pathway rather than modifications in behaviour. Although PTH2-R-KO dams showed increased anxiety in the elevated zero-maze test, no differences from WT dams in maternal behaviour were observed. Taken together, our findings suggest the involvement of the TIP39/PTH2-R system in the pathways involved in the successful development of the pups.
C1 [Coutellier, L.; Logemann, A.; Rusnak, M.; Usdin, T. B.] NIMH, Sect Fundamental Neurosci, NIH, Bethesda, MD 20892 USA.
RP Usdin, TB (reprint author), 35 Convent Dr,Room 1B-215, Bethesda, MD 20892 USA.
EM usdint@mail.nih.gov
FU NIH, National Institute of Mental Health
FX This research was supported by the Intramural Program of the NIH,
National Institute of Mental Health. The authors declare that there are
no conflicts of interest.
NR 36
TC 2
Z9 2
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-8194
J9 J NEUROENDOCRINOL
JI J. Neuroendocrinol.
PD JUL
PY 2011
VL 23
IS 7
BP 612
EP 619
DI 10.1111/j.1365-2826.2011.02149.x
PG 8
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 788SU
UT WOS:000292465500008
PM 21535248
ER
PT J
AU Perdivara, I
Peddada, SD
Miller, FW
Tomer, KB
Deterding, LJ
AF Perdivara, Irina
Peddada, Shyamal D.
Miller, Frederick W.
Tomer, Kenneth B.
Deterding, Leesa J.
TI Mass Spectrometric Determination of IgG Subclass-Specific Glycosylation
Profiles in Siblings Discordant for Myositis Syndromes
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE myositis; plasma; twin-sibling clinical study; antibody glycosylation;
glycopeptide; mass spectrometry
ID IDIOPATHIC INFLAMMATORY MYOPATHIES; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
ORDER-RESTRICTED INFERENCE; RHEUMATOID-ARTHRITIS; DIAGNOSTIC-CRITERIA;
ANTIINFLAMMATORY ACTIVITY; BINDING LECTIN; N-GLYCANS; DISEASE;
AUTOANTIBODIES
AB Many autoimmune conditions are believed to result from chronic inflammation as a consequence of the interaction of genetic and environmental factors in susceptible individuals. One common feature in some autoimmune diseases is the decrease in terminal galactosylation of the constant region N-glycan of the total plasma immunoglobulin. To determine whether a similar pattern is characteristic for the autoimmune disorder myositis, we analyzed the antibody subclass specific glycosylation in patients with myositis, their asymptomatic siblings, and healthy unrelated age- and sex-matched controls. The antibody subclass specific glycosylation was determined from the LC-MS analyses of the IgG glycopeptides generated by trypsin digestion of the antibody heavy chain. The glycosylation profiles of the IgG subclasses were determined relative to the total abundance of all glycoforms. We found elevated amounts of glycoforms lacking terminal galactose in myositis patients. Pairwise statistical analyses reveals that galactosylation is statistically different between the myositis patients and control groups. Furthermore, the trend analysis for glycosylation indicates a pattern of decreasing galactosylation in the order controls >= siblings >= myositis patients, suggesting the existence of a genetic, immune-related predisposition in the group of asymptomatic siblings that can be detected before the onset of clinical symptoms at the level of plasma proteins.
C1 [Perdivara, Irina; Tomer, Kenneth B.; Deterding, Leesa J.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Peddada, Shyamal D.] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Miller, Frederick W.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Deterding, LJ (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, DHHS, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM deterdi2@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012; Tomer, Kenneth/E-8018-2013;
OI Miller, Frederick/0000-0003-2831-9593
FU NIH, National Institutes of Environmental Health Sciences [ES050171,
ES101074-07, ES045005-14]
FX This research was supported by the Intramural Research Program of the
NIH, National Institutes of Environmental Health Sciences, projects
ES050171, ES101074-07, ES045005-14. We acknowledge the technical
assistance of Dr. Terrance O'Hanlon (NIEHS/NIH) in the preparation of
the patient samples, Dr. Jason Williams (NIEHS/NIH) and Dr. Alina Zamfir
(University of Aurel Vlaicu Arad) for critical review of the manuscript,
and the NIEHS Protein Microcharacterization Core Facility for assistance
with in-gel digestions.
NR 59
TC 16
Z9 16
U1 1
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD JUL
PY 2011
VL 10
IS 7
BP 2969
EP 2978
DI 10.1021/pr200397h
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 788AI
UT WOS:000292417400010
PM 21609021
ER
PT J
AU Derbala, MF
Amer, AM
Almohanadi, M
John, A
Amin, A
John, A
Sharma, M
Alkaabi, SR
Al Dweik, NZ
Pasic, F
Yaqoob, R
Butt, MT
Shebl, FM
AF Derbala, M. F.
Amer, A. M.
Almohanadi, M.
John, A.
Amin, A.
John, A.
Sharma, M.
Alkaabi, S. R.
Al Dweik, N. Z.
Pasic, F.
Yaqoob, R.
Butt, M. T.
Shebl, F. M.
TI Hepatitis C virus genotype 4 with normal transaminases: histological
changes, schistosomiasis and response to treatment
SO JOURNAL OF VIRAL HEPATITIS
LA English
DT Article
DE HCV; persistently normal alanine aminotransferase; response to treatment
ID NORMAL ALANINE AMINOTRANSFERASE; PEGINTERFERON ALPHA-2A; PLUS RIBAVIRIN;
RISK-FACTORS; INFECTION; EGYPT; DISEASE; LIVER; CARRIERS; MANSONI
AB Among individuals with chronic hepatitis C virus (HCV) infection, approximately 30% of patients show persistently normal alanine aminotransferase (PNALT). Individuals with PNALT have been historically excluded from antiviral treatment. However, some studies have reported sudden worsening of disease in patients with PNALT, suggesting the need to treat such individuals. To evaluate this further, we compared fibrosis severity and response to treatment in patients with PNALT to patients with abnormal ALT. In addition, we investigated whether liver histology and schistosomiasis affect response to treatment differently in those with PNALT and abnormal ALT. A retrospective cohort study of 176 HCV-Genotype 4 (HCV-G4) patients treated with pegylated interferon (PEG-IFN) and ribavirin. Of 176 cases studied, 53 (30.1%) had normal ALT. Prevalence of pretreatment severe fibrosis, sustained virological response (SVR) and relapse were not significantly different in patients with PNALT (26%, 66% and 5.7% respectively) compared to those with abnormal ALT (32.5%, 60.7%, and 6.6% respectively). Multivariable logistic regression revealed that pretreatment ALT, pretreatment viral load, inflammation and schistosomiasis were not significantly associated with SVR [OR (95% CI), 0.75 (0.34-1.65); 0.92 (0.61-1.37); 1.64 (0.64-4.18); 0.90 (0.44-1.84) respectively]. Severe fibrosis was the only significant predictor of SVR [OR (95% CI), 0.38 (0.14-0.99)]. PNALT does not reflect the degree of fibrotic changes or predict SVR. Furthermore, schistosomiasis is a predictor of neither fibrosis nor poor response in patients with PNALT. Severe fibrosis is a strong and independent predictor of response to treatment. Therefore, it is important to treat individuals with PNALT levels regardless of schistosomiasis.
C1 [Derbala, M. F.; Almohanadi, M.; John, A.; Amin, A.; Sharma, M.; Alkaabi, S. R.; Al Dweik, N. Z.; Pasic, F.; Yaqoob, R.; Butt, M. T.] Hamad Hosp, Dept Gastroenterol & Hepatol, Doha, Qatar.
[Amer, A. M.] Hamad Hosp, Hematol Sect, Dept Lab Med & Pathol, Doha, Qatar.
[John, A.] Hamad Hosp, Med Res Ctr, Doha, Qatar.
[Shebl, F. M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Shebl, F. M.] Natl Liver Inst, Publ Hlth Branch, Menoufia, Egypt.
RP Derbala, MF (reprint author), Hamad Med Corp, Dept Gastroenterol & Hepatol, POB 3050, Doha, Qatar.
EM moutazderbala@hotmail.com
FU Intramural NIH HHS [Z99 CA999999]
NR 25
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1352-0504
J9 J VIRAL HEPATITIS
JI J. Viral Hepatitis
PD JUL
PY 2011
VL 18
IS 7
BP E258
EP E262
DI 10.1111/j.1365-2893.2010.01403.x
PG 5
WC Gastroenterology & Hepatology; Infectious Diseases; Virology
SC Gastroenterology & Hepatology; Infectious Diseases; Virology
GA 785XE
UT WOS:000292265400014
PM 21108700
ER
PT J
AU An, L
Warach, S
Shen, J
AF An, Li
Warach, Steven
Shen, Jun
TI Spectral Localization by Imaging Using Multielement Receiver Coils
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE MRS; CSI; SLIM; stroke; tumor
ID MAGNETIC-RESONANCE; SPECTROSCOPY; BRAIN; SENSE; NMR; MRI
AB A new spectral localization technique for in vivo magnetic resonance spectroscopy is introduced. Structural information extracted from anatomical imaging is used for defining compartments which provide the basis for spectral localization. The inherent spatial heterogeneity of multiple receiver coil elements is used along with optional phase encoding to resolve signals from different compartments. This technique allows a few compartmental spectra to be reconstructed from multichannel data acquired with no or very few phase encoding steps, resulting in short scan time and high efficiency. Alternatively, this technique also allows a significant number of compartmental spectra to be reconstructed if sufficient phase encoding steps are used. A procedure is developed to semiautomatically generate a significant number of compartments of comparable sizes, which allows one to obtain spectra from small regions of interest with curvilinear shapes. This may be useful for obtaining spectra from relatively small stroke lesions or tumors. Phantom experiments and in vivo magnetic resonance spectroscopy of stroke patients have been performed to demonstrate this technique. Magn Reson Med 66:1-10,2011. (C) 2011 Wiley-Liss, Inc.
C1 [An, Li; Warach, Steven] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Shen, Jun] NIMH, NIH, Bethesda, MD 20892 USA.
RP An, L (reprint author), Bldg 10,Room B1D733,10 Ctr Dr,MSC 1063, Bethesda, MD 20892 USA.
EM lian1025@gmail.com
FU NIH; NINDS; NIMH
FX Grant sponsors: NIH, NINDS, NIMH (intramural programs).
NR 19
TC 9
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2011
VL 66
IS 1
BP 1
EP 10
DI 10.1002/mrm.22783
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 788DH
UT WOS:000292425100001
PM 21287595
ER
PT J
AU Blaimer, M
Ponce, IP
Breuer, FA
Jakob, PM
Griswold, MA
Kellman, P
AF Blaimer, Martin
Ponce, Irene P.
Breuer, Felix A.
Jakob, Peter M.
Griswold, Mark A.
Kellman, Peter
TI Temporal Filtering Effects in Dynamic Parallel MRI
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE dynamic MRI; parallel MRI; GRAPPA; TSENSE; k-t SENSE; temporal filtering
ID K-T SENSE; GRAPPA; RECONSTRUCTION
AB Autocalibrated parallel MRI methods such as TSENSE or k-t SENSE have been presented for dynamic imaging studies as they are able to provide images with high temporal resolution. One key element of these techniques is the temporal averaging of the undersampled raw data to obtain an unaliased image. This image represents the temporal average (also known as direct current, DC) and is used to derive the reconstruction parameters. In this work, we show that aliasing artifacts can be introduced in the DC signal obtained from the undersampled raw data. These artifacts lead to undesired temporal filtering effects when the DC signal is used for coil sensitivity calibration or when the DC signal is subtracted from the raw data. It is demonstrated that the temporal filtering effects can be reduced significantly by filtering the DC signal. Magn Reson Med 66:192-198, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Blaimer, Martin; Breuer, Felix A.; Jakob, Peter M.] Res Ctr Magnet Resonance Bavaria MRB, Dept Diagnost Imaging, D-97074 Wurzburg, Germany.
[Ponce, Irene P.; Jakob, Peter M.] Univ Wurzburg, Dept Expt Phys 5, Wurzburg, Germany.
[Griswold, Mark A.] Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA.
[Griswold, Mark A.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
RP Blaimer, M (reprint author), Res Ctr Magnet Resonance Bavaria MRB, Dept Diagnost Imaging, D-97074 Wurzburg, Germany.
EM blaimer@mr-bavaria.de
OI Jakob, Peter/0000-0002-3481-5545
NR 18
TC 11
Z9 11
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2011
VL 66
IS 1
BP 192
EP 198
DI 10.1002/mrm.22795
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 788DH
UT WOS:000292425100022
PM 21695723
ER
PT J
AU Kwon, D
Little, MP
Miller, DL
AF Kwon, Deukwoo
Little, Mark P.
Miller, Donald L.
TI Reference air kerma and kerma-area product as estimators of peak skin
dose for fluoroscopically guided interventions
SO MEDICAL PHYSICS
LA English
DT Article
DE peak skin dose; reference air kerma; kerma-area product
ID RADIOLOGY PROCEDURES; RAD-IR; RADIATION; GUIDELINES; CARDIOLOGY; TIME
AB Purpose: To determine more accurate regression formulas for estimating peak skin dose (PSD) from reference air kerma (RAK) or kerma-area product (KAP).
Methods: After grouping of the data from 21 procedures into 13 clinically similar groups, assessments were made of optimal clustering using the Bayesian information criterion to obtain the optimal linear regressions of (log-transformed) PSD vs RAK, PSD vs KAP, and PSD vs RAK and KAP.
Results: Three clusters of clinical groups were optimal in regression of PSD vs RAK, seven clusters of clinical groups were optimal in regression of PSD vs KAP, and six clusters of clinical groups were optimal in regression of PSD vs RAK and KAP. Prediction of PSD using both RAK and KAP is significantly better than prediction of PSD with either RAK or KAP alone. The regression of PSD vs RAK provided better predictions of PSD than the regression of PSD vs KAP. The partial-pooling (clustered) method yields smaller mean squared errors compared with the complete-pooling method.
Conclusion: PSD distributions for interventional radiology procedures are log-normal. Estimates of PSD derived from RAK and KAP jointly are most accurate, followed closely by estimates derived from RAK alone. Estimates of PSD derived from KAP alone are the least accurate. Using a stochastic search approach, it is possible to cluster together certain dissimilar types of procedures to minimize the total error sum of squares. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3590358]
C1 [Kwon, Deukwoo; Little, Mark P.; Miller, Donald L.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
[Miller, Donald L.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
EM mark.little@nih.gov
OI Little, Mark/0000-0003-0980-7567
FU Navy Bureau of Medicine and Surgery, Washington, D.C. [NNMC.2008.0044];
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics
FX The Chief, Navy Bureau of Medicine and Surgery, Washington, D.C.,
Clinical Investigation Program sponsored this study, Grant No.
NNMC.2008.0044. This research was partially supported by the Intramural
Research Program of the National Institutes of Health, the National
Cancer Institute, Division of Cancer Epidemiology and Genetics.
NR 28
TC 11
Z9 11
U1 0
U2 2
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUL
PY 2011
VL 38
IS 7
BP 4196
EP 4204
DI 10.1118/1.3590358
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 789NB
UT WOS:000292521100036
PM 21859021
ER
PT J
AU Liu, JM
Kabadi, S
Van Uitert, R
Petrick, N
Deriche, R
Summers, RM
AF Liu, Jiamin
Kabadi, Suraj
Van Uitert, Robert
Petrick, Nicholas
Deriche, Rachid
Summers, Ronald M.
TI Improved computer-aided detection of small polyps in CT colonography
using interpolation for curvature estimation
SO MEDICAL PHYSICS
LA English
DT Article
DE curvature estimation; polyp detection; interpolation; Deriche filter
ID COLONIC POLYPS; FALSE POSITIVES; OBSERVER; CAD; POPULATION; REDUCTION;
IMAGES; PERFORMANCE; EVOLUTION; DIAGNOSIS
AB Purpose: Surface curvatures are important geometric features for the computer-aided analysis and detection of polyps in CT colonography (CTC). However, the general kernel approach for curvature computation can yield erroneous results for small polyps and for polyps that lie on haustral folds. Those erroneous curvatures will reduce the performance of polyp detection. This paper presents an analysis of interpolation's effect on curvature estimation for thin structures and its application on computer-aided detection of small polyps in CTC.
Methods: The authors demonstrated that a simple technique, image interpolation, can improve the accuracy of curvature estimation for thin structures and thus significantly improve the sensitivity of small polyp detection in CTC.
Results: Our experiments showed that the merits of interpolating included more accurate curvature values for simulated data, and isolation of polyps near folds for clinical data. After testing on a large clinical data set, it was observed that sensitivities with linear, quadratic B-spline and cubic B-spline interpolations significantly improved the sensitivity for small polyp detection.
Conclusions: The image interpolation can improve the accuracy of curvature estimation for thin structures and thus improve the computer-aided detection of small polyps in CTC. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3596529]
C1 [Liu, Jiamin; Kabadi, Suraj; Van Uitert, Robert; Summers, Ronald M.] NIH, Imaging Biomarkers & Computer Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Deriche, Rachid] French Natl Inst Res Comp Sci & Control, Sophia Antipolis, France.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Computer Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU NIH Clinical Center
FX This research was supported by the Intramural Research Program of the
NIH Clinical Center. We thank Dr. Perry Pickhardt, Dr. J. Richard Choi,
and Dr. William Schindler for providing CT colonography data.
NR 44
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Z9 5
U1 0
U2 5
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUL
PY 2011
VL 38
IS 7
BP 4276
EP 4284
DI 10.1118/1.3596529
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 789NB
UT WOS:000292521100044
PM 21859029
ER
PT J
AU Ying, ZG
Yong, C
Udupa, JK
Miller, RW
AF Ying Zhuge
Yong Cao
Udupa, Jayaram K.
Miller, Robert W.
TI Parallel fuzzy connected image segmentation on GPU
SO MEDICAL PHYSICS
LA English
DT Article
DE image segmentation; fuzzy connectedness; fuzzy affinity; GPU
ID OBJECT DEFINITION; ALGORITHMS; QUANTIFICATION; PRINCIPLES; SYSTEM
AB Purpose: Image segmentation techniques using fuzzy connectedness (FC) principles have shown their effectiveness in segmenting a variety of objects in several large applications. However, one challenge in these algorithms has been their excessive computational requirements when processing large image datasets. Nowadays, commodity graphics hardware provides a highly parallel computing environment. In this paper, the authors present a parallel fuzzy connected image segmentation algorithm implementation on NVIDIA's compute unified device Architecture (CUDA) platform for segmenting medical image data sets.
Methods: In the FC algorithm, there are two major computational tasks: (i) computing the fuzzy affinity relations and (ii) computing the fuzzy connectedness relations. These two tasks are implemented as cuda kernels and executed on GPU. A dramatic improvement in speed for both tasks is achieved as a result.
Results: Our experiments based on three data sets of small, medium, and large data size demonstrate the efficiency of the parallel algorithm, which achieves a speed-up factor of 24.4x, 18.1x, and 10.3x, correspondingly, for the three data sets on the NVIDIA Tesla C1060 over the implementation of the algorithm on CPU, and takes 0.25, 0.72, and 15.04 s, correspondingly, for the three data sets.
Conclusions: The authors developed a parallel algorithm of the widely used fuzzy connected image segmentation method on the NVIDIA GPUs, which are far more cost- and speed-effective than both cluster of workstations and multiprocessing systems. A near-interactive speed of segmentation has been achieved, even for the large data set. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3599725]
C1 [Ying Zhuge; Miller, Robert W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Yong Cao] Virginia Polytech Inst & State Univ, Dept Comp Sci, Blacksburg, VA 24060 USA.
[Udupa, Jayaram K.] Univ Penn, Dept Radiol, Med Image Proc Grp, Philadelphia, PA 19104 USA.
RP Ying, ZG (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhugey@mail.nih.gov
FU National Cancer Institute, NIH
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, NIH.
NR 35
TC 0
Z9 1
U1 2
U2 5
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUL
PY 2011
VL 38
IS 7
BP 4365
EP 4371
DI 10.1118/1.3599725
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 789NB
UT WOS:000292521100052
ER
PT J
AU Zhang, CY
Elkahloun, AG
Liao, HL
Delaney, S
Saber, B
Morrow, B
Prendergast, GC
Hollander, MC
Gills, JJ
Dennis, PA
AF Zhang, Chunyu
Elkahloun, Abdel G.
Liao, Hongling
Delaney, Shannon
Saber, Barbara
Morrow, Betsy
Prendergast, George C.
Hollander, M. Christine
Gills, Joell J.
Dennis, Phillip A.
TI Expression Signatures of the Lipid-Based Akt Inhibitors
Phosphatidylinositol Ether Lipid Analogues in NSCLC Cells
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID LUNG-CANCER CELLS; TUMOR-SUPPRESSOR PROTEIN; PROSTATE-CANCER;
GENE-EXPRESSION; RHOB EXPRESSION; BREAST-CANCER; KINASE; PATHWAY;
TRANSFORMATION; PROGRESSION
AB Activation of the serine/threonine kinase Akt contributes to the formation, maintenance, and therapeutic resistance of cancer, which is driving development of compounds that inhibit Akt. Phosphatidylinositol ether lipid analogues (PIA) are analogues of the products of phosphoinositide-3-kinase (PI3K) that inhibit Akt activation, translocation, and the proliferation of a broad spectrum of cancer cell types. To gain insight into the mechanism of PIAs, time-dependent transcriptional profiling of five active PIAs and the PI3K inhibitor LY294002 (LY) was conducted in non-small cell lung carcinoma cells using high-density oligonucleotide arrays. Gene ontology analysis revealed that genes involved in apoptosis, wounding response, and angiogenesis were upregulated by PIAs, whereas genes involved in DNA replication, repair, and mitosis were suppressed. Genes that exhibited early differential expression were partitioned into three groups; those induced by PIAs only (DUSP1, KLF6, CENTD2, BHLHB2, and PREX1), those commonly induced by PIAs and LY (TRIB1, KLF2, RHOB, and CDKN1A), and those commonly suppressed by PIAs and LY (IGFBP3, PCNA, PRIM1, MCM3, and HSPA1B). Increased expression of the tumor suppressors RHOB (RhoB), KLF6 (COPEB), and CDKN1A (p21Cip1/Waf1) was validated as an Akt-independent effect that contributed to PIA-induced cytotoxicity. Despite some overlap with LY, active PIAs have a distinct expression signature that contributes to their enhanced cytotoxicity. Mol Cancer Ther; 10(7); 1137-48. (C) 2011 AACR.
C1 [Zhang, Chunyu; Delaney, Shannon; Saber, Barbara; Morrow, Betsy; Hollander, M. Christine; Gills, Joell J.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Liao, Hongling] NCI Frederick, Sequencing Facil, SAIC Frederick, Gaithersburg, MD USA.
[Prendergast, George C.] Lankenau Inst Med Res, Wynnewood, PA USA.
RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 37 Convent Dr,Rm 1118B, Bethesda, MD 20892 USA.
EM dennisp@mail.nih.gov
FU NIH, NCI, Center for Cancer Research; NCI, NIH, under contract NCI
[NO1-CO-12400]
FX This research was supported in part by the Intramural Research Program
of the NIH, NCI, Center for Cancer Research, and in part with federal
funds from the NCI, NIH, under contract NCI Contract NO1-CO-12400.
NR 43
TC 5
Z9 5
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUL
PY 2011
VL 10
IS 7
BP 1137
EP 1148
DI 10.1158/1535-7163.MCT-10-1028
PG 12
WC Oncology
SC Oncology
GA 789FA
UT WOS:000292498500002
PM 21551261
ER
PT J
AU Legrain, P
Aebersold, R
Archakov, A
Bairoch, A
Bala, K
Beretta, L
Bergeron, J
Borchers, CH
Corthals, GL
Costello, CE
Deutsch, EW
Domon, B
Hancock, W
He, FC
Hochstrasser, D
Marko-Varga, G
Salekdeh, GH
Sechi, S
Snyder, M
Srivastava, S
Uhlen, M
Wu, CH
Yamamoto, T
Paik, YK
Omenn, GS
AF Legrain, Pierre
Aebersold, Ruedi
Archakov, Alexander
Bairoch, Amos
Bala, Kumar
Beretta, Laura
Bergeron, John
Borchers, Christoph H.
Corthals, Garry L.
Costello, Catherine E.
Deutsch, Eric W.
Domon, Bruno
Hancock, William
He, Fuchu
Hochstrasser, Denis
Marko-Varga, Gyorgy
Salekdeh, Ghasem Hosseini
Sechi, Salvatore
Snyder, Michael
Srivastava, Sudhir
Uhlen, Mathias
Wu, Cathy H.
Yamamoto, Tadashi
Paik, Young-Ki
Omenn, Gilbert S.
TI The Human Proteome Project: Current State and Future Direction
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID DATABASE; ASSAYS
AB After the successful completion of the Human Genome Project, the Human Proteome Organization has recently officially launched a global Human Proteome Project (HPP), which is designed to map the entire human protein set. Given the lack of protein-level evidence for about 30% of the estimated 20,300 protein-coding genes, a systematic global effort will be necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP research groups will use the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge bases. The HPP participants will take advantage of the output and cross-analyses from the ongoing Human Proteome Organization initiatives and a chromosome-centric protein mapping strategy, termed C-HPP, with which many national teams are currently engaged. In addition, numerous biologically driven and disease-oriented projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents, and tools for protein studies and analyses, and a stronger basis for personalized medicine. The Human Proteome Organization urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators. Molecular & Cellular Proteomics 10: 10.1074/mcp.M111.009993, 1-5, 2011.
C1 [Legrain, Pierre] CEA, Div Life Sci, Fontenay Aux Roses, France.
[Aebersold, Ruedi] ETH, Dept Biol, Inst Mol Syst Biol, Zurich, Switzerland.
[Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8006 Zurich, Switzerland.
[Archakov, Alexander] Russian Acad Med Sci, Inst Biomed Chem, Moscow, Russia.
[Bairoch, Amos] SIB, Geneva, Switzerland.
[Bairoch, Amos; Hochstrasser, Denis] Univ Geneva, Geneva, Switzerland.
[Bala, Kumar] Bridge4Bio, Biotechnol, San Francisco, CA USA.
[Beretta, Laura] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Bergeron, John] McGill Univ, Montreal, PQ, Canada.
[Borchers, Christoph H.] Univ Victoria, Prote Ctr, Victoria, BC V8W 2Y2, Canada.
[Corthals, Garry L.] Univ Turku, Turku Ctr Biotechnol, Turku, Finland.
[Corthals, Garry L.] Abo Akad Univ, Turku, Finland.
[Costello, Catherine E.] Boston Univ, Boston, MA 02215 USA.
[Deutsch, Eric W.] Inst Syst Biol, Seattle, WA USA.
[Domon, Bruno] Luxembourg Univ, Luxembourg, Luxembourg.
[Hancock, William] Northeastern Univ, Boston, MA 02115 USA.
[He, Fuchu] Beijing Proteome Res Ctr, Beijing, Peoples R China.
[Marko-Varga, Gyorgy] Lund Univ, Lund, Sweden.
[Salekdeh, Ghasem Hosseini] Royan Inst, Tehran, Iran.
[Sechi, Salvatore] NIDDK, NIH, Bethesda, MD USA.
[Snyder, Michael] Stanford Univ, Palo Alto, CA 94304 USA.
[Srivastava, Sudhir] NCI, NIH, Bethesda, MD 20892 USA.
[Uhlen, Mathias] Royal Inst Technol, Stockholm, Sweden.
[Wu, Cathy H.] PIR, Newark, DE USA.
[Wu, Cathy H.] Univ Delaware, Newark, DE USA.
[Yamamoto, Tadashi] Niigata Univ, Niigata, Japan.
[Paik, Young-Ki] Yonsei Univ, Seoul 120749, South Korea.
[Omenn, Gilbert S.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
RP Legrain, P (reprint author), CEA, Div Life Sci, Fontenay Aux Roses, France.
EM pierre.legrain@cea.fr; paikyk@yonsei.ac.kr; gomenn@umich.edu
RI Crozier, Laura/A-4821-2010; Archakov, Alexander/B-5194-2012; Salekdeh,
Ghasem Hosseini/E-4198-2012; Corthals, Garry/G-9417-2016; Salekdeh,
Ghasem Hosseini/R-8716-2016
OI Costello, Catherine/0000-0003-1594-5122; Bairoch,
Amos/0000-0003-2826-6444; Omenn, Gilbert S./0000-0002-8976-6074;
Corthals, Garry/0000-0001-9423-5596;
NR 15
TC 65
Z9 65
U1 2
U2 23
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD JUL
PY 2011
VL 10
IS 7
DI 10.1074/mcp.M111.009993
PG 5
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 789UJ
UT WOS:000292541500012
ER
PT J
AU Armaleo, D
Sun, XM
Culberson, C
AF Armaleo, Daniele
Sun, Xiameng
Culberson, Chicita
TI Insights from the first putative biosynthetic gene cluster for a lichen
depside and depsidone
SO MYCOLOGIA
LA English
DT Article
DE Cladonia grayi; depsides; depsidones; lichen fungi; metabolic gene
clusters; polyketide synthases; secondary metabolites; symbiosis
ID POLYKETIDE SYNTHASE GENES; FUNGAL; PHYLOGENY; METABOLITES; EVOLUTION;
ACID; MYCOBIONT; ENZYMES; ACCUMULATION; ASCOMYCOTA
AB The genes for polyketide synthases (PKSs), enzymes that assemble the carbon backbones of many secondary metabolites, often cluster with other secondary pathway genes. We describe here the first lichen PKS cluster likely to be implicated in the biosynthesis of a depside and a depsidone, compounds in a class almost exclusively produced by lichen fungi (mycobionts). With degenerate PCR with primers biased toward presumed PKS genes for depsides and depsidones we identified among the many PKS genes in Cladonia grayi four (CgrPKS1346) potentially responsible for grayanic acid (GRA), the orcinol depsidone characteristic of this lichen. To single out a likely GRA PKS we compared mRNA and GRA induction in mycobiont cultures using the four candidate PKS genes plus three controls; only CgrPKS16 expression closely matched GRA induction. CgrPKS16 protein domains were compatible with orcinol depside biosynthesis. Phylogenetically CgrPKS16 fell in a new subclade of fungal PKSs uniquely producing orcinol compounds. In the C. grayi genom e CgrPKS16 clustered with a CytP450 and an O-methyltransferase gene, appropriately matching the three compounds in the GRA pathway. Induction, domain organization, phylogeny and cluster pathway correspondence in indicated that the CgrPKS16 cluster is most likely responsible for GRA biosynthesis. Specifically we propose that (i) a single PKS synthesizes two aromatic rings and links them into a depside, (ii) the depside to depsidone transition requires only a cytochrome P450 and (iii) lichen compounds evolved early in the radiation of filamentous fungi.
C1 [Armaleo, Daniele; Culberson, Chicita] Duke Univ, Dept Biol, Durham, NC 27708 USA.
[Sun, Xiameng] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Armaleo, D (reprint author), Duke Univ, Dept Biol, Durham, NC 27708 USA.
EM darmaleo@duke.edu
NR 66
TC 24
Z9 24
U1 1
U2 27
PU ALLEN PRESS INC
PI LAWRENCE
PA 810 E 10TH ST, LAWRENCE, KS 66044 USA
SN 0027-5514
J9 MYCOLOGIA
JI Mycologia
PD JUL-AUG
PY 2011
VL 103
IS 4
BP 741
EP 754
DI 10.3852/10-335
PG 14
WC Mycology
SC Mycology
GA 787XE
UT WOS:000292409200006
PM 21289108
ER
PT J
AU De Lucca, AJ
Boue, S
Sien, T
Cleveland, TE
Walsh, TJ
AF De Lucca, Anthony J.
Boue, Stephen
Sien, Tin
Cleveland, Thomas E.
Walsh, Thomas J.
TI Silver enhances the in vitro antifungal activity of the saponin, CAY-1
SO MYCOSES
LA English
DT Article
DE Aspergillus; Fusarium; fungicidal; saponin; CAY-1; silver
ID ANTIMICROBIAL ACTIVITIES; CANDIDA-ALBICANS; RESISTANCE; COMPLEXES;
BACTERIA; BURNS; MODEL; EDTA
AB The fungicidal properties of purified CAY-1, dissolved silver ion and ethylenediamine tetraacetic acid (EDTA) separately were studied in vitro as were the abilities of silver and EDTA to enhance CAY-1 fungicidal properties. Non-germinated and germinating conidia of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Fusarium verticillioides (Fusarium moniliforme), Fusarium oxysporum and Fusarium solani were incubated separately with CAY-1 (0-24.8 mu g ml(-1)), silver (0-111.1 mu g ml(-1)), and EDTA (0-2400 mu g ml(-1)). Controls consisted of non-germinated or germinated conidia in test medium. To assess combined activity, compounds, based on the sub-lethal doses of each as defined in the initial experiments, were combined and tested in bioassays. Controls for the mixed sets consisted of non-germinated or germinated conidia only or with the sub-lethal CAY-1 test concentrations. The minimum inhibitory concentrations (MICs) for CAY-1 and silver, both separate and combined, were determined. Viability assays showed CAY-1 activity only against the germinating conidia of A. flavus, A. niger and F. solani. Silver was active against the germinating conidia of all fungi and the non-germinated conidia of F. oxysporum and F. solani. Combined silver and CAY-1 produced significant viability loss at concentrations not effective separately. EDTA was not fungicidal separately and did not enhance CAY-1 fungicidal properties. MIC data showed that CAY-1 plus silver had an additive effect. Results indicate that dissolved silver was fungicidal in vitro and enhanced the fungicidal properties of CAY-1 at concentrations ineffective when tested separately.
C1 [De Lucca, Anthony J.; Boue, Stephen; Cleveland, Thomas E.] ARS, So Reg Res Ctr, USDA, New Orleans, LA USA.
[Sien, Tin; Walsh, Thomas J.] NCI, NIH, Bethesda, MD USA.
RP De Lucca, AJ (reprint author), 1100 Robert E Lee Blvd, New Orleans, LA 70124 USA.
EM adelucca@srrc.ars.usda.gov
NR 26
TC 0
Z9 0
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0933-7407
J9 MYCOSES
JI Mycoses
PD JUL
PY 2011
VL 54
IS 4
BP E1
EP E9
DI 10.1111/j.1439-0507.2009.01811.x
PG 9
WC Dermatology; Mycology
SC Dermatology; Mycology
GA 789FY
UT WOS:000292501600001
PM 20002309
ER
PT J
AU Jovanovic-Talisman, T
Zilman, A
AF Jovanovic-Talisman, Tijana
Zilman, Anton
TI NANOBIOTECHNOLOGY Building a basic nanomachine
SO NATURE NANOTECHNOLOGY
LA English
DT News Item
ID NUCLEAR-PORE COMPLEX; SINGLE-MOLECULE; SELECTIVE TRANSPORT;
TRANSLOCATION
C1 [Jovanovic-Talisman, Tijana] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Zilman, Anton] Univ Toronto, Dept Phys, Toronto, ON M5S 1A7, Canada.
RP Jovanovic-Talisman, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM talismant@mail.nih.gov; zilmana@physics.utoronto.ca
RI Boskovic, Danijel/C-4129-2012;
OI Jovanovic-Talisman, Tijana/0000-0003-1928-4763
NR 13
TC 1
Z9 1
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1748-3387
EI 1748-3395
J9 NAT NANOTECHNOL
JI Nat. Nanotechnol.
PD JUL
PY 2011
VL 6
IS 7
BP 397
EP 398
PG 3
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA 788RV
UT WOS:000292463000004
PM 21731070
ER
PT J
AU Bonnemann, CG
AF Bonnemann, Carsten G.
TI The collagen VI-related myopathies: muscle meets its matrix
SO NATURE REVIEWS NEUROLOGY
LA English
DT Review
ID CONGENITAL MUSCULAR-DYSTROPHY; IN-FRAME DELETION; BETHLEM-MYOPATHY;
ULLRICH-DISEASE; MITOCHONDRIAL DYSFUNCTION; CONNECTIVE-TISSUE;
TRIPLE-HELIX; COL6A1 GENE; BINDING-PROPERTIES; GLYCINE MUTATIONS
AB The collagen VI-related myopathy known as Ullrich congenital muscular dystrophy is an early-onset disease that combines substantial muscle weakness with striking joint laxity and progressive contractures. Patients might learn to walk in early childhood; however, this ability is subsequently lost, concomitant with the development of frequent nocturnal respiratory failure. Patients with intermediate phenotypes of collagen VI-related myopathy display a lesser degree of weakness and a longer period of ambulation than do individuals with Ullrich congenital muscular dystrophy, and the spectrum of disease finally encompasses mild Bethlem myopathy, in which ambulation persists into adulthood. Dominant and recessive autosomal mutations in the three major collagen VI genes-COL6A1, COL6A2, and COL6A3-can underlie this entire clinical spectrum, and result in deficient or dysfunctional microfibrillar collagen VI in the extracellular matrix of muscle and other connective tissues, such as skin and tendons. The potential effects on muscle include progressive dystrophic changes, fibrosis and evidence for increased apoptosis, which potentially open avenues for pharmacological intervention. Optimized respiratory management, including noninvasive nocturnal ventilation together with careful orthopedic management, are the current mainstays of treatment and have already led to a considerable improvement in life expectancy for children with Ullrich congenital muscular dystrophy.
C1 NINDS, Neuromuscular Neurogenet Disorders Childhood Sect, Neurogenet Branch, NIH, Bethesda, MD 20824 USA.
RP Bonnemann, CG (reprint author), NINDS, Neuromuscular Neurogenet Disorders Childhood Sect, Neurogenet Branch, NIH, POB 5801, Bethesda, MD 20824 USA.
EM carsten.bonnemann@nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 121
TC 65
Z9 68
U1 2
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4758
J9 NAT REV NEUROL
JI Nat. Rev. Neurol.
PD JUL
PY 2011
VL 7
IS 7
BP 379
EP 390
DI 10.1038/nrneurol.2011.81
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 789FQ
UT WOS:000292500400007
PM 21691338
ER
PT J
AU Gross, RA
Knopman, DS
Cascino, GD
Corboy, JR
Elkind, MSV
Engel, AG
Mink, JW
Ransohoff, RM
Uitti, RJ
Worrall, BB
AF Gross, Robert A.
Knopman, David S.
Cascino, Gregory D.
Corboy, John R.
Elkind, Mitchell S. V.
Engel, Andrew G.
Mink, Jonathan W.
Ransohoff, Richard M.
Uitti, Ryan J.
Worrall, Bradford B.
TI Untitled
SO NEUROLOGY
LA English
DT Editorial Material
C1 [Gross, Robert A.] UCB, Berkeley, CA USA.
[Elkind, Mitchell S. V.] Bristol Myers Squibb Co, New York, NY 10154 USA.
[Elkind, Mitchell S. V.] Boehringer Ingelheim Inc, Ingelheim, Germany.
[Worrall, Bradford B.] NHLBI, AREDS2, Bethesda, MD USA.
[Worrall, Bradford B.] NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL
PY 2011
VL 77
IS 1
BP 5
EP 11
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 789TB
UT WOS:000292538100003
ER
PT J
AU Kaminski, RM
Rogawski, MA
AF Kaminski, Rafal M.
Rogawski, Michael A.
TI 11 beta-Hydroxylase inhibitors protect against seizures in mice by
increasing endogenous neurosteroid synthesis
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Neurosteroid; Allotetrahydrodeoxycorticosterone; Steroid 11
beta-hydroxylase (CYP11B1) inhibitor; Metyrapone; Etomidate; Finasteride
ID GENERAL ANESTHETIC ETOMIDATE; ANTICONVULSANT ACTIVITY; A RECEPTOR;
ADRENAL STEROIDOGENESIS; GABA(A) RECEPTORS; PLASMA ACTH; RAT-BRAIN;
METYRAPONE; ACID; BIOSYNTHESIS
AB Steroid 11 beta-hydroxylase (CYP11B1; EC 1.14.15.4) is a mitochondrial enzyme located in the zona fasciculata of the adrenal cortex and also in the brain that mediates the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone (DOC) to corticosterone. Inhibitors of CYP11B1, such as metyrapone and etomidate, reduce glucocorticoid synthesis and raise levels of DOC providing greater availability for metabolic conversion to the GABA(A) receptor modulating neurosteroid allotetrahydrodeoxycorticosterone (THDOC). Because THDOC is a potent anticonvulsant, it is plausible that CYP11B1 inhibitors could protect against seizures. Here we demonstrate that metyrapone affords dose-dependent protection against 6-Hz seizures 30 min after injection (ED50, 191 mg/kg), but is markedly more potent at 6 h (ED50, 30 mg/kg). Similarly, etomidate is also protective at 30 min and 6 h (ED50 values, 4.5 and 1.7 mg/kg). Finasteride, an inhibitor of neurosteroid synthesis, attenuated the anticonvulsant effects of both CYP11B1 inhibitors at 6 h, but not 30 min following their injection. Plasma THDOC levels measured by liquid chromatography-mass spectrometry were markedly increased 6 h after injection of both CYP11B1 inhibitors and this increase was attenuated by finasteride pretreatment. We conclude that inhibition of CYP11B1 causes delayed seizure protection due to slow build-up of neurosteroids. Early seizure protection is independent of neurosteroids. Published by Elsevier Ltd.
C1 [Rogawski, Michael A.] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
[Rogawski, Michael A.] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA.
[Kaminski, Rafal M.; Rogawski, Michael A.] Natl Inst Neurol Disorders & Stroke, Epilepsy Res Sect, NIH, Bethesda, MD USA.
RP Rogawski, MA (reprint author), Univ Calif Davis, Dept Neurol, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA.
EM rogawski@ucdavis.edu
RI Rogawski, Michael/B-6353-2009
OI Rogawski, Michael/0000-0002-3296-8193
FU Intramural NIH HHS [Z01 NS002877-14]
NR 37
TC 8
Z9 8
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JUL-AUG
PY 2011
VL 61
IS 1-2
BP 133
EP 137
DI 10.1016/j.neuropharm.2011.03.019
PG 5
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 787WU
UT WOS:000292408200015
PM 21458468
ER
PT J
AU Burr, JS
Jenkins, TL
Harrison, R
Meert, K
Anand, KJS
Berger, JT
Zimmerman, J
Carcillo, J
Dean, JM
Newth, CJL
Willson, DF
Sanders, RC
Pollack, MM
Harvill, E
Nicholson, CE
AF Burr, Jeri S.
Jenkins, Tammara L.
Harrison, Rick
Meert, Kathleen
Anand, K. J. S.
Berger, John T.
Zimmerman, Jerry
Carcillo, Joseph
Dean, J. Michael
Newth, Christopher J. L.
Willson, Douglas F.
Sanders, Ronald C., Jr.
Pollack, Murray M.
Harvill, Eric
Nicholson, Carol E.
TI The Collaborative Pediatric Critical Care Research Network Critical
Pertussis Study: Collaborative research in pediatric critical care
medicine
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE pertussis; respiratory failure; study design; out-comes; multiple organ
system failure; advanced life support
ID EXTRACORPOREAL MEMBRANE-OXYGENATION; IMMUNIZATION PRACTICES ACIP;
BORDETELLA-PERTUSSIS; INTENSIVE-CARE; UNITED-STATES;
PULMONARY-HYPERTENSION; NOSOCOMIAL PERTUSSIS; ADVISORY-COMMITTEE; INFANT
PERTUSSIS; YOUNG INFANTS
AB Objective: To provide an updated overview of critical pertussis to the pediatric critical care community and describe a study of critical pertussis recently undertaken.
Setting: The six sites, seven hospitals of the Collaborative Pediatric Critical Care Research Network, and 17 outside sites at academic medical centers with pediatric intensive care units.
Results: Despite high coverage for childhood vaccination, pertussis causes substantial morbidity and mortality in US children, especially among infants. In pediatric intensive care units, Bordetella pertussis is a community-acquired pathogen associated with critical illness and death. The incidence of medical and developmental sequelae in critical pertussis survivors remains unknown, and the appropriate strategies for treatment and support remain unclear. The Collaborative Pediatric Critical Care Research Network Critical Pertussis Study has begun to evaluate critical pertussis in a prospective cohort.
Conclusion: Research is urgently needed to provide an evidence base that might optimize management for critical pertussis, a serious, disabling, and too often fatal illness for U. S. children and those in the developing world. (Pediatr Crit Care Med 2011; 12:387-392)
C1 [Burr, Jeri S.] Univ Utah, Salt Lake City, UT 84112 USA.
[Jenkins, Tammara L.; Nicholson, Carol E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Harrison, Rick] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA.
[Meert, Kathleen] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Anand, K. J. S.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Berger, John T.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Zimmerman, Jerry] Seattle Childrens Hosp, Seattle, WA USA.
[Carcillo, Joseph] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Willson, Douglas F.] Univ Virginia, Childrens Hosp, Charlottesville, VA USA.
[Sanders, Ronald C., Jr.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA.
[Pollack, Murray M.] Phoenix Childrens Hosp, Phoenix, AZ USA.
[Harvill, Eric] Penn State Univ, University Pk, PA 16802 USA.
RP Burr, JS (reprint author), Univ Utah, Salt Lake City, UT 84112 USA.
EM jeri.burr@hsc.utah.edu
OI Jardine, David/0000-0001-9000-271X; Anand,
Kanwaljeet/0000-0001-6498-1483
FU NCRR NIH HHS [UL1 RR025014]; NIAID NIH HHS [R56 AI065507, R56
AI065507-01A2]; NICHD NIH HHS [U01 HD049934, U10 HD050096, UG1 HD049981,
UG1 HD050096]; NIGMS NIH HHS [R01 GM083113, R01 GM083113-04]
NR 58
TC 10
Z9 11
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1529-7535
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD JUL
PY 2011
VL 12
IS 4
BP 387
EP 392
DI 10.1097/PCC.0b013e3181fe4058
PG 6
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA 788ME
UT WOS:000292448200007
PM 21057366
ER
PT J
AU Ryan, P
Atreya, C
AF Ryan, Patricia
Atreya, Chintamani
TI Blood Cell MicroRNAs: What Are They and What Future Do They Hold?
SO TRANSFUSION MEDICINE REVIEWS
LA English
DT Review
ID HUMAN PLATELETS; MICROPROCESSOR COMPLEX; PROTEIN-SYNTHESIS; EXPRESSION;
STORAGE; ERYTHROCYTES; BIOGENESIS; BIOMARKERS; PATHWAYS; GENOMICS
AB The advent of blood component storage revolutionized health care by allowing for a managed supply of transfusion quality blood products. During storage, blood components undergo a series of physiological changes that affect the product quality, which ultimately can interfere with the safety and efficacy of such products after transfusion. Despite continuous improvements in blood component quality and safety, it is still desirable to have in vitro standard markers of measurable characteristics that predict blood component safety and efficacy in vivo following their transfusion. Over the last decade, research on the feasibility of using microRNAs as biomarkers for various clinical manifestations and cellular pathologies has exploded. Here, we review the literature on blood cell microRNAs and discuss the potential of these molecules to act as measurable characteristics (product biomarkers) for stored blood component quality and safety. Published by Elsevier Inc.
C1 [Ryan, Patricia; Atreya, Chintamani] US FDA, Sect Cell Biol, Lab Cellular Hematol, Div Hematol,Off Blood Res & Review,Ctr Biol Evalu, Rockville, MD 20857 USA.
RP Atreya, C (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA.
EM Chintamani.Atreya@fda.hhs.gov
FU Center for Biologics Evaluation and Research
FX PR is a recipient of-a postdoctoral fellowship at the Center for
Biologics Evaluation and Research administered by the Oak Ridge
Institute for Science and Education through an intra-agency agreement
between the US Department of Energy and the US Food and Drug
Administration. The authors thank Drs Ketha and Rao. Center for
Biologics Evaluation and Research, Food and Drug Administration, for
their review of this manuscript.
NR 40
TC 3
Z9 3
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0887-7963
J9 TRANSFUS MED REV
JI Transf. Med. Rev.
PD JUL
PY 2011
VL 25
IS 3
BP 247
EP 251
DI 10.1016/j.tmrv.2011.01.005
PG 5
WC Hematology
SC Hematology
GA 789AH
UT WOS:000292485200007
PM 21419598
ER
PT J
AU Kwako, LE
Glass, N
Campbell, J
Melvin, KC
Barr, T
Gill, JM
AF Kwako, Laura E.
Glass, Nancy
Campbell, Jacquelyn
Melvin, Kristal C.
Barr, Taura
Gill, Jessica M.
TI Traumatic Brain Injury in Intimate Partner Violence: A Critical Review
of Outcomes and Mechanisms
SO TRAUMA VIOLENCE & ABUSE
LA English
DT Review
DE intimate partner violence; traumatic brain injury; neuropsychological
functioning; postconcussive syndrome; PTSD
ID POSTTRAUMATIC-STRESS-DISORDER; 18 US STATES/TERRITORIES; PHYSICAL
HEALTH; BATTERED WOMEN; NEUROTROPHIC FACTOR; FEMALE VICTIMS;
RISK-FACTORS; CHILDHOOD MALTREATMENT; INTERPERSONAL VIOLENCE; ADVERSE
EXPERIENCES
AB The prevalence of intimate partner violence (IPV) is striking, as are its consequences to the lives of women. The IPV often includes physical assault, which can include injuries to the head and attempted strangulation injuries. Both types of injuries can result in traumatic brain injury (TBI). The TBI sustained during IPV often occurs over time, which can increase the risk for health declines and postconcussive syndrome (PCS). Current studies have identified sequelae of cognitive dysfunction, posttraumatic stress disorder, and depression in women experiencing IPV, yet, most fail to determine the role of TBI in the onset and propagation of these disorders. Although imaging studies indicate functional differences in neuronal activation in IPV, they also have not considered the possibility of TBI contributing to these outcomes. This review highlights the significant gaps in current findings related to neuropsychological complications and medical and psychosocial symptoms that likely result in greater morbidity, as well as the societal costs of failing to acknowledge the association of IPV and TBI in women.
C1 [Kwako, Laura E.; Barr, Taura] NINR, NIH, Bethesda, MD 20892 USA.
[Campbell, Jacquelyn] Johns Hopkins Univ, Sch Nursing, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Gill, Jessica M.] George Mason Univ, Sch Nursing, Fairfax, VA 22030 USA.
[Gill, Jessica M.] Krasnow Inst Adv Study, Fairfax, VA USA.
RP Kwako, LE (reprint author), NIAAA, NIH, Bethesda, MD USA.
EM laura.kwako@nih.gov
NR 92
TC 23
Z9 23
U1 13
U2 21
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1524-8380
J9 TRAUMA VIOLENCE ABUS
JI Trauma Violence Abus.
PD JUL
PY 2011
VL 12
IS 3
BP 115
EP 126
DI 10.1177/1524838011404251
PG 12
WC Criminology & Penology; Family Studies; Social Work
SC Criminology & Penology; Family Studies; Social Work
GA 788QS
UT WOS:000292460100001
PM 21511686
ER
PT J
AU Lahousse, SA
Hoenerhoff, M
Collins, J
Ton, TVT
Masinde, T
Olson, D
Rebolloso, Y
Koujitani, T
Tomer, KB
Hong, HHL
Bucher, J
Sills, RC
AF Lahousse, S. A.
Hoenerhoff, M.
Collins, J.
Ton, T-V. T.
Masinde, T.
Olson, D.
Rebolloso, Y.
Koujitani, T.
Tomer, K. B.
Hong, H-H. L.
Bucher, J.
Sills, R. C.
TI Gene Expression and Mutation Assessment Provide Clues of Genetic and
Epigenetic Mechanisms in Liver Tumors of Oxazepam-Exposed Mice
SO VETERINARY PATHOLOGY
LA English
DT Article
DE mouse; liver; cancer; beta-catenin; DNA methylation; epigenetics;
microarray; oxidative stress
ID BETA-CATENIN MUTATIONS; B6C3F1 MICE; HEPATOCELLULAR CARCINOMAS;
OXIDATIVE STRESS; HEPATOCARCINOGEN OXAZEPAM; DNA METHYLATION; GC-RICH;
MOUSE; CARCINOGENESIS; TUMORIGENESIS
AB Liver tumors from a previous National Toxicology Program study were examined using global gene expression and mutation analysis to define the mechanisms of carcinogenesis in mice exposed to oxazepam. Five hepatocellular adenomas and 5 hepatocellular carcinomas from male B6C3F1 mice exposed to 5000 ppm oxazepam and 6 histologically normal liver samples from control animals were examined. One of the major findings in the study was upregulation of the Wnt/beta-catenin signaling pathway. Genes that activate beta-catenin, such as Sox4, were upregulated, whereas genes that inhibit Wnt signaling, such as APC and Crebbp, were downregulated. In addition, liver tumors from oxazepam-exposed mice displayed beta-catenin mutations and increased protein expression of glutamine synthetase, a downstream target in the Wnt signaling pathway. Another important finding in this study was the altered expression of oxidative stress-related genes, specifically increased expression of cytochrome p450 genes, including Cyp1a2 and Cyp2b10, and decreased expression of genes that protect against oxidative stress, such as Sod2 and Cat. Increased oxidative stress was confirmed by measuring isoprostane expression using mass spectrometry. Furthermore, global gene expression identified altered expression of genes that are associated with epigenetic mechanisms of cancer. There was decreased expression of genes that are hypermethylated in human liver cancer, including tumor suppressors APC and Pten. Oxazepam-induced tumors also exhibited decreased expression of genes involved in DNA methylation (Crebbp, Dnmt3b) and histone modification (Sirt1). These data suggest that formation of hepatocellular adenomas and carcinomas in oxazepam-exposed mice involves alteration of the Wnt signaling pathway, oxidative stress, and potential epigenetic alterations.
C1 [Lahousse, S. A.; Hoenerhoff, M.; Ton, T-V. T.; Masinde, T.; Olson, D.; Rebolloso, Y.; Koujitani, T.; Hong, H-H. L.; Sills, R. C.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA.
[Collins, J.] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA.
[Tomer, K. B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA.
[Bucher, J.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA.
RP Sills, RC (reprint author), Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC USA.
EM sills@niehs.nih.gov
RI Tomer, Kenneth/E-8018-2013
FU National Institute of Environmental Health Sciences/National Institutes
of Health
FX This research was supported in part by the Intramural Research Program
of the National Institute of Environmental Health Sciences/National
Institutes of Health.
NR 30
TC 7
Z9 7
U1 0
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD JUL
PY 2011
VL 48
IS 4
BP 875
EP 884
DI 10.1177/0300985810390019
PG 10
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 787RV
UT WOS:000292395300016
PM 21147764
ER
PT J
AU Storry, JR
Castilho, L
Daniels, G
Flegel, WA
Garratty, G
Francis, CL
Moulds, JM
Moulds, JJ
Olsson, ML
Poole, J
Reid, ME
Rouger, P
van der Schoot, E
Scott, M
Smart, E
Tani, Y
Yu, LC
Wendel, S
Westhoff, C
Yahalom, V
Zelinski, T
AF Storry, J. R.
Castilho, L.
Daniels, G.
Flegel, W. A.
Garratty, G.
Francis, C. L.
Moulds, J. M.
Moulds, J. J.
Olsson, M. L.
Poole, J.
Reid, M. E.
Rouger, P.
van der Schoot, E.
Scott, M.
Smart, E.
Tani, Y.
Yu, L. -C.
Wendel, S.
Westhoff, C.
Yahalom, V.
Zelinski, T.
TI International Society of Blood Transfusion Working Party on red cell
immunogenetics and blood group terminology: Berlin report
SO VOX SANGUINIS
LA English
DT Article
DE blood groups; genetics; terminology
ID GROUP SYSTEM; P-PHENOTYPE; SURFACE-ANTIGENS; EXPRESSION; COMMITTEE;
CLONING
C1 [Storry, J. R.] Univ & Reg Labs, SE-22185 Lund, Sweden.
[Castilho, L.] Univ Campinas Hemocentro, Campinas, Brazil.
[Daniels, G.; Poole, J.; Scott, M.] NHSBT, Bristol Inst Transfus Sci, Bristol, Avon, England.
[Daniels, G.; Poole, J.; Scott, M.] NHSBT, IBGRL, Bristol, Avon, England.
[Flegel, W. A.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
[Garratty, G.] Amer Red Cross Blood Serv, Pomona, CA USA.
[Francis, C. L.; Reid, M. E.; Westhoff, C.] New York Blood Ctr, New York, NY 10021 USA.
[Moulds, J. M.; Moulds, J. J.] LifeShare Blood Ctr, Shreveport, LA USA.
[Olsson, M. L.] Lund Univ, Dept Lab Med, Div Haematol & Transfus Med, Lund, Sweden.
[Rouger, P.] Ctr Natl Reference Grp Sanguines, Paris, France.
[van der Schoot, E.] Sanquin Res CLB, Amsterdam, Netherlands.
[Tani, Y.] Osaka Red Cross Blood Ctr, Osaka, Japan.
[Yu, L. -C.] Mackay Mem Hosp, Taipei, Taiwan.
[Yu, L. -C.] Natl Taiwan Univ, Taipei 10764, Taiwan.
[Wendel, S.] Hosp Sirio Libanes, Blood Bank, Sao Paulo, Brazil.
[Yahalom, V.] NBGRL Magen David Adom, Ramat Gan, Israel.
[Zelinski, T.] Rh Lab, Winnipeg, MB, Canada.
RP Storry, JR (reprint author), Univ & Reg Labs, Klinikgatan 21, SE-22185 Lund, Sweden.
EM jill.storry@med.lu.se
RI Castilho, Lilian/F-6123-2012
OI Castilho, Lilian/0000-0002-3104-647X
NR 23
TC 38
Z9 41
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2011
VL 101
IS 1
BP 77
EP 82
DI 10.1111/j.1423-0410.2010.01462.x
PG 6
WC Hematology
SC Hematology
GA 789VM
UT WOS:000292545500011
PM 21401621
ER
PT J
AU Jumpertz, R
Le, DS
Turnbaugh, PJ
Trinidad, C
Bogardus, C
Gordon, JI
Krakoff, J
AF Jumpertz, Reiner
Duc Son Le
Turnbaugh, Peter J.
Trinidad, Cathy
Bogardus, Clifton
Gordon, Jeffrey I.
Krakoff, Jonathan
TI Energy-balance studies reveal associations between gut microbes, caloric
load, and nutrient absorption in humans
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID DIET-INDUCED OBESITY; RESTING METABOLIC-RATE; WEIGHT-LOSS; BODY-WEIGHT;
OVERWEIGHT; ADOLESCENTS; EXPENDITURE; ECOLOGY; INDIANS; WOMEN
AB Background: Studies in mice indicate that the gut microbiome influences both sides of the energy-balance equation by contributing to nutrient absorption and regulating host genes that affect adiposity. However, it remains uncertain as to what extent gut microbiota are an important regulator of nutrient absorption in humans.
Objective: With the use of a carefully monitored inpatient study cohort, we tested how gut bacterial community structure is affected by altering the nutrient load in lean and obese individuals and whether their microbiota are correlated with the efficiency of dietary energy harvest.
Design: We investigated dynamic changes of gut microbiota during diets that varied in caloric content (2400 compared with 3400 kcal/d) by pyrosequencing bacterial 16S ribosomal RNA (rRNA) genes present in the feces of 12 lean and 9 obese individuals and by measuring ingested and stool calories with the use of bomb calorimetry.
Results: The alteration of the nutrient load induced rapid changes in the gut microbiota. These changes were directly correlated with stool energy loss in lean individuals such that a 20% increase in Firmicutes and a corresponding decrease in Bacteroidetes were associated with an increased energy harvest of approximate to 150 kcal. A high degree of over-feeding in lean individuals was accompanied by a greater fractional decrease in stool energy loss.
Conclusions: These results show that the nutrient load is a key variable that can influence the gut (fecal) bacterial community structure over short time scales. Furthermore, the observed associations between gut microbes and nutrient absorption indicate a possible role of the human gut microbiota in the regulation of the nutrient harvest. This trial was registered at clinicaltrials. gov as NCT00414063. Am J Clin Nutr 2011;94:58-65.
C1 [Jumpertz, Reiner] NIDDK, Obes & Diabet Clin Res Sect, NIH, Dept Hlth & Human Serv, Phoenix, AZ 85016 USA.
[Duc Son Le] Nutr Ctr Ho Chi Minh City, Ho Chi Minh City, Vietnam.
[Turnbaugh, Peter J.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
[Turnbaugh, Peter J.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO USA.
RP Jumpertz, R (reprint author), NIDDK, Obes & Diabet Clin Res Sect, NIH, Dept Hlth & Human Serv, 4212 N 16th St, Phoenix, AZ 85016 USA.
EM jumpertzr@mail.nih.gov
OI Turnbaugh, Peter/0000-0002-0888-2875
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health [DK78669, GM068763]
FX Supported by the intramural research program of the National Institute
of Diabetes and Digestive and Kidney Diseases and National Institutes of
Health grants DK78669 (to JIG) and GM068763 (to PJT).
NR 33
TC 274
Z9 287
U1 22
U2 159
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 JUL
PY 2011
VL 94
IS 1
BP 58
EP 65
DI 10.3945/ajcn.110.010132
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 779QK
UT WOS:000291794800011
PM 21543530
ER
PT J
AU Hall, KD
Chow, CC
AF Hall, Kevin D.
Chow, Carson C.
TI Estimating changes in free-living energy intake and its confidence
interval
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID WITHIN-SUBJECT VARIATION; BODY-WEIGHT-CHANGE; FAT-FREE MASS;
FOOD-INTAKE; METABOLIC ADAPTATION; EXPENDITURE; OBESITY;
INTERRELATIONSHIPS; INDIVIDUALITY; MAINTENANCE
AB Background: Free-living energy intake in humans is notoriously difficult to measure but is required to properly assess outpatient weight-control interventions.
Objective: Our objective was to develop a simple methodology that uses longitudinal body weight measurements to estimate changes in energy intake and its 95% CI in individual subjects.
Design: We showed how an energy balance equation with 2 parameters can be derived from any mathematical model of human metabolism. We solved the energy balance equation for changes in free-living energy intake as a function of body weight and its rate of change. We tested the predicted changes in energy intake by using weight-loss data from controlled inpatient feeding studies as well as simulated free-living data from a group of "virtual study subjects" that included realistic fluctuations in body water and day-to-day variations in energy intake.
Results: Our method accurately predicted individual energy intake changes with the use of weight-loss data from controlled inpatient feeding experiments. By applying the method to our simulated free-living virtual study subjects, we showed that daily weight measurements over periods >28 d were required to obtain accurate estimates of energy intake change with a 95% CI of <300 kcal/d. These estimates were relatively insensitive to initial body composition or physical activity level.
Conclusions: Frequent measurements of body weight over extended time periods are required to precisely estimate changes in energy intake in free-living individuals. Such measurements are feasible, relatively inexpensive, and can be used to estimate diet adherence during clinical weight-management programs. Am J Clin Nutr 2011;94:66-74.
C1 [Hall, Kevin D.; Chow, Carson C.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), NIDDK, Lab Biol Modeling, 12A South Dr,Room 4007, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
RI Chow, Carson/A-7970-2009
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX Supported by the Intramural Research Program of the NIH, National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 32
TC 25
Z9 25
U1 2
U2 10
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 JUL
PY 2011
VL 94
IS 1
BP 66
EP 74
DI 10.3945/ajcn.111.014399
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 779QK
UT WOS:000291794800012
PM 21562087
ER
PT J
AU Mason, C
Xiao, LR
Imayama, I
Duggan, CR
Bain, C
Foster-Schubert, KE
Kong, A
Campbell, KL
Wang, CY
Neuhouser, ML
Li, L
Jeffery, RW
Robien, K
Alfano, CM
Blackburn, GL
McTiernan, A
AF Mason, Caitlin
Xiao, Liren
Imayama, Ikuyo
Duggan, Catherine R.
Bain, Carolyn
Foster-Schubert, Karen E.
Kong, Angela
Campbell, Kristin L.
Wang, Ching-Yun
Neuhouser, Marian L.
Li, Li
Jeffery, Robert W.
Robien, Kim
Alfano, Catherine M.
Blackburn, George L.
McTiernan, Anne
TI Effects of weight loss on serum vitamin D in postmenopausal women
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; 25-HYDROXYVITAMIN D; CARDIOVASCULAR-DISEASE;
DOUBLE-BLIND; PHYSICAL-ACTIVITIES; OBESE-PATIENTS; D DEFICIENCY; CANCER
RISK; ORLISTAT; ASSOCIATION
AB Background: Low concentrations of circulating vitamin D are common with obesity and may represent a potential mechanism explaining the elevated risk of certain cancers and cardiovascular outcomes observed in individuals who are overweight or obese.
Objective: The objective of this study was to investigate the effects of 12 mo of weight loss through caloric restriction, exercise intervention, or both on serum 25-hydroxyvitamin D [25(OH) D] concentrations.
Design: Overweight and obese postmenopausal women (n = 439) were randomly assigned to 1 of 4 groups: 1) diet modification (n = 118), 2) exercise (n = 117), 3) diet + exercise (n = 117), or 4) control (n = 87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention consisted of 45 min of moderate-to-vigorous intensity aerobic activity daily for 5 d/wk. Serum 25(OH)D concentrations were measured by using a competitive chemiluminescent immunoassay at baseline and 12 mo.
Results: No significant change in serum 25(OH)D was found between the intervention and control groups. Women who lost <5%, 5-9.9%, 10-14.9%, or >= 15% of baseline weight had mean increases in 25(OH)D of 2.1, 2.7, 3.3, and 7.7 ng/mL, respectively (P for trend = 0.002). Baseline vitamin D status did not modify the effect of the interventions on weight loss or body-composition changes at the 12-mo follow-up.
Conclusion: A greater degree of weight loss, achieved through either a reduced-calorie diet or increased exercise, is associated with increased circulating 25(OH)D concentrations. This trial is registered at clinicaltrials.gov as NCT00470119. Am J Clin Nutr 2011;94:95-103.
C1 [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Prevent Ctr, Seattle, WA 98104 USA.
[Foster-Schubert, Karen E.; Wang, Ching-Yun; Neuhouser, Marian L.; McTiernan, Anne] Univ Washington, Seattle, WA 98195 USA.
[Kong, Angela] Univ Illinois, Chicago, IL USA.
[Campbell, Kristin L.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Li, Li] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Jeffery, Robert W.; Robien, Kim] Univ Minnesota, Minneapolis, MN USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Blackburn, George L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Nutr, Boston, MA 02215 USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Prevent Ctr, M4-B874,POB 19024, Seattle, WA 98104 USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015; Biguzzi, Felipe/E-4724-2015;
OI Duggan, Catherine/0000-0001-7369-4021; Robien, Kim/0000-0002-2120-2280
FU NIH [R01 CA102504, U54-CA116847, 5KL2RR025015-03]; NCI [R25 CA94880,
2R25CA057699-16]; Canadian Institutes of Health Research
FX Supported by grants NIH R01 CA102504 and NIH U54-CA116847. KEF-S was
supported by grant NIH 5KL2RR025015-03. AK was supported by grants NCI
R25 CA94880 and NCI 2R25CA057699-16. CM and KLC were supported by a
Canadian Institutes of Health Research Fellowship Award.
NR 43
TC 39
Z9 40
U1 3
U2 10
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL
PY 2011
VL 94
IS 1
BP 95
EP 103
DI 10.3945/ajcn.111.015552
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 779QK
UT WOS:000291794800015
PM 21613554
ER
PT J
AU Yetley, EA
Coates, PM
Johnson, CL
AF Yetley, Elizabeth A.
Coates, Paul M.
Johnson, Clifford L.
TI Overview of a roundtable on NHANES monitoring of biomarkers of folate
and vitamin B-12 status: measurement procedure issues
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
AB A roundtable dialogue to discuss "NHANES Monitoring of Biomarkers of Folate and Vitamin B-12 Status" took place in July 2010. This article provides an overview of the meeting and this supplement issue. Although the focus of the roundtable dialogue was on the measurement of folate and vitamin B-12 status biomarkers in NHANES, this article also describes the relevance and importance of these issues for clinical and research laboratories. The roundtable identified the microbiological assay (MA) as the gold standard for measurement of serum and red blood cell folate concentrations. The roundtable noted that differences in results between the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA) that NHANES1991-1994 and 1999-2006 used and the MA that NHANES 2007-2010 used will require adjustment equations to evaluate time trends. The roundtable found that the close agreement between the serum results for the MA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedures supported the conversion to LC-MS/MS for serum folate in future NHANES. The roundtable recognized the uncertainty about whether subclinical vitamin B-12 deficiency is a public health concern but encouraged reinstatement of at least one circulating vitamin B-12 measure and one functional vitamin B-12 status measure in future NHANES. The use of serum vitamin B-12 and plasma methylmalonic acid would provide continuity with past NHANES. The roundtable supported the continued use of the National Institute of Standards and Technology (NIST) reference materials in NHANES biomarker analyses and the further development of additional reference materials by the NIST. Am J Clin Nutr 2011;94(suppl):297S-302S.
C1 [Yetley, Elizabeth A.; Coates, Paul M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Coates, PM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA.
EM beth@yetley.com; coatesp@od.nih.gov
FU Office of Dietary Supplements, NIH; National Center for Health
Statistics, CDC
FX Supported by the National Center for Health Statistics, CDC, and the
Office of Dietary Supplements, NIH.
NR 11
TC 14
Z9 14
U1 0
U2 6
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL
PY 2011
VL 94
IS 1
BP 297S
EP 302S
DI 10.3945/ajcn.111.017392
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 779QK
UT WOS:000291794800044
PM 21593504
ER
EF