FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Musset, B
Clark, RA
DeCoursey, TE
Petheo, GL
Geiszt, M
Chen, YM
Cornell, JE
Eddy, CA
Brzyski, RG
El Jamali, A
AF Musset, Boris
Clark, Robert A.
DeCoursey, Thomas E.
Petheo, Gabor L.
Geiszt, Miklos
Chen, Yumin
Cornell, John E.
Eddy, Carlton A.
Brzyski, Robert G.
El Jamali, Amina
TI NOX5 in Human Spermatozoa EXPRESSION, FUNCTION, AND REGULATION
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NADPH OXIDASE NOX5-S; ESOPHAGEAL ADENOCARCINOMA CELLS; OXYGEN SPECIES
PRODUCTION; HUMAN SPERM SUSPENSIONS; GATED PROTON CHANNEL; HUMAN
EOSINOPHILS; SUPEROXIDE-PRODUCTION; RESPIRATORY BURST; ELECTRON
CURRENTS; HUMAN NEUTROPHILS
AB Physiological and pathological processes in spermatozoa involve the production of reactive oxygen species (ROS), but the identity of the ROS-producing enzyme system(s) remains a matter of speculation. We provide the first evidence that NOX5 NADPH oxidase is expressed and functions in human spermatozoa. Immunofluorescence microscopy detected NOX5 protein in both the flagella/neck region and the acrosome. Functionally, spermatozoa exposed to calcium ionophore, phorbol ester, or H2O2 exhibited superoxide anion production, which was blocked by addition of superoxide dismutase, a Ca2+ chelator, or inhibitors of either flavoprotein oxidases (diphenylene iododonium) or NOX enzymes (GKT136901). Consistent with our previous overexpression studies, we found that H2O2-induced superoxide production by primary sperm cells was mediated by the non-receptor tyrosine kinase c-Abl. Moreover, the H(V)1 proton channel, which was recently implicated in spermatozoa motility, was required for optimal superoxide production by spermatozoa. Immunoprecipitation experiments suggested an interaction among NOX5, c-Abl, and H(V)1. H2O2 treatment increased the proportion of motile sperm in a NOX5-dependent manner. Statistical analyses showed a pH-dependent correlation between superoxide production and enhanced sperm motility. Collectively, our findings show that NOX5 is a major source of ROS in human spermatozoa and indicate a role for NOX5-dependent ROS generation in human spermatozoa motility.
C1 [Clark, Robert A.; El Jamali, Amina] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Chen, Yumin; Cornell, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Eddy, Carlton A.; Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Musset, Boris; DeCoursey, Thomas E.] Rush Univ, Med Ctr, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA.
[Petheo, Gabor L.; Geiszt, Miklos] Semmelweis Univ, Fac Med, Dept Physiol, H-1085 Budapest, Hungary.
RP El Jamali, A (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM AkoulouzeBik@uthscsa.edu
RI Musset, Boris/J-2520-2013;
OI Musset, Boris/0000-0001-8242-8817; DeCoursey, Thomas/0000-0002-4263-180X
FU National Institutes of Health [T32 HL04776, UL1 RR025767, KL2 RR025766,
K01 DK084297, R01-GM087507, P30 CA054174, P30 AG013319, P01 AG019316];
Iacocca Family Foundation
FX This work was supported, in whole or in part, by National Institutes of
Health Grants T32 HL04776 (to A. E. J.), UL1 RR025767 (to A. E. J.),
Clinical and Translational Science Awards pilot funding (to A. E. J.),
KL2 RR025766 (to A. E. J.), K01 DK084297 (to A. E. J.), and Career
Development Award R01-GM087507 (to T. E. D.) and an award from the
Iacocca Family Foundation (to B. M.). Robert Clark is a scientific
co-founder, member of the Scientific Advisory Board, and equity holder
in GenKyoTex SA, a Swiss biotechnology start-up company with a primary
goal of developing clinically useful inhibitors of the NOX family of
NADPH oxidases.; Optical Imaging Facility of the University of Texas
Health Science Center at San Antonio, which is supported by National
Institutes of Health Grants P30 CA054174 (Cancer Therapy and Research
Center), P30 AG013319 (Nathan Shock Center), and P01 AG019316 (Aging,
Oxidative Stress and Cell Death). We thank Dr. Craig Witz for arranging
initial access to human sperm samples from the University of Texas
Medicine Fertility Center, Drs. Victoria Frohlich and Shivani Maffi for
expert guidance on confocal microscopy image acquisition and analysis,
Maria Gamez and Mario de la Pena for expert technical assistance, and
Drs. Susan Smith, Yves Gorin, and Denis Feliers for helpful discussions.
NR 72
TC 44
Z9 45
U1 0
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 MAR 16
PY 2012
VL 287
IS 12
BP 9376
EP 9388
DI 10.1074/jbc.M111.314955
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 912KV
UT WOS:000301797800068
PM 22291013
ER
PT J
AU Cherry, ABC
Daley, GQ
AF Cherry, Anne B. C.
Daley, George Q.
TI Reprogramming Cellular Identity for Regenerative Medicine
SO CELL
LA English
DT Review
ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; IPS CELLS; DEFINED FACTORS;
PARKINSONS-DISEASE; MOTOR-NEURONS; HEMATOPOIETIC DIFFERENTIATION;
GENETIC CORRECTION; DNA METHYLATION; IN-VIVO
AB Although development leads unidirectionally toward more restricted cell fates, recent work in cellular reprogramming has proven that one cellular identity can strikingly convert into another, promising countless applications in biomedical research and paving the way for modeling diseases with patient-derived stem cells. To date, there has been little discussion of which disease models are likely to be most informative. Here, we review evidence demonstrating that, because environmental influences and epigenetic signatures are largely erased during reprogramming, patient-specific models of diseases with strong genetic bases and high penetrance are likely to prove most informative in the near term. We also discuss the implications of the new reprogramming paradigm in biomedicine and outline how reprogramming of cell identities is enhancing our understanding of cell differentiation and prospects for cellular therapies and in vivo regeneration.
C1 [Cherry, Anne B. C.; Daley, George Q.] Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA.
[Cherry, Anne B. C.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cherry, Anne B. C.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Cherry, Anne B. C.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Cherry, Anne B. C.; Daley, George Q.] Broad Inst, Cambridge, MA 02142 USA.
[Cherry, Anne B. C.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Daley, GQ (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
RI perumal, murugiah/D-1565-2012; Cherry, Anne/E-7333-2011
FU NIH [RO1-DK70055, UO1-HL100001, RC4-DK090913, P50HG005550]; ARRA
[RC2-HL102815]; Roche Foundation for Anemia Research; Alex's Lemonade
Stand; Ellison Medical Foundation; Doris Duke Medical Foundation;
Harvard Stem Cell Institute
FX G.Q.D. is supported by grants from the NIH (RO1-DK70055, UO1-HL100001,
RC4-DK090913, P50HG005550, and special funds from the ARRA stimulus
package RC2-HL102815), the Roche Foundation for Anemia Research, Alex's
Lemonade Stand, Ellison Medical Foundation, Doris Duke Medical
Foundation, and the Harvard Stem Cell Institute. G.Q.D. is an affiliate
member of the Broad Institute and the Leukemia and Lymphoma Society, and
an investigator of the Howard Hughes Medical Institute and the Manton
Center for Orphan Disease Research.
NR 99
TC 78
Z9 79
U1 8
U2 59
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 16
PY 2012
VL 148
IS 6
BP 1110
EP 1122
DI 10.1016/j.cell.2012.02.031
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 913PI
UT WOS:000301889500010
PM 22424223
ER
PT J
AU Kathiresan, S
Srivastava, D
AF Kathiresan, Sekar
Srivastava, Deepak
TI Genetics of Human Cardiovascular Disease
SO CELL
LA English
DT Review
ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; FAMILIAL HYPERTROPHIC
CARDIOMYOPATHY; EPITHELIAL SODIUM-CHANNEL; C-REACTIVE PROTEIN; LONG-QT
SYNDROME; PLURIPOTENT STEM-CELLS; HOLT-ORAM-SYNDROME; HEART-DISEASE;
MYOCARDIAL-INFARCTION
AB Cardiovascular disease encompasses a range of conditions extending from myocardial infarction to congenital heart disease, most of which are heritable. Enormous effort has been invested in understanding the genes and specific DNA sequence variants that are responsible for this heritability. Here, we review the lessons learned for monogenic and common, complex forms of cardiovascular disease. We also discuss key challenges that remain for gene discovery and for moving from genomic localization to mechanistic insights, with an emphasis on the impact of next-generation sequencing and the use of pluripotent human cells to understand the mechanism by which genetic variation contributes to disease.
C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Kathiresan, Sekar] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Srivastava, Deepak] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
[Srivastava, Deepak] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
[Srivastava, Deepak] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM skathiresan@partners.org; dsrivastava@gladstone.ucsf.edu
RI perumal, murugiah/D-1565-2012
FU NHLBI/NIH; Foundation Leducq; Massachusetts General Hospital; Pfizer;
Merck; Alnylam; Shire Therapeutics; California Institute for
Regenerative Medicine; Younger Family Foundation; Roddenberry
Foundation; Whittier Foundation
FX The authors wish to apologize in advance to authors of outstanding work
that is not acknowledged in this Review due to space constraints. The
authors wish to thank Drs. Ron Do, Nathan O. Stitziel, Gina M. Peloso,
and Kiran Musunuru for assistance with analyses and critical review of
the manuscript. S.K. was supported by grants from NHLBI/NIH, Foundation
Leducq, the Howard Goodman Fellowship from Massachusetts General
Hospital, Pfizer, Merck, Alnylam, and Shire Therapeutics. D.S. was
supported by grants from the NHLBI/NIH, the California Institute for
Regenerative Medicine, the Younger Family Foundation, the Roddenberry
Foundation, and the Whittier Foundation.
NR 132
TC 113
Z9 117
U1 6
U2 61
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 16
PY 2012
VL 148
IS 6
BP 1242
EP 1257
DI 10.1016/j.cell.2012.03.001
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 913PI
UT WOS:000301889500019
PM 22424232
ER
PT J
AU Hajjarian, Z
Nadkarni, SK
AF Hajjarian, Zeinab
Nadkarni, Seemantini K.
TI Evaluating the Viscoelastic Properties of Tissue from Laser Speckle
Fluctuations
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DIFFUSING-WAVE-SPECTROSCOPY; DYNAMIC LIGHT-SCATTERING; ATHEROSCLEROTIC
PLAQUES; COMPLEX FLUIDS; CANCER; MICRORHEOLOGY; BIOMECHANICS; RUPTURE;
DISEASE; STRESS
AB Most pathological conditions such as atherosclerosis, cancer, neurodegenerative, and orthopedic disorders are accompanied with alterations in tissue viscoelasticity. Laser Speckle Rheology (LSR) is a novel optical technology that provides the invaluable potential for mechanical assessment of tissue in situ. In LSR, the specimen is illuminated with coherent light and the time constant of speckle fluctuations, tau, is measured using a high speed camera. Prior work indicates that tau is closely correlated with tissue microstructure and composition. Here, we investigate the relationship between LSR measurements of tau and sample mechanical properties defined by the viscoelastic modulus, G(star). Phantoms and tissue samples over a broad range of viscoelastic properties are evaluated using LSR and conventional mechanical testing. Results demonstrate a strong correlation between tau and vertical bar G(star)vertical bar for both phantom (r = 0.79, p < 0.0001) and tissue (r = 0.88, p<0.0001) specimens, establishing the unique capability of LSR in characterizing tissue viscoelasticity.
C1 [Hajjarian, Zeinab; Nadkarni, Seemantini K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA.
RP Nadkarni, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA.
EM snadkarni@partners.org
FU NIH [R21 HL 088306]; ARRA [R21 HL 088306-02S1]
FX This work was supported in part by the NIH grant No. R21 HL 088306 (S.N)
and the ARRA grant No. R21 HL 088306-02S1 (S.N.).
NR 40
TC 15
Z9 15
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 16
PY 2012
VL 2
AR 316
DI 10.1038/srep00316
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912DI
UT WOS:000301774500001
PM 22428085
ER
PT J
AU Mijailovich, SM
Li, XC
Griffiths, RH
Geeves, MA
AF Mijailovich, Srboljub M.
Li, Xiaochuan
Griffiths, R. Hugh
Geeves, Michael A.
TI The Hill Model for Binding Myosin S1 to Regulated Actin Is not
Equivalent to the McKillop-Geeves Model
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE Ca2+ sensitivity; tropomyosin-troponin-actin; stop flow; titrations;
cooperativity
ID TROPONIN-TROPOMYOSIN COMPLEX; MUSCLE THIN-FILAMENTS; COOPERATIVE
BINDING; SUBFRAGMENT-1; SENSITIVITY; MICROSCOPY; COMPONENTS; ISOFORMS
AB The Hill two-state cooperativity model and the McKillop-Geeves (McK-G) three-state model predict very similar binding traces of myosin subfragment 1 (S1) binding to regulated actin filaments in the presence and absence of calcium, and both fit the experimental data reasonably well [Chen et al., Biophys. J., 80, 2338-2349]. Here, we compared the Hill model and the McK-G model for binding myosin S1 to regulated actin against three sets of experimental data: the titration of regulated actin with S1 and the kinetics of S1 binding of regulated actin with either excess S1 to actin or excess actin to S1. Each data set was collected for a wide range of specified calcium concentrations. Both models were able to generate reasonable fits to the time course data and to titration data. The McK-G model can fit all three data sets with the same calcium-concentration-sensitive parameters. Only K-B and K-T show significant calcium dependence, and the parameters have a classic pCa curve. A unique set of the Hill model parameters was extremely difficult to estimate from the best fits of multiple sets of data. In summary, the McK-G cooperativity model more uniquely resolves parameters estimated from kinetic and titration data than the Hill model, predicts a sigmoidal dependence of key parameters with calcium concentration, and is simpler and more suitable for practical use. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Mijailovich, Srboljub M.; Li, Xiaochuan] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Griffiths, R. Hugh; Geeves, Michael A.] Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England.
[Mijailovich, Srboljub M.] Tufts Med Sch, CBR, Dept Med, Steward St Elizabeth Med Ctr, Boston, MA 02135 USA.
RP Mijailovich, SM (reprint author), Tufts Med Sch, CBR, Dept Med, Steward St Elizabeth Med Ctr, Room 406,736 Cambridge St, Boston, MA 02135 USA.
EM smijailo@hsph.harvard.edu; m.a.geeves@kent.ac.uk
RI Geeves, Michael/F-7583-2011;
OI Mijailovich, Srboljub/0000-0003-1498-308X
FU National Institutes of Health [R01 AR048776]; Wellcome Trust [085309]
FX This work was supported by National Institutes of Health grant no. R01
AR048776 to S.M. and Wellcome Trust Program grant no. 085309 to M.G. We
gratefully acknowledge Dr. Thomas Irving for critical reading of this
article.
NR 24
TC 5
Z9 5
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAR 16
PY 2012
VL 417
IS 1-2
BP 112
EP 128
DI 10.1016/j.jmb.2012.01.011
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 910XW
UT WOS:000301682900009
PM 22306466
ER
PT J
AU Hohmann, EL
Kim, J
AF Hohmann, Elizabeth L.
Kim, JiYeon
TI Case 8-2012: A 53-Year-Old Man with Crohn's Disease, Diarrhea, Fever,
and Bacteremia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID LISTERIA-MONOCYTOGENES; GASTROENTERITIS
C1 [Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kim, JiYeon] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Kim, JiYeon] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Hohmann, EL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
NR 7
TC 5
Z9 5
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 15
PY 2012
VL 366
IS 11
BP 1039
EP 1045
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 908HZ
UT WOS:000301482800009
PM 22417258
ER
PT J
AU Thomas, T
Karr, S
Kelley, KW
McBane, S
AF Thomas, Tyan
Karr, Samantha
Kelley, Kristi W.
McBane, Sarah
TI Overcoming barriers to scholarly activity in a clinical practice setting
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Editorial Material
ID PHARMACY PRACTICE FACULTY
C1 [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA 19104 USA.
[Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Karr, Samantha] Glendale Midwestern Univ, Coll Pharm, Glendale, AZ USA.
[Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA.
[Kelley, Kristi W.] Baptist Hlth Syst Inc, Trinity Med Ctr, Continu Clin, Birmingham, AL USA.
[McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
RP Thomas, T (reprint author), Univ Sci Philadelphia, Philadelphia Coll Pharm, 600 S 43rd St, Philadelphia, PA 19104 USA.
EM t.thomas@usp.edu
NR 7
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD MAR 15
PY 2012
VL 69
IS 6
BP 465
EP 467
DI 10.2146/ajhp110290
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 943LO
UT WOS:000304123700005
PM 22382476
ER
PT J
AU Poon, LH
Lee, AJ
Chiao, TB
Kang, GA
Heath, S
Glass, GA
AF Poon, Linda H.
Lee, Audrey J.
Chiao, Teresa B.
Kang, Gail A.
Heath, Susan
Glass, Graham A.
TI Pharmacist's role in a Parkinson's disease and movement disorders clinic
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE Ambulatory care; Clinical pharmacists; Clinical pharmacy; Department of
Veterans Affairs; Movement disorders; Parkinson disease; Patient
information; Pharmaceutical services; Team
ID MANAGEMENT
AB Purpose. The expanding role of a clinical pharmacist at a Veterans Affairs (VA) outpatient clinic for patients with Parkinson's disease (PD) and movement disorders is described.
Summary. San Francisco VA Medical Center added a clinical pharmacist to the multidisciplinary team serving patients at an outpatient clinic operated by its Parkinson's Disease Research, Education and Clinical Center (PADRECC). During the first six months after joining the clinic team, the pharmacist met with 131 patients and made a total of 69 drug therapy recommendations that were implemented by neurologists, clinical nurse specialists, and other PADRECC providers. The results of a retrospective chart review suggested that in about 21% of the cases evaluated, the pharmacist's recommendations contributed to an improved medical outcome or the resolution of a medical problem. Anonymous surveys indicated that clinic providers (n = 33) and patients (n = 20) were satisfied with the pharmacist's services. Using a five-point Likert scale (scores ranged from 1 for "strongly disagree" to 5 for "strongly agree") that they had more time to devote to other clinic responsibilities with the pharmacist present in the clinic (mean score, 4.79); patients indicated that they had an improved understanding of their medications after speaking with the pharmacist (mean score, 4.88).
Conclusion. A clinical pharmacist's regular involvement in an outpatient PD and movement disorders clinic has been well received by patients and clinic providers. The study results suggest that the pharmacist has made important contributions in areas such as therapeutic problem solving and medication education while freeing up providers for other responsibilities.
C1 [Poon, Linda H.] San Francisco Vet Affairs Med Ctr VAMC, San Francisco, CA USA.
[Poon, Linda H.; Chiao, Teresa B.] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA.
[Poon, Linda H.; Lee, Audrey J.] Univ Pacific, Thomas J Long Sch Pharm & Hlth Sci, Stockton, CA 95211 USA.
[Kang, Gail A.] Univ Calif San Francisco, Neurol Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Kang, Gail A.] San Francisco VA Med Ctr, Educ & Clin Ctr PADRECC, San Francisco, CA USA.
[Heath, Susan; Glass, Graham A.] San Francisco VA Med Ctr, PADRECC, San Francisco, CA USA.
[Glass, Graham A.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA.
RP Poon, LH (reprint author), San Francisco Vet Affairs Med Ctr 119, 4150 Clement St, San Francisco, CA 94121 USA.
EM linda.poon@va.gov
NR 10
TC 2
Z9 3
U1 1
U2 3
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD MAR 15
PY 2012
VL 69
IS 6
BP 518
EP 520
DI 10.2146/ajhp110127
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 943LO
UT WOS:000304123700013
PM 22382484
ER
PT J
AU Yang, XWH
Mirchev, R
Deng, XY
Yacono, P
Yang, HL
Golan, DE
Hemler, ME
AF Yang, Xiuwei H.
Mirchev, Rossen
Deng, Xinyu
Yacono, Patrick
Yang, Helen L.
Golan, David E.
Hemler, Martin E.
TI CD151 restricts the alpha 6 integrin diffusion mode
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Integrin; Tetraspanin; CD151; Single particle tracking; Laminin
ID TETRASPANIN-ENRICHED MICRODOMAINS; CELL-MIGRATION; BREAST-CANCER;
IN-VIVO; BRANCHING MORPHOGENESIS; ALPHA-3-BETA-1 INTEGRIN;
CONFORMATIONAL-CHANGES; CLINICAL-SIGNIFICANCE; ACTIN CYTOSKELETON;
BETA(1) INTEGRINS
AB Laminin-binding integrins (alpha 3 beta 1, alpha 6 beta 1, alpha 6 beta 4, alpha 7 beta 1) are almost always expressed together with tetraspanin CD151. In every coexpressing cell analyzed to date, CD151 makes a fundamental contribution to integrin-dependent motility, invasion, morphology, adhesion and/or signaling. However, there has been minimal mechanistic insight into how CD151 affects integrin functions. In MDA-MB-231 mammary cells, tetraspanin CD151 knockdown impairs alpha 6 integrin clustering and functions without decreasing alpha 6 integrin expression or activation. Furthermore, CD151 knockdown minimally affects the magnitude of a6 integrin diffusion, as measured using single particle tracking. Instead, CD151 knockdown has a novel and unexpected dysregulating effect on the mode of alpha 6 integrin diffusion. In control cells alpha 6 integrin shows mostly random-confined diffusion (RCD) and some directed motion (DMO). In sharp contrast, in CD151-knockdown cells alpha 6 integrin shows mostly DMO. In control cells alpha 6 diffusion mode is sensitive to actin disruption, talin knockdown and phorbol ester stimulation. By contrast, CD151 knockdown cell alpha 6 integrin is sensitive to actin disruption but desensitized to talin knockdown or phorbol ester stimulation, indicating dysregulation. Both phorbol ester and EGF stimulate cell spreading and promote alpha 6 RCD in control cells. By contrast, CD151-ablated cells retain EGF effects but lose phorbol-ester-stimulated spreading and alpha 6 RCD. For alpha 6 integrins, physical association with CD151 promotes alpha 6 RCD, in support of alpha 6-mediated cable formation and adhesion. By comparison, for integrins not associated with CD151 (e.g. av integrins), CD151 affects neither diffusion mode nor alpha v function. Hence, CD151 support of alpha 6 RCD is specific and functionally relevant, and probably underlies diverse CD151 functions in skin, kidney and cancer cells.
C1 [Deng, Xinyu; Yang, Helen L.] Univ Kentucky, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA.
[Mirchev, Rossen; Yacono, Patrick; Golan, David E.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA.
[Yang, Xiuwei H.; Hemler, Martin E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Golan, David E.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
RP Hemler, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM xya222@uky.edu; martin_hemler@dfci.harvard.edu
RI Deng, Xinyu/J-5732-2015
FU National Institutes of Health [CA42368, HL32854]; S.G. Komen Career
Catalyst Award [KG081481]; DOD [W81XWH-07-1-0568]
FX This work was supported by National Institutes of Health [grant numbers
CA42368 to M.E.H. and HL32854 to D.E.G.]; and by a S.G. Komen Career
Catalyst Award [grant number KG081481 to X.H.Y.] and a DOD Concept Award
[grant number W81XWH-07-1-0568 to X.H.Y.]. Deposited in PMC for release
after 12 months.
NR 79
TC 24
Z9 24
U1 2
U2 6
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 15
PY 2012
VL 125
IS 6
BP 1478
EP 1487
DI 10.1242/jcs.093963
PG 10
WC Cell Biology
SC Cell Biology
GA 930QY
UT WOS:000303155400012
PM 22328509
ER
PT J
AU Tokhtaeva, E
Sachs, G
Sun, HY
Dada, LA
Sznajder, JI
Vagin, O
AF Tokhtaeva, Elmira
Sachs, George
Sun, Haiying
Dada, Laura A.
Sznajder, Jacob I.
Vagin, Olga
TI Identification of the amino acid region involved in the intercellular
interaction between the beta(1) subunits of Na+/K+-ATPase
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Na+/K+-ATPase beta(1) subunit; Epithelial junction; Trans-dimerization
ID NECTIN-LIKE MOLECULES; CELL-CELL-ADHESION; EPITHELIAL-CELLS; E-CADHERIN;
NA,K-ATPASE; JUNCTIONS; ANKYRIN; ROLES; GLYCOSYLATION; MIGRATION
AB Epithelial junctions depend on intercellular interactions between beta(1) subunits of the Na+/K+-ATPase molecules of neighboring cells. The interaction between dog and rat subunits is less effective than the interaction between two dog b1 subunits, indicating the importance of species-specific regions for beta(1)-beta(1) binding. To identify these regions, the species-specific amino acid residues were mapped on a high-resolution structure of the Na+/K+-ATPase beta(1) subunit to select those exposed towards the beta(1) subunit of the neighboring cell. These exposed residues were mutated in both dog and rat YFP-linked beta(1) subunits (YFP-beta(1)) and also in the secreted extracellular domain of the dog beta(1) subunit. Five rat-like mutations in the amino acid region spanning residues 198-207 of the dog YFP-beta(1) expressed in Madin Darby canine kidney (MDCK) cells decreased co-precipitation of the endogenous dog beta(1) subunit with YFP-beta(1) to the level observed between dog beta(1) and rat YFP-beta(1). In parallel, these mutations impaired the recognition of YFP-beta(1) by the dog-specific antibody that inhibits cell adhesion between MDCK cells. Accordingly, dog-like mutations in rat YFP-beta(1) increased both the (YFP-beta(1))-beta(1) interaction in MDCK cells and recognition by the antibody. Conversely, rat-like mutations in the secreted extracellular domain of the dog beta(1) subunit increased its interaction with rat YFP-beta(1) in vitro. In addition, these mutations resulted in a reduction of intercellular adhesion between rat lung epithelial cells following addition of the secreted extracellular domain of the dog beta(1) subunit to a cell suspension. Therefore, the amino acid region 198-207 is crucial for both trans-dimerization of the Na+/K+-ATPase beta(1) subunits and cell-cell adhesion.
C1 [Tokhtaeva, Elmira; Sachs, George; Vagin, Olga] Univ Calif Los Angeles, Dept Physiol, Sch Med, Los Angeles, CA 90073 USA.
[Tokhtaeva, Elmira; Sachs, George; Vagin, Olga] Vet Adm Greater Los Angeles Hlth Care Syst, VAGLAHS W LA, Los Angeles, CA 90073 USA.
[Sun, Haiying; Dada, Laura A.; Sznajder, Jacob I.] Northwestern Univ, Div Pulm & Crit Care Med, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Vagin, O (reprint author), Univ Calif Los Angeles, Dept Physiol, Sch Med, Bldg 113,Room 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM olgav@ucla.edu
FU National Institutes of Health [DK077149, DK058333, R37-HL48129]
FX The work was supported by the National Institutes of Health [grant
numbers DK077149 to O.V., DK058333 to G.S. and R37-HL48129 to J.I.S.].
Deposited in PMC for release after 12 months.
NR 29
TC 9
Z9 11
U1 0
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 15
PY 2012
VL 125
IS 6
BP 1605
EP 1616
DI 10.1242/jcs.100149
PG 12
WC Cell Biology
SC Cell Biology
GA 930QY
UT WOS:000303155400023
PM 22328500
ER
PT J
AU Grossi, PA
Costa, AN
Fehily, D
Blumberg, EA
Kuehnert, MJ
Fishman, JA
Ison, MG
Lattes, R
Kotton, CN
Lilleri, D
Kabanova, A
Lanzavecchia, A
Gerna, G
Razonable, RR
Comoli, P
Zecca, M
Basso, S
Ginevri, F
Grossi, A
Schena, FP
Rimola, A
Burra, P
De Martin, E
Rodriguez-Castro, KI
Fagiuoli, S
Pasulo, L
Bruno, R
Andreone, P
Loggi, E
Arena, F
Rossolini, GM
Sganga, G
Cozza, V
AF Grossi, Paolo A.
Costa, Alessandro Nanni
Fehily, Deirdre
Blumberg, Emily A.
Kuehnert, Matthew J.
Fishman, Jay A.
Ison, Michael G.
Lattes, Roberta
Kotton, Camille N.
Lilleri, Daniele
Kabanova, Anne
Lanzavecchia, Antonio
Gerna, Giuseppi
Razonable, Raymund R.
Comoli, Patrizia
Zecca, Marco
Basso, Sabrina
Ginevri, Fabrizio
Grossi, Alessandra
Schena, Francesco P.
Rimola, Antoni
Burra, Patrizia
De Martin, Elenora
Rodriguez-Castro, Kryssia Isabel
Fagiuoli, Stefano
Pasulo, Luisa
Bruno, Raffaele
Andreone, Pietro
Loggi, Elisabetta
Arena, Fabio
Rossolini, Gian Maria
Sganga, Gabriele
Cozza, Valerio
TI Infections and Organ Transplantation: New Challenges for Prevention and
Treatment-A Colloquium
SO TRANSPLANTATION
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; B
SURFACE-ANTIGEN; RESISTANT ACINETOBACTER-BAUMANNII; HIV-POSITIVE
PATIENTS; CYTOTOXIC T-CELLS; ORTHOTOPIC LIVER-TRANSPLANTATION; ACTIVE
ANTIRETROVIRAL THERAPY; RENAL-ALLOGRAFT RECIPIENTS
C1 [Grossi, Paolo A.] Univ Insubria, Dept Infect Dis, Varese, Italy.
[Grossi, Paolo A.] Natl Ctr Transplantat, ISMETT UPMC Palermo, Rome, Italy.
[Costa, Alessandro Nanni; Fehily, Deirdre] Italian Natl Transplant Ctr, Rome, Italy.
[Blumberg, Emily A.] Univ Penn, Dept Med, Div Infect Dis, Perelman Sch Med,Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Kuehnert, Matthew J.] Ctr Dis Control & Prevent, Off Blood Organ & Other Tissue Safety, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA.
[Ison, Michael G.] NW Mem Hosp, Div Infect Dis, Chicago, IL 60611 USA.
[Ison, Michael G.] Div Organ Transplantat, Chicago, IL USA.
[Lattes, Roberta] Inst Nefrol Nephrol, Dept Transplantat, Infect Dis Unit, Buenos Aires, DF, Argentina.
[Kotton, Camille N.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, Boston, MA 02114 USA.
[Kotton, Camille N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lilleri, Daniele; Gerna, Giuseppi] Fdn IRCCS Policlin San Matteo, Area Trapiantol, Lab Sperimentali Ric, Pavia, Italy.
[Kabanova, Anne; Lanzavecchia, Antonio] IRB, Bellinzona, Switzerland.
[Razonable, Raymund R.] Mayo Clin, Coll Med, Div Infect Dis, Rochester, MN USA.
[Comoli, Patrizia; Zecca, Marco; Basso, Sabrina] Fdn IRCCS Policlin S Matteo, Pediat Hematol Oncol & Res Labs, Pavia, Italy.
[Ginevri, Fabrizio] G Gaslini Inst Children, Dept Nephrol, Clin & Expt Kidney Transplantat Unit, Genoa, Italy.
[Grossi, Alessandra] Univ Svizzera Italiana, Fac Commun Sci, ICP, Lugano, Switzerland.
[Schena, Francesco P.] Univ Bari, Dept Emergency & Transplantat, Nephrol Dialysis & Transplantat Unit, Bari, Italy.
[Rimola, Antoni] Hosp Clin Barcelona, Liver Unit, IDIBAPS, CIBEREHD, Barcelona, Spain.
[Burra, Patrizia; De Martin, Elenora; Rodriguez-Castro, Kryssia Isabel] Univ Hosp, Gastroenterol Multivisceral Transplant Unit, Dept Surg & Gastroenterol Sci, Padua, Italy.
[Fagiuoli, Stefano; Pasulo, Luisa] OO RR, Gastroenterol & Liver Transplant Unit, Bergamo, Italy.
[Bruno, Raffaele] Univ Pavia, Dept Infect Dis, IRCCS San Matteo Hosp, I-27100 Pavia, Italy.
[Andreone, Pietro; Loggi, Elisabetta] Univ Bologna, Dept Clin Med, Bologna, Italy.
[Arena, Fabio; Rossolini, Gian Maria] Univ Siena, Dept Biotechnol, Microbiol Sect, I-53100 Siena, Italy.
[Sganga, Gabriele] Catholic Univ, Dept Gen Surg, Div Gen Surg & Organ Transplantat, Rome, Italy.
[Cozza, Valerio] Univ Roma La Sapienza, Dept Surg, Rome, Italy.
RP Grossi, PA (reprint author), Univ Insubria, Dept Infect Dis, Varese, Italy.
EM paolo.grossi@uninsubria.it; blumbere@mail.med.upenn.edu;
mgison@northwestern.edu; roberta.lattes@gmail.com; ckotton@partners.org;
pcomoli@smatteo.pv.it; fp.schena@nephro.uniba.it; arimola@clinic.ub.es;
burra@unipd.it; sfagiuoli@ospedaliriuniti.bergamo.it;
pietro.andreone@unibo.it
RI GROSSI, PAOLO/A-6158-2013; Schena, Francesco /K-6982-2016; Lilleri,
Daniele/K-7776-2016
OI Schena, Francesco /0000-0001-7927-5207;
NR 334
TC 12
Z9 12
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD MAR 15
PY 2012
VL 93
IS 5
SU S
BP S4
EP S39
PG 36
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 906FE
UT WOS:000301329500002
PM 22374265
ER
PT J
AU Cassier, PA
Gelderblom, H
Stacchiotti, S
Thomas, D
Maki, RG
Kroep, JR
van der Graaf, WT
Italiano, A
Seddon, B
Domont, J
Bompas, E
Wagner, AJ
Blay, JY
AF Cassier, Philippe A.
Gelderblom, Hans
Stacchiotti, Silvia
Thomas, David
Maki, Robert G.
Kroep, Judith R.
van der Graaf, Winette T.
Italiano, Antoine
Seddon, Beatrice
Domont, Julien
Bompas, Emanuelle
Wagner, Andrew J.
Blay, Jean-Yves
TI Efficacy of imatinib mesylate for the treatment of locally advanced
and/or metastatic tenosynovial giant cell tumor/pigmented villonodular
synovitis
SO CANCER
LA English
DT Article
DE tenosynovial giant cell tumor; pigmented villonodular synovitis; drug
therapy; imatinib; colony-stimulating factor 1; colony-stimulating
factor 1 receptor
ID GASTROINTESTINAL STROMAL TUMORS; TRANSLOCATION; EXPRESSION; RECEPTOR;
SARCOMA; DIFFUSE; CSF1; FMS
AB BACKGROUND: Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non-neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect. METHODS: Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi-institutional retrospective study to assess the activity of IM in patients with locally advanced/ metastatic PVNS/ TGCT. RESULTS: Twenty-nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n 17; 59%). Two patients had metastatic disease to the lung and/ or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason. CONCLUSIONS: IM displayed interesting activity in patients with PVNS/ TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/ TGCT must be balanced against the potential toxicity of chronic drug therapy. Cancer 2012; 118: 1649-55. VC 2011 American Cancer Society.
C1 [Cassier, Philippe A.; Blay, Jean-Yves] Ctr Leon Berard, Dept Med, F-69008 Lyon, France.
[Gelderblom, Hans; Kroep, Judith R.] Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands.
[Stacchiotti, Silvia] Natl Canc Inst, Dept Canc Med, I-20133 Milan, Italy.
[Thomas, David] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic, Australia.
[Maki, Robert G.] Mem Sloan Kettering Canc Ctr, Sarcoma Program, New York, NY 10021 USA.
[van der Graaf, Winette T.] Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, NL-6525 ED Nijmegen, Netherlands.
[Italiano, Antoine] Bergonie Inst, Dept Med Oncol, Bordeaux, France.
[Seddon, Beatrice] Univ Coll London Hosp, Dept Oncol, London, England.
[Domont, Julien] Inst Gustave Roussy, Dept Med, Villejuif, France.
[Bompas, Emanuelle] Rene Gauducheau Canc Ctr, Dept Med Oncol, Nantes, France.
[Wagner, Andrew J.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
[Blay, Jean-Yves] Univ Lyon, Villeurbanne, France.
RP Cassier, PA (reprint author), Ctr Leon Berard, Dept Med, 28 Rue Laennec, F-69008 Lyon, France.
EM cassierp@hotmail.com
RI van der Graaf, Winette/A-5006-2014; Blay, Jean-Yves/N-3966-2016;
Stacchiotti, Silvia/C-2017-2017
OI Blay, Jean-Yves/0000-0001-7190-120X; Stacchiotti,
Silvia/0000-0002-1742-8666
FU Fondation de France; Federation des Centres de Luttes Contre le Cancer
FX P.A.C. was supported by a grant from the Fondation de France and the
Federation des Centres de Luttes Contre le Cancer.
NR 18
TC 61
Z9 62
U1 1
U2 3
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 MAR 15
PY 2012
VL 118
IS 6
BP 1649
EP 1655
DI 10.1002/cncr.26409
PG 7
WC Oncology
SC Oncology
GA 901NE
UT WOS:000300973000021
PM 21823110
ER
PT J
AU Ponce, NA
Tsui, J
Knight, SJ
Afable-Munsuz, A
Ladabaum, U
Hiatt, RA
Haas, JS
AF Ponce, Ninez A.
Tsui, Jennifer
Knight, Sara J.
Afable-Munsuz, Aimee
Ladabaum, Uri
Hiatt, Robert A.
Haas, Jennifer S.
TI Disparities in cancer screening in individuals with a family history of
breast or colorectal cancer
SO CANCER
LA English
DT Article
DE family history; cancer screening; cancer disparities; breast cancer;
colorectal cancer
ID AFRICAN-AMERICAN WOMEN; SERVICES TASK-FORCE; RISK-ASSESSMENT;
RECOMMENDATION STATEMENT; ETHNIC-DIFFERENCES; OVARIAN-CANCER;
MAMMOGRAPHY; BARRIERS; AVERAGE; VALIDATION
AB BACKGROUND: Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population-based survey. METHODS: By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years. RESULTS: The authors found no significant BC screening disparities by race/ ethnicity or income in the family history risk groups. Racial/ ethnic disparities were more evident in CRC screening, and the Latino-white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino-white difference in CRC screening ( odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.60) was more substantial than that for individuals with no family history ( OR, 0.74; 95% CI, 0.59-0.92). CONCLUSIONS: Knowledge of their family history widened the Latino-white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino-white screening disparity in Latinos most susceptible to CRC. Cancer 2012; 118: 1656-63. (C) 2011 American Cancer Society.
C1 [Ponce, Ninez A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA.
[Ponce, Ninez A.; Tsui, Jennifer] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
[Knight, Sara J.; Afable-Munsuz, Aimee; Hiatt, Robert A.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Afable-Munsuz, Aimee] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA.
[Ladabaum, Uri] Stanford Univ, Sch Med, Div Gastroenterol, Stanford, CA 94305 USA.
[Hiatt, Robert A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Haas, Jennifer S.] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Ponce, NA (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, 650 Charles Young Dr S, Los Angeles, CA 90095 USA.
EM nponce@ucla.edu
OI Ponce, Ninez/0000-0001-5151-6718
FU University of California at San Francisco Center for Translational and
Policy Research on Personalized Medicine (TRANSPERS)-National Cancer
Institute (NCI) [P01 CA 130818, NCI K07 CA100097]; Network for
Multicultural Research on Health and Healthcare; Department of Family
Medicine; David Geffen School of Medicine; University of California at
Los Angeles (UCLA); Robert Wood Johnson Foundation; Harvard
Catalyst/Harvard Clinical and Translational Science Center (NIH) [UL1 RR
025758]; Harvard University
FX This study was supported by the University of California at San
Francisco Center for Translational and Policy Research on Personalized
Medicine (TRANSPERS)-National Cancer Institute (NCI) P01 CA 130818
(principal investigator [PI], K. Phillips), NCI K07 CA100097 (PI,
N.A.P.), Network for Multicultural Research on Health and Healthcare,
Department of Family Medicine, David Geffen School of Medicine,
University of California at Los Angeles (UCLA), funded by the Robert
Wood Johnson Foundation, and UCLA Summer Graduate Research Mentorship
Program. This research was also conducted with support from the Health
Disparities Research Program of Harvard Catalyst/Harvard Clinical and
Translational Science Center (NIH award #UL1 RR 025758 to J.S.H. and
financial contributions from Harvard University and its affiliated
academic health care centers).
NR 52
TC 16
Z9 16
U1 3
U2 8
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 MAR 15
PY 2012
VL 118
IS 6
BP 1656
EP 1663
DI 10.1002/cncr.26480
PG 8
WC Oncology
SC Oncology
GA 901NE
UT WOS:000300973000022
PM 22009719
ER
PT J
AU Avruch, J
Zhou, DW
Bardeesy, N
AF Avruch, Joseph
Zhou, Dawang
Bardeesy, Nabeel
TI YAP oncogene overexpression supercharges colon cancer proliferation
SO CELL CYCLE
LA English
DT Review
DE YAP; Hippo; intestinal stem cell; beta-catenin; colon cancer; liver
cancer
ID YES-ASSOCIATED PROTEIN; ORGAN SIZE CONTROL; TUMOR-SUPPRESSOR PATHWAY;
HIPPO PATHWAY; WW DOMAIN; TRANSCRIPTIONAL COACTIVATOR;
HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION; GROWTH-CONTROL; STEM-CELLS
AB The transcriptional co-activator YAP is an evolutionarily conserved regulator of organ size and progenitor cell proliferation. YAP is overexpressed at high frequency in many common human cancers and can directly drive cancer development in mouse models. YAP abundance and nuclear localization are negatively regulated by the Hippo kinase cascade, which, in epithelia, is activated by physiological cell-cell contact. Recent work in intestinal epithelium has established that YAP is constitutively inhibited by the Hippo pathway and entirely dispensable for normal development and homeostasis. YAP serves only in a standby capacity; should cell-cell contact be abrogated, as after intestinal damage, the loss of Hippo input permits increased YAP abundance and nuclear residence. In turn, YAP cooperates with beta-catenin to transactivate genes that promote stem cell expansion for epithelial repair. This interplay between overexpressed YAP and beta-catenin also drives proliferation of colon cancer cells. The dispensability of YAP in normal intestine makes YAP's expression or outputs attractive targets for cancer therapy.
C1 [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Avruch, Joseph; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Zhou, Dawang] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen, Fujian, Peoples R China.
RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM avruch@molbio.mgh.harvard.edu
OI Zhou, Dawang/0000-0002-9053-5249
FU NIH [DK17776, CA136567]; Sidney Kimmel Foundation for Cancer Research;
Linda J. Verville Cancer Research Foundation; 111 Project of Education
of China [B06016]; Fundamental Research Funds for the Central
Universities of China [2010111079]; National Natural Science Foundation
of China [81101503]; Natural Science Foundation of Fujian [2011J05096]
FX The work cited herein from the au labs was supported by NIH grants
DK17776 (J.A.) and CA136567 (to J.A. and N.B.), the Sidney Kimmel
Foundation for Cancer Research (N.B.), the Linda J. Verville Cancer
Research Foundation (N.B.), 111 Project of Education of China (NO.
B06016, D.Z.), the Fundamental Research Funds for the Central
Universities of China (NO. 2010111079, D.Z.), National Natural Science
Foundation of China (NO. 81101503, D.Z.) and Natural Science Foundation
of Fujian (NO. 2011J05096, D.Z.).
NR 80
TC 38
Z9 41
U1 2
U2 23
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 15
PY 2012
VL 11
IS 6
BP 1090
EP 1096
DI 10.4161/cc.11.6.19453
PG 7
WC Cell Biology
SC Cell Biology
GA 913DD
UT WOS:000301851700013
PM 22356765
ER
PT J
AU Kim, J
Kim, WJ
Liu, ZQ
Loda, MF
Freeman, MR
AF Kim, Jayoung
Kim, Wun-Jae
Liu, Zhiqian
Loda, Massimo F.
Freeman, Michael R.
TI The ubiquitin-specific protease USP2a enhances tumor progression by
targeting cyclin A1 in bladder cancer
SO CELL CYCLE
LA English
DT Article
DE USP2a; cyclin A1; bladder cancer; cisplatin resistance; deubiquitination
ID FATTY-ACID SYNTHASE; DEUBIQUITINATING ENZYME USP2A; GROWTH-FACTOR;
PROSTATE-CANCER; CELL-CYCLE; AURORA-A; ANTIPROLIFERATIVE FACTOR;
UROTHELIAL CANCER; CARCINOMA CELLS; DOWN-REGULATION
AB The deubiquitinating enzyme USP2a has shown oncogenic properties in many cancer types by impairing ubiquitination of FASN, MDM2, MDMX or Aurora A. Aberrant expression of USP2a has been linked to progression of human tumors, particularly prostate cancer. However, little is known about the role of USP2a or its mechanism of action in bladder cancer. Here, we provide evidence that USP2a is an oncoprotein in bladder cancer cells. Enforced expression of USP2a caused enhanced proliferation, invasion, migration and resistance to several chemotherapeutic reagents, while USP2a loss resulted in slower proliferation, greater chemosensitivity and reduced migratory/invasive capability compared with control cells. USP2a, but not a catalytically inactive mutant, enhanced proliferation in immortalized TRT-HU1 normal human bladder epithelial cells. USP2a bound to cyclin A1 and prevented cyclin A1 ubiquitination, leading to accumulation of cyclin A1 by a block in degradation. Enforced expression of wild-type USP2a, but not an inactive USP2a mutant, resulted in cyclin A1 accumulation and increased cell proliferation. We conclude that USP2a impairs ubiquitination and stabilizes an important cell cycle regulator, cyclin A1, raising the possibility of USP2a targeting as a therapeutic strategy against bladder tumors in combination with chemotherapy.
C1 [Kim, Jayoung; Freeman, Michael R.] Cedars Sinai Med Ctr, Div Canc Biol & Therapeut, Dept Surg, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Kim, Jayoung; Freeman, Michael R.] Cedars Sinai Med Ctr, Dept Biomed Sci, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Kim, Jayoung; Freeman, Michael R.] Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA.
[Kim, Jayoung; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Kim, Jayoung; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Kim, Wun-Jae] Chungbuk Natl Univ, Dept Urol, Cheongju, Chungbuk, South Korea.
[Kim, Wun-Jae] Chungbuk Natl Univ, Chungbuk Biomed Sci Ctr BK21, Sch Med, Cheongju, Chungbuk, South Korea.
[Liu, Zhiqian; Loda, Massimo F.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Loda, Massimo F.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Loda, Massimo F.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA.
RP Kim, J (reprint author), Cedars Sinai Med Ctr, Div Canc Biol & Therapeut, Dept Surg, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
EM Jayoung.Kim@cshs.org
FU NIH [R01 DK087806, R01 CA143777, P50 DK65298]; Fishbein Family IC
Research Foundation/Interstitial Cystitis Association (ICA); ICA; New
York Academy of Medicine; Children's Hospital Boston
FX We thank Dr. Leland W. Chung (Cedars-Sinai Medical Center) for critical
review of the manuscript and helpful advice. This work was supported by
the following funding sources: NIH grants R01 DK087806, R01 CA143777 and
P50 DK65298 (to M. R. F.); the Fishbein Family IC Research
Foundation/Interstitial Cystitis Association (ICA), Pilot Research
Program/ICA, New York Academy of Medicine and Children's Hospital Boston
Faculty Development (to J.K.). J.K. is an American Urological
Association Foundation Research Scholar and a Harvard Medical School
Eleanor and Miles Shore Scholar.
NR 59
TC 20
Z9 25
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 15
PY 2012
VL 11
IS 6
BP 1123
EP 1130
DI 10.4161/cc.11.6.19550
PG 8
WC Cell Biology
SC Cell Biology
GA 913DD
UT WOS:000301851700017
PM 22370483
ER
PT J
AU Santo, L
Hideshima, T
Kung, AL
Tseng, JC
Tamang, D
Yang, M
Jarpe, M
van Duzer, JH
Mazitschek, R
Ogier, WC
Cirstea, D
Rodig, S
Eda, H
Scullen, T
Canavese, M
Bradner, J
Anderson, KC
Jones, SS
Raje, N
AF Santo, Loredana
Hideshima, Teru
Kung, Andrew L.
Tseng, Jen-Chieh
Tamang, David
Yang, Min
Jarpe, Matthew
van Duzer, John H.
Mazitschek, Ralph
Ogier, Walter C.
Cirstea, Diana
Rodig, Scott
Eda, Homare
Scullen, Tyler
Canavese, Miriam
Bradner, James
Anderson, Kenneth C.
Jones, Simon S.
Raje, Noopur
TI Preclinical activity, pharmacodynamic, and pharmacokinetic properties of
a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in
multiple myeloma
SO BLOOD
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; ENDOPLASMIC-RETICULUM STRESS; DEPENDENT
KINASE INHIBITOR; CANCER-THERAPY; DNA-DAMAGE; CELL-DEATH; PHASE-I;
PROTEASOME; APOPTOSIS; VORINOSTAT
AB Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated alpha-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated alpha-tubulin use as a pharmacodynamic biomarker in future clinical trials. (Blood. 2012;119(11):2579-2589)
C1 [Santo, Loredana; Eda, Homare; Scullen, Tyler; Canavese, Miriam; Raje, Noopur] Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol & Oncol, Boston, MA 02114 USA.
[Kung, Andrew L.; Tseng, Jen-Chieh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA.
[Kung, Andrew L.; Tseng, Jen-Chieh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Tamang, David; Yang, Min; Jarpe, Matthew; van Duzer, John H.; Ogier, Walter C.; Jones, Simon S.] Acetylon Pharmaceut, Boston, MA USA.
[Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Rodig, Scott] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Raje, N (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol & Oncol, POB 216,55 Fruit St, Boston, MA 02114 USA.
EM nraje@partners.org
RI perumal, murugiah/D-1565-2012; Mazitschek, Ralph/E-3741-2013;
OI Mazitschek, Ralph/0000-0002-1105-689X; Kung, Andrew/0000-0002-9091-488X
FU AstraZeneca; Acetylon Pharmaceuticals; Leukemia & Lymphoma Society;
Multiple Myeloma Research Foundation
FX N.R. is a Leukemia & Lymphoma Society clinical scholar and recipient of
the Claflin Distinguished Scholar Award. L.S. is a recipient of the
Multiple Myeloma Research Foundation fellow award. K.C.A. is an American
Cancer Society clinical research professor.; K.C.A. is an advisor for
Celgene, Novartis, Millennium, Onyx, BMS, and Merck and is the founder
of Acetylon Pharmaceuticals. T.H., A.L.K, and J.B. are consultants for
Acetylon Pharmaceuticals. R.M. is cofounder and member of the scientific
advisory board of Acetylon Pharmaceuticals. J.B. is a scientific
founder, shareholder, and consultant for Acetylon Pharmaceuticals. M.J.,
D.T., M.Y., W.C.O., and S.J. are employees of Acetylon Pharmaceuticals.
N.R. is on the advisory boards of Celgene, Novartis, Millennium, and
Amgen. N.R. has received research funding from AstraZeneca and Acetylon
Pharmaceuticals. The remaining authors declare no competing financial
interests.
NR 43
TC 174
Z9 177
U1 2
U2 45
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 15
PY 2012
VL 119
IS 11
BP 2579
EP 2589
DI 10.1182/blood-2011-10-387365
PG 11
WC Hematology
SC Hematology
GA 914HZ
UT WOS:000301941700026
PM 22262760
ER
PT J
AU O'sullivan, JF
Leblond, AL
Kelly, G
Kumar, AHS
Metharom, P
Buneker, CK
Alizadeh-Vikali, N
Hynes, BG
O'connor, R
Caplice, NM
AF O'sullivan, J. F.
Leblond, A. L.
Kelly, G.
Kumar, A. H. S.
Metharom, P.
Buneker, C. K.
Alizadeh-Vikali, N.
Hynes, B. G.
O'connor, R.
Caplice, N. M.
TI Potent long-term cardioprotective effects of single low dose
insulin-like growth factor-1 (LD-IGF-1) treatment post myocardial
infarction
SO CARDIOVASCULAR RESEARCH
LA English
DT Meeting Abstract
CT 2nd Congress of the European-Society-of-Cardiology Council on Basic
Cardiovascular Science - Frontiers in Cardiovascular Biology
CY MAR 30-APR 01, 2012
CL London, ENGLAND
SP European Soc Cardiol
C1 [O'sullivan, J. F.] Mater Misericordiae Univ Hosp, Dublin, Ireland.
[Leblond, A. L.; Kumar, A. H. S.; Metharom, P.; Buneker, C. K.; Alizadeh-Vikali, N.; Caplice, N. M.] CRVB, Cork, Ireland.
[Kelly, G.; O'connor, R.] Natl Univ Ireland Univ Coll Cork, Cork, Ireland.
[Hynes, B. G.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RI O'Connor, Rosemary/B-7902-2014
OI O'Connor, Rosemary/0000-0002-0687-3422
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 15
PY 2012
VL 93
SU 1
BP S59
EP S59
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 914TQ
UT WOS:000301975800241
ER
PT J
AU Horst, D
Chen, J
Morikawa, T
Ogino, S
Kirchner, T
Shivdasani, RA
AF Horst, David
Chen, Justina
Morikawa, Teppei
Ogino, Shuji
Kirchner, Thomas
Shivdasani, Ramesh A.
TI Differential WNT Activity in Colorectal Cancer Confers Limited
Tumorigenic Potential and Is Regulated by MAPK Signaling
SO CANCER RESEARCH
LA English
DT Article
ID BETA-CATENIN; STEM-CELLS; COLON-CANCER; TUMOR PROGRESSION; APC;
EXPRESSION; MUTATIONS; MARKER; ACTIVATION; MODEL
AB Colorectal cancers (CRC) express the WNT effector protein beta-catenin in a heterogeneous subcellular pattern rather than uniformly in the nucleus. In this study, we investigated this important aspect of molecular heterogeneity in CRCs by analyzing its basis and relationship with tumor-initiating capability. CRC cells with the highest WNT levels showed only a marginal increase in tumor initiation capacity. Notably, high WNT activity correlated with a coincident activation of robust mitogen-activated protein kinase (MAPK) signaling, which when upregulated by KRAS expression or downregulated by epidermal growth factor receptor inhibition elicited parallel effects on WNT activity. These findings suggested that on its own high WNT activity may not be a reliable signifier of tumor-initiating potential or stem-like potential. Furthermore, they suggest that MAPK signaling is a. critical modifier of intratumoral heterogeneity that contributes significantly to determining the impact of WNT activity on sternness phenotypes in colon cancer cells. Cancer Res; 72(6); 1547-56. (C) 2012 AACR.
C1 [Horst, David; Kirchner, Thomas] LMU, Inst Pathol, D-80337 Munich, Germany.
[Horst, David; Chen, Justina; Morikawa, Teppei; Ogino, Shuji; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Horst, David; Chen, Justina; Morikawa, Teppei; Ogino, Shuji; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA.
RP Horst, D (reprint author), LMU, Inst Pathol, Thalkirchner Str 36, D-80337 Munich, Germany.
EM david.horst@med.uni-muenchen.de; ramesh_shivdasani@dfci.harvard.edu
FU Harvard Stem Cell Institute; Deutsche Forschungsgemeinschaft; NIH [R01
CA151993, P50CA127003]
FX The work was supported by a grant from the Harvard Stem Cell Institute
Shivdasani, a fellowship from the Deutsche Forschungsgemeinschaft (D.
Horst), and grants R01 CA151993 (S. Ogino) and P50CA127003 from the NIH.
NR 40
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Z9 42
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2012
VL 72
IS 6
BP 1547
EP 1556
DI 10.1158/0008-5472.CAN-11-3222
PG 10
WC Oncology
SC Oncology
GA 910UC
UT WOS:000301667300024
PM 22318865
ER
PT J
AU O'Dell, MR
Huang, JL
Whitney-Miller, CL
Deshpande, V
Rothberg, P
Grose, V
Rossi, RM
Zhu, AX
Land, H
Bardeesy, N
Hezel, AF
AF O'Dell, Michael R.
Huang, Jing Li
Whitney-Miller, Christa L.
Deshpande, Vikram
Rothberg, Paul
Grose, Valerie
Rossi, Randall M.
Zhu, Andrew X.
Land, Hartmut
Bardeesy, Nabeel
Hezel, Aram F.
TI Kras(G12D) and p(53) Mutation Cause Primary intrahepatic
Cholangiocarcinoma
SO CANCER RESEARCH
LA English
DT Article
ID CHOLANGIOCELLULAR CARCINOMA; HEPATOCELLULAR-CARCINOMA; K-RAS; LIVER;
CANCER; PROGRESSION; P16(INK4A); AUTOPHAGY; P53; EXPRESSION
AB Intrahepatic cholangiocarcinoma (IHCC) is a primary cancer of the liver with an increasing incidence and poor prognosis. Preclinical studies of the etiology and treatment of this disease are hampered by the relatively small number of available IHCC cell lines or genetically faithful animal models. Here we report the development of a genetically engineered mouse model of IHCC that incorporates two of the most common mutations in human activating mutations of Kras (Kras(G12D)) and deletion of p53. Tissue-specific activation of Kras(G12D) alone resulted in the development of invasive IHCC with low penetrance and long latency. Latency was shortened by combining Kras(G12D)) activation with heterozygous or homozygous deletion of p53 (mean survival of 56 weeks vs. 19 weeks, respectively), which also resulted in widespread local and distant metastasis. Serial analysis showed that the murine models closely recapitulated the multistage histopathologic progression of the human disease, including the development of stroma-rich tumors and the :premalignant biliary lesions, intraductal papillary biliary neoplasms (IPBN), and Von Meyenburg complexes (VMC; also known as biliary hamartomas). These findings establish a new genetically and histo:pathologically faithful model of IHCC and lend experimental support: to the hypothesis that IPBN and VMC are precursors to invasive cancers. Cancer Res; 72(6); 1557-67. (C) 2012 AACR
C1 [O'Dell, Michael R.; Huang, Jing Li; Grose, Valerie; Rossi, Randall M.; Hezel, Aram F.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
[Whitney-Miller, Christa L.; Rothberg, Paul] Univ Rochester, Sch Med, Dept Pathol & Lab Med, Rochester, NY 14642 USA.
[Land, Hartmut] Univ Rochester, Sch Med, Dept Biomed Genet Med, Rochester, NY USA.
[Zhu, Andrew X.; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Hezel, AF (reprint author), Univ Rochester, Sch Med, James P Wilmot Canc Ctr, 300 Elmwood Ave, Rochester, NY 14642 USA.
EM Aram_Hezel@URMC.Rochester.edu
FU Granara-Skerry Trust; Wilmot Cancer Center at the University of
Rochester Medical Center; HHMI; Edelman-Gardner foundation;
Target-Cancer Foundation; NUL [1R01CA136567-01A1]
FX This work was supported by the Granara-Skerry Trust and was accomplished
in the Translational Research Core Facility of the Wilmot Cancer Center
at the University of Rochester Medical Center.; A.F. Heed is supported
by a HHMI early career award and the Edelman-Gardner foundation award.
N. Bardeesy is supported by grants from Target-Cancer Foundation and
from the NUL (1R01CA136567-01A1).
NR 49
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Z9 51
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2012
VL 72
IS 6
BP 1557
EP 1567
DI 10.1158/0008-5472.CAN-11-3596
PG 11
WC Oncology
SC Oncology
GA 910UC
UT WOS:000301667300025
PM 22266220
ER
PT J
AU Koyama, H
Zhuang, TG
Light, JE
Kolla, V
Higashi, M
McGrady, PW
London, WB
Brodeur, GM
AF Koyama, Hiroshi
Zhuang, Tiangang
Light, Jennifer E.
Kolla, Venkatadri
Higashi, Mayumi
McGrady, Patrick W.
London, Wendy B.
Brodeur, Garrett M.
TI Mechanisms of CHD5 Inactivation in Neuroblastomas
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; EPITHELIAL OVARIAN-CANCER;
PEDIATRIC-ONCOLOGY-GROUP; SQUAMOUS-CELL CARCINOMA; N-MYC AMPLIFICATION;
CHROMOSOME 1P; EPIGENETIC INACTIVATION; METHYLATION ANALYSIS; FAVORABLE
PROGNOSIS; RISK STRATIFICATION
AB Purpose: Neuroblastomas (NBs) have genomic, biological, and clinical heterogeneity. High-risk NBs are characterized by several genomic changes, including MYCN amplification and 1p36 deletion. We identified the chromatin-remodeling gene CHD5 as a tumor suppressor gene that maps to 1p36.31. Low or absent CHD5 expression is associated with a 1p36 deletion and an unfavorable outcome, but the mechanisms of CHD5 inactivation in NBs are unknown.
Experimental Design: We examined (i) the CHD5 sequence in 188 high-risk NBs investigated through the TARGET initiative, (ii) the methylation status of the CHD5 promoter in 108 NBs with or without 1p36 deletion and/or MYCN amplification, and (iii) mRNA expression of CHD5 and MYCN in 814 representative NBs using TaqMan low-density array microfluidic cards.
Results: We found noexamples of somatically acquired CHD5 mutations, even incases with 1p36 deletion, indicating that homozygous genomic inactivation is rare. Methylation of the CHD5 promoter was common in the high-risk tumors, and it was generally associated with both 1p36 deletion and MYCN amplification. High CHD5 expression was a powerful predictor of favorable outcome, and it showed prognostic value even in multivariable analysis after adjusting for MYCN amplification, 1p36 deletion, and/or 11q deletion.
Conclusions: We conclude that (i) somatically acquired CHD5 mutations are rare in primary NBs, so inactivation probably occurs by deletion and epigenetic silencing; (ii) CHD5 expression and promoter methylation are associated with MYCN amplification, suggesting a possible interaction between these 2 genes; and (iii) high CHD5 expression is strongly correlated with favorable clinical/biological features and outcome. Clin Cancer Res; 18(6); 1588-97. (C)2012 AACR.
C1 [Koyama, Hiroshi; Zhuang, Tiangang; Light, Jennifer E.; Kolla, Venkatadri; Higashi, Mayumi; Brodeur, Garrett M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Brodeur, Garrett M.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[McGrady, Patrick W.; London, Wendy B.] Stat & Data Ctr, Childrens Oncol Grp, Gainesville, FL USA.
[London, Wendy B.] Childrens Hosp, Boston, MA 02115 USA.
[London, Wendy B.] Dana Farber Harvard Canc Ctr, Boston, MA USA.
RP Brodeur, GM (reprint author), CTRB Rm 3018,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM Brodeur@email.chop.edu
FU NIH [R01-CA39771, U10 CA98413]; Alex's Lemonade Stand Foundation;
Philadelphia Foundation; TARGET Initiative [NIH U10CA098543]; Audrey E.
Evans Chair in Molecular Oncology
FX This work was supported, in part, from the NIH (R01-CA39771 to G.M.
Brodeur) and (U10 CA98413 to W.B. London), Alex's Lemonade Stand
Foundation (to G.M. Brodeur), the Philadelphia Foundation (to G.M.
Brodeur), the TARGET Initiative (grant no. NIH U10CA098543, Principal
Investigator, John M. Maris), and the Audrey E. Evans Chair in Molecular
Oncology (to G.M. Brodeur).
NR 53
TC 27
Z9 29
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1588
EP 1597
DI 10.1158/1078-0432.CCR-11-2644
PG 10
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400016
PM 22294723
ER
PT J
AU Green, MR
Rodig, S
Juszczynski, P
Ouyang, J
Sinha, P
O'Donnell, E
Neuberg, D
Shipp, MA
AF Green, Michael R.
Rodig, Scott
Juszczynski, Przemyslaw
Ouyang, Jing
Sinha, Papiya
O'Donnell, Evan
Neuberg, Donna
Shipp, Margaret A.
TI Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin
Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications
for Targeted Therapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; CD8 T-CELLS; LATENT MEMBRANE PROTEIN-1; CLASSICAL
HODGKIN; COSTIMULATORY MOLECULE; CLINICAL-SIGNIFICANCE;
PANCREATIC-CANCER; STERNBERG CELLS; VIRAL-INFECTION; LIGAND 1
AB Purpose: Programmed cell death ligand 1 (PD-L1) is a molecule expressed on antigen-presenting cells that engages the PD-1 receptor on T cells and inhibits T-cell receptor signaling. The PD-1 axis can be exploited by tumor cells to dampen host antitumor immune responses and foster tumor cell survival. PD-1 blockade has shown promise in multiple malignancies but should be directed toward patients in whom it will be most effective. In recent studies, we found that the chromosome 9p24.1 amplification increased the gene dosage of PD-L1 and its induction by JAK2 in a subset of patients with classical Hodgkin lymphoma (cHL). However, cHLs with normal 9p24.1 copy numbers also expressed detectable PD-L1, prompting analyses of additional PD-L1 regulatory mechanisms.
Experimental Design: Herein, we utilized immunohistochemical, genomic, and functional analyses to define alternative mechanisms of PD-L1 activation in cHL and additional EBV+ lymphoproliferative disorders.
Results: We identified an AP-1-responsive enhancer in the PD-L1 gene. In cHL Reed-Sternberg cells, which exhibit constitutive AP-1 activation, the PD-L1 enhancer binds AP-1 components and increases PD-L1 promoter activity. In addition, we defined Epstein-Barr virus (EBV) infection as an alternative mechanism for PD-L1 induction in cHLs with diploid 9p24.1. PD-L1 was also expressed by EBV-transformed lymphoblastoid cell lines as a result of latent membrane protein 1-mediated, JAK/STAT-dependent promoter and AP-1-associated enhancer activity. In addition, more than 70% of EBV+ posttransplant lymphoproliferative disorders expressed detectable PD-L1.
Conclusions: AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade. Clin Cancer Res; 18(6); 1611-8. (C)2012 AACR.
C1 [Green, Michael R.; Juszczynski, Przemyslaw; Ouyang, Jing; O'Donnell, Evan; Neuberg, Donna; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Rodig, Scott; Sinha, Papiya] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Green, Michael R.; Rodig, Scott; Juszczynski, Przemyslaw; Ouyang, Jing; Neuberg, Donna; Shipp, Margaret A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Shipp, MA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM margaret_shipp@dfci.harvard.edu
RI Green, Michael/F-3482-2013
OI Green, Michael/0000-0001-6309-9472
FU Miller Family Research Fund; NIH [RO1 CA161026]
FX The work was supported by funding from the Miller Family Research Fund
and the NIH (RO1 CA161026).
NR 49
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U1 3
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1611
EP 1618
DI 10.1158/1078-0432.CCR-11-1942
PG 8
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400018
PM 22271878
ER
PT J
AU He, M
Capelletti, M
Nafa, K
Yun, CH
Arcila, ME
Miller, VA
Ginsberg, MS
Zhao, BS
Kris, MG
Eck, MJ
Janne, PA
Ladanyi, M
Oxnard, GR
AF He, Mai
Capelletti, Marzia
Nafa, Khedoudja
Yun, Cai-Hong
Arcila, Maria E.
Miller, Vincent A.
Ginsberg, Michelle S.
Zhao, Binsheng
Kris, Mark G.
Eck, Michael J.
Jaenne, Pasi A.
Ladanyi, Marc
Oxnard, Geoffrey R.
TI EGFR Exon 19 Insertions: A New Family of Sensitizing EGFR Mutations in
Lung Adenocarcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; GENE-MUTATIONS;
POSTOPERATIVE RECURRENCE; GEFITINIB TREATMENT; TUMOR RESPONSE; T790M
MUTATION; CANCER; SENSITIVITY; GUIDELINES
AB Purpose: Epidermal growth factor receptor (EGFR) genotyping is now standard in the management of advanced lung adenocarcinoma, as this biomarker predicts marked benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). EGFR exon 19 insertions are a poorly described family of EGFR mutations, and their association with EGFR-TKI sensitivity in lung adenocarcinoma is uncertain.
Experimental Design: Patients with lung cancers harboring EGFR exon 19 insertions were studied. The predicted effects of the insertions on the structure of the EGFR protein were examined, and EGFR exon 19 insertions were introduced into Ba/F3 cells to assess oncogenicity and in vitro sensitivity to EGFR-TKIs. In patients receiving TKI, response magnitude was assessed with serial computed tomographic (CT) measurement.
Results: Twelve tumors harboring EGFR exon 19 insertions were identified; patients were predominately female (92%) and never-smokers (75%). The 11 specimens available for full sequencing all showed an 18-bp insertion that resulted in the substitution of a Pro for Leu at residue 747. The mutant EGFR transformed the Ba/F3 cells, which were then sensitive to EGFR-TKI. Six patients with measurable disease received TKI and five had a response on serial CT.
Conclusions: EGFR exon 19 insertions are a newly appreciated family of EGFR-TKI-sensitizing mutations, and patients with tumors harboring these mutations should be treated with EGFR-TKI. While these mutations may be missed through the use of some mutation-specific assays, the addition of PCR product size analysis to multigene assays allows sensitive detection of both exon 19 insertion and deletion mutations. Clin Cancer Res; 18(6); 1790-7. (C) 2011 AACR.
C1 [He, Mai; Nafa, Khedoudja; Arcila, Maria E.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, Mol Diagnost Serv, New York, NY 10065 USA.
[Miller, Vincent A.; Kris, Mark G.] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10065 USA.
[Ginsberg, Michelle S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA.
[Zhao, Binsheng] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10065 USA.
[Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Kris, Mark G.] Weill Cornell Med Coll, New York, NY USA.
[Capelletti, Marzia; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Yun, Cai-Hong; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Yun, Cai-Hong; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA.
[Jaenne, Pasi A.; Oxnard, Geoffrey R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Ladanyi, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, Mol Diagnost Serv, 1275 York Ave, New York, NY 10065 USA.
EM ladanyim@mskcc.org
OI Kris, Mark/0000-0002-7317-5341
FU National Cancer Institute [P01-CA129243, P50-CA090578, R01-CA114465]
FX The work was supported by the National Cancer Institute grants
P01-CA129243 (M. Ladanyi and M.G. Kris) and P50-CA090578 and
R01-CA114465 (P.A. Janne)
NR 42
TC 51
Z9 56
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1790
EP 1797
DI 10.1158/1078-0432.CCR-11-2361
PG 8
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400036
PM 22190593
ER
PT J
AU Schwab, J
Gasbarrini, A
Bandiera, S
Boriani, L
Amendola, L
Picci, P
Ferrari, S
Boriani, S
AF Schwab, Joseph
Gasbarrini, Alessandro
Bandiera, Stefano
Boriani, Luca
Amendola, Luca
Picci, Piero
Ferrari, Stefano
Boriani, Stefano
TI Osteosarcoma of the Mobile Spine
SO SPINE
LA English
DT Article
DE en bloc resection; mobile spine; osteosarcoma
ID OSTEOGENIC-SARCOMA; EXPERIENCE; CHEMOTHERAPY
AB Study Design. Retrospective case series.
Objective. Our goal was to assess whether en bloc resection had an impact on survival. Summary of
Background Data. Osteogenic sarcoma occurs rarely in the mobile spine, but when it does, the prognosis is poor. Wide resection is recommended for osteogenic sarcoma of the extremities, but wide resection is difficult and often dangerous in the spine. The goal of this study was to examine whether en bloc removal of osteogenic sarcomas in the mobile spine improves survival.
Methods. We performed a retrospective review of all cases of high-grade, osteogenic sarcoma of the mobile spine treated with high-dose methotrexate and adrimaycin-based chemotherapy between 1985 through 2005. There were 9 male patients and 8 female patients. Patients were followed for a median of 38 months or until death, and surviving patients were followed for a minimum of 6.4 years. Patients were grouped on the basis of whether they underwent en bloc spondylectomy. The Enneking stage and Weinstein, Boriani, and Biagini stage, as well as the pre- and postoperative Frankel grades, were collected on all patients. Local recurrence and metastasis data were collected for all patients. Overall survival was calculated using Kaplan-Meier methods with the log rank test utilized to evaluate the effect of en bloc resection on survival.
Results. Twelve (71%) of 17 patients with osteogenic sarcoma of the mobile spine died. Median disease-specific survival for the entire cohort was 38.1 months (standard error 29.6; 95% confidence interval 0-96). Nine patients underwent en bloc resection. Median overall survival for patients after en bloc resection was 77.3 months (standard error 62; 95% confidence interval 96) versus 17 months (standard error 6.5; 95% confidence interval 4-29.6) (P = 0.09). Eleven (65%)of 17 patients developed pulmonary metastasis, and 9 of those 11 died from their disease (P = 0.04). Six (35%) patients developed a local recurrence, and all 6 died from their disease (P = 0.07).
Conclusion. Osteogenic sarcoma of the mobile spine presents a signifi cant challenge, and most patients die from their disease in spite of aggressive surgery and chemotherapy. Metastastic disease is associated with a worse prognosis. There is a trend toward improved survival with en bloc resection when compared with intralesional resection. Osteogenic sarcoma of the mobile spine is rare and historically has a very poor prognosis. We reviewed our cases of osteogenic sarcoma of the mobile spine to assess whether modern en bloc resection improved survival. Survival remains poor, but there is a trend toward improved survival with en bloc resection.
C1 [Schwab, Joseph] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA.
[Gasbarrini, Alessandro; Bandiera, Stefano; Boriani, Luca; Amendola, Luca; Boriani, Stefano] Univ Bologna, Dept Med Oncol, Rizzoli Inst, Bologna, Italy.
[Picci, Piero] Univ Bologna, Rizzoli Inst, Expt Oncol Lab, Bologna, Italy.
[Ferrari, Stefano] Univ Bologna, Rizzoli Inst, Dept Orthoped Oncol & Degenerat Spine Surg, Bologna, Italy.
RP Schwab, J (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkey 3,55 Fruit St, Boston, MA 02114 USA.
EM schwabj36@gmail.com
RI Picci, Piero/J-5979-2016;
OI Picci, Piero/0000-0002-8519-4101; Amendola, Luca/0000-0003-2052-4437
NR 17
TC 14
Z9 14
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD MAR 15
PY 2012
VL 37
IS 6
BP E381
EP E386
DI 10.1097/BRS.0b013e31822fb1a7
PG 6
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 912CN
UT WOS:000301772300004
PM 22422440
ER
PT J
AU Ayala, R
Kett, LR
Leach, TL
Young, AB
Dunah, AW
Orlando, LR
AF Ayala, Ramses
Kett, Lauren R.
Leach, Tiffany L.
Young, Anne B.
Dunah, Anthone W.
Orlando, Lianna R.
TI Metabotropic glutamate receptor 1 (mGluR1): Antibody specificity and
receptor expression in cultured primary neurons
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Metabotropic glutamate receptors; mGluR1; Neuronal culture; Antibody
specificity; Western blot; Immunocytochemistry
ID IMMUNOHISTOCHEMICAL LOCALIZATION; GROUP-I; PHOSPHORYLATION;
EXCITOTOXICITY
AB The availability of high quality, well-characterized antibodies for molecular and cellular neuroscience studies is important. However, not all available antibodies are rigorously evaluated, nor are limitations of particular antibodies often reported. We have examined a panel of currently available mGluR1 antibodies and have identified which ones are selective for use by western blots and immunocytochemistry. We have also specifically determined whether the antibodies cross-react to recognize mGluR5, by examining (1) tissue from both mGluR1 and mGluR5 knock-out mice and (2) primary cortical cultures, in which mGluR5 is widely expressed but mGluR1 is not. Together, these data provide a baseline characterization of antibodies that can and cannot be reliably used in these types of studies, and will hopefully facilitate and positively impact the research efforts of others studying mGluR1. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Ayala, Ramses; Kett, Lauren R.; Leach, Tiffany L.; Young, Anne B.; Dunah, Anthone W.; Orlando, Lianna R.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Boston, MA 02129 USA.
[Young, Anne B.; Dunah, Anthone W.; Orlando, Lianna R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Orlando, LR (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, 114 16th St B114-2000, Boston, MA 02129 USA.
EM lianna_orlando@post.harvard.edu
FU National Institute of Health [AG13617, NS049006]; Harvard NeuroDiscovery
Center
FX We thank F. Ferraguti for sharing valuable insight about different
mGluR1 antibodies he has worked with, and R. Shigemoto for providing us
with his selective mGluR1a antibody. We also thank Y. Xu and M.
Schwarzschild for the mGluR5 knock-out mice. This work was supported by
National Institute of Health Grants AG13617 (ABY) and NS049006 (AWD),
and the Harvard NeuroDiscovery Center (formerly the Harvard Center for
Neurodegeneration and Repair) (LRO).
NR 20
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD MAR 15
PY 2012
VL 204
IS 2
BP 221
EP 226
DI 10.1016/j.jneumeth.2011.11.014
PG 6
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 910BR
UT WOS:000301612700002
PM 22155385
ER
PT J
AU Wang, R
Zhu, JH
Dong, XC
Shi, ML
Lu, CF
Springer, TA
AF Wang, Rui
Zhu, Jianghai
Dong, Xianchi
Shi, Minlong
Lu, Chafen
Springer, Timothy A.
TI GARP regulates the bioavailability and activation of TGF beta
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID GROWTH-FACTOR-BETA; T-CELLS; LATENT TGF-BETA-1; EXPRESSION; INTEGRIN;
MICE; PROTEIN; BINDING; LYMPHOCYTES; PRECURSOR
AB Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-beta (proTGF beta) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGF beta activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGF beta 1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGF beta 1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGF beta-binding protein for binding to proTGF beta 1. Association between GARP and proTGF beta 1 prevents the secretion of TGF beta 1. Integrin alpha V beta(6) and to a lesser extent alpha V beta(8) are able to activate TGF beta from the GARP-proTGF beta 1 complex. Activation requires the RGD motif of latent TGF beta, disulfide linkage between GARP and latent TGF beta, and membrane association of GARP. Our results show that GARP is a latent TGF beta-binding protein that functions in regulating the bioavailability and activation of TGF beta.
C1 [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
Childrens Hosp, Boston, MA 02115 USA.
Immune Dis Inst, Boston, MA 02115 USA.
RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM springer@idi.harvard.edu
RI shi, minlong/G-8734-2013; Zhu, Jianghai/B-7339-2014; Dong,
Xianchi/C-1393-2015
OI Dong, Xianchi/0000-0001-5121-1236
FU National Institutes of Health [HL103526]; GlaxoSmithKline
FX This work was supported by National Institutes of Health Grant HL103526
and a fellowship from GlaxoSmithKline. We thank D. Rifkin (New York
University) for providing the TMLC cell line, Dean Sheppard (University
of California, San Francisco) for the anti-beta6 antibody,
Stephen Nishimura (University of California, San Francisco) for the
anti-beta8 antibody, Vesna Todorovic (New York University)
for the LTBP1 cDNA, and Katri Koli (University of Helsinki) for the TGF
beta 1 cDNA.
NR 45
TC 44
Z9 46
U1 0
U2 10
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAR 15
PY 2012
VL 23
IS 6
BP 1129
EP 1139
DI 10.1091/mbc.E11-12-1018
PG 11
WC Cell Biology
SC Cell Biology
GA 907XO
UT WOS:000301453700029
PM 22278742
ER
PT J
AU Andrews, JR
Noubary, F
Walensky, RP
Cerda, R
Losina, E
Horsburgh, CR
AF Andrews, Jason R.
Noubary, Farzad
Walensky, Rochelle P.
Cerda, Rodrigo
Losina, Elena
Horsburgh, C. Robert
TI Risk of Progression to Active Tuberculosis Following Reinfection With
Mycobacterium tuberculosis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID EXOGENOUS REINFECTION; MEDICAL-STUDENTS; INFECTION; PATHOGENESIS;
RECURRENCE; EPIDEMICS; IMMUNITY; RELAPSE; DISEASE; TESTS
AB Background. The risk of progression to active tuberculosis is greatest in the several years following initial infection. The extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. Indirect estimates from population models have been highly variable.
Methods. We reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of latent tuberculosis to estimate the incidence of tuberculosis among individuals with latent tuberculosis infection (LTBI group) and without latent tuberculosis (uninfected; UI group). We calculated the incidence rate ratio (IRR) of tuberculosis disease following infection between these 2 groups. We then adjusted incidence for expected reactivation, proportion of each group that was infected, and median time of observation following infection during the study.
Results. We identified 18 publications reporting tuberculosis incidence among 23 paired cohorts of individuals with and without latent infection (total N = 19 886). The weighted mean adjusted incidence rate of tuberculosis in the LTBI and UI groups attributable to reinfection was 13.5 per 1000 person-years (95% confidence interval [CI]: 5.0-26.2 per 1000 person-years) and that attributable to primary infection was 60.1 per 1000 person-years (95% CI: 38.6-87.4 per 1000 person-years). The adjusted IRR for tuberculosis in the LTBI group compared with the UI group was 0.21 (95% CI: .14-.30).
Conclusions. Individuals with latent tuberculosis had 79% lower risk of progressive tuberculosis after reinfection than uninfected individuals. The risk reduction estimated in this study is greater than most previous estimates made through population models.
C1 [Andrews, Jason R.; Noubary, Farzad; Walensky, Rochelle P.; Losina, Elena] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Cerda, Rodrigo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Horsburgh, C. Robert] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Andrews, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM jandrews6@partners.org
OI Walensky, Rochelle P./0000-0002-8795-379X; Andrews,
Jason/0000-0002-5967-251X
FU National Institute of Allergy and Infectious Diseases [R01 AI058736, T32
AI007433-20]; AIDS Clinical Trials Group [U01 AI068636]; Doris Duke
Charitable Foundation; National Institute of General Medical Sciences
[U54 GM088558]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases [grants R01 AI058736 and T32 AI007433-20]; the AIDS
Clinical Trials Group [grant U01 AI068636]; the Doris Duke Charitable
Foundation [Clinical Scientist Development Award]; and the National
Institute of General Medical Sciences [grant U54 GM088558]
NR 40
TC 80
Z9 80
U1 1
U2 8
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 MAR 15
PY 2012
VL 54
IS 6
BP 784
EP 791
DI 10.1093/cid/cir951
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 899CK
UT WOS:000300790900009
PM 22267721
ER
PT J
AU Baker, MA
Lin, HH
Chang, HY
Murray, MB
AF Baker, Meghan A.
Lin, Hsien-Ho
Chang, Hsing-Yi
Murray, Megan B.
TI The Risk of Tuberculosis Disease Among Persons With Diabetes Mellitus: A
Prospective Cohort Study
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID CLAIMS DATA; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; CARE
UTILIZATION; TAIWAN; MICE; SUSCEPTIBILITY; ASSOCIATION; PREVALENCE;
INSURANCE
AB Background. Evidence suggests a causal link between diabetes mellitus and tuberculosis risk. However, to date, few studies have used a prospective design to estimate the impact of diabetes on tuberculosis in a general population. In this study, we prospectively investigated the risk of tuberculosis among persons with diabetes stratified by severity.
Methods. A cohort study was performed that involved 17 715 Taiwanese persons on whom baseline data were collected during Taiwan's 2001 National Health Interview Survey. Participants' subsequent medical care until December 2004 was captured from the National Health Insurance database. The diagnosis and severity of diabetes were established using self-report, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and pharmacy records; incident tuberculosis disease was identified using these codes and pharmacy records. Covariates were obtained through in-person interviews. We used Cox proportional hazards regression analyses to measure the association between tuberculosis and both diabetes and diabetes severity.
Results. Diabetes in general and treated diabetes were significantly associated with tuberculosis (adjusted hazard ratio, 2.09 [95% confidence interval {CI}, 1.10-3.95] and 2.60 [95% CI, 1.34-5.03], respectively). Compared with persons without treated diabetes, participants' risk of tuberculosis increased as the number of complications of diabetes mellitus increased (P = .0016), with >3-fold risk among those with >= 2 diabetes-related complications (odds ratio, 3.45; 95% CI, 1.59-7.50). Similarly, the risk increased among those with higher Diabetes Complications Severity Index scores (P = .0002).
Conclusions. The risk of developing tuberculosis increased among those with increasing diabetes severity.
C1 [Baker, Meghan A.; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Baker, Meghan A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Murray, Megan B.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
[Lin, Hsien-Ho] Mennonite Christian Hosp, Dept Community Hlth, Hualien, Taiwan.
[Lin, Hsien-Ho] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan.
[Chang, Hsing-Yi] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
RP Murray, MB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 641 Huntington Ave, Boston, MA 02115 USA.
EM mmurray@hsph.harvard.edu
RI Chang, Hsing-Yi /E-3973-2010;
OI LIN, HSIEN-HO/0000-0002-7481-6016
NR 40
TC 39
Z9 41
U1 0
U2 11
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 MAR 15
PY 2012
VL 54
IS 6
BP 818
EP 825
DI 10.1093/cid/cir939
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 899CK
UT WOS:000300790900015
PM 22238171
ER
PT J
AU Liu, WT
Xiao, X
Demirci, G
Madsen, J
Li, XC
AF Liu, Wentao
Xiao, Xiang
Demirci, Gulcin
Madsen, Joren
Li, Xian C.
TI Innate NK Cells and Macrophages Recognize and Reject Allogeneic Nonself
In Vivo via Different Mechanisms
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; ALLOGRAFT-REJECTION; XENOGRAFT REJECTION; MEDIATED
REJECTION; GRAFT-REJECTION; T-CELLS; ACTIVATED MACROPHAGES; TRANSPLANT
TOLERANCE; MICE; RECEPTORS
AB Both innate and adaptive immune cells are involved in the allograft response. But how the innate immune cells respond to allotrans-plants remains poorly defined. In the current study, we examined the roles of NK cells and macrophages in recognizing and rejecting allogeneic cells in vivo. We found that in naive mice NK cells are the primary effector cells in the killing of allogeneic cells via "missing self" recognition. However, in alloantigen-presensitized mice, NK cells are dispensable. Instead, macrophages become alloreactive and readily recognize and reject allogeneic nonself. This effect requires help from activated CD4(+) T cells and involves CD40/CD40L engagement, because blocking CD40/CD40L interactions prevents macrophage-mediated rejection of allogeneic cells. Conversely, actively stimulating CD40 triggers macrophage-mediated rejection in the absence of CD4(+) T cells. Importantly, alloantigen-primed and CD4(+) T cell-helped macrophages (licensed macrophages) exhibit potent regulatory function in vivo in an acute graft-versus-host disease model. Together, our data uncover an important role for macrophages in the alloimmune response and may have important clinical implications. The Journal of Immunology, 2012, 188: 2703-2711.
C1 [Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Li, Xian C.] Brigham & Womens Hosp, Transplant Res Ctr, Boston, MA 02115 USA.
[Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Li, Xian C.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA.
[Madsen, Joren] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02224 USA.
[Madsen, Joren] Harvard Univ, Sch Med, Boston, MA 02224 USA.
RP Li, XC (reprint author), Brigham & Womens Hosp, Transplant Res Ctr, 221 Longwood Ave,LM 303, Boston, MA 02115 USA.
EM xli28@partners.org
OI Li, Xian Chang/0000-0002-5981-2762
FU National Institutes of Health [R01AI080779, R56AI080779, T32AI070085]
FX This work was supported by the National Institutes of Health (Grants
R01AI080779 and R56AI080779 to X. C. L.). X. X. was supported by Award
T32AI070085 from the National Institutes of Health.
NR 32
TC 25
Z9 29
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2012
VL 188
IS 6
BP 2703
EP 2711
DI 10.4049/jimmunol.1102997
PG 9
WC Immunology
SC Immunology
GA 903OD
UT WOS:000301126000026
PM 22327074
ER
PT J
AU Meng, R
Ji, XM
Dornbos, D
Feeney, K
Ding, YC
Wang, XY
AF Meng, Ran
Ji, Xunming
Dornbos, David, III
Feeney, Kathleen
Ding, Yuchuan
Wang, Xiaoying
TI A case of Susac's syndrome in a Chinese male
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Letter
C1 [Meng, Ran; Ji, Xunming] Capital Med Univ, Cerebral Vasc Dis Res Inst, Xuanwu Hosp,Chinese Amer United Lab, Key Lab Neurodegenerat Dis,Minist Educ, Beijing 100053, Peoples R China.
[Meng, Ran] Peking Univ, Clin Med Coll 9, Capital Med Univ, Dept Neurol,Beijing Shijitan Hosp, Beijing 100038, Peoples R China.
[Meng, Ran; Feeney, Kathleen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Dornbos, David, III; Ding, Yuchuan] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI 48201 USA.
[Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Ji, XM (reprint author), Capital Med Univ, Cerebral Vasc Dis Res Inst, Xuanwu Hosp,Chinese Amer United Lab, Key Lab Neurodegenerat Dis,Minist Educ, 45 Changchun St, Beijing 100053, Peoples R China.
EM jixm@ccmu.edu.cn
NR 5
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD MAR 15
PY 2012
VL 314
IS 1-2
BP 181
EP 182
DI 10.1016/j.jns.2011.11.031
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 905LF
UT WOS:000301273000037
PM 22178082
ER
PT J
AU Wang, LL
Neuberg, D
Wu, CJ
AF Wang, Lili
Neuberg, Donna
Wu, Catherine J.
TI SF3B1 in Chronic Lymphocytic Leukemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Wang, Lili; Neuberg, Donna; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Wang, LL (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM cwu@partners.org
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 15
PY 2012
VL 366
IS 11
BP 1057
EP 1058
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 908HZ
UT WOS:000301482800016
ER
PT J
AU Fingold, DR
AF Fingold, Diane R.
TI The Road Less Traveled Reply
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Fingold, DR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 15
PY 2012
VL 366
IS 11
BP 1062
EP 1062
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 908HZ
UT WOS:000301482800024
ER
PT J
AU Mears, RP
Spencer, KM
AF Mears, Ryan P.
Spencer, Kevin M.
TI Electrophysiological Assessment of Auditory Stimulus-Specific Plasticity
in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Auditory processing; ERP; event-related brain potential; NMDA receptor;
plasticity; schizophrenia
ID LONG-TERM POTENTIATION; VISUAL-EVOKED POTENTIALS; LTP-LIKE CHANGES;
RECEPTOR ANTAGONIST; SENSORY STIMULATION; PLANUM TEMPORALE; HESCHL
GYRUS; CORTEX; INDUCTION; COMPONENT
AB Background: Disrupted neuroplasticity may be an important aspect of the neural basis of schizophrenia. We used event-related brain potentials (ERPs) to assay neuroplasticity after auditory conditioning in chronic schizophrenia patients (SZ) and matched healthy control subjects (HC).
Methods: Subjects (15 HC, 14 SZ) performed an auditory oddball task during electroencephalogram recording before and after auditory tetanic stimulation (Pre/Post Blocks). Each oddball block consisted of 1000-Hz and 1500-Hz standards and 400-Hz targets. During tetanic conditioning, 1000-Hz tones were presented at 11 Hz for 2.4 min. We analyzed the standard trials, comparing the ERPs evoked by the tetanized stimuli (1000 Hz tones: TS+) and untetanized stimuli (1500 Hz tones: TS-) in the Post Blocks with ERPs from the Pre Blocks (averaged into Baseline ERPs).
Results: In Post Block 1 in HC, TS+ tones evoked a negative shift (60-350 msec) at right temporal electrodes relative to Baseline. No pre-/post-tetanus effects were found in SZ. In Post Block 2 in HC, TS+ tones evoked a positive shift (200-300 msec) at bilateral frontal electrodes. In SZ, TS+ tones evoked a positive shift (100-400 msec) at right frontotemporal electrodes. No pre-/post-tetanus effects were found in either subject group for the TS-tones. The right temporal Post Block 1 and 2 effects were correlated in SZ, suggesting a trade-off in the expression of these effects.
Conclusions: These results suggest that stimulus-specific auditory neuroplasticity is abnormal in schizophrenia. The electrophysiologic assessment of stimulus-specific plasticity may yield novel targets for drug treatment in schizophrenia.
C1 [Mears, Ryan P.; Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res Serv,Dept Psychiat, Boston, MA 02130 USA.
RP Spencer, KM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res Serv,Dept Psychiat, 150 S Huntington Ave, Boston, MA 02130 USA.
EM kevin_spencer@hms.harvard.edu
OI Spencer, Kevin/0000-0002-5500-7627
FU U.S. Department of Veterans Affairs [CX000154]; U.S. National Institutes
of Health [R03 MH076760, R01 MH080187]; Galenea Inc.; Bristol-Myers
Squibb
FX This study was supported by grants to KMS from the U.S. Department of
Veterans Affairs (Merit Review Award CX000154) and the U.S. National
Institutes of Health (Grant Nos. R03 MH076760, R01 MH080187).; RPM
reported no biomedical financial interests or potential conflicts of
interest. KMS reported receiving consultation fees from Galenea Inc. and
Bristol-Myers Squibb.
NR 50
TC 17
Z9 17
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 15
PY 2012
VL 71
IS 6
BP 503
EP 511
DI 10.1016/j.biopsych.2011.12.016
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 899BX
UT WOS:000300789100010
PM 22277333
ER
PT J
AU Cavus, I
Reinhart, RMG
Roach, BJ
Gueorguieva, R
Teyler, TJ
Clapp, WC
Ford, JM
Krystal, JH
Mathalon, DH
AF Cavus, Idil
Reinhart, Robert M. G.
Roach, Brian J.
Gueorguieva, Ralitza
Teyler, Timothy J.
Clapp, Wesley C.
Ford, Judith M.
Krystal, John H.
Mathalon, Daniel H.
TI Impaired Visual Cortical Plasticity in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Evoked potential; long-term potentiation; plasticity; schizophrenia;
visual cortex
ID LONG-TERM POTENTIATION; PRINCIPAL-COMPONENTS-ANALYSIS; EVOKED
POTENTIALS; SYNAPTIC PLASTICITY; CORTEX; IDENTIFICATION; INDUCTION;
DEFICITS; CONVERGENCE; STIMULATION
AB Background: Impaired cortical plasticity may be part of the core pathophysiology of schizophrenia (SZ). Long-term potentiation is a form of neuroplasticity that has been recently demonstrated in humans by showing that repetitive visual stimulation produces lasting enhancement of visual evoked potentials (VEP). Using this paradigm, we examined whether visual cortical plasticity is impaired in SZ.
Methods: Electroencephalographic data were recorded from 19 SZ and 22 healthy control (HC) subjects during a visual long-term potentiation paradigm. Visual evoked potentials were elicited by standard visual stimuli (similar to.83 Hz, 2-minute blocks) at baseline and at 2, 4, and 20 minutes following exposure to visual high-frequency stimulation (HFS) (similar to 8.8 Hz, 2 minutes) designed to induce VEP potentiation. To ensure attentiveness during VEP assessments, subjects responded with a button press to infrequent (10%) target stimuli. Visual evoked potentials were subjected to principal components analysis. Two negative-voltage components prominent over occipital-parietal electrode sites were evident at 92 msec (C1) and at 146 msec (N1b). Changes in C1 and N1b component scores from baseline to the post-HFS assessments were compared between groups.
Results: High-frequency stimulation produced sustained potentiation of visual C1 and N1b in HCs but not in SZs. The HCs and SZs had comparable HFS-driven electroencephalographic visual steady state responses. However, greater visual steady state responses to the HFS predicted greater N1b potentiation in HCs but not in SZs. Schizophrenia patients with greater N1b potentiation decreased their reaction times to target stimuli.
Conclusions: Visual cortical plasticity is impaired in schizophrenia, consistent with hypothesized deficits in N-methyl-D-aspartate receptor function.
C1 [Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv 116D, San Francisco, CA 94121 USA.
[Cavus, Idil; Reinhart, Robert M. G.; Gueorguieva, Ralitza; Ford, Judith M.; Krystal, John H.; Mathalon, Daniel H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Roach, Brian J.; Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Gueorguieva, Ralitza] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Gueorguieva, Ralitza] Yale Univ, Sch Med, New Haven, CT USA.
[Teyler, Timothy J.] Univ Idaho, Washington Wyoming Alaska Montana Idaho Reg Med E, Moscow, ID 83843 USA.
[Clapp, Wesley C.] NeuroScouting LLC, Cambridge, MA USA.
[Krystal, John H.] Vet Affairs Connecticut Healthcare Syst, Schizophrenia Biol Res Ctr, New Haven, CT USA.
[Krystal, John H.] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA.
RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA.
EM daniel.mathalon@ucsf.edu
OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974;
Gueorguieva, Ralitza/0000-0003-0944-5973
FU National Institutes of Health-National Institute of Mental Health
[1RO1MH06508-01A2]; VA Schizophrenia Biological Research Center; Janssen
Research Foundation; AstraZeneca, Inc; Pfizer, Inc.
FX This study was funded by National Institutes of Health-National
Institute of Mental Health Grant# 1RO1MH06508-01A2 (TT, IC), and by the
VA Schizophrenia Biological Research Center (JMF).; Dr. Cavus, is
currently employed by Bristol-Myers Squibb, Inc, receives Bristol-Myers
Squibb stock options, and reports that her name is included under a
provisional patent titled "A noninvasive biomarker of human cortical
plasticity and cognition," United States Patent and Trademark Office
(USPTO) serial number 61/140,833. Previously she was employed by Pfizer
Inc. This work was done during Dr. Cavus' employment at Yale University.
Dr. Teyler reportsaconsulting appointment with Pfizer Laboratories and
that his name is included under a provisional patent titled " A
noninvasive biomarker of human cortical plasticity and cognition," USPTO
serial number 61/140,833. Dr. Clapp reports that his name is included
under a provisional patent titled " A noninvasive biomarker of human
cortical plasticity and cognition," USPTO serial number 61/140,833. Dr.
Clapp is currently employed full-time as a co-founder and chief
scientist at NeuroScouting LLC. This work was done prior to the founding
of NeuroScouting, while at Auckland University and University of
California San Francisco. Dr. Krystal reports individual consultant
agreements (each less than $10,000 per year) from Aisling Capital, LLC,
AstraZeneca Pharmaceuticals, Biocortech, Brintnall & Nicolini, Inc.,
Easton Associates, Gilead Sciences, Inc., GlaxoSmithKline, Janssen
Pharmaceuticals, Lundbeck Research USA, Medivation, Inc., Merz
Pharmaceuticals, MK Medical Communications, F. Hoffmann-La Roche Ltd, SK
Holdings Co., Ltd, Sunovion Pharmaceuticals, Inc., Takeda Industries,
and Teva Pharmaceutical Industries, Ltd. Dr. Krystal also reports
serving on the Scientific Advisory Boards for Abbott Laboratories,
Bristol-Myers Squibb, Eisai, Inc., Eli Lilly and Co., Forest
Laboratories, Inc., Lohocla Research Corporation, Mnemosyne
Pharmaceuticals, Inc., Naurex, Inc., Pfizer Pharmaceuticals and Shire
Pharmaceuticals. Dr. Krystal also reports Exercisable Warrant Options
from Tetragenex Pharmaceuticals (value less than $ 150). Dr. Krystal
also reports serving on the Board of Directors of the Coalition for
Translational Research in Alcohol and Substance Use Disorders. Dr.
Krystal also reports receiving research support from Janssen Research
Foundation (provided drug and some study support to the Department of
Veterans Affairs). Dr. Krystal also reports serving as Editor of
Biological Psychiatry, which is associated with income greater than $
10,000 per year. Dr. Krystal also reports being President for the
American College of Neuropsychopharmacology. Dr. Krystal also reports
that his name is included on a patent titled "Dopamine and noradrenergic
reuptake inhibitors in treatment of schizophrenia" (Patent #: 5,447,948,
September 5, 1995), and on provisional patents titled "Targeting the
glutamatergic system for the treatment of neuropsychiatric disorders"
(PCTWO06108055A1) and "Intranasal administration of ketamine to treat
depression" (pending). Dr. Mathalon reports research funding from
AstraZeneca, Inc, consulting fees from Pfizer, Inc. and that his name is
included under a provisional patent titled "A noninvasive biomarker of
human cortical plasticity and cognition," USPTO serial number
61/140,833. All other authors report no biomedical financial interests
or potential conflicts of interest.
NR 68
TC 25
Z9 25
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 15
PY 2012
VL 71
IS 6
BP 512
EP 520
DI 10.1016/j.biopsych.2012.01.013
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 899BX
UT WOS:000300789100011
PM 22364738
ER
PT J
AU Nguyen, PL
Chen, MH
Beckman, JA
Beard, CJ
Martin, NE
Choueiri, TK
Hu, JC
Hoffman, KE
Dosoretz, DE
Moran, BJ
Salenius, SA
Braccioforte, MH
Kantoff, PW
D'Amico, AV
Ennis, RD
AF Nguyen, Paul L.
Chen, Ming-Hui
Beckman, Joshua A.
Beard, Clair J.
Martin, Neil E.
Choueiri, Toni K.
Hu, Jim C.
Hoffman, Karen E.
Dosoretz, Daniel E.
Moran, Brian J.
Salenius, Sharon A.
Braccioforte, Michelle H.
Kantoff, Philip W.
D'Amico, Anthony V.
Ennis, Ronald D.
TI INFLUENCE OF ANDROGEN DEPRIVATION THERAPY ON ALL-CAUSE MORTALITY IN MEN
WITH HIGH-RISK PROSTATE CANCER AND A HISTORY OF CONGESTIVE HEART FAILURE
OR MYOCARDIAL INFARCTION
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Androgen deprivation therapy; Prostate cancer; Cardiovascular; Mortality
ID CARDIOVASCULAR-DISEASE; SUPPRESSION THERAPY; FOLLOW-UP; RADIOTHERAPY;
RADIATION; TRIAL
AB Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease.
Methods and Materials: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT.
Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075).
Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT. (C) 2012 Elsevier Inc.
C1 [Nguyen, Paul L.; Beard, Clair J.; Martin, Neil E.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Chen, Ming-Hui] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Cardiol, Boston, MA 02115 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Dosoretz, Daniel E.; Salenius, Sharon A.] 21st Century Oncol, Ft Myers, FL USA.
[Moran, Brian J.; Braccioforte, Michelle H.] Chicago Prostate Ctr, Westmont, IL USA.
[Ennis, Ronald D.] Albert Einstein Coll Med, Continuum Canc Ctr New York, St Lukes Roosevelt Hosp, Dept Radiat Oncol, New York, NY USA.
[Ennis, Ronald D.] Albert Einstein Coll Med, Continuum Canc Ctr New York, Beth Israel Hosp, Dept Radiat Oncol, New York, NY USA.
[Choueiri, Toni K.; Kantoff, Philip W.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
[Hu, Jim C.] Harvard Univ, Sch Med, Brigham & Womens Faulkner Hosp, Div Urol Surg, Boston, MA USA.
RP Nguyen, PL (reprint author), Dana Farber Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
EM pnguyen@LROC.harvard.edu
RI Martin, Neil/E-2193-2014;
OI Martin, Neil/0000-0002-8164-8516; Beckman, Joshua/0000-0001-8332-8439
NR 20
TC 39
Z9 41
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2012
VL 82
IS 4
BP 1411
EP 1416
DI 10.1016/j.ijrobp.2011.04.067
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 901PW
UT WOS:000300980300054
PM 21708431
ER
PT J
AU Halasz, LM
Sreedhara, M
Chen, YH
Bellon, JR
Punglia, RS
Wong, JS
Harris, JR
Brock, JE
AF Halasz, Lia M.
Sreedhara, Meera
Chen, Yu-Hui
Bellon, Jennifer R.
Punglia, Rinaa S.
Wong, Julia S.
Harris, Jay R.
Brock, Jane E.
TI Improved Outcomes of Breast-Conserving Therapy for Patients With Ductal
Carcinoma in Situ
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article; Proceedings Paper
CT 33rd Annual San Antonio Breast Cancer Symposium
CY DEC 08-12, 2010
CL San Antonio, TX
SP European Soc Coloproctol (ESCP), Finnish Breast Canc Grp
DE DCIS; Breast-conserving therapy; HER-2; Breast-conserving surgery;
Adjuvant radiation therapy
ID RECURRENCE; HER-2/NEU; EXPRESSION; FEATURES; OVEREXPRESSION;
AMPLIFICATION; CANCER
AB Purpose: Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2(+) DCIS.
Methods and Materials: We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (> 2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003.
Results: With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR+HER-2(-), 27 were ER/PR+HER-2(+), 6 were ER-/PR-HER-2(+), and 6 were ER-/PR-HER-2(-). On univariable analysis, HER-2(+) was significantly associated with Grade III, ER-/PR-, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2(+).
Conclusions: In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated with HER-2(+)DCIS included more extensive DCIS, Grade III, ER-/PR-, central necrosis, comedo subtype, and postmenopausal status. Further follow-up and additional studies are required to confirm these results. (C) 2012 Elsevier Inc.
C1 [Brock, Jane E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Halasz, Lia M.] Harvard Radiat Oncol Program, Boston, MA USA.
[Sreedhara, Meera; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Harris, Jay R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Sreedhara, Meera; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Harris, Jay R.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Brock, JE (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM jebrock@partners.org
NR 19
TC 19
Z9 19
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2012
VL 82
IS 4
BP E581
EP E586
DI 10.1016/j.ijrobp.2011.08.015
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 901PW
UT WOS:000300980300001
PM 22208975
ER
PT J
AU Kotton, CN
AF Kotton, Camille N.
TI Preventative Tools of the Future: Predicting the Individual Risk of
Cytomegalovirus Infection After Transplant
SO TRANSPLANTATION
LA English
DT Editorial Material
ID RECIPIENTS
C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA.
EM ckotton@partners.org
NR 7
TC 2
Z9 2
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD MAR 15
PY 2012
VL 93
IS 5
BP 467
EP 468
DI 10.1097/TP.0b013e318242165d
PG 2
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 899DC
UT WOS:000300793700005
PM 22222786
ER
PT J
AU Busser, BW
Shokri, L
Jaeger, SA
Gisselbrecht, SS
Singhania, A
Berger, MF
Zhou, B
Bulyk, ML
Michelson, AM
AF Busser, Brian W.
Shokri, Leila
Jaeger, Savina A.
Gisselbrecht, Stephen S.
Singhania, Aditi
Berger, Michael F.
Zhou, Bo
Bulyk, Martha L.
Michelson, Alan M.
TI Molecular mechanism underlying the regulatory specificity of a
Drosophila homeodomain protein that specifies myoblast identity
SO DEVELOPMENT
LA English
DT Article
DE Homeodomain; Myoblast; Gene regulation
ID TRANSCRIPTION FACTORS; SEQUENCE LOGOS; HOMEOBOX GENE; HOX PROTEINS;
MUSCLE; DNA; MESODERM; DIVERSIFICATION; EXPRESSION; DIFFERENTIATION
AB A subfamily of Drosophila homeodomain (HD) transcription factors (TFs) controls the identities of individual muscle founder cells (FCs). However, the molecular mechanisms by which these TFs generate unique FC genetic programs remain unknown. To investigate this problem, we first applied genome-wide mRNA expression profiling to identify genes that are activated or repressed by the muscle HD TFs Slouch (Slou) and Muscle segment homeobox (Msh). Next, we used protein-binding microarrays to define the sequences that are bound by Slou, Msh and other HD TFs that have mesodermal expression. These studies revealed that a large class of HDs, including Slou and Msh, predominantly recognize TAAT core sequences but that each HD also binds to unique sites that deviate from this canonical motif. To understand better the regulatory specificity of an individual FC identity HD, we evaluated the functions of atypical binding sites that are preferentially bound by Slou relative to other HDs within muscle enhancers that are either activated or repressed by this TF. These studies showed that Slou regulates the activities of particular myoblast enhancers through Slou-preferred sequences, whereas swapping these sequences for sites that are capable of binding to multiple HD family members does not support the normal regulatory functions of Slou. Moreover, atypical Slou-binding sites are overrepresented in putative enhancers associated with additional Slou-responsive FC genes. Collectively, these studies provide new insights into the roles of individual HD TFs in determining cellular identity, and suggest that the diversity of HD binding preferences can confer regulatory specificity.
C1 [Shokri, Leila; Gisselbrecht, Stephen S.; Berger, Michael F.; Zhou, Bo; Bulyk, Martha L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Bulyk, Martha L.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol HST, Boston, MA 02115 USA.
[Busser, Brian W.; Singhania, Aditi; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, Genet & Dev Biol Ctr, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Jaeger, Savina A.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
[Bulyk, Martha L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Bulyk, Martha L.] Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA.
[Bulyk, Martha L.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.
RP Bulyk, ML (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM mlbulyk@receptor.med.harvard.edu; michelsonam@nhlbi.nih.gov
OI Gisselbrecht, Stephen/0000-0001-8723-902X
FU National Institutes of Health/National Institutes of General Medical
Sciences (NIH/NIGMS) [U01 GM076603]; NIH/National Human Genome Research
Institute (NHGRI) [R01 HG005287]; National Heart, Blood and Lung
Institute (NHLBI) Division of Intramural Research; NIH [5 T32
GM007748-31]; NIH NRSA [1 F32 GM090645-01A1]
FX This work was funded by National Institutes of Health/National
Institutes of General Medical Sciences (NIH/NIGMS) [U01 GM076603 to M.
L. B.], by NIH/National Human Genome Research Institute (NHGRI) [R01
HG005287 to M. L. B.], by the National Heart, Blood and Lung Institute
(NHLBI) Division of Intramural Research (A. M. M.), by a NIH Training
Grant [5 T32 GM007748-31 to L. S.], and by a NIH NRSA [1 F32
GM090645-01A1 to L. S.]. Deposited in PMC for immediate release.
NR 64
TC 20
Z9 20
U1 0
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD MAR 15
PY 2012
VL 139
IS 6
BP 1164
EP 1174
DI 10.1242/dev.077362
PG 11
WC Developmental Biology
SC Developmental Biology
GA 897HY
UT WOS:000300640700013
PM 22296846
ER
PT J
AU Ter-Minassian, M
Asomaning, K
Zhao, Y
Chen, F
Su, L
Carmella, SG
Lin, XH
Hecht, SS
Christiani, DC
AF Ter-Minassian, Monica
Asomaning, Kofi
Zhao, Yang
Chen, Feng
Su, Li
Carmella, Steven G.
Lin, Xihong
Hecht, Stephen S.
Christiani, David C.
TI Genetic variability in the metabolism of the tobacco-specific
nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE NNK; NNAL; tobacco specific nitrosamine; genetic polymorphism; HSD11B1
ID ALDO-KETO REDUCTASES; LUNG-CANCER; CARBONYL REDUCTION; CARCINOGEN NNK;
HUMAN LIVER; CIGARETTE CONSUMPTION; SMOKING-CESSATION; N-NITROSAMINES;
DEHYDROGENASE; ASSOCIATION
AB Urinary metabolites of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, termed total NNAL, have recently been shown to be good predictors of lung cancer risk, years before diagnosis. We sought to determine the contribution of several genetic polymorphisms to total NNAL output and inter-individual variability. The study subjects were derived from the Harvard/Massachusetts General Hospital Lung cancer case-control study. We analyzed 87 self-described smokers (35 lung cancer cases and 52 controls), with urine samples collected at time of diagnosis (19921996). We tested 82 tagging SNPs in 16 genes related to the metabolism of NNK to total NNAL. Using weighted case status least squares regression, we tested for the association of each SNP with square-root (sqrt) transformed total NNAL (pmol per mg creatinine), controlling for age, sex, sqrt packyears and sqrt nicotine (ng per mg creatinine). After a sqrt transformation, nicotine significantly predicted a 0.018 (0.014, 0.023) pmol/mg creatinine unit increase in total NNAL for every ng/mg creatinine increase in nicotine at p < 10E-16. Three HSD11B1 SNPs and AKR1C4 rs7083869 were significantly associated with decreasing total NNAL levels: HSD11B1 rs2235543 (p = 4.84E-08) and rs3753519 (p = 0.0017) passed multiple testing adjustment at FDR q = 1.13E-05 and 0.07 respectively, AKR1C4 rs7083869 (p = 0.019) did not, FDR q = 0.51. HSD11B1 and AKR1C4 enzymes are carbonyl reductases directly involved in the single step reduction of NNK to NNAL. The HSD11B1 SNPs may be correlated with the functional variant rs13306401 and the AKR1C4 SNP is correlated with the enzyme activity reducing variant rs17134592, L311V.
C1 [Ter-Minassian, Monica] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol EOME Program, Boston, MA 02115 USA.
[Carmella, Steven G.; Hecht, Stephen S.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
[Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
RP Ter-Minassian, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol EOME Program, 677 Huntington Ave, Boston, MA 02115 USA.
EM mtermina@hsph.harvard.edu
OI Hecht, Stephen/0000-0001-7228-1356
FU Harvard National Institute for Environmental Health Sciences (NIEHS)
Center for Environmental Health [ES00002]; National Institutes of Health
Office of Extramural Research (NIH-OER); National Cancer Institute (NCI)
[CA074386]; NIH-OER Ruth L. Kirschstein-National Research Service Award
[T32 ES 007069]
FX Grant sponsor: Harvard National Institute for Environmental Health
Sciences (NIEHS) Center for Environmental Health; Grant number: ES00002;
Grant sponsors: National Institutes of Health Office of Extramural
Research (NIH-OER), National Cancer Institute (NCI), NIH-OER Ruth L.
Kirschstein-National Research Service Award; Grant number: T32 ES
007069; Grant sponsor: NCI; Grant number: CA074386
NR 49
TC 10
Z9 10
U1 0
U2 9
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 MAR 15
PY 2012
VL 130
IS 6
BP 1338
EP 1346
DI 10.1002/ijc.26162
PG 9
WC Oncology
SC Oncology
GA 878IV
UT WOS:000299250700011
PM 21544809
ER
PT J
AU Bao, Y
Nimptsch, K
Chan, AT
Ng, K
Meyerhardt, JA
Willett, WC
Giovannucci, E
Fuchs, CS
AF Bao, Ying
Nimptsch, Katharina
Chan, Andrew T.
Ng, Kimmie
Meyerhardt, Jeffrey A.
Willett, Walter C.
Giovannucci, Edward
Fuchs, Charles S.
TI Reported behavior of eating anything at anytime and risk of colorectal
cancer in women
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE Eating behavior; colorectal cancer; cohort study
ID DISINHIBITION; RESTRAINT
AB Although numerous studies have assessed the effect of foods and nutrients on colorectal carcinogenesis, few studies have investigated human eating behavior in relation to risk of colorectal cancer. In our study, we assessed whether the reported behavior of eating anything at anytime influenced colorectal cancer risk and related plasma biomarkers. We prospectively followed up 55,540 women in the Nurses' Health Study who were aged 4873 years, had no history of cancer, ulcerative colitis or diabetes and responded to the item I eat anything I want, anytime I want in the 1994 questionnaire. We also analyzed blood samples for 1,994 women, which were collected in 19891990. During 12 years of follow-up, 552 colorectal cancer cases were documented. After adjusting for age, smoking, body mass index, physical activity, red and processed meat and other known risk factors for colorectal cancer, women who reported eating anything at anytime experienced an increased risk of colorectal cancer (relative risk = 1.28, 95% confidence interval = 1.061.56) compared to those who did not report this behavior. In addition, reporting eating anything at anytime was associated with higher fasting plasma levels of insulin (p = 0.04) and C-peptide (p = 0.05). In conclusion, reports of eating anything at anytime are associated with an increased risk of colorectal cancer in this large prospective cohort study, independent of other potential risk factors for colorectal cancer.
C1 [Bao, Ying; Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Bao, Ying; Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Nimptsch, Katharina; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Ng, Kimmie; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Bao, Y (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM ying.bao@channing.harvard.edu
OI Nimptsch, Katharina/0000-0001-7877-205X
FU National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003]
FX Grant sponsor: National Institutes of Health; Grant numbers: P01
CA87969, P01 CA55075, P50 CA127003
NR 10
TC 2
Z9 2
U1 0
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 MAR 15
PY 2012
VL 130
IS 6
BP 1395
EP 1400
DI 10.1002/ijc.26150
PG 6
WC Oncology
SC Oncology
GA 878IV
UT WOS:000299250700017
PM 21520042
ER
PT J
AU Stirman, SW
Kimberly, J
Cook, N
Calloway, A
Castro, F
Charns, M
AF Stirman, Shannon Wiltsey
Kimberly, John
Cook, Natasha
Calloway, Amber
Castro, Frank
Charns, Martin
TI The sustainability of new programs and innovations: a review of the
empirical literature and recommendations for future research
SO IMPLEMENTATION SCIENCE
LA English
DT Review
ID HEALTH-PROMOTION INTERVENTIONS; SMOKING-CESSATION COMMIT; 5-YEAR
FOLLOW-UP; MENTAL-HEALTH; COMMUNITY INTERVENTION; PREVENTION PROGRAM;
BEHAVIORAL INTERVENTIONS; ORGANIZATIONAL CULTURE; MULTISYSTEMIC THERAPY;
QUALITY IMPROVEMENT
AB Background: The introduction of evidence-based programs and practices into healthcare settings has been the subject of an increasing amount of research in recent years. While a number of studies have examined initial implementation efforts, less research has been conducted to determine what happens beyond that point. There is increasing recognition that the extent to which new programs are sustained is influenced by many different factors and that more needs to be known about just what these factors are and how they interact. To understand the current state of the research literature on sustainability, our team took stock of what is currently known in this area and identified areas in which further research would be particularly helpful. This paper reviews the methods that have been used, the types of outcomes that have been measured and reported, findings from studies that reported long-term implementation outcomes, and factors that have been identified as potential influences on the sustained use of new practices, programs, or interventions. We conclude with recommendations and considerations for future research.
Methods: Two coders identified 125 studies on sustainability that met eligibility criteria. An initial coding scheme was developed based on constructs identified in previous literature on implementation. Additional codes were generated deductively. Related constructs among factors were identified by consensus and collapsed under the general categories. Studies that described the extent to which programs or innovations were sustained were also categorized and summarized.
Results: Although "sustainability" was the term most commonly used in the literature to refer to what happened after initial implementation, not all the studies that were reviewed actually presented working definitions of the term. Most study designs were retrospective and naturalistic. Approximately half of the studies relied on self-reports to assess sustainability or elements that influence sustainability. Approximately half employed quantitative methodologies, and the remainder employed qualitative or mixed methodologies. Few studies that investigated sustainability outcomes employed rigorous methods of evaluation (e.g., objective evaluation, judgement of implementation quality or fidelity). Among those that did, a small number reported full sustainment or high fidelity. Very little research has examined the extent, nature, or impact of adaptations to the interventions or programs once implemented. Influences on sustainability included organizational context, capacity, processes, and factors related to the new program or practice themselves.
Conclusions: Clearer definitions and research that is guided by the conceptual literature on sustainability are critical to the development of the research in the area. Further efforts to characterize the phenomenon and the factors that influence it will enhance the quality of future research. Careful consideration must also be given to interactions among influences at multiple levels, as well as issues such as fidelity, modification, and changes in implementation over time. While prospective and experimental designs are needed, there is also an important role for qualitative research in efforts to understand the phenomenon, refine hypotheses, and develop strategies to promote sustainment.
C1 [Stirman, Shannon Wiltsey; Cook, Natasha; Calloway, Amber; Castro, Frank] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA.
[Stirman, Shannon Wiltsey; Cook, Natasha; Calloway, Amber; Castro, Frank; Charns, Martin] VA Boston Healthcare Syst, Boston, MA USA.
[Stirman, Shannon Wiltsey; Calloway, Amber; Castro, Frank] Boston Univ, Dept Psychiat, Boston, MA 02215 USA.
[Kimberly, John] Univ Penn, Wharton Sch, Dept Healthcare Management, Philadelphia, PA 19104 USA.
[Charns, Martin] VA Ctr Org Leadership & Management Res, Boston, MA USA.
[Charns, Martin] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
RP Stirman, SW (reprint author), Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA.
EM Shannon.wiltsey-stirman@va.gov
OI Charns, Martin/0000-0002-7102-5331; Wiltsey Stirman,
Shannon/0000-0001-9917-5078
FU National Institute of Mental Health [R00 MH 01800, T32 MH 019836, R25
MH080916-01A2]; Implementation Research Institute (IRI), at the George
Warren Brown School of Social Work, Washington University in St. Louis;
Department of Veterans Affairs, Health Services Research & Development
Service, Quality Enhancement Research Initiative (QUERI)
FX The preparation of this article was supported through funding from the
National Institute of Mental Health (R00 MH 01800 [Dr. Stirman] and T32
MH 019836 [Dr. Castro; PI: Keane]); through the Implementation Research
Institute (IRI), at the George Warren Brown School of Social Work,
Washington University in St. Louis, which is funded through an award
from the National Institute of Mental Health (R25 MH080916-01A2) and the
Department of Veterans Affairs, Health Services Research & Development
Service, Quality Enhancement Research Initiative (QUERI). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute of Mental Health,
the National Institutes of Health, or the Department of Veterans
Affairs. Dr. Castro is now affiliated with the VA Maryland Healthcare
System
NR 208
TC 114
Z9 114
U1 9
U2 89
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD MAR 14
PY 2012
VL 7
AR 17
DI 10.1186/1748-5908-7-17
PG 19
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 921LO
UT WOS:000302479300001
ER
PT J
AU Moussaieff, A
Yu, J
Zhu, H
Gattoni-Celli, S
Shohami, E
Kindy, MS
AF Moussaieff, Arieh
Yu, Jin
Zhu, Hong
Gattoni-Celli, Sebastiano
Shohami, Esther
Kindy, Mark S.
TI Protective effects of incensole acetate on cerebral ischemic injury
SO BRAIN RESEARCH
LA English
DT Article
DE Cerebral ischemia; Inflammation; NF-kappa B; Neuroprotection; Incensole
acetate; Boswellia
ID KAPPA-B ACTIVATION; BRAIN-INJURY; IN-VIVO; BEHAVIORAL DEFICITS; DRUG
DEVELOPMENT; BOSWELLIC ACIDS; NEUROPROTECTION; STROKE; RECEPTOR;
CHANNELS
AB The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-kappa B activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reper-fusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-alpha, IL-1 beta and TGF-beta expression, as well as NF-kappa B activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6 h after ischemic injury. Finally, the protective effects of IA were partially mediated by TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage. Published by Elsevier B.V.
C1 [Yu, Jin; Zhu, Hong; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29403 USA.
[Moussaieff, Arieh] Ariel Univ, Ctr Samaria, Ariel, Israel.
[Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29403 USA.
[Gattoni-Celli, Sebastiano; Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Shohami, Esther] Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel.
[Kindy, Mark S.] Clemson Univ, Dept Bioengn, Clemson, SC USA.
RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, Strom Thurmond Biomed Res Bldg,Room 503,114 Dough, Charleston, SC 29403 USA.
EM kindyms@musc.edu
FU National Institutes of Health [ES 016774]; Veterans Administration;
National Science Foundation EPSCoR [EPS-0132573, EPS-0447660]
FX We thank Aruna Bhat for her technical support and Eileen McFadden for
secretarial support. Supported by grants from the National Institutes of
Health (ES 016774, MSK), and the Veterans Administration (MSK, SGC) and
the National Science Foundation EPSCoR grants (MSK, EPS-0132573 and
EPS-0447660).
NR 42
TC 11
Z9 12
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD MAR 14
PY 2012
VL 1443
BP 89
EP 97
DI 10.1016/j.brainres.2012.01.001
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 920RU
UT WOS:000302425800008
PM 22284622
ER
PT J
AU Kalscheuer, H
Danzl, N
Onoe, T
Faust, T
Winchester, R
Goland, R
Greenberg, E
Spitzer, TR
Savage, DG
Tahara, H
Choi, G
Yang, YG
Sykes, M
AF Kalscheuer, Hannes
Danzl, Nichole
Onoe, Takashi
Faust, Ted
Winchester, Robert
Goland, Robin
Greenberg, Ellen
Spitzer, Thomas R.
Savage, David G.
Tahara, Hiroyuki
Choi, Goda
Yang, Yong-Guang
Sykes, Megan
TI A Model for Personalized in Vivo Analysis of Human Immune Responsiveness
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID T-CELL RESPONSES; BONE-MARROW-TRANSPLANTATION; HOMEOSTATIC EXPANSION;
MULTIPLE-SCLEROSIS; THYMUS GRAFTS; MOUSE MODEL; MICE; TYPE-1;
AUTOIMMUNITY; DEFECTS
AB Studies of human immune diseases are generally limited to the analysis of peripheral blood lymphocytes of heterogeneous patient populations. Improved models are needed to allow analysis of fundamental immunologic abnormalities predisposing to disease and in which to assess immunotherapies. Immunodeficient mice receiving human fetal thymus grafts and fetal CD34(+) cells intravenously produce robust human immune systems, allowing analysis of human T cell development and function. However, to use humanized mice to study human immune-mediated disorders, immune systems must be generated from adult hematopoietic cells. Here, we demonstrated robust immune reconstitution in mice with hematopoietic stem cells (HSCs) aspirated from bone marrow of adults with type 1 diabetes (T1D) and healthy control volunteers. In these humanized mice, cryopreservation of human leukocyte antigen allele-matched fetal thymic tissue prevented allogeneic adult HSC rejection. Newly generated T cells, which included regulatory T cells (T-regs), were functional and self-tolerant and had a diverse repertoire. The immune recognition of these mice mimicked that of the adult CD34(+) cell donor, but the T cell phenotypes were more predominantly "naive" than those of the adult donors. HSCs from T1D and control donors generated similar numbers of natural T-regs intrathymically; however, peripheral T cells from T1D subjects showed increased proportions of activated or memory cells compared to controls, suggesting possible HSC-intrinsic differences in T cell homeostasis that might underlie immune pathology in T1D. This "personalized immune" mouse provides a new model for individualized analysis of human immune responses that may provide new insights into not only T1D but also other forms of immune function and dysfunction as well.
C1 [Kalscheuer, Hannes; Onoe, Takashi; Faust, Ted; Yang, Yong-Guang; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02129 USA.
[Kalscheuer, Hannes; Danzl, Nichole; Tahara, Hiroyuki; Choi, Goda; Yang, Yong-Guang; Sykes, Megan] Columbia Univ, Coll Phys & Surg, Dept Med, Columbia Ctr Translat Immunol, New York, NY 10032 USA.
[Winchester, Robert] Columbia Univ, Dept Pathol, Coll Phys & Surg, New York, NY 10032 USA.
[Goland, Robin; Greenberg, Ellen] Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, New York, NY 10032 USA.
[Spitzer, Thomas R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Bone Marrow Transplantat,Dept Med, Boston, MA 02114 USA.
[Savage, David G.] Columbia Univ, Coll Phys & Surg, Dept Med, Div Hematol Oncol, New York, NY 10032 USA.
[Sykes, Megan] Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY 10032 USA.
[Sykes, Megan] Columbia Univ, Coll Phys & Surg, Dept Microbiol Immunol, New York, NY 10032 USA.
RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02129 USA.
EM megan.sykes@columbia.edu
FU JDRF Autoimmunity Center at Harvard University; NIH [RO1 AI084903];
Deutsche Forschungsgemeinschaft (German Research Foundation); American
Diabetes Association
FX Funding: Supported by the JDRF Autoimmunity Center at Harvard University
and by NIH grant RO1 AI084903. H. K. was supported by the Deutsche
Forschungsgemeinschaft (German Research Foundation) and N.D. was
supported by the American Diabetes Association.
NR 44
TC 10
Z9 11
U1 1
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 14
PY 2012
VL 4
IS 125
AR 125ra30
DI 10.1126/scitranslmed.3003481
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 909BY
UT WOS:000301538300003
PM 22422991
ER
PT J
AU Zhu, JQ
Choi, WS
McCoy, JG
Negri, A
Zhu, JH
Naini, S
Li, JH
Shen, M
Huang, WW
Bougie, D
Rasmussen, M
Aster, R
Thomas, CJ
Filizola, M
Springer, TA
Coller, BS
AF Zhu, Jieqing
Choi, Won-Seok
McCoy, Joshua G.
Negri, Ana
Zhu, Jianghai
Naini, Sarasija
Li, Jihong
Shen, Min
Huang, Wenwei
Bougie, Daniel
Rasmussen, Mark
Aster, Richard
Thomas, Craig J.
Filizola, Marta
Springer, Timothy A.
Coller, Barry S.
TI Structure-Guided Design of a High-Affinity Platelet Integrin
alpha(IIb)beta(3) Receptor Antagonist That Disrupts Mg2+ Binding to the
MIDAS
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID EPTIFIBATIDE-INDUCED THROMBOCYTOPENIA; GLYCOPROTEIN IIB/IIIA
ANTAGONISTS; ACUTE MYOCARDIAL-INFARCTION; GPIIB/IIIA ANTAGONISTS;
CONFORMATIONAL-CHANGES; FIBRINOGEN BINDING; PRIMARY PCI; IIB-IIIA;
RECOGNITION; ACTIVATION
AB An integrin found on platelets, alpha(IIb)beta(3) mediates platelet aggregation, and alpha(IIb)beta(3) antagonists are effective antithrombotic agents in the clinic. Ligands bind to integrins in part by coordinating a magnesium ion (Mg2+) located in the beta subunit metal ion-dependent adhesion site (MIDAS). Drugs patterned on the integrin ligand sequence Arg-Gly-Asp have a basic moiety that binds the alpha(IIb) subunit and a carboxyl group that coordinates the MIDAS Mg2+ in the beta(3) subunits. They induce conformational changes in the beta(3) subunit that may have negative consequences such as exposing previously hidden epitopes and inducing the active conformation of the receptor. We recently reported an inhibitor of alpha(IIb)beta(3) (RUC-1) that binds exclusively to the alpha(IIb) subunit; here, we report the structure-based design and synthesis of RUC-2, a RUC-1 derivative with a similar to 100-fold higher affinity. RUC-2 does not induce major conformational changes in beta(3) as judged by monoclonal antibody binding, light scattering, gel chromatography, electron microscopy, and a receptor priming assay. X-ray crystallography of the RUC-2-alpha(IIb)beta(3) headpiece complex in 1 mM calcium ion (Ca2+)/5 mM Mg2+ at 2.6 angstrom revealed that RUC-2 binds to aIIb the way RUC-1 does, but in addition, it binds to the beta(3) MIDAS residue glutamic acid 220, thus displacing Mg2+ from the MIDAS. When the Mg2+ concentration was increased to 20 mM, however, Mg2+ was identified in the MIDAS and RUC-2 was absent. RUC-2's ability to inhibit ligand binding and platelet aggregation was diminished by increasing the Mg2+ concentration. Thus, RUC-2 inhibits ligand binding by a mechanism different from that of all other alpha(IIb)beta(3) antagonists and may offer advantages as a therapeutic agent.
C1 [Choi, Won-Seok; Naini, Sarasija; Li, Jihong; Coller, Barry S.] Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10065 USA.
[Zhu, Jieqing; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
[Zhu, Jieqing; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Zhu, Jieqing; Bougie, Daniel; Rasmussen, Mark; Aster, Richard] Med Coll Wisconsin, BloodCtr Wisconsin, Milwaukee, WI 53201 USA.
[McCoy, Joshua G.; Shen, Min; Huang, Wenwei; Thomas, Craig J.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Negri, Ana; Filizola, Marta] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA.
RP Coller, BS (reprint author), Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10065 USA.
EM collerb@rockefeller.edu
FU National Heart, Lung, and Blood Institute [HL19278, HL13629, HL48675];
National Center for Research Resources, NIH [ULRR024143]; Molecular
Libraries Initiative of the NIH Roadmap for Medical Research; National
Human Genome Research Institute; Stony Brook University; National
Research Foundation of Korea; Korean Government [NRF-2009-352-E00042];
NSF by Texas Advanced Computing Center [TG-MCB080109N]
FX Funding: Supported, in part, by grants HL19278, HL13629, and HL48675
from the National Heart, Lung, and Blood Institute; Clinical and
Translational Science Award grant ULRR024143 from the National Center
for Research Resources, NIH; the Molecular Libraries Initiative of the
NIH Roadmap for Medical Research and the Intramural Research Program of
the National Human Genome Research Institute; funds from Stony Brook
University; and the National Research Foundation of Korea Grant funded
by the Korean Government (NRF-2009-352-E00042). The computations were
supported in part by the NSF through TeraGrid advanced computing
resources provided by Texas Advanced Computing Center under grant
TG-MCB080109N (principal investigator: M.F.).
NR 54
TC 11
Z9 11
U1 1
U2 19
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 14
PY 2012
VL 4
IS 125
AR 125ra32
DI 10.1126/scitranslmed.3003576
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 909BY
UT WOS:000301538300007
PM 22422993
ER
PT J
AU Joynt, KE
Jha, AK
AF Joynt, Karen E.
Jha, Ashish K.
TI The Relationship Between Cost and Quality No Free Lunch
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID REGIONAL-VARIATIONS; CARE; HOSPITALS; OUTCOMES
C1 [Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
[Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA.
RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
EM ajha@hsph.harvard.edu
NR 8
TC 14
Z9 15
U1 1
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 MAR 14
PY 2012
VL 307
IS 10
BP 1082
EP 1083
DI 10.1001/jama.2012.287
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 908GU
UT WOS:000301479700030
PM 22416105
ER
PT J
AU Azad, A
Pyne, S
Pothen, A
AF Azad, Ariful
Pyne, Saumyadipta
Pothen, Alex
TI Matching phosphorylation response patterns of
antigen-receptor-stimulated T cells via flow cytometry
SO BMC BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT 1st Annual Meeting of the Great Lakes Bioinformatics (GLBIO)
CY MAY 02-04, 2011
CL Ohio Univ, Athens, OH
HO Ohio Univ
ID MEMORY; EFFECTERS; MIXTURE; NAIVE
AB Background: When flow cytometric data on mixtures of cell populations are collected from samples under different experimental conditions, computational methods are needed (a) to classify the samples into similar groups, and (b) to characterize the changes within the corresponding populations due to the different conditions. Manual inspection has been used in the past to study such changes, but high-dimensional experiments necessitate developing new computational approaches to this problem. A robust solution to this problem is to construct distinct templates to summarize all samples from a class, and then to compare these templates to study the changes across classes or conditions.
Results: We designed a hierarchical algorithm, flowMatch, to first match the corresponding clusters across samples for producing robust meta-clusters, and to then construct a high-dimensional template as a collection of meta-clusters for each class of samples. We applied the algorithm on flow cytometry data obtained from human blood cells before and after stimulation with anti-CD3 monoclonal antibody, which is reported to change phosphorylation responses of memory and naive T cells. The flowMatch algorithm is able to construct representative templates from the samples before and after stimulation, and to match corresponding meta-clusters across templates. The templates of the pre-stimulation and post-stimulation data corresponding to memory and naive T cell populations clearly show, at the level of the meta-clusters, the overall phosphorylation shift due to the stimulation.
Conclusions: We concisely represent each class of samples by a template consisting of a collection of meta-clusters (representative abstract populations). Using flowMatch, the meta-clusters across samples can be matched to assess overall differences among the samples of various phenotypes or time-points.
C1 [Pyne, Saumyadipta] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Azad, Ariful; Pothen, Alex] Purdue Univ, Dept Comp Sci, W Lafayette, IN 47906 USA.
[Pyne, Saumyadipta] MIT, Broad Inst, Cambridge, MA 02142 USA.
[Pyne, Saumyadipta] Harvard Univ, Cambridge, MA 02142 USA.
RP Pyne, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM spyne@broad.mit.edu; apothen@purdue.edu
NR 15
TC 7
Z9 7
U1 2
U2 4
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 MAR 13
PY 2012
VL 13
SU 2
AR S10
DI 10.1186/1471-2105-13-S2-S10
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 941BE
UT WOS:000303936000011
PM 22536861
ER
PT J
AU Haines, M
Brown, B
Craig, J
D'Este, C
Elliott, E
Klineberg, E
McInnes, E
Middleton, S
Paul, C
Redman, S
Yano, EM
AF Haines, Mary
Brown, Bernadette
Craig, Jonathan
D'Este, Catherine
Elliott, Elizabeth
Klineberg, Emily
McInnes, Elizabeth
Middleton, Sandy
Paul, Christine
Redman, Sally
Yano, Elizabeth M.
CA Clin Networks Res Grp
TI Determinants of successful clinical networks: the conceptual framework
and study protocol
SO IMPLEMENTATION SCIENCE
LA English
DT Article
ID HEALTH-CARE; QUALITY; CANCER; IMPLEMENTATION; IMPROVEMENT; GUIDELINES;
PROGRAM; IMPACT; MODEL
AB Background: Clinical networks are increasingly being viewed as an important strategy for increasing evidence-based practice and improving models of care, but success is variable and characteristics of networks with high impact are uncertain. This study takes advantage of the variability in the functioning and outcomes of networks supported by the Australian New South Wales (NSW) Agency for Clinical Innovation's non-mandatory model of clinical networks to investigate the factors that contribute to the success of clinical networks.
Methods/Design: The objective of this retrospective study is to examine the association between external support, organisational and program factors, and indicators of success among 19 clinical networks over a three-year period (2006-2008). The outcomes (health impact, system impact, programs implemented, engagement, user perception, and financial leverage) and explanatory factors will be collected using a web-based survey, interviews, and record review. An independent expert panel will provide judgements about the impact or extent of each network's initiatives on health and system impacts. The ratings of the expert panel will be the outcome used in multivariable analyses. Following the rating of network success, a qualitative study will be conducted to provide a more in-depth examination of the most successful networks.
Discussion: This is the first study to combine quantitative and qualitative methods to examine the factors that contribute to the success of clinical networks and, more generally, is the largest study of clinical networks undertaken. The adaptation of expert panel methods to rate the impacts of networks is the methodological innovation of this study. The proposed project will identify the conditions that should be established or encouraged by agencies developing clinical networks and will be of immediate use in forming strategies and programs to maximise the effectiveness of such networks.
C1 [Haines, Mary; Brown, Bernadette; Redman, Sally] Sax Inst, Haymarket, Australia.
[Haines, Mary; Craig, Jonathan] Univ Sydney, Sch Publ Hlth, Camperdown, NSW, Australia.
[D'Este, Catherine] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia.
[Elliott, Elizabeth; Klineberg, Emily] Univ Sydney, Sch Clin, Childrens Hosp Westmead, Westmead, NSW 2145, Australia.
[McInnes, Elizabeth; Middleton, Sandy] Australian Catholic Univ, Natl Ctr Clin Outcomes Res NaCCOR, Darlinghurst, NSW, Australia.
[McInnes, Elizabeth; Middleton, Sandy] Nursing Res Inst St Vincents & Mater Hlth Sydney, Darlinghurst, NSW, Australia.
[Paul, Christine] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia.
[Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA.
RP Haines, M (reprint author), Sax Inst, Haymarket, Australia.
EM mary.haines@saxinstitute.org.au
RI D'ESTE, CATHERINE/G-7392-2013; Craig, Jonathan/E-2813-2013; Scott,
Anthony/E-6636-2010;
OI Craig, Jonathan/0000-0002-2548-4035; McInnes, Liz/0000-0002-0567-9679;
Scott, Anthony/0000-0002-2851-5378; Middleton, Sandy/0000-0002-7201-4394
FU National Health and Medical Research Council of Australia [571447]; NSW
Agency for Clinical Innovation as part of the National Health and
Medical Research Council of Australia's (NHMRC)
FX This research is supported by the National Health and Medical Research
Council of Australia through their partnership project grant scheme (ID:
571447). This protocol has been approved by the University of Sydney,
Human Research Ethics Committee in August 2011 (ID: 13988).; Hunter Watt
and Kate Needham, who are part of the 'Clinical Networks Research
Group', are employed by the NSW Agency for Clinical Innovation. This
Agency has provided funds to support this research as part of the
National Health and Medical Research Council of Australia's (NHMRC)
partnership project grant scheme. These funds have been awarded on the
basis of a NHMRC deed of agreement governing the governance and conduct
of research in Australia. The other authors declare that they have no
competing interests.
NR 42
TC 10
Z9 10
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD MAR 13
PY 2012
VL 7
AR 16
DI 10.1186/1748-5908-7-16
PG 10
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 930PK
UT WOS:000303151400001
PM 22414246
ER
PT J
AU Levison, JH
Orrell, C
Gallien, S
Kuritzkes, DR
Fu, N
Losina, E
Freedberg, KA
Wood, R
AF Levison, Julie H.
Orrell, Catherine
Gallien, Sebastien
Kuritzkes, Daniel R.
Fu, Naishin
Losina, Elena
Freedberg, Kenneth A.
Wood, Robin
TI Virologic Failure of Protease Inhibitor-Based Second-Line Antiretroviral
Therapy without Resistance in a Large HIV Treatment Program in South
Africa
SO PLOS ONE
LA English
DT Article
ID TREATMENT-NAIVE PATIENTS; DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE;
LOPINAVIR-RITONAVIR; EARLY MORTALITY; PATIENTS LOST; FOLLOW-UP; CLADE-C;
OUTCOMES; MUTATIONS
AB Background: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa.
Methodology/ Principal Findings: HIV-infected patients >= 15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.
Conclusions/ Significance: Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.
C1 [Levison, Julie H.; Fu, Naishin; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Levison, Julie H.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Orrell, Catherine; Wood, Robin] Univ Cape Town, Dept Med, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Levison, Julie H.; Gallien, Sebastien; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Gallien, Sebastien; Kuritzkes, Daniel R.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA.
RP Levison, JH (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
EM jlevison@partners.org
RI Gallien, Sebastien/F-9930-2015;
OI Gallien, Sebastien/0000-0002-8033-0936; Orrell,
Catherine/0000-0003-1134-7475
FU United States National Institute of Allergy and Infectious Diseases
[NIAID T32 AI007433, R01AI058736, K24 A1062476]; National Center for
Research Resources [K24 RR016482]; Harvard University Center for AIDS
Research [P30-AI060354]; Virology Specialty Laboratory from AIDS
Clinical Trials Group [U01 AI068636]; "Agence Nationale de Recherche sur
le SIDA" (French National Agency for Research on AIDS), France; Abbott;
Boehringer Ingelheim; Gilead; GlaxoSmithKline; Merck; ViiV
FX This project was supported by the United States National Institute of
Allergy and Infectious Diseases (NIAID T32 AI007433, R01AI058736, K24
A1062476), the National Center for Research Resources (K24 RR016482),
Harvard University Center for AIDS Research (P30-AI060354), Virology
Specialty Laboratory subcontract from the AIDS Clinical Trials Group
(U01 AI068636). SG was a recipient of the "Agence Nationale de Recherche
sur le SIDA" (French National Agency for Research on AIDS) Fellowship
Grant for Post-Graduate Studies, France. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the funding agencies. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.; The authors have read the journal's
policy and have the following competing interest: DRK is a consultant to
and has received honoraria or research support from Abbott, Boehringer
Ingelheim, Gilead, GlaxoSmithKline, Merck and ViiV. This does not alter
the authors' adherence to all the PloS ONE policies on sharing data and
materials. All other authors have declared that no competing interests
exist.
NR 40
TC 21
Z9 21
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 13
PY 2012
VL 7
IS 3
AR e32144
DI 10.1371/journal.pone.0032144
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930IA
UT WOS:000303129700006
PM 22427821
ER
PT J
AU Liu, EB
Wadford, DA
Seto, J
Vu, M
Hudson, NR
Thrasher, L
Torres, S
Dyer, DW
Chodosh, J
Seto, D
Jones, MS
AF Liu, Elizabeth B.
Wadford, Debra A.
Seto, Jason
Vu, Maria
Hudson, Nolan Ryan
Thrasher, Lisa
Torres, Sarah
Dyer, David W.
Chodosh, James
Seto, Donald
Jones, Morris S.
TI Computational and Serologic Analysis of Novel and Known Viruses in
Species Human Adenovirus D in Which Serology and Genomics Do Not
Correlate
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPIDEMIC KERATOCONJUNCTIVITIS; MOLECULAR
EVOLUTION; PROVIDES EVIDENCE; RECOMBINATION; IDENTIFICATION; INFECTION;
STRAINS; TYPE-15; SYSTEM
AB In November of 2007 a human adenovirus (HAdV) was isolated from a bronchoalveolar lavage (BAL) sample recovered from a biopsy of an AIDS patient who presented with fever, cough, tachycardia, and expiratory wheezes. To better understand the isolated virus, the genome was sequenced and analyzed using bioinformatic and phylogenomic analysis. The results suggest that this novel virus, which is provisionally named HAdV-D59, may have been created from multiple recombination events. Specifically, the penton, hexon, and fiber genes have high nucleotide identity to HAdV-D19C, HAdV-D25, and HAdV-D56, respectively. Serological results demonstrated that HAdV-D59 has a neutralization profile that is similar yet not identical to that of HAdV-D25. Furthermore, we observed a two-fold difference between the ability of HAdV-D15 and HAdV-D25 to be neutralized by reciprocal antiserum indicating that the two hexon proteins may be more similar in epitopic conformation than previously assumed. In contrast, hexon loops 1 and 2 of HAdV-D15 and HAdV-D25 share 79.13 and 92.56 percent nucleotide identity, respectively. These data suggest that serology and genomics do not always correlate.
C1 [Liu, Elizabeth B.; Seto, Jason; Seto, Donald; Jones, Morris S.] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA.
[Wadford, Debra A.; Vu, Maria] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA USA.
[Hudson, Nolan Ryan; Thrasher, Lisa; Torres, Sarah] Travis AFB, David Grant USAF Med Ctr, Fairfield, CA USA.
[Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA.
[Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab, Boston, MA USA.
RP Jones, MS (reprint author), George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA.
EM drmorrisj@yahoo.com
FU United States Air Force Surgeon General [FDG20040024E]; Research to
Prevent Blindness, Inc.; [R01EY013124]; [P30EY014104]
FX This research was financially supported by grant R01EY013124 (DWD, DS,
MSJ and JC) and P30EY014104 (JC). LS, NRH, and MSJ were supported by
United States Air Force Surgeon General grant FDG20040024E. JC is also
funded by an unrestricted grant to the Department of Ophthalmology,
Harvard Medical School, from Research to Prevent Blindness, Inc. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 32
TC 14
Z9 17
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 13
PY 2012
VL 7
IS 3
AR e33212
DI 10.1371/journal.pone.0033212
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930IA
UT WOS:000303129700038
PM 22427992
ER
PT J
AU Panagia, M
Winston, B
Click, JW
Sabatine, MS
Resnic, FS
AF Panagia, Marcello
Winston, Brion
Click, James W.
Sabatine, Marc S.
Resnic, Frederic S.
TI A Rare Complication of Infective Endocarditis
SO CIRCULATION
LA English
DT Editorial Material
ID CORONARY-ARTERY; ANEURYSM
C1 [Panagia, Marcello] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02144 USA.
[Click, James W.] Brigham & Womens Hosp, Dept Med, Div Internal Med, Boston, MA 02115 USA.
[Winston, Brion; Sabatine, Marc S.; Resnic, Frederic S.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02115 USA.
RP Panagia, M (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St,YAW 5700, Boston, MA 02144 USA.
EM mpanagia@partners.org
NR 4
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAR 13
PY 2012
VL 125
IS 10
BP 1316
EP 1317
DI 10.1161/CIRCULATIONAHA.110.982702
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 914GM
UT WOS:000301937500025
PM 22412092
ER
PT J
AU Shivdasani, RA
AF Shivdasani, Ramesh A.
TI GEFs on the RhoAd to a Colossal Nucleus
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
ID MEGAKARYOCYTES; POLYPLOIDY
AB Cytokinesis in normal cell division requires RhoA-regulated actomyosin contraction of the cleavage furrow; this process is aborted in megakaryocyte endomitosis, leading to polyploidy. In this issue of Developmental Cell, Gao et al. (2012) trace the basis of endomitosis to sequential downregulation of guanine nucleotide exchange factors GEF-H1 and ECT2.
C1 [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Shivdasani, RA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA.
EM ramesh_shivdasani@dfci.harvard.edu
NR 10
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD MAR 13
PY 2012
VL 22
IS 3
BP 471
EP 472
DI 10.1016/j.devcel.2012.02.010
PG 2
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 911FB
UT WOS:000301701600002
PM 22421037
ER
PT J
AU Xu, C
Fan, ZP
Muller, P
Fogley, R
DiBiase, A
Trompouki, E
Unternaehrer, J
Xiong, FZ
Torregroza, I
Evans, T
Megason, SG
Daley, GQ
Schier, AF
Young, RA
Zon, LI
AF Xu, Cong
Fan, Zi Peng
Mueller, Patrick
Fogley, Rachel
DiBiase, Anthony
Trompouki, Eirini
Unternaehrer, Juli
Xiong, Fengzhu
Torregroza, Ingrid
Evans, Todd
Megason, Sean G.
Daley, George Q.
Schier, Alexander F.
Young, Richard A.
Zon, Leonard I.
TI Nanog-like Regulates Endoderm Formation through the Mxbc2-Nodal Pathway
SO DEVELOPMENTAL CELL
LA English
DT Article
ID EMBRYONIC STEM-CELLS; YOLK SYNCYTIAL LAYER; ONE-EYED PINHEAD; PRIMITIVE
ENDODERM; ZEBRAFISH BLASTOMERES; GROUND-STATE; PROTEIN; PLURIPOTENCY;
MESODERM; GENE
AB In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog, but the in vivo analysis of Nanog has been hampered by its requirement for early mouse development. In an effort to examine the role of Nanog in vivo, we identified a zebrafish Nanog ortholog and found that its knockdown impaired endoderm formation. Genome-wide transcription analysis revealed that nanog-like morphants fail to develop the extraembryonic yolk syncytial layer (YSL), which produces Nodal, required for endoderm induction. We examined the genes that were regulated by Nanog-like and identified the homeobox gene mxtx2, which is both necessary and sufficient for YSL induction. Chromatin immunoprecipitation assays and genetic studies indicated that Nanog-like directly activates mxtx2, which, in turn, specifies the YSL lineage by directly activating YSL genes. Our study identifies a Nanog-like-Mxtx2-Nodal pathway and establishes a role for Nanog-like in regulating the formation of the extraembryonic tissue required for endoderm induction.
C1 [Xu, Cong; Fogley, Rachel; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Daley, George Q.; Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Xu, Cong; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Daley, George Q.; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Xu, Cong; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Daley, George Q.; Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Fan, Zi Peng; Young, Richard A.] MIT, Whitehead Inst, Cambridge, MA 02142 USA.
[Fan, Zi Peng; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Mueller, Patrick; Schier, Alexander F.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Xiong, Fengzhu; Megason, Sean G.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA.
[Torregroza, Ingrid; Evans, Todd] Cornell Univ, Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA.
RP Zon, LI (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
RI Young, Richard/F-6495-2012; Muller, Patrick/C-8096-2014; XIONG,
FENGZHU/A-9590-2015
OI Young, Richard/0000-0001-8855-8647; Muller, Patrick/0000-0002-0702-6209;
XIONG, FENGZHU/0000-0002-6153-0254
FU National Institutes of Health [5R01HL048801-18, 5U01HL10001-02, R01
HG002668, HL056182]
FX This work was supported by National Institutes of Health grants
5R01HL048801-18 and 5U01HL10001-02 (L.I.Z.), R01 HG002668 (R.A.Y.), and
HL056182 (T.E.). We thank I. Swinburne, J. Mullor, and R. Zhao for
providing reagents; Y. Zhou, A. Chen, and L. Lawson for technical
assistance; and O. Tamplin for critical appraisal of the work. L.I.Z.
and G.Q.D. are Howard Hughes Medical Institute investigators. L.I.Z. is
a founder and stockholder of Fate, Inc., and a scientific advisor for
Stemgent.
NR 57
TC 33
Z9 34
U1 1
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD MAR 13
PY 2012
VL 22
IS 3
BP 625
EP 638
DI 10.1016/j.devcel.2012.01.003
PG 14
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 911FB
UT WOS:000301701600016
PM 22421047
ER
PT J
AU Martins, Y
Lederman, RI
Lowenstein, CL
Joffe, S
Neville, BA
Hastings, BT
Abel, GA
AF Martins, Y.
Lederman, R. I.
Lowenstein, C. L.
Joffe, S.
Neville, B. A.
Hastings, B. T.
Abel, G. A.
TI Increasing response rates from physicians in oncology research: a
structured literature review and data from a recent physician survey
SO BRITISH JOURNAL OF CANCER
LA English
DT Review
DE surveys; response rates; health services research; oncology
ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PHYSICIANS; FOLLOW-UP CARE;
MAIL SURVEY; POSTAL SURVEY; GENERAL-PRACTITIONERS; ORTHOPEDIC SURGEONS;
MONETARY INCENTIVES; COST-EFFECTIVENESS; CANCER SURVIVORS
AB Although the physician survey has become an important tool for oncology-focused health services research, such surveys often achieve low response rates. This mini-review reports the results of a structured review of the literature relating to increasing response rates for physician surveys, as well as our own experience from a survey of physicians as to their referral practices for suspected haematologic malignancy in the United States. PubMed and PsychINFO databases were used to identify methodological articles assessing factors that influence response rates for physician surveys; the results were tabulated and reviewed for trends. We also analysed the impact of a follow-up telephone call by a physician investigator to initial non-responders in our own mailed physician survey, comparing the characteristics of those who responded before vs after the call. The systematic review suggested that monetary incentives and paper (vs web or email) surveys increase response rates. In our own survey, follow-up telephone calls increased the response rate from 43.7% to 70.5%, with little discernible difference in the characteristics of early vs later responders. We conclude that in addition to monetary incentives and paper surveys, physician-to-physician follow-up telephone calls are an effective method to increase response rates in oncology-focused physician surveys. British Journal of Cancer (2012) 106, 1021-1026. doi:10.1038/bjc.2012.28 www.bjcancer.com Published online 28 February 2012 (C) 2012 Cancer Research UK
C1 [Martins, Y.; Lederman, R. I.; Lowenstein, C. L.; Joffe, S.; Hastings, B. T.; Abel, G. A.] Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02215 USA.
[Martins, Y.; Joffe, S.] Childrens Hosp, Dept Med, Boston, MA 02215 USA.
[Joffe, S.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Neville, B. A.; Hastings, B. T.; Abel, G. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Abel, GA (reprint author), Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02215 USA.
EM gregory_abel@dfci.harvard.edu
OI Martins, Yolanda/0000-0002-3983-3531; Joffe, Steven/0000-0002-0667-7384
FU Division of Cancer Prevention and Control of the Centers for Disease
Control and Prevention (CDC) in Atlanta GA
FX This work was partially supported by a contract from the Division of
Cancer Prevention and Control of the Centers for Disease Control and
Prevention (CDC) in Atlanta GA. The findings and conclusions do not
necessarily represent the CDC's views.
NR 58
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Z9 31
U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 13
PY 2012
VL 106
IS 6
BP 1021
EP 1026
DI 10.1038/bjc.2012.28
PG 6
WC Oncology
SC Oncology
GA 909DA
UT WOS:000301541200001
PM 22374464
ER
PT J
AU Chang, JJ
Lacas, A
Lindsay, RJ
Doyle, EH
Axten, KL
Pereyra, F
Rosenberg, ES
Walker, BD
Allen, TM
Altfeld, M
AF Chang, J. Judy
Lacas, Aurore
Lindsay, Robert J.
Doyle, Erin H.
Axten, Karen L.
Pereyra, Florencia
Rosenberg, Eric S.
Walker, Bruce D.
Allen, Todd M.
Altfeld, Marcus
TI Differential regulation of toll-like receptor pathways in acute and
chronic HIV-1 infection
SO AIDS
LA English
DT Article
DE dendritic cells; HIV-1; innate immunity; monocytes; pathogenesis;
toll-like receptor
ID PLASMACYTOID DENDRITIC CELLS; ACTIVE ANTIRETROVIRAL THERAPY;
ALPHA-INTERFERON PRODUCTION; PRODUCE IFN-ALPHA; I INTERFERON;
HIV-1-INFECTED PATIENTS; IMMUNE ACTIVATION; VIRUS-INFECTIONS; BLOOD;
INDIVIDUALS
AB Objective and design: The objective of this study was to determine changes in toll-like receptor (TLR) responses of monocytes, myeloid dendritic cells and plasmacytoid dendritic cells during primary and chronic HIV-1 infection. TLRs serve as important innate receptors to sense pathogens, and have been implicated in mediating immune activation in HIV-1 infection. Studies assessing the consequences of HIV-1 infection on the ability of innate immune cells to respond to TLR stimulation have come to varying conclusions.
Methods: Using intracellular flow cytometry, cytokine production by cryopreserved peripheral blood mononuclear cells from healthy controls and HIV-1-infected individuals were examined after TLR stimulation.
Results: We observed that the effect of HIV-1 infection on TLR responses not only depended on the stage of HIV-1 infection, but was also dependent on the individual receptor and cell type examined. Monocyte and myeloid dendritic cell responses to TLR8 stimulation were associated with HIV-1 viral load and CD4(+) T-cell count, whereas plasmacytoid dendritic cell responses to TLR7 stimulation were not. Responses to TLR2 stimulation were not affected by HIV-1 infection, whereas responses to TLR9 stimulation were universally decreased in all HIV-1-infected individuals examined regardless of treatment or clinical parameters.
Conclusion: Responsiveness to TLR7/8 stimulation, which have been shown to recognize HIV-1 ssRNA, did not decrease in chronic infection, and may represent a contributing factor to ongoing T-cell immune activation in the setting of chronic viremic HIV-1 infection. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Chang, J. Judy; Lacas, Aurore; Lindsay, Robert J.; Doyle, Erin H.; Axten, Karen L.; Pereyra, Florencia; Walker, Bruce D.; Allen, Todd M.; Altfeld, Marcus] Harvard Univ, Sch Med, Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA.
[Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Bldg 149,13th St,6th Floor, Navy Yard, MA 02129 USA.
EM maltfeld@partners.org
RI Ghartouchent, malek/B-9088-2012; Allen, Todd/F-5473-2011;
OI Doyle, Erin/0000-0001-9380-2819
FU NIH/NIAID [R21 AI071806, R01 AI078784, P01 AI074415]; National Health
and Medical Research Council of Australia [519578]; Phillip T. and Susan
M. Ragon Foundation; Bill & Melinda Gates Foundation
FX These studies were supported by NIH/NIAID grants R21 AI071806, R01
AI078784 and P01 AI074415 (MA); a fellowship awarded from the National
Health and Medical Research Council of Australia (519578) and Ragon
Fellowship by the Phillip T. and Susan M. Ragon Foundation to JJC, and
the Bill & Melinda Gates Foundation.
NR 43
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Z9 33
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2012
VL 26
IS 5
BP 533
EP 541
DI 10.1097/QAD.0b013e32834f3167
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 906GN
UT WOS:000301333000002
PM 22210629
ER
PT J
AU Li, N
Spiegelman, D
Drain, P
Mwiru, RS
Mugusi, F
Chalamilla, G
Fawzi, WW
AF Li, Nan
Spiegelman, Donna
Drain, Paul
Mwiru, Ramadhani S.
Mugusi, Ferdinand
Chalamilla, Guerino
Fawzi, Wafaie W.
TI Predictors of weight loss after HAART initiation among HIV-infected
adults in Tanzania
SO AIDS
LA English
DT Article
DE Africa; HAART; HIV/AIDS; weight loss
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RESTING
ENERGY-EXPENDITURE; MULTICENTER AIDS COHORT; WASTING SYNDROME; DISEASE
PROGRESSION; NUTRITIONAL-STATUS; ERA; MORTALITY; SURVIVAL
AB Objective: To explore the predictors of weight loss after highly active antiretroviral therapy (HAART) initiation in a large cohort of HIV-infected adults living in Dar es Salaam, Tanzania.
Design: Cross-sectional and longitudinal analysis of a cohort of HIV-infected adults on HAART.
Methods: HIV-infected adults (n = 18 965) were enrolled between November 2004 to December 2009 in Dar es Salaam, Tanzania. Log-binomial regression and Cox proportional hazard regression were used to explore the predictors of short-term (3 months) and long-term significant weight loss (>= 5%) after HAART initiation.
Results: At 3 months after HAART initiation, 8% patients lost greater than or equal to 5% weight. Underweight patients at initiation gained more weight than other body mass index (BMI) groups. Younger or older than age group 30-39, lower socioeconomic status (SES), higher BMI, lower hemoglobin, difficulty breathing, loss of appetite, nausea/vomiting at baseline were associated with the risk of significant weight loss at 3 months after initiation. During a median follow-up period of 10 months [interquartile range (IQR) 4-20 months], 31% patients had experienced an initial significant weight loss after HAART initiation. In addition to time-varying CD4 cell count and hemoglobin level, age, sex, baseline BMI and having loss of appetite, and nausea/vomiting at baseline were associated with the risk of long-term significant weight loss.
Conclusion: Our study suggested that a significant percentage of patients continue to lose weight after HAART initiation. Our findings on the effect of socio-demographics, symptoms and diseases, biomedical indicators in relation to weight loss provide important information that has significant practical implications. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Li, Nan; Mwiru, Ramadhani S.; Fawzi, Wafaie W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02120 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02120 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02120 USA.
[Drain, Paul] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Drain, Paul] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Mugusi, Ferdinand] Muhimbili Univ Hlth & Allied Sci, Dept Internal Med, Dar Es Salaam, Tanzania.
[Chalamilla, Guerino] MDH, Dar Es Salaam, Tanzania.
[Fawzi, Wafaie W.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02120 USA.
RP Li, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 1633 Tremont St, Boston, MA 02120 USA.
EM nli@hsph.harvard.edu
OI Drain, Paul/0000-0003-3300-3817
FU US President's Emergency Plan for AIDS Relief (PEPFAR)
FX This study is supported by US President's Emergency Plan for AIDS Relief
(PEPFAR).
NR 43
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Z9 3
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2012
VL 26
IS 5
BP 577
EP 585
DI 10.1097/QAD.0b013e32834f9851
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 906GN
UT WOS:000301333000007
PM 22156968
ER
PT J
AU Fitch, K
Abbara, S
Lee, H
Stavrou, E
Sacks, R
Michel, T
Hemphill, L
Torriani, M
Grinspoon, S
AF Fitch, Kathleen
Abbara, Suhny
Lee, Hang
Stavrou, Eleni
Sacks, Rachel
Michel, Theresa
Hemphill, Linda
Torriani, Martin
Grinspoon, Steven
TI Effects of lifestyle modification and metformin on atherosclerotic
indices among HIV-infected patients with the metabolic syndrome
SO AIDS
LA English
DT Article
DE atherosclerosis; HIV; lifestyle modification; metformin
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; INTRAMYOCELLULAR
LIPID-ACCUMULATION; IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE
ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; ACUTE
MYOCARDIAL-INFARCTION; INTIMA-MEDIA THICKNESS; RISK-FACTORS; INSULIN
SENSITIVITY
AB Objective: Metabolic abnormalities including diabetes, dyslipidemia, hypertension, and abdominal obesity occur commonly in HIV patients, are associated with increased coronary artery calcification (CAC), and contribute to increased cardiovascular disease (CVD) in this population. We hypothesized that lifestyle modification (LSM) and metformin would improve CVD indices in HIV patients with metabolic syndrome.
Design: A randomized, placebo-controlled trial to investigate LSM and metformin, alone and in combination, over 1 year, among 50 HIV-infected patients with metabolic syndrome.
Methods: We assessed CAC, cardiovascular and metabolic indices.
Results: Among the participants, duration of HIV-infection was 14 +/- 1 year and duration of antiretroviral therapy was 6 +/- 1 year. Metformin-treated patients demonstrated significantly less progression of CAC (-1 +/- 2 vs. 33 +/- 17, P = 0.004, metformin vs. placebo), whereas the effect of LSM on CAC progression was not significant (8 +/- 6 vs. 21 +/- 14, P = 0.82, LSM vs. no-LSM). Metformin had a significantly greater effect on CAC than LSM (P = 0.01). Metformin-treated patients also demonstrated less progression in calcified plaque volume (-0.4 +/- 1.9 vs. 27.6 +/- 13.8 mu l, P = 0.008) and improved homeostatic model of assessment-insulin resistance (HOMA-IR) (P = 0.05) compared with placebo. Participants randomized to LSM vs. no-LSM showed significant improvement in HDL (P = 0.03), high-sensitivity C-reactive protein (hsCRP) (P = 0.05), and cardiorespiratory fitness. Changes in CAC among the four groups - no-LSM-placebo (43 +/- 30); LSM-placebo (19 +/- 7); no-LSM-metformin (1 +/- 1) and LSM-metformin (-4 +/- 6) - were different (P 0.03 for ANOVA and linear trend across groups), and the majority of this effect was mediated by metformin. Results are mean +/- SEM.
Conclusion: Metformin prevents plaque progression in HIV-infected patients with the metabolic syndrome. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Fitch, Kathleen; Stavrou, Eleni; Sacks, Rachel; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Abbara, Suhny] Massachusetts Gen Hosp, Cardiovasc Imaging Sect, Boston, MA 02114 USA.
[Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Michel, Theresa] Massachusetts Gen Hosp, Dept Phys Therapy, Boston, MA 02114 USA.
[Hemphill, Linda] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA.
[Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA.
RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON5-207,55 Fruit St, Boston, MA 02114 USA.
EM sgrinspoon@partners.org
RI Ghartouchent, malek/B-9088-2012
FU NIH [R01 DK49302, M01-RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and
Translational Science Center; National Center for Research Resources;
Theratechnologies; Bristol Meyers Squibb
FX Funding was provided by NIH R01 DK49302 and by NIH M01-RR-01066 and 1
UL1 RR025758-01, Harvard Clinical and Translational Science Center, from
the National Center for Research Resources.; There are no conflicts of
interest related to this work. S.G. has received research funding from
Theratechnologies and Bristol Meyers Squibb and consulted for
Theratechnologies and EMD Serono, unrelated to this work.
NR 47
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U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2012
VL 26
IS 5
BP 587
EP 597
DI 10.1097/QAD.0b013e32834f33cc
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 906GN
UT WOS:000301333000008
PM 22112605
ER
PT J
AU Ouattara, EN
Anglaret, X
Wong, AY
Chu, J
Hsu, HE
Danel, C
Eholie, S
Moh, R
Gabillard, D
Walensky, RP
Freedberg, KA
AF Ouattara, Eric N.
Anglaret, Xavier
Wong, Angela Y.
Chu, Jennifer
Hsu, Heather E.
Danel, Christine
Eholie, Serge
Moh, Raoul
Gabillard, Delphine
Walensky, Rochelle P.
Freedberg, Kenneth A.
TI Projecting the clinical benefits and risks of using efavirenz-containing
antiretroviral therapy regimens in women of childbearing age
SO AIDS
LA English
DT Article
DE antiretroviral therapy; efavirenz; pregnancy; sub-Saharan Africa;
survival; teratogenicity; women
ID HIV-INFECTED ADULTS; COTE-DIVOIRE; COST-EFFECTIVENESS; BIRTH-DEFECTS;
INITIAL TREATMENT; CONTRACEPTIVE USE; 7-YEAR COHORT; WEST-AFRICA;
NEVIRAPINE; PREGNANCY
AB Objectives: To project the outcomes of using either efavirenz or nevirapine as part of initial antiretroviral therapy (ART) in women of childbearing age in Cote d'Ivoire.
Methods: We used an HIV computer simulation model to project both the mother's survival and the birth defects at 10 years for a cohort of women who started ART with either efavirenz or nevirapine. The primary outcome was the ratio at 10 years of the difference in the number of women alive to the difference in the cumulative number of birth defects in women who started ART with efavirenz compared with nevirapine. In the base case analysis, the birth defect rate was 2.9% on efavirenz and 2.7% on nevirapine. In sensitivity analyses, we varied all inputs across confidence intervals reported in the literature.
Results: In the base case analysis, for a cohort of 100 000 women, the additional number of women alive initiating ART with efavirenz at 10 years was 15 times the additional number of birth defects (women alive: nevirapine 67 969, efavirenz 68 880, difference 911; birth defects: nevirapine 1128, efavirenz 1187, difference 59). In sensitivity analysis, the teratogenicity rate with efavirenz had to be 6.3%, or 2.3 times higher than the rate with nevirapine, for the excess number of birth defects to outweigh the additional number of women alive at 10 years.
Conclusion: In Cote d'Ivoire, initiating ART with efavirenz instead of nevirapine is likely to substantially increase the number of women alive at 10 years with a smaller potential number of birth defects. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Ouattara, Eric N.; Anglaret, Xavier; Danel, Christine; Eholie, Serge; Moh, Raoul] CHU Treichville, PAC CI Program, Abidjan 01, Cote Ivoire.
[Ouattara, Eric N.; Anglaret, Xavier; Danel, Christine; Gabillard, Delphine] Univ Bordeaux Segalen, Unite INSERM U897, Bordeaux, France.
[Wong, Angela Y.; Chu, Jennifer; Hsu, Heather E.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA.
[Wong, Angela Y.; Chu, Jennifer; Hsu, Heather E.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA.
[Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Ouattara, EN (reprint author), CHU Treichville, PAC CI Program, 01 BP 1954, Abidjan 01, Cote Ivoire.
EM eric.ouattara@isped.u-bordeaux2.fr
RI Ghartouchent, malek/B-9088-2012; Anglaret, Xavier/F-7333-2013;
OI Walensky, Rochelle P./0000-0002-8795-379X
FU Agence Nationale de recherche sur le Sida et les hepatites virales,
France [ANRS 12212]; National Institute of Allergy and Infectious
Diseases, USA [R01 085276]
FX This research was supported by the Agence Nationale de recherche sur le
Sida et les hepatites virales (ANRS 12212), France and the National
Institute of Allergy and Infectious Diseases (R01 085276), USA.
NR 45
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2012
VL 26
IS 5
BP 625
EP 634
DI 10.1097/QAD.0b013e328350fbfb
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 906GN
UT WOS:000301333000012
PM 22398569
ER
PT J
AU Tanaka, A
Shimada, K
Tearney, GJ
Kitabata, H
Taguchi, H
Fukuda, S
Kashiwagi, M
Kubo, T
Takarada, S
Hirata, K
Mizukoshi, M
Yoshikawa, J
Bouma, BE
Akasaka, T
AF Tanaka, Atsushi
Shimada, Kenei
Tearney, Guillermo J.
Kitabata, Hironori
Taguchi, Haruyuki
Fukuda, Shota
Kashiwagi, Manabu
Kubo, Takashi
Takarada, Shigeho
Hirata, Kumiko
Mizukoshi, Masato
Yoshikawa, Junichi
Bouma, Brett E.
Akasaka, Takashi
TI "Framing" the Vessel The Critical Importance of Volumetric Analysis
During Serial Intravascular Imaging Studies Reply
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Letter
ID OPTICAL COHERENCE TOMOGRAPHY; ULTRASOUND; ANGINA; SPASM
C1 [Tanaka, Atsushi] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
RP Tanaka, A (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA.
EM atanaka1@partners.org
NR 7
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 13
PY 2012
VL 59
IS 11
BP 1039
EP 1039
DI 10.1016/j.jacc.2011.11.042
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 904UF
UT WOS:000301222700014
ER
PT J
AU Lin, L
Bass, AJ
Lockwood, WW
Wang, ZW
Silvers, AL
Thomas, DG
Chang, AC
Lin, J
Orringer, MB
Li, WQ
Glover, TW
Giordano, TJ
Lam, WL
Meyerson, M
Beer, DG
AF Lin, Lin
Bass, Adam J.
Lockwood, William W.
Wang, Zhuwen
Silvers, Amy L.
Thomas, Dafydd G.
Chang, Andrew C.
Lin, Jules
Orringer, Mark B.
Li, Weiquan
Glover, Thomas W.
Giordano, Thomas J.
Lam, Wan L.
Meyerson, Matthew
Beer, David G.
TI Activation of GATA binding protein 6 (GATA6) sustains oncogenic
lineage-survival in esophageal adenocarcinoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE lineage-survival oncogene; transcriptional reprogramming; extrinsic
apoptosis pathway; p38 alpha and TNF-related apoptosis-inducing ligand
activation
ID TRANSCRIPTION FACTOR GENES; EMBRYONIC STEM-CELLS; BARRETTS-ESOPHAGUS;
CANCER; DIFFERENTIATION; AMPLIFICATION; EXPRESSION; LUNG; ADDICTION;
ENDODERM
AB Gene amplification is a tumor-specific event during malignant transformation. Recent studies have proposed a lineage-dependency (addiction) model of human cancer whereby amplification of certain lineage transcription factors predisposes a survival mechanism in tumor cells. These tumor cells are derived from tissues where the lineage factors play essential developmental and maintenance roles. Here, we show that recurrent amplification at 18q11.2 occurs in 21% of esophageal adenocarcinomas (EAC). Utilization of an integrative genomic strategy reveals a single gene, the embryonic endoderm transcription factor GATA6, as the selected target of the amplification. Overexpression of GATA6 is found in EACs that contain gene amplification. We find that EAC patients whose tumors carry GATA6 amplification have a poorer survival. We show that ectopic expression of GATA6, together with FGFR2 isoform IIIb, increases anchorage-independent growth in immortalized Barrett's esophageal cells. Conversely, siRNA-mediated silencing of GATA6 significantly reduces both cell proliferation and anchorage-independent growth in EAC cells. We further demonstrate that induction of apoptotic/anoikis pathways is triggered upon silencing of GATA6 in EAC cells but not in esophageal squamous cells. We show that activation of p38 alpha signaling and up-regulation of TNF-related apoptosis-inducing ligand are detected in apoptotic EAC cells upon GATA6 deprivation. We conclude that selective gene amplification of GATA6 during EAC development sustains oncogenic lineage-survival of esophageal adenocarcinoma.
C1 [Lin, Lin; Wang, Zhuwen; Silvers, Amy L.; Chang, Andrew C.; Lin, Jules; Orringer, Mark B.; Li, Weiquan; Beer, David G.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[Thomas, Dafydd G.; Giordano, Thomas J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Glover, Thomas W.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Bass, Adam J.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bass, Adam J.; Meyerson, Matthew] Broad Inst Harvard, Boston, MA 02115 USA.
[Bass, Adam J.; Meyerson, Matthew] MIT, Boston, MA 02115 USA.
[Lockwood, William W.; Lam, Wan L.] British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC V5Z 1L3, Canada.
RP Lin, L (reprint author), Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
EM linlin@umich.edu; dgbeer@umich.edu
RI Li, Weiquan/B-4897-2011; Meyerson, Matthew/E-7123-2012
OI Chang, Andrew/0000-0001-9506-0425; Giordano, Thomas/0000-0003-0641-8873;
FU National Cancer Institute [R01CA071606-12, K08CA134931, P50CA90578];
University of Michigan Surgery Research Advisory Committee (RAC)
FX We thank Dr. Aarif Ahsan for sharing laboratory protocols; Drs. X. X. Xu
and C. D. Capo-Chichi for the kind gifts of the pMT-CB6/GATA4 and
pMT-CB6/GATA6 constructs. This work was supported by National Cancer
Institute Grants R01CA071606-12 (to D.G.B.), K08CA134931 (to A.J.B.),
P50CA90578 (to M.M.), and the University of Michigan Surgery Research
Advisory Committee (RAC) Grant (to L.L.).
NR 42
TC 29
Z9 29
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 13
PY 2012
VL 109
IS 11
BP 4251
EP 4256
DI 10.1073/pnas.1011989109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 907OH
UT WOS:000301426700048
PM 22375031
ER
PT J
AU Ahonkhai, AA
Noubary, F
Munro, A
Stark, R
Wilke, M
Freedberg, KA
Wood, R
Losina, E
AF Ahonkhai, Aima A.
Noubary, Farzad
Munro, Alison
Stark, Ruth
Wilke, Marisa
Freedberg, Kenneth A.
Wood, Robin
Losina, Elena
TI Not All Are Lost: Interrupted Laboratory Monitoring, Early Death, and
Loss to Follow-Up (LTFU) in a Large South African Treatment Program
SO PLOS ONE
LA English
DT Article
ID ANTIRETROVIRAL THERAPY PROGRAMS; HIV-INFECTED PATIENTS; PRIMARY-CARE;
MORTALITY; RETENTION; ROUTINE; SERVICE; TRENDS; UGANDA; TESTS
AB Background: Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU). Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up.
Methods: We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART) in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM), defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes.
Results: In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39-0.62].
Conclusions: In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU.
C1 [Ahonkhai, Aima A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Noubary, Farzad; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Educ Ctr, Boston, MA 02114 USA.
[Munro, Alison] So African Catholic Bishops Conf, Pretoria, Gauteng, South Africa.
[Stark, Ruth; Wilke, Marisa] Catholic Relief Serv S Africa, Johannesburg, Gauteng, South Africa.
[Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Freedberg, Kenneth A.; Losina, Elena] Harvard Univ Ctr AIDS Res, Boston, MA USA.
[Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, Western Cape, South Africa.
[Wood, Robin] Univ Cape Town, Dept Med, ZA-7925 Cape Town, Western Cape, South Africa.
[Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Ahonkhai, AA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM aahonkhai@partners.org
FU National Institutes of Allergy and Infectious Disease [T32 A007433, R01
AI058736]
FX Supported in part by National Institutes of Allergy and Infectious
Disease (T32 A007433, R01 AI058736). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 30
TC 16
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 12
PY 2012
VL 7
IS 3
AR e32993
DI 10.1371/journal.pone.0032993
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 920DF
UT WOS:000302381500071
PM 22427925
ER
PT J
AU Temiyasathit, S
Tang, WJ
Leucht, P
Anderson, CT
Monica, SD
Castillo, AB
Helms, JA
Stearns, T
Jacobs, CR
AF Temiyasathit, Sara
Tang, W. Joyce
Leucht, Philipp
Anderson, Charles T.
Monica, Stefanie D.
Castillo, Alesha B.
Helms, Jill A.
Stearns, Tim
Jacobs, Christopher R.
TI Mechanosensing by the Primary Cilium: Deletion of Kif3A Reduces Bone
Formation Due to Loading
SO PLOS ONE
LA English
DT Article
ID POLYCYSTIC KIDNEY-DISEASE; INTRAFLAGELLAR TRANSPORT PROTEINS;
FLUID-FLOW; KINESIN-II; MOUSE; CELLS; OSTEOCYTES; EXPRESSION; MICE;
SKELETOGENESIS
AB Primary cilia, solitary microtubule-based structures that grow from the centriole and extend into the extracellular space, have increasingly been implicated as sensors of a variety of biochemical and biophysical signals. Mutations in primary cilium-related genes have been linked to a number of rare developmental disorders as well as dysregulation of cell proliferation. We propose that primary cilia are also important in mechanically regulated bone formation in adults and that their malfunction could play a role in complex multi-factorial bone diseases, such as osteoporosis. In this study, we generated mice with an osteoblast-and osteocyte-specific knockout of Kif3a, a subunit of the kinesin II intraflagellar transport (IFT) protein; IFT is required for primary cilia formation, maintenance, and function. These Col alpha 1(I) 2.3-Cre;Kif3a(fl/fl) mice exhibited no obvious morphological skeletal abnormalities. Skeletally mature Col alpha 1(I) 2.3-Cre;Kif3a(fl/fl) and control mice were exposed to 3 consecutive days of cyclic axial ulna loading, which resulted in a significant increase in bone formation in both the conditional knockouts and controls. However, Col alpha 1(I) 2.3-Cre;Kif3a(fl/fl) mice did exhibit decreased formation of new bone in response to mechanical ulnar loading compared to control mice. These results suggest that primary cilia act as cellular mechanosensors in bone and that their function may be critical for the regulation of bone physiology due to mechanical loading in adults.
C1 [Temiyasathit, Sara; Tang, W. Joyce; Castillo, Alesha B.; Jacobs, Christopher R.] US Dept Vet Affairs, Bone & Joint Rehabil R&D Ctr, Palo Alto, CA USA.
[Temiyasathit, Sara; Jacobs, Christopher R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Stearns, Tim] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA.
[Jacobs, Christopher R.] Columbia Univ, Dept Biomed Engn, New York, NY USA.
[Stearns, Tim] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Castillo, Alesha B.; Jacobs, Christopher R.] Stanford Univ, Dept Mech Engn, Stanford, CA 94305 USA.
[Leucht, Philipp] Stanford Univ, Dept Orthopaed Surg, Stanford, CA 94305 USA.
[Monica, Stefanie D.; Helms, Jill A.] Stanford Univ, Dept Surg Plast & Reconstruct Surg, Stanford, CA 94305 USA.
[Anderson, Charles T.] Univ Calif Berkeley, Energy Biosci Inst, Berkeley, CA 94720 USA.
RP Temiyasathit, S (reprint author), US Dept Vet Affairs, Bone & Joint Rehabil R&D Ctr, Palo Alto, CA USA.
EM crj2111@columbia.edu
RI Castillo, Alesha/A-8728-2014;
OI Castillo, Alesha/0000-0002-1371-7567; Leucht,
Philipp/0000-0002-8409-8513; Anderson, Charles/0000-0001-7481-3571
FU National Institutes of Health [R21AR054156]; Department of Veterans
Affairs
FX This work was supported by a National Institutes of Health grant
R21AR054156 (CRJ), and ST was granted a fellowship by the Department of
Veterans Affairs. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 55
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Z9 22
U1 2
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 12
PY 2012
VL 7
IS 3
AR e33368
DI 10.1371/journal.pone.0033368
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 920DF
UT WOS:000302381500135
PM 22428034
ER
PT J
AU Tso, FY
Tully, DC
Gonzalez, S
Quince, C
Ho, O
Polacino, P
Ruprecht, RM
Hu, SL
Wood, C
AF Tso, For Yue
Tully, Damien C.
Gonzalez, Sandra
Quince, Christopher
Ho, On
Polacino, Patricia
Ruprecht, Ruth M.
Hu, Shiu-Lok
Wood, Charles
TI Dynamics of Envelope Evolution in Clade C SHIV-Infected Pig-Tailed
Macaques during Disease Progression Analyzed by Ultra-Deep
Pyrosequencing
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIBODY NEUTRALIZATION; HIV-1
TRANSMISSION; MACACA-NEMESTRINA; ZAMBIAN INFANT; V3 LOOP; TYPE-1; ENV;
CORECEPTOR; SEQUENCES
AB Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of non-human primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a non-progressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep pyrosequencing. Our results showed substantial envelope variations emerging in the progressor animal after the onset of AIDS. These envelope variations impacted the length of the variable loops and charges of different envelope regions. Additionally, multiple mutations were located at the CD4 and CCR5 binding sites, potentially affecting receptor binding affinity, viral fitness and they might be selected at late stages of disease. More importantly, these envelope mutations are not random since they had repeatedly been observed in a rhesus macaque and a human infant infected by either SHIV or HIV-1, respectively, carrying the parental envelope of the infectious molecular clone SHIV-1157ipd3N4. Moreover, similar mutations were also observed from other studies on different clades of envelopes regardless of the host species. These recurring mutations in different envelopes suggest that there may be a common evolutionary pattern and selection pathway for the HIV-1 envelope during disease progression.
C1 [Tso, For Yue; Tully, Damien C.; Gonzalez, Sandra; Wood, Charles] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA.
[Tso, For Yue; Tully, Damien C.; Gonzalez, Sandra; Wood, Charles] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA.
[Ho, On; Hu, Shiu-Lok] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Polacino, Patricia; Hu, Shiu-Lok] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
[Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA.
[Quince, Christopher] Univ Glasgow, Sch Engn, Glasgow, Lanark, Scotland.
RP Tso, FY (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA.
EM cwood@unlnotes.unl.edu
RI Hu, Shiu-Lok/A-3196-2008
OI Hu, Shiu-Lok/0000-0003-4336-7964
FU Public Health Service [CA75903, TW001429, T32 AI060547]; National Center
for Research Resource, Center for Biomedical Research Excellence [P30
RR031151, P01 AI48240, RR000166, N01 AI060006]; American Recovery and
Reinvestment Act [3P01AI048240-08S1]; National Institute of Allergy and
Infectious Disease
FX This work was supported by Public Health Service grants, CA75903,
TW001429, T32 AI060547 and National Center for Research Resource, Center
for Biomedical Research Excellence grant P30 RR031151 to CW; P01 AI48240
to RMR, CW and SLH; and RR000166 and N01 AI060006 to the Washington
National Primate Research Center; American Recovery and Reinvestment Act
funding 3P01AI048240-08S1 to RMR, CW; SG was supported by a Ruth L.
Kirschstein National Service Award from the National Institute of
Allergy and Infectious Disease. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 50
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U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 12
PY 2012
VL 7
IS 3
AR e32827
DI 10.1371/journal.pone.0032827
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 920DF
UT WOS:000302381500053
PM 22427893
ER
PT J
AU Walker, RH
Moore, C
Davies, G
Dirling, LB
Koch, RJ
Meshul, CK
AF Walker, Ruth H.
Moore, Cindy
Davies, Georgia
Dirling, Lisa B.
Koch, Rick J.
Meshul, Charles K.
TI Effects of Subthalamic Nucleus Lesions and Stimulation upon
Corticostriatal Afferents in the 6-Hydroxydopamine- Lesioned Rat
SO PLOS ONE
LA English
DT Article
ID HIGH-FREQUENCY STIMULATION; DEEP-BRAIN-STIMULATION; MEDIUM SPINY
NEURONS; INDUCED CONTRALATERAL ROTATIONS; EXTRACELLULAR GLUTAMATE
LEVELS; TIME-DEPENDENT CHANGES; NIGRA PARS RETICULATA; HEMI-PARKINSON
RATS; L-DOPA TREATMENT; STRIATAL GLUTAMATE
AB Abnormalities of striatal glutamate neurotransmission may play a role in the pathophysiology of Parkinson's disease and may respond to neurosurgical interventions, specifically stimulation or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate. Corticostriatal terminals can be distinguished within the striatum at the electron microscopic level as their synaptic vesicles contain the vesicular glutamate transporter, VGLUT1. The majority of terminals which are immunolabeled for glutamate but are not VGLUT1 positive are likely to be thalamostriatal afferents. We compared the effects of short term, high frequency, STN stimulation and lesioning in 6-hydroxydopamine (6OHDA)-lesioned rats upon striatal terminals immunolabeled for both presynaptic glutamate and VGLUT1. 6OHDA lesions resulted in a small but significant increase in the proportions of VGLUT1-labeled terminals making synapses on dendritic shafts rather than spines. STN stimulation for one hour, but not STN lesions, increased the proportion of synapses upon spines. The density of presynaptic glutamate immuno-gold labeling was unchanged in both VGLUT1-labeled and -unlabeled terminals in 6OHDA-lesioned rats compared to controls. Rats with 6OHDA lesions+STN stimulation showed a decrease in nerve terminal glutamate immuno-gold labeling in both VGLUT1-labeled and -unlabeled terminals. STN lesions resulted in a significant decrease in the density of presynaptic immuno-gold-labeled glutamate only in VGLUT1-labeled terminals. STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission.
C1 [Walker, Ruth H.; Davies, Georgia; Koch, Rick J.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA.
[Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Moore, Cindy; Dirling, Lisa B.; Meshul, Charles K.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Neurocytol Lab, Res Serv, Portland, OR 97201 USA.
[Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci & Pathol, Portland, OR 97201 USA.
RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA.
EM ruth.walker@mssm.edu
FU Department of Veterans Affairs
FX This work was funded by Department of Veterans Affairs Merit awards to
RHW and CKM. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 78
TC 7
Z9 7
U1 2
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 12
PY 2012
VL 7
IS 3
AR e32919
DI 10.1371/journal.pone.0032919
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 920DF
UT WOS:000302381500062
PM 22427909
ER
PT J
AU Nakamura, K
Berry, NC
An, PG
Dudzinski, DM
AF Nakamura, Kenta
Berry, Natalia C.
An, Perry G.
Dudzinski, David M.
TI Significance of ST-Segment Elevation in Lead aVR
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY; LEFT MAIN;
ELECTROCARDIOGRAPHY; V-1
C1 [Nakamura, Kenta; Berry, Natalia C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Dudzinski, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
[An, Perry G.] Newton Wellesley Hosp, Dept Med, Newton, MA USA.
RP Nakamura, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 55 Fruit St,Med GRB 740, Boston, MA 02114 USA.
EM knakamura@partners.org
NR 10
TC 3
Z9 3
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAR 12
PY 2012
VL 172
IS 5
BP 389
EP 391
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 906XB
UT WOS:000301381300002
PM 22412103
ER
PT J
AU Luo, JH
Rossouw, J
Tong, E
Giovino, GA
Lee, C
Chen, C
Ockene, JK
Qi, LH
Margolis, KL
AF Luo, Juhua
Rossouw, Jacques
Tong, Elisa
Giovino, Gary A.
Lee, Cathy
Chen, Chu
Ockene, Judith K.
Qi, Lihong
Margolis, Karen L.
TI Smoking Cessation, Weight Gain, and Risk of Type 2 Diabetes Mellitus
Among Postmenopausal Women
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID METAANALYSIS; COHORT
C1 [Luo, Juhua] W Virginia Univ, Dept Community Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
[Rossouw, Jacques] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Tong, Elisa] Univ Calif, Davis Med Ctr, Div Gen Internal Med, Sacramento, CA USA.
[Giovino, Gary A.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Community Hlth & Hlth Behav, Buffalo, NY 14260 USA.
[Lee, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Div Geriatr, Los Angeles, CA 90095 USA.
[Lee, Cathy] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA.
[Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Ockene, Judith K.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Qi, Lihong] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA.
[Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA.
RP Luo, JH (reprint author), W Virginia Univ, Dept Community Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
EM Jiluo@hsc.wvu.edu
NR 9
TC 10
Z9 10
U1 1
U2 4
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 MAR 12
PY 2012
VL 172
IS 5
BP 438
EP 440
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 906XB
UT WOS:000301381300017
PM 22412112
ER
PT J
AU Hajjar, I
Hart, M
Chen, YL
Mack, W
Milberg, W
Chui, H
Lipsitz, L
AF Hajjar, Ihab
Hart, Meaghan
Chen, Yu-Ling
Mack, Wendy
Milberg, William
Chui, Helena
Lipsitz, Lewis
TI Effect of Antihypertensive Therapy on Cognitive Function in Early
Executive Cognitive Impairment: A Double-blind Randomized Clinical Trial
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID II TYPE-2 RECEPTOR; HEALTH; HYPERTENSION; DEMENTIA; BRAIN
C1 [Hajjar, Ihab] Univ So Calif, Dept Med, Los Angeles, CA 90033 USA.
[Hajjar, Ihab] Univ So Calif, Div Geriatr, Hos & Gen Internal Med, Los Angeles, CA 90033 USA.
[Chen, Yu-Ling] Univ So Calif, Alzheimer Dis Res Ctr, Dept Neurol, Los Angeles, CA 90033 USA.
[Mack, Wendy] Univ So Calif, Dept Biostat, Los Angeles, CA 90033 USA.
[Chui, Helena] Univ So Calif, Dept Neurol, Raymond & Betty McCarron Chair Neurol, Los Angeles, CA 90033 USA.
[Hart, Meaghan; Lipsitz, Lewis] Inst Aging Res, Boston, MA USA.
[Milberg, William] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Milberg, William] VA Boston Healthcare, New England Geriatr Res, Educ & Clin Ctr GRECC, Boston Div, Boston, MA USA.
[Lipsitz, Lewis] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA.
RP Hajjar, I (reprint author), Univ So Calif, Dept Med, 2020 Zonal Ave,IRD 320, Los Angeles, CA 90033 USA.
EM ihajjar@usc.edu
FU NCATS NIH HHS [UL1 TR000130]; NCRR NIH HHS [UL1RR031986]; NIA NIH HHS [1
K23 AG030057, K23 AG030057, P01 AG004390, P01-AG004390, R37 AG025037,
R37-AG025037]
NR 8
TC 31
Z9 32
U1 1
U2 8
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 MAR 12
PY 2012
VL 172
IS 5
BP 442
EP 444
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 906XB
UT WOS:000301381300019
PM 22412114
ER
PT J
AU Juric, D
Baselga, J
AF Juric, Dejan
Baselga, Jose
TI Tumor Genetic Testing for Patient Selection in Phase I Clinical Trials:
The Case of PI3K Inhibitors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID DUAL PI3K/MTOR INHIBITOR; BREAST-CANCER CELLS; HEDGEHOG PATHWAY;
MUTATIONS; SENSITIVITY; NVP-BEZ235; BRAF
C1 [Juric, Dejan; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Baselga, Jose] Harvard Univ, Sch Med, Boston, MA USA.
RP Juric, D (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
NR 18
TC 30
Z9 30
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 MAR 10
PY 2012
VL 30
IS 8
BP 765
EP 766
DI 10.1200/JCO.2011.39.6390
PG 2
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600005
PM 22271482
ER
PT J
AU Hershman, DL
Wilde, ET
Wright, JD
Buono, DL
Kalinsky, K
Malin, JL
Neugut, AI
AF Hershman, Dawn L.
Wilde, Elizabeth T.
Wright, Jason D.
Buono, Donna L.
Kalinsky, Kevin
Malin, Jennifer L.
Neugut, Alfred I.
TI Uptake and Economic Impact of First-Cycle Colony-Stimulating Factor Use
During Adjuvant Treatment of Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SINGLE-ADMINISTRATION PEGFILGRASTIM; ACUTE MYELOID-LEUKEMIA; DAILY
FILGRASTIM; DOSE-DENSE; MYELODYSPLASTIC SYNDROME; SURGEON
CHARACTERISTICS; CONSERVATION SURGERY; RANDOMIZED-TRIAL; PHASE-III;
CHEMOTHERAPY
AB Purpose
In 2002, pegfilgrastim was approved by the US Food and Drug Administration and the benefits of dose-dense breast cancer chemotherapy, especially for hormone receptor (HR)-negative tumors, were reported. We examined first-cycle colony-stimulating factor use (FC-CSF) before and after 2002 and estimated US expenditures for dose-dense chemotherapy.
Methods
We identified patients in Surveillance, Epidemiology, and End Results-Medicare greater than 65 years old with stages I to III breast cancer who had greater than one chemotherapy claim within 6 months of diagnosis(1998 to 2005) and classified patients with an average cycle length less than 21 days as having received dose-dense chemotherapy. The associations of patient, tumor, and physician-related factors with the receipt of any colony-stimulating factor (CSF) and FC-CSF use were analyzed by using generalized estimating equations. CSF costs were estimated for patients who were undergoing dose-dense chemotherapy.
Results
Among the 10,773 patients identified, 5,266 patients (48.9%) had a CSF claim. CSF use was stable between 1998 and 2002 and increased from 36.8% to 73.7% between 2002 and 2005, FC-CSF use increased from 13.2% to 67.9%, and pegfilgrastim use increased from 4.1% to 83.6%. In a multivariable analysis, CSF use was associated with age and chemotherapy type and negatively associated with black/Hispanic race, rural residence, and shorter chemotherapy duration. FC-CSF use was associated with high socioeconomic status but not with age or race/ethnicity. The US annual CSF expenditure for women with HR-positive tumors treated with dose-dense chemotherapy is estimated to be $38.8 million.
Conclusion
A rapid increase in FC-CSF use occurred over a short period of time, which was likely a result of the reported benefits of dose-dense chemotherapy and the ease of pegfilgrastim administration. Because of the increasing evidence that elderly HR-positive patients do not benefit from dose-dense chemotherapy, limiting pegfilgrastim use would combat the increasing costs of cancer care. J Clin Oncol 30: 806-812. (C) 2012 by American Society of Clinical Oncology
C1 [Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY 10032 USA.
[Hershman, Dawn L.; Wilde, Elizabeth T.; Wright, Jason D.; Buono, Donna L.; Kalinsky, Kevin; Neugut, Alfred I.] New York Presbyterian Hosp, New York, NY USA.
[Malin, Jennifer L.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA.
RP Hershman, DL (reprint author), Columbia Univ, Med Ctr, 161 Ft Washington Ave,10-1068, New York, NY 10032 USA.
EM dlh23@columbia.edu
FU National Cancer Institute [NCI R01CA134964]
FX Supported by Grant No. NCI R01CA134964 from the National Cancer
Institute (D.L.H.).
NR 30
TC 18
Z9 20
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 MAR 10
PY 2012
VL 30
IS 8
BP 806
EP 812
DI 10.1200/JCO.2011.37.7499
PG 7
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600015
PM 22312106
ER
PT J
AU Bergethon, K
Shaw, AT
Ou, SHI
Katayama, R
Lovly, CM
McDonald, NT
Massion, PP
Siwak-Tapp, C
Gonzalez, A
Fang, R
Mark, EJ
Batten, JM
Chen, HQ
Wilner, KD
Kwak, EL
Clark, JW
Carbone, DP
Ji, HB
Engelman, JA
Mino-Kenudson, M
Pao, W
Iafrate, AJ
AF Bergethon, Kristin
Shaw, Alice T.
Ou, Sai-Hong Ignatius
Katayama, Ryohei
Lovly, Christine M.
McDonald, Nerina T.
Massion, Pierre P.
Siwak-Tapp, Christina
Gonzalez, Adriana
Fang, Rong
Mark, Eugene J.
Batten, Julie M.
Chen, Haiquan
Wilner, Keith D.
Kwak, Eunice L.
Clark, Jeffrey W.
Carbone, David P.
Ji, Hongbin
Engelman, Jeffrey A.
Mino-Kenudson, Mari
Pao, William
Iafrate, A. John
TI ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ANAPLASTIC LYMPHOMA KINASE; FUSION; GLIOBLASTOMA; GEFITINIB; EML4-ALK;
MUTATIONS; TUMORS; GENE; INHIBITORS; FEATURES
AB Purpose
Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non-small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement.
Patients and Methods
Using a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort.
Results
Of 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P < .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and-negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response.
Conclusion
ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC. J Clin Oncol 30: 863-870. (C) 2012 by American Society of Clinical Oncology
C1 [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ou, Sai-Hong Ignatius; Siwak-Tapp, Christina] Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA.
[Wilner, Keith D.] Pfizer, La Jolla, CA USA.
[Lovly, Christine M.; McDonald, Nerina T.; Massion, Pierre P.; Gonzalez, Adriana; Carbone, David P.; Pao, William] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Massion, Pierre P.] Nashville Vet Affairs Med Ctr, Nashville, TN USA.
[Fang, Rong; Ji, Hongbin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China.
[Chen, Haiquan] Fudan Univ, Shanghai Canc Ctr, Shanghai 200433, Peoples R China.
[Chen, Haiquan] Fudan Univ, Shanghai Med Coll, Shanghai 200433, Peoples R China.
RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM aiafrate@partners.org
FU National Institutes of Health [1R21CA161590-01]; Pfizer
FX Supported by National Institutes of Health Grant No. 1R21CA161590-01
(A.J.I.) and by Pfizer, which supported the crizotinib phase I trial.
NR 22
TC 493
Z9 532
U1 10
U2 50
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2012
VL 30
IS 8
BP 863
EP 870
DI 10.1200/JCO.2011.35.6345
PG 8
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600023
PM 22215748
ER
PT J
AU Schutz, FAB
Je, YJ
Richards, CJ
Choueiri, TK
AF Schutz, Fabio A. B.
Je, Youjin
Richards, Christopher J.
Choueiri, Toni K.
TI Meta-Analysis of Randomized Controlled Trials for the Incidence and Risk
of Treatment-Related Mortality in Patients With Cancer Treated With
Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RENAL-CELL CARCINOMA; ADVANCED HEPATOCELLULAR-CARCINOMA; FOOT SKIN
REACTION; PHASE-III; CLINICAL-TRIALS; DOUBLE-BLIND; LUNG-CANCER;
SORAFENIB; SUNITINIB; ANGIOGENESIS
AB Purpose
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have become the cornerstone in the treatment of several malignancies. These drugs have also been associated with an increase in the risk of potentially life-threatening adverse events, such as arterial thrombotic events, bleeding, congestive heart failure, and others. We performed an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in patients with cancer treated with VEGFR TKIs.
Methods
MEDLINE and PubMed databases were searched for articles published from January 1966 to February 2011. Eligible studies were limited to trials of US Food and Drug Administration-approved VEGFR TKIs (pazopanib, sunitinib, and sorafenib) that reported on patients with cancer with any primary tumor type, randomized design, and adequate safety profile. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95% CIs by using random-effects or fixed-effects models on the basis of the heterogeneity of included studies.
Results
In all, 4,679 patients from 10 randomized controlled trials (RCTs) were included, with 2,856 from sorafenib, 1,388 from sunitinib, and 435 from pazopanib trials. The incidence of FAEs related to VEGFR TKIs was 1.5% (95% CI, 0.8% to 2.4%) with an RR of 2.23 (95% CI, 1.12 to 4.44; P = .023) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between different VEGFR TKIs or tumor types. No evidence of publication bias was observed.
Conclusion
In a meta-analysis of RCTs, the use of VEGFR TKIs was associated with an increased risk of FAEs compared with control patients. J Clin Oncol 30: 871-877. (C) 2012 by American Society of Clinical Oncology
C1 [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Schutz, Fabio A. B.; Richards, Christopher J.; Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Je, Youjin] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Schutz, Fabio A. B.] Hosp Sao Jose & Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil.
RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA.
EM toni_choueiri@dfci.harvard.edu
FU Trust Family
FX Supported by the Trust Family Research Fund for Kidney Cancer.
NR 45
TC 75
Z9 75
U1 4
U2 9
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2012
VL 30
IS 8
BP 871
EP 877
DI 10.1200/JCO.2011.37.1195
PG 7
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600024
PM 22312105
ER
PT J
AU Janne, PA
Meyerson, M
AF Jaenne, Pasi A.
Meyerson, Matthew
TI ROS1 Rearrangements in Lung Cancer: A New Genomic Subset of Lung
Adenocarcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID ANAPLASTIC LYMPHOMA KINASE; CHEMOTHERAPY; MUTATIONS; GEFITINIB; EGFR
C1 [Jaenne, Pasi A.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Jaenne, Pasi A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Meyerson, Matthew] Broad Inst, Cambridge, MA USA.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
RI Meyerson, Matthew/E-7123-2012
NR 15
TC 26
Z9 26
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2012
VL 30
IS 8
BP 878
EP 879
DI 10.1200/JCO.2011.39.4197
PG 2
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600025
PM 22215755
ER
PT J
AU Smith, TJ
Temin, S
Alesi, ER
Abernethy, AP
Balboni, TA
Basch, EM
Ferrell, BR
Loscalzo, M
Meier, DE
Paice, JA
Peppercorn, JM
Somerfield, M
Stovall, E
Von Roenn, JH
AF Smith, Thomas J.
Temin, Sarah
Alesi, Erin R.
Abernethy, Amy P.
Balboni, Tracy A.
Basch, Ethan M.
Ferrell, Betty R.
Loscalzo, Matt
Meier, Diane E.
Paice, Judith A.
Peppercorn, Jeffrey M.
Somerfield, Mark
Stovall, Ellen
Von Roenn, Jamie H.
TI American Society of Clinical Oncology Provisional Clinical Opinion: The
Integration of Palliative Care Into Standard Oncology Care
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; CELL LUNG-CANCER; MEDICINE CONSULTATION;
OUTPATIENT; INTERVENTION; OUTCOMES; THERAPY; COSTS; TEAM; LIFE
AB Based on strong evidence from a phase III RCT, patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and standard oncologic care at initial diagnosis. While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology settings, substantial evidence demonstrates that palliative care-when combined with standard cancer care or as the main focus of care-leads to better patient and caregiver outcomes. These include improvement in symptoms, QOL, and patient satisfaction, with reduced caregiver burden. Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice, and reduced use of futile intensive care. While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving, no trials to date have demonstrated harm to patients and caregivers, or excessive costs, from early involvement of palliative care. Therefore, it is the Panel's expert consensus that combined standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care, with evaluation of its impact on important patient and caregiver outcomes (eg, QOL, survival, health care services utilization, and costs) and on society, should be an area of intense research.
C1 [Smith, Thomas J.] Sidney Kimmel Canc Ctr Johns Hopkins Med, Baltimore, MD USA.
[Stovall, Ellen] Natl Coalit Canc Survivorship, Silver Spring, MD USA.
[Temin, Sarah; Somerfield, Mark] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
[Alesi, Erin R.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA.
[Abernethy, Amy P.; Peppercorn, Jeffrey M.] Duke Univ, Med Ctr, Durham, NC USA.
[Balboni, Tracy A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Meier, Diane E.] Mt Sinai Sch Med, Ctr Adv Palliat Care, New York, NY USA.
[Ferrell, Betty R.; Loscalzo, Matt] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Paice, Judith A.; Von Roenn, Jamie H.] Northwestern Univ, Chicago, IL 60611 USA.
RP Temin, S (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
OI Paice, Judith/0000-0001-7534-1756
NR 31
TC 402
Z9 406
U1 8
U2 51
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2012
VL 30
IS 8
BP 880
EP 887
DI 10.1200/JCO.2011.38.5161
PG 8
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600026
PM 22312101
ER
PT J
AU Mroz, EA
Forastiere, AA
Rocco, JW
AF Mroz, Edmund A.
Forastiere, Arlene A.
Rocco, James W.
TI Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal
Cancer Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Forastiere, Arlene A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Rocco, James W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Mroz, EA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 6
TC 3
Z9 3
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2012
VL 30
IS 8
BP 891
EP 892
DI 10.1200/JCO.2011.40.6884
PG 3
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600032
ER
PT J
AU Tse, WKF
Chow, SC
Wong, CKC
AF Tse, William K. F.
Chow, Sheung C.
Wong, Chris K. C.
TI Eel osmotic stress transcriptional factor 1 (Ostf1) is highly expressed
in gill mitochondria-rich cells, where ERK phosphorylated
SO FRONTIERS IN ZOOLOGY
LA English
DT Article
DE Immunohistochemical staining; Mitochondria-rich cells; Osmotic stress
transcriptional factor 1
ID ANGUILLA-JAPONICA; PAVEMENT CELLS; JAPANESE EEL; ACTIVATION; PATHWAYS;
EXCHANGE; CULTURE; ATPASE
AB Background: Osmotic stress transcriptional factor 1 (Ostf1) was firstly identified in tilapia in 2005. Then numerous studies have investigated its regulation and expression profile in fish gill tissues in related to osmoregulation. Generally, hyperosmotic stress induced ostf1 mRNA expression level, however there is no report studying the cellular localization of Ostf1 expression in any osmoregulatory tissue. In this study immunohistochemical (IHC) approach was used to study the cellular localization of Ostf1 in gill cells of Japanese eels.
Findings: Ostf1 protein was found to be localized in branchial mitochondria-rich/chloride cell (MRC/CC) as revealed by Na alpha 5 and CFTR co-localization. The protein was detectable at day 3 after fresh water to seawater transfer and was mainly localized in MRCs. Moreover, elevated levels of extracellular signal regulated kinase (ERK) phosphorylation was observed at day 3 of the transfer and was co-localized with MRCs.
Conclusions: Our data identified Ostf1 expression in gill MRCs. The observation supports the role of Ostf1 in osmosensing and/or osmoregulation in fish gills, particularly its functional relationship with MRCs. The observation of the co-expression of pERK and Ostf1 in MRCs suggests a cross-talk mechanism between the mitogen-activated protein kinases (MAPKs) and Ostf1 in response to hyperosmotic challenge. To summarize, this report has addressed the cellular localization of Ostf1 and provides evidence to illustrate the involvement of Ostf1 and ERK on osmosensing and osmoregulatory function of gill MRCs.
C1 [Tse, William K. F.; Chow, Sheung C.; Wong, Chris K. C.] Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Hong Kong, Peoples R China.
[Tse, William K. F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA.
RP Tse, WKF (reprint author), Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Hong Kong, Peoples R China.
EM kftse@partners.org; ckcwong@hkbu.edu.hk
RI TSE, KA FAI WILLIAM/C-9384-2012
OI TSE, KA FAI WILLIAM/0000-0002-3738-0460
FU University Grants Committee [HKBU 261610]
FX This work was supported by General Research Fund (HKBU 261610),
University Grants Committee to CKCW.
NR 14
TC 10
Z9 10
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-9994
J9 FRONT ZOOL
JI Front. Zool.
PD MAR 10
PY 2012
VL 9
AR 3
DI 10.1186/1742-9994-9-3
PG 5
WC Zoology
SC Zoology
GA 921LH
UT WOS:000302478600001
PM 22405401
ER
PT J
AU Ptaszek, LM
Mansour, M
Ruskin, JN
Chien, KR
AF Ptaszek, Leon M.
Mansour, Moussa
Ruskin, Jeremy N.
Chien, Kenneth R.
TI Towards regenerative therapy for cardiac disease
SO LANCET
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; BONE-MARROW-CELLS; HEMATOPOIETIC
STEM-CELLS; PROGENITOR CELLS; MYOBLAST TRANSPLANTATION; INTRACORONARY
INJECTION; HEART REGENERATION; MAMMALIAN HEART; DEFINED FACTORS;
SMOOTH-MUSCLE
AB Development of regenerative therapeutic strategies to reverse the progression of advanced heart failure is one of the most urgent clinical needs of this century. Insights gained from clinical trials of adult stem cells, together with fundamental scientific advances in cardiac stem cell and regenerative biology, are beginning to yield potential new targets and strategies for regenerative therapies. Of particular importance are new scientific discoveries related to intrinsic cardiac regeneration, renewal factors that can trigger regeneration, and tissue-engineering technology, which are beginning to change the way investigators view the scientific and clinical position of cardiovascular regenerative therapy.
C1 [Ptaszek, Leon M.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ptaszek, Leon M.; Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Boston, MA 02114 USA.
[Ptaszek, Leon M.; Mansour, Moussa; Ruskin, Jeremy N.] Harvard Univ, Sch Med, Boston, MA USA.
[Ptaszek, Leon M.; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 3250, Boston, MA 02114 USA.
EM kchien@harvard.edu
FU de Gunzburg Family Foundation; Deane Institute for Integrative Research
in Atrial Fibrillation and Stroke at the Massachusetts General Hospital
(Boston, MA, USA)
FX We apologise to those of our colleagues whose work could not be cited
because of constraints on space. LMP thanks the de Gunzburg Family
Foundation and the Deane Institute for Integrative Research in Atrial
Fibrillation and Stroke at the Massachusetts General Hospital (Boston,
MA, USA) for their support.
NR 82
TC 111
Z9 113
U1 5
U2 47
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 MAR 10
PY 2012
VL 379
IS 9819
BP 933
EP 942
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 906NY
UT WOS:000301353700034
PM 22405796
ER
PT J
AU Altshuler, D
AF Altshuler, David
TI 2011 Curt Stern Award Address
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Editorial Material
C1 [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol & Med, Boston, MA 02114 USA.
[Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Altshuler, D (reprint author), Massachusetts Gen Hosp, Dept Mol Biol & Med, Boston, MA 02114 USA.
EM altshuler@molbio.mgh.harvard.edu
RI Altshuler, David/A-4476-2009
OI Altshuler, David/0000-0002-7250-4107
NR 0
TC 2
Z9 2
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 9
PY 2012
VL 90
IS 3
BP 407
EP 409
DI 10.1016/j.ajhg.2012.02.017
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 911ZI
UT WOS:000301762800006
PM 22405086
ER
PT J
AU Saxena, R
Elbers, CC
Guo, YR
Peter, I
Gaunt, TR
Mega, JL
Lanktree, MB
Tare, A
Castillo, BA
Li, YR
Johnson, T
Bruinenberg, M
Gilbert-Diamond, D
Rajagopalan, R
Voight, BF
Balasubramanyam, A
Barnard, J
Bauer, F
Baumert, J
Bhangale, T
Bohm, BO
Braund, PS
Burton, PR
Chandrupatla, HR
Clarke, R
Cooper-DeHoff, RM
Crook, ED
Davey-Smith, G
Day, IN
de Boer, A
de Groot, MCH
Drenos, F
Ferguson, J
Fox, CS
Furlong, CE
Gibson, Q
Gieger, C
Gilhuijs-Pederson, LA
Glessner, JT
Goel, A
Gong, Y
Grant, SFA
Grobbee, DE
Hastie, C
Humphries, SE
Kim, CE
Kivimaki, M
Kleber, M
Meisinger, C
Kumari, M
Langaee, TY
Lawlor, DA
Li, MY
Lobmeyer, MT
Maitland-van der Zee, AH
Meijs, MFL
Molony, CM
Morrow, DA
Murugesan, G
Musani, SK
Nelson, CP
Newhouse, SJ
O'Connell, JR
Padmanabhan, S
Palmen, J
Patel, SR
Pepine, CJ
Pettinger, M
Price, TS
Rafelt, S
Ranchalis, J
Rasheed, A
Rosenthal, E
Ruczinski, I
Shah, S
Shen, HQ
Silbernagel, G
Smith, EN
Spijkerman, AWM
Stanton, A
Steffes, MW
Thorand, B
Trip, M
van der Harst, P
van der A, DL
van Iperen, EPA
van Setten, J
van Vliet-Ostaptchouk, JV
Verweij, N
Wolffenbuttel, BHR
Young, T
Zafarmand, MH
Zmuda, JM
Boehnke, M
Altshuler, D
McCarthy, M
Kao, WHL
Pankow, JS
Cappola, TP
Sever, P
Poulter, N
Caulfield, M
Dominiczak, A
Shields, DC
Bhatt, DL
Zhang, L
Curtis, SP
Danesh, J
Casas, JP
van der Schouw, YT
Onland-Moret, NC
Doevendans, PA
Dorn, GW
Farrall, M
FitzGerald, GA
Hamsten, A
Hegele, R
Hingorani, AD
Hofker, MH
Huggins, GS
Illig, T
Jarvik, GP
Johnson, JA
Klungel, OH
Knowler, WC
Koenig, W
Marz, W
Meigs, JB
Melander, O
Munroe, PB
Mitchell, BD
Bielinski, SJ
Rader, DJ
Reilly, MP
Rich, SS
Rotter, JI
Saleheen, D
Samani, NJ
Schadt, EE
Shuldiner, AR
Silverstein, R
Kottke-Marchant, K
Talmud, PJ
Watkins, H
Asselbergs, FW
de Bakker, PIW
McCaffery, J
Wijmenga, C
Sabatine, MS
Wilson, JG
Reiner, A
Bowden, DW
Hakonarson, H
Siscovick, DS
Keating, BJ
AF Saxena, Richa
Elbers, Clara C.
Guo, Yiran
Peter, Inga
Gaunt, Tom R.
Mega, Jessica L.
Lanktree, Matthew B.
Tare, Archana
Almoguera Castillo, Berta
Li, Yun R.
Johnson, Toby
Bruinenberg, Marcel
Gilbert-Diamond, Diane
Rajagopalan, Ramakrishnan
Voight, Benjamin F.
Balasubramanyam, Ashok
Barnard, John
Bauer, Florianne
Baumert, Jens
Bhangale, Tushar
Boehm, Bernhard O.
Braund, Peter S.
Burton, Paul R.
Chandrupatla, Hareesh R.
Clarke, Robert
Cooper-DeHoff, Rhonda M.
Crook, Errol D.
Davey-Smith, George
Day, Ian N.
de Boer, Anthonius
de Groot, Mark C. H.
Drenos, Fotios
Ferguson, Jane
Fox, Caroline S.
Furlong, Clement E.
Gibson, Quince
Gieger, Christian
Gilhuijs-Pederson, Lisa A.
Glessner, Joseph T.
Goel, Anuj
Gong, Yan
Grant, Struan F. A.
Grobbee, Diederick E.
Hastie, Claire
Humphries, Steve E.
Kim, Cecilia E.
Kivimaki, Mika
Kleber, Marcus
Meisinger, Christa
Kumari, Meena
Langaee, Taimour Y.
Lawlor, Debbie A.
Li, Mingyao
Lobmeyer, Maximilian T.
Maitland-van der Zee, Anke-Hilse
Meijs, Matthijs F. L.
Molony, Cliona M.
Morrow, David A.
Murugesan, Gurunathan
Musani, Solomon K.
Nelson, Christopher P.
Newhouse, Stephen J.
O'Connell, Jeffery R.
Padmanabhan, Sandosh
Palmen, Jutta
Patel, Sanjey R.
Pepine, Carl J.
Pettinger, Mary
Price, Thomas S.
Rafelt, Suzanne
Ranchalis, Jane
Rasheed, Asif
Rosenthal, Elisabeth
Ruczinski, Ingo
Shah, Sonia
Shen, Haiqing
Silbernagel, Guenther
Smith, Erin N.
Spijkerman, Annemieke W. M.
Stanton, Alice
Steffes, Michael W.
Thorand, Barbara
Trip, Mieke
van der Harst, Pim
van der A, Daphne L.
van Iperen, Erik P. A.
van Setten, Jessica
van Vliet-Ostaptchouk, Jana V.
Verweij, Niek
Wolffenbuttel, Bruce H. R.
Young, Taylor
Zafarmand, M. Hadi
Zmuda, Joseph M.
Boehnke, Michael
Altshuler, David
McCarthy, Mark
Kao, W. H. Linda
Pankow, James S.
Cappola, Thomas P.
Sever, Peter
Poulter, Neil
Caulfield, Mark
Dominiczak, Anna
Shields, Denis C.
Bhatt, Deepak L.
Zhang, Li
Curtis, Sean P.
Danesh, John
Casas, Juan P.
van der Schouw, Yvonne T.
Onland-Moret, N. Charlotte
Doevendans, Pieter A.
Dorn, Gerald W., II
Farrall, Martin
FitzGerald, Garret A.
Hamsten, Anders
Hegele, Robert
Hingorani, Aroon D.
Hofker, Marten H.
Huggins, Gordon S.
Illig, Thomas
Jarvik, Gail P.
Johnson, Julie A.
Klungel, Olaf H.
Knowler, William C.
Koenig, Wolfgang
Maerz, Winfried
Meigs, James B.
Melander, Olle
Munroe, Patricia B.
Mitchell, Braxton D.
Bielinski, Susan J.
Rader, Daniel J.
Reilly, Muredach P.
Rich, Stephen S.
Rotter, Jerome I.
Saleheen, Danish
Samani, Nilesh J.
Schadt, Eric E.
Shuldiner, Alan R.
Silverstein, Roy
Kottke-Marchant, Kandice
Talmud, Philippa J.
Watkins, Hugh
Asselbergs, Folkert W.
de Bakker, Paul I. W.
McCaffery, Jeanne
Wijmenga, Cisca
Sabatine, Marc S.
Wilson, James G.
Reiner, Alex
Bowden, Donald W.
Hakonarson, Hakon
Siscovick, David S.
Keating, Brendan J.
CA Look AHEAD Res Grp
Diagram Consortium
ASCOT Investigators
PROCARDIS
TI Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type
2 Diabetes Loci
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMMON
VARIANTS; EUROPEAN AMERICANS; AFRICAN-AMERICANS; BLOOD-PRESSURE;
RESOURCE CARE; RISK-FACTORS; SNP ARRAY
AB To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.
C1 [Saxena, Richa; Tare, Archana; Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Saxena, Richa; Tare, Archana; Voight, Benjamin F.; Young, Taylor; Altshuler, David; de Bakker, Paul I. W.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Elbers, Clara C.] Univ Penn, Dept Genet, Sch Med, Philadelphia, PA 19104 USA.
[Elbers, Clara C.; Bauer, Florianne; Onland-Moret, N. Charlotte; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Complex Genet Sect, Dept Med Genet, Utrecht, Netherlands.
[Elbers, Clara C.; Bauer, Florianne; Grobbee, Diederick E.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Guo, Yiran; Almoguera Castillo, Berta; Li, Yun R.; Glessner, Joseph T.; Grant, Struan F. A.; Kim, Cecilia E.; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA.
[Guo, Yiran] BGI Shenzhen, Shenzhen 518083, Peoples R China.
[Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Gaunt, Tom R.; Davey-Smith, George; Day, Ian N.; Lawlor, Debbie A.] Univ Bristol, Med Res Council Ctr Causal Anal Translat Epidemio, Dept Social Med, Bristol BS8 2BN, Avon, England.
[Mega, Jessica L.; Morrow, David A.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, Thrombolysis Myocardial Infarct Study Grp, Boston, MA 02115 USA.
[Lanktree, Matthew B.; Hegele, Robert] Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada.
[Almoguera Castillo, Berta] Fdn Jimenez Diaz, Serv Genet, Inst Invest Sanitaria, Madrid 228040, Spain.
[Johnson, Toby; Newhouse, Stephen J.; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Genome Ctr, London EC1M 6BQ, England.
[Johnson, Toby; Newhouse, Stephen J.; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England.
[Bruinenberg, Marcel] Univ Groningen, LifeLines Cohort Study & Biobank, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
[Gilbert-Diamond, Diane] Childrens Environm Hlth & Dis Prevent Ctr Dartmou, Hanover, NH 03755 USA.
[Gilbert-Diamond, Diane] Dartmouth Med Sch, Sect Biostat & Epidemiol, Dept Community & Family Med, Hanover, NH 03756 USA.
[Rajagopalan, Ramakrishnan; Furlong, Clement E.; Ranchalis, Jane; Rosenthal, Elisabeth; Jarvik, Gail P.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Balasubramanyam, Ashok] Baylor Coll Med, Translat Metab Unit, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA.
[Barnard, John; Zhang, Li] Cleveland Clin, Dept Quantitat Hlth Sci, Lerner Res Inst, Cleveland, OH 44195 USA.
[Baumert, Jens; Meisinger, Christa; Thorand, Barbara] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Bhangale, Tushar; Furlong, Clement E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Boehm, Bernhard O.] Cardiol Grp Frankfurt Sachsenhausen, D-60598 Frankfurt, Germany.
[Braund, Peter S.; Nelson, Christopher P.; Rafelt, Suzanne; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester LE3 9QP, Leics, England.
[Burton, Paul R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
[Chandrupatla, Hareesh R.; Ferguson, Jane; Li, Mingyao; Cappola, Thomas P.; Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Clarke, Robert] Clin Trial Serv Unit, Oxford OX3 7LF, England.
[Cooper-DeHoff, Rhonda M.; Langaee, Taimour Y.; Johnson, Julie A.] Univ Florida, Dept Pharmacotherapy & Translat Res, Coll Pharm, Gainesville, FL 32610 USA.
[Cooper-DeHoff, Rhonda M.; Gong, Yan; Lobmeyer, Maximilian T.; Pepine, Carl J.; Johnson, Julie A.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32610 USA.
[Crook, Errol D.] Univ S Alabama, Mobile, AL 36608 USA.
[de Boer, Anthonius; de Groot, Mark C. H.; Gilhuijs-Pederson, Lisa A.; Maitland-van der Zee, Anke-Hilse; Klungel, Olaf H.] Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Fac Sci, Utrecht, Netherlands.
[Drenos, Fotios; Humphries, Steve E.; Palmen, Jutta; Talmud, Philippa J.] UCL, Ctr Cardiovasc Genet, Dept Med, London WC1E 6JF, England.
[Fox, Caroline S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Gibson, Quince; O'Connell, Jeffery R.; Shen, Haiqing; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Gieger, Christian; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Goel, Anuj; McCarthy, Mark; Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Hastie, Claire; Padmanabhan, Sandosh; Dominiczak, Anna] Univ Glasgow, British Heart Fdn Glasgow, Cardiovasc Res Ctr, Div Cardiovasc & Med Sci,Western Infirm, Glasgow G12 8TA, Lanark, Scotland.
[Kivimaki, Mika; Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Kivimaki, Mika; Kumari, Meena] UCL, Genet Epidemiol Grp, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
[Kleber, Marcus] LURIC Study, D-79098 Freiburg, Germany.
[Kleber, Marcus; Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, D-69037 Heidelberg, Germany.
[Meijs, Matthijs F. L.; Zafarmand, M. Hadi; Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
[Molony, Cliona M.] Rosetta Inpharmat, Dept Genet, Seattle, WA 98109 USA.
[Murugesan, Gurunathan] Cleveland Clin, Dept Clin Pathol, Pathol & Lab Med Inst, Cleveland, OH 44106 USA.
[Musani, Solomon K.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Patel, Sanjey R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
[Pettinger, Mary; Reiner, Alex] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Price, Thomas S.] Kings Coll London, Med Res Council, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England.
[Rasheed, Asif; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Shah, Sonia] UCL, Univ Coll Genet Inst, London WC1E 6BT, England.
[Silbernagel, Guenther] Univ Tubingen, Div Endocrinol Diabetol Nephrol Vasc Dis & Clin C, Dept Internal Med, D-72074 Tubingen, Germany.
[Smith, Erin N.] Scripps Genom Med, La Jolla, CA 92037 USA.
[Spijkerman, Annemieke W. M.; van der A, Daphne L.] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Stanton, Alice] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Trip, Mieke] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[van der Harst, Pim; Verweij, Niek] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
[van der Harst, Pim; Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
[van Iperen, Erik P. A.] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[van Setten, Jessica; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[van Vliet-Ostaptchouk, Jana V.] Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 AV Groningen, Netherlands.
[van Vliet-Ostaptchouk, Jana V.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
[Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Zmuda, Joseph M.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.
[Altshuler, David; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[McCarthy, Mark] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
[Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA.
[Sever, Peter; Poulter, Neil] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London W2 1PG, England.
[Shields, Denis C.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA.
[Curtis, Sean P.; Saleheen, Danish] Merck Res Labs, Rahway, NJ 07065 USA.
[Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Casas, Juan P.] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Dorn, Gerald W., II; Watkins, Hugh] Washington Univ, Ctr Pharmacogenet, St Louis, MO 63110 USA.
[Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, John Radcliffe Hosp, Oxford OX3 9DU, England.
[FitzGerald, Garret A.] Univ Penn, Inst Translat Med & Therapeut, Sch Med, Philadelphia, PA 19146 USA.
[Hamsten, Anders] Karolinska Inst, Cardiovasc Genet Grp, Atherosclerosis Res Unit, Dept Med Solna, SE-17176 Stockholm, Sweden.
[Hingorani, Aroon D.] UCL, Ctr Clin Pharmacol, Dept Med, London WC1E 6JF, England.
[Huggins, Gordon S.] Tufts Med Ctr, Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA 02114 USA.
[Huggins, Gordon S.] Tufts Univ, Boston, MA 02114 USA.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany.
[Knowler, William C.] NIDDK, Phoenix, AZ 85104 USA.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.
[Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth Social & Prevent Med, Med Fac Mannheim, D-68167 Mannheim, Germany.
[Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8010 Graz, Austria.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Melander, Olle] Malmo Univ Hosp, Clin Res Ctr, SE-20502 Malmo, Sweden.
[Bielinski, Susan J.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN 55905 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22902 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Schadt, Eric E.] Sage Bionetworks, Seattle, WA 98109 USA.
[Silverstein, Roy] Case Western Reserve Univ, Dept Cell Biol, Lerner Res Inst,Dept Mol Med, Cleveland Clin Fdn,Cleveland Clin Lerner Coll Med, Cleveland, OH 44195 USA.
[Kottke-Marchant, Kandice] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
[de Bakker, Paul I. W.] Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp, Boston, MA 02115 USA.
[McCaffery, Jeanne] Brown Univ, Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA.
[McCaffery, Jeanne] Brown Univ, Warren Alpert Sch Med, Providence, RI 02906 USA.
[Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27106 USA.
[Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp, Div Human Genet, Abramson Res Ctr, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon; Keating, Brendan J.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
RP Saxena, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM rsaxena@chgr.mgh.harvard.edu; keatingb@email.chop.edu
RI Davey Smith, George/A-7407-2013; Price, Thomas/B-7372-2008; Thorand,
Barbara/B-5349-2014; Jarvik, Gail/N-6476-2014; Gaunt, Tom/O-3918-2014;
Onland-Moret, N. Charlotte/G-9185-2011; de Groot, Mark/A-9891-2012;
Hegele, Robert/G-3301-2011; Bielinski, Suzette/A-2238-2009; Burton,
Paul/H-7527-2016; Klungel, Olaf/I-9563-2016; Padmanabhan,
Sandosh/S-3963-2016; Verweij, Niek/A-4499-2017; Guo, Yiran/H-4120-2011;
Smith, Erin/E-5933-2011; Newhouse, Stephen/C-9330-2011; Wijmenga,
Cisca/D-2173-2009; Ferguson, Jane/C-7154-2011; Wolffenbuttel,
Bruce/A-8419-2011; Stanton, Alice/F-4697-2012; Altshuler,
David/A-4476-2009; de Bakker, Paul/B-8730-2009; Shah, Sonia/N-7547-2013;
Meisinger, Christine/B-5358-2014; Grobbee, Diederick/C-7651-2014
OI Lawlor, Debbie A/0000-0002-6793-2262; Pankow, James/0000-0001-7076-483X;
Kleber, Marcus/0000-0003-0663-7275; Gieger,
Christian/0000-0001-6986-9554; Wijmenga, Cisca/0000-0002-5635-1614;
Patel, Sanjay/0000-0002-9142-5172; Kumari, Meena/0000-0001-9716-1035;
Verweij, Niek/0000-0002-4303-7685; Meisinger,
Christa/0000-0002-9026-6544; Watkins, Hugh/0000-0002-5287-9016; van
Iperen, Erik/0000-0001-7107-3168; Mitchell, Braxton/0000-0003-4920-4744;
Davey Smith, George/0000-0002-1407-8314; Lanktree,
Matthew/0000-0002-5750-6286; Stanton, Alice/0000-0002-4961-165X; van
Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Kivimaki,
Mika/0000-0002-4699-5627; Talmud, Philippa/0000-0002-5560-1933; Johnson,
Toby/0000-0002-5998-3270; Padmanabhan, Sandosh/0000-0003-3869-5808;
Humphries, Stephen E/0000-0002-8221-6547; Price,
Thomas/0000-0001-7356-2109; Thorand, Barbara/0000-0002-8416-6440;
Jarvik, Gail/0000-0002-6710-8708; Gaunt, Tom/0000-0003-0924-3247; de
Groot, Mark/0000-0002-5764-5788; Bielinski, Suzette/0000-0002-2905-5430;
Guo, Yiran/0000-0002-6549-8589; Newhouse, Stephen/0000-0002-1843-9842;
Ferguson, Jane/0000-0001-6896-1025; Wolffenbuttel,
Bruce/0000-0001-9262-6921; Altshuler, David/0000-0002-7250-4107; de
Bakker, Paul/0000-0001-7735-7858; Shah, Sonia/0000-0001-5860-4526;
Grobbee, Diederick/0000-0003-4472-4468
FU National Heart, Lung, and Blood Institute; NIDDK NIH [DK089378];
Netherlands Organization for Scientific Research (NWO); Massachusetts
Institute of Technology [N01-HC-65226]
FX The CARe Consortium wishes to acknowledge the support of the National
Heart, Lung, and Blood Institute and the contributions of the research
institutions, study investigators, field staff, and study participants
in creating this resource for biomedical research. The following nine
parent studies have contributed parent study data, ancillary study data,
and DNA samples through the Broad Institute of Harvard University and
the Massachusetts Institute of Technology (N01-HC-65226) to create this
genotype/phenotype database for wide dissemination to the biomedical
research community: the Atherosclerosis Risk in Communities (ARIC)
study, the Cardiovascular Health Study (CHS), the Cleveland Family Study
(CFS), the Cooperative Study of Sickle Cell Disease (CSSCD), the
Coronary Artery Risk Development in Young Adults (CARDIA) study, the
Framingham Heart Study (FHS), the Jackson Heart Study OHS), the
Multi-Ethnic Study of Atherosclerosis (MESA), and the Sleep Heart Health
Study (SHHS). R.S. is partially supported by NIDDK NIH R21 (DK089378).
C.C.E is supported by a Rubicon grant from the Netherlands Organization
for Scientific Research (NWO). Additional acknowledgements for each
cohort are listed in the Supplemental Data. Also see the Supplemental
Data for conflict-of-interest disclosures for some of the authors.
NR 80
TC 127
Z9 129
U1 1
U2 30
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 9
PY 2012
VL 90
IS 3
BP 410
EP 425
DI 10.1016/j.ajhg.2011.12.022
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 911ZI
UT WOS:000301762800007
PM 22325160
ER
PT J
AU Lee, JM
Gillis, T
Mysore, JS
Ramos, EM
Myers, RH
Hayden, MR
Morrison, PJ
Nance, M
Ross, CA
Margolis, RL
Squitieri, F
Griguoli, A
Di Donato, S
Gomez-Tortosa, E
Ayuso, C
Suchowersky, O
Trent, RJ
McCusker, E
Novelletto, A
Frontali, M
Jones, R
Ashizawa, T
Frank, S
Saint-Hilaire, MH
Hersch, SM
Rosas, HD
Lucente, D
Harrison, MB
Zanko, A
Abramson, RK
Marder, K
Sequeiros, J
MacDonald, ME
Gusella, JF
AF Lee, Jong-Min
Gillis, Tammy
Mysore, Jayalakshmi Srinidhi
Ramos, Eliana Marisa
Myers, Richard H.
Hayden, Michael R.
Morrison, Patrick J.
Nance, Martha
Ross, Christopher A.
Margolis, Russell L.
Squitieri, Ferdinando
Griguoli, Annamaria
Di Donato, Stefano
Gomez-Tortosa, Estrella
Ayuso, Carmen
Suchowersky, Oksana
Trent, Ronald J.
McCusker, Elizabeth
Novelletto, Andrea
Frontali, Marina
Jones, Randi
Ashizawa, Tetsuo
Frank, Samuel
Saint-Hilaire, Marie-Helene
Hersch, Steven M.
Rosas, Herminia D.
Lucente, Diane
Harrison, Madaline B.
Zanko, Andrea
Abramson, Ruth K.
Marder, Karen
Sequeiros, Jorge
MacDonald, Marcy E.
Gusella, James F.
TI Common SNP-Based Haplotype Analysis of the 4p16.3 Huntington Disease
Gene Region
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID EXPANDED CAG REPEAT; AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; HD;
ASSOCIATION; EXPANSION; MODIFIER; LENGTH
AB Age at the onset of motor symptoms in Huntington disease (HD) is determined largely by the length of a GAG repeat expansion in HIT but is also influenced by other genetic factors. We tested whether common genetic variation near the mutation site is associated with differences in the distribution of expanded GAG alleles or age at the onset of motor symptoms. To define disease-associated single-nucleotide polymorphisms (SNPs), we compared 4p16.3 SNPs in HD subjects with population controls in a case:control strategy, which revealed that the strongest signals occurred at a great distance from the HD mutation as a result of "synthetic association" with SNP alleles that are of low frequency in population controls. Detailed analysis delineated a prominent ancestral haplotype that accounted for similar to 50% of HD chromosomes and extended to at least 938 kb on about half of these. Together, the seven most abundant haplotypes accounted for similar to 83% of HD chromosomes. Neither the extended shared haplotype nor the individual local HTT haplotypes were associated with altered GAG-repeat length distribution or residual age at the onset of motor symptoms, arguing against modification of these disease features by common cis-regulatory elements. Similarly, the 11 most frequent control haplotypes showed no trans-modifier effect on age at the onset of motor symptoms. Our results argue against common local regulatory variation as a factor influencing HD pathogenesis, suggesting that genetic modifiers be sought elsewhere in the genome. They also indicate that genome-wide association analysis with a small number of cases can be effective for regional localization of genetic defects, even when a founder effect accounts for only a fraction of the disorder.
C1 [Lee, Jong-Min; Gillis, Tammy; Mysore, Jayalakshmi Srinidhi; Ramos, Eliana Marisa; Lucente, Diane; MacDonald, Marcy E.; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Lee, Jong-Min; MacDonald, Marcy E.; Gusella, James F.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Ramos, Eliana Marisa; Sequeiros, Jorge] Univ Porto, UnIGENe, Inst Mol & Cell Biol, P-4150180 Oporto, Portugal.
[Myers, Richard H.; Frank, Samuel; Saint-Hilaire, Marie-Helene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Hayden, Michael R.] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada.
[Morrison, Patrick J.] Belfast Hlth & Social Care Trust, Reg Med Genet Ctr, Belfast BT9 7AB, Antrim, North Ireland.
[Morrison, Patrick J.] Univ Ulster, Coleraine BT52 1SA, Londonderry, North Ireland.
[Nance, Martha] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Ross, Christopher A.; Margolis, Russell L.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Squitieri, Ferdinando; Griguoli, Annamaria] Inst Ricovero & Cura Carattere Sci Neuromed, Neurogenet Unit, I-86077 Pozzilli, IS, Italy.
[Squitieri, Ferdinando; Griguoli, Annamaria] Inst Ricovero & Cura Carattere Sci Neuromed, Ctr Rare Dis, I-86077 Pozzilli, IS, Italy.
[Di Donato, Stefano] Fdn IRCCS, Ist Nazl Neurol C Besta, I-20133 Milan, Italy.
[Gomez-Tortosa, Estrella] Fdn Jimenez Diaz, Dept Neurol, E-28040 Madrid, Spain.
[Ayuso, Carmen] Fdn Jimenez Diaz, Dept Genet, IIS, CIBERER, E-28040 Madrid, Spain.
[Suchowersky, Oksana] Univ Alberta, Dept Med Neurol, Edmonton, AB T6G 2B7, Canada.
[Suchowersky, Oksana] Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2B7, Canada.
[Trent, Ronald J.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[McCusker, Elizabeth] Westmead Hosp, Dept Neurol, Sydney, NSW 2145, Australia.
[Novelletto, Andrea] Univ Tor Vergata, Dept Biol, I-00133 Rome, Italy.
[Frontali, Marina] CNR, Ist Farmacol Traslaz, I-00133 Rome, Italy.
[Jones, Randi] Emory Univ, Dept Neurol, Atlanta, GA 30329 USA.
[Ashizawa, Tetsuo] Univ Florida, Dept Neurol, Gainesville, FL 32610 USA.
[Hersch, Steven M.; Rosas, Herminia D.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Harrison, Madaline B.] Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA.
[Zanko, Andrea] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Abramson, Ruth K.] Univ S Carolina, Sch Med, Dept Neuropsychiat & Behav Sci, Columbia, SC 29209 USA.
[Marder, Karen] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA.
[Sequeiros, Jorge] Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4099003 Oporto, Portugal.
RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM gusella@helix.mgh.harvard.edu
RI Di Donato, Stefano/B-9717-2012; Ross, Christopher/H-8395-2013; Hayden,
Michael/D-8581-2011;
OI Hayden, Michael/0000-0001-5159-1419; Saint-Hilaire,
Marie-Helene/0000-0002-2355-5979; Sequeiros, Jorge/0000-0002-9846-1037;
Myers, Richard/0000-0002-8365-2674; Novelletto,
Andrea/0000-0002-1146-7680; Ayuso, Carmen/0000-0002-9242-7065;
Squitieri, Ferdinando /0000-0002-7397-1727
FU U.S. National Institutes of Health; National Heart, Lung, and Blood
Institute [R01 HL087676]; National Center for Research Resources [U54
RR020278]; National Institute of Neurological Disorders and Stroke
[NS16367, NS32765]; CHDI Foundation; Huntington's Disease Society of
America's Coalition for the Cure; Fundacao para a Ciencia e a Tecnologia
of Portugal [SFRH/BD/44335/2008]
FX We thank the HD research participants and their families, who made this
work possible; the Harvard Brain Tissue Resource Center; the COHORT
Study of the Huntington Study Group; and the Myocardial Infarction
Genetics Consortium (MIGen) study, which was funded by grants from the
U.S. National Institutes of Health and National Heart, Lung, and Blood
Institute's STAMPEED genomics research program (R01 HL087676) and the
National Center for Research Resources (U54 RR020278). We also thank
investigators anti contributors to the I-ID-MAPS study: Alexandra Durr,
Adam Rosenblatt, Luigi Frati, Susan Perlman, P. Michael Conneally, Mary
Lou Klimek, Melissa Diggin, Tiffany Hadzi, and Ayana Duckett. This work
was supported by grants from the National Institute of Neurological
Disorders and Stroke (NS16367) (Huntington's Disease Center Without
Walls) and NS32765, the CHDI Foundation, and the Huntington's Disease
Society of America's Coalition for the Cure. E.M.R. received a
scholarship from the Fundacao para a Ciencia e a Tecnologia of Portugal
(SFRH/BD/44335/2008).
NR 24
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Z9 19
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 MAR 9
PY 2012
VL 90
IS 3
BP 434
EP 444
DI 10.1016/j.ajhg.2012.01.005
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 911ZI
UT WOS:000301762800009
PM 22387017
ER
PT J
AU Riazuddin, SA
Parker, DS
McGlumphy, EJ
Oh, EC
Iliff, BW
Schmedt, T
Jurkunas, U
Schleif, R
Katsanis, N
Gottsch, JD
AF Riazuddin, S. Amer
Parker, David S.
McGlumphy, Elyse J.
Oh, Edwin C.
Iliff, Benjamin W.
Schmedt, Thore
Jurkunas, Ula
Schleif, Robert
Katsanis, Nicholas
Gottsch, John D.
TI Mutations in LOXHD1, a Recessive-Deafness Locus, Cause Dominant
Late-Onset Fuchs Corneal Dystrophy
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ENDOTHELIAL DYSTROPHY; MISSENSE MUTATIONS; PROTEIN; COL8A2; GENE;
COLLAGEN; LINKAGE
AB Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHDI mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes.
C1 [Riazuddin, S. Amer; McGlumphy, Elyse J.; Iliff, Benjamin W.; Gottsch, John D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Parker, David S.; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Dept Cell Biol, Durham, NC 27710 USA.
[Schmedt, Thore; Jurkunas, Ula] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Schleif, Robert] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
RP Gottsch, JD (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
EM igottsch@jhmi.edu
RI Katsanis, Nicholas/E-1837-2012;
OI Katsanis, Nicholas/0000-0002-2480-0171
FU National Eye Institute [R01 EY016835]; Kwok Research Fund
FX We thank all family members for their enthusiastic participation in this
study. None of the contributing authors have any financial interest
related to this work. We are thankful to Ulrich Mueller for providing
the Loxhd1 construct. This study was supported in part by the National
Eye Institute grant R01 EY016835 (J.D.G.) and the Kwok Research Fund
(J.D.G.). J.D.G. is a distinguished Margaret C. Mosher Professor of
Ophthalmology. N.K. is a distinguished Brumley Professor.
NR 27
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U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 9
PY 2012
VL 90
IS 3
BP 533
EP 539
DI 10.1016/j.ajhg.2012.01.013
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 911ZI
UT WOS:000301762800020
PM 22341973
ER
PT J
AU Shi, S
Deng, YZ
Zhao, JS
Ji, XD
Shi, J
Feng, YX
Li, G
Li, JJ
Zhu, D
Koeffler, HP
Zhao, Y
Xie, D
AF Shi, Shuo
Deng, Yue-Zhen
Zhao, Jiang-Sha
Ji, Xiao-Dan
Shi, Jun
Feng, Yu-Xiong
Li, Guo
Li, Jing-Jing
Zhu, Di
Koeffler, H. Phillip
Zhao, Yun
Xie, Dong
TI RACK1 Promotes Non-small-cell Lung Cancer Tumorigenicity through
Activating Sonic Hedgehog Signaling Pathway
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; DEVELOPMENTAL PATHWAYS; PATCHED-GLI;
CARCINOMA; WNT; PHOSPHORYLATION; EXPRESSION; DROSOPHILA; TRANSDUCTION;
REQUIREMENT
AB Non-small-cell lung cancer (NSCLC) is a deadly disease due to lack of effective diagnosis biomarker and therapeutic target. Much effort has been made in defining gene defects in NSCLC, but its full molecular pathogenesis remains unexplored. Here, we found RACK1 (receptor of activated kinase 1) was elevated in most NSCLC, and its expression level correlated with key pathological characteristics including tumor differentiation, stage, and metastasis. In addition, RACK1 activated sonic hedgehog signaling pathway by interacting with and activating Smoothened to mediate Gli1-dependent transcription in NSCLC cells. And silencing RACK1 dramatically inhibited in vivo tumor growth and metastasis by blocking the sonic hedgehog signaling pathway. These results suggest that RACK1 represents a new promising diagnosis biomarker and therapeutic target for NSCLC.
C1 [Shi, Shuo; Deng, Yue-Zhen; Zhao, Jiang-Sha; Ji, Xiao-Dan; Feng, Yu-Xiong; Li, Guo; Li, Jing-Jing; Xie, Dong] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China.
[Shi, Shuo; Deng, Yue-Zhen; Zhao, Jiang-Sha; Ji, Xiao-Dan; Feng, Yu-Xiong; Li, Guo; Li, Jing-Jing; Xie, Dong] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China.
[Shi, Jun] Second Peoples Hosp Zhuhai, Zhuhai 519000, Guangdong, Peoples R China.
[Zhu, Di] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Koeffler, H. Phillip] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 119077, Singapore.
[Zhao, Yun] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Mol Cell Biol, Shanghai 200031, Peoples R China.
RP Xie, D (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Mol Oncol Lab, 294 Tai Yuan Rd, Shanghai 200031, Peoples R China.
EM dxie@sibs.ac.cn
FU National Basic Research Program of China [2010CB912102]; Ministry of
Science and Technology [2012ZX10002009-017]; National Natural Science
Foundation of China [30930023, 90813023, Y239X31111, 81021002, 31100551,
81070325]; National Natural Science Funds for Distinguished Young
Scholar [30725010]; Nature Science Foundation of China-Guangdong
[U0932001]
FX This work was supported by National Basic Research Program of China
Grant 2010CB912102, Ministry of Science and Technology Key Program
2012ZX10002009-017, National Natural Science Foundation of China
30930023, 90813023, Y239X31111, 81021002, 31100551, 81021002, and
81070325, National Natural Science Funds for Distinguished Young Scholar
Grant 30725010, and Nature Science Foundation of China-Guangdong Joint
Fund U0932001.
NR 54
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U1 0
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 9
PY 2012
VL 287
IS 11
BP 7845
EP 7858
DI 10.1074/jbc.M111.315416
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 906MN
UT WOS:000301349400002
PM 22262830
ER
PT J
AU Kim, WJ
Rivera, MN
Coffman, EJ
Haber, DA
AF Kim, Woo Jae
Rivera, Miguel N.
Coffman, Erik J.
Haber, Daniel A.
TI The WTX Tumor Suppressor Enhances p53 Acetylation by CBP/p300
SO MOLECULAR CELL
LA English
DT Article
ID WILMS-TUMOR; TRANSCRIPTIONAL COACTIVATORS; FUNCTIONAL INTERACTION; SUMO
MODIFICATION; GENE-MUTATIONS; CELL-GROWTH; DNA-BINDING; IN-VITRO;
ADENOVIRUS; PROTEIN
AB WTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in beta-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53, and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA-binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 373/382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell-cycle arrest, apoptosis, and p53 target-gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300.
C1 [Kim, Woo Jae; Rivera, Miguel N.; Coffman, Erik J.; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
[Rivera, Miguel N.; Coffman, Erik J.] Harvard Univ, Dept Pathol, Sch Med, Charlestown, MA 02129 USA.
[Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
EM haber@helix.mgh.harvard.edu
FU NIH [5R37CA058596, P50CA101942, T32CA009216]; NIDDK; Burroughs Wellcome
Fund; HHMI
FX This work was supported by NIH 5R37CA058596, P50CA101942, HHMI (D.A.H.);
NIH T32CA009216 (W.J.K.); NIDDK; the Burroughs Wellcome Fund; and HHMI
(M.N.R.). The authors would like to thank Nick Dyson, Shyamala
Maheswaran, and Ho-June Lee for helpful discussions and critical
comments. We are grateful to Anders Naar and Joshua Black for providing
reagents.
NR 55
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U1 3
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 MAR 9
PY 2012
VL 45
IS 5
BP 587
EP 597
DI 10.1016/j.molcel.2011.12.025
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 908BN
UT WOS:000301465500004
PM 22285752
ER
PT J
AU Kriesel, JD
Hobbs, MR
Jones, BB
Milash, B
Nagra, RM
Fischer, KF
AF Kriesel, John D.
Hobbs, Maurine R.
Jones, Brandt B.
Milash, Brett
Nagra, Rashed M.
Fischer, Kael F.
TI Deep Sequencing for the Detection of Virus-Like Sequences in the Brains
of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain
SO PLOS ONE
LA English
DT Article
ID HEPATITIS-G-VIRUS; C/HEPATITIS-G VIRUS; A-E HEPATITIS;
MOLECULAR-CLONING; BLOOD-DONORS; INFECTION; PREVALENCE; DISEASE; GENOME;
TRANSMISSION
AB Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis G is a flavivirus that is found in the serum of 1-2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a "hit''. Normalized MS specimen hit rates for each viral taxon were compared to the distribution of hits in the normal controls. Seventeen MS and 11 control brain extracts were sequenced, yielding 4-10 million sequences ("reads'') each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here.
C1 [Kriesel, John D.; Hobbs, Maurine R.; Jones, Brandt B.] Univ Utah, Dept Internal Med, Div Infect Dis, Salt Lake City, UT 84112 USA.
[Milash, Brett] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Nagra, Rashed M.] W Los Angeles VA Med Ctr, Human Brain & Spinal Fluid Resource Ctr, Los Angeles, CA USA.
[Fischer, Kael F.] ARUP Labs, Salt Lake City, UT USA.
[Fischer, Kael F.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
RP Kriesel, JD (reprint author), Univ Utah, Dept Internal Med, Div Infect Dis, Salt Lake City, UT 84112 USA.
EM John.Kriesel@hsc.utah.edu
RI Fischer, Kael/F-7756-2015
OI Fischer, Kael/0000-0002-7547-330X
FU National Multiple Sclerosis Society
FX This investigation was supported by grants from the National Multiple
Sclerosis Society. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 47
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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 MAR 8
PY 2012
VL 7
IS 3
AR e31886
DI 10.1371/journal.pone.0031886
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KT
UT WOS:000303062000003
PM 22412845
ER
PT J
AU Uthamalingam, S
Sidhu, MS
Gurm, GS
Yasuda, T
Francis, S
Scott, J
Gregory, SA
AF Uthamalingam, Shanmugam
Sidhu, Manavjot S.
Gurm, Gagandeep S.
Yasuda, Tsunehiro
Francis, Sanjeev
Scott, James
Gregory, Shawn A.
TI Male breast uptake of 99m-Tc sestamibi in myocardial perfusion imaging
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Letter
DE Male breast; 99m-Tc sestamibi; Myocardial perfusion imaging
ID NONCARDIAC FINDINGS; CANCER
C1 [Uthamalingam, Shanmugam; Sidhu, Manavjot S.; Francis, Sanjeev] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Uthamalingam, Shanmugam; Sidhu, Manavjot S.; Gurm, Gagandeep S.; Yasuda, Tsunehiro; Francis, Sanjeev; Gregory, Shawn A.] Harvard Univ, Sch Med, Boston, MA USA.
[Gurm, Gagandeep S.; Yasuda, Tsunehiro; Francis, Sanjeev; Gregory, Shawn A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Yasuda, Tsunehiro; Scott, James] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA.
RP Sidhu, MS (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM msidhu1@partners.org
NR 9
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD MAR 8
PY 2012
VL 155
IS 2
BP E22
EP E23
DI 10.1016/j.ijcard.2011.06.080
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 891RG
UT WOS:000300233700002
PM 21741712
ER
PT J
AU Graff, J
Rei, D
Guan, JS
Wang, WY
Seo, J
Hennig, KM
Nieland, TJF
Fass, DM
Kao, PF
Kahn, M
Su, SC
Samiei, A
Joseph, N
Haggarty, SJ
Delalle, I
Tsai, LH
AF Graeff, Johannes
Rei, Damien
Guan, Ji-Song
Wang, Wen-Yuan
Seo, Jinsoo
Hennig, Krista M.
Nieland, Thomas J. F.
Fass, Daniel M.
Kao, Patricia F.
Kahn, Martin
Su, Susan C.
Samiei, Alireza
Joseph, Nadine
Haggarty, Stephen J.
Delalle, Ivana
Tsai, Li-Huei
TI An epigenetic blockade of cognitive functions in the neurodegenerating
brain
SO NATURE
LA English
DT Article
ID LONG-TERM-MEMORY; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY;
CLINICAL-IMPLICATIONS; TRANSGENIC MICE; REMOTE MEMORIES; CDK5;
PHOSPHORYLATION; EXPRESSION; CHROMATIN
AB Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer's disease(1). The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge(2). Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer's-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer's disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade.
C1 [Graeff, Johannes; Rei, Damien; Guan, Ji-Song; Wang, Wen-Yuan; Seo, Jinsoo; Kahn, Martin; Su, Susan C.; Samiei, Alireza; Joseph, Nadine; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
[Graeff, Johannes; Rei, Damien; Guan, Ji-Song; Wang, Wen-Yuan; Seo, Jinsoo; Su, Susan C.; Joseph, Nadine; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
[Graeff, Johannes; Guan, Ji-Song; Wang, Wen-Yuan; Hennig, Krista M.; Nieland, Thomas J. F.; Fass, Daniel M.; Joseph, Nadine; Haggarty, Stephen J.; Tsai, Li-Huei] Broad Inst Harvard Univ & Massachusetts Inst Tech, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Hennig, Krista M.; Fass, Daniel M.; Haggarty, Stephen J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kao, Patricia F.; Delalle, Ivana] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA.
RP Tsai, LH (reprint author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA.
EM lhtsai@mit.edu
OI Graff, Johannes/0000-0002-3219-3578; Guan, Ji-Song /0000-0001-5219-0289;
Haggarty, Stephen J./0000-0002-7872-168X
FU Stanley Medical Research Institution; National Institutes of
Health/National Institute on Drug Abuse [RO1DA028301]; National
Institutes of Health/National Institute of Neurological Disorders and
Stroke [RO1NS078839]; Bard Richmond fellowship; Swiss National Science
Foundation; Simons Foundation; Theodor und Ida Herzog-Egli foundation
FX We thank A. Mungenast, S. Jemielity, R. Madabushi, F. Calderon de Anda
and M. Horn for reading the manuscript, A. M. for manuscript editing, M.
Eichler for mouse colony maintenance, K. Fitch for sectioning the human
brain samples and M. H. for quantification of Fig. 2a. This work was
partly supported by the Stanley Medical Research Institution (to S.J.H.
and L.-H.T.), National Institutes of Health/National Institute on Drug
Abuse (RO1DA028301, to S.J.H.) and National Institutes of
Health/National Institute of Neurological Disorders and Stroke
(RO1NS078839, to L.-H.T.). J.G. was supported by a Bard Richmond
fellowship and by the Swiss National Science Foundation, W.Y.W. by the
Simons Foundation and M.K. by the Theodor und Ida Herzog-Egli
foundation. L.-H.T. is an investigator of the Howard Hughes Medical
Institute.
NR 38
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Z9 279
U1 8
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 222
EP U123
DI 10.1038/nature10849
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900041
PM 22388814
ER
PT J
AU Jiang, XD
Clark, RA
Liu, LZ
Wagers, AJ
Fuhlbrigge, RC
Kupper, TS
AF Jiang, Xiaodong
Clark, Rachael A.
Liu, Luzheng
Wagers, Amy J.
Fuhlbrigge, Robert C.
Kupper, Thomas S.
TI Skin infection generates non-migratory memory CD8(+) T-RM cells
providing global skin immunity
SO NATURE
LA English
DT Article
ID DERMAL MICROVESSELS; NONLYMPHOID TISSUE; VIRAL-INFECTION; MIGRATION;
TRAFFICKING; EFFECTOR; RESIDENT; HETEROGENEITY; IMMUNIZATION; ACTIVATION
AB Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (T-RM) cells has been proposed(1-5). Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8(+) skin T-RM cells that reside within the entire skin. These skin T-RM cells are potent effector cells, and are superior to circulating central memory T (T-CM) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8(+) T cells are rapidly recruited to skin after acute VACV infection. CD8(+) T-cell recruitment to skin is independent of CD4(+) T cells and interferon-c, but requires the expression of E-and P-selectin ligands by CD8(+) T cells. Using parabiotic mice, we further show that circulating CD8(+) T-CM and CD8(+) skin T-RM cells are both generated after skin infection; however, CD8(+) T-CM cells recirculate between blood and lymph nodes whereas T-RM cells remain in the skin. Cutaneous CD8(+) T-RM cells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8(+) skin T-RM cells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating T-CM but no skin T-RM cells showed greatly impaired viral clearance, indicating that T-RM cells provide superior protection. Finally, we show that T-RM cells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective T-RM cells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms.
C1 [Jiang, Xiaodong; Clark, Rachael A.; Liu, Luzheng; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Jiang, Xiaodong; Clark, Rachael A.; Liu, Luzheng; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA.
[Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Kupper, TS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
EM tkupper@partners.org
FU National Institutes of Health (NIH) [R01AI041707, R37AI025082,
TR01AI097128]
FX We thank T. Tian, R. Purwar and Q. Zhan for technical assistance. We
thank J. J. Campbell for discussion of the project. This work was
supported by National Institutes of Health (NIH) grants R01AI041707,
R37AI025082 and TR01AI097128 to T.S.K.
NR 30
TC 241
Z9 245
U1 2
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 227
EP U129
DI 10.1038/nature10851
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900042
PM 22388819
ER
PT J
AU Aaron, HJ
Frakt, AB
AF Aaron, Henry J.
Frakt, Austin B.
TI Why Now Is Not the Time for Premium Support
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Aaron, Henry J.] Brookings Inst, Washington, DC 20036 USA.
[Frakt, Austin B.] Boston Univ, Sch Med, Dept Vet Affairs, VA Boston Healthcare Syst, Boston, MA 02118 USA.
[Frakt, Austin B.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
RP Aaron, HJ (reprint author), Brookings Inst, Washington, DC 20036 USA.
NR 5
TC 8
Z9 8
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 8
PY 2012
VL 366
IS 10
BP 877
EP 879
DI 10.1056/NEJMp1200448
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CY
UT WOS:000301172500003
PM 22276779
ER
PT J
AU Whyte, MP
Greenberg, CR
Salman, NJ
Bober, MB
McAlister, WH
Wenkert, D
Van Sickle, BJ
Simmons, JH
Edgar, TS
Bauer, ML
Hamdan, MA
Bishop, N
Lutz, RE
McGinn, M
Craig, S
Moore, JN
Taylor, JW
Cleveland, RH
Cranley, WR
Lim, R
Thacher, TD
Mayhew, JE
Downs, M
Millan, JL
Skrinar, AM
Crine, P
Landy, H
AF Whyte, Michael P.
Greenberg, Cheryl R.
Salman, Nada J.
Bober, Michael B.
McAlister, William H.
Wenkert, Deborah
Van Sickle, Bradley J.
Simmons, Jill H.
Edgar, Terence S.
Bauer, Martin L.
Hamdan, Mohamed A.
Bishop, Nick
Lutz, Richard E.
McGinn, Mairead
Craig, Stanley
Moore, Jean N.
Taylor, John W.
Cleveland, Robert H.
Cranley, William R.
Lim, Ruth
Thacher, Tom D.
Mayhew, Jill E.
Downs, Matthew
Millan, Jose Luis
Skrinar, Alison M.
Crine, Philippe
Landy, Hal
TI Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID NONSPECIFIC ALKALINE-PHOSPHATASE; INFANTILE HYPOPHOSPHATASIA; MURINE
HYPOPHOSPHATASIA; INTRAVENOUS-INFUSION; BONE; DISEASE; GENE;
PYRIDOXAL-5'-PHOSPHATE; TRANSPLANTATION; MINERALIZATION
AB BACKGROUND
Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice.
METHODS
We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040.
RESULTS
Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment.
CONCLUSIONS
ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.)
C1 [Whyte, Michael P.; Wenkert, Deborah] Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, St Louis, MO 63131 USA.
[Whyte, Michael P.] Washington Univ, Sch Med, Div Bone & Mineral Dis, Barnes Jewish Hosp, St Louis, MO 63130 USA.
[McAlister, William H.] Washington Univ, Sch Med, St Louis Childrens Hosp, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA.
[Greenberg, Cheryl R.] Univ Manitoba, Winnipeg, MB, Canada.
[Greenberg, Cheryl R.] Winnipeg Reg Hlth Author, Winnipeg, MB, Canada.
[Salman, Nada J.; Hamdan, Mohamed A.] Tawam Hosp, Al Ain, U Arab Emirates.
[Bober, Michael B.] Alfred I Dupont Hosp Children, Wilmington, DE USA.
[Van Sickle, Bradley J.; Simmons, Jill H.] Vanderbilt Childrens Hosp, Nashville, TN USA.
[Edgar, Terence S.; Taylor, John W.] Prevea Hlth Clin, Green Bay, WI USA.
[Taylor, John W.] St Vincents Hosp, Green Bay, WI USA.
[Bauer, Martin L.] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA.
[Bishop, Nick] Sheffield Childrens Hosp, Sheffield, S Yorkshire, England.
[McGinn, Mairead; Craig, Stanley] Royal Belfast Hosp Sick Children, Belfast, Antrim, North Ireland.
[Lutz, Richard E.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Moore, Jean N.] St Johns Hosp, Springfield, MO USA.
[Cleveland, Robert H.] Childrens Hosp, Boston, MA 02115 USA.
[Cranley, William R.] Boston Med Ctr, Boston, MA USA.
[Lim, Ruth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Thacher, Tom D.] Mayo Clin, Rochester, MN USA.
[Mayhew, Jill E.; Skrinar, Alison M.; Crine, Philippe; Landy, Hal] Enobia Pharma, Montreal, PQ, Canada.
[Downs, Matthew] Stat Collaborat, Washington, DC USA.
[Millan, Jose Luis] Sanford Burnham Med Res Inst, La Jolla, CA USA.
RP Whyte, MP (reprint author), Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, 2001 S Lindbergh Blvd, St Louis, MO 63131 USA.
EM mwhyte@shrinenet.org
OI Bober, Michael/0000-0002-6178-1264
FU Enobia Pharma Hospital for Children; Shriners Hospital for Children
FX Supported by Enobia Pharma and Shriners Hospitals for Children.
NR 40
TC 118
Z9 122
U1 4
U2 25
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 8
PY 2012
VL 366
IS 10
BP 904
EP 913
DI 10.1056/NEJMoa1106173
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CY
UT WOS:000301172500007
PM 22397652
ER
PT J
AU Colao, A
Petersenn, S
Newell-Price, J
Findling, JW
Gu, F
Maldonado, M
Schoenherr, U
Mills, D
Salgado, LR
Biller, BMK
AF Colao, Annamaria
Petersenn, Stephan
Newell-Price, John
Findling, James W.
Gu, Feng
Maldonado, Mario
Schoenherr, Ulrike
Mills, David
Salgado, Luiz Roberto
Biller, Beverly M. K.
CA Pasireotide B2305 Study Grp
TI A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CONSENSUS STATEMENT; CABERGOLINE; SOM230; SECRETION; ADENOMAS; RELEASE
AB BACKGROUND
Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5.
METHODS
In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 mu g (82 patients) or 900 mu g (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 mu g twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12.
RESULTS
Twelve of the 82 patients in the 600-mu g group and 21 of the 80 patients in the 900-mu g group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose- lowering medication was initiated in 74 of 162 patients.
CONCLUSIONS
The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropinsecreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.)
C1 [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Neuroendocrine Clin Ctr, Boston, MA 02459 USA.
[Colao, Annamaria] Univ Naples Federico 2, Endocrinol Sect, Dept Mol & Clin Endocrinol & Oncol, Naples, Italy.
[Petersenn, Stephan] ENDOC Ctr Endocrine Tumors, Hamburg, Germany.
[Petersenn, Stephan] Univ Duisburg Essen, Fac Med, Essen, Germany.
[Newell-Price, John] Univ Sheffield, Dept Human Metab, Sheffield, S Yorkshire, England.
[Findling, James W.] Med Coll Wisconsin, Div Endocrinol Metab & Clin Nutr, Milwaukee, WI 53226 USA.
[Gu, Feng] Beijing Union Med Coll Hosp, Minist Hlth, Key Lab Endocrinol, Dept Endocrinol, Beijing, Peoples R China.
[Maldonado, Mario; Schoenherr, Ulrike; Mills, David] Novartis Pharmaceut, Oncol Business Unit, Clin Dev, Basel, Switzerland.
[Salgado, Luiz Roberto] Univ Sao Paulo, Sch Med, Hosp Clin, Div Gen Internal Med, Sao Paulo, Brazil.
RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Neuroendocrine Clin Ctr, 55 Fruit St,Bulfinch 457B, Boston, MA 02459 USA.
EM bbiller@partners.org
RI Webb, Susan/C-7294-2008; IBIS, ENDOCRINAS/P-3831-2015;
OI Brue, Thierry/0000-0001-8482-6691; Carvalho, Davide/0000-0002-3156-3741
FU Novartis Pharma
FX Supported by Novartis Pharma.
NR 20
TC 213
Z9 224
U1 4
U2 24
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 8
PY 2012
VL 366
IS 10
BP 914
EP 924
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CY
UT WOS:000301172500008
PM 22397653
ER
PT J
AU David, WS
Chad, DA
Kambadakone, A
Hedley-Whyte, ET
AF David, William S.
Chad, David A.
Kambadakone, Avinash
Hedley-Whyte, E. Tessa
TI Case 7-2012: A 79-Year-Old Man with Pain and Weakness in the Legs
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MEDIATED NECROTIZING MYOPATHY; 000 STATIN USERS; THERAPY;
RHABDOMYOLYSIS; ROSUVASTATIN; SAFETY
C1 [David, William S.; Chad, David A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Kambadakone, Avinash] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[David, William S.; Chad, David A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Kambadakone, Avinash] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP David, WS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 12
TC 2
Z9 3
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 8
PY 2012
VL 366
IS 10
BP 944
EP 954
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CY
UT WOS:000301172500013
PM 22397657
ER
PT J
AU Koreth, J
Ritz, J
Soiffer, RJ
AF Koreth, John
Ritz, Jerome
Soiffer, Robert J.
TI Regulatory T Cells in Graft-versus-Host Disease REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Koreth, John; Ritz, Jerome; Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Koreth, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM john_koreth@dfci.harvard.edu
NR 4
TC 0
Z9 0
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 MAR 8
PY 2012
VL 366
IS 10
BP 963
EP 963
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CY
UT WOS:000301172500019
ER
PT J
AU Roberts, DJ
Celi, AC
Riley, LE
Onderdonk, AB
Boyd, TK
Johnson, LC
Lieberman, E
AF Roberts, Drucilla J.
Celi, Ann C.
Riley, Laura E.
Onderdonk, Andrew B.
Boyd, Theonia K.
Johnson, Lise Carolyn
Lieberman, Ellice
TI Acute Histologic Chorioamnionitis at Term: Nearly Always Noninfectious
SO PLOS ONE
LA English
DT Article
ID ACUTE PLACENTAL INFLAMMATION; RECEPTOR ANTAGONIST; EPIDURAL ANALGESIA;
INFECTION; LABOR; PATTERNS; DELIVERY; FEVER; BIRTH; CYTOKINES
AB Background: The link between histologic acute chorioamnionitis and infection is well established in preterm deliveries, but less well-studied in term pregnancies, where infection is much less common.
Methodology/Principal Findings: We conducted a secondary analysis among 195 low-risk women with term pregnancies enrolled in a randomized trial. Histologic and microbiologic evaluation of placentas included anaerobic and aerobic cultures (including mycoplasma/ureaplasma species) as well as PCR. Infection was defined as >= 1,000 cfu of a single known pathogen or a >= 2 log difference in counts for a known pathogen versus other organisms in a mixed culture. Placental membranes were scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis). Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas (67/195), but infection was present in only 4% (8/195). Histologic chorioamnionitis was strongly associated with intrapartum fever >38 degrees C [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n = 36) of women. Most febrile women [92% (33/36)] had received epidural for pain relief, though the association with fever was present with and without epidural. The association remained significant in a logistic regression controlling for potential confounders (OR = 5.8, 95% CI = 2.2, 15.0). Histologic chorioamnionitis was also associated with elevated serum levels of interleukin-8 (median = 1.3 pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P = 0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as higher admission WBC counts (mean = 12,000cells/mm(3) no chorioamnionitis, 13,400cells/mm(3) Grade 1, 15,700cells/mm(3) Grade 2, P = 0.0005).
Conclusion/Significance: Our results suggest histologic chorioamnionitis at term most often results from a noninfectious inflammatory process. It was strongly associated with fever, most of which was related to epidural used for pain relief. A more 'activated' maternal immune system at admission was also associated with histologic chorioamnionitis.
C1 [Roberts, Drucilla J.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Celi, Ann C.] Harvard Univ, Brigham & Womens Hosp, Div Gen Med, Sch Med, Boston, MA 02115 USA.
[Riley, Laura E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA.
[Onderdonk, Andrew B.] Harvard Univ, Brigham & Womens Hosp, Clin Microbiol Lab, Sch Med, Boston, MA 02115 USA.
[Boyd, Theonia K.] Harvard Univ, Childrens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA.
[Lieberman, Ellice] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Sch Med, Boston, MA 02115 USA.
[Lieberman, Ellice] Harvard Univ, Brigham & Womens Hosp, Dept Newborn Med, Sch Med, Boston, MA 02115 USA.
RP Roberts, DJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM elieberman@partners.org
FU Maternal Child Health Bureau, Health Resources and Services
Administration [R40 MC00248]; National Heart, Lung, and Blood Institute
[RO1HL081663]
FX This study was funded by the Maternal Child Health Bureau, Health
Resources and Services Administration (R40 MC00248). ACC's work on the
current manuscript was in part supported by National Heart, Lung, and
Blood Institute reentry award RO1HL081663. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 36
TC 34
Z9 34
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 7
PY 2012
VL 7
IS 3
AR e31819
DI 10.1371/journal.pone.0031819
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KK
UT WOS:000303060800005
PM 22412842
ER
PT J
AU Lin, LY
Tiemann, KM
Li, Y
Pinkner, JS
Walker, JN
Hultgren, SJ
Hunstad, DA
Wooley, KL
AF Lin, Lily Yun
Tiemann, Kristin M.
Li, Yali
Pinkner, Jerome S.
Walker, Jennifer N.
Hultgren, Scott J.
Hunstad, David A.
Wooley, Karen L.
TI Synthetic Polymer Nanoparticles Conjugated with FimH(A) from E. coli
Pili to Emulate the Bacterial Mode of Epithelial Internalization
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID UROPATHOGENIC ESCHERICHIA-COLI; URINARY-TRACT-INFECTION; UROTHELIAL
RECEPTOR; UROPLAKIN-IA; ADHESIN FIMH; EPIDEMIOLOGY; BLADDER;
VACCINATION; PARTICLE; BINDING
AB Amphiphilic block copolymer nanoparticles are conjugated with uropathogenic Escherichia coli type 1 pilus adhesin FimH(A) through amidation chemistry to enable bladder epithelial cell binding and internalization of the nanoparticles in vitro.
C1 [Tiemann, Kristin M.; Walker, Jennifer N.; Hunstad, David A.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Pinkner, Jerome S.; Hultgren, Scott J.; Hunstad, David A.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Pinkner, Jerome S.; Hultgren, Scott J.; Hunstad, David A.] Washington Univ, Sch Med, Ctr Womens Infect Dis Res, St Louis, MO 63110 USA.
[Lin, Lily Yun; Wooley, Karen L.] Texas A&M Univ, Dept Chem & Chem Engn, College Stn, TX 77842 USA.
[Li, Yali] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA.
RP Hunstad, DA (reprint author), Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
EM dhunstad@wusth.edu; wooley@chem.tamu.edu
RI Wooley, Karen/D-4399-2015;
OI Wooley, Karen/0000-0003-4086-384X; Hunstad, David/0000-0002-9848-0975
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health [R01-DK082546]; March of Dimes
[5-FY09-105]; Welch Foundation [A-0001]
FX We thank W. Beatty for technical imaging expertise. This project has
been funded by the National Institute of Diabetes and Digestive and
Kidney Diseases of the National Institutes of Health (R01-DK082546), by
a March of Dimes Basil O'Connor Award (5-FY09-105), and by the Welch
Foundation through the W. T. Doherty-Welch Chair in Chemistry, grant no.
A-0001.
NR 30
TC 3
Z9 3
U1 1
U2 18
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 MAR 7
PY 2012
VL 134
IS 9
BP 3938
EP 3941
DI 10.1021/ja2091917
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 909GL
UT WOS:000301550800002
PM 22360307
ER
PT J
AU Pihlajamaki, J
Lerin, C
Kaminska, D
Venesmaa, S
Itkonen, P
Boes, T
Floss, T
Schroeder, J
Dearie, F
Crunkhorn, S
Burak, F
Jimenez-Chillaron, JC
Kuulasmaa, T
Miettinen, P
Park, PJ
Nasser, I
Zhao, ZW
Zhang, ZY
Xu, Y
Wurst, W
Ren, HM
Morris, AJ
Stamm, S
Goldfine, AB
Laakso, M
Patti, ME
AF Pihlajamaeki, Jussi
Lerin, Carles
Kaminska, Dorota
Venesmaa, Sari
Itkonen, Paula
Boes, Tanner
Floss, Thomas
Schroeder, Joshua
Dearie, Farrell
Crunkhorn, Sarah
Burak, Furkan
Jimenez-Chillaron, Josep C.
Kuulasmaa, Tiina
Miettinen, Pekka
Park, Peter J.
Nasser, Imad
Zhao, Zhenwen
Zhang, Zhaiyi
Xu, Yan
Wurst, Wolfgang
Ren, Hongmei
Morris, Andrew J.
Stamm, Stefan
Goldfine, Allison B.
Laakso, Markku
Patti, Mary Elizabeth
TI SFRS10-A Splicing Factor Gene Reduced in Human Obesity? Response
SO CELL METABOLISM
LA English
DT Letter
ID EXPRESSION
C1 [Pihlajamaeki, Jussi; Lerin, Carles; Boes, Tanner; Schroeder, Joshua; Dearie, Farrell; Crunkhorn, Sarah; Burak, Furkan; Jimenez-Chillaron, Josep C.; Goldfine, Allison B.; Patti, Mary Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Park, Peter J.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02215 USA.
[Nasser, Imad] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Pihlajamaeki, Jussi; Venesmaa, Sari; Itkonen, Paula; Kuulasmaa, Tiina; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70211, Finland.
[Pihlajamaeki, Jussi; Kaminska, Dorota] Univ Eastern Finland, Dept Clin Nutr, Kuopio 70211, Finland.
[Miettinen, Pekka] Univ Eastern Finland, Dept Surg, Kuopio 70211, Finland.
[Lerin, Carles] IDIBAPS CIBERDEM, Diabet & Obes Lab, Barcelona 08036, Spain.
[Floss, Thomas; Wurst, Wolfgang] Tech Univ Munich, Inst Entwicklungsgenetik, Helmholtz Zentrum Munchen, D-85764 Munich, Neuherberg, Germany.
[Zhao, Zhenwen; Xu, Yan] Indiana Univ, Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA.
[Zhang, Zhaiyi; Ren, Hongmei; Morris, Andrew J.; Stamm, Stefan] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA.
[Wurst, Wolfgang] MPI Psychiat, D-80804 Munich, Germany.
[Wurst, Wolfgang] Tech Univ Weihenstephan, Lehrstuhl Entwicklungsgenetik, Helmholtz Zentrum Munchen, D-80336 Munich, Germany.
[Wurst, Wolfgang] LMU, Adolf Butenandt Inst, DZNE Site Munich, D-80336 Munich, Germany.
RP Patti, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
EM mary.elizabeth.patti@joslin.harvard.edu
FU NIDDK NIH HHS [P30 DK036836, R01 DK062948]
NR 7
TC 2
Z9 2
U1 0
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD MAR 7
PY 2012
VL 15
IS 3
BP 267
EP 269
DI 10.1016/j.cmet.2012.02.005
PG 3
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 911EZ
UT WOS:000301701400002
PM 25960695
ER
PT J
AU Ohno, H
Shinoda, K
Spiegelman, BM
Kajimura, S
AF Ohno, Haruya
Shinoda, Kosaku
Spiegelman, Bruce M.
Kajimura, Shingo
TI PPAR gamma agonists Induce a White-to-Brown Fat Conversion through
Stabilization of PRDM16 Protein
SO CELL METABOLISM
LA English
DT Article
ID ACTIVATED-RECEPTOR-GAMMA; ADIPOSE-TISSUE; TRANSCRIPTIONAL CONTROL; ADULT
HUMANS; ADIPOCYTE DIFFERENTIATION; OLIGONUCLEOTIDE ARRAYS;
INSULIN-RESISTANCE; EXPRESSION; GENE; LIGAND
AB Brown adipose tissue dissipates energy through heat and functions as a defense against cold and obesity. PPAR gamma ligands have been shown to induce the browning of white adipocytes; however, the underlying mechanisms remain unclear. Here, we show that PPAR gamma ligands require full agonism to induce a brown fat gene program preferentially in subcutaneous white adipose. These effects require expression of PRDM16, a factor that controls the development of classical brown fat. Depletion of PRDM16 blunts the effects of the PPAR gamma agonist rosiglitazone on the induced brown fat gene program. Conversely, PRDM16 and rosiglitazone synergistically activate the brown fat gene program in vivo. This synergy is tightly associated with an increased accumulation of PRDM16 protein, due in large measure to an increase in the half-life of the protein in agonist treated cells. Identifying compounds that stabilize PRDM16 protein may represent a plausible therapeutic pathway for the treatment of obesity and diabetes.
C1 [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Ohno, Haruya; Shinoda, Kosaku; Kajimura, Shingo] Univ Calif San Francisco, UCSF Diabet Ctr, San Francisco, CA 94143 USA.
[Ohno, Haruya; Shinoda, Kosaku; Kajimura, Shingo] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA.
RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu; skajimura@diabetes.ucsf.edu
FU NIH [DK31405, DK090861, DK087853]; DERC [NIH P30 DK063720]
FX We thank Dr. Patrick Griffin at the Scripps Institute for providing
partial PPAR gamma agonists. We are grateful to Dr. Jang-Hyun Choi, Ms.
Emi Tomoda, and Ms. Lauren Ruiz for discussion, technical help, and
editorial assistance with the manuscript. This work was supported by
grants from the NIH to B.M.S. (DK31405 and DK090861) and to S.K.
(DK087853). We also acknowledge the DERC grant (NIH P30 DK063720).
NR 46
TC 190
Z9 200
U1 4
U2 23
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD MAR 7
PY 2012
VL 15
IS 3
BP 395
EP 404
DI 10.1016/j.cmet.2012.01.019
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 911EZ
UT WOS:000301701400019
PM 22405074
ER
PT J
AU Blankstein, R
Hoffmann, U
AF Blankstein, Ron
Hoffmann, Udo
TI Evaluation for Coronary Artery Disease and Medicare Spending
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID COMPUTED-TOMOGRAPHY; ANGIOGRAPHY; CT
C1 [Blankstein, Ron] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
RP Blankstein, R (reprint author), Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, 75 Francis St, Boston, MA 02115 USA.
EM uhoffmann@partners.org
NR 5
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 7
PY 2012
VL 307
IS 9
BP 911
EP 912
DI 10.1001/jama.307.9.911-b
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CU
UT WOS:000301172100011
PM 22396507
ER
PT J
AU Blinderman, CD
Krakauer, EL
Solomon, MZ
AF Blinderman, Craig D.
Krakauer, Eric L.
Solomon, Mildred Z.
TI Time to Revise the Approach to Determining Cardiopulmonary Resuscitation
Status
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CARE
C1 [Blinderman, Craig D.] Columbia Univ, Med Ctr, Dept Anesthesiol, New York, NY 10032 USA.
[Solomon, Mildred Z.] Harvard Univ, Sch Med, Div Med Eth, Boston, MA USA.
[Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Krakauer, Eric L.; Solomon, Mildred Z.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
[Krakauer, Eric L.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA.
[Krakauer, Eric L.] Massachusetts Gen Hosp, Optimum Care Comm, Boston, MA 02114 USA.
[Solomon, Mildred Z.] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
RP Blinderman, CD (reprint author), Columbia Univ, Med Ctr, Dept Anesthesiol, 622 W 168th St,PH5-530B, New York, NY 10032 USA.
EM cdb21@columbia.edu
NR 7
TC 32
Z9 32
U1 0
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 7
PY 2012
VL 307
IS 9
BP 917
EP 918
DI 10.1001/jama.2012.236
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CU
UT WOS:000301172100017
PM 22396511
ER
PT J
AU Seal, KH
Shi, Y
Cohen, G
Cohen, BE
Maguen, S
Krebs, EE
Neylan, TC
AF Seal, Karen H.
Shi, Ying
Cohen, Gregory
Cohen, Beth E.
Maguen, Shira
Krebs, Erin E.
Neylan, Thomas C.
TI Association of Mental Health Disorders With Prescription Opioids and
High-Risk Opioid Use in US Veterans of Iraq and Afghanistan
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; OPERATIONS ENDURING FREEDOM; VIETNAM
COMBAT VETERANS; CHRONIC NONCANCER PAIN; COMORBID CHRONIC PAIN;
PRIMARY-CARE PATIENTS; MEDICATION USE; WAR; PTSD; PREVALENCE
AB Context Record numbers of Iraq and Afghanistan veterans survive their war injuries and yet continue to experience pain and mental health problems, particularly post-traumatic stress disorder (PTSD). Little is known about the association of mental health disorders and prescription opioid use.
Objective To investigate the effect of mental health disorders, particularly PTSD, on risks and adverse clinical outcomes associated with prescription opioid use.
Design Retrospective cohort study involving 141 029 Iraq and Afghanistan veterans who received at least 1 non-cancer-related pain diagnosis within 1 year of entering the Department of Veterans Affairs (VA) health care system from October 1, 2005, through December 31, 2010.
Main Outcome Measures Independent association of mental health disorders and the prescription of opioids, higher risk opioid use, and adverse clinical outcomes (eg, accidents and overdose) within 1 year of receiving a pain-related diagnosis.
Results A total of 15 676 veterans were prescribed opioids within 1 year of their initial pain diagnosis. Compared with 6.5% of veterans without mental health disorders, 17.8% (adjusted relative risk [RR], 2.58; 95% CI, 2.49-2.67) of veterans with PTSD and 11.7% (adjusted RR, 1.74; 95% CI, 1.67-1.82) with other mental health diagnoses but without PTSD were significantly more likely to receive opioids for pain diagnoses. Of those who were prescribed pain medication, veterans with PTSD were more likely than those without mental health disorders to receive higher-dose opioids (22.7% vs 15.9%, adjusted RR, 1.42; 95% CI, 1.31-1.54), receive 2 or more opioids concurrently (19.8% vs 10.7%, adjusted RR, 1.87; 95% CI, 1.70-2.06), receive sedative hypnotics concurrently (40.7% vs 7.6%, adjusted RR, 5.46; 95% CI, 4.91-6.07), or obtain early opioid refills (33.8% vs 20.4%; adjusted RR, 1.64; 95% CI, 1.531.75). Receiving prescription opioids (vs not) was associated with an increased risk of adverse clinical outcomes for all veterans (9.5% vs 4.1%; RR, 2.33; 95% CI, 2.20-2.46), which was most pronounced in veterans with PTSD.
Conclusion Among US veterans of Iraq and Afghanistan, mental health diagnoses, especially PTSD, were associated with an increased risk of receiving opioids for pain, high-risk opioid use, and adverse clinical outcomes. JAMA. 2012;307(9):940-947 www.jama.com
C1 [Seal, Karen H.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA.
[Krebs, Erin E.] Indiana Univ Sch Med, Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA.
[Krebs, Erin E.] Regenstrief Inst Inc, Indianapolis, IN USA.
RP Seal, KH (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, 4150 Clement St,POB 111A-1, San Francisco, CA 94121 USA.
EM karen.seal@ucsf.edu
FU Department of Veterans Affairs (VA), Health Services Research and
Development (HSRD) at the San Francisco VA Medical Center; VA HSRD [RCD
06-042, CD2 07-215]; National Institutes of Health, National Heart,
Lung, and Blood Institute [K23 HL 094765-01]
FX This work was financially supported by the Department of Veterans
Affairs (VA), Health Services Research and Development (HSRD) Research
Enhancement Award Program at the San Francisco VA Medical Center (Dr
Seal), by VA HSRD Career Development Awards RCD 06-042 (Dr Maguen), and
CD2 07-215 (Dr Krebs), and grant K23 HL 094765-01 from the National
Institutes of Health, National Heart, Lung, and Blood Institute (Dr
Cohen).
NR 52
TC 135
Z9 135
U1 1
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 7
PY 2012
VL 307
IS 9
BP 940
EP 947
DI 10.1001/jama.2012.234
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CU
UT WOS:000301172100022
PM 22396516
ER
PT J
AU Schomer, DL
Lewis, RJ
AF Schomer, Donald L.
Lewis, Roger J.
TI Stopping Seizures Early and the Surgical Epilepsy Trial That Stopped
Even Earlier
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CLINICAL-TRIALS; BENEFIT; SURGERY
C1 [Schomer, Donald L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Lewis, Roger J.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA.
[Lewis, Roger J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Schomer, DL (reprint author), BIDMC, Clin Neurophysiol Lab, Baker 504,330 Brookline Ave, Boston, MA 02215 USA.
EM dschomer@bidmc.harvard.edu
NR 21
TC 5
Z9 5
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 7
PY 2012
VL 307
IS 9
BP 966
EP 968
DI 10.1001/jama.2012.251
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CU
UT WOS:000301172100026
PM 22396519
ER
PT J
AU Markmann, JF
Kawai, T
AF Markmann, James F.
Kawai, Tatsuo
TI The Quest for Transplantation Tolerance: Have We Finally Sipped from the
Cup?
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID PREPARATIVE REGIMEN; MIXED CHIMERISM; ALLOGRAFTS
C1 [Markmann, James F.; Kawai, Tatsuo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Kawai, T (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM tkawai@partners.org
FU NIAID NIH HHS [R01 AI057851]
NR 10
TC 7
Z9 7
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 7
PY 2012
VL 4
IS 124
AR 124fs5
DI 10.1126/scitranslmed.3003678
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 905UY
UT WOS:000301302600001
PM 22399262
ER
PT J
AU Shi, YC
Kirwan, P
Smith, J
MacLean, G
Orkin, SH
Livesey, FJ
AF Shi, Yichen
Kirwan, Peter
Smith, James
MacLean, Glenn
Orkin, Stuart H.
Livesey, Frederick J.
TI A Human Stem Cell Model of Early Alzheimer's Disease Pathology in Down
Syndrome
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID AMYLOID PLAQUE-FORMATION; TRANSGENIC MICE; BETA-PROTEIN; TAU-PROTEIN;
BRAIN; CONVERSION; DEMENTIA; GENETICS; DEFECTS; NEURONS
AB Human cellular models of Alzheimer's disease (AD) pathogenesis would enable the investigation of candidate pathogenic mechanisms in AD and the testing and developing of new therapeutic strategies. We report the development of AD pathologies in cortical neurons generated from human induced pluripotent stem (iPS) cells derived from patients with Down syndrome. Adults with Down syndrome (caused by trisomy of chromosome 21) develop early-onset AD, probably due to increased expression of a gene on chromosome 21 that encodes the amyloid precursor protein (APP). We found that cortical neurons generated from iPS cells and embryonic stem cells from Down syndrome patients developed AD pathologies over months in culture, rather than years in vivo. These cortical neurons processed the transmembrane APP protein, resulting in secretion of the pathogenic peptide fragment amyloid-beta 42 (A beta 42), which formed insoluble intracellular and extracellular amyloid aggregates. Production of A beta peptides was blocked by a gamma-secretase inhibitor. Finally, hyperphosphorylated tau protein, a pathological hallmark of AD, was found to be localized to cell bodies and dendrites in iPS cell-derived cortical neurons from Down syndrome patients, recapitulating later stages of the AD pathogenic process.
C1 [Shi, Yichen; Kirwan, Peter; Smith, James; Livesey, Frederick J.] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England.
[Shi, Yichen; Kirwan, Peter; Smith, James; Livesey, Frederick J.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England.
[MacLean, Glenn; Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Dept Pediat Oncol, Dana Farber Canc Inst,Div Hematol Oncol, Boston, MA 02115 USA.
[MacLean, Glenn; Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
RP Livesey, FJ (reprint author), Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM rick@gurdon.cam.ac.uk
OI Kirwan, Peter/0000-0003-1446-7544; Smith, James/0000-0001-9131-5849
FU Wellcome Trust; Cancer Research UK; Alzheimer's Research UK
FX This research benefits from core support to the Gurdon Institute from
the Wellcome Trust and Cancer Research UK and grants to F.J.L. from the
Wellcome Trust and Alzheimer's Research UK.
NR 38
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PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 7
PY 2012
VL 4
IS 124
AR 124ra29
DI 10.1126/scitranslmed.3003771
PG 9
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 905UY
UT WOS:000301302600005
PM 22344463
ER
PT J
AU Clasie, B
Depauw, N
Fransen, M
Goma, C
Panahandeh, HR
Seco, J
Flanz, JB
Kooy, HM
AF Clasie, Benjamin
Depauw, Nicolas
Fransen, Maurice
Goma, Carles
Panahandeh, Hamid Reza
Seco, Joao
Flanz, Jacob B.
Kooy, Hanne M.
TI Golden beam data for proton pencil-beam scanning
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID MONTE-CARLO SIMULATIONS; THERAPY; ALGORITHM; DELIVERY; DESIGN; NOZZLE
AB Proton, as well as other ion, beams applied by electro-magnetic deflection in pencil-beam scanning (PBS) are minimally perturbed and thus can be quantified a priori by their fundamental interactions in a medium. This a priori quantification permits an optimal reduction of characterizing measurements on a particular PBS delivery system. The combination of a priori quantification and measurements will then suffice to fully describe the physical interactions necessary for treatment planning purposes. We consider, for proton beams, these interactions and derive a 'Golden' beam data set. The Golden beam data set quantifies the pristine Bragg peak depth-dose distribution in terms of primary, multiple Coulomb scatter, and secondary, nuclear scatter, components. The set reduces the required measurements on a PBS delivery system to the measurement of energy spread and initial phase space as a function of energy. The depth doses are described in absolute units of Gy(RBE) mm(2) Gp(-1), where Gp equals 10(9) (giga) protons, thus providing a direct mapping from treatment planning parameters to integrated beam current. We used these Golden beam data on our PBS delivery systems and demonstrated that they yield absolute dosimetry well within clinical tolerance.
C1 [Clasie, Benjamin; Depauw, Nicolas; Fransen, Maurice; Goma, Carles; Panahandeh, Hamid Reza; Seco, Joao; Flanz, Jacob B.; Kooy, Hanne M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Clasie, Benjamin; Depauw, Nicolas; Fransen, Maurice; Goma, Carles; Panahandeh, Hamid Reza; Seco, Joao; Flanz, Jacob B.; Kooy, Hanne M.] Harvard Univ, Sch Med, Boston, MA USA.
[Fransen, Maurice] Eindhoven Univ Technol, Dept Appl Phys, NL-5600 MB Eindhoven, Netherlands.
RP Clasie, B (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM bclasie@partners.org
RI Seco, Joao/J-4451-2012;
OI Goma, Carles/0000-0003-0336-390X
FU Massachusetts General Hospital; La Caixa Foundation Spain
FX Funded in part through the Massachusetts General Hospital managed
National Cancer Institute federal share program. One of us, CG, was
supported by a La Caixa Foundation fellowship, Spain.
NR 14
TC 35
Z9 35
U1 0
U2 5
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2012
VL 57
IS 5
BP 1147
EP 1158
DI 10.1088/0031-9155/57/5/1147
PG 12
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 898XL
UT WOS:000300775600005
PM 22330090
ER
PT J
AU Carabe, A
Moteabbed, M
Depauw, N
Schuemann, J
Paganetti, H
AF Carabe, Alejandro
Moteabbed, Maryam
Depauw, Nicolas
Schuemann, Jan
Paganetti, Harald
TI Range uncertainty in proton therapy due to variable biological
effectiveness
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID LOW-ENERGY PROTONS; LINEAR-QUADRATIC MODEL; HAMSTER V79 CELLS;
EFFECTIVENESS RBE; BEAM THERAPY; INACTIVATION; SURVIVAL; VALUES
AB Traditionally, dose in proton radiotherapy is prescribed as Gy(RBE) by scaling up the physical dose by 10%. The relative biological effectiveness (RBE) of protons is considered to vary with dose-averaged linear energy transfer (LETd), dose (d) and (alpha/beta)(x). The increase of RBE with depth causes a shift of the falloff of the beam, i.e. a change of the beam range. The magnitude of this shift will depend on dose and (alpha/beta)(x). The aim of this project was to quantify the dependence of the range shift on these parameters. Three double-scattered beams of different ranges incident on a computational phantom consisting of different regions of interest (ROIs) were used. Each ROI was assigned with (alpha/beta)(x) values between 0.5 and 20 Gy. The distribution of LETd within each ROI was obtained from a Monte Carlo simulation. The LETd distribution depends on the beam energy and thus its nominal range. The RBE values within the ROIs were calculated for doses between 1 and 15 Gy using an in-house developed biophysical model. Dose-volume histograms of the RBE-weighted doses were extracted for each ROI for a 'fixed RBE' (RBE = 1.1) and a 'variable RBE' (RBE = f (d, alpha/beta, LETd)), and the percentage difference in range was obtained from the difference of the percentage volumes at the distal 80% of the dose. Range differences in normal tissue ((alpha/beta)(x) = 3 Gy) of the order of 3-2 mm were obtained, respectively, for a shallow (physical range 4.8 cm) and a deep (physical range 12.8 cm) beam, when a dose of 1 Gy normalized to the mid-SOBP was delivered. As the dose increased to 15 Gy, the variable RBE decreases below 1.1 which induces ranges of about 1 mm shorter than those obtained with an RBE of 1.1. The shift in the range of an SOBP when comparing biological dose distributions obtained with a fixed or a variable RBE was quantified as a function of dose, (alpha/beta)(x) and physical range (as a surrogate of the initial beam energy). The shift increases with the physical range but decreases with increasing dose or (alpha/beta)(x). The results of our study allow a quantitative consideration of RBE-caused range uncertainties as a function of treatment site and dose in treatment planning.
C1 [Carabe, Alejandro; Moteabbed, Maryam; Depauw, Nicolas; Schuemann, Jan; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Carabe, Alejandro; Moteabbed, Maryam; Depauw, Nicolas; Schuemann, Jan; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Carabe, Alejandro] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
RP Carabe, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM a.carabe@uphs.upenn.edu
NR 23
TC 53
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U1 5
U2 21
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2012
VL 57
IS 5
BP 1159
EP 1172
DI 10.1088/0031-9155/57/5/1159
PG 14
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 898XL
UT WOS:000300775600006
PM 22330133
ER
PT J
AU Ramakrishnan, J
Craft, D
Bortfeld, T
Tsitsiklis, JN
AF Ramakrishnan, Jagdish
Craft, David
Bortfeld, Thomas
Tsitsiklis, John N.
TI A dynamic programming approach to adaptive fractionation
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID VARIABLE INTRAFRACTION MOTION; RADIATION-THERAPY; ONLINE MODIFICATION;
PROSTATE-CANCER; BY-FRACTION; IMRT; DELIVERY; STRATEGY; IMAGES; TARGET
AB We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are as follows: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a 'favorable' anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5-85%) depending on the amount of motion in the anatomy, the number of fractions and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting) and (iii) we allow large daily fraction size deviations.
C1 [Ramakrishnan, Jagdish; Tsitsiklis, John N.] MIT, Lab Informat & Decis Syst, Cambridge, MA 02139 USA.
[Craft, David; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Craft, David; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ramakrishnan, J (reprint author), MIT, Lab Informat & Decis Syst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM jagdish@mit.edu; dcraft@partners.org; tbortfeld@partners.org;
jnt@mit.edu
FU Siemens
FX This work was partially supported by Siemens.
NR 23
TC 2
Z9 2
U1 0
U2 1
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2012
VL 57
IS 5
BP 1203
EP 1216
DI 10.1088/0031-9155/55/5/1203
PG 14
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 898XL
UT WOS:000300775600009
PM 22330328
ER
PT J
AU St James, S
Mishra, P
Hacker, F
Berbeco, RI
Lewis, JH
AF St James, Sara
Mishra, Pankaj
Hacker, Fred
Berbeco, Ross I.
Lewis, John H.
TI Quantifying ITV instabilities arising from 4DCT: a simulation study
using patient data
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; LUNG-TUMOR TRACKING; INTENSITY
PROJECTION; RESPIRATORY MOTION; TARGET VOLUME; RADIOTHERAPY; CANCER;
SIZE
AB Treatment planning for patients undergoing radiation therapy is often performed based on four-dimensional computed tomography (4DCT) when respiratory motion is present, as in lung cancer patients. 4DCT is used to define the internal target volume (ITV) that, ideally, incorporates all potential locations of the tumour. In this work, we use the locations of gold fiducial markers implanted in lung tumours of eight patients to represent tumour motion. These fiducial locations are used in a simulation of a four-slice CT scanner to generate the ITV for 10, 20 and 30 mm diameter model tumours. To demonstrate instabilities in the ITV definition based on 4DCT, the ITV calculation was repeated for the same patients for consecutive scan start times, staggered by 1 s. The volumetric difference in the ITV and the per cent of time that the ITV contains in the tumour are both evaluated. The ITV from a single patient was found to vary by 46%-127% for a tumour diameter of 10 mm. The ITV did not cover the entirety of the tumour 11%-74% of the time for a 10 mm tumour diameter.
C1 [St James, Sara] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP St James, S (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA.
EM sara.stjames@gmail.com; jhlewis@lroc.harvard.edu
FU NIH [R21CA156068-01A1]
FX The authors would like to thank Dr Seiko Nishioka of the Department of
Radiology, NTT Hospital, Sapporo, Japan and Hiroki Shirato of the
Department of Radiation Medicine, Hokkaido University School of
Medicine, Sapporo, Japan for sharing the Hokkaido dataset with them. The
authors would also like to thank Dr Mike Makrigiorgos for insightful
discussions during the preparation of the manuscript. The work presented
here was supported, in part, by NIH R21CA156068-01A1.
NR 13
TC 3
Z9 3
U1 0
U2 1
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2012
VL 57
IS 5
BP L1
EP L7
DI 10.1088/0031-9155/57/5/L1
PG 7
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 898XL
UT WOS:000300775600001
ER
PT J
AU Zhang, HM
Dang, H
Kamat, A
Yeh, CK
Zhang, BX
AF Zhang, Hong-Mei
Dang, Howard
Kamat, Amrita
Yeh, Chih-Ko
Zhang, Bin-Xian
TI Geldanamycin Derivative Ameliorates High Fat Diet-Induced Renal Failure
in Diabetes
SO PLOS ONE
LA English
DT Article
ID INDUCED INSULIN-RESISTANCE; MITOCHONDRIAL CA2+ EFFLUX; PROXIMAL TUBULAR
CELLS; BLOOD-GLUCOSE CONTROL; OXIDATIVE STRESS; MESANGIAL CELLS;
MOLECULAR-MECHANISMS; BARDOXOLONE METHYL; SKELETAL-MUSCLE;
KIDNEY-FUNCTION
AB Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90 beta 1 (hsp90 beta 1) is indispensable for the PUFA action. Here we investigated the effects of high fat diet (HFD) on kidney function and structure of db/db mice, a widely used rodent model of type 2 diabetes. Our results indicated that HFD dramatically increased the 24 h-urine output and worsened albuminuria in db/db mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the increased urine output. Prolonged HFD feeding resulted in early death of db/db mice, which was associated with oliguria and anuria. Treatment with the geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated glomerular and tubular damage by HFD. 17-DMAG also significantly extended survival of the animals and protected them from the high mortality associated with renal failure. The benefit effect of 17-DMAG on renal function and structure was associated with a decreased level of kidney nitrotyrosine and a diminished kidney mitochondrial Ca2+ efflux in HFD-fed db/db mice. These results suggest that hsp90 beta 1 is a potential target for the treatment of nephropathy and renal failure in diabetes.
C1 [Zhang, Hong-Mei] Fourth Mil Med Univ, Dept Clin Oncol, Xijing Hosp, Xian 710032, Peoples R China.
[Zhang, Hong-Mei; Kamat, Amrita; Zhang, Bin-Xian] Univ Texas San Antonio, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA.
[Dang, Howard; Yeh, Chih-Ko; Zhang, Bin-Xian] Univ Texas San Antonio, Hlth Sci Ctr, Dept Comprehens Dent, San Antonio, TX USA.
[Kamat, Amrita; Yeh, Chih-Ko; Zhang, Bin-Xian] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA.
RP Zhang, HM (reprint author), Fourth Mil Med Univ, Dept Clin Oncol, Xijing Hosp, Xian 710032, Peoples R China.
EM zhangb2@uthscsa.edu
FU Mike Hogg Fund; National Institutes of Health (NIH); Department of
Veterans Health Care; National Natural Science Foundation of China
[30900673]; Natural Science Foundation of Shaanxi Province [SJ08-ZT10]
FX This work was supported by the Mike Hogg Fund, National Institutes of
Health (NIH), The Department of Veterans Health Care, the National
Natural Science Foundation of China (No. 30900673), and Natural Science
Foundation of Shaanxi Province(SJ08-ZT10). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 57
TC 11
Z9 12
U1 1
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 6
PY 2012
VL 7
IS 3
AR e32746
DI 10.1371/journal.pone.0032746
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928XD
UT WOS:000303021100027
PM 22412919
ER
PT J
AU Thombs, BD
Coyne, JC
Cuijpers, P
de Jonge, P
Gilbody, S
Ioannidis, JPA
Johnson, BT
Patten, SB
Turner, EH
Ziegelstein, RC
AF Thombs, Brett D.
Coyne, James C.
Cuijpers, Pim
de Jonge, Peter
Gilbody, Simon
Ioannidis, John P. A.
Johnson, Blair T.
Patten, Scott B.
Turner, Erick H.
Ziegelstein, Roy C.
TI Rethinking recommendations for screening for depression in primary care
SO CANADIAN MEDICAL ASSOCIATION JOURNAL
LA English
DT Article
ID CASE-FINDING INSTRUMENTS; ANTIDEPRESSANT TRIALS; NATIONAL PATTERNS;
RANDOMIZED-TRIAL; METAANALYSIS; EFFICACY; SEVERITY; OUTCOMES;
PUBLICATION; DIAGNOSIS
C1 [Thombs, Brett D.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Biostat, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Dept Occupat Hlth, Montreal, PQ, Canada.
[Thombs, Brett D.] McGill Univ, Sch Nursing, Montreal, PQ, Canada.
McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
[Coyne, James C.] Univ Penn, Sch Med, Behav Oncol Program, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Coyne, James C.] Univ Groningen, Hlth Psychol Sect, Dept Hlth Sci, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
[Cuijpers, Pim] Vrije Univ Amsterdam, Dept Clin Psychol, Amsterdam, Netherlands.
[Cuijpers, Pim] Vrije Univ Amsterdam, EMGO Inst, Amsterdam, Netherlands.
[de Jonge, Peter] Univ Groningen, Interdisciplinary Ctr Psychiat Epidemiol, Univ Med Ctr, Groningen, Netherlands.
[Gilbody, Simon] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England.
Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.
[Ioannidis, John P. A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Inst Clin Res & Hlth Policy Studies, Tufts Med Ctr, Boston, MA 02111 USA.
Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA.
[Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA.
[Johnson, Blair T.] Univ Connecticut, Dept Psychol, Storrs, CT USA.
[Johnson, Blair T.] Univ Connecticut, Ctr Hlth Intervent & Prevent, Storrs, CT USA.
[Patten, Scott B.] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Patten, Scott B.] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada.
[Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
Portland VA Med Ctr, Portland, OR USA.
[Ziegelstein, Roy C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
RP Thombs, BD (reprint author), McGill Univ, Dept Psychiat, Montreal, PQ, Canada.
EM brett.thombs@mcgill.ca
RI Turner, Erick/A-4848-2008; de Jonge, peter/L-6395-2013; Cuijpers,
Pim/G-1703-2013; Patten, Scott/B-4434-2011;
OI Turner, Erick/0000-0002-3522-3357; de Jonge, peter/0000-0002-0866-6929;
Patten, Scott/0000-0001-9871-4041; Cuijpers, Pim/0000-0001-5497-2743;
Thombs, Brett/0000-0002-5644-8432
FU Canadian Institutes of Health Research [MIN 92725]; NCCIH NIH HHS [R24
AT004641, R24AT004641]
NR 47
TC 63
Z9 63
U1 1
U2 16
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA
SN 0820-3946
J9 CAN MED ASSOC J
JI Can. Med. Assoc. J.
PD MAR 6
PY 2012
VL 184
IS 4
BP 413
EP 418
DI 10.1503/cmaj.111035
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 908BM
UT WOS:000301465400009
PM 21930744
ER
PT J
AU Reynolds, MR
Magnuson, EA
Wang, KJ
Lei, Y
Vilain, K
Walczak, J
Kodali, SK
Lasala, JM
O'Neill, WW
Davidson, CJ
Smith, CR
Leon, MB
Cohen, DJ
AF Reynolds, Matthew R.
Magnuson, Elizabeth A.
Wang, Kaijun
Lei, Yang
Vilain, Katherine
Walczak, Joshua
Kodali, Susheel K.
Lasala, John M.
O'Neill, William W.
Davidson, Charles J.
Smith, Craig R.
Leon, Martin B.
Cohen, David J.
CA PARTNER Investigators
TI Cost-Effectiveness of Transcatheter Aortic Valve Replacement Compared
With Standard Care Among Inoperable Patients With Severe Aortic Stenosis
Results From the Placement of Aortic Transcatheter Valves (PARTNER)
Trial (Cohort B)
SO CIRCULATION
LA English
DT Article
DE aortic stenosis; transcatheter valve therapy; cost-effectiveness;
clinical trials
ID HEART-FAILURE; ECONOMIC-EVALUATION; HEALTH; OUTCOMES; THERAPY; SURGERY;
MEDICINE; MEDICARE; DISEASE; RISK
AB Background-In patients with severe aortic stenosis who cannot have surgery, transcatheter aortic valve replacement (TAVR) has been shown to improve survival and quality of life compared with standard therapy, but the costs and cost-effectiveness of this strategy are not yet known.
Methods and Results-The PARTNER trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgery to TAVR (n = 179) or standard therapy (n = 179). Empirical data regarding survival, quality of life, medical resource use, and hospital costs were collected during the trial and used to project life expectancy, quality-adjusted life expectancy, and lifetime medical care costs to estimate the incremental cost-effectiveness of TAVR from a US perspective. For patients treated with TAVR, mean costs for the initial procedure and hospitalization were $42 806 and $78 542, respectively. Follow-up costs through 12 months were lower with TAVR ($29 289 versus $53 621) because of reduced hospitalization rates, but cumulative 1-year costs remained higher ($106 076 versus $53 621). We projected that over a patient's lifetime, TAVR would increase discounted life expectancy by 1.6 years (1.3 quality-adjusted life-years) at an incremental cost of $79 837. The incremental cost-effectiveness ratio for TAVR was thus estimated at $50 200 per year of life gained or $61 889 per quality-adjusted life-year gained. These results were stable across a broad range of uncertainty and sensitivity analyses.
Conclusions-For patients with severe aortic stenosis who are not candidates for surgery, TAVR increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies.
Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. (Circulation. 2012;125:1102-1109.)
C1 [Magnuson, Elizabeth A.; Wang, Kaijun; Lei, Yang; Vilain, Katherine; Cohen, David J.] Univ Missouri Kansas City, St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO 64111 USA.
[Reynolds, Matthew R.; Walczak, Joshua] Harvard Clin Res Inst, Boston, MA USA.
[Reynolds, Matthew R.] Boston VA Healthcare Syst, Boston, MA USA.
[Kodali, Susheel K.; Smith, Craig R.; Leon, Martin B.] Columbia Presbyterian Med Ctr, New York, NY USA.
[Lasala, John M.] Washington Univ, Sch Med, St Louis, MO USA.
[O'Neill, William W.] Univ Miami, Sch Med, Miami, FL USA.
[Davidson, Charles J.] Northwestern Univ, Sch Med, Chicago, IL USA.
RP Cohen, DJ (reprint author), Univ Missouri Kansas City, Sch Med, St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA.
EM dcohen@saint-lukes.org
FU Edwards Lifesciences, Inc.; Edwards Lifesciences; Biosense Webster;
Sanofi-aventis; St. Jude Medical; Medtronic; Eli Lilly; Daiichi Sankyo;
Bristol-Myers Squibb; Abbott Vascular; MedRad; Merck/Schering-Plough;
Eli Lilly-Daiichi Sankyo; Schering-Plough; Cordis
FX This study was funded by Edwards Lifesciences, Inc.; Dr Reynolds reports
receiving research support from Edwards Lifesciences, Biosense Webster,
and Sanofi-aventis and consulting income from Biosense Webster,
Sanofi-aventis, St. Jude Medical, and Medtronic. Dr Magnuson reports
receiving grant support from Eli Lilly, Daiichi Sankyo, Sanofi-aventis,
and Bristol-Myers Squibb. Dr Kodali reports receiving consulting income
from Edwards Lifesciences (clinical proctor). Dr O'Neill reports
receiving consulting fees from Medtronic. Dr Davidson reports receiving
research support from Edwards Lifesciences and Abbott Vascular and
serving on the advisory board of Abbott Vascular. Dr Smith reports
receiving research support from Edwards Lifesciences. Dr Leon reports
receiving research support from Edwards Lifesciences and consulting
income from Medtronic, and he holds stock options in Sadra Medical. Dr
Cohen reports receiving research support from Edwards Lifesciences,
Medtronic, Boston Scientific, Abbott Vascular, MedRad,
Merck/Schering-Plough, and Eli Lilly-Daiichi Sankyo; consulting income
from Schering-Plough, Eli Lilly, Medtronic, and Cordis; and speaking
honoraria from Eli Lilly, The Medicines Company, and St. Jude Medical.
The other authors report no conflicts.
NR 34
TC 98
Z9 111
U1 2
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAR 6
PY 2012
VL 125
IS 9
BP 1102
EP 1109
DI 10.1161/CIRCULATIONAHA.111.054072
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 904LK
UT WOS:000301197700017
PM 22308299
ER
PT J
AU Hiatt, WR
Thomas, A
Goldfine, AB
AF Hiatt, William R.
Thomas, Abraham
Goldfine, Allison B.
TI What Cost Weight Loss?
SO CIRCULATION
LA English
DT Article
DE adverse drug event; cardiovascular events; drugs; obesity; safety
ID CARDIOVASCULAR RISK-FACTORS; BARIATRIC SURGERY; OBESE-PATIENTS;
SIBUTRAMINE; NUCLEUS; TRIAL
C1 [Hiatt, William R.] Univ Colorado, Sch Med, Div Cardiol, Dept Med, Aurora, CO 80045 USA.
[Hiatt, William R.] CPC Clin Res, Aurora, CO USA.
[Thomas, Abraham] Henry Ford Hosp, Div Endocrinol Diabet Bone & Mineral Disorders, Detroit, MI 48202 USA.
[Goldfine, Allison B.] Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02215 USA.
[Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA.
RP Hiatt, WR (reprint author), Univ Colorado, Sch Med, Div Cardiol, Dept Med, 13199 E Montview Blvd,Suite 200, Aurora, CO 80045 USA.
EM Will.Hiatt@UCDenver.edu
OI Thomas, Abraham/0000-0002-3941-1195
NR 17
TC 11
Z9 12
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD MAR 6
PY 2012
VL 125
IS 9
BP 1171
EP 1177
DI 10.1161/CIRCULATIONAHA.111.023499
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 904LK
UT WOS:000301197700023
PM 22392864
ER
PT J
AU Xu, AJ
Springer, TA
AF Xu, Amy J.
Springer, Timothy A.
TI Calcium stabilizes the von Willebrand factor A2 domain by promoting
refolding
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID THROMBOTIC THROMBOCYTOPENIC PURPURA; ADAMTS-13; PLASMA; MULTIMERS;
CLEAVAGE; ADHESION; BONDS
AB Von Willebrand factor (VWF) is a large, multimeric plasma glycoprotein that critically mediates hemostasis at sites of vascular injury. Very large VWF multimers have the greatest thrombogenic activity, which is attenuated by cleavage in the A2 domain by the metalloproteinase ADAMTS13. ADAMTS13 proteolysis requires mechanical force to expose the scissile bond and is regulated by a calcium-binding site within A2. In this study, we characterized the interaction between VWF A2 and calcium by examining the effect of calcium on VWF A2 stability and mechanical unfolding and refolding. Isothermal calorimetry yielded a calcium binding K-d = 3.8 +/- 1.0 mu M and reversible thermal denaturation showed that 5 mM calcium stabilized the unfolding transition from 56.7 +/- 0.1 to 69.1 +/- 0.1 degrees C. Using optical tweezers to apply tensile force to single domains, we found that calcium did not affect VWF A2 unfolding, but rather enhanced refolding kinetics fivefold, resulting in a 0.9 kcal/mol stabilization in the folding activation energy in the presence of calcium. Taken together, our data demonstrate that VWF binds calcium at physiologic calcium concentrations and that calcium stabilizes VWF A2 by accelerating refolding.
C1 [Springer, Timothy A.] Harvard Univ, Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst,Sch Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Springer, TA (reprint author), Harvard Univ, Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst,Sch Med, 3 Blackfan Circle,Room 3103, Boston, MA 02115 USA.
EM springer@idi.harvard.edu
FU National Institutes of Health (NIH) [HL-48675]; NIH/National Institute
of General Medical Sciences [T32 GM008313]
FX The authors thank Dr. S. C. Blacklow for isothermal calorimetry and CD
equipment and advice. This work was supported by National Institutes of
Health (NIH) HL-48675 (T. A. S.) and NIH/National Institute of General
Medical Sciences T32 GM008313 Molecular Biophysics Training Grant
(A.J.X.). A.J.X. is an MD/PhD candidate at Harvard Medical School and
this work is submitted in partial fulfillment of the requirement for the
PhD.
NR 26
TC 24
Z9 24
U1 1
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 MAR 6
PY 2012
VL 109
IS 10
BP 3742
EP 3747
DI 10.1073/pnas.1121261109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700034
PM 22357761
ER
PT J
AU Lohr, JG
Stojanov, P
Lawrence, MS
Auclair, D
Chapuy, B
Sougnez, C
Cruz-Gordillo, P
Knoechel, B
Asmann, YW
Slager, SL
Novak, AJ
Dogan, A
Ansell, SM
Link, BK
Zou, LH
Gould, J
Saksena, G
Stransky, N
Rangel-Escareno, C
Fernandez-Lopez, JC
Hidalgo-Miranda, A
Melendez-Zajgla, J
Hernandez-Lemus, E
Celis, ASCY
Imaz-Rosshandler, I
Ojesina, AI
Jung, J
Pedamallu, CS
Lander, ES
Habermann, TM
Cerhan, JR
Shipp, MA
Getz, G
Golub, TR
AF Lohr, Jens G.
Stojanov, Petar
Lawrence, Michael S.
Auclair, Daniel
Chapuy, Bjoern
Sougnez, Carrie
Cruz-Gordillo, Peter
Knoechel, Birgit
Asmann, Yan W.
Slager, Susan L.
Novak, Anne J.
Dogan, Ahmet
Ansell, Stephen M.
Link, Brian K.
Zou, Lihua
Gould, Joshua
Saksena, Gordon
Stransky, Nicolas
Rangel-Escareno, Claudia
Carlos Fernandez-Lopez, Juan
Hidalgo-Miranda, Alfredo
Melendez-Zajgla, Jorge
Hernandez-Lemus, Enrique
Schwarz-Cruz y Celis, Angela
Imaz-Rosshandler, Ivan
Ojesina, Akinyemi I.
Jung, Joonil
Pedamallu, Chandra S.
Lander, Eric S.
Habermann, Thomas M.
Cerhan, James R.
Shipp, Margaret A.
Getz, Gad
Golub, Todd R.
TI Discovery and prioritization of somatic mutations in diffuse large
B-cell lymphoma (DLBCL) by whole-exome sequencing
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE next-generation sequencing; human genetics; activation-induced deaminase
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA;
NON-HODGKIN-LYMPHOMA; GENOME; RITUXIMAB; THERAPY; BCL2; DISRUPTION;
EXOCYTOSIS; LANDSCAPE
AB To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase-mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease.
C1 [Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Zou, Lihua; Gould, Joshua; Saksena, Gordon; Stransky, Nicolas; Ojesina, Akinyemi I.; Jung, Joonil; Pedamallu, Chandra S.; Lander, Eric S.; Getz, Gad; Golub, Todd R.] Eli & Edythe Broad Inst, Cambridge, MA 02412 USA.
[Lohr, Jens G.; Stojanov, Petar; Chapuy, Bjoern; Knoechel, Birgit; Shipp, Margaret A.; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Habermann, Thomas M.; Cerhan, James R.] Mayo Clin Coll Med, Rochester, MN 55902 USA.
[Knoechel, Birgit] Childrens Hosp Boston, Boston, MA 02115 USA.
[Link, Brian K.] Univ Iowa Coll Med, Iowa City, IA 52245 USA.
[Rangel-Escareno, Claudia; Carlos Fernandez-Lopez, Juan; Hidalgo-Miranda, Alfredo; Melendez-Zajgla, Jorge; Hernandez-Lemus, Enrique; Schwarz-Cruz y Celis, Angela; Imaz-Rosshandler, Ivan] Inst Nacl Med Genom, Mexico City 14610, DF, Mexico.
[Lander, Eric S.; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Lander, Eric S.] MIT, Cambridge, MA 02142 USA.
[Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Lander, ES (reprint author), Eli & Edythe Broad Inst, Cambridge, MA 02412 USA.
EM lander@broadinstitute.org
RI Fernandez, Juan Carlos/C-4976-2013; Hidalgo-Miranda,
Alfredo/B-2123-2010; Rangel-Escareno, Claudia/F-4587-2012;
OI Fernandez, Juan Carlos/0000-0003-3680-4193; Hidalgo-Miranda,
Alfredo/0000-0003-2315-3977; Rangel-Escareno,
Claudia/0000-0003-1303-0834; Ojesina, Akinyemi/0000-0003-0755-3639;
Cerhan, James/0000-0002-7482-178X
FU Carlos Slim Health Institute; National Cancer Institute [5P01
CA092625-07, P50 CA97274]
FX We thank the members of the T.R.G. laboratory, Maria Cortez, Jadwiga
Grabarek, Ami S. Bhatt, Niall J. Lennon, and all members of the Broad
Institute's Biological Samples Platform; Genetic Analysis Platform; and
Genome Sequencing Platform, without whom this work would not have been
possible. This work was conducted as part of the Slim Initiative for
Genomic Medicine (SIGMA), a joint US-Mexico project funded by the Carlos
Slim Health Institute, and was also supported by National Cancer
Institute Grants 5P01 CA092625-07 and P50 CA97274.
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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 MAR 6
PY 2012
VL 109
IS 10
BP 3879
EP 3884
DI 10.1073/pnas.1121343109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700057
PM 22343534
ER
PT J
AU Varadarajan, N
Kwon, DS
Law, KM
Ogunniyi, AO
Anahtar, MN
Richter, JM
Walker, BD
Love, JC
AF Varadarajan, Navin
Kwon, Douglas S.
Law, Kenneth M.
Ogunniyi, Adebola O.
Anahtar, Melis N.
Richter, James M.
Walker, Bruce D.
Love, J. Christopher
TI Rapid, efficient functional characterization and recovery of
HIV-specific human CD8(+) T cells using microengraving
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE T-cell cloning; single-cell analysis; nanowells; microarrays; soft
lithography
ID CYTOKINE FLOW-CYTOMETRY; VIRAL LOAD; ANTIRETROVIRAL THERAPY; VIRUS
CONTROL; RESPONSES; ANTIGEN; INFECTION; ELISPOT; LYMPHOCYTES; MECHANISMS
AB The nature of certain clinical samples (tissue biopsies, fluids) or the subjects themselves (pediatric subjects, neonates) often constrain the number of cells available to evaluate the breadth of functional T-cell responses to infections or therapeutic interventions. The methods most commonly used to assess this functional diversity ex vivo and to recover specific cells to expand in vitro usually require more than 106 cells. Here we present a process to identify antigen-specific responses efficiently ex vivo from 10(4)-10(5) single cells from blood or mucosal tissues using dense arrays of subnanoliter wells. The approach combines on-chip imaging cytometry with a technique for capturing secreted proteins-called "microengraving"-to enumerate antigen-specific responses by single T cells in a manner comparable to conventional assays such as ELISpot and intracellular cytokine staining. Unlike those assays, however, the individual cells identified can be recovered readily by micromanipulation for further characterization in vitro. Applying this method to assess HIV-specific T-cell responses demonstrates that it is possible to establish clonal CD8(+) T-cell lines that represent the most abundant specificities present in circulation using 100- to 1,000-fold fewer cells than traditional approaches require and without extensive genotypic analysis a priori. This rapid (<24 h), efficient, and inexpensive process should improve the comparative study of human T-cell immunology across ages and anatomic compartments.
C1 [Varadarajan, Navin; Ogunniyi, Adebola O.; Love, J. Christopher] MIT, Dept Chem Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Kwon, Douglas S.; Law, Kenneth M.; Anahtar, Melis N.; Walker, Bruce D.; Love, J. Christopher] MIT, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA.
[Kwon, Douglas S.; Law, Kenneth M.; Anahtar, Melis N.; Walker, Bruce D.; Love, J. Christopher] Harvard Univ, Charlestown, MA 02129 USA.
[Kwon, Douglas S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Richter, James M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Love, JC (reprint author), MIT, Dept Chem Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
EM clove@mit.edu
RI Ghartouchent, malek/B-9088-2012;
OI Varadarajan, Navin/0000-0001-7524-8228
FU Charles A. Dana Foundation; W.M. Keck Foundation; Ragon Institute of
Massachusetts General Hospital; Massachusetts Institute of Technology;
Harvard University; National Institute of Allergy and Infectious
Diseases/National Institutes of Health [U54-AI057156]; National
Institutes of Health [K08, NIGMS 5T32GM008334]; Burroughs Wellcome Fund;
United Negro College-Merck
FX This research was supported by the Charles A. Dana Foundation, the W.M.
Keck Foundation, and the Ragon Institute of Massachusetts General
Hospital, Massachusetts Institute of Technology, and Harvard University.
N.V. received support from National Institute of Allergy and Infectious
Diseases/National Institutes of Health GrantU54-AI057156. D.S.K. is
supported by a National Institutes of Health Mentored Clinical Scientist
Development Award (K08) and the Burroughs Wellcome Fund. A.O.O. was
supported in part by National Institutes of Health Biotechnology
Training Fellowship NIGMS 5T32GM008334 and by a United Negro College
Fund-Merck Graduate Science Research Dissertation Fellowship. J.C.L. is
a Latham Family Career Development Professor.
NR 42
TC 42
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U1 0
U2 31
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 6
PY 2012
VL 109
IS 10
BP 3885
EP 3890
DI 10.1073/pnas.1111205109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700058
PM 22355106
ER
PT J
AU Annes, JP
Ryu, JH
Lam, K
Carolan, PJ
Utz, K
Hollister-Lock, J
Arvanites, AC
Rubin, LL
Weir, G
Melton, DA
AF Annes, Justin P.
Ryu, Jennifer Hyoje
Lam, Kelvin
Carolan, Peter J.
Utz, Katrina
Hollister-Lock, Jennifer
Arvanites, Anthony C.
Rubin, Lee L.
Weir, Gordon
Melton, Douglas A.
TI Adenosine kinase inhibition selectively promotes rodent and porcine
islet beta-cell replication
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chemical screening; regeneration
ID ADULT-MOUSE PANCREAS; COMPENSATORY GROWTH; GLUCOSE-INFUSION;
HUMAN-PREGNANCY; IN-VIVO; REGENERATION; EXPRESSION; PROGENITORS;
ENDOCRINE; MICE
AB Diabetes is a pathological condition characterized by relative insulin deficiency, persistent hyperglycemia, and, consequently, diffuse micro-and macrovascular disease. One therapeutic strategy is to amplify insulin-secretion capacity by increasing the number of the insulin-producing beta cells without triggering a generalized proliferative response. Here, we present the development of a small-molecule screening platform for the identification of molecules that increase beta-cell replication. Using this platform, we identify a class of compounds [ adenosine kinase inhibitors (ADK-Is)] that promote replication of primary beta cells in three species (mouse, rat, and pig). Furthermore, the replication effect of ADK-Is is cell type-selective: treatment of islet cell cultures with ADK-Is increases replication of beta cells but not that of alpha cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases beta-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes.
C1 [Annes, Justin P.; Ryu, Jennifer Hyoje; Lam, Kelvin; Carolan, Peter J.; Utz, Katrina; Arvanites, Anthony C.; Rubin, Lee L.; Melton, Douglas A.] Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Annes, Justin P.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Annes, Justin P.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Carolan, Peter J.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA.
[Hollister-Lock, Jennifer; Weir, Gordon] Harvard Univ, Sch Med, Dept Med, Sect Islet Cell & Regenerat Biol,Joslin Diabet Ct, Boston, MA 02115 USA.
[Melton, Douglas A.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
RP Melton, DA (reprint author), Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
EM dmelton@harvard.edu
FU Howard Hughes Medical Institute; National Institutes of Health
[DK084206, U01DK072505]; Diabetes Research and Wellness Foundation
FX We thank Yuval Dor, Qiao Zhao, Dena Cohen, Jayaraj Rajagopal, Julie
Sneddon, and Susan Bonner-Weir for their thoughtful input throughout the
development of this work. We are grateful for the technical support of
George Kenty, Kathryn Koszka, Bridget Molloy, Josh Cohen, Vaja
Tchipashvili, and Karolina Siniakowicz. This work was supported by the
Howard Hughes Medical Institute (D.A.M.), National Institutes of Health
Grants DK084206 (to J.P.A.) and U01DK072505 (to D.A.M.), and the
Diabetes Research and Wellness Foundation (G.W.).
NR 53
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U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 6
PY 2012
VL 109
IS 10
BP 3915
EP 3920
DI 10.1073/pnas.1201149109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700063
PM 22345561
ER
PT J
AU Kim, TH
Escudero, S
Shivdasani, RA
AF Kim, Tae-Hee
Escudero, Silvia
Shivdasani, Ramesh A.
TI Intact function of Lgr5 receptor-expressing intestinal stem cells in the
absence of Paneth cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID TRANSGENIC MICE; DIFFERENTIATION; EPITHELIUM; GENE; CANCER; MATH1;
MAINTENANCE; POPULATIONS; HOMEOSTASIS; ABLATION
AB Lifelong self-renewal of the adult intestinal epithelium requires the activity of stem cells located in mucosal crypts. Lgr5 and Bmi1 are two molecular markers of crypt-cell populations that replenish all lineages over time and hence function as stem cells. Intestinal stem cells require Wnt signaling, but the understanding of their cellular niche is incomplete. Lgr5-expressing crypt base columnar cells (CBCs) reside deep in the crypt, mingled among mature Paneth cells that are well positioned for short-range signaling. Partial lineage ablation previously had implied that Paneth cells are nonessential constituents of the stem-cell niche, but recently their absence was reported to interfere with Lgr5(+) CBCs, resurrecting an appealing idea. However, previous mouse models failed to remove Paneth cells completely or permanently; defining the intestinal stem-cell niche requires clarity with respect to the Paneth cell role. We find that Lgr5+ cells with stem-cell activity cluster in future crypts early in life, before Paneth cells develop. We also crossed conditional Atoh1(-/-) mice, which lack Paneth cells entirely, with Lgr5(GFP) mice to visualize Lgr5(+) CBCs and to track their stem-cell function. In the sustained absence of Paneth cells, Lgr5(+) CBCs occupied the full crypt base, proliferated briskly, and generated differentiated progeny over many months. Gene expression in fluorescence-sorted Lgr5(+) CBCs reflected intact Wnt signaling despite the loss of Paneth cells. Thus, Paneth cells are dispensable for survival, proliferation, and stem-cell activity of CBCs, and direct contact with Lgr5-nonexpressing cells is not essential for CBC function.
C1 [Kim, Tae-Hee; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kim, Tae-Hee; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Escudero, Silvia] Harvard Univ, Grad Program Biol & Biomed Sci, Cambridge, MA 02138 USA.
[Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM ramesh_shivdasani@dfci.harvard.edu
FU National Institutes of Health [R01DK081113, R01DK082889, RC2CA148222];
Harvard Stem Cell Institute; Dana Farber-Harvard Cancer Center
[P50CA127003]; Harvard Digestive Diseases Center [P50DK34854]
FX We thank Andre Ouellette for generously providing Crs4c1 Ab; Sylvie
Robine for kindly sharing VillinCreER mice; Susumu Ito for
assisting with electron microscopy; and Li-Lun Ho, Kodanda Nalapareddy,
and Michael Verzi for technical assistance and helpful discussions. This
work was supported by National Institutes of Health Grants R01DK081113,
R01DK082889, and RC2CA148222 and by an award from the Harvard Stem Cell
Institute and was enabled by core facilities supported by the Dana
Farber-Harvard Cancer Center Specialized Program in Research Excellence
in Gastrointestinal Cancers Grant P50CA127003 and Harvard Digestive
Diseases Center Grant P50DK34854.
NR 37
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U1 1
U2 15
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 6
PY 2012
VL 109
IS 10
BP 3932
EP 3937
DI 10.1073/pnas.1113890109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700066
PM 22355124
ER
PT J
AU Bakken, TE
Roddey, JC
Djurovic, S
Akshoomoff, N
Amaral, DG
Bloss, CS
Casey, BJ
Chang, L
Ernst, TM
Gruen, JR
Jernigan, TL
Kaufmann, WE
Kenet, T
Kennedy, DN
Kuperman, JM
Murray, SS
Sowell, ER
Rimol, LM
Mattingsdal, M
Melle, I
Agartz, I
Andreassen, OA
Schork, NJ
Dale, AM
AF Bakken, Trygve E.
Roddey, J. Cooper
Djurovic, Srdjan
Akshoomoff, Natacha
Amaral, David G.
Bloss, Cinnamon S.
Casey, B. J.
Chang, Linda
Ernst, Thomas M.
Gruen, Jeffrey R.
Jernigan, Terry L.
Kaufmann, Walter E.
Kenet, Tal
Kennedy, David N.
Kuperman, Joshua M.
Murray, Sarah S.
Sowell, Elizabeth R.
Rimol, Lars M.
Mattingsdal, Morten
Melle, Ingrid
Agartz, Ingrid
Andreassen, Ole A.
Schork, Nicholas J.
Dale, Anders M.
CA Alzheimer's Dis Neuroimaging
Pediat Imaging Neurocognition
TI Association of common genetic variants in GPCPD1 with scaling of visual
cortical surface area in humans
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE allometry; brain morphometry; imaging genetics; V1
ID GENOME-WIDE ASSOCIATION; GERMLINE MUTATIONS; MONOZYGOTIC TWINS; BRAIN
STRUCTURE; CORTEX; EMX2; PAX6; SIZE; EVOLUTION; PERFORMANCE
AB Visual cortical surface area varies two-to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P-combined = 3.2 x 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 x 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.
C1 [Bakken, Trygve E.; Bloss, Cinnamon S.; Murray, Sarah S.; Schork, Nicholas J.] Scripps Res Inst, Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA 92037 USA.
[Bakken, Trygve E.] Univ Calif San Diego, Med Scientist Training Program, La Jolla, CA 92093 USA.
[Roddey, J. Cooper] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Djurovic, Srdjan; Rimol, Lars M.; Mattingsdal, Morten; Melle, Ingrid; Agartz, Ingrid; Andreassen, Ole A.] Univ Oslo, Inst Clin Med, N-0450 Oslo, Norway.
[Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, N-0424 Oslo, Norway.
[Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA.
[Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA.
[Casey, B. J.] Weill Cornell Med Coll, Sackler Inst Dev Psychobiol, New York, NY 10065 USA.
[Chang, Linda; Ernst, Thomas M.] Univ Hawaii, Dept Med, Honolulu, HI 96813 USA.
[Chang, Linda; Ernst, Thomas M.] Queens Med Ctr, Honolulu, HI 96813 USA.
[Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA.
[Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
[Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA.
[Jernigan, Terry L.; Kuperman, Joshua M.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Kaufmann, Walter E.] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD 21205 USA.
[Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Kenet, Tal] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Kennedy, David N.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01605 USA.
[Sowell, Elizabeth R.] Univ So Calif, Dept Pediat, Los Angeles, CA 90027 USA.
[Sowell, Elizabeth R.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA.
[Mattingsdal, Morten; Melle, Ingrid; Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway.
[Agartz, Ingrid] Diakonhjemmet Hosp, Dept Res & Dev, N-0319 Oslo, Norway.
[Schork, Nicholas J.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
RP Schork, NJ (reprint author), Scripps Res Inst, Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA 92037 USA.
EM nschork@scripps.edu; amdale@ucsd.edu
RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin,
Andrew/A-1318-2007; Melle, Ingrid /B-4858-2011;
OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438;
Agartz, Ingrid/0000-0002-9839-5391; Andreassen, Ole
A./0000-0002-4461-3568; Saykin, Andrew/0000-0002-1376-8532; Melle,
Ingrid /0000-0002-9783-548X; Norbash, Alexander/0000-0003-2986-2563;
Bakken, Trygve/0000-0003-3373-7386; Rimol, Lars M./0000-0002-1243-0396;
de Leon, Mony/0000-0003-2245-4380
FU Oslo University Hospital-Ulleval; South-Eastern Norway Health Authority
[2004-123]; Research Council of Norway [167153/V50, 163070/V50];
Alzheimer's Disease Neuroimaging Initiative (ADNI) [U01 AG024904];
National Institute on Aging; National Institute of Biomedical Imaging
and Bioengineering; Pfizer Inc.; Wyeth Research; Bristol-Myers Squibb;
Eli Lilly and Company; GlaxoSmithKline; Merck and Co. Inc.; AstraZeneca
AB; Novartis Pharmaceuticals Corporation; Alzheimer's Association; Eisai
Global Clinical Development; Elan Corporation plc; Forest Laboratories;
Institute for the Study of Aging; US Food and Drug Administration;
National Institutes of Health [R01AG031224, R01AG22381, U54NS056883,
P50NS22343, P50MH081755, 5UL1RR025774, U01DA024417, R01AG030474,
R01MH080134, R01HL089655, U54CA143906, R01AG035020, R01DA030976,
U19AG023122-01, R01MH078151-01A1, N01MH22005, RC2DA029475]; Price
Foundation; Scripps Genomic Medicine
FX We thank the study participants and the members of the Thematically
Organized Psychosis Study group involved in data collection, especially
Drs. Jimmy Jensen, Per Nakstad, and Andres Server. We also thank Eivind
Bakken, Thomas Doug Bjella, Alan Koyama, Robin G. Jennings, Chris J.
Pung, and Dr. Christine Fennema-Notestine. This work was supported by
the Oslo University Hospital-Ulleval, South-Eastern Norway Health
Authority Grant 2004-123, Research Council of Norway Grants 167153/V50
and 163070/V50, and Eli Lilly Inc. for parts of the genotyping costs of
the TOP sample. Data collection and sharing for a portion of this
project was funded by the Alzheimer's Disease Neuroimaging Initiative
(ADNI; National Institute of Health Grant U01 AG024904). ADNI is funded
by the National Institute on Aging and the National Institute of
Biomedical Imaging and Bioengineering, and it is also funded through
generous contributions from Pfizer Inc., Wyeth Research, Bristol-Myers
Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck and Co. Inc.,
AstraZeneca AB, Novartis Pharmaceuticals Corporation, Alzheimer's
Association, Eisai Global Clinical Development, Elan Corporation plc,
Forest Laboratories, and the Institute for the Study of Aging, with
participation from the US Food and Drug Administration. Industry
partnerships are coordinated through the Foundation for the National
Institutes of Health. 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 at San Diego. ADNI data are disseminated by the
Laboratory of Neuroimaging at the University of California, Los Angeles.
This work was also supported in part by National Institutes of Health
Grants R01AG031224, R01AG22381, U54NS056883, P50NS22343, P50MH081755,
5UL1RR025774, U01DA024417, R01AG030474, R01MH080134, R01HL089655,
U54CA143906, R01AG035020, R01DA030976, U19AG023122-01, R01MH078151-01A1,
N01MH22005, and RC2DA029475. This work was also supported by the Price
Foundation and Scripps Genomic Medicine.
NR 57
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U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 6
PY 2012
VL 109
IS 10
BP 3985
EP 3990
DI 10.1073/pnas.1105829109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700075
PM 22343285
ER
PT J
AU Ananthakrishnan, AN
Higuchi, LM
Huang, ES
Khalili, H
Richter, JM
Fuchs, CS
Chan, AT
AF Ananthakrishnan, Ashwin N.
Higuchi, Leslie M.
Huang, Edward S.
Khalili, Hamed
Richter, James M.
Fuchs, Charles S.
Chan, Andrew T.
TI Aspirin, Nonsteroidal Anti-inflammatory Drug Use, and Risk for Crohn
Disease and Ulcerative Colitis A Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; LONG-TERM USE;
SPHINGOSINE KINASE; OLMSTED COUNTY; PREVALENCE; MICE; IBD;
REPRODUCIBILITY; PERMEABILITY
AB Background: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC).
Objective: To assess the association between aspirin and NSAID use and incident CD and UC.
Design: Prospective cohort study.
Setting: Nurses' Health Study I.
Patients: 76 795 U. S. women who provided biennially updated data about aspirin and NSAID use.
Measurements: Incident CD and UC between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure).
Results: 123 incident cases of CD and 117 cases of UC occurred over 18 years and 1 295 317 person-years of follow-up. Compared with nonusers, women who used NSAIDs at least 15 days per month seemed to have increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100 000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference, 7 cases per 100 000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk for CD or UC, and there was no clear association between aspirin use and disease.
Limitations: Cohort participants were exclusively women, most of whom were white. Aspirin and NSAID use were self-reported.
Conclusion: Frequent use of NSAIDs but not aspirin seemed to be associated with increased absolute incidence of CD and UC. The findings have more mechanistic than clinical implications, because the absolute incidence of CD or UC associated with NSAIDs was low and the increase in risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more common and clinically significant risks and benefits associated with these agents.
C1 [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit,Childrens Hosp Boston, Brigham & Womens Hosp,Sch Med, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Chan, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit,Childrens Hosp Boston, Brigham & Womens Hosp,Sch Med, 55 Fruit St,GRJ 722, Boston, MA 02114 USA.
EM achan@partners.org
FU American Gastroenterological Association; IBD Working Group; Broad
Medical Research Program; National Institutes of Health [R01 CA137178,
P01 CA87969, P30 DK043351, K08 DK064256]; Broad Medical Research
Foundation
FX American Gastroenterological Association, IBD Working Group, Broad
Medical Research Program, and National Institutes of Health.; By the
American Gastroenterological Association (Dr. Ananthakrishnan), the
Broad Medical Research Foundation ( Dr. Chan), the IBD Working Group (
Dr. Khalili), and the National Institutes of Health (R01 CA137178, P01
CA87969, P30 DK043351, and K08 DK064256).
NR 41
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U1 2
U2 9
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 6
PY 2012
VL 156
IS 5
BP 350
EP U170
DI 10.7326/0003-4819-156-5-201203060-00007
PG 18
WC Medicine, General & Internal
SC General & Internal Medicine
GA 902OC
UT WOS:000301046800003
PM 22393130
ER
PT J
AU Liu, CF
Bryson, CL
Burgess, JF
Sharp, N
Perkins, M
Maciejewski, ML
AF Liu, Chuan-Fen
Bryson, Chris L.
Burgess, James F., Jr.
Sharp, Nancy
Perkins, Mark
Maciejewski, Matthew L.
TI Use of outpatient care in VA and Medicare among disability-eligible and
age-eligible veteran patients
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
DE Outpatient; Utilization; Primary care; Veterans; Medicare
ID TRAUMATIC BRAIN-INJURY; HEALTH-CARE; RISK ADJUSTMENT; DUAL ELIGIBLES;
BENEFICIARIES; AFFAIRS; SERVICES; AFGHANISTAN; POPULATION; IRAQ
AB Background: More than half of veterans who use Veterans Health Administration (VA) care are also eligible for Medicare via disability or age, but no prior studies have examined variation in use of outpatient services by Medicare-eligible veterans across health system, type of care or time.
Objectives: To examine differences in use of VA and Medicare outpatient services by disability-eligible or age-eligible veterans among veterans who used VA primary care services and were also eligible for Medicare.
Methods: A retrospective cohort study of 4,704 disability-and 10,816 age-eligible veterans who used VA primary care services in fiscal year (FY) 2000. We tracked their outpatient utilization from FY2001 to FY2004 using VA administrative and Medicare claims data. We examined utilization differences for primary care, specialty care, and mental health outpatient visits using generalized estimating equations.
Results: Among Medicare-eligible veterans who used VA primary care, disability-eligible veterans had more VA primary care visits (p < 0.001) and more VA specialty care visits (p < 0.001) than age-eligible veterans. They were more likely to have mental health visits in VA (p < 0.01) and Medicare-reimbursed visits (p < 0.01). Disability-eligible veterans also had more total (VA+Medicare) visits for primary care (p < 0.01) and specialty care (p < 0.01), controlling for patient characteristics.
Conclusions: Greater use of primary care and specialty care visits by disability-eligible veterans is most likely related to greater health needs not captured by the patient characteristics we employed and eligibility for VA care at no cost. Outpatient care patterns of disability-eligible veterans may foreshadow care patterns of veterans returning from Afghanistan and Iraq wars, who are entering the system in growing numbers. This study provides an important baseline for future research assessing utilizations among returning veterans who use both VA and Medicare systems. Establishing effective care coordination protocols between VA and Medicare providers can help ensure efficient use of taxpayer resources and high quality care for disabled veterans.
C1 [Liu, Chuan-Fen; Bryson, Chris L.; Sharp, Nancy; Perkins, Mark] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA.
[Liu, Chuan-Fen; Sharp, Nancy] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Bryson, Chris L.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA.
[Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA.
[Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27706 USA.
RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM Chuan-Fen.Liu@va.gov
OI Burgess, James/0000-0002-6646-7071
FU Office of Research and Development, Health Services Research and
Development Service, Department of Veterans Affairs [IIR 04- 292]
FX This work was supported by the Office of Research and Development,
Health Services Research and Development Service, Department of Veterans
Affairs, project number IIR 04- 292. Drs. Liu, Bryson, Sharp, and
Perkins are at the Northwest Center for Outcomes Research in Older
Adults at the VA Puget Sound Health Care System, Seattle Division. Dr.
Burgess is at the Center for Organization, Leadership and Management
Research at the VA Boston Healthcare System. Dr. Maciejewski is at
Center for Health Services Research in Primary Care at the Durham VA
Medical Center and a VA Research Career Scientist. The views expressed
herein are those of the authors and do not necessarily represent the
views of the Department of Veterans Affairs, the University of
Washington, Boston University, or Duke University.
NR 56
TC 2
Z9 2
U1 4
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD MAR 5
PY 2012
VL 12
AR 51
DI 10.1186/1472-6963-12-51
PG 13
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 947DV
UT WOS:000304407900001
ER
PT J
AU Mueller, R
Dawson, ES
Meiler, J
Rodriguez, AL
Chauder, BA
Bates, BS
Felts, AS
Lamb, JP
Menon, UN
Jadhav, SB
Kane, AS
Jones, CK
Gregory, KJ
Niswender, CM
Conn, PJ
Olsen, CM
Winder, DG
Emmitte, KA
Lindsley, CW
AF Mueller, Ralf
Dawson, Eric S.
Meiler, Jens
Rodriguez, Alice L.
Chauder, Brian A.
Bates, Brittney S.
Felts, Andrew S.
Lamb, Jeffrey P.
Menon, Usha N.
Jadhav, Sataywan B.
Kane, Alexander S.
Jones, Carrie K.
Gregory, Karen J.
Niswender, Colleen M.
Conn, P. Jeffrey
Olsen, Christopher M.
Winder, Danny G.
Emmitte, Kyle A.
Lindsley, Craig W.
TI Discovery of 2-(2-Benzoxazoyl amino)-4-Aryl-5-Cyanopyrimidine as
Negative Allosteric Modulators (NAMs) of Metabotropic Glutamate Receptor
5 (mGlu5): From an Artificial Neural Network Virtual Screen to an In
Vivo Tool Compound
SO CHEMMEDCHEM
LA English
DT Article
DE addiction; allosteric modulators; artificial neural networks;
metabotropic glutamate receptors; structure-activity relationships
ID LOCOMOTOR-ACTIVITY; MICE; IDENTIFICATION; ANTAGONISTS; SUBTYPE-5; LEAD;
2-METHYL-6-(PHENYLETHYNYL)PYRIDINE; POTENTIATORS; PHARMACOLOGY;
DISORDERS
C1 [Mueller, Ralf; Meiler, Jens; Emmitte, Kyle A.; Lindsley, Craig W.] Vanderbilt Univ, Dept Chem, Stevenson Ctr 7330, Nashville, TN 37232 USA.
[Dawson, Eric S.; Rodriguez, Alice L.; Chauder, Brian A.; Bates, Brittney S.; Felts, Andrew S.; Lamb, Jeffrey P.; Menon, Usha N.; Jadhav, Sataywan B.; Kane, Alexander S.; Jones, Carrie K.; Gregory, Karen J.; Niswender, Colleen M.; Conn, P. Jeffrey; Emmitte, Kyle A.; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr MRBIV 12475, Dept Pharmacol, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA.
[Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst TVHS, Nashville, TN 37212 USA.
[Gregory, Karen J.] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic, Australia.
[Olsen, Christopher M.; Winder, Danny G.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Med Ctr, Nashville, TN 37232 USA.
RP Mueller, R (reprint author), Vanderbilt Univ, Dept Chem, Stevenson Ctr 7330, Stn B 351822, Nashville, TN 37232 USA.
EM jens.meiler@vanderbilt.edu; craig.lindsley@vanderbilt.edu
RI Conn, Peter/D-7848-2012; Olsen, Christopher/C-3542-2008; Winder,
Danny/H-4857-2013;
OI Olsen, Christopher/0000-0003-2700-0310; Gregory,
Karen/0000-0002-3833-2137
FU US National Institutes of Health (NIH); US National Institute on Drug
Abuse (NIDA) [R01DA023947-01]; US National Institute of Mental Health
(NIMH) [R01090192-01]
FX The authors warmly thank the US National Institutes of Health (NIH), and
in particular the US National Institute on Drug Abuse (NIDA;
R01DA023947-01) and the US National Institute of Mental Health (NIMH;
R01090192-01), for support of our programs in drug discovery. The
authors also thank Daryl F. Venable (Vanderbilt University, Nashville,
USA) for technical assistance with the calcium flux and radioligand
binding assays.
NR 51
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Z9 15
U1 0
U2 5
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD MAR 5
PY 2012
VL 7
IS 3
SI SI
BP 406
EP 414
DI 10.1002/cmdc.201100510
PG 9
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 901DQ
UT WOS:000300942300009
PM 22267125
ER
PT J
AU Choi, SH
Tanzi, RE
AF Choi, Se Hoon
Tanzi, Rudolph E.
TI iPSCs to the Rescue in Alzheimer's Research
SO CELL STEM CELL
LA English
DT Editorial Material
ID PLURIPOTENT STEM-CELLS; DISEASE; GENE
AB A crucial limitation to our understanding of Alzheimer's disease has been the inability to test hypotheses on live, patient-specific neurons. A recent study in Nature by Israel et al. (2012) reports that iPSC-derived neurons from AD patients recapitulate multiple aspects of disease pathology.
C1 [Choi, Se Hoon; Tanzi, Rudolph E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 02129 USA.
RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 02129 USA.
EM tanzi@helix.mgh.harvard.edu
NR 9
TC 10
Z9 11
U1 0
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAR 2
PY 2012
VL 10
IS 3
BP 235
EP 236
DI 10.1016/j.stem.2012.02.011
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 908BX
UT WOS:000301466500003
PM 22385650
ER
PT J
AU Park, D
Spencer, JA
Koh, BI
Kobayashi, T
Fujisaki, J
Clemens, TL
Lin, CP
Kronenberg, HM
Scadden, DT
AF Park, Dongsu
Spencer, Joel A.
Koh, Bong Ihn
Kobayashi, Tatsuya
Fujisaki, Joji
Clemens, Thomas L.
Lin, Charles P.
Kronenberg, Henry M.
Scadden, David T.
TI Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants in
Bone Maintenance and Regeneration
SO CELL STEM CELL
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; HEMATOPOIETIC STEM; PROGENITOR CELLS;
OSTEOBLAST; MICROENVIRONMENT; NICHE; DIFFERENTIATION; SPECIFICATION;
POPULATION
AB Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1(+) stromal cells with "MSC" features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1(+) population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton.
C1 [Park, Dongsu; Koh, Bong Ihn; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Spencer, Joel A.; Fujisaki, Joji; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Program, Boston, MA 02114 USA.
[Spencer, Joel A.; Fujisaki, Joji; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Park, Dongsu; Spencer, Joel A.; Koh, Bong Ihn; Fujisaki, Joji; Lin, Charles P.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Clemens, Thomas L.] Johns Hopkins Med, Ctr Musculoskeletal Res, Baltimore, MD 21287 USA.
[Park, Dongsu; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.
EM david_scadden@harvard.edu
RI Spencer, Joel/A-4590-2013
FU Leukemia & Lymphoma Society; National Institutes of Health
FX We thank C. Lo Celso, S. Mukherjee, J. Schoonmaker, S. Guo, R.
Schlanger, and M. Kim for advice and technical assistance; N. Jeanson,
A. Catic, J. Dietrich, and D. Sykes for reading the manuscript; the
HSCl/MGH CRM Flow Core (L. Prickett, K. Folz-Donahue, and D.
Dombkowski); and the Leukemia & Lymphoma Society (Fellowship Award to
D.P.) and the National Institutes of Health (grants to T.L.C., C.P.L.,
H.M.K., and D.T.S.).
NR 33
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U1 6
U2 46
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAR 2
PY 2012
VL 10
IS 3
BP 259
EP 272
DI 10.1016/j.stem.2012.02.003
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 908BX
UT WOS:000301466500008
PM 22385654
ER
PT J
AU Cavasin, MA
Demos-Davies, K
Horn, TR
Walker, LA
Lemon, DD
Birdsey, N
Weiser-Evans, MCM
Harral, J
Irwin, DC
Anwar, A
Yeager, ME
Li, M
Watson, PA
Nemenoff, RA
Buttrick, PM
Stenmark, KR
McKinsey, TA
AF Cavasin, Maria A.
Demos-Davies, Kim
Horn, Todd R.
Walker, Lori A.
Lemon, Douglas D.
Birdsey, Nicholas
Weiser-Evans, Mary C. M.
Harral, Julie
Irwin, David C.
Anwar, Adil
Yeager, Michael E.
Li, Min
Watson, Peter A.
Nemenoff, Raphael A.
Buttrick, Peter M.
Stenmark, Kurt R.
McKinsey, Timothy A.
TI Selective Class I Histone Deacetylase Inhibition Suppresses
Hypoxia-Induced Cardiopulmonary Remodeling Through an Antiproliferative
Mechanism
SO CIRCULATION RESEARCH
LA English
DT Article
DE histone deacetylase; pulmonary hypertension; proliferation; gene
expression; signaling pathways
ID PULMONARY ARTERIAL-HYPERTENSION; FORKHEAD TRANSCRIPTION FACTOR;
CARDIAC-HYPERTROPHY; SURVIVAL; PROLIFERATION; INFLAMMATION; ACTIVATION;
EMERGENCE; GROWTH; CELLS
AB Rationale: Histone deacetylase (HDAC) inhibitors are efficacious in models of hypertension-induced left ventricular heart failure. The consequences of HDAC inhibition in the context of pulmonary hypertension with associated right ventricular cardiac remodeling are poorly understood.
Objective: This study was performed to assess the utility of selective small-molecule inhibitors of class I HDACs in a preclinical model of pulmonary hypertension.
Methods and Results: Rats were exposed to hypobaric hypoxia for 3 weeks in the absence or presence of a benzamide HDAC inhibitor, MGCD0103, which selectively inhibits class I HDACs 1, 2, and 3. The compound reduced pulmonary arterial pressure more dramatically than tadalafil, a standard-of-care therapy for human pulmonary hypertension that functions as a vasodilator. MGCD0103 improved pulmonary artery acceleration time and reduced systolic notching of the pulmonary artery flow envelope, which suggests a positive impact of the HDAC inhibitor on pulmonary vascular remodeling and stiffening. Similar results were obtained with an independent class I HDAC-selective inhibitor, MS-275. Reduced pulmonary arterial pressure in MGCD0103-treated animals was associated with blunted pulmonary arterial wall thickening because of suppression of smooth muscle cell proliferation. Right ventricular function was maintained in MGCD0103-treated animals. Although the class I HDAC inhibitor only modestly reduced right ventricular hypertrophy, it had multiple beneficial effects on the right ventricle, which included suppression of pathological gene expression, inhibition of proapoptotic caspase activity, and repression of proinflammatory protein expression.
Conclusions: By targeting distinct pathogenic mechanisms, isoform-selective HDAC inhibitors have potential as novel therapeutics for pulmonary hypertension that will complement vasodilator standards of care. (Circ Res. 2012;110:739-748.)
C1 [Cavasin, Maria A.; Demos-Davies, Kim; Horn, Todd R.; Walker, Lori A.; Lemon, Douglas D.; Irwin, David C.; Buttrick, Peter M.; McKinsey, Timothy A.] Univ Colorado Denver, Dept Med, Div Cardiol, Aurora, CO 80045 USA.
[Birdsey, Nicholas; Watson, Peter A.] Univ Colorado Denver, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA.
[Weiser-Evans, Mary C. M.; Nemenoff, Raphael A.] Univ Colorado Denver, Div Renal Dis & Hypertens, Aurora, CO 80045 USA.
[Harral, Julie; Anwar, Adil; Yeager, Michael E.; Li, Min; Stenmark, Kurt R.] Univ Colorado Denver, Dept Pediat, Div Pulm & Crit Care Med, Aurora, CO 80045 USA.
[Watson, Peter A.] Denver VA Med Ctr, Denver, CO USA.
RP McKinsey, TA (reprint author), Univ Colorado Denver, Dept Med, Div Cardiol, 12700 E 19th Ave, Aurora, CO 80045 USA.
EM timothy.mckinsey@ucdenver.edu
RI Walker, Lori/J-7098-2013
OI Walker, Lori/0000-0003-2556-8076
FU Department of Veterans Affairs
FX P.A.W. was supported by a Department of Veterans Affairs Merit Award.
NR 33
TC 67
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U1 0
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD MAR 2
PY 2012
VL 110
IS 5
BP 739
EP U250
DI 10.1161/CIRCRESAHA.111.258426
PG 22
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 902NP
UT WOS:000301045500014
PM 22282194
ER
PT J
AU Mandal, PK
Rossi, DJ
AF Mandal, Pankaj K.
Rossi, Derrick J.
TI DNA-Damage-Induced Differentiation in Hematopoietic Stem Cells
SO CELL
LA English
DT Editorial Material
AB Aging of hematopoietic stem cells (HSCs) is accompanied by diminished functional potential. Wang et al. now provide evidence for an HSC-specific differentiation checkpoint mediated by the transcription factor BATF, which limits self-renewal of HSCs in response to the accumulation of DNA damage.
C1 [Mandal, Pankaj K.; Rossi, Derrick J.] Harvard Univ, Program Cellular & Mol Med, Childrens Hosp Boston, Dept Stem Cell & Regenerat Biol,Immune Dis Inst, Boston, MA 02116 USA.
RP Rossi, DJ (reprint author), Harvard Univ, Program Cellular & Mol Med, Childrens Hosp Boston, Dept Stem Cell & Regenerat Biol,Immune Dis Inst, Boston, MA 02116 USA.
EM rossi@idi.harvard.edu
RI mandal, pankaj/B-4885-2016
NR 10
TC 8
Z9 8
U1 3
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 2
PY 2012
VL 148
IS 5
BP 847
EP 848
DI 10.1016/j.cell.2012.02.011
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 901RR
UT WOS:000300985000006
PM 22385954
ER
PT J
AU Ding, ZH
Wu, CJ
Jaskelioff, M
Ivanova, E
Kost-Alimova, M
Protopopov, A
Chu, GC
Wang, GC
Lu, X
Labrot, ES
Hu, J
Wang, W
Xiao, YH
Zhang, HL
Zhang, JH
Zhang, JF
Gan, BY
Perry, SR
Jiang, S
Li, LR
Horner, JW
Wang, YA
Chin, LD
DePinho, RA
AF Ding, Zhihu
Wu, Chang-Jiun
Jaskelioff, Mariela
Ivanova, Elena
Kost-Alimova, Maria
Protopopov, Alexei
Chu, Gerald C.
Wang, Guocan
Lu, Xin
Labrot, Emma S.
Hu, Jian
Wang, Wei
Xiao, Yonghong
Zhang, Hailei
Zhang, Jianhua
Zhang, Jingfang
Gan, Boyi
Perry, Samuel R.
Jiang, Shan
Li, Liren
Horner, James W.
Wang, Y. Alan
Chin, Lynda
DePinho, Ronald A.
TI Telomerase Reactivation following Telomere Dysfunction Yields Murine
Prostate Tumors with Bone Metastases
SO CELL
LA English
DT Article
ID GENE-EXPRESSION ANALYSIS; INTRAEPITHELIAL NEOPLASIA; CANCER PROGRESSION;
GENOME INSTABILITY; BREAST-CANCER; CARCINOMA; TUMORIGENESIS; MICE;
PROTEIN; DAMAGE
AB To determine the role of telomere dysfunction and telomerase reactivation in generating pro-oncogenic genomic events and in carcinoma progression, an inducible telomerase reverse transcriptase (mTert) allele was crossed onto a prostate cancer-prone mouse model null for Pten and p53 tumor suppressors. Constitutive telomerase deficiency and associated telomere dysfunction constrained cancer progression. In contrast, telomerase reactivation in the setting of telomere dysfunction alleviated intratumoral DNA-damage signaling and generated aggressive cancers with rearranged genomes and new tumor biological properties (bone metastases). Comparative oncogenomic analysis revealed numerous recurrent amplifications and deletions of relevance to human prostate cancer. Murine tumors show enrichment of the TGF-beta/SMAD4 network, and genetic validation studies confirmed the cooperative roles of Pten, p53, and Smad4 deficiencies in prostate cancer progression, including skeletal metastases. Thus, telomerase reactivation in tumor cells experiencing telomere dysfunction enables full malignant progression and provides a mechanism for acquisition of cancer-relevant genomic events endowing new tumor biological capabilities.
C1 [Wu, Chang-Jiun; Kost-Alimova, Maria; Protopopov, Alexei; Zhang, Jianhua; Horner, James W.; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
[Ding, Zhihu; Wang, Guocan; Lu, Xin; Hu, Jian; Wang, Wei; Jiang, Shan; Wang, Y. Alan; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Kost-Alimova, Maria; Protopopov, Alexei; Zhang, Jianhua; Horner, James W.; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA.
[Ding, Zhihu; Wu, Chang-Jiun; Jaskelioff, Mariela; Ivanova, Elena; Kost-Alimova, Maria; Protopopov, Alexei; Chu, Gerald C.; Wang, Guocan; Lu, Xin; Labrot, Emma S.; Hu, Jian; Wang, Wei; Xiao, Yonghong; Zhang, Hailei; Zhang, Jianhua; Zhang, Jingfang; Gan, Boyi; Perry, Samuel R.; Jiang, Shan; Li, Liren; Horner, James W.; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Ding, Zhihu; Jaskelioff, Mariela; Wang, Guocan; Lu, Xin; Hu, Jian; Wang, Wei; Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Ding, Zhihu; Jaskelioff, Mariela; Wang, Guocan; Lu, Xin; Hu, Jian; Wang, Wei; Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Chu, Gerald C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
RP Chin, LD (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
EM lchin@mdanderson.org; rdepinho@mdanderson.org
RI perumal, murugiah/D-1565-2012
FU Damon Runyon Cancer Research Foundation; Multiple Myeloma Research
Foundation; Prostate Cancer Foundation; DOD [W81XWH-07-PCRP-IDA]; Robert
A. and Renee E. Belfer Foundation; [NCI R01CA084628]; [U01CA141508]
FX We thank S. Zhou and J.P. Morin for excellent mouse husbandry and care,
J. Paik, M. Kim, and H. Ying for helpful discussion. We thank W. Hahn
for shRNA constructs. Z.D. was supported by the Damon Runyon Cancer
Research Foundation. Y.A.W. was supported by the Multiple Myeloma
Research Foundation. This work is supported by NCI R01CA084628 (R.A.D.),
U01CA141508 (L.C. and R.A.D.), the Prostate Cancer Foundation (R.A.D.
and Z.D.), and DOD W81XWH-07-PCRP-IDA (R.A.D. and Z.D.). R.A.D. was an
American Cancer Society Research Professor and supported by the Robert
A. and Renee E. Belfer Foundation. The gene signature and technology
developed in this paper have been licensed by Metamark GENETICS
(http://www.metamarkgenetics.com/). L.C. and R.A.D. are the founders of
Metamark GENETICS. Z.D. and C.J.W. are consultants for Metamark
GENETICS.
NR 57
TC 93
Z9 97
U1 1
U2 25
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 2
PY 2012
VL 148
IS 5
BP 896
EP 907
DI 10.1016/j.cell.2012.01.039
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 901RR
UT WOS:000300985000011
PM 22341455
ER
PT J
AU Zhang, Y
McCord, RP
Ho, YJ
Lajoie, BR
Hildebrand, DG
Simon, AC
Becker, MS
Alt, FW
Dekker, J
AF Zhang, Yu
McCord, Rachel Patton
Ho, Yu-Jui
Lajoie, Bryan R.
Hildebrand, Dominic G.
Simon, Aline C.
Becker, Michael S.
Alt, Frederick W.
Dekker, Job
TI Spatial Organization of the Mouse Genome and Its Role in Recurrent
Chromosomal Translocations
SO CELL
LA English
DT Article
ID DOUBLE-STRAND BREAKS; V(D)J RECOMBINATION; SEQUENCING REVEALS; B-CELLS;
C-MYC; MECHANISMS; CANCER; REARRANGEMENTS; LYMPHOCYTES; STABILITY
AB The extent to which the three-dimensional organization of the genome contributes to chromosomal translocations is an important question in cancer genomics. We generated a high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome and used high-throughput genome-wide translocation sequencing to map translocations from target DNA double-strand breaks (DSBs) within it. RAG endonuclease-cleaved antigen-receptor loci are dominant translocation partners for target DSBs regardless of genomic position, reflecting high-frequency DSBs at these loci and their colocalization in a fraction of cells. To directly assess spatial proximity contributions, we normalized genomic DSBs via ionizing radiation. Under these conditions, translocations were highly enriched in cis along single chromosomes containing target DSBs and within other chromosomes and subchromosomal domains in a manner directly related to pre-existing spatial proximity. By combining two high-throughput genomic methods in a genetically tractable system, we provide a new lens for viewing cancer genomes.
C1 [Zhang, Yu; Ho, Yu-Jui; Hildebrand, Dominic G.; Simon, Aline C.; Becker, Michael S.; Alt, Frederick W.] Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Zhang, Yu; Ho, Yu-Jui; Hildebrand, Dominic G.; Simon, Aline C.; Becker, Michael S.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Zhang, Yu; Ho, Yu-Jui; Hildebrand, Dominic G.; Simon, Aline C.; Becker, Michael S.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[McCord, Rachel Patton; Lajoie, Bryan R.; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Programs Syst Biol, Worcester, MA 01605 USA.
[McCord, Rachel Patton; Lajoie, Bryan R.; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Programs Gene Funct & Express, Worcester, MA 01605 USA.
RP Alt, FW (reprint author), Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu; job.dekker@umassmed.edu
FU NIH [3P01CA092625-09S1, R01 HG003143]; Leukemia and Lymphoma Society of
America (LLS) SCOR; W.M. Keck Foundation; German National Merit
Foundation
FX This work was supported by NIH grant ARRA Supplement 3P01CA092625-09S1
and a Leukemia and Lymphoma Society of America (LLS) SCOR grant to F. W.
A. and by NIH grant R01 HG003143 and a W.M. Keck Foundation
Distinguished Young Scholar Award to J.D. Y.Z. was supported by CRI
postdoctoral fellowship. D. G. H., A. C. S., and M. G. B. were supported
by the German National Merit Foundation. F. W. A. is an Investigator of
the Howard Hughes Medical Institute.
NR 49
TC 234
Z9 243
U1 4
U2 40
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 2
PY 2012
VL 148
IS 5
BP 908
EP 921
DI 10.1016/j.cell.2012.02.002
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 901RR
UT WOS:000300985000012
PM 22341456
ER
PT J
AU Chipuk, JE
McStay, GP
Bharti, A
Kuwana, T
Clarke, CJ
Siskind, LJ
Obeid, LM
Green, DR
AF Chipuk, Jerry E.
McStay, Gavin P.
Bharti, Archana
Kuwana, Tomomi
Clarke, Christopher J.
Siskind, Leah J.
Obeid, Lina M.
Green, Douglas R.
TI Sphingolipid Metabolism Cooperates with BAK and BAX to Promote the
Mitochondrial Pathway of Apoptosis
SO CELL
LA English
DT Article
ID RADIATION-INDUCED APOPTOSIS; PROGRAMMED CELL-DEATH;
ENDOPLASMIC-RETICULUM; NEUTRAL SPHINGOMYELINASE; OUTER-MEMBRANE; BCL-2
FAMILY; CYTOCHROME-C; BH3 DOMAINS; HELA-CELLS; CERAMIDE
AB Mitochondria are functionally and physically associated with heterotypic membranes, yet little is known about how these interactions impact mitochondrial outer-membrane permeabilization (MOMP) and apoptosis. We observed that dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX-dependent cytochrome c (cyto c) release. Biochemical purification of neutral sphingomyelinases that correlated with MOMP sensitization suggested that sphingolipid metabolism coordinates BAK/BAX activation. Using purified lipids and enzymes, sensitivity to MOMP was achieved by in vitro reconstitution of the sphingolipid metabolic pathway. Sphingolipid metabolism inhibitors blocked MOMP from heavy membrane preparations but failed to influence MOMP in the presence of sphingolipid-reconstituted, purified mitochondria. Furthermore, the sphingolipid products, sphingosine-1-PO4 and hexadecenal, cooperated specifically with BAK and BAX, respectively. Sphingolipid metabolism was also required for cellular responses to apoptosis. Our studies suggest that BAK/BAX activation and apoptosis are coordinated through BH3-only proteins and a specific lipid milieu that is maintained by heterotypic membrane-mitochondrial interactions.
C1 [Chipuk, Jerry E.; Bharti, Archana] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA.
[McStay, Gavin P.; Green, Douglas R.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA.
[Kuwana, Tomomi] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52252 USA.
[Clarke, Christopher J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Siskind, Leah J.; Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
[Siskind, Leah J.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Div Gen Med & Geriatr, Charleston, SC 29425 USA.
RP Chipuk, JE (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM jerry.chipuk@mssm.edu; douglas.green@stjude.org
OI Chipuk, Jerry Edward/0000-0002-1337-842X; obeid,
lina/0000-0002-0734-0847
FU NIH [CA157740, P20AA017067, AI52735, CA69381, AG024478]; NCI Cancer
Center Core [P30CA21765]; VA Merit; VA [CDA-2]; VA REAP; ACS
[IRG-97-219-11]; Cancer Center [P30 CA138313]; COBRE in Lipidomics and
Pathobiology [NIH/NCRRP20 RR17677]; American Lebanese Syrian Associated
Charities; March of Dimes Foundation [5-FY11-74]
FX We would like to thank Dr. Ronald Gordon (MSSM) for TEM analysis; Dr.
Richard Kolesnick (Memorial Sloan-Kettering) for the asm-/-
liver; Dr. Joseph Opferman (SJCRH) for the MxCre bak-/-
bax-/f animals; all members of the Obeid and Hannun
laboratories (MUSC) for excellent discussion and training in
sphingolipid biology, especially Drs. K. Alexa Orr Gandy, Stefka
Spassieva, and Xingjun Wu; The Hartwell Center for Bioinformatics and
Biotechnology; and members of the Kuwana Laboratory for technical
assistance. This work was supported by: NIH CA157740 (to J.E.C.), pilot
project from NIH P20AA017067 (to J.E.C.), NIH AI52735 (to D. R. G.),
CA69381 (to D. R. G.), NIH AG024478 (to T. K.), an NCI Cancer Center
Core Grant P30CA21765 (SJCRH), VA Merit (to L.M.O.), VA CDA-2 Award (to
L.J.S), pilot project from the VA REAP (to L.J.S., and L.M.O.), the ACS
IRG # IRG-97-219-11 (subaward to L.J.S.), Lipidomics Shared Resource of
the Hollings Cancer Center supported by a Cancer Center Support Grant
(P30 CA138313), pilot project (to L.J.S) from the NIH/NCRRP20 RR17677
COBRE in Lipidomics and Pathobiology, and the American Lebanese Syrian
Associated Charities. This work was also supported in part by a Research
Grant 5-FY11-74 from the March of Dimes Foundation (to J.E.C.).
NR 62
TC 140
Z9 146
U1 0
U2 41
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 2
PY 2012
VL 148
IS 5
BP 988
EP 1000
DI 10.1016/j.cell.2012.01.038
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 901RR
UT WOS:000300985000018
PM 22385963
ER
PT J
AU Gnant, M
Hortobagyi, GN
Rugo, H
Burris, HA
Noguchi, S
Pritchard, KI
Baselga, J
Sahmoud, T
Bauly, H
Piccart, M
AF Gnant, M.
Hortobagyi, G. N.
Rugo, H.
Burris, H. A.
Noguchi, S.
Pritchard, K. I.
Baselga, J.
Sahmoud, T.
Bauly, H.
Piccart, M.
TI Everolimus Added to Exemestane Reduced Bone Markers and Disease
Progression in Bone in Postmenopausal Women with Advanced Breast Cancer:
Updated Results From the BOLERO-2 Trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Gnant, M.] Univ Vienna, Dept Surg, Vienna, Austria.
[Hortobagyi, G. N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Rugo, H.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Burris, H. A.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA.
[Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan.
[Pritchard, K. I.] Univ Toronto, Toronto, ON, Canada.
[Pritchard, K. I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Baselga, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sahmoud, T.] Novartis Pharmaceut, Florham Pk, NJ USA.
[Bauly, H.] Novartis Pharma AG, Basel, Switzerland.
[Piccart, M.] Inst Jules Bordet, B-1000 Brussels, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 3
MA 3LBA
BP S2
EP S2
PG 1
WC Oncology
SC Oncology
GA 063VC
UT WOS:000313029100004
ER
PT J
AU Greenstein, J
AF Greenstein, Julia
TI Juvenile Diabetes Research Foundation: Seeding Novel Insights in
Diabetes Research
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
C1 [Greenstein, Julia] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Greenstein, Julia] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD MAR
PY 2012
VL 1
IS 3
BP 175
EP 176
DI 10.5966/sctm.2012-0007
PG 2
WC Cell & Tissue Engineering
SC Cell Biology
GA 057NY
UT WOS:000312571500006
PM 23197776
ER
PT J
AU Carroll, DL
AF Carroll, D. L.
TI Nurses perceptions of family presence in the intensive care unit during
resuscitation and invasive procedures
SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Meeting Abstract
C1 [Carroll, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1474-5151
J9 EUR J CARDIOVASC NUR
JI Eur. J. Cardiovasc. Nurs.
PD MAR
PY 2012
VL 11
SU 1
BP S70
EP S71
PG 2
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA 046YT
UT WOS:000311802500138
ER
PT J
AU Matura, LA
Mc Donough, A
Carroll, DL
AF Matura, L. A.
Mc Donough, A.
Carroll, D. L.
TI Determinants of health-related quality of life in pulmonary arterial
hypertension
SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING
LA English
DT Meeting Abstract
C1 [Matura, L. A.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
[Mc Donough, A.] Univ Massachusetts, Lowell, MA USA.
[Carroll, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1474-5151
J9 EUR J CARDIOVASC NUR
JI Eur. J. Cardiovasc. Nurs.
PD MAR
PY 2012
VL 11
SU 1
BP S82
EP S83
PG 2
WC Cardiac & Cardiovascular Systems; Nursing
SC Cardiovascular System & Cardiology; Nursing
GA 046YT
UT WOS:000311802500163
ER
PT J
AU Wasfy, MM
Brady, TJ
Abbara, S
Nasir, K
Hoffmann, U
Cury, RC
Di Carli, MF
Blankstein, R
AF Wasfy, Meagan M.
Brady, Thomas J.
Abbara, Suhny
Nasir, Khurram
Hoffmann, Udo
Cury, Ricardo C.
Di Carli, Marcelo F.
Blankstein, Ron
TI Comparison of cardiac computed tomography examination appropriateness
under the 2010 revised versus the 2006 original Appropriate Use Criteria
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Article
DE Appropriateness; Cardiac CT; CT coronary angiography; Coronary artery
disease; Imaging
ID CARDIOVASCULAR-MAGNETIC-RESONANCE; NORTH-AMERICAN-SOCIETY;
NUCLEAR-CARDIOLOGY; INTERVENTIONS; ANGIOGRAPHY; RADIOLOGY; COLLEGE;
DISEASE
AB BACKGROUND: The 2006 Cardiac CT Appropriate Use Criteria (AUC) were recently revised in 2010. In addition to rating an expanded number of indications, the new criteria adjusted the appropriateness of existing indications to reflect changes in clinical practice and new evidence since 2006.
OBJECTIVE: We sought to determine how the appropriateness of cardiac CT examinations performed at a tertiary-care hospital changed under the revised criteria compared with the original AUC.
METHODS: Data were collected from the medical records and personal interview of 267 consecutive patients referred for cardiac CT in 2008. With the use of the 2010 and 2006 AUCs, two physicians designated each examination's indication as appropriate, inappropriate, uncertain, or "not classified" if examination indication could not be assigned.
RESULTS: With the use the new 2010 AUC, a highly significant change was observed in the classification of examination appropriateness (P < 0.001), with 40% of examinations changing appropriateness level compared with the 2006 AUC. Under the 2010 AUC, there were an increased proportion of both appropriate examinations (59% vs. 45%; P < 0.001) and inappropriate examinations (15% vs. 10%: P < 0.001), and approximately the same proportion with uncertain appropriateness (13% vs. 16%; P = 0.33). Consequently, the proportion of examinations that were not classified was significantly reduced under the 2010 AUC (29% vs. 13%; P < 0.001).
CONCLUSION: The revision of the AUC for cardiac CT had a significant effect on examination appropriateness. In comparison to the 2006 AUC, the 2010 AUC provided improved clarification of examination appropriateness. This shift was because of the inclusion of many previously unaddressed indications and the designation of more examinations as either appropriate or inappropriate. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved.
C1 [Wasfy, Meagan M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
[Brady, Thomas J.; Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Brady, Thomas J.; Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Nasir, Khurram] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA.
[Cury, Ricardo C.] Baptist Hosp Miami, Baptist Cardiac & Vasc Inst, Miami, FL USA.
[Di Carli, Marcelo F.; Blankstein, Ron] Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA.
RP Wasfy, MM (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St,PB 147, Boston, MA 02115 USA.
EM mkmurphy@gmail.com
FU National Institutes of Health [1T32 HL076136-02]
FX Drs. Blankstein and Nasir received financial support from the National
Institutes of Health (grant 1T32 HL076136-02).
NR 14
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD MAR-APR
PY 2012
VL 6
IS 2
BP 99
EP 107
DI 10.1016/j.jcct.2011.12.005
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 035HL
UT WOS:000310933900005
PM 22440425
ER
PT J
AU McKenna, JT
Christie, MA
Jeffrey, BA
McCoy, JG
Lee, E
Connolly, NP
Ward, CP
Strecker, RE
AF McKenna, J. T.
Christie, M. A.
Jeffrey, B. A.
McCoy, J. G.
Lee, E.
Connolly, N. P.
Ward, C. P.
Strecker, R. E.
TI Chronic ramelteon treatment in a mouse model of Alzheimer's disease
SO ARCHIVES ITALIENNES DE BIOLOGIE
LA English
DT Article
DE Melatonin; Alzheimer's disease; Amyloid plaques; Apoptosis; Maze
learning; Ramelteon
ID MELATONIN; APOPTOSIS; DEFICITS; THERAPY; SYSTEM; MICE
AB Prior research has reported beneficial effects of melatonin in rodent models of Alzheimer's disease (AD). This study evaluated the effect of ramelteon (Rozerem (R), a melatonin receptor agonist) on. spatial learning & memory and neuropathological markers in a transgenic murine model of AD (the B6C3-Tg(APPswe, PSEN1dE9)85Dbo/J transgenic mouse strain; hereafter 'AD mice'). Three months of daily ramelteon treatment (similar to 3 mg/kg/day), starting at 3 months of age, did not produce an. improvement in the cognitive performance of AD mice (water maze). In contrast to wildtype control mice, AD mice did not show any evidence of having learned the location of the escape platform. The cortex and hippocampus of AD mice contained significant quantities of beta-amyloid plaques and PARP-positive (poly ADP ribose polymerase) cells, indicating apoptosis. Six months of ramelteon treatment. starting at 3 months of age, did not produce any change in these neuropathological markers. The ability of long term melatonin treatment to improve cognition and attenuate neuropathology in AD mice did not generalize to this dosage of ramelteon.
C1 [McKenna, J. T.; Christie, M. A.; Jeffrey, B. A.; McCoy, J. G.; Lee, E.; Connolly, N. P.; Ward, C. P.; Strecker, R. E.] VA Boston Healthcare Syst, Res Serv, Brockton, MA 02301 USA.
[McKenna, J. T.; Christie, M. A.; Jeffrey, B. A.; McCoy, J. G.; Lee, E.; Connolly, N. P.; Ward, C. P.; Strecker, R. E.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA.
[Jeffrey, B. A.] Hebrew Rehabil Ctr, Inst Aging Res, Musculoskeletal Dept, Roslindale, MA USA.
[McCoy, J. G.] Stonehill Coll, Dept Psychol, Easton, MA USA.
[Lee, E.] SK Holdings, Psychiat Lab, Taejon 305772, South Korea.
[Connolly, N. P.] American Univ, Dept Psychol, Washington, DC 20016 USA.
[Ward, C. P.] Univ Houston Clear Lake, Houston, TX USA.
RP McKenna, JT (reprint author), VA Boston Healthcare Syst, Res Serv, Res 151-C,940 Belmont St,Bldg 44,Rm 111, Brockton, MA 02301 USA.
EM james_mckenna@hms.harvard.edu
OI Jeffrey, Brianne/0000-0002-3337-4434
FU Takeda Pharmaceuticals North America, Inc.; SK Holdings; U.S. Dept. of
Veterans Affairs Medical Research; NIH
FX We thank Jeremy Beech, Yunren Bolortuya, Gina Ciovacco, and Jessin
Varghese for technical assistance and John Franco for care of the
animals. This study was supported by a grant from Takeda Pharmaceuticals
North America, Inc. EL was supported by a fellowship from SK Holdings.
The authors have indicated no financial conflicts of interest. Salary
support for some of the investigators was from the U.S. Dept. of
Veterans Affairs Medical Research and NIH.
NR 23
TC 9
Z9 9
U1 0
U2 1
PU UNIV PISA
PI PISA
PA LUNGARNO A PACINOTTI 43, 56100 PISA, ITALY
SN 0003-9829
J9 ARCH ITAL BIOL
JI Arch. Ital. Biol.
PD MAR
PY 2012
VL 150
IS 1
BP 5
EP 14
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 031UV
UT WOS:000310668800002
PM 22786833
ER
PT J
AU Broyles, LM
Tate, JA
Happ, MB
AF Broyles, Lauren M.
Tate, Judith A.
Happ, Mary Beth
TI USE OF AUGMENTATIVE AND ALTERNATIVE COMMUNICATION STRATEGIES BY FAMILY
MEMBERS IN THE INTENSIVE CARE UNIT
SO AMERICAN JOURNAL OF CRITICAL CARE
LA English
DT Article
ID POSTTRAUMATIC-STRESS; VENTILATED PATIENTS; CRITICAL ILLNESS;
DECISION-MAKING; HIGH-RISK; PATIENT; SYMPTOMS; LIFE; ICU; EXPERIENCES
AB Background Little is known about communication between patients and their family members during critical illness and mechanical ventilation in the intensive care unit, including use of augmentative and alternative communication tools and strategies.
Objectives To identify (1) which augmentative and alternative communication tools families use with nonspeaking intensive care patients and how they are used, and (2) what families and nurses say about communication of family members with nonspeaking intensive care patients.
Methods A qualitative secondary analysis was conducted of existing data from a clinical trial testing interventions to improve communication between nurses and intensive care patients. Narrative study data (field notes, intervention logs, nurses' interviews) from 127 critically ill adults were reviewed for evidence of family involvement with augmentative and alternative communication tools. Qualitative content analysis was applied for thematic description of family members' and nurses' accounts of patient-family communication.
Results Family involvement with augmentative and alternative communication tools was evident in 44% of the 93 patients who completed the parent study protocol. Spouses or significant others communicated with patients most often. Main themes describing patient-family communication included (1) families being unprepared and unaware, (2) families' perceptions of communication effectiveness, (3) nurses deferring to or guiding patient-family communication, (4) patients' communication characteristics, and (5) families' experience with and interest in augmentative and alternative communication tools.
Conclusions Assessment by skilled bedside clinicians can reveal patients' communication potential and facilitate useful augmentative and alternative communication tools and strategies for patients and their families. (American Journal of Critical Care. 2012; 21(2): e21-e32)
C1 [Broyles, Lauren M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Broyles, Lauren M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15260 USA.
[Tate, Judith A.] Univ Pittsburgh, Dept Psychiat, NIMH, Pittsburgh, PA 15260 USA.
[Happ, Mary Beth] Univ Pittsburgh, Dept Acute & Tertiary Care, UPMC Hlth Syst, Sch Nursing,Chair Nursing Sci, Pittsburgh, PA 15260 USA.
RP Broyles, LM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA.
EM Lauren.Broyles@va.gov
RI Tate, Judith/C-7447-2015
FU National Institute for Nursing Research [5K24- NR010244]; National
Institute for Child Health and Human Development [5R01 HD043988]; US
Department of Veterans Affairs [CDA 10-014]
FX This study was supported by grants (M. Happ, principal investigator)
from the National Institute for Nursing Research (5K24- NR010244) and
the National Institute for Child Health and Human Development (5R01
HD043988). Dr Broyles is currently supported by a Career Development
Award (CDA 10-014) from the US Department of Veterans Affairs. This
material is the result of work supported with resources and the use of
facilities at the VA Pittsburgh Healthcare System, Pittsburgh,
Pennsylvania. Dr Tate is a National Institute of Mental Health
postdoctoral research fellow in the clinical research training program
in geriatric psychiatry at the University of Pittsburgh Department of
Psychiatry (T32 MH19986, principal investigator, Reynolds).
NR 61
TC 3
Z9 3
U1 2
U2 30
PU AMER ASSOC CRITICAL CARE NURSES
PI ALISO VIEJO
PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA
SN 1062-3264
J9 AM J CRIT CARE
JI Am. J. Crit. Care
PD MAR 1
PY 2012
VL 21
IS 2
BP E21
EP E32
DI 10.4037/ajcc2012752
PG 12
WC Critical Care Medicine; Nursing
SC General & Internal Medicine; Nursing
GA 031LC
UT WOS:000310640300001
PM 22381993
ER
PT J
AU Burghardt, AJ
Pialat, JB
Kazakia, GJ
Boutroy, S
Patsch, J
Valentinitsch, A
Liu, DM
Szabo, E
Bogado, CE
Engelke, K
Zanchetta, MB
Mckay, H
Shane, E
Boyd, SK
Bouxsein, ML
Chapurlat, R
Khosla, S
Majumdar, S
AF Burghardt, Andrew J.
Pialat, Jean-Baptiste
Kazakia, Galateia J.
Boutroy, Stephanie
Patsch, Janina
Valentinitsch, Alexander
Liu, Danmei
Szabo, Eva
Bogado, Cesar E.
Engelke, Klaus
Zanchetta, Maria B.
Mckay, Heather
Shane, Elizabeth
Boyd, Steven K.
Bouxsein, Mary L.
Chapurlat, Roland
Khosla, Sundeep
Majumdar, Sharmila
TI MULTICENTER REPRODUCIBILITY OF CORTICAL AND TRABECULAR BONE QUALITY
MEASURES ASSESSED BY HR-PQCT
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT IOF-ECCEO European Congress on Osteoporosis and Osteoarthritis / 2nd
IOF-ESCEO Pre-Clinical Symposium
CY MAR 21-24, 2012
CL Bordeaux, FRANCE
SP Int Osteoporosis Fdn (IOF), European Soc Clin & Econom Aspects Osteoporosis & Osteoarthritis (ESCEO), Rottapharm, Madaus, Wisepress, Servier Int, Amgen, GlaxoSmithKline (GSK), MSD, B-Cube AG, Beammed, Danone, Dfine Europe, D3A, Eli Lilly, Expanscience, GE Healthcare, Hologic, IDS, Medi, Medtron, Mindways, Nycomed, Optasia Med, Pfizer
C1 [Burghardt, Andrew J.; Pialat, Jean-Baptiste; Kazakia, Galateia J.; Patsch, Janina; Valentinitsch, Alexander; Majumdar, Sharmila] Univ Calif San Francisco, Musculoskeletal Quantitat Imaging Res Grp, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Pialat, Jean-Baptiste; Boutroy, Stephanie; Chapurlat, Roland] INSERM, F-69008 Lyon, France.
[Pialat, Jean-Baptiste; Boutroy, Stephanie; Chapurlat, Roland] Univ Lyon, Res Unit 1033, Team 1, Lyon, France.
[Boutroy, Stephanie; Shane, Elizabeth] Columbia Univ, Med Ctr, Div Endocrinol, Dept Med,Coll Phys & Surg, New York, NY USA.
[Patsch, Janina; Valentinitsch, Alexander] Med Univ Vienna, Dept Radiol, Vienna, Austria.
[Liu, Danmei; Mckay, Heather] Univ British Columbia, Ctr Hip Hlth & Mobil, Dept Orthoped, Vancouver, BC V5Z 1M9, Canada.
[Szabo, Eva; Boyd, Steven K.] Univ Calgary, Schulich Sch Engn, Calgary, AB, Canada.
[Engelke, Klaus] Inc Synarc, Hamburg, Germany.
[Engelke, Klaus] Univ Erlangen Nurnberg, Inst Med Phys, D-91054 Erlangen, Germany.
[Bouxsein, Mary L.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Bouxsein, Mary L.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
[Khosla, Sundeep] Mayo Clin, Coll Med, Div Endocrinol Metab & Nutr, Dept Internal Med, Rochester, MN USA.
[Bogado, Cesar E.; Zanchetta, Maria B.] Inst Buenos Aires, Buenos Aires, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD MAR
PY 2012
VL 23
SU 2
BP S184
EP S185
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 012TN
UT WOS:000309259600251
ER
PT J
AU Rozental, T
Day, C
Earp, B
Deschamps, L
Taylor, A
Bouxsein, ML
AF Rozental, Tamara
Day, Charles
Earp, B.
Deschamps, Laura
Taylor, Alex
Bouxsein, Mary L.
TI PREMENOPAUSAL WOMEN WITH DISTAL RADIUS FRACTURES HAVE DETERIORATED
TRABECULAR BONE ARCHITECTURE COMPARED TO NON-FRACTURE CONTROLS
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT IOF-ECCEO European Congress on Osteoporosis and Osteoarthritis / 2nd
IOF-ESCEO Pre-Clinical Symposium
CY MAR 21-24, 2012
CL Bordeaux, FRANCE
SP Int Osteoporosis Fdn (IOF), European Soc Clin & Econom Aspects Osteoporosis & Osteoarthritis (ESCEO), Rottapharm, Madaus, Wisepress, Servier Int, Amgen, GlaxoSmithKline (GSK), MSD, B-Cube AG, Beammed, Danone, Dfine Europe, D3A, Eli Lilly, Expanscience, GE Healthcare, Hologic, IDS, Medi, Medtron, Mindways, Nycomed, Optasia Med, Pfizer
C1 [Rozental, Tamara; Day, Charles; Earp, B.; Deschamps, Laura; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Rozental, Tamara; Day, Charles; Earp, B.; Deschamps, Laura; Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA USA.
[Taylor, Alex] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD MAR
PY 2012
VL 23
SU 2
BP S290
EP S291
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 012TN
UT WOS:000309259600463
ER
PT J
AU Zamarioli, A
Battaglino, R
Morse, L
Okubo, R
Maranho, D
Shimano, AC
AF Zamarioli, Ariane
Battaglino, Ricardo
Morse, Leslie
Okubo, Rodrigo
Maranho, Daniel
Shimano, Antonio C.
TI PASSIVE STANDING AND FUNCTIONAL ELECTRICAL STIMULATION PRESERVES BONE
STRENGTH IN PARAPLEGIC RATS FOLLOWING ACUTE SPINAL CORD INJURY
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT IOF-ECCEO European Congress on Osteoporosis and Osteoarthritis / 2nd
IOF-ESCEO Pre-Clinical Symposium
CY MAR 21-24, 2012
CL Bordeaux, FRANCE
SP Int Osteoporosis Fdn (IOF), European Soc Clin & Econom Aspects Osteoporosis & Osteoarthritis (ESCEO), Rottapharm, Madaus, Wisepress, Servier Int, Amgen, GlaxoSmithKline (GSK), MSD, B-Cube AG, Beammed, Danone, Dfine Europe, D3A, Eli Lilly, Expanscience, GE Healthcare, Hologic, IDS, Medi, Medtron, Mindways, Nycomed, Optasia Med, Pfizer
C1 [Zamarioli, Ariane; Okubo, Rodrigo; Maranho, Daniel; Shimano, Antonio C.] Univ Sao Paulo, Dept Biomech Med & Rehabil, Sao Paulo, Brazil.
[Battaglino, Ricardo] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA.
[Morse, Leslie] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA.
RI Zamarioli, Ariane/K-7001-2012; Maranho, Daniel Augusto/C-1337-2013;
Shimano, Antonio/E-1455-2014
OI Zamarioli, Ariane/0000-0002-7939-0528; Maranho, Daniel
Augusto/0000-0002-3893-0292;
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD MAR
PY 2012
VL 23
SU 2
BP S415
EP S416
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 012TN
UT WOS:000309259600697
ER
PT J
AU Bleier, BS
AF Bleier, Benjamin S.
TI Regional expression of epithelial MDR1/P-glycoprotein in chronic
rhinosinusitis with and without nasal polyposis
SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
LA English
DT Article; Proceedings Paper
CT Annual Scientific Meeting of the American-Rhinologic-Society
CY SEP 10, 2011
CL San Francisco, CA
SP Amer Rhinol Soc (ARS)
DE active efflux pumps; chronic sinusitis; inflammation; nasal polyposis;
P-glycoprotein; Th1; Th2
ID P-GLYCOPROTEIN; MUCOSA
AB Background: P-glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein encoded by the MDR1 (ABCB1) gene and is constitutively expressed on lower airway epithelium. P-gp has been shown to function as an immunomodulator regulating efflux of T-helper 1/T-helper 2 (Th1/Th2) cytokines from its host cell; however, its association with sinonasal inflammation has not been described. The purpose of this study is to determine the pattern and degree of epithelial P-gp expression in chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP) or CRS without nasal polyposis (CRSsNP).
Methods: Institutional Review Board (IRB)-approved study utilizing sinus, septal, and inferior turbinate mucosa in patients with no disease, CRS, and CRSwNP (n = 4 each). Quantitative fluorescent immunohistochemistry (Q-FIHC) was performed using an anti-P-gp antibody and a secondary fluorescein isothiocyanate (FITC)-conjugated Fc specific fragment. Protein expression was quantified by calculating the epithelial to nonspecific background intensity ratio (4 images/subsite). Scores less than 1 suggested negligible expression. Staining ratios between patient groups and subsites were compared using a 2-tailed Student t test.
Results: Among the sinus mucosa, P-gp expression in CRSwNP (1.570 +/- 0.354) was significantly greater than both CRS (1.224 +/- 0.248) and control (0.762 +/- 0.128) (p < 0.001, p = 0.002; respectively). CRS scores were significantly greater than control (p = 0.002). Among the septal mucosa, there was no significant difference between CRSwNP (0.914 +/- 0.264), CRS (1.126 +/- 0.476), or control (0.966 +/- 0.327). Among the inferior turbinate mucosa, there was no significant difference between CRSwNP (1.047 +/- 0.157), CRS (1.099 +/- 0.362), or control (0.824 +/- 0.181).
Conclusion: MDR1/P-gp is overexpressed in the epithelial layer of sinus mucosa in patients with both CRSwNP and CRS relative to other sinonasal subsites. Expression in healthy mucosa is negligible. Given its known immunomodulatory function this suggests that P-gp may play a role in the pathogenesis or maintenance of chronic sinonasal inflammation. (C) 2011 ARS-AAOA, LLC.
C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
EM bleierb@gmail.com
FU PHS HHS [P30 05209]
NR 11
TC 14
Z9 14
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2042-6976
J9 INT FORUM ALLERGY RH
JI Int. Forum Allergy Rhinol.
PD MAR-APR
PY 2012
VL 2
IS 2
BP 122
EP 125
DI 10.1002/alr.21004
PG 4
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 007ZD
UT WOS:000308926000006
PM 22223515
ER
PT J
AU Al Gadban, MM
German, J
Truman, JP
Soodavar, F
Riemer, EC
Twal, WO
Smith, KJ
Heller, D
Hofbauer, AF
Oates, JC
Hammad, SM
AF Al Gadban, Mohammed M.
German, Jashalynn
Truman, Jean-Philip
Soodavar, Farzan
Riemer, Ellen C.
Twal, Waleed O.
Smith, Kent J.
Heller, Demarcus
Hofbauer, Ann F.
Oates, Jim C.
Hammad, Samar M.
TI Lack of nitric oxide synthases increases lipoprotein immune complex
deposition in the aorta and elevates plasma sphingolipid levels in lupus
SO CELLULAR IMMUNOLOGY
LA English
DT Article
DE Lupus; Nitric oxide synthase; Sphingosine 1-phosphate; Sphingosine
kinase; Ceramide; Oxidized LDL
ID TUMOR-NECROSIS-FACTOR; HIGH-DENSITY-LIPOPROTEIN; GIANT-CELL VASCULITIS;
U937 MONOCYTIC CELLS; HUMAN T-CELLS; ENDOTHELIAL DYSFUNCTION;
RHEUMATOID-ARTHRITIS; ACCELERATED ATHEROSCLEROSIS; MOLECULAR-MECHANISMS;
SIGNAL-TRANSDUCTION
AB Systemic lupus erythematosus (SLE) patients display impaired endothelial nitric oxide synthase (eNOS) function required for normal vasodilatation. SLE patients express increased compensatory activity of inducible nitric oxide synthase (iNOS) generating excess nitric oxide that may result in inflammation. We examined the effects of genetic deletion of NOS2 and NOS3, encoding iNOS and eNOS respectively, on accelerated vascular disease in MRL/lpr lupus mouse model. NOS2 and NOS3 knockout (KO) MRL/lpr mice had higher plasma levels of triglycerides (23% and 35%, respectively), ceramide (45% and 21%, respectively), and sphingosine 1-phosphate (S1P) (21%) compared to counterpart MRL/lpr controls. Plasma levels of the anti-inflammatory cytokine interleukin 10 (IL-10) in NOS2 and NOS3 KO MRL/lpr mice were lower (53% and 80%, respectively) than counterpart controls. Nodule-like lesions in the adventitia were detected in aortas from both NOS2 and NOS3 KO MRL/lpr mice. Immunohistochemical evaluation of the lesions revealed activated endothelial cells and lipid-laden macrophages (foam cells), elevated sphingosine kinase 1 expression, and oxidized low-density lipoprotein immune complexes (oxLDL-IC). The findings suggest that advanced vascular disease in NOS2 and NOS3 KO MRL/lpr mice maybe mediated by increased plasma triglycerides, ceramide and S1P; decreased plasma IL-10; and accumulation of oxLDL-IC in the vessel wall. The results expose possible new targets to mitigate lupus-associated complications. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Al Gadban, Mohammed M.; Truman, Jean-Philip; Soodavar, Farzan; Twal, Waleed O.; Smith, Kent J.; Hammad, Samar M.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
[German, Jashalynn; Heller, Demarcus] Med Univ S Carolina, Coll Grad Studies, Summer Undergrad Res Program, Charleston, SC 29425 USA.
[Riemer, Ellen C.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Hofbauer, Ann F.; Oates, Jim C.] Med Univ S Carolina, Dept Rheumatol & Immunol, Charleston, SC 29425 USA.
[Hofbauer, Ann F.; Oates, Jim C.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
RP Hammad, SM (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, 114 Doughty St 629A,MSC 815, Charleston, SC 29425 USA.
EM hammadsm@musc.edu
FU NIH [HL079274, K08AR002193, AR045476]; NIH (ARRA) [R01 HL079274-04S1];
South Carolina COBRE in Lipidomics and Pathobiology (from NCRR) [P20
RR17677]; Medical Research Service [NIH/NHLBI R25 HL092611]; Cancer
Center Support Grant [P30 CA138313]
FX This study was funded by NIH HL079274, NIH (ARRA) R01 HL079274-04S1, and
the South Carolina COBRE in Lipidomics and Pathobiology (P20 RR17677
from NCRR) to SMH; NIH K08AR002193, NIH AR045476, and funding from
Medical Research Service, Ralph H. Johnson VAMC, Charleston, to JCO;
NIH/NHLBI R25 HL092611 for the MUSC College of Graduate Studies (J.G.
and D.H.). We thank the MUSC Lipidomics Core Facility for sphingolipid
analysis, the Histology Laboratory, Department of Pathology & Laboratory
Medicine for tissue processing, and the MUSC Proteogenomics Facility for
the use of the Bioplex system for cytokine determination. Imaging
facilities were supported, in part, by Cancer Center Support Grant P30
CA138313 to the Hollings Cancer Center, MUSC. We thank Dr. Toshi
Kawamori and Dr. Gabe Virella (MUSC) for providing antibodies.
NR 80
TC 6
Z9 6
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0008-8749
J9 CELL IMMUNOL
JI Cell. Immunol.
PD MAR-APR
PY 2012
VL 276
IS 1-2
BP 42
EP 51
DI 10.1016/j.cellimm.2012.03.007
PG 10
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 985JQ
UT WOS:000307260800007
PM 22560558
ER
PT J
AU Peraino, JS
Hermanrud, CE
Springett, L
Zhang, HP
Li, GY
Srinivasan, S
Gusha, A
Sachs, DH
Huang, CA
Wang, ZR
AF Peraino, Jaclyn Stromp
Hermanrud, Christina E.
Springett, Lauren
Zhang, Huiping
Li, Guoying
Srinivasan, Srimathi
Gusha, Ashley
Sachs, David H.
Huang, Christene A.
Wang, Zhirui
TI Expression and characterization of recombinant soluble porcine CD3
ectodomain molecules: Mapping the epitope of an anti-porcine CD3
monoclonal antibody 898H2-6-15
SO CELLULAR IMMUNOLOGY
LA English
DT Article
DE Porcine CD3; 898H2-6-15 monoclonal antibody; T cell; Immunotoxin
ID TOXIN-BASED IMMUNOTOXIN; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; TOLERANCE;
AFFINITY; COMPLEX; DISPLAY
AB The porcine CD3 specific monoclonal antibody 898H2-6-15 has been used in allo- and xeno-transplantation studies as a porcine CD3 marker and as an effective T cell depletion reagent when conjugated to the diphtheria toxin mutant, CRM9. A recombinant anti-porcine CD3 immuntoxin was recently developed using single-chain variable fragments (scFv) derived from 898H2-6-15. In this study, using published sequence data, we have expressed the porcine CD3 ectodomain molecules in E. coli through inclusion body isolation and in vitro refolding approach. The expressed and refolded porcine CD3 ectodomain molecules include CD3 epsilon, CD3 gamma, CD3 delta, CD3 epsilon gamma heterodimer, CD3 epsilon delta heterodimer, CD3 epsilon gamma, single-chain fusion protein and CD3 epsilon delta single-chain fusion protein. These refolded porcine CD3 ectodomain molecules were purified with a strong anion exchange resin Poros 50HQ. ELISA analysis demonstrated that only the porcine CD3 epsilon gamma ectodomain single-chain fusion protein can bind to the porcine CD3 specific monoclonal antibody 898H2-6-15. The availability of this porcine CD3 epsilon gamma ectodomain single-chain fusion protein will allow screening for affinity matured variants of scEv derived from 898H2-6-15 to improve the recombinant anti-porcine CD3 immunotoxin. Porcine CD3 epsilon gamma ectodomain single-chain fusion protein will also be a very useful reagent to study the soluble phase interaction between porcine CD3 epsilon gamma and porcine CD3 antibodies such as 898H2-6-15. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Peraino, Jaclyn Stromp; Hermanrud, Christina E.; Springett, Lauren; Zhang, Huiping; Li, Guoying; Srinivasan, Srimathi; Gusha, Ashley; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
[Peraino, Jaclyn Stromp; Hermanrud, Christina E.; Springett, Lauren; Zhang, Huiping; Li, Guoying; Srinivasan, Srimathi; Gusha, Ashley; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Peraino, Jaclyn Stromp; Hermanrud, Christina E.; Springett, Lauren; Zhang, Huiping; Li, Guoying; Gusha, Ashley; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] DF HCC MGH Recombinant Prot Express & Purificat C, Boston, MA 02129 USA.
RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-6113,13th St, Boston, MA 02129 USA.
EM zhirui.wang@tbrc.mgh.harvard.edu
FU National Institutes of Health [R01AI084657-02S1, R01AI084657-02S2]; Dana
Farber/Harvard Cancer Center Core development grant
FX The authors would like to acknowledge Drs. Josef Kurtz and Vimukthi
Pathiraja for critical review of the manuscript and J. Scott Am for
generation of the monoclonal antibody 898H2-6-15. This work was
supported by National Institutes of Health (R01AI084657-02S1 to CAH and
R01AI084657-02S2 to CAH) and Dana Farber/Harvard Cancer Center Core
development grant.
NR 17
TC 7
Z9 7
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 0008-8749
EI 1090-2163
J9 CELL IMMUNOL
JI Cell. Immunol.
PD MAR-APR
PY 2012
VL 276
IS 1-2
BP 162
EP 167
DI 10.1016/j.cellimm.2012.05.004
PG 6
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 985JQ
UT WOS:000307260800022
PM 22672968
ER
PT J
AU Hung, J
Solis, J
Handschumacher, MD
Guerrero, JL
Levine, RA
AF Hung, Judy
Solis, Jorge
Handschumacher, Mark D.
Guerrero, J. Luis
Levine, Robert A.
TI Persistence of Mitral Regurgitation Following Ring Annuloplasty: Is the
Papillary Muscle Outside or Inside the Ring?
SO JOURNAL OF HEART VALVE DISEASE
LA English
DT Article
ID 3-DIMENSIONAL ECHOCARDIOGRAPHY; DETERMINANTS; DYSFUNCTION; INSIGHTS;
REPAIR; VALVE; REVASCULARIZATION; MECHANISM; SEVERITY; VOLUME
AB Background and aim of the study: Ischemic mitral regurgitation (IMR) often persists, despite annular ring reduction. It has been hypothesized that persistent IMR following ring annuloplasty was related to a continued tethering of the mitral leaflets, as defined by the distance by which the papillary muscles (PMs) were displaced outside the mitral annular ring.
Methods: Seven sheep (four acute, three chronic) with persistent mitral regurgitation (MR) following ring annuloplasty for IMR were studied using three-dimensional (3D) echocardiography to examine the mitral valve geometry. The three stages examined were: Stage 1, baseline; Stage 2, post myocardial infarction (via ligation of the obtuse marginal branches); and Stage 3, post undersized ring annuloplasty. The 3D echocardiography measurements included mitral annular area, tethering distance from the ischemic PM to the anterior annulus, and the outside displacement of the PM relative to ring PM displacement.
Results: Persistent moderate MR remained in these seven sheep following undersized ring annuloplasty (MR vena contracta change (pre versus post ring): 7.0 versus 5.8 +/- 2.4 mm, p = NS), despite a reduction in the mitral annular area of 50 +/- 18% (10.3 +/- 6.3 versus 4.7 +/- 1.3 cm(2)). Ring annuloplasty shifted the posterior annulus towards the anterior annulus, such that the infarcted PM became displaced outside the mitral annulus. The projected displacement distance of the PM outside versus inside the annular ring was 8.4 +/- 2.4 mm outside mitral annulus post ring versus 3.6 +/- 2.5 mm within mitral annulus pre ring, p <0001). The displacement distance from the infarcted PM to the mitral annulus restricted the ability of the posterior leaflet to move anteriorly, preventing effective coaptation. By multivariate analysis, this displacement distance was an important determinant of residual MR (p <0.02).
Conclusion: Persistent MR following ring annuloplasty for IMR relates to persistently abnormal leaflet tethering, with restricted posterior leaflet motion due to PM displacement outside of the mitral annulus.
The Journal of Heart Valve Disease 2012;21:218-224
C1 [Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA.
EM jhung@partners.org
FU NIH/National Institute for Biomedical Imaging and Bioengineering (NIBIB)
[R21 EB005294]; NIH/(National Heart Lung Blood Institute) NHLBI [R01
HL092101, R01 038176, K24 HL67434]; Fondation Leducq, Paris, France
[07CVD04]; American Society of echocardiography; Spanish Society of
Cardiology
FX These studies were supported in part by NIH/National Institute for
Biomedical Imaging and Bioengineering (NIBIB) R21 EB005294,
NIH/(National Heart Lung Blood Institute R01 HL092101 (J.H.),
NIH/(National Heart Lung Blood Institute) NHLBI R01 038176 and K24
HL67434, grant 07CVD04 of Fondation Leducq, Paris, France (R.A.L.) and
Echo-Investigator Award from the American Society of echocardiography
(to J.H.), and an American Society of Echocardiography Career
Development Award and Spanish Society of Cardiology (post-residency
grant) (to J.S.).
NR 32
TC 7
Z9 8
U1 0
U2 1
PU I C R PUBLISHERS
PI NORTHWOOD
PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET,
ENGLAND
SN 0966-8519
J9 J HEART VALVE DIS
JI J. Heart Valve Dis.
PD MAR
PY 2012
VL 21
IS 2
BP 218
EP 224
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 977OX
UT WOS:000306675400013
PM 22645858
ER
PT J
AU Clark, JW
AF Clark, Jeffrey W.
TI Drug Interactions: The Importance of Looking Inside Cancer Cells
SO CANCER DISCOVERY
LA English
DT Editorial Material
ID ADVANCED PANCREATIC-CANCER; GEMCITABINE; INFUSION; TRIAL
AB nab-Paclitaxel increased intratumoral gemcitabine levels by reactive oxygen species-mediated degradation of cytidine deaminase, the rate-limiting enzyme in gemcitabine inactivation. This not only has implications for how this drug combination mediates anticancer effects but also demonstrates the importance of evaluating mechanisms of drug activity within malignant cells. Cancer Discovery; 2(3); 208-10. (c) 2012 AACR.
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Clark, JW (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM jclark@partners.org
NR 12
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD MAR
PY 2012
VL 2
IS 3
BP 208
EP 210
DI 10.1158/2159-8290.CD-12-0040
PG 3
WC Oncology
SC Oncology
GA 973AG
UT WOS:000306322700026
PM 22585991
ER
PT J
AU Garraway, LA
Janne, PA
AF Garraway, Levi A.
Jaenne, Pasi A.
TI Circumventing Cancer Drug Resistance in the Era of Personalized Medicine
SO CANCER DISCOVERY
LA English
DT Review
ID CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER;
GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITORS; SURFACE
P-GLYCOPROTEIN; BRAF V600E MUTATION; ACQUIRED-RESISTANCE; BCR-ABL;
BREAST-CANCER
AB All successful cancer therapies are limited by the development of drug resistance. The increase in the understanding of the molecular and biochemical bases of drug efficacy has also facilitated studies elucidating the mechanism(s) of drug resistance. Experimental approaches that can help predict the eventual clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, are rapidly identifying novel resistance mechanisms. In this review, we provide a historical background on drug resistance and a framework for understanding the common ways by which cancers develop resistance to targeted therapies. We further discuss advantages and disadvantages of experimental strategies that can be used to identify drug resistance mechanism(s).
Significance: Increased knowledge of drug resistance mechanisms will aid in the development of effective therapies for patients with cancer. We provide a summary of current knowledge on drug resistance mechanisms and experimental strategies to identify and study additional drug resistance pathways. Cancer Discovery; 2(3); 214-26. (c) 2012 AACR.
C1 [Garraway, Levi A.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA.
[Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA.
[Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA.
[Garraway, Levi A.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA USA.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,M422A, Boston, MA 02215 USA.
EM pasi_janne@dfci.harvard.edu
FU NIH Director's New Innovator Award; Lung Cancer SPORE [P50 CA090578,
R01CA135257]; Starr Cancer Consortium; Melanoma Research Alliance
FX This work was supported by the NIH Director's New Innovator Award (L.A.
Garraway), Lung Cancer SPORE P50 CA090578 (P.A. Janne), R01CA135257
(P.A. Janne), the Starr Cancer Consortium (L.A. Garraway), and the
Melanoma Research Alliance (L.A. Garraway).
NR 92
TC 154
Z9 155
U1 9
U2 50
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD MAR
PY 2012
VL 2
IS 3
BP 214
EP 226
DI 10.1158/2159-8290.CD-12-0012
PG 13
WC Oncology
SC Oncology
GA 973AG
UT WOS:000306322700028
PM 22585993
ER
PT J
AU Corcoran, RB
Ebi, H
Turke, AB
Coffee, EM
Nishino, M
Cogdill, AP
Brown, RD
Della Pelle, P
Dias-Santagata, D
Hung, KE
Flaherty, KT
Piris, A
Wargo, JA
Settleman, J
Mino-Kenudson, M
Engelman, JA
AF Corcoran, Ryan B.
Ebi, Hiromichi
Turke, Alexa B.
Coffee, Erin M.
Nishino, Michiya
Cogdill, Alexandria P.
Brown, Ronald D.
Della Pelle, Patricia
Dias-Santagata, Dora
Hung, Kenneth E.
Flaherty, Keith T.
Piris, Adriano
Wargo, Jennifer A.
Settleman, Jeffrey
Mino-Kenudson, Mari
Engelman, Jeffrey A.
TI EGFR-Mediated Reactivation of MAPK Signaling Contributes to
Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with
Vemurafenib
SO CANCER DISCOVERY
LA English
DT Article
ID WILD-TYPE BRAF; ANTITUMOR-ACTIVITY; MEK INHIBITORS; MELANOMA; KINASE;
CELLS; KRAS; RESISTANCE; CETUXIMAB; MUTATION
AB BRAF mutations occur in 10% to 15% of colorectal cancers and confer adverse outcome in the metastatic setting. Although RAF inhibitors such as vemurafenib (PLX4032) have proven effective in the treatment of BRAF-mutant melanoma, they are surprisingly ineffective in BRAF-mutant colorectal cancers, and the reason for this disparity remains unclear. Compared with BRAF-mutant melanoma cells, BRAF-mutant colorectal cancer cells were less sensitive to vemurafenib, and phospho-extracellular signal-regulated kinase (P-ERK) suppression was not sustained in response to treatment. Although transient inhibition of P-ERK by vemurafenib was observed in colorectal cancer, rapid ERK reactivation occurred through epidermal growth factor receptor (EGFR)-mediated activation of RAS and CRAF. BRAF-mutant colorectal cancers expressed greater levels of phospho-EGFR than BRAF-mutant melanomas, suggesting that colorectal cancers are specifically poised for EGFR-mediated resistance. Combined RAF and EGFR inhibition blocked reactivation of mitogen-activated protein kinase (MAPK) signaling in BRAF-mutant colorectal cancer cells and markedly improved efficacy in vitro and in vivo. These findings support the evaluation of combined RAF and EGFR inhibition in patients with BRAF-mutant colorectal cancer.
SIGNIFICANCE: BRAF valine 600 (V600) mutations occur in 10% to 15% of colorectal cancers, yet these tumors show a surprisingly low clinical response rate (similar to 5%) to selective RAF inhibitors such as vemurafenib, which have produced dramatic response rates (60%-80%) in melanomas harboring the identical BRAF V600 mutation. We found that EGFR-mediated MAPK pathway reactivation leads to resistance to vemurafenib in BRAF-mutant colorectal cancers and that combined RAF and EGFR inhibition can lead to sustained MAPK pathway suppression and improved efficacy in vitro and in tumor xenografts. Cancer Discovery; 2(3); 227-35. (c) 2012 AACR.
C1 [Corcoran, Ryan B.; Ebi, Hiromichi; Turke, Alexa B.; Cogdill, Alexandria P.; Brown, Ronald D.; Flaherty, Keith T.; Wargo, Jennifer A.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Corcoran, Ryan B.; Ebi, Hiromichi; Turke, Alexa B.; Flaherty, Keith T.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Coffee, Erin M.; Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Boston, MA USA.
[Nishino, Michiya; Della Pelle, Patricia; Dias-Santagata, Dora; Piris, Adriano; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Cogdill, Alexandria P.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Settleman, Jeffrey] Genentech Inc, San Francisco, CA 94080 USA.
RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St,7th Floor, Charlestown, MA 02129 USA.
EM jengelman@partners.org
OI Cogdill, Alexandria/0000-0001-8917-9462; Ebi,
Hiromichi/0000-0003-3155-7576
FU NIH Gastrointestinal Cancer SPORE [P50 CA127003]; K08 grant
[CA120060-01, R01CA137008-01, R01CA140594, 1U01CA141457-01]; National
Cancer Institute Lung SPORE [P50CA090578]; V Foundation; American Cancer
Society [RSG-06-102-01-CCE]; Ellison Foundation Scholar
FX This study is supported by grants from the NIH Gastrointestinal Cancer
SPORE P50 CA127003, K08 grant CA120060-01, R01CA137008-01, R01CA140594,
1U01CA141457-01, National Cancer Institute Lung SPORE P50CA090578, the V
Foundation, American Cancer Society RSG-06-102-01-CCE, and the Ellison
Foundation Scholar (all J. A. Engelman).
NR 20
TC 281
Z9 284
U1 5
U2 36
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD MAR
PY 2012
VL 2
IS 3
BP 227
EP 235
DI 10.1158/2159-8290.CD-11-0341
PG 9
WC Oncology
SC Oncology
GA 973AG
UT WOS:000306322700029
PM 22448344
ER
PT J
AU Benassi, B
Flavin, R
Marchionni, L
Zanata, S
Pan, YF
Chowdhury, D
Marani, M
Strano, S
Muti, P
Blandino, G
Loda, M
AF Benassi, Barbara
Flavin, Richard
Marchionni, Luigi
Zanata, Silvio
Pan, Yunfeng
Chowdhury, Dipanjan
Marani, Marina
Strano, Sabrina
Muti, Paola
Blandino, Giovanni
Loda, Massimo
TI MYC Is Activated by USP2a-Mediated Modulation of MicroRNAs in Prostate
Cancer
SO CANCER DISCOVERY
LA English
DT Article
ID C-MYC; TRANSCRIPTIONAL REGULATION; INDEPENDENT GROWTH; P53; EXPRESSION;
CELLS; ONCOGENE; PATHWAY; HAUSP; DEUBIQUITINATION
AB Ubiquitin-specific protease 2a (USP2a) is overexpressed in almost half of human prostate cancers and c-Myc is amplified in one third of these tumor types. Transgenic MYC expression drives invasive adenocarcinomas in the murine prostate. We show that overexpression of USP2a downregulates a set of microRNAs that collectively increase MYC levels by MDM2 deubiquitination and subsequent p53 inactivation. By establishing MYC as a target of miR-34b/c, we demonstrate that this cluster functions as a tumor suppressor in prostate cancer cells. We identify a distinct mRNA signature that is enriched for MYC-regulated transcripts and transcription factor binding sites in USP2a overexpressing prostate cancer cells. We demonstrate that these genes are associated with an invasive phenotype in human prostate cancer and that the proliferative and invasive properties of USP2a overexpressing cells are MYC-dependent. These results highlight an unrecognized mechanism of MYC regulation in prostate cancer and suggest alternative therapeutic strategies in targeting MYC.
SIGNIFICANCE: The deubiquitinating enzyme USP2a has previously been shown to be oncogenic, overexpressed in almost half of human prostate adenocarcinomas, and prolongs the half-life of targets such as fatty acid synthase, MDM2, and cyclin D1. Here, we highlight a new mechanism by which USP2a enhances MYC levels through the modulation of specific subsets of microRNAs in prostate cancer, suggesting alternative therapeutic strategies for targeting MYC. Cancer Discovery; 2(3); 236-47. (c) 2012 AACR.
C1 [Benassi, Barbara] ENEA Casaccia, Toxicol Lab, Rome, Italy.
[Flavin, Richard; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Zanata, Silvio; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med Oncol, Boston, MA 02115 USA.
[Pan, Yunfeng; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Loda, Massimo] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Marchionni, Luigi] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA.
[Zanata, Silvio] Univ Fed Parana, Dept Basic Pathol & Cell Biol, BR-80060000 Curitiba, Parana, Brazil.
[Loda, Massimo] Kings Coll London, London Sch Med, Div Canc Studies, London WC2R 2LS, England.
RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
EM blandino@ifo.it; massimo_loda@dfci.harvard.edu
RI Blandino, Giovanni/B-1137-2013; strano, sabrina/B-6743-2013;
OI Blandino, Giovanni/0000-0002-6970-2241; strano,
sabrina/0000-0002-6341-4230; Marani, Marina/0000-0003-1585-3586
FU National Cancer Institute [RO1CA131945, PO1CA89021, P50CA90381]; NIH
grant [P30CA006973]; European Community (EC) Active p53 Program;
Brazilian Government
FX This work was supported by National Cancer Institute grants RO1CA131945,
PO1CA89021, and P50CA90381 to M. Loda and a gift from Nuclea Biomarkers
to the laboratory of M. Loda; NIH grant P30CA006973 to L. Marchionni;
and European Community (EC) Active p53 Program to G. Blandino.
Sabbatical research fellowship (CAPES #3665/10-0) and salary support are
provided by Brazilian Government to S. Zanata.
NR 47
TC 30
Z9 31
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD MAR
PY 2012
VL 2
IS 3
BP 236
EP 247
DI 10.1158/2159-8290.CD-11-0219
PG 12
WC Oncology
SC Oncology
GA 973AG
UT WOS:000306322700030
PM 22585994
ER
PT J
AU Mitchell, C
AF Mitchell, Christine
TI AN INTERVIEW WITH JANE D. SCHABERG
SO JOURNAL OF FEMINIST STUDIES IN RELIGION
LA English
DT Article
C1 [Mitchell, Christine] Harvard Univ, Sch Divin, Cambridge, MA 02138 USA.
[Mitchell, Christine] Dana Farber Canc Inst, Sch Divin, Boston, MA 02115 USA.
[Mitchell, Christine] Brigham & Womens Hosp, Sch Divin, Boston, MA 02115 USA.
RP Mitchell, C (reprint author), Harvard Univ, Sch Divin, Cambridge, MA 02138 USA.
EM cmitchell@mail.harvard.edu
NR 3
TC 0
Z9 0
U1 0
U2 0
PU INDIANA UNIV PRESS
PI BLOOMINGTON
PA 601 N MORTON STREET, BLOOMINGTON, IN 47404-3797 USA
SN 8755-4178
J9 J FEMINIST STUD REL
JI J. Fem. Stud. Relig.
PD SPR
PY 2012
VL 28
IS 1
BP 63
EP 73
PG 11
WC Religion
SC Religion
GA 970WQ
UT WOS:000306163400005
ER
PT J
AU Bromley, E
Adams, GF
Brekke, JS
AF Bromley, Elizabeth
Adams, Gail Fox
Brekke, John S.
TI A Video Ethnography Approach for Linking Naturalistic Behaviors to
Research Constructs of Neurocognition in Schizophrenia
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID ECOLOGICAL MOMENTARY ASSESSMENT; COMPLEX FIGURE TEST; QUALITY-OF-LIFE;
COGNITIVE DEFICITS; SOCIAL COGNITION; CODING SYSTEM; TIME USE;
NEUROPSYCHOLOGICAL ASSESSMENT; SELF-DETERMINATION; BIPOLAR DISORDER
AB Few methods are available to explore the impact of neurocognition in schizophrenia on behaviors performed in usual contexts. The authors developed a video ethnography approach to examine the relationship between naturalistic behaviors and research constructs of neurocognition. Video ethnographers accompanied subjects through usual routines gathering continuous video data. Researchers developed codes to measure four behavioral domains observed on video. This paper describes the psychometric characteristics to be considered in the development of observational approaches. It also highlights differences between behaviors performed in usual environments and neuropsychological constructs. The authors demonstrate that everyday behaviors that have been shown to correspond to neurocognitive skills in a pilot feasibility study can be identified and rated. They further suggest that observational methods could provide novel strategies for linking research findings and clinical concerns. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:125-140)
C1 [Bromley, Elizabeth; Adams, Gail Fox; Brekke, John S.] Univ Calif Los Angeles, Ctr Hlth Serv & Soc, Semel Inst,Dept Psychiat & Biobehav Sci, W Los Angeles VA Healthcare Ctr,Desert Pacific Mi, Los Angeles, CA 90024 USA.
RP Bromley, E (reprint author), 10920 Wilshire Blvd,Suite 300, Los Angeles, CA USA.
EM ebromley@ucla.edu
FU VA Desert Pacific Mental Illness Research, Education and Clinical Center
(MIRECC); University of California, Los Angeles Faculty Senate Council
on Research; Foundation for Psychocultural Research-UCLA Center for
Culture, Brain and Development; University of Southern California
Clinical and Translational Science Institute (CTSI)
FX This work was supported by the VA Desert Pacific Mental Illness
Research, Education and Clinical Center (MIRECC; Bromley, PI); the
University of California, Los Angeles Faculty Senate Council on Research
(Bromley, PI); the Foundation for Psychocultural Research-UCLA Center
for Culture, Brain and Development (Adams), and the University of
Southern California Clinical and Translational Science Institute (CTSI;
Brekke, PI).
NR 144
TC 0
Z9 0
U1 5
U2 9
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0895-0172
J9 J NEUROPSYCH CLIN N
JI J. Neuropsychiatr. Clin. Neurosci.
PD SPR
PY 2012
VL 24
IS 2
BP 125
EP 140
PG 16
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 972MN
UT WOS:000306281300101
PM 22772661
ER
PT J
AU Meyer, HB
Katsman, A
Sones, AC
Auerbach, DE
Ames, D
Rubin, RT
AF Meyer, Hilary B.
Katsman, Alina
Sones, Alexander C.
Auerbach, Daniel E.
Ames, Donna
Rubin, Robert T.
TI Yoga as an Ancillary Treatment for Neurological and Psychiatric
Disorders: A Review
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; MULTIPLE-SCLEROSIS; REFRACTORY EPILEPSY;
BIPOLAR DISORDER; DEPRESSION SCALE; MENTAL-HEALTH; HATHA-YOGA; THERAPY;
SCHIZOPHRENIA; MEDITATION
AB Yoga is gaining acceptance as an ancillary medical treatment, but there have been few studies evaluating its therapeutic benefits in neurological and major psychiatric conditions. The authors reviewed the literature in English on the efficacy of yoga for these disorders. Only randomized, controlled trials were included, with the exception of the only study of yoga for bipolar disorder, which was observational. Trials were excluded if yoga was not the central component of the intervention. Of seven randomized, controlled trials of yoga in patients with neurological disorders, six found significant, positive effects. Of 13 randomized, controlled trials of yoga in patients with psychiatric disorders, 10 found significant, positive effects. These results, although encouraging, indicate that additional randomized, controlled studies are needed to critically define the benefits of yoga for both neurological and psychiatric disorders. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:152-164)
C1 [Ames, Donna; Rubin, Robert T.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Meyer, Hilary B.] W Los Angeles VA Med Ctr, Dept Psychiat, Los Angeles, CA USA.
[Sones, Alexander C.] Washington Univ, St Louis, MO 63130 USA.
[Auerbach, Daniel E.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
RP Ames, D (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA.
EM donna.ames@va.gov
NR 93
TC 11
Z9 11
U1 1
U2 26
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0895-0172
J9 J NEUROPSYCH CLIN N
JI J. Neuropsychiatr. Clin. Neurosci.
PD SPR
PY 2012
VL 24
IS 2
BP 152
EP 164
PG 13
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 972MN
UT WOS:000306281300103
PM 22772663
ER
PT J
AU Beversdorf, DQ
Nordgren, RE
Bonab, AA
Fischman, AJ
Weise, SB
Dougherty, DD
Felopulos, GJ
Zhou, FC
Bauman, ML
AF Beversdorf, David Q.
Nordgren, Richard E.
Bonab, Ali A.
Fischman, Alan J.
Weise, Steven B.
Dougherty, Darin D.
Felopulos, Gretchen J.
Zhou, Feng C.
Bauman, Margaret L.
TI 5-HT2 Receptor Distribution Shown by [F-18] Setoperone PET in
High-Functioning Autistic Adults
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID TRANSPORTER BINDING; SEROTONIN; DISORDER; CHILDREN; ANXIETY; SPECT;
DEPRESSION; LANGUAGE; SYSTEM
AB The serotonergic system is implicated in disordered emotional behavior. Autism is characterized by impaired processing of emotional information. The serotonergic (5-HT) system is also critically involved in brain development, and abnormal brain synthesis of serotonin is observed in autism. Furthermore, whole blood and platelet serotonin have been reported to be elevated in autism. The authors examined the CNS serotonin system in autism in vivo. 5-HT2 receptors were visualized by PET imaging of [F-18] setoperone-binding in this pilot study of 6 high-functioning autistic adults and 10 matched-control participants. Autism subjects had less thalamic [F-18] setoperone binding than controls, when covaried for age, but no difference reached significance in other areas. A negative relationship between thalamic binding and history of language impairment was also observed. Further studies will be needed to gain a clearer picture of the role of the 5-HT system in autism. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:191-197)
C1 [Beversdorf, David Q.] Univ Missouri, Dept Radiol, Columbia, MO 65211 USA.
[Beversdorf, David Q.] Univ Missouri, Dept Neurol, Columbia, MO 65211 USA.
[Beversdorf, David Q.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA.
[Beversdorf, David Q.] Univ Missouri, Thompson Ctr, Columbia, MO 65211 USA.
[Nordgren, Richard E.] Dartmouth Med Sch, Dept Pediat & Med Neurol, Hanover, NH USA.
[Bonab, Ali A.; Fischman, Alan J.; Weise, Steven B.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA.
[Dougherty, Darin D.; Felopulos, Gretchen J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Beversdorf, DQ (reprint author), Univ Missouri, Dept Radiol, Columbia, MO 65211 USA.
EM beversdorfd@health.missouri.edu
RI Beversdorf, David/M-2786-2016
OI Beversdorf, David/0000-0002-0298-0634
FU Stallone Fund, Los Angeles, CA
FX This research was funded by a grant from the Stallone Fund, Los Angeles,
CA.
NR 36
TC 9
Z9 9
U1 4
U2 10
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0895-0172
J9 J NEUROPSYCH CLIN N
JI J. Neuropsychiatr. Clin. Neurosci.
PD SPR
PY 2012
VL 24
IS 2
BP 191
EP 197
PG 7
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 972MN
UT WOS:000306281300107
PM 22772667
ER
PT J
AU Patti, JA
AF Patti, John A.
TI Radiology's Role in Enhanced International Health Care
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA.
EM jpatti@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD MAR
PY 2012
VL 9
IS 3
BP 155
EP 155
DI 10.1016/j.jacr.2012.01.017
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 961FL
UT WOS:000305449500001
PM 22386156
ER
PT J
AU Fixen, KR
Janakiraman, A
Garrity, S
Slade, DJ
Gray, AN
Karahan, N
Hochschild, A
Goldberg, MB
AF Fixen, Kathryn R.
Janakiraman, Anuradha
Garrity, Sean
Slade, Daniel J.
Gray, Andrew N.
Karahan, Nilay
Hochschild, Ann
Goldberg, Marcia B.
TI Genetic Reporter System for Positioning of Proteins at the Bacterial
Pole
SO MBIO
LA English
DT Article
ID CELL-DIVISION PROTEINS; ESCHERICHIA-COLI K-12; AMP RECEPTOR PROTEIN;
ACTIN-BASED MOTILITY; SHIGELLA-FLEXNERI; INTRACELLULAR MOVEMENT;
UNIPOLAR LOCALIZATION; SEPTAL LOCALIZATION; BETA-LACTAMASE;
RNA-POLYMERASE
AB Spatial organization within bacteria is fundamental to many cellular processes, although the basic mechanisms underlying localization of proteins to specific sites within bacteria are poorly understood. The study of protein positioning has been limited by a paucity of methods that allow rapid large-scale screening for mutants in which protein positioning is altered. We developed a genetic reporter system for protein localization to the pole within the bacterial cytoplasm that allows saturation screening for mutants in Escherichia coli in which protein localization is altered. Utilizing this system, we identify proteins required for proper positioning of the Shigella autotransporter IcsA. Autotransporters, widely distributed bacterial virulence proteins, are secreted at the bacterial pole. We show that the conserved cell division protein FtsQ is required for localization of IcsA and other autotransporters to the pole. We demonstrate further that this system can be applied to the study of proteins other than autotransporters that display polar positioning within bacterial cells.
IMPORTANCE Many proteins localize to specific sites within bacterial cells, and localization to these sites is frequently critical to proper protein function. The mechanisms that underlie protein localization are incompletely understood, in part because of the paucity of methods that allow saturation screening for mutants in which protein localization is altered. We developed a genetic reporter assay that enables screening of bacterial populations for changes in localization of proteins to the bacterial pole, and we demonstrate the utility of the system in identifying factors required for proper localization of the polar Shigella autotransporter protein IcsA. Using this method, we identify the conserved cell division protein FtsQ as being required for positioning of IcsA to the bacterial pole. We demonstrate further that the requirement for FtsQ for polar positioning applies to other autotransporters and that the method can be applied to polar proteins other than autotransporters.
C1 [Fixen, Kathryn R.; Garrity, Sean; Gray, Andrew N.; Hochschild, Ann; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Janakiraman, Anuradha; Slade, Daniel J.; Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA USA.
[Karahan, Nilay] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Goldberg, MB (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
EM mgoldberg1@partners.org
OI Slade, Daniel/0000-0001-5634-7220
FU National Institutes of Health [R01 AI035817]; American Heart Association
fellowship [0425855T]
FX This work was supported by Public Health Service grant R01 AI035817 from
the National Institutes of Health (to M.B.G.) and American Heart
Association fellowship 0425855T (to A.J.).
NR 38
TC 4
Z9 4
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2012
VL 3
IS 2
AR e00251-11
DI 10.1128/mBio.00251-11
PG 9
WC Microbiology
SC Microbiology
GA 959FA
UT WOS:000305297100022
ER
PT J
AU Fagenholz, PJ
AF Fagenholz, Peter J.
TI The role of serum proteins in sepsis
SO VIRULENCE
LA English
DT Editorial Material
DE sepsis; LTA; serum protein; LPS; host-pathogen interactions
ID SEPTIC SHOCK
C1 [Fagenholz, Peter J.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Crit Care, Boston, MA 02114 USA.
[Fagenholz, Peter J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Crit Care, Boston, MA 02114 USA.
EM pfagenholz@partners.org
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2150-5594
J9 VIRULENCE
JI Virulence
PD MAR-APR
PY 2012
VL 3
IS 2
BP 107
EP 108
DI 10.4161/viru.19830
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 963GG
UT WOS:000305607700002
PM 22460633
ER
PT J
AU El Khoury, J
AF El Khoury, Joseph
TI The blood-brain barrier and pathogens Hadrian's Wall or a Dardanian
gate?
SO VIRULENCE
LA English
DT Editorial Material
DE blood-brain barrier; endothelial cells; HTLV-1; HIV; Listeria
monocytogenes; Cryptococcus neoformans; Plasmodium falciparum;
Toxoplasma gondii; Trypanosoma crusii
C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Neuroimmunol Lab, Div Infect Dis, Charlestown, MA 02129 USA.
RP El Khoury, J (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Neuroimmunol Lab, Div Infect Dis, Charlestown, MA 02129 USA.
EM jelkhoury@partners.org
NR 16
TC 4
Z9 4
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2150-5594
J9 VIRULENCE
JI Virulence
PD MAR-APR
PY 2012
VL 3
IS 2
BP 157
EP 158
DI 10.4161/viru.19751
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 963GG
UT WOS:000305607700008
PM 22460634
ER
PT J
AU Dunn, GP
Nahed, BV
Walcott, BP
Jung, H
Tierney, TS
Ogilvy, CS
AF Dunn, Gavin P.
Nahed, Brian V.
Walcott, Brian P.
Jung, Henry
Tierney, Travis S.
Ogilvy, Christopher S.
TI Dual Ipsilateral Craniotomies Through a Single Incision for the Surgical
Management of Multiple Intracranial Aneurysms
SO WORLD NEUROSURGERY
LA English
DT Article
DE Dual craniotomies; Multiple intracranial aneurysms
ID BILATERAL CEREBRAL ANEURYSMS; ARTERY ANEURYSMS; RISKS; SURGERY; ANXIETY
AB OBJECTIVE: To examine whether multiple aneurysms located in the anterior cerebral artery (ACA), middle cerebral artery (MCA), or internal carotid artery (ICA) could be treated through single-stage, ipsilateral dual craniotomies.
METHODS: Investigators reviewed records of nine patients who underwent dual ipsilateral craniotomies through one incision for surgical treatment of multiple aneurysms in the anterior circulation at a single institution from 1994-2010. In all cases, a single-stage pterional and frontal interhemispheric approach through two separate, ipsilateral craniotomies under a single, extended pterional incision was used.
RESULTS: Dual craniotomies through one incision were performed on nine patients with multiple aneurysms without complications. This series included eight women and one man with an average age of 57 years. The mean number of aneurysms treated was 2.7 (range 2-5 aneurysms). Most patients underwent elective treatment. The pterional craniotomy approach was used to treat MCA and ICA aneurysms, whereas distal ACA aneurysms were treated through the frontal parasagittal craniotomy approach. All aneurysms were successfully treated via clip ablation. There were no perioperative or postoperative complications at an average follow-up of 29 months (range 1-131 months).
CONCLUSIONS: Single-stage, ipsilateral dual pterional and frontal craniotomies through one incision constitute a safe approach that can be employed for the effective surgical treatment of multiple aneurysms in joint unilateral and axial locations with excellent clinical results.
C1 [Dunn, Gavin P.; Nahed, Brian V.; Walcott, Brian P.; Jung, Henry; Tierney, Travis S.; Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA.
RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA.
EM cogilvy@partners.org
NR 21
TC 3
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 1878-8750
J9 WORLD NEUROSURG
JI World Neurosurg.
PD MAR-APR
PY 2012
VL 77
IS 3-4
BP 502
EP 506
DI 10.1016/j.wneu.2011.07.005
PG 5
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 961GG
UT WOS:000305451600036
PM 22120339
ER
PT J
AU Braunstein, I
Werth, VP
AF Braunstein, Inbal
Werth, Victoria P.
TI Update on management of connective tissue panniculitides
SO DERMATOLOGIC THERAPY
LA English
DT Article
DE dermatomyositis; lupus erythematosus panniculitis; lupus profundus;
morphea; morphea profunda
ID LUPUS-ERYTHEMATOSUS PANNICULITIS; OF-THE-LITERATURE; T-CELL LYMPHOMA;
LOCALIZED SCLERODERMA; SYSTEMIC-SCLEROSIS; JUVENILE DERMATOMYOSITIS;
CUTANEOUS MANIFESTATION; LINEAR SCLERODERMA; MORPHEA PROFUNDA; DEEP
MORPHEA
AB In connective tissue diseases, panniculitis can be the sole manifestation or can occur along with the underlying disease process. The best described forms of connective tissue panniculitis are lupus erythematosus panniculitis and lupus profundus, panniculitis associated with dermatomyositis, and morphea- and scleroderma-associated panniculitis. These processes cause significant morbidity, such as deep atrophic scars, cosmetic disfigurement, and psychiatric sequelae. Because the inflammation is located in the subcutaneous adipose layer, topical therapies may not penetrate enough to be effective, and systemic agents are required. Despite the large number of reported cases and therapies, recommendations for treatment are based largely on case series and expert opinion due to a lack of controlled therapeutic trials. All treatments are off-label in the United States. The lack of validated clinical outcome measures makes systematic and controlled studies difficult. Nonetheless, further investigation into the most effective therapies for these conditions is needed.
C1 [Braunstein, Inbal; Werth, Victoria P.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Div Dermatol, Philadelphia, PA USA.
RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, PCAM Suite 1-330S,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM werth@mail.med.upenn.edu
FU Department of Veterans Affairs (Veterans Health Administration, Office
of Research and Development, Biomedical Laboratory Research and
Development); National Institutes of Health (NIH) [K24-AR 02207]
FX This material is based upon work supported by the Department of Veterans
Affairs (Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and Development) and by the
National Institutes of Health (NIH K24-AR 02207) to VPW. No conflict of
interest to report.
NR 83
TC 4
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1396-0296
EI 1529-8019
J9 DERMATOL THER
JI Dermatol. Ther.
PD MAR-APR
PY 2012
VL 25
IS 2
SI SI
BP 173
EP 182
DI 10.1111/j.1529-8019.2012.01489.x
PG 10
WC Dermatology
SC Dermatology
GA 959AK
UT WOS:000305281900006
PM 22741936
ER
PT J
AU Schnall, E
Kalkstein, S
Fitchett, G
Salmoirago-Blotcher, E
Ockene, J
Tindle, HA
Thomas, A
Hunt, JR
Wassertheil-Smoller, S
AF Schnall, Eliezer
Kalkstein, Solomon
Fitchett, George
Salmoirago-Blotcher, Elena
Ockene, Judith
Tindle, Hilary Aurora
Thomas, Asha
Hunt, Julie R.
Wassertheil-Smoller, Sylvia
TI Psychological and Social Characteristics Associated with Religiosity in
Women's Health Initiative Participants
SO JOURNAL OF RELIGION & HEALTH
LA English
DT Article
DE Religion and health; Religion and psychology; Religious behavior and
health; Religious attendance and health; Religious behavior and social
support; Religious behavior and social strain; Religious behavior and
psychological characteristics
ID PHYSICAL HEALTH; SUPPORT; MORTALITY; ATTENDANCE; DETERMINANT;
INTEGRATION; HOSTILITY; OPTIMISM; ANXIETY; HISTORY
AB Measures of religiosity are linked to health outcomes, possibly indicating mediating effects of associated psychological and social factors. We examined cross-sectional data from 92,539 postmenopausal participants of the Women's Health Initiative Observational Study who responded to questions on religious service attendance, psychological characteristics, and social support domains. We present odds ratios from multiple logistic regressions controlling for covariates. Women attending services weekly during the past month, compared with those not attending at all in the past month, were less likely to be depressed [OR = 0.78; CI = 0.74-0.83] or characterized by cynical hostility [OR = 0.94; CI = 0.90-0.98], and more likely to be optimistic [OR = 1.22; CI = 1.17-1.26]. They were also more likely to report overall positive social support [OR = 1.28; CI = 1.24-1.33], as well as social support of four subtypes (emotional/informational support, affection support, tangible support, and positive social interaction), and were less likely to report social strain [OR = 0.91; CI = 0.88-0.94]. However, those attending more or less than weekly were not less likely to be characterized by cynical hostility, nor were they less likely to report social strain, compared to those not attending during the past month.
C1 [Schnall, Eliezer] Yeshiva Univ, Yeshiva Coll, New York, NY 10033 USA.
[Kalkstein, Solomon] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
[Fitchett, George] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Salmoirago-Blotcher, Elena; Ockene, Judith] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Tindle, Hilary Aurora] Univ Pittsburgh, Pittsburgh, PA USA.
[Thomas, Asha] Sinai Hosp, Baltimore, MD 21215 USA.
[Hunt, Julie R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, New York, NY USA.
RP Schnall, E (reprint author), Yeshiva Univ, Yeshiva Coll, 500 W 185th St, New York, NY 10033 USA.
EM schnall@yu.edu
OI Salmoirago-Blotcher, Elena/0000-0003-4636-8698
FU NCI NIH HHS [R01 CA141596]; WHI NIH HHS [N01WH42110, N01WH22110,
N01WH24152, N01WH32100, N01WH32101, N01WH32102, N01WH32105, N01WH32106,
N01WH32108, N01WH32109, N01WH32111, N01WH32112, N01WH32113, N01WH32115,
N01WH32118, N01WH32119, N01WH32122, N01WH42107, N01WH42108, N01WH42109,
N01WH42111, N01WH42112, N01WH42113, N01WH42114, N01WH42115, N01WH42116,
N01WH42117, N01WH42118, N01WH42119, N01WH42120, N01WH42121, N01WH42122,
N01WH42123, N01WH42124, N01WH42125, N01WH42126, N01WH42129, N01WH42130,
N01WH42131, N01WH42132, N01WH44221]
NR 37
TC 7
Z9 7
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-4197
EI 1573-6571
J9 J RELIG HEALTH
JI J. Relig. Health
PD MAR
PY 2012
VL 51
IS 1
BP 20
EP 31
DI 10.1007/s10943-011-9549-6
PG 12
WC Public, Environmental & Occupational Health; Religion
SC Public, Environmental & Occupational Health; Religion
GA 958GS
UT WOS:000305225100003
PM 22069057
ER
PT J
AU Trevino, KM
Archambault, E
Schuster, J
Richardson, P
Moye, J
AF Trevino, Kelly M.
Archambault, Elizabeth
Schuster, Jennifer
Richardson, Peter
Moye, Jennifer
TI Religious Coping and Psychological Distress in Military Veteran Cancer
Survivors
SO JOURNAL OF RELIGION & HEALTH
LA English
DT Article
DE Religious coping; Cancer survivor; Veteran; Psychological distress
ID BECK-DEPRESSION-INVENTORY; POSTTRAUMATIC-STRESS-DISORDER;
QUALITY-OF-LIFE; BREAST-CANCER; PRIMARY-CARE; MEDICAL OUTPATIENTS;
CIVILIAN VERSION; PTSD CHECKLIST; HEALTH; ADJUSTMENT
AB Research on the relationship between religious coping and psychological wellbeing in cancer survivors is limited. Forty-eight veteran cancer survivors completed measures of psychological distress, posttraumatic growth, and positive and negative religious coping. Negative religious coping was associated with greater distress and growth. Positive religious coping was associated with greater growth. Gender, race, and religious affiliation were significant predictors of positive and negative religious coping. Veteran cancer survivors who utilize negative religious coping may benefit from referral to clergy or a mental health professional. Assessment of religious coping may be particularly important for female, non-White, and Christian cancer survivors.
C1 [Trevino, Kelly M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Archambault, Elizabeth] VA Boston Healthcare Syst, Geriatr Mental Hlth, Brockton, MA USA.
[Schuster, Jennifer] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Richardson, Peter] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA.
RP Trevino, KM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,SM 271, Boston, MA 02215 USA.
EM trevino.kelly@gmail.com
RI Moye, Jennifer/F-2240-2017
OI Moye, Jennifer/0000-0002-3434-347X
FU RRD VA [I01 RX000104]
NR 48
TC 12
Z9 12
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-4197
J9 J RELIG HEALTH
JI J. Relig. Health
PD MAR
PY 2012
VL 51
IS 1
BP 87
EP 98
DI 10.1007/s10943-011-9526-0
PG 12
WC Public, Environmental & Occupational Health; Religion
SC Public, Environmental & Occupational Health; Religion
GA 958GS
UT WOS:000305225100008
PM 21822744
ER
PT J
AU Kaleyias, J
Manley, P
Kothare, SV
AF Kaleyias, Joseph
Manley, Peter
Kothare, Sanjeev V.
TI Sleep Disorders in Children With Cancer
SO SEMINARS IN PEDIATRIC NEUROLOGY
LA English
DT Review
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EXCESSIVE DAYTIME SLEEPINESS;
CENTRAL-NERVOUS-SYSTEM; QUALITY-OF-LIFE; PRACTICE PARAMETERS;
CIRCADIAN-RHYTHMS; CHILDHOOD-CANCER; WAKEFULNESS TEST; ADULT SURVIVORS;
FATIGUE
AB Approximately three-fourths of all pediatric cancer patients will be long-term survivors; however, there can be a steep cost for cancer survivorship. Cancer treatment involves exposure to chemotherapy, surgical intervention, and radiation, which can cause lasting long-term toxicities. Children with brain tumors have the highest prevalence of long-term morbidities. These effects can be attributed to direct neurologic damage to the developing brain caused by tumor, hydrocephalus, surgical removal of the tumor, and the effects of irradiation. The late effects experienced by childhood cancer survivors involve multiple domains, one of which is sleep disorders. Sleep dysfunction has an increased prevalence in the pediatric cancer survivor population. These issues are disruptive to patients and cause a decrease in quality of life. This review focuses on sleep disorders that occur in pediatric cancer survivors and discusses the possible causes, the assessments used to determine specific sleep disorders, and treatment modalities used to ameliorate this dysfunction with the hope of improving patient's quality of life. Semin Pediatr Neurol 19:25-34 (C) 2012 Elsevier Inc. All rights reserved.
C1 [Kothare, Sanjeev V.] Childrens Hosp, Pediat Sleep Med Training Program, Ctr Pediat Sleep Disorders, Div Epilepsy & Clin Neurophysiol,Dept Neurol, Boston, MA 02115 USA.
[Manley, Peter] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Kaleyias, Joseph] Med Sch Patras, Dept Pediat, Div Pediat Neurol, Patras, Greece.
RP Kothare, SV (reprint author), Childrens Hosp, Pediat Sleep Med Training Program, Ctr Pediat Sleep Disorders, Div Epilepsy & Clin Neurophysiol,Dept Neurol, Fegan 9,300 Longwood Ave, Boston, MA 02115 USA.
EM sanjeev.kothare@childrens.harvard.edu
OI Kothare, Sanjeev/0000-0001-7849-6649
NR 67
TC 9
Z9 10
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 1071-9091
EI 1558-0776
J9 SEMIN PEDIATR NEUROL
JI Semin. Pediatr. Neurol.
PD MAR
PY 2012
VL 19
IS 1
BP 25
EP 34
DI 10.1016/j.spen.2012.02.013
PG 10
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 958TP
UT WOS:000305263900005
PM 22641073
ER
PT J
AU Ullrich, NJ
Embry, L
AF Ullrich, Nicole J.
Embry, Leanne
TI Neurocognitive Dysfunction in Survivors of Childhood Brain Tumors
SO SEMINARS IN PEDIATRIC NEUROLOGY
LA English
DT Review
ID QUALITY-OF-LIFE; CENTRAL-NERVOUS-SYSTEM; LONG-TERM SURVIVORS; CONFORMAL
RADIATION-THERAPY; CANCER SURVIVOR; COGNITIVE FUNCTION; ADULT SURVIVORS;
DEVELOPMENTAL MODEL; CHILDRENS ONCOLOGY; PEDIATRIC-PATIENTS
AB Newer treatments have resulted in increasing numbers of survivors of childhood cancer, for whom neurological and neurocognitive toxicity directly impacts overall functioning and quality of life. There are multiple disease- and host-related factors that influence the development of cancer-related neurocognitive dysfunction, which can progress over time and lead to significant functional impairments. This article provides an overview of the types of neurocognitive deficits seen in survivors of childhood brain tumors, the tools used to assess neurocognitive function, and the factors that impact its severity. This provides a framework for consideration of potential areas for primary prevention by reducing treatment-related toxicity as well as interventions, using behavioral and pharmacologic treatments. Semin Pediatr Neurol 19:35-42 (C) 2012 Elsevier Inc. All rights reserved.
C1 [Ullrich, Nicole J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Ullrich, Nicole J.] Dana Farber Canc Inst, Pediat Brain Tumor Program, Boston, MA 02115 USA.
[Embry, Leanne] Univ Texas Hlth Sci Ctr, San Antonio, TX USA.
RP Ullrich, NJ (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA.
EM nicole.ullrich@childrens.harvard.edu
NR 59
TC 15
Z9 16
U1 2
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1071-9091
EI 1558-0776
J9 SEMIN PEDIATR NEUROL
JI Semin. Pediatr. Neurol.
PD MAR
PY 2012
VL 19
IS 1
BP 35
EP 42
DI 10.1016/j.spen.2012.02.014
PG 8
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 958TP
UT WOS:000305263900006
PM 22641074
ER
PT J
AU Chen, YQ
Hu, N
Cheng, SC
Musoke, P
Zhao, LP
AF Chen, Ying Qing
Hu, Nan
Cheng, Su-Chun
Musoke, Philippa
Zhao, Lue Ping
TI Estimating Regression Parameters in an Extended Proportional Odds Model
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Counting process; Estimating function; HIV/AIDS; Maximum likelihood
estimation; Semiparametric model; Time-varying covariate
ID SEMIPARAMETRIC TRANSFORMATION MODELS; CENSORED-DATA; EFFICIENT
ESTIMATION; INFERENCE; HAZARDS; TRANSMISSION; HIVNET-012; NEVIRAPINE;
HIV-1
AB The proportional odds model may serve as a useful alternative to the Cox proportional hazards model to study association between covariates and their survival functions in medical studies. In this article, we study an extended proportional odds model that incorporates the so-called "external" time-varying covariates. In the extended model, regression parameters have a direct interpretation of comparing survival functions, without specifying the baseline survival odds function. Semiparametric and maximum likelihood estimation procedures are proposed to estimate the extended model. Our methods are demonstrated by Monte Carlo simulations, and applied to a landmark randomized clinical trial of a short-course nevirapine (NVP) for mother-to-child transmission (MTCT) of human immunodeficiency virus type-1 (HIV-1). Additional application includes an analysis of the well-known Veterans Administration (VA) lung cancer trial.
C1 [Hu, Nan] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84132 USA.
[Cheng, Su-Chun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Musoke, Philippa] Makerere Univ, Dept Paediat & Child Hlth, Kampala, Uganda.
EM yqchen@fhcrc.org; nan.hu@hci.utah.edu; scheng@jimmy.harvard.edu;
pmusoke@mujhu.org; lzhao@fhcrc.org
FU National Institute of Allergy and Infectious Diseases (NIH/NIAID) [R01
AI089341, R01 AI78835]; National Cancer Institute (NIH/NCI) [P01
CA053996, R01 CA 119225]; University of Utah's Study Design and
Biostatistics Center; National Center for Research Resources
[UL1-RR025764, C06-RR11234]; National Institute of Mental Health
(NIH/NIMH) [R01 MH 084621]
FX Ying Qing Chen is Full Member, Program in Biostatistics and
Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, WA
98109 (E-mail: yqchen@fhcrc.org). Nan Hu is Assistant Professor,
Department of Internal Medicine, School of Medicine, University of Utah,
Salt Lake City, UT 84132 nan.hu@hci.utah.edu). Su-Chun Cheng is Senior
Research Scientist, Department of Biostatistics and Computational
Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail:
scheng@jimmy.harvard.edu). Philippa Musoke is Associate Professor,
Department of Paediatrics and Child Health, Makerere University,
Kampala, Uganda (E-mail: pmusoke@mujhu.org). Lue Ping Zhao is Full
Member, Program in Biostatistics and Biomathematics, Fred Hutchinson
Cancer Research Center, Seattle, WA 98109 (E-mail: Izhaa@fhcrc.org).
Chen's research was partially supported by grants from the National
Institute of Allergy and Infectious Diseases (NIH/NIAID R01 AI089341,
R01 AI78835) and the National Cancer Institute (NIH/NCI P01 CA053996),
Hu's research was partially supported by the University of Utah's Study
Design and Biostatistics Center, with funding in part from the Public
Health Services research grant numbers UL1-RR025764 and C06-RR11234 and
from the National Center for Research Resources, and Zhao's research was
partially supported by grants from the National Institute of Mental
Health (NIH/NIMH R01 MH 084621) and the National Cancer Institute
(NIH/NCI R01 CA 119225). The authors thank the editor, an associate
editor, and two referees for their valuable comments that helped improve
a previous version of the article.
NR 31
TC 2
Z9 2
U1 0
U2 4
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
EI 1537-274X
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD MAR
PY 2012
VL 107
IS 497
BP 318
EP 330
DI 10.1080/01621459.2012.656021
PG 13
WC Statistics & Probability
SC Mathematics
GA 951QN
UT WOS:000304735200026
PM 22904583
ER
PT J
AU Tang, CY
Eaves, E
Dams-O'Connor, K
Ho, L
Leung, E
Wong, E
Carpenter, D
Ng, J
Gordon, W
Pasinetti, G
AF Tang, Cheuk Ying
Eaves, Emily
Dams-O'Connor, Kristen
Ho, Lap
Leung, Eric
Wong, Edmund
Carpenter, David
Ng, Johnny
Gordon, Wayne
Pasinetti, Giulio
TI DIFFUSE DISCONNECTIVITY IN TBI: A RESTING STATE FMRI AND DTI STUDY
SO TRANSLATIONAL NEUROSCIENCE
LA English
DT Article
DE Traumatic Brain Injury (TBI); Functional magnetic resonance imaging
(fMRI); DTI; Cognitive Function
ID TRAUMATIC BRAIN-INJURY; DEFAULT-MODE NETWORK; LATE-LIFE DEPRESSION;
AXONAL INJURY; WORKING-MEMORY; FUNCTIONAL CONNECTIVITY;
ALZHEIMERS-DISEASE; MRI; TASK; ABNORMALITIES
AB Diffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.
C1 [Tang, Cheuk Ying; Eaves, Emily; Leung, Eric; Wong, Edmund; Carpenter, David; Ng, Johnny] Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA.
[Tang, Cheuk Ying; Pasinetti, Giulio] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Dams-O'Connor, Kristen; Gordon, Wayne] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA.
[Pasinetti, Giulio] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Pasinetti, Giulio] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
RP Tang, CY (reprint author), Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA.
EM giulio.pasinetti@mssm.edu
FU National Center for Research Resources (NCRR), National Institutes of
Health (NIH) [UL1RR029887]
FX The study was supported by discretionary funding to GMP and Grant Number
#UL1RR029887, National Center for Research Resources (NCRR), a component
of the National Institutes of Health (NIH). The authors would also like
to thank the Image Analysis Core of the Mount Sinai Translational and
Molecular Imaging Institute.
NR 38
TC 16
Z9 18
U1 1
U2 11
PU VERSITA
PI WARSAW
PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND
SN 2081-3856
J9 TRANSL NEUROSCI
JI Transl. Neurosci.
PD MAR
PY 2012
VL 3
IS 1
BP 9
EP 14
DI 10.2478/s13380-012-0003-3
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 951CN
UT WOS:000304698400002
PM 23459252
ER
PT J
AU Sharma, NS
Jindal, R
Mitra, B
Lee, S
Li, LL
Maguire, TJ
Schloss, R
Yarmush, ML
AF Sharma, Nripen S.
Jindal, Rohit
Mitra, Bhaskar
Lee, Serom
Li, Lulu
Maguire, Tim J.
Schloss, Rene
Yarmush, Martin L.
TI Perspectives on Non-Animal Alternatives for Assessing Sensitization
Potential in Allergic Contact Dermatitis
SO CELLULAR AND MOLECULAR BIOENGINEERING
LA English
DT Article
DE Immunobiology; Skin sensitization; In silico approaches; QSAR; 2D cell
based models; 3D skin tissue models; Integrated Testing Strategies;
Microfabrication; Microfluidics
ID LYMPH-NODE ASSAY; RECONSTRUCTED HUMAN EPIDERMIS; DENDRITIC CELL-LINE;
INSULT PATCH TEST; TEST H-CLAT; IN-VITRO; SKIN SENSITIZATION; LANGERHANS
CELLS; STRATUM-CORNEUM; QSAR MODELS
AB Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development of in vitro methods to assess chemical sensitivity. In this paper, we examine existing approaches including in silico models, cell and tissue based assays for distinguishing between sensitizers and irritants. The in silico approaches that have been discussed include Quantitative Structure Activity Relationships (QSAR) and QSAR based expert models that correlate chemical molecular structure with biological activity and mechanism based read-across models that incorporate compound electrophilicity. The cell and tissue based assays rely on an assortment of mono and coculture cell systems in conjunction with 3D skin models. Given the complexity of allergen induced immune responses, and the limited ability of existing systems to capture the entire gamut of cellular and molecular events associated with these responses, we also introduce a microfabricated platform that can capture all the key steps involved in allergic contact sensitivity. Finally, we describe the development of an integrated testing strategy comprised of two or three tier systems for evaluating sensitization potential of chemicals.
C1 [Sharma, Nripen S.; Jindal, Rohit; Mitra, Bhaskar; Lee, Serom; Li, Lulu; Maguire, Tim J.; Schloss, Rene; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA.
[Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd,231 Piscataway, Piscataway, NJ 08854 USA.
EM yarmush@rci.rutgers.edu
FU NIBIB NIH HHS [P41 EB002503]; NIGMS NIH HHS [T32 GM008339]
NR 170
TC 1
Z9 2
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1865-5025
J9 CELL MOL BIOENG
JI Cell. Mol. Bioeng.
PD MAR
PY 2012
VL 5
IS 1
BP 52
EP 72
DI 10.1007/s12195-011-0189-4
PG 21
WC Cell & Tissue Engineering; Biophysics; Cell Biology
SC Cell Biology; Biophysics
GA 940EJ
UT WOS:000303872500005
PM 24741377
ER
PT J
AU Hahn, JO
Reisner, AT
Jaffer, FA
Asada, HH
AF Hahn, Jin-Oh
Reisner, Andrew T.
Jaffer, Farouc A.
Asada, H. Harry
TI Subject-Specific Estimation of Central Aortic Blood Pressure Using an
Individualized Transfer Function: A Preliminary Feasibility Study
SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE
LA English
DT Article
DE Cardiovascular monitoring; central aortic blood pressure; individualized
transfer function (ITF)
ID PERIPHERAL ARTERIAL-PRESSURE; WAVE-FORM; PULSE; VALIDATION; EXERCISE;
TIME; HYPERTENSION; DERIVATION; REST
AB This paper presents a new approach to the estimation of unknown central aortic blood pressure waveform from a directly measured peripheral blood pressure waveform, in which a physics-based model is employed to solve for a subject-and state-specific individualized transfer function (ITF). The ITF provides the means to estimate the unknown central aortic blood pressure from the peripheral blood pressure. Initial proof-of-principle for the ITF is demonstrated experimentally through an in vivo protocol. In swine subjects taken through wide range of physiologic conditions, the ITF was on average able to provide central aortic blood pressure waveforms more accurately than a nonindividualized transfer function. Its usefulness was most evident when the subject's pulse transit time deviated from normative values. In these circumstances, the ITF yielded statistically significant reductions over a nonindividualized transfer function in the following three parameters: 1) 30% reduction in the root-mean-squared error between estimated versus actual central aortic blood pressure waveform (p < 10(-4)), 2) >50% reduction in the error between estimated versus actual systolic and pulse pressures (p < 10(-4)), and 3) a reduction in the overall breakdown rate (i.e., the frequency of estimation errors >3 mmHg, p < 10(-4)). In conclusion, the ITF may offer an attractive alternative to existing methods that estimates the central aortic blood pressure waveform, and may be particularly useful in nonnormative physiologic conditions.
C1 [Hahn, Jin-Oh] Univ Alberta, Dept Mech Engn, Edmonton, AB T6G 2G8, Canada.
[Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02142 USA.
[Reisner, Andrew T.; Jaffer, Farouc A.] Harvard Univ, Sch Med, Boston, MA 02142 USA.
[Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02142 USA.
[Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02142 USA.
[Asada, H. Harry] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
RP Hahn, JO (reprint author), Univ Alberta, Dept Mech Engn, Edmonton, AB T6G 2G8, Canada.
EM jinoh.hahn@alum.mit.edu; areisner@partners.org; fjaffer@mgh.harvard.edu;
asada@mit.edu
OI Jaffer, Farouc/0000-0001-7980-384X
NR 28
TC 12
Z9 12
U1 2
U2 14
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 MAR
PY 2012
VL 16
IS 2
SI SI
BP 212
EP 220
DI 10.1109/TITB.2011.2177668
PG 9
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA 943WZ
UT WOS:000304158600005
PM 22147332
ER
PT J
AU Frakt, AB
Pizer, SD
Feldman, R
AF Frakt, Austin B.
Pizer, Steven D.
Feldman, Roger
TI The Effects of Market Structure and Payment Rate on the Entry of Private
Health Plans into the Medicare Market
SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING
LA English
DT Article
ID RAISING RIVALS COSTS; INSTRUMENTAL VARIABLES; HMO PARTICIPATION;
INSURANCE MARKETS; MANAGED CARE; INDUSTRY; MODEL; POWER; RISK;
BENEFICIARIES
AB Private insurance firms participating in Medicare can offer up to three principal plan types: coordinated care plans (CCPs), prescription drug plans (PDPs), and private fee-for-service (FEES) plans. Firms can make entry and marketing decisions separately across plan types and geographic regions. In this study, we estimate firm-level models of Medicare private plan entry using data from the years 2007 to 2009. Our models include a measure of market structure and separately identify CCP, PDP, and PFFS entry. We find evidence that entry barriers associated with CCP market concentration affect three product types. We also find evidence of cross-product competition and common cost or demand factors that make entry with certain product combinations more likely. We predict that the market presence of CCPs and PFFS plans will decrease and that of PDPs will increase in response to payment reductions included in the new health reform law.
C1 [Frakt, Austin B.; Pizer, Steven D.] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Pizer, Steven D.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Feldman, Roger] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA.
RP Frakt, AB (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,Mail Stop 152H, Boston, MA 02130 USA.
EM frakt@bu.edu
NR 83
TC 4
Z9 4
U1 2
U2 10
PU BLUE CROSS BLUE SHIELD ASSOC
PI ROCHESTER
PA 150 EAST MAIN ST, ROCHESTER, NY 14647 USA
SN 0046-9580
EI 1945-7243
J9 INQUIRY-J HEALTH CAR
JI Inquiry-J. Health Care Organ. Provis. Financ.
PD SPR
PY 2012
VL 49
IS 1
BP 15
EP 36
DI 10.5034/inquiryjrnl_49.01.03
PG 22
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 942UR
UT WOS:000304075900003
PM 22650015
ER
PT J
AU Duong, TQ
AF Duong, Timothy Q.
TI Multimodal MRI of Experimental Stroke
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Review
DE MRI; Perfusion-diffusion mismatch; ADC; CBF; DWI; PWI; Experimental
stroke model; Rodents; Oxygen challenge; Predictive mode; Magnetic
resonance imaging; Rats; Hyperperfusion; fMRI
ID CEREBRAL-BLOOD-FLOW; ISCHEMIC TISSUE-FATE; APPARENT
DIFFUSION-COEFFICIENT; QUANTITATIVE PERFUSION; POSTISCHEMIC
HYPERPERFUSION; PLASMINOGEN ACTIVATOR; ARTERY OCCLUSION; FOCAL ISCHEMIA;
BRAIN-INJURY; RAT-BRAIN
AB Stroke is the fourth leading cause of death and the leading cause of long-term disability in USA. Brain imaging data from experimental stroke models and stroke patients have shown that there is often a gradual progression of potentially reversible ischemic injury toward infarction. Reestablishing tissue perfusion and/or treating with neuroprotective drugs in a timely fashion are expected to salvage some ischemic tissues. Diffusion-weighted imaging based on magnetic resonance imaging (MRI) in which contrast is based on water motion can detect ischemic injury within minutes after onsets, whereas computed tomography and other imaging modalities fail to detect stroke injury for at least a few hours. Along with quantitative perfusion imaging, the perfusion-diffusion mismatch which approximates the ischemic penumbra could be imaged noninvasively. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study ischemic tissue at risk in experimental stroke in rats.
C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Dept Vet Affairs, S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Duong, Timothy Q.] SW Fdn Biomed Res, SW Natl Primate Res Ctr, San Antonio, TX 78284 USA.
RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM duongt@uthscsa.edu
RI Duong, Timothy/B-8525-2008
FU NINDS NIH HHS [R01 NS045879]
NR 67
TC 5
Z9 5
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-4483
J9 TRANSL STROKE RES
JI Transl. Stroke Res.
PD MAR
PY 2012
VL 3
IS 1
SI SI
BP 8
EP 15
DI 10.1007/s12975-011-0140-y
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 943YP
UT WOS:000304164300003
PM 24323751
ER
PT J
AU Wey, HY
Duong, TQ
AF Wey, Hsiao-Ying
Duong, Timothy Q.
TI Multimodal MRI of Nonhuman Primate Stroke
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Review
DE Nonhuman primate; MRI; Perfusion; Diffusion; Functional MRI; MCAO
ID FOCAL CEREBRAL-ISCHEMIA; APPARENT DIFFUSION-COEFFICIENT; TRANSORBITAL
BABOON MODEL; PERFUSION MRI; REPERFUSED STROKE; ARTERY OCCLUSION; WATER
DIFFUSION; RHESUS-MONKEYS; BRAIN ISCHEMIA; TISSUE SODIUM
AB Stroke is the fourth leading cause of death. Despite decades of research, no neuroprotective drug has proven to be effective clinically. One widely accepted view to account for this negative outcome is that the rodent stroke model simply does not adequately reflect the complexity of human stroke. Recent failures of several high-profile neuroprotective drugs for stroke treatment in phase III clinical trials further under-score the importance of developing adequate animal models for stroke research. The brain organization and vascular circuitry of nonhuman primates (NHPs) are more homologous with humans than the widely used rodent for stroke modeling. The Stroke Therapy Academic Industry Roundtable, a national committee commissioned by the American Heart Association, recommended that clinically relevant NHP stroke models be established for developing and assessing neuroprotective drugs. The aim of this article is to review the challenges and applications of magnetic resonance imaging studies of NHP stroke models.
C1 [Wey, Hsiao-Ying; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Wey, Hsiao-Ying] Harvard Univ, Sch Med, Dept Radiol,Massachussetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA.
[Wey, Hsiao-Ying; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM wey@nmr.mgh.harvard.edu; duongt@uthscsa.edu
RI Duong, Timothy/B-8525-2008; Wey, Hsiao-Ying/G-3031-2012
FU American Heart Association [0940104N, 11PRE5670005]; National Institute
of Health (NINDS) [R01 NS45879]; Clinical Translational Science Award
[UL1RR025767]; Institute for Integration of Medicine and Science,
University of Texas Health Science Center
FX This work was supported by the American Heart Association Established
Investigator Award 0940104N, National Institute of Health (NINDS R01
NS45879) and Clinical Translational Science Award's imaging supplement
(parent grant UL1RR025767) to TQD. HYW was supported by a predoctoral
fellowship (11PRE5670005) from the American Heart Association and by a
Translational Science Training Grant from the Institute for Integration
of Medicine and Science, University of Texas Health Science Center.
NR 47
TC 1
Z9 1
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-4483
J9 TRANSL STROKE RES
JI Transl. Stroke Res.
PD MAR
PY 2012
VL 3
IS 1
SI SI
BP 84
EP 89
DI 10.1007/s12975-012-0145-1
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 943YP
UT WOS:000304164300011
PM 24323756
ER
PT J
AU Lynch, J
Lathan, CL
AF Lynch, J.
Lathan, C. L.
TI DIFFUSION OF THE EGFR ASSAY IN UNITED STATES
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Lynch, J.; Lathan, C. L.] Univ Massachusetts, Dana Farber Canc Inst, Boston, MA 02125 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 37
EP 38
PG 2
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100096
ER
PT J
AU Wen, LS
Geduld, HI
Nagurney, JT
Wallis, LA
AF Wen, Leana S.
Geduld, Heike I.
Nagurney, J. Tobias
Wallis, Lee A.
TI Perceptions of graduates from Africa's first emergency medicine training
program at the University of Cape Town/Stellenbosch University
SO CANADIAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE internatonal emergency medicine; medical education; residency; South
Africa
ID DEPARTMENTS
AB Objective: Africa's first postgraduate training program in emergency medicine (EM) was established at the University of Cape Town/Stellenbosch University (UCT/SUN) in 2004. This study of the UCT/SUN EM program investigated the backgrounds, perceptions, and experiences of its graduates.
Methods: This was a cross-sectional descriptive study. The study population was the 30 graduates from the first four classes in the UCT/SUN EM program (2007-2010). We employed a scripted interview with a combination of closed and open-ended questions. Data were analyzed using the thematic method of qualitative analysis.
Results: Twenty-seven (90%) graduates were interviewed. Initial career goals were primarily (78%) to practice EM in a nonacademic clinical capacity. At the time of the interview, 52% held academic positions, 15% had nonacademic clinical positions, and 33% had temporary positions and were looking for other posts. The three most commonly cited strengths of their program were diversity of clinical rotations (85%), autonomy and procedural experience (63%), and importance of being pioneers within Africa (52%). The three most commonly cited weaknesses were lack of bedside teaching in the ED (96%), lack of career options after graduation (74%), and lack of preparation for academic careers (70%).
Conclusions: The lessons identified from structured interviews with graduates from Africa's first EM training include the importance of strong clinical training, difficulty of ensuring bedside teaching in a new program, the necessity of ensuring postgraduation positions, and the need for academic training. These findings may be useful for other developing countries looking to start EM training programs.
C1 [Wen, Leana S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA.
[Geduld, Heike I.; Wallis, Lee A.] Univ Cape Town, Div Emergency Med, ZA-7925 Cape Town, South Africa.
[Geduld, Heike I.; Wallis, Lee A.] Univ Stellenbosch, Div Emergency Med, ZA-7600 Stellenbosch, South Africa.
RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Emergency Med, Harvard Affiliated Emergency Med Residency, 75 Francis St,Neville House 236-A, Boston, MA 02115 USA.
EM Wen.Leana@gmail.com
FU Partners Healthcare
FX Dr. Wen received a travel grant from Partners Healthcare.
NR 15
TC 2
Z9 2
U1 0
U2 5
PU DECKER PUBL INC
PI HAMILTON
PA 69 JOHN ST S, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA
SN 1481-8035
J9 CAN J EMERG MED
JI Can. J. Emerg. Med.
PD MAR
PY 2012
VL 14
IS 2
BP 97
EP 105
DI 10.2310/8000.2012.110639
PG 9
WC Emergency Medicine
SC Emergency Medicine
GA 940QC
UT WOS:000303907100006
PM 22554441
ER
PT J
AU Hoy, CL
Everett, WN
Yildirim, M
Kobler, J
Zeitels, SM
Ben-Yakar, A
AF Hoy, Christopher L.
Everett, W. Neil
Yildirim, Murat
Kobler, James
Zeitels, Steven M.
Ben-Yakar, Adela
TI Towards endoscopic ultrafast laser microsurgery of vocal folds
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE ultrafast lasers; femtosecond laser surgery; second-harmonic generation;
endoscope; nonlinear optics; multiphoton process; laser-induced damage
ID MULTIPHOTON MICROSCOPY; SURGERY; LARYNGOLOGY; PROBE
AB Vocal fold scarring is a predominant cause of voice disorders yet lacks a reliable treatment method. The injection of soft biomaterials to improve mechanical compliance of the vocal folds has emerged as a promising treatment. Here, we study the use of precise femtosecond laser microsurgery to ablate subsurface voids, with a goal of eventually creating a plane in dense subepithelial scar tissue into which biomaterials can be injected for their improved localization. Specifically, we demonstrate the ablation of small subepithelial voids in porcine vocal fold tissue up to 120 mu m below the surface such that larger voids in the active area of vocal fold mucosa (similar to 3 x 10 mm(2)) can eventually be ablated in about 3 min. We use sub-mu J, 776-nm pulses from a compact femtosecond fiber laser system operating at a 500-kHz repetition rate. The use of relatively high repetition rates, with a small number of overlapping pulses, is critical to achieving ablation in a very short time while still avoiding significant heat deposition. Additionally, we use the same laser for nonlinear optical imaging to provide visual feedback of tissue structure and to confirm successful ablation. The ablation parameters, including pulse duration, pulse energy, spot size, and scanning speed, are comparable to the specifications in our recently developed miniaturized femtosecond laser surgery probes, illustrating the feasibility of developing an ultrafast laser surgical instrument. 2072 Society of Photooptical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.038002]
C1 [Hoy, Christopher L.; Everett, W. Neil; Yildirim, Murat; Ben-Yakar, Adela] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA.
[Kobler, James; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
RP Ben-Yakar, A (reprint author), Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA.
EM ben-yakar@mail.utexas.edu
RI Hoy, Christopher/H-5004-2013
OI Hoy, Christopher/0000-0002-4567-6958
FU National Science Foundation [IDR: CBET-1014953, CBET-0846868]; Texas
Ignition Fund
FX This work was supported by grants from the National Science Foundation
(IDR: CBET-1014953 and Career Award: CBET-0846868) and a grant from the
Texas Ignition Fund. The authors would like to thank Raydiance, Inc. for
use of their Discovery fiber laser, as well as Dr. R. Rox Anderson and
Dr. Nicholas Durr for consultation.
NR 20
TC 8
Z9 8
U1 0
U2 8
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAR
PY 2012
VL 17
IS 3
AR 038002
DI 10.1117/1.JBO.17.3.038002
PG 8
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 937XJ
UT WOS:000303697000032
PM 22502583
ER
PT J
AU Wang, TY
Mancuso, JJ
Sapozhnikova, V
Dwelle, J
Ma, LL
Willsey, B
Kazmi, SMS
Qiu, JZ
Li, XK
Asmis, R
Johnston, KP
Feldman, MD
Milner, TE
AF Wang, Tianyi
Mancuso, J. Jacob
Sapozhnikova, Veronika
Dwelle, Jordan
Ma, Li L.
Willsey, Brian
Kazmi, S. M. Shams
Qiu, Jinze
Li, Xiankai
Asmis, Reto
Johnston, Keith P.
Feldman, Marc D.
Milner, Thomas E.
TI Dual-wavelength multifrequency photothermal wave imaging combined with
optical coherence tomography for macrophage and lipid detection in
atherosclerotic plaques using gold nanoparticles
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE atherosclerosis; macrophage; lipid; nanorose; photothermal wave imaging;
optical coherence tomography; two-photon luminescence microscopy
ID CENTRAL-NERVOUS-SYSTEM; IRON-OXIDE; MAGNETIC-RESONANCE; CORONARY PLAQUE;
IN-VITRO; CELLS; EXPRESSION; INFLAMMATION; MICROSCOPY; RUPTURE
AB The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P < 0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P < 0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.036009]
C1 [Wang, Tianyi; Dwelle, Jordan; Kazmi, S. M. Shams; Qiu, Jinze; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Ma, Li L.; Willsey, Brian; Johnston, Keith P.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.
[Mancuso, J. Jacob; Sapozhnikova, Veronika; Li, Xiankai; Asmis, Reto; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA.
[Feldman, Marc D.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RP Milner, TE (reprint author), Univ Texas Austin, Dept Biomed Engn, 1 Univ Stn,C0800, Austin, TX 78712 USA.
EM terra.laser@gmail.com
RI Qiu, Jinze /I-2272-2013
OI Qiu, Jinze /0000-0001-8466-1460
FU Veterans Administration; Welch Foundation [F-1319]; NSF [CBET-0968038];
Department of Energy Center for Frontiers of Subsurface Energy Security
FX The authors would like to acknowledge the technical support from the
University of Texas Health Science Center at San Antonio. This work was
supported by a Veterans Administration merit grant to Feldman, a Welch
Foundation grant F-1319 and NSF grant CBET-0968038 to Johnston, and the
Department of Energy Center for Frontiers of Subsurface Energy Security.
NR 59
TC 6
Z9 6
U1 1
U2 12
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAR
PY 2012
VL 17
IS 3
AR 036009
DI 10.1117/1.JBO.17.3.036009
PG 10
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 937XJ
UT WOS:000303697000016
PM 22502567
ER
PT J
AU Zettergren, E
Vickers, D
Runnels, J
Murthy, SK
Lin, CP
Niedre, M
AF Zettergren, Eric
Vickers, Dwayne
Runnels, Judith
Murthy, Shashi K.
Lin, Charles P.
Niedre, Mark
TI Instrument for fluorescence sensing of circulating cells with diffuse
light in mice in vivo
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE road image; diffuse; in vivo; flow cytometry; fluorescence
ID METASTATIC BREAST-CANCER; TUMOR-CELLS; PERIPHERAL-BLOOD; DISEASE
PROGRESSION; MULTIPLE-MYELOMA; FLOW-CYTOMETRY; MOUSE; SURVIVAL
AB Accurate quantification of circulating cell populations in mice is important in many areas of preclinical biomedical research. Normally, this is done either by extraction and analysis of small blood samples or, more recently, by using microscopy-based in vivo fluorescence flow cytometry. We describe a new technological approach to this problem using detection of diffuse fluorescent light from relatively large blood vessels in vivo. The diffuse fluorescence flow cytometer (DFFC) uses a laser to illuminate a mouse limb and an array of optical fibers coupled to a high-sensitivity photomultiplier tube array operating in photon counting mode to detect weak fluorescence signals from cells. We first demonstrate that the DFFC instrument is capable of detecting fluorescent microspheres and Vybrant-DiD-labeled cells in a custom-made optical flow phantom with similar size, optical properties, linear flow rates, and autofluorescence as a mouse limb. We also present preliminary data demonstrating that the DFFC is capable of detecting circulating cells in nude mice in vivo. In principle, this device would allow interrogation of the whole blood volume of a mouse in minutes, with sensitivity improvement by several orders of magnitude compared to current approaches. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.037001]
C1 [Zettergren, Eric; Vickers, Dwayne; Murthy, Shashi K.; Niedre, Mark] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA.
[Runnels, Judith; Lin, Charles P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Runnels, Judith; Lin, Charles P.] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
[Runnels, Judith; Lin, Charles P.] Wellman Ctr Photomed, Boston, MA 02114 USA.
RP Niedre, M (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA.
EM mniedre@ece.neu.edu
RI Vickers, Dwayne/I-5819-2012
OI Vickers, Dwayne/0000-0002-9218-7348
FU National Institutes of Health [R21 HL098750-01]; Northeastern University
FX This work was funded with a grant from the National Institutes of Health
(R21 HL098750-01) and from a Northeastern University laboratory startup
grant. The assistance of Dr. Riikka Pastila and Tushar Swamy in
conducting experiments is also gratefully acknowledged.
NR 26
TC 7
Z9 7
U1 0
U2 9
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAR
PY 2012
VL 17
IS 3
AR 037001
DI 10.1117/1.JBO.17.3.037001
PG 8
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 937XJ
UT WOS:000303697000022
PM 22502573
ER
PT J
AU Ren, XF
Akiyoshi, K
Grafe, MR
Vandenbark, AA
Hurn, PD
Herson, PS
Offner, H
AF Ren, Xuefang
Akiyoshi, Kozaburo
Grafe, Marjorie R.
Vandenbark, Arthur A.
Hurn, Patricia D.
Herson, Paco S.
Offner, Halina
TI Myelin specific cells infiltrate MCAO lesions and exacerbate stroke
severity
SO METABOLIC BRAIN DISEASE
LA English
DT Article
DE Experimental stroke; Myelin reactive splenocytes; Inflammatory
responses; Neurologic deficit
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC
ENCEPHALOMYELITIS; MURINE EXPERIMENTAL STROKE; FOCAL CEREBRAL-ISCHEMIA;
GROWTH-FACTOR-BETA; BASIC-PROTEIN; T-CELLS; MULTIPLE-SCLEROSIS; IMMUNE
PRIVILEGE; IMMUNOLOGICAL-TOLERANCE
AB Although inflammatory responses increase stroke severity, the role of immune cells specific for central nervous system (CNS) antigens remains controversial. Disruption of the blood-brain barrier (BBB) during stroke allows CNS antigens to leak into the peripheral circulation and enhances access of circulating leukocytes to the brain, including those specific for CNS antigens such as myelin oligodendrocyte glycoprotein (MOG) that can induce experimental autoimmune encephalomyelitis (EAE). We here demonstrate for the first time that myelin reactive splenocytes specific for MOG transferred into severe combined immunodeficient (SCID) mice can migrate into the infarct hemisphere of recipients subjected to 60 min middle cerebral artery occlusion (MCAO) and 96 h reperfusion; moreover these cells exacerbate infarct volume and worsen neurological deficits compared to animals transferred with naive splenocytes. These findings indicate that autoimmunity in the CNS can exert detrimental injury on brain cells and worsen the damage from ischemic stroke.
C1 [Ren, Xuefang; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA.
[Grafe, Marjorie R.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA.
[Vandenbark, Arthur A.] Dept Vet Affairs Med Ctr, Res Serv, Portland, OR USA.
[Ren, Xuefang; Akiyoshi, Kozaburo; Grafe, Marjorie R.; Herson, Paco S.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA.
[Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
[Hurn, Patricia D.] Univ Texas Syst, Off Hlth Affairs, Austin, TX USA.
RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM offnerva@ohsu.edu
FU NIH [NR03521, NS49210]; Collins Medical Trust; Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and Development
FX We thank Dr. Heng Hu, Dr. Sushmita Sinha, Dr. Sheetal Bodhankar, Dr.
Suzan Dziennis, Dr. Takeru Shimizu and Ms. Sandhya Subramanian for
helpful discussions; Ms. Xiao Jing Nie for performing histological
staining and Ms. Lisa Miller for help with experiments; and Ms. Eva
Niehaus for assistance in preparing the manuscript. This work was
supported by NIH Grants NR03521 (PDH), NS49210 (PDH) and the Collins
Medical Trust (XR). This material is based upon work supported in part
by the Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development, Biomedical Laboratory Research and
Development. The contents do not represent the views of the Department
of Veterans Affairs or the United States Government.
NR 44
TC 16
Z9 16
U1 0
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7490
J9 METAB BRAIN DIS
JI Metab. Brain Dis.
PD MAR
PY 2012
VL 27
IS 1
BP 7
EP 15
DI 10.1007/s11011-011-9267-5
PG 9
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 940BM
UT WOS:000303865000002
PM 21989743
ER
PT J
AU Xin, JP
Fargo, KN
Tanzer, L
Sanders, VM
Jones, KJ
AF Xin, Junping
Fargo, Keith N.
Tanzer, Lisa
Sanders, Virginia M.
Jones, Kathryn J.
TI Immune cell-mediated neuroprotection is independent of estrogen action
through estrogen receptor-alpha
SO METABOLIC BRAIN DISEASE
LA English
DT Article
DE Estrogen; CD4(+) T cell; Facial motoneuron; Axotomy; Neuroprotection
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REGULATORY T-CELLS; FACIAL
MOTONEURON SURVIVAL; NERVE TRANSECTION; EXPRESSION; TESTOSTERONE;
AXOTOMY; MICE; LYMPHOCYTES; CNS
AB It has been well documented that both estrogen and immune cells (CD4(+) T cells) mediate neuroprotection in the mouse facial nerve axotomy model. Estrogen has been shown to play an important role in regulating the immune response. However, it is unclear whether immune cell-mediated neuroprotection is dependent on estrogen signaling. In this study, using FACS staining, we confirmed that the majority of CD4(+) T cells express high levels of estrogen receptor-alpha (ER alpha), suggesting that CD4(+) T cell-mediated neuroprotection may be modulated by estrogen signaling. We previously found that immunodeficient Rag-2KO mice showed a significant increase in axotomy-induced facial motoneuron death compared to immunocompetent wild-type mice. Therefore, we investigated axotomy-induced facial motoneuron loss in immunodeficient Rag-2KO mice that received 17 beta-estradiol treatment or adoptive transfer of immune cells from mice lacking functional ER alpha. Our results indicate that while estradiol treatment failed to rescue facial motoneurons from axotomy-induced cell death in Rag-2KO mice, immune cells lacking ERa successfully restored facial motoneuron survival in Rag-2 KO mice to a wild-type level. Collectively, we concluded that CD4(+) T cell-mediated neuroprotection is independent of estrogen action through ERa.
C1 [Xin, Junping; Fargo, Keith N.; Tanzer, Lisa] Loyola Univ, Med Ctr, Inst Neurosci, Maywood, IL 60153 USA.
[Xin, Junping; Fargo, Keith N.; Tanzer, Lisa] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA.
[Sanders, Virginia M.] Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Jones, Kathryn J.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA.
RP Xin, JP (reprint author), Loyola Univ, Med Ctr, Inst Neurosci, 2160 S 1st Ave, Maywood, IL 60153 USA.
EM neuroimmune@gmail.com
FU National Institutes of Health [NS40433]; VA [RRD CDA-2 B6598-W];
Muscular Dystrophy Association [MDA202906]
FX K.J.J. and V.M.S. were supported by National Institutes of Health grant
NS40433, and K.N.F. was supported by VA grant RR&D CDA-2 B6598-W. J.X.
was supported by Muscular Dystrophy Association grant (MDA202906). We
thank Tom Alexander for technical support, as well as Linda Poggensee
and Dr. Nichole Mesnard for their editorial assistance.
NR 40
TC 1
Z9 2
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7490
J9 METAB BRAIN DIS
JI Metab. Brain Dis.
PD MAR
PY 2012
VL 27
IS 1
BP 23
EP 28
DI 10.1007/s11011-011-9265-7
PG 6
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 940BM
UT WOS:000303865000004
PM 21975535
ER
PT J
AU Subramanian, S
Miller, LM
Grafe, MR
Vandenbark, AA
Offner, H
AF Subramanian, Sandhya
Miller, Lisa M.
Grafe, Marjorie R.
Vandenbark, Arthur A.
Offner, Halina
TI Contribution of GPR30 for 1,25 dihydroxyvitamin D-3 protection in EAE
SO METABOLIC BRAIN DISEASE
LA English
DT Article
DE GPR30; EAE; 1,25 dihydroxyvitamin D-3; Estrogen
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; RECEPTOR;
ACTIVATION; MICE
AB Previous studies have demonstrated that vitamin D3-mediated protection in EAE occurs only in females and is dependent on the presence of diestrus levels of 17 beta-estradiol (E2). To evaluate the role of estrogen receptors in vitamin D3 treatment of EAE, we compared disease severity, CNS histopathology and immunological responses in vehicle and calcitrol (1,25 dihydroxyvitamin D-3) treated WT C57BL/6 mice vs. GPR30 membrane estrogen receptor (MER) knockout mice with MOG-35-55 peptide-induced EAE. Our results demonstrated that vitamin D-3-mediated prevention of clinical signs, CNS cellular lesions and demyelination observed in WT mice was abrogated in GPR30-KO mice with EAE. Regulatory effects of vitamin D-3 treatment that were MER dependent included increased levels of IL-10 and IL-6 secreted by MOG peptide-reactive splenocytes and increased expression of CCL5, CCR1 & CCR3 in spleen tissue. These results demonstrate for the first time that the MER is a key contributor to the E2-dependent effects of vitamin D-3-mediated protection in EAE.
C1 [Subramanian, Sandhya; Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA.
[Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Grafe, Marjorie R.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA.
[Vandenbark, Arthur A.] Dept Vet Affairs Med Ctr, Res Serv, Portland, OR 97239 USA.
[Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA.
[Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA.
RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM offnerva@ohsu.edu
FU National Multiple Sclerosis Society [RG3107-D-6]; Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and Development
FX The authors wish to thank Ms. Eva Niehaus for assistance in preparing
the manuscript. This work was supported by National Multiple Sclerosis
Society grant RG3107-D-6. This material is based upon work supported in
part by the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development, Biomedical
Laboratory Research and Development. The contents do not represent the
views of the Department of Veterans Affairs or the United States
Government.
NR 22
TC 8
Z9 9
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7490
J9 METAB BRAIN DIS
JI Metab. Brain Dis.
PD MAR
PY 2012
VL 27
IS 1
BP 29
EP 35
DI 10.1007/s11011-011-9266-6
PG 7
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 940BM
UT WOS:000303865000005
PM 21994003
ER
PT J
AU Van den Stock, J
de Gelder, B
AF Van den Stock, Jan
de Gelder, Beatrice
TI Emotional information in body and background hampers recognition memory
for faces
SO NEUROBIOLOGY OF LEARNING AND MEMORY
LA English
DT Article
DE Context; Face; Emotion; Memory; Body; Scene
ID FACIAL EXPRESSIONS; NEURAL MECHANISMS; PERCEPTION; RETRIEVAL; CONTEXT;
INTEGRATION; VOICE
AB Emotional influences on memory for events have long been documented yet surprisingly little is known about how emotional signals conveyed by contextual cues influence memory for face identity. This study investigated how positively and negatively valenced contextual emotion cues conveyed by body expressions or background scenes influence face memory. The results provide evidence of emotional context influence on face recognition memory and show that faces encoded in emotional (either fearful or happy) contexts (either the body or background scene) are less well recognized than faces encoded in neutral contexts and this effect is larger for body context than for scene context. The findings are compatible with the hypothesis that emotional signals in visual scenes trigger orienting responses which may lead to a less elaborate processing of featural details like the identity of a face, in turn resulting in a decreased facial recognition memory. (C) 2012 Elsevier Inc. All rights reserved.
C1 [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[de Gelder, Beatrice] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Van den Stock, Jan; de Gelder, Beatrice] Katholieke Univ Leuven, BELL, Div Psychiat, Dept Neurosci, Louvain, Belgium.
[Van den Stock, Jan; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
RP de Gelder, B (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Room 417,Bldg 36,1st St, Charlestown, MA 02129 USA.
EM jan.vandenstock@med.kuleuven.be; degelder@nmr.mgh.harvard.edu
RI Van den Stock, Jan/F-1906-2014
OI Van den Stock, Jan/0000-0001-5756-3195
FU European Commission (COBOL); FWO-Vlaanderen; FET-Open, COBOL
FX We are grateful to two anonymous reviewers for their helpful
suggestions. J.V.d.S. and B.d.G. are partly supported by European
Commission (COBOL) Grant. J.V.d.S. is a post-doctoral researcher
supported by FWO-Vlaanderen. B.d.G is partly supported by FP 6 FET-Open,
COBOL Grant en FP7-FET-Open Grants.
NR 28
TC 24
Z9 24
U1 1
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1074-7427
J9 NEUROBIOL LEARN MEM
JI Neurobiol. Learn. Mem.
PD MAR
PY 2012
VL 97
IS 3
BP 321
EP 325
DI 10.1016/j.nlm.2012.01.007
PG 5
WC Behavioral Sciences; Neurosciences; Psychology; Psychology,
Multidisciplinary
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 937ZM
UT WOS:000303702700006
PM 22406473
ER
PT J
AU Taneja, R
Bhargava, P
Cuevas, C
Dighe, MK
AF Taneja, Ranu
Bhargava, Puneet
Cuevas, Carlos
Dighe, Manjiri K.
TI Common and Less-Common Renal Masses and Masslike Conditions
SO RADIOLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Renal mass; Incidental renal mass; Genitourinary imaging; Kidney
disease; Renal disease
ID SOLITARY FIBROUS TUMOR; LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; UPPER
URINARY-TRACT; IMAGING FINDINGS; CELL CARCINOMA; AUTOIMMUNE
PANCREATITIS; PATHOLOGICAL CORRELATION; LYMPHOBLASTIC-LEUKEMIA; ACUTE
PYELONEPHRITIS; MEDULLARY CARCINOMA
AB As an increasing number of imaging examinations are performed, a greater number of incidental renal lesions are detected. Apart from the usual cysts and solid renal cell carcinomas, a variety of unusual benign and malignant renal lesions exist. Imaging is invaluable in characterizing these lesions and is confirmatory in some benign lesions. Renal cell carcinoma remains the diagnosis of exclusion; however, assessment of the imaging pattern in the appropriate clinical context can improve diagnostic accuracy. The objective of this article is to familiarize the radiologist with the imaging appearance of unusual non-neoplastic and neoplastic lesions and correlate with histopathologic studies when available.
C1 [Bhargava, Puneet] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA.
[Taneja, Ranu] Changi Gen Hosp, Dept Radiol, Singapore 529889, Singapore.
[Cuevas, Carlos; Dighe, Manjiri K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA.
RP Bhargava, P (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Mail Box 358280,S-114 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA.
EM bhargp@uw.edu
OI Bhargava, Puneet/0000-0002-3849-9666
NR 57
TC 1
Z9 1
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-8389
EI 1557-8275
J9 RADIOL CLIN N AM
JI Radiol. Clin. N. Am.
PD MAR
PY 2012
VL 50
IS 2
BP 245
EP +
DI 10.1016/j.rcl.2012.02.006
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 941HW
UT WOS:000303955300005
PM 22498441
ER
PT J
AU Bhargava, P
Dighe, MK
Lee, JH
Wang, C
AF Bhargava, Puneet
Dighe, Manjiri K.
Lee, Jean Hwa
Wang, Carolyn
TI Multimodality Imaging of Ureteric Disease
SO RADIOLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Ureter; Imaging; Transitional cell carcinoma; Calculi; Urography
ID TRANSITIONAL-CELL CARCINOMA; UNENHANCED HELICAL CT; UPPER URINARY-TRACT;
URETEROPELVIC JUNCTION OBSTRUCTION; MAGNETIC-RESONANCE UROGRAPHY; SHOT
INTRAVENOUS PYELOGRAM; UNSTABLE TRAUMA PATIENTS; RETROPERITONEAL
FIBROSIS; VOIDING CYSTOURETHROGRAPHY; COMPUTED-TOMOGRAPHY
AB The proximal ureter (upper) extends from the ureteropelvic junction to where the ureter crosses the sacroiliac joint, the middle ureter courses over the bony pelvis and iliac vessels, and the distal or pelvic (lower) ureter extends from the iliac vessels to the bladder. Benign and malignant lesions can affect the ureter and these may be caused by contiguous involvement from the kidney or bladder. The ureter can be imaged by computed tomography; magnetic resonance imaging; direct pyelography, both antegrade and retrograde; nuclear medicine diuretic scan; and voiding cystourethrography. This article discusses benign, malignant, neoplastic, nonneoplastic processes involving the ureter.
C1 [Dighe, Manjiri K.; Lee, Jean Hwa; Wang, Carolyn] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA.
[Bhargava, Puneet] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA.
RP Dighe, MK (reprint author), Univ Washington, Med Ctr, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA.
EM dighe@u.washington.edu
OI Bhargava, Puneet/0000-0002-3849-9666
NR 117
TC 1
Z9 1
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 0033-8389
J9 RADIOL CLIN N AM
JI Radiol. Clin. N. Am.
PD MAR
PY 2012
VL 50
IS 2
BP 271
EP +
DI 10.1016/j.rcl.2012.02.008
PG 30
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 941HW
UT WOS:000303955300007
PM 22498443
ER
PT J
AU Mirochnik, B
Bhargava, P
Dighe, MK
Kanth, N
AF Mirochnik, Brandon
Bhargava, Puneet
Dighe, Manjiri K.
Kanth, Nalini
TI Ultrasound Evaluation of Scrotal Pathology
SO RADIOLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Ultrasound; Testis; Scrotum imaging; Scrotal imaging; Torsion; Orchitis
ID COLOR DOPPLER SONOGRAPHY; TESTICULAR EPIDERMOID CYSTS; RETE TESTIS;
TUNICA ALBUGINEA; TUBULAR ECTASIA; GRAY-SCALE; DIAGNOSIS; TRAUMA;
LYMPHOMA; APPEARANCE
AB Palpable scrotal mass, acute scrotal pain, and enlarged scrotum are common scenarios in clinical practice. The imaging modality of choice to evaluate scrotal pathology is ultrasound (US). US is key in determining if a palpable abnormality is extratesticular or intratesticular and cystic or solid. US findings help narrow the differential to benign or malignant causes. Extratesticular lesions are more common and usually benign. Rarely, extratesticular solid lesions are malignant but US features are nonspecific. Accurately diagnosing rare benign intratesticular lesions is vital to avoid unnecessary orchiectomy. This article reviews extratesticular and intratesticular lesions presenting as a palpable mass and other conditions commonly seen.
C1 [Bhargava, Puneet] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA.
[Mirochnik, Brandon; Kanth, Nalini] Nassau Univ, Med Ctr, Dept Radiol, E Meadow, NY 11554 USA.
[Dighe, Manjiri K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA.
RP Bhargava, P (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Mail Box 358280,S-114 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA.
EM bhargp@uw.edu
OI Bhargava, Puneet/0000-0002-3849-9666
NR 49
TC 15
Z9 16
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-8389
J9 RADIOL CLIN N AM
JI Radiol. Clin. N. Am.
PD MAR
PY 2012
VL 50
IS 2
BP 317
EP +
DI 10.1016/j.rcl.2012.02.005
PG 17
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 941HW
UT WOS:000303955300009
PM 22498445
ER
PT J
AU Khor, TS
Fujita, H
Nagata, K
Shimizu, M
Lauwers, GY
AF Khor, Tze S.
Fujita, Hiroshi
Nagata, Koji
Shimizu, Michio
Lauwers, Gregory Y.
TI Biopsy interpretation of colonic biopsies when inflammatory bowel
disease is excluded
SO JOURNAL OF GASTROENTEROLOGY
LA English
DT Review
DE Non-idiopathic inflammatory bowel disease; Biopsy interpretation;
Inflammatory bowel disease; Differential diagnosis
ID SOLITARY RECTAL ULCER; FOCAL ACTIVE COLITIS; MUCOSAL MAST-CELLS;
OF-THE-LITERATURE; PNEUMATOSIS CYSTOIDES INTESTINALIS; SUBEPITHELIAL
COLLAGEN TABLE; SELF-LIMITED COLITIS; MICROSCOPIC COLITIS; LYMPHOCYTIC
COLITIS; ISCHEMIC COLITIS
AB The interpretation of colonic biopsies related to inflammatory conditions can be challenging because the colorectal mucosa has a limited repertoire of morphologic responses to various injurious agents. Only few processes have specific diagnostic features, and many of the various histological patterns reflect severity and duration of the disease. Importantly the correlation with endoscopic and clinical information is often cardinal to arrive at a specific diagnosis in many cases.
C1 [Khor, Tze S.; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA.
[Khor, Tze S.] Queen Elizabeth II Med Ctr, PathW Lab Med, Nedlands, WA 6009, Australia.
[Fujita, Hiroshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima Univ Hosp, Dept Gastroenterol, Kagoshima 890, Japan.
[Nagata, Koji; Shimizu, Michio] Saitama Med Univ, Int Med Ctr, Dept Pathol, Saitama, Japan.
RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Warren 219,55 Fruit St, Boston, MA 02114 USA.
EM tzesk@member.rcpa.edu.au; GLAUWERS@partners.org
NR 195
TC 7
Z9 7
U1 0
U2 0
PU SPRINGER TOKYO
PI TOKYO
PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN
SN 0944-1174
J9 J GASTROENTEROL
JI J. Gastroenterol.
PD MAR
PY 2012
VL 47
IS 3
BP 226
EP 248
DI 10.1007/s00535-012-0539-6
PG 23
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 934PF
UT WOS:000303455700002
PM 22322659
ER
PT J
AU Calkins, H
Kuck, KH
Cappato, R
Brugada, J
Camm, AJ
Chen, SA
Crijns, HJG
Damiano, RJ
Davies, DW
DiMarco, J
Edgerton, J
Ellenbogen, K
Ezekowitz, MD
Haines, DE
Haissaguerre, M
Hindricks, G
Iesaka, Y
Jackman, W
Jalife, J
Jais, P
Kalman, J
Keane, D
Kim, YH
Kirchhof, P
Klein, G
Kottkamp, H
Kumagai, K
Lindsay, BD
Mansour, M
Marchlinski, FE
McCarthy, PM
Mont, JL
Morady, F
Nademanee, K
Nakagawa, H
Natale, A
Nattel, S
Packer, DL
Pappone, C
Prystowsky, E
Raviele, A
Reddy, V
Ruskin, JN
Shemin, RJ
Tsao, HM
Wilber, D
AF Calkins, Hugh
Kuck, Karl Heinz
Cappato, Riccardo
Brugada, Josep
Camm, A. John
Chen, Shih-Ann
Crijns, Harry J. G.
Damiano, Ralph J., Jr.
Davies, D. Wyn
DiMarco, John
Edgerton, James
Ellenbogen, Kenneth
Ezekowitz, Michael D.
Haines, David E.
Haissaguerre, Michel
Hindricks, Gerhard
Iesaka, Yoshito
Jackman, Warren
Jalife, Jose
Jais, Pierre
Kalman, Jonathan
Keane, David
Kim, Young-Hoon
Kirchhof, Paulus
Klein, George
Kottkamp, Hans
Kumagai, Koichiro
Lindsay, Bruce D.
Mansour, Moussa
Marchlinski, Francis E.
McCarthy, Patrick M.
Mont, J. Lluis
Morady, Fred
Nademanee, Koonlawee
Nakagawa, Hiroshi
Natale, Andrea
Nattel, Stanley
Packer, Douglas L.
Pappone, Carlo
Prystowsky, Eric
Raviele, Antonio
Reddy, Vivek
Ruskin, Jeremy N.
Shemin, Richard J.
Tsao, Hsuan-Ming
Wilber, David
TI 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical
ablation of atrial fibrillation: recommendations for patient selection,
procedural techniques, patient management and follow-up, definitions,
endpoints, and research trial design
SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY
LA English
DT Article
DE Atrial fibrillation; Catheter ablation; Surgical ablation
ID PULMONARY-VEIN ISOLATION; QUALITY-OF-LIFE; CIRCULAR MAPPING CATHETER;
INTENSITY FOCUSED ULTRASOUND; OBSTRUCTIVE SLEEP-APNEA; MITRAL-VALVE
SURGERY; PHRENIC-NERVE INJURY; BIPOLAR RADIOFREQUENCY ABLATION;
MAGNETIC-RESONANCE ANGIOGRAPHY; ANTIARRHYTHMIC-DRUG THERAPY
AB This is a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation, developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch the European Society of Cardiology and the European Cardiac Arrhythmia Society (ECAS), and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). This is endorsed by the governing bodies of the ACC Foundation, the AHA, the ECAS, the EHRA, the STS, the APHRS, and the HRS.
C1 [Cappato, Riccardo] IRCCS Policlin San Donato, Arrhythmia & EP Ctr, Milan, Italy.
[Calkins, Hugh] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Kuck, Karl Heinz] Allgemeines Krankenhaus St Georg, Hamburg, Germany.
[Chen, Shih-Ann] Taipei Vet Gen Hosp, Taipei, Taiwan.
[Prystowsky, Eric] Care Grp LLC, Indianapolis, IN USA.
[Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA.
[Haines, David E.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Marchlinski, Francis E.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Davies, D. Wyn] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England.
[Lindsay, Bruce D.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Damiano, Ralph J., Jr.] Washington Univ, Sch Med, St Louis, MO USA.
[Packer, Douglas L.] Mayo Fdn, Rochester, MN USA.
[Brugada, Josep] Univ Barcelona, Hosp Clin, Barcelona, Spain.
[Camm, A. John] St Georges Univ London, London, England.
[Crijns, Harry J. G.] Univ Hosp Maastricht, Maastricht, Netherlands.
[DiMarco, John] Univ Virginia Hlth Syst, Charlottesville, VA USA.
[Edgerton, James] Heart Hosp Baylor Plano & Cardiopulmonary Res Sci, Plano, TX USA.
[Ellenbogen, Kenneth] Virginia Commonwealth Univ, Richmond, VA USA.
[Ezekowitz, Michael D.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Haissaguerre, Michel] Univ Bordeaux, Hop Cardiol, Bordeaux, France.
[Hindricks, Gerhard; Jais, Pierre] Univ Leipzig, Leipzig, Germany.
[Iesaka, Yoshito] Tsuchiura Kyodo Gen Hosp, Tsuchiura, Ibaraki, Japan.
[Jackman, Warren; Nakagawa, Hiroshi] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Jalife, Jose] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kalman, Jonathan] Royal Melbourne Hosp, Melbourne, Vic, Australia.
[Keane, David] St Vincents Univ Hosp, Dublin 4, Ireland.
[Kim, Young-Hoon] Korea Univ, Med Ctr, Seoul, South Korea.
[Kirchhof, Paulus] Univ Birmingham, Ctr Cardiovasc Sci, Birmingham, W Midlands, England.
[Kirchhof, Paulus] Univ Munster, Dept Cardiol, Munster, Germany.
[Klein, George] Univ Western Ontario, Univ Hosp, London, ON N6A 5A5, Canada.
[Kottkamp, Hans] Clin Hirslanden, Zurich, Switzerland.
[Kumagai, Koichiro] Fukuoka Sanno Hosp, Fukuoka, Japan.
[Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[McCarthy, Patrick M.] NW Mem Hosp, Chicago, IL 60611 USA.
[Mont, J. Lluis] Univ Barcelona, FESC Hosp Clin, Barcelona, Spain.
[Morady, Fred] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Nademanee, Koonlawee] Pacific Rim EP Res Inst Ctr, Inglewood, CA USA.
[Nattel, Stanley] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Pappone, Carlo] Maria Cecilia Hosp, Cotignola, Italy.
[Raviele, Antonio] Umberto I Hosp, Venice, Italy.
[Reddy, Vivek] Mt Sinai Sch Med, New York, NY USA.
[Shemin, Richard J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Tsao, Hsuan-Ming] Natl Yang Ming Univ Hosp, Taipei, Taiwan.
[Wilber, David] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
RP Cappato, R (reprint author), IRCCS Policlin San Donato, Arrhythmia & EP Ctr, Milan, Italy.
EM segreteriaelettrofisiologia.ipsd@grupposandonato.it
RI Pappone, Carlo/J-9853-2016; Jalife, Jose/L-4833-2015;
OI Pappone, Carlo/0000-0002-0901-6135; Kirchhof,
Paulus/0000-0002-1881-0197; Jalife, Jose/0000-0003-0080-3500; BRUGADA,
JOSEP/0000-0002-5662-8302
FU St. Jude Medical; Biotronik; Sorin; Boston Scientific; Medtronic; Sanofi
Aventis; Daiichi Sankyo; BMS; Pfizer; Servier; Johnson Johnsonm;
Biosense Webster; Sorin Group; Bard; Merck; Boehringer Ingelheim;
Atricure; Toray Medical; 3M Medica/MEDA Pharma; Cardovascular
Therapeutics; OMRON; BMBF; Fondation Leducq; German Research Foundation;
DFG; European Union; CryoCath Technologies, Inc.; Stereotaxis; Cordis
Webster - Johnson Johnson; Edwards Lifesciences; Rhythmia; MC10; Voyage
Medical; Rhythmia Medical; Endosense SA; AstraZeneca; NIH; Thermedical;
EpiEP; Minnesota Partnership for Biotechnology and Medical Genomic /
University of Minnesota; Endosense; CardioFocus; Atritech; Phillips;
SentreHeart
FX Research Grant St. Jude Medical (b), Biotronik (b), Sorin (b), Boston
Scientific, (b), Medtronic (b), Medtronic (d), Boston Scientific (d),
St. Jude Medical (d), Sanofi Aventis (e), Daiichi Sankyo (f), BMS (e),
Pfizer (e), Servier (e), Johnson & Johnsonm(e), Boston Scientific (c),
Biosense Webster (c), Sorin Group (c), Bard (c), St. Jude Medical (c),
St Jude Medical (e), Merck (f), Sanofi Aventis (e), Boehringer Ingelheim
(f), Boston Scientific (f), None Atricure (c), Medtronic (e), None
Atricure (c), Medtronic (d), Boston Scientific (d), St. Jude Medical
(b), Biosense Webster (d), None St. Jude Medical (b), Medtronic (b),
Toray Medical (b), None Biosense Webster (c), Biotronik (d), St. Jude
Medical (f), None None None None Medtronic (e), None St. Jude Medical
(d), 3M Medica/MEDA Pharma (d), Cardovascular Therapeutics (d),
Medtronic (d), OMRON (d), Sanofi aventis (d), St. Jude Medical (d), BMBF
(d), Fondation Leducq (d), German Research Foundation (d), DFG (d),
European Union (d), None None Biosense Webster (b), CryoCath
Technologies, Inc. (b), Stereotaxis (b), Medtronic (b), St. Jude Medical
(b), Cordis Webster - Johnson & Johnson (b), Edwards Lifesciences (b),
None None Biosense Webster (d), St Jude Medical (d), Rhythmia (d), MC10
(c), Voyage Medical (c) Biosense Webster (b), St. Jude Medical (b), None
St. Jude Medical (d), Boston Scientific (d), Sanofi Aventis (d),
Biosense Webster (d), Medtronic (d), None Biosense Webster (a), Biosense
Webster (e), St. Jude Medical (d), Stereotaxis (d), Rhythmia Medical
(d), Endosense SA (d), None AstraZeneca (f), NIH (f), Medtronic (f),
Thermedical (d), EpiEP (c), St. Jude Medical (f), Minnesota Partnership
for Biotechnology and Medical Genomic / University of Minnesota (f),
Biosense Webster (f), Biotronik (e), None None St. Jude Medical (b),
Biosense Webster (b), Endosense (b), Medtronic (b), CardioFocus (b),
Atritech (b), Phillips (b), Voyage Medical (b) SentreHeart (b), None
None None None
NR 756
TC 106
Z9 111
U1 0
U2 19
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1383-875X
J9 J INTERV CARD ELECTR
JI J. Interv. Card. Electrophysiol.
PD MAR
PY 2012
VL 33
IS 2
BP 171
EP 257
DI 10.1007/s10840-012-9672-7
PG 87
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 935SL
UT WOS:000303540600006
PM 22382715
ER
PT J
AU Vakharia, KT
Henstrom, D
Lindsay, R
Cunnane, MB
Cheney, M
Hadlock, T
AF Vakharia, Kalpesh T.
Henstrom, Douglas
Lindsay, Robin
Cunnane, Mary Beth
Cheney, Mack
Hadlock, Tessa
TI Color Doppler Ultrasound: Effective Monitoring of the Buried Free Flap
in Facial Reanimation
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
DE facial paralysis; gracilis; ultrasound; Doppler; buried free flap
ID FREE TISSUE TRANSFER; HEAD
AB Objective. The gracilis muscle free flap has become a reliable means for smile reanimation for patients with facial paralysis. Because it is a buried flap, it presents a postoperative monitoring challenge. We sought to evaluate our experience with color Doppler ultrasound in the monitoring of gracilis free flap viability in the immediate postoperative setting.
Study Design. Case series with planned data collection.
Setting. Tertiary medical center.
Methods. Patients with facial paralysis treated with gracilis muscle free flap for smile reanimation performed between March 2009 and November 2010 were evaluated by color Doppler ultrasound and included in the study. Our experience with the use of the color Doppler ultrasound to monitor the gracilis muscle flap is presented.
Results. Forty-six patients were identified. In all cases, color Doppler ultrasound was used postoperatively to assess flow through the vascular pedicle. Outcomes included an early flap survival rate of 100%, with no instances of equivocal or absent flow on either the arterial or venous side. Color Doppler ultrasound provided important objective information regarding muscle perfusion postoperatively in several instances of equivocal postoperative perfusion of the flap.
Conclusion. Color Doppler ultrasound is a safe, noninvasive method that can be performed serially to evaluate a buried free flap. We have had success in verifying normal arterial and venous flow through the pedicle using this method of monitoring of the gracilis muscle free flap during facial reanimation, and in 3 instances, it eliminated the need for wound exploration to verify appropriate muscle perfusion.
C1 [Vakharia, Kalpesh T.; Cunnane, Mary Beth; Cheney, Mack; Hadlock, Tessa] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Vakharia, Kalpesh T.; Cunnane, Mary Beth; Cheney, Mack; Hadlock, Tessa] Harvard Univ, Sch Med, Boston, MA USA.
[Henstrom, Douglas] Univ Iowa, Dept Otolaryngol, Iowa City, IA USA.
[Lindsay, Robin] Natl Naval Med Ctr, Dept Otolaryngol Head & Neck Surg, Bethesda, MD USA.
RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
EM tessa_hadlock@meei.harvard.edu
NR 11
TC 12
Z9 12
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD MAR
PY 2012
VL 146
IS 3
BP 372
EP 376
DI 10.1177/0194599811427377
PG 5
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 935TX
UT WOS:000303545100006
PM 22261491
ER
PT J
AU Lin, HW
Bhattacharyya, N
AF Lin, Harrison W.
Bhattacharyya, Neil
TI Contemporary Assessment of Medical Morbidity and Mortality in Head and
Neck Surgery
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article; Proceedings Paper
CT AAO-HNSF Annual Meeting and OTO EXPO
CY SEP 10-14, 2011
CL San Francisco, CA
SP AAO, HNSF
DE head and neck cancer; morbidity; mortality; complications
ID QUALITY-OF-LIFE; ELDERLY-PATIENTS; CANCER; COMPLICATIONS; COMORBIDITY;
STAY
AB Objective. To update the incidence of medical morbidity and mortality in head and neck surgery and factors that influence length of stay (LOS).
Study Design. Cross-sectional analysis of a national database.
Setting. Academic medical center.
Methods. A specific database for head and neck surgical procedures was extracted from the National Hospital Data Survey for 2005 through 2007. Records of inpatient admissions for patients undergoing head and neck surgery as the primary procedure were examined to establish the frequency of medical complications, mortality, and LOS. The association of these medical complications with mortality and LOS was determined.
Results. A total of 330,629 head and neck procedures were analyzed. The overall medical morbidity and mortality rates were 5.0% +/- 0.7% and 0.4% +/- 0.2%, respectively. The most common medical complication was hospital-acquired pneumonia (3.3% +/- 0.6%), whereas acute renal failure, stroke, acute myocardial infarction, pulmonary embolism, and deep venous thrombosis were substantially less frequent (combined incidence, 2.1%). The mean LOS for patients without a major complication was 3.3 +/- 0.2 days vs 14.0 +/- 1.9 days for those with a major complication (P < .001).
Conclusions. Medical morbidity and mortality in patients undergoing head and neck surgical procedures continue to be exceedingly low. Although medical complications are associated with a longer LOS, the influence of medical complications on mortality has declined. Enhancements in perioperative medical management of head and neck surgical patients are likely responsible for these improved results.
C1 [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA.
RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM harrison_lin@meei.harvard.edu
NR 17
TC 5
Z9 5
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD MAR
PY 2012
VL 146
IS 3
BP 385
EP 389
DI 10.1177/0194599811428557
PG 5
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 935TX
UT WOS:000303545100009
PM 22075078
ER
PT J
AU Wiechers, IR
Viron, M
Stoklosa, J
Freudenreich, O
Henderson, DC
Weiss, A
AF Wiechers, Ilse R.
Viron, Mark
Stoklosa, Joseph
Freudenreich, Oliver
Henderson, David C.
Weiss, Anthony
TI Impact of a Metabolic Screening Bundle on Rates of Screening for
Metabolic Syndrome in a Psychiatry Resident Outpatient Clinic
SO ACADEMIC PSYCHIATRY
LA English
DT Article
ID ANTIPSYCHOTIC MEDICATIONS; SCHIZOPHRENIA
AB Objective: Although it is widely acknowledged that second-generation antipsychotics are associated with cardiometabolic side effects, rates of metabolic screening have remained low. The authors created a quality-improvement (QI) intervention in an academic medical center outpatient psychiatry resident clinic with the aim of improving rates of screening for metabolic syndrome in patients being prescribed antipsychotic medications.
Methods: The core components of the QI intervention included resident education and creation of a metabolic screening bundle for the electronic medical record. Quarterly audits of individual patient electronic medical records assessed whether a patient was currently prescribed antipsychotics and whether metabolic-syndrome screening had been documented at any time in the preceding 12 months.
Results: In each audit period, from 131 to 156 patients (30%-36% of total clinic sample) were prescribed antipsychotic medication. After the intervention, rates of documentation of the components of the metabolic screening bundle increased between 3.5- and 10-fold (final rates: 39% for blood pressure, 44% for BMI, and 55% for glucose and lipid panel). Rates of documenting the full bundle increased nearly 30-fold (final rate: 31%).
Conclusion: Provider-education combined with introduction of a documentation bundle in the electronic medical record increased rates of documented metabolic screening in patients being prescribed antipsychotic medications by psychiatry residents.
C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Stoklosa, Joseph] McLean Hosp, Belmont, MA USA.
RP Wiechers, IR (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA.
EM ilse.wiechers@yale.edu
NR 10
TC 3
Z9 3
U1 2
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1042-9670
J9 ACAD PSYCHIATR
JI Acad. Psych.
PD MAR-APR
PY 2012
VL 36
IS 2
BP 118
EP 121
PG 4
WC Education & Educational Research; Psychiatry
SC Education & Educational Research; Psychiatry
GA 932GL
UT WOS:000303278300009
PM 22532201
ER
PT J
AU Blumenthal, KG
Patil, SU
Long, ADA
AF Blumenthal, Kimberly G.
Patil, Sarita U.
Long, Aidan A.
TI The importance of vancomycin in drug rash with eosinophilia and systemic
symptoms (dress) syndrome
SO ALLERGY AND ASTHMA PROCEEDINGS
LA English
DT Article
ID INDUCED HYPERSENSITIVITY SYNDROME; HERPESVIRUS 6 INFECTION;
REACTIVATION; ASSOCIATION; HUMAN-HERPESVIRUS-6; TEICOPLANIN; USAGE
AB Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome characterized by fever, rash, eosinophilia, atypical lymphocytes, and multiorgan involvement has a significant mortality. Inpatient vancomycin use is increasing and appears to be emerging as an important etiology of DRESS syndrome. This study highlights the importance of vancomycin as a cause of DRESS syndrome. We reviewed all cases of DRESS syndrome among inpatients consulted by the Allergy & Immunology service at Massachusetts General Hospital (MGH) from July 2009 through December 2010. We also reviewed the use of inpatient parenteral vancomycin over the past 4 years at MGH. Six patients fulfilled clinical criteria for DRESS syndrome, including rash, fever, eosinophilia, and hepatitis, with five (83%) having vancomycin as the attributable cause. Onset of symptoms varied from 12 days to 4 weeks after start of vancomycin treatment. Systemic findings included atypical lymphocytes, lymphadenopathy, nephritis, hypotension, tachycardia, and pharyngitis. Treatment with corticosteroids was required in three cases. Recurrence of peripheral eosinophilia was a marker of disease relapse. In three of the five patients (60%), elevated human herpesvirus 6 (HHV6) IgG titers correlated with greater systemic involvement and prolonged time to resolution. MGH pharmacy records indicate a progressive increase in the number of patients treated with parenteral vancomycin over the last 4 years. Causative agents for DRESS syndrome in an inpatient setting is likely different from that seen in the general population. With increasing use of vancomycin, we are likely to see more cases of DRESS syndrome caused by vancomycin. Recognition of vancomycin as a common cause of inpatient DRESS syndrome is important.
C1 [Blumenthal, Kimberly G.; Patil, Sarita U.; Long, Aidan A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Patil, Sarita U.; Long, Aidan A.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA.
EM kblumenthal1@partners.org
NR 34
TC 14
Z9 14
U1 0
U2 1
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1088-5412
J9 ALLERGY ASTHMA PROC
JI Allergy Asthma Proc.
PD MAR-APR
PY 2012
VL 33
IS 2
BP 165
EP 171
DI 10.2500/aap.2012.33.3498
PG 7
WC Allergy
SC Allergy
GA 932FJ
UT WOS:000303275500008
PM 22525393
ER
PT J
AU Soler, ZM
Mace, JC
Litvack, JR
Smith, TL
AF Soler, Zachary M.
Mace, Jess C.
Litvack, Jamie R.
Smith, Timothy L.
TI Chronic rhinosinusitis, race, and ethnicity
SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
LA English
DT Article
ID ENDOSCOPIC SINUS SURGERY; ALLERGIC FUNGAL RHINOSINUSITIS;
QUALITY-OF-LIFE; SOCIOECONOMIC-FACTORS; SURGICAL OUTCOMES; DISEASE
BURDEN; BONE EROSION; HEALTH; PERSPECTIVE; DIAGNOSIS
AB Background: Little is known regarding the epidemiology of chronic rhinosinusitis (CRS) in racial and ethnic minorities in the United States. This study was designed to comprehensively evaluate the current prevalence of CRS across various treatment settings to identify possible disparities in health care access and use between racial and ethnic populations.
Methods: The National Health Interview Survey (NHIS), National Ambulatory Medical Care Survey (NAMCS), and National Hospital Ambulatory Medical Care Survey (NHAMCS) database registries were extracted to identify the national prevalence of CRS in race/ethnic populations and resource use in ambulatory care settings. Systematic literature review identified studies reporting treatment outcomes in minority patients electing endoscopic sinus surgery (ESS). Data were supplemented using a multi-institutional cohort of patients undergoing surgical treatment.
Results: National survey data suggest CRS is a significant health condition for all major race/ethnic groups in the United States, accounting for a sizable portion of office, emergency, and outpatient visits. Differences in insurance status, work absenteeism, and resource use were found between race/ethnic groups. Despite its prevalence, few published studies include information regarding minority patients with CRS. Most (90%) cohort studies did not provide details of race/ethnicity for ESS outcomes. Prospective cohort analysis indicated that minority surgical patients accounted for only 18%, when compared with national census estimates (35%).
Conclusion: CRS is an important health condition for all major race/ethnic groups in the United States. Significant differences may exist across racial and ethnic categories with regard to CRS health status and health care use. Given current demographic shifts in the United States, specific attention should be given to understanding CRS within the context of racial and ethnic populations. Public clinical trial registration (www.clinicaltrials.gov) I. D. No. NCT00799097. (Am J Rhinol Allergy 26, 110-116, 2012; doi: 10.2500/ajra.2012.26.3741)
C1 [Mace, Jess C.; Smith, Timothy L.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Oregon Sinus Ctr, Portland, OR 97239 USA.
[Soler, Zachary M.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA.
[Litvack, Jamie R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
RP Smith, TL (reprint author), Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Oregon Sinus Ctr, 3181 SW Sam Jackson Pk Rd PV-01, Portland, OR 97239 USA.
EM smithtim@ohsu.edu
FU National Institute on Deafness and Other Communication Disorders, one of
the National Institutes of Health [DC005805]; National Institute on
Deafness and Other Communication Disorders, one of the National
Institutes of Health, Bethesda, MD [DC005805]
FX Funded by a grant from the National Institute on Deafness and Other
Communication Disorders, one of the National Institutes of Health
(DC005805; PI: T. Smith); TL Smith is a consultant for Intersect ENT,
Inc., Palo Alto, CA, which provided no financial support for this
investigation. TL Smith and JC Mace also received grant funding
(DC005805) from the National Institute on Deafness and Other
Communication Disorders, one of the National Institutes of Health,
Bethesda, MD, for data collection associated with this investigation.
The remaining author had no conflicts of interest to declare pertaining
to this article
NR 32
TC 29
Z9 29
U1 0
U2 4
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1945-8924
J9 AM J RHINOL ALLERGY
JI Am. J. Rhinol. Allergy
PD MAR-APR
PY 2012
VL 26
IS 2
BP 110
EP 116
DI 10.2500/ajra.2012.26.3741
PG 7
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 930OI
UT WOS:000303148400012
PM 22487286
ER
PT J
AU Trippa, L
Rosner, GL
Muller, P
AF Trippa, Lorenzo
Rosner, Gary L.
Mueller, Peter
TI Bayesian Enrichment Strategies for Randomized Discontinuation Trials
SO BIOMETRICS
LA English
DT Article
DE Clinical trials; Enrichment designs; Randomized discontinuation design;
Tumor growth models
ID RENAL-CELL CARCINOMA; TUMOR-GROWTH; STOCHASTIC-MODEL; DESIGN; AGENTS;
PARAMETER; POWER
AB We propose optimal choice of the design parameters for random discontinuation designs (RDD) using a Bayesian decision-theoretic approach. We consider applications of RDDs to oncology phase II studies evaluating activity of cytostatic agents. The design consists of two stages. The preliminary open-label stage treats all patients with the new agent and identifies a possibly sensitive subpopulation. The subsequent second stage randomizes, treats, follows, and compares outcomes among patients in the identified subgroup, with randomization to either the new or a control treatment. Several tuning parameters characterize the design: the number of patients in the trial, the duration of the preliminary stage, and the duration of follow-up after randomization. We define a probability model for tumor growth, specify a suitable utility function, and develop a computational procedure for selecting the optimal tuning parameters.
C1 [Trippa, Lorenzo] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Trippa, Lorenzo] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Rosner, Gary L.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Biostat & Bioinformat, Baltimore, MD 21205 USA.
[Mueller, Peter] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
RP Trippa, L (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM lorenzo.trippa@jimmi.harvard.com; grosner@jhmi.edu;
pmueller@mdanderson.org
FU U.S. National Cancer Institute [CA075981]
FX This research was supported in part by grant CA075981 from the U.S.
National Cancer Institute. We thank the CALGB and Ms Susan Sutherland
for the historical tumor growth data.
NR 29
TC 7
Z9 7
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2012
VL 68
IS 1
BP 203
EP 211
DI 10.1111/j.1541-0420.2011.01623.x
PG 9
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 914BT
UT WOS:000301924400023
PM 21714780
ER
PT J
AU Gray, SW
Landrum, MB
Lamont, EB
McNeil, BJ
Jaklitsch, MT
Keating, NL
AF Gray, Stacy W.
Landrum, Mary Beth
Lamont, Elizabeth B.
McNeil, Barbara J.
Jaklitsch, Michael T.
Keating, Nancy L.
TI Improved Outcomes Associated With Higher Surgery Rates for Older
Patients With Early Stage Nonsmall Cell Lung Cancer
SO CANCER
LA English
DT Article
DE nonsmall cell lung cancer; surgery; survival; geriatric oncology;
comorbidity
ID CLINICAL-PRACTICE GUIDELINES; ACUTE MYOCARDIAL-INFARCTION;
ELDERLY-PATIENTS; REGIONAL-VARIATIONS; CLAIMS DATA; RESECTION;
MORTALITY; SURVIVAL; MANAGEMENT; DIAGNOSIS
AB BACKGROUND: Although surgery offers the greatest chance of a cure for patients with early stage nonsmall cell lung cancer (NSCLC), older and sicker patients often fail to undergo resection. The benefits of surgery in older patients and patients with multiple comorbidities are uncertain. METHODS: The authors identified a national cohort of 17,638 Medicare beneficiaries aged >= 66 years living in Surveillance, Epidemiology, and End Results (SEER) areas who were diagnosed with stage I or II NSCLC during 2001 to 2005. Areas with high and low rates of curative surgery for early stage lung cancer were compared to estimate the effectiveness of surgery in older and sicker patients. Logistic regression models were used to assess mortality according to the quintile of area-level surgery rates, adjusting for potential confounders. RESULTS: Less than 63% of patients underwent surgery in low-surgery areas, whereas >79% underwent surgery in high-surgery areas. High-surgery areas operated on more patients of advanced age and patients with chronic obstructive pulmonary disease than low-surgery areas. The adjusted all-cause 1 year mortality was 18% in high-surgery areas versus 22.8% in low-surgery areas (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.86-0.93) for each 10% increase in the surgery rate). The 1-year lung-cancer-specific mortality similarly was lower in high-surgery areas (12%) versus low-surgery areas (16.9%; adjusted OR, 0.86; 95% CI, 0.82-0.91) for each 10% increase in the surgery rate. CONCLUSIONS: Higher rates of surgery for stage I/II NSCLC were associated with improved survival, even when older patients and sicker patients underwent resection. The authors concluded that more work is needed to identify and reduce barriers to surgery for early stage NSCLC. Cancer 2012; 118: 1404-11. (C) 2011 American Cancer Society.
C1 [Landrum, Mary Beth; Lamont, Elizabeth B.; McNeil, Barbara J.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Gray, Stacy W.; Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Gray, Stacy W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lamont, Elizabeth B.] Massachusetts Gen Hosp, Div Adult Oncol, Boston, MA 02114 USA.
[McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Jaklitsch, Michael T.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
FU Department of Veterans Affairs; National Cancer Institute [R01CA142744]
FX The work was supported by the Department of Veterans Affairs as part of
a larger evaluation of oncology care and by the National Cancer
Institute (R01CA142744). The funders had no role in the design or
conduct of the study; in the collection, management, analysis, or
interpretation of the data; or in the preparation, review, or approval
of the article.
NR 31
TC 14
Z9 14
U1 0
U2 0
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 MAR 1
PY 2012
VL 118
IS 5
BP 1404
EP 1411
DI 10.1002/cncr.26363
PG 8
WC Oncology
SC Oncology
GA 897QD
UT WOS:000300667800028
PM 21800285
ER
PT J
AU Perrin, JM
AF Perrin, James M.
TI How Can Quality Improvement Enhance the Lives of Children with
Disabilities?
SO FUTURE OF CHILDREN
LA English
DT Article
ID MEDICAL HOME MODEL; HEALTH-CARE; UNITED-STATES; DISEASE; ATTENTION;
DISORDER; ASTHMA; AUTISM; YOUTH; CLASSIFICATION
AB Much attention has aided measurement and improvement in the quality of health care during the past two decades, with new ways to define and measure quality, recognition that doing so can identify strategies to enhance care, and systematic efforts by both government and private insurers to apply these principles. In this article, James Perrin reviews these gains. Although children have benefited; these quality measurement efforts have focused mainly on adult health care. Now, two recent federal programs promise to expand quality measurement of child health care.
Enacted in 2009, the Children's Health Insurance Program Reauthorization Act provides systematic support for efforts to develop and implement a set of child health quality measures. This federal support represents the first major public investment in improving child health care quality. The Affordable Care Act, which became law in 2010, extends those activities by focusing attention on improving care for people with chronic conditions, including new ways to organize care using teams of doctors, nurses, and others focused on improving chronic care outcomes. For children especially, this team care should also focus on prevention of chronic conditions and their consequences.
Despite these significant efforts to expand quality measurement among children and youth, Perrin finds that most measures and improvement activities focus on children without chronic conditions, and few measures of chronic conditions go beyond examining what kinds of monitoring children with specific conditions receive. Only limited attention is paid to how well the children are functioning. A number of networks working with children with specific chronic health conditions (such as cancer, cystic fibrosis, and sickle cell disease) have developed effective measures of functioning for children with those conditions and active programs to improve such outcomes. These networks offer the best examples of how to improve care and outcomes for young people with disabilities. Broadening their impact to larger numbers of children with disabilities will require developing measures of functioning and quality of life and targeting interventions and efforts to improve those outcomes.
C1 [Perrin, James M.] MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA.
[Perrin, James M.] Harvard Univ, Med Sch, Cambridge, MA 02138 USA.
RP Perrin, JM (reprint author), MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA.
NR 63
TC 6
Z9 6
U1 1
U2 11
PU PRINCETON UNIV
PI PRINCETON
PA 277 WALLACE HALL, PRINCETON, NJ 08544 USA
SN 1054-8289
J9 FUTURE CHILD
JI Future Child.
PD SPR
PY 2012
VL 22
IS 1
BP 149
EP 168
PG 20
WC Family Studies; Health Policy & Services; Social Sciences,
Interdisciplinary
SC Family Studies; Health Care Sciences & Services; Social Sciences - Other
Topics
GA 930LA
UT WOS:000303139700007
PM 22550689
ER
PT J
AU Barroilhet, L
Garrett, L
Bernstein, M
Esselen, K
Goldstein, D
Berkowitz, R
AF Barroilhet, L.
Garrett, L.
Bernstein, M.
Esselen, K.
Goldstein, D.
Berkowitz, R.
TI Update on subsequent pregnancy outcomes in patients with molar pregnancy
and persistent gestational trophoblastic neoplasia
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Barroilhet, L.; Bernstein, M.; Esselen, K.; Goldstein, D.; Berkowitz, R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Garrett, L.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 200
BP S83
EP S84
DI 10.1016/j.ygyno.2011.12.201
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600200
ER
PT J
AU Boruta, D
Bradford, L
AF Boruta, D.
Bradford, L.
TI Laparoendoscopic single-site extraperitoneal paraaortic lymphadenectomy
for endometrial cancer staging
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Boruta, D.; Bradford, L.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 16
BP S9
EP S9
DI 10.1016/j.ygyno.2011.12.017
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600018
ER
PT J
AU Bradford, L
Zhang, L
Groeneweg, J
Borger, D
Engelman, J
Foster, R
Growdon, W
Schorge, J
Rueda, B
AF Bradford, L.
Zhang, L.
Groeneweg, J.
Borger, D.
Engelman, J.
Foster, R.
Growdon, W.
Schorge, J.
Rueda, B.
TI Inhibition of PI3K-AKT signaling precludes endometrial cancer growth in
a primary human xenograft model harboring an oncogenic PIK3CA mutation
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Bradford, L.; Zhang, L.; Groeneweg, J.; Borger, D.; Engelman, J.; Foster, R.; Growdon, W.; Schorge, J.; Rueda, B.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 312
BP S128
EP S129
DI 10.1016/j.ygyno.2011.12.313
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600310
ER
PT J
AU Brooks, R
Darcy, K
Tritchler, D
Gold, D
Birrer, M
Rader, J
Kizer, N
Thaker, P
Mutch, D
Goodfellow, P
AF Brooks, R.
Darcy, K.
Tritchler, D.
Gold, D.
Birrer, M.
Rader, J.
Kizer, N.
Thaker, P.
Mutch, D.
Goodfellow, P.
TI Single nucleotide polymorphisms in IL8RB, EGFR, ABL1, and SPAG9 Are
associated with lymph node metastasis in endometrial cancer: A
Gynecologic Oncology Group and Washington University School of Medicine
study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Brooks, R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Darcy, K.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Tritchler, D.] Univ Toronto, Toronto, ON, Canada.
[Gold, D.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Rader, J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Kizer, N.; Thaker, P.; Mutch, D.; Goodfellow, P.] Washington Univ, Sch Med, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 39
BP S17
EP S17
DI 10.1016/j.ygyno.2011.12.040
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600041
ER
PT J
AU Campos, S
Berlin, S
Lundquist, C
Roche, M
Whalen, C
Horowitz, N
Penson, R
AF Campos, S.
Berlin, S.
Lundquist, C.
Roche, M.
Whalen, C.
Horowitz, N.
Penson, R.
TI A phase I study AZD2171 and Temsirolimus in advanced GYN cancers
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Campos, S.] Harvard Univ, Sch Med, Boston, MA USA.
[Berlin, S.; Lundquist, C.; Whalen, C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Roche, M.; Penson, R.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 188
BP S78
EP S79
DI 10.1016/j.ygyno.2011.12.189
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600188
ER
PT J
AU Chan, J
Java, J
Monk, B
Alvarez-Secord, A
Kapp, D
Birrer, M
Aghajanian, C
Bookman, M
Kattan, M
Burger, R
AF Chan, J.
Java, J.
Monk, B.
Alvarez-Secord, A.
Kapp, D.
Birrer, M.
Aghajanian, C.
Bookman, M.
Kattan, M.
Burger, R.
TI A practical prediction model for determining bevacizumab response and
toxicity in the treatment of advanced ovarian and peritoneal cancers -
An analysis of GOG 218
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Chan, J.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA.
[Java, J.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Monk, B.] Creighton Univ, Sch Med, Phoenix, AZ USA.
[Alvarez-Secord, A.] Duke Univ, Med Ctr, Durham, NC USA.
[Kapp, D.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Aghajanian, C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Bookman, M.] Univ Arizona, Ctr Canc, Tucson, AZ USA.
[Kattan, M.] Cleveland Clin, Cleveland, OH 44106 USA.
[Burger, R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
NR 0
TC 2
Z9 2
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 69
BP S31
EP S31
DI 10.1016/j.ygyno.2011.12.070
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600071
ER
PT J
AU Diver, E
O'Connor, O
Garrett, L
Bradford, L
Boruta, D
Goodman, A
Del Carmen, M
Schorge, J
Mueller, P
Growdon, W
AF Diver, E.
O'Connor, O.
Garrett, L.
Bradford, L.
Boruta, D.
Goodman, A.
Del Carmen, M.
Schorge, J.
Mueller, P.
Growdon, W.
TI Modest benefit of total parenteral nutrition and chemotherapy after
venting gastrostomy tube placement
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Diver, E.] Brigham & Womens Massachusetts Gen Hosp, Boston, MA USA.
[O'Connor, O.; Garrett, L.; Bradford, L.; Boruta, D.; Goodman, A.; Del Carmen, M.; Schorge, J.; Mueller, P.; Growdon, W.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 171
BP S72
EP S72
DI 10.1016/j.ygyno.2011.12.172
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600171
ER
PT J
AU Goodman, A
Sullivan, L
Lafleur, K
Penson, R
Schorge, J
Del Carmen, M
Boruta, D
Growdon, W
Krasner, C
Birrer, M
AF Goodman, A.
Sullivan, L.
Lafleur, K.
Penson, R.
Schorge, J.
Del Carmen, M.
Boruta, D.
Growdon, W.
Krasner, C.
Birrer, M.
TI Impact of drug shortages on cancer care: The story of pegylated
liposomal doxorubicin in ovarian cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Goodman, A.; Sullivan, L.; Lafleur, K.; Penson, R.; Schorge, J.; Del Carmen, M.; Boruta, D.; Growdon, W.; Krasner, C.; Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 158
BP S66
EP S67
DI 10.1016/j.ygyno.2011.12.159
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600158
ER
PT J
AU Holman, L
Lu, K
Hernandez, M
Bast, R
Bodurka, D
Skates, S
Gershenson, D
Sun, C
AF Holman, L.
Lu, K.
Hernandez, M.
Bast, R.
Bodurka, D.
Skates, S.
Gershenson, D.
Sun, C.
TI Perception of risk, cancer worry, anxiety, and acceptability of
screening among low-risk women undergoing ovarian cancer screening with
the risk of ovarian cancer algorithm
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Holman, L.; Lu, K.; Hernandez, M.; Bast, R.; Bodurka, D.; Gershenson, D.; Sun, C.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Skates, S.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RI Bast, Robert/E-6585-2011
OI Bast, Robert/0000-0003-4621-8462
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 280
BP S116
EP S117
DI 10.1016/j.ygyno.2011.12.281
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600278
ER
PT J
AU Kim, S
Vathipadiekal, V
Kikuchi, J
Mohapatra, G
Cho, H
Nam, E
Kim, S
Kim, J
Kim, Y
Birrer, M
AF Kim, S.
Vathipadiekal, V.
Kikuchi, J.
Mohapatra, G.
Cho, H.
Nam, E.
Kim, S.
Kim, J.
Kim, Y.
Birrer, M.
TI Role of synaptotagmin-like 2 (SYTL2) in ovarian cancer progression
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Kim, S.; Cho, H.; Nam, E.; Kim, S.; Kim, J.; Kim, Y.] Yonsei Univ, Coll Med, Seoul, South Korea.
[Vathipadiekal, V.; Kikuchi, J.; Mohapatra, G.; Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 336
BP S138
EP S138
DI 10.1016/j.ygyno.2011.12.337
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600334
ER
PT J
AU May, T
Shoni, M
Vitonis, A
Quick, C
Growdon, W
Muto, M
AF May, T.
Shoni, M.
Vitonis, A.
Quick, C.
Growdon, W.
Muto, M.
TI Can we safely omit paraaortic lymphadenectomy from the surgical staging
of high-grade endometrioid, clear cell and papillary serous endometrial
adenocarcinoma?
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [May, T.; Shoni, M.; Vitonis, A.; Muto, M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Quick, C.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Growdon, W.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 399
BP S162
EP S163
DI 10.1016/j.ygyno.2011.12.400
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600395
ER
PT J
AU May, T
Yang, J
Shoni, M
Liu, S
He, H
Gali, R
Berkowitz, R
Ng, S
AF May, T.
Yang, J.
Shoni, M.
Liu, S.
He, H.
Gali, R.
Berkowitz, R.
Ng, S.
TI BRCA1 expression is suppressed in sporadic ovarian cancer cells by
overexpression of C-terminal binding protein-2
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [May, T.; Yang, J.; Shoni, M.; Liu, S.; Berkowitz, R.; Ng, S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[He, H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gali, R.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 348
BP S142
EP S142
DI 10.1016/j.ygyno.2011.12.349
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600346
ER
PT J
AU May, T
Virtanen, C
Crum, C
Xian, W
Vathipadiekal, V
Birrer, M
Rosen, B
Murphy, K
Tone, A
AF May, T.
Virtanen, C.
Crum, C.
Xian, W.
Vathipadiekal, V.
Birrer, M.
Rosen, B.
Murphy, K.
Tone, A.
TI Multi-center gene expression analysis of Mullerian low-grade and
high-grade serous carcinoma highlights genes potentially involved in
chemotherapy resistance
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [May, T.; Crum, C.; Xian, W.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Virtanen, C.] Univ Hlth Network Microarray Ctr, Toronto, ON, Canada.
[Vathipadiekal, V.; Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Rosen, B.; Murphy, K.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Tone, A.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 256
BP S107
EP S108
DI 10.1016/j.ygyno.2011.12.257
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600255
ER
PT J
AU Oduyebo, T
Seidman, M
Rauh-Hain, A
Jessel, R
Del Carmen, M
Horowitz, N
Muto, M
AF Oduyebo, T.
Seidman, M.
Rauh-Hain, A.
Jessel, R.
Del Carmen, M.
Horowitz, N.
Muto, M.
TI The role of re-exploration in patients with morcellated leiomyosarcoma
and smooth muscle tumor of uncertain malignant potential
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Oduyebo, T.; Seidman, M.; Rauh-Hain, A.; Jessel, R.; Horowitz, N.; Muto, M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Del Carmen, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 375
BP S152
EP S153
DI 10.1016/j.ygyno.2011.12.376
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600371
ER
PT J
AU Rauh-Hain, J
Winograd, D
Growdon, W
Schorge, J
Good-man, A
Boruta, D
Horowitz, N
Del Carmen, M
AF Rauh-Hain, J.
Winograd, D.
Growdon, W.
Schorge, J.
Good-man, A.
Boruta, D.
Horowitz, N.
Del Carmen, M.
TI Prognostic determinants in patients with uterine and ovarian clear
carcinoma
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Winograd, D.; Growdon, W.; Schorge, J.; Good-man, A.; Boruta, D.; Del Carmen, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 220
BP S91
EP S92
DI 10.1016/j.ygyno.2011.12.221
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600220
ER
PT J
AU Semaan, A
Oliva, E
Nucci, M
Morris, R
Al-Wahab, Z
Mert, I
Hussein, Y
Munkarah, A
Ali-Fehmi, R
AF Semaan, A.
Oliva, E.
Nucci, M.
Morris, R.
Al-Wahab, Z.
Mert, I.
Hussein, Y.
Munkarah, A.
Ali-Fehmi, R.
TI Clinical and pathologic characteristics of uterine serous carcinoma
without myometrial invasion: A multi institutional study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Semaan, A.; Morris, R.; Al-Wahab, Z.; Mert, I.; Hussein, Y.; Ali-Fehmi, R.] Wayne State Univ, Detroit, MI USA.
[Oliva, E.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Munkarah, A.] Henry Ford Hosp, Detroit, MI 48202 USA.
[Nucci, M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 410
BP S167
EP S167
DI 10.1016/j.ygyno.2011.12.411
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600406
ER
PT J
AU Shah, N
Akileswaran, C
Garrett, L
Bradford, L
Del Carmen, M
Goodman, A
Schorge, J
Boruta, D
Growdon, W
AF Shah, N.
Akileswaran, C.
Garrett, L.
Bradford, L.
Del Carmen, M.
Goodman, A.
Schorge, J.
Boruta, D.
Growdon, W.
TI The effect of a paradigm shift towards minimally invasive surgery on
hospitalization costs of hysterectomy for endometrial cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Akileswaran, C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Garrett, L.; Bradford, L.; Del Carmen, M.; Goodman, A.; Schorge, J.; Boruta, D.; Growdon, W.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Shah, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 46
BP S19
EP S20
DI 10.1016/j.ygyno.2011.12.047
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600047
ER
PT J
AU Taylor, S
Kelley, J
Rauh-Hain, J
Boisen, M
Sukumvanich, P
Richard, S
Zorn, K
Christopherson, W
Krivak, T
Olawaiye, A
AF Taylor, S.
Kelley, J.
Rauh-Hain, J.
Boisen, M.
Sukumvanich, P.
Richard, S.
Zorn, K.
Christopherson, W.
Krivak, T.
Olawaiye, A.
TI An assessment of risk factors for superficial surgical site infection
(SSI) and superficial wound separation (SWS) in gynecologic oncology
patients
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Taylor, S.; Kelley, J.; Boisen, M.; Sukumvanich, P.; Richard, S.; Zorn, K.; Christopherson, W.; Krivak, T.; Olawaiye, A.] Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Pittsburgh, PA 15213 USA.
[Rauh-Hain, J.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 180
BP S75
EP S76
DI 10.1016/j.ygyno.2011.12.181
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600180
ER
PT J
AU Wethington, S
Cibula, D
Duska, L
Garrett, L
Kim, C
Sonoda, Y
Abu-Rustum, N
AF Wethington, S.
Cibula, D.
Duska, L.
Garrett, L.
Kim, C.
Sonoda, Y.
Abu-Rustum, N.
TI An international series on abdominal trachelectomy: 101 patients and 28
pregnancies
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Wethington, S.; Kim, C.; Sonoda, Y.; Abu-Rustum, N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Duska, L.] Univ Virginia Hlth Syst, Charlottesville, VA USA.
[Garrett, L.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 4
BP S4
EP S4
DI 10.1016/j.ygyno.2011.12.005
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600006
ER
PT J
AU Carvunis, AR
Dreze, M
AF Carvunis, Anne-Ruxandra
Dreze, Matija
TI Virulence effectors target key proteins of interactome networks of host
plant cells
SO M S-MEDECINE SCIENCES
LA French
DT News Item
ID IMMUNE-SYSTEM; ARABIDOPSIS; INFECTION; VIRUS
C1 [Carvunis, Anne-Ruxandra] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA.
Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Carvunis, AR (reprint author), Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA.
EM anne-ruxandra_carvunis@dfci.harvard.edu
OI , /0000-0001-7002-8488; Carvunis, Anne-Ruxandra/0000-0002-6474-6413
NR 10
TC 1
Z9 1
U1 0
U2 5
PU EDP SCIENCES S A
PI LES ULIS CEDEX A
PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A,
FRANCE
SN 0767-0974
J9 M S-MED SCI
JI M S-Med. Sci.
PD MAR
PY 2012
VL 28
IS 3
BP 237
EP 239
DI 10.1051/medsci/2012283003
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 933MF
UT WOS:000303365100003
PM 22480639
ER
PT J
AU Stathatos, N
AF Stathatos, Nikolaos
TI Thyroid Physiology
SO MEDICAL CLINICS OF NORTH AMERICA
LA English
DT Article
DE Thyroid physiology; Thyroxine; Triiodothyronine; Deiodinase; Nuclear
receptors
ID OF-THE-LITERATURE; HORMONE-RECEPTORS; PENDRED SYNDROME; THYROXINE;
HYPOTHYROIDISM; THYROTROPIN; DISEASE; PROTEIN; IODIDE; GLAND
AB The thyroid gland produces thyroid hormone, which has clinically important actions practically in every system in the human body. Detailed knowledge of the physiology of the thyroid gland is critical for the proper management of thyroid disorders. The molecular biology of thyroid function is being studied in great detail. Clinically important molecules, such as the thyroid-stimulating hormone receptor and the sodium/iodide symporter, have been identified and well characterized. Such discoveries have significantly improved our understanding of thyroid physiology. As a result, new diagnostic and therapeutic approaches for the management of thyroid disorders are now available or in development.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Thyroid Unit, Boston, MA 02114 USA.
RP Stathatos, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Thyroid Unit, 15 Parkman St,WACC 730S, Boston, MA 02114 USA.
EM nstathatos@partners.org
NR 49
TC 8
Z9 8
U1 5
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0025-7125
J9 MED CLIN N AM
JI Med. Clin. N. Am.
PD MAR
PY 2012
VL 96
IS 2
BP 165
EP +
DI 10.1016/j.mcna.2012.01.007
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 932HT
UT WOS:000303282000002
PM 22443969
ER
PT J
AU Shakeri, R
Kamangar, F
Nasrollahzadeh, D
Nouraie, M
Khademi, H
Etemadi, A
Islami, F
Marjani, H
Fahimi, S
Sepehr, A
Rahmati, A
Abnet, CC
Dawsey, SM
Brennan, P
Boffetta, P
Malekzadeh, R
Majdzadeh, R
AF Shakeri, Ramin
Kamangar, Farin
Nasrollahzadeh, Dariush
Nouraie, Mehdi
Khademi, Hooman
Etemadi, Arash
Islami, Farhad
Marjani, Hajiamin
Fahimi, Saman
Sepehr, Alireza
Rahmati, Atieh
Abnet, Christian C.
Dawsey, Sanford M.
Brennan, Paul
Boffetta, Paolo
Malekzadeh, Reza
Majdzadeh, Reza
TI Is Opium a Real Risk Factor for Esophageal Cancer or Just a
Methodological Artifact? Hospital and Neighborhood Controls in
Case-Control Studies
SO PLOS ONE
LA English
DT Article
ID POPULATION-CONTROLS; GOLESTAN COHORT; NORTHERN IRAN; ALCOHOL; SELECTION;
QUESTION; TOBACCO; TRACT; AREA; DIET
AB Background: Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC).
Methodology/Principal Findings: We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age-and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age-and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17-2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure.
Conclusions/Significance: Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.
C1 [Shakeri, Ramin; Kamangar, Farin; Nasrollahzadeh, Dariush; Nouraie, Mehdi; Khademi, Hooman; Etemadi, Arash; Islami, Farhad; Marjani, Hajiamin; Fahimi, Saman; Sepehr, Alireza; Rahmati, Atieh; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
[Shakeri, Ramin; Kamangar, Farin; Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
[Nasrollahzadeh, Dariush] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Nouraie, Mehdi] Howard Univ, Dept Internal Med, Washington, DC 20059 USA.
[Nouraie, Mehdi] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
[Khademi, Hooman; Islami, Farhad; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Fahimi, Saman] Univ Cambridge, Cambridge, England.
[Sepehr, Alireza] Harvard Univ, Sch Med, Dept Pathol, BIDMC, Boston, MA 02115 USA.
[Rahmati, Atieh] Univ Tehran Med Sci, Firoozgar Hosp, Gastrointestinal & Liver Dis Res Ctr, Tehran, Iran.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Majdzadeh, Reza] Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran.
[Majdzadeh, Reza] Univ Tehran Med Sci, Knowledge Utilizat Res Ctr, Tehran, Iran.
RP Shakeri, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
EM rezamajd@tums.ac.ir
RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016;
OI Abnet, Christian/0000-0002-3008-7843; Etemadi,
Arash/0000-0002-3458-1072; , Ramin/0000-0003-0487-3629; Malekzadeh,
Reza/0000-0003-1043-3814
NR 23
TC 8
Z9 8
U1 0
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 MAR 1
PY 2012
VL 7
IS 3
AR e32711
DI 10.1371/journal.pone.0032711
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928SU
UT WOS:000303005000036
PM 22396792
ER
PT J
AU Hobai, I
Buys, E
Armoundas, A
Siwik, D
Brouckaert, P
AF Hobai, Ion
Buys, Emmanuel
Armoundas, Antonis
Siwik, Deborah
Brouckaert, Peter
TI Cellular mechanisms of cardiac dysfunction in endotoxemic mice
SO BRITISH JOURNAL OF ANAESTHESIA
LA English
DT Meeting Abstract
CT 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World
Congress of Anaesthesiologists
CY MAR 25-30, 2012
CL Buenos Aires, ARGENTINA
SP World Federat Soc Anaesthesiol (WFSA)
C1 [Hobai, Ion; Buys, Emmanuel; Armoundas, Antonis] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Siwik, Deborah] Boston Univ, Med Ctr, Boston, MA USA.
[Brouckaert, Peter] Flanders Inst Biotechnol VIB, Ghent, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-0912
J9 BRIT J ANAESTH
JI Br. J. Anaesth.
PD MAR
PY 2012
VL 108
SU 2
BP 146
EP 146
PG 1
WC Anesthesiology
SC Anesthesiology
GA 919CT
UT WOS:000302299100243
ER
PT J
AU Bugembe, R
Duan, M
Dubowitz, G
Costello, F
Ttendo, S
AF Bugembe, Richard
Duan, Melissa
Dubowitz, Gerald
Costello, Frank
Ttendo, Stephen
TI A pilot project of anesthesia education by video-conferencing between
Uganda and the United States
SO BRITISH JOURNAL OF ANAESTHESIA
LA English
DT Meeting Abstract
CT 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World
Congress of Anaesthesiologists
CY MAR 25-30, 2012
CL Buenos Aires, ARGENTINA
SP World Federat Soc Anaesthesiol (WFSA)
C1 [Bugembe, Richard; Costello, Frank] Mbarara Univ Sci & Technol, Mbarara, Uganda.
[Duan, Melissa; Ttendo, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dubowitz, Gerald] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-0912
J9 BRIT J ANAESTH
JI Br. J. Anaesth.
PD MAR
PY 2012
VL 108
SU 2
BP 175
EP 176
PG 2
WC Anesthesiology
SC Anesthesiology
GA 919CT
UT WOS:000302299100291
ER
PT J
AU Vassallo, S
AF Vassallo, Susan
TI Digitizing Our Past: The Wood Library-Museum of Anesthesiology and The
Ether Controversy Experience
SO BRITISH JOURNAL OF ANAESTHESIA
LA English
DT Meeting Abstract
CT 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World
Congress of Anaesthesiologists
CY MAR 25-30, 2012
CL Buenos Aires, ARGENTINA
SP World Federat Soc Anaesthesiol (WFSA)
C1 [Vassallo, Susan] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA.
NR 3
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-0912
J9 BRIT J ANAESTH
JI Br. J. Anaesth.
PD MAR
PY 2012
VL 108
SU 2
BP 182
EP 183
PG 2
WC Anesthesiology
SC Anesthesiology
GA 919CT
UT WOS:000302299100302
ER
PT J
AU El Ouaamari, A
Kawamori, D
Liew, CW
Dirice, E
Hu, J
Katsuta, H
Shadrach, J
Hollister-Lock, J
Wagers, A
Kulkarni, R
AF El Ouaamari, A.
Kawamori, D.
Liew, C. W.
Dirice, E.
Hu, J.
Katsuta, H.
Shadrach, J.
Hollister-Lock, J.
Wagers, A.
Kulkarni, R.
TI Systemic origins of hepatic origin regulates pancreatic beta cell mass
in animals resistent to insulin
SO DIABETES & METABOLISM
LA French
DT Meeting Abstract
C1 [El Ouaamari, A.; Kawamori, D.; Liew, C. W.; Dirice, E.; Hu, J.; Katsuta, H.; Shadrach, J.; Hollister-Lock, J.; Wagers, A.; Kulkarni, R.] Joslin Diabet Ctr, Boston, MA 02215 USA.
RI Dirice, Ercument/B-2825-2017
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MASSON EDITEUR
PI MOULINEAUX CEDEX 9
PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE
SN 1262-3636
J9 DIABETES METAB
JI Diabetes Metab.
PD MAR
PY 2012
VL 38
SI 2
BP A8
EP A8
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 926GN
UT WOS:000302819400033
ER
PT J
AU Ruggiero, KJ
Gros, K
McCauley, JL
Resnick, HS
Morgan, M
Kilpatrick, DG
Muzzy, W
Acierno, R
AF Ruggiero, Kenneth J.
Gros, Kirstin
McCauley, Jenna L.
Resnick, Heidi S.
Morgan, Mark
Kilpatrick, Dean G.
Muzzy, Wendy
Acierno, Ron
TI Mental Health Outcomes Among Adults in Galveston and Chambers Counties
After Hurricane Ike
SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS
LA English
DT Article
DE disaster mental health; Hurricane Ike; resilience; recovery
ID POSTTRAUMATIC-STRESS-DISORDER; PREVALENCE; DISASTER; COMORBIDITY;
ILLNESS; KATRINA; TEXAS; PTSD
AB Objective: To examine the mental health effects of Hurricane Ike, the third costliest hurricane in US history, which devastated the upper Texas coast in September 2008.
Method: Structured telephone interviews assessing immediate effects of Hurricane Ike (damage, loss, displacement) and mental health diagnoses were administered via random digit-dial methods to a household probability sample of 255 Hurricane Ike-affected adults in Galveston and Chambers counties.
Results: Three-fourths of respondents evacuated the area because of Hurricane Ike and nearly 40% were displaced for at least one week. Postdisaster mental health prevalence estimates were 5.9% for posttraumatic stress disorder, 4.5% for major depressive episode, and 9.3% for generalized anxiety disorder. Bivariate analyses suggested that peritraumatic indicators of hurricane exposure severity-such as lack of adequate clean clothing, electricity, food, money, transportation, or water for at least one week-were most consistently associated with mental health problems.
Conclusions: The significant contribution of factors such as loss of housing, financial means, clothing, food, and water to the development and/or maintenance of negative mental health consequences highlights the importance of systemic postdisaster intervention resources targeted to meet basic needs in the postdisaster period. (Disaster Med Public Health Preparedness. 2012;6:26-32)
C1 [Ruggiero, Kenneth J.; Gros, Kirstin; McCauley, Jenna L.; Resnick, Heidi S.; Kilpatrick, Dean G.; Muzzy, Wendy; Acierno, Ron] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Ruggiero, Kenneth J.; Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Morgan, Mark] Abt SRBI, New York, NY USA.
RP Ruggiero, KJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,MSC 861, Charleston, SC 29425 USA.
EM ruggierk@musc.edu
FU National Institute of Mental Health (NIMH) [R34 MH77149]
FX This study was supported by National Institute of Mental Health (NIMH)
grant R34 MH77149 (Dr Ruggiero).
NR 29
TC 11
Z9 11
U1 6
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 1935-7893
J9 DISASTER MED PUBLIC
JI Dis. Med. Public Health Prep.
PD MAR
PY 2012
VL 6
IS 1
BP 26
EP 32
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 925SO
UT WOS:000302781800006
PM 22490934
ER
PT J
AU Valassi, E
Brick, DJ
Johnson, JC
Biller, BMK
Klibanski, A
Miller, KK
AF Valassi, Elena
Brick, Danielle J.
Johnson, Jessica C.
Biller, Beverly M. K.
Klibanski, Anne
Miller, Karen K.
TI EFFECT OF GROWTH HORMONE REPLACEMENT THERAPY ON THE QUALITY OF LIFE IN
WOMEN WITH GROWTH HORMONE DEFICIENCY WHO HAVE A HISTORY OF ACROMEGALY
VERSUS OTHER DISORDERS
SO ENDOCRINE PRACTICE
LA English
DT Article
ID ADULT GH DEFICIENCY; LONG-TERM CURE; MYOCARDIAL-INFARCTION; FOLLOW-UP;
TRIAL; HYPOPITUITARISM; QUESTIONNAIRE; IMPAIRMENTS; DIAGNOSIS; DISEASE
AB Objective: To compare the response in quality of life (QoL) to growth hormone (GH) replacement in women with GH deficiency (GHD) and a history of acromegaly with that in women with GHD of other causes.
Methods: Fifty-five women with GHD were studied: 17 with prior acromegaly and 38 with other causes of GHD. We compared two 6-month, randomized, placebo-controlled studies of GM therapy in women with hypopituitarism conducted with use of the same design-one in women with a history of acromegaly and one in women with no prior acromegaly. QoL was assessed with the following questionnaires: the QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA), the Symptom Questionnaire, and the 36-Item Short-Form Health Survey (SF-36).
Results: The 2 groups had comparable mean pretreatment age, body mass index, and QoL scores and comparable mean GH dose at 6 months (0.61 +/- 0.30 versus 0.67 +/- 0.27 mg daily). After 6 months of GH replacement therapy, women with GHD and prior acromegaly demonstrated a greater improvement in AGHDA score, four SF-36 subscales (Role Limitations due to Physical Health, Energy or Fatigue, Emotional Well-Being, and Social Functioning), and the Somatic Symptoms subscale of the Symptom Questionnaire than did women with GHD of other causes. Poorer pretreatment QoL was associated with a greater improvement in QoL after administration of GH.
Conclusion: In this study, GM replacement therapy improved QoL in women with GHD and a history of acromegaly but not in women with GHD due to other hypothalamic and pituitary disorders. Further studies are needed to determine the long-term risks versus benefits of GH replacement in patients who develop GHD after definitive treatment for acromegaly. (Endocr Pract. 2012;18:209-218)
C1 [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA.
EM KKMiller@Partners.org
FU National Institutes of Health [MO1 RR01066, ULI RR02578]; Pfizer Inc.;
Guthart Family Foundation
FX We thank the nurses of the Massachusetts General Hospital General
Clinical Research Center and the Harvard Catalyst Clinical Translational
Science Center as well as the patients who participated in this study.
This work was supported in part by the following grants: National
Institutes of Health grants MO1 RR01066 and ULI RR02578, an
investigator-initiated grant from Pfizer Inc., and a grant from the
Guthart Family Foundation.
NR 29
TC 8
Z9 8
U1 0
U2 0
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
EI 1934-2403
J9 ENDOCR PRACT
JI Endocr. Pract.
PD MAR-APR
PY 2012
VL 18
IS 2
BP 209
EP 218
DI 10.4158/EP11134.OR
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 929AL
UT WOS:000303033500013
PM 22440981
ER
PT J
AU Azim, H
Kroman, N
Ameye, L
Rotmensz, N
Gelber, S
Cordoba, O
Pinto, A
Jensen, M
de Azambuja, E
Peccatori, F
AF Azim, H., Jr.
Kroman, N.
Ameye, L.
Rotmensz, N.
Gelber, S.
Cordoba, O.
Pinto, A.
Jensen, M.
de Azambuja, E.
Peccatori, F.
TI Pregnancy Following Estrogen Receptor-Positive Breast Cancer is Safe -
Results From a Large Multi-center Case-control Study
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Azim, H., Jr.] Inst Jules Bordet, Breast Canc Translat Res Lab, B-1000 Brussels, Belgium.
[Kroman, N.; Jensen, M.] Danish Breast Canc Cooperat Grp, Copenhagen, Denmark.
[Ameye, L.] Inst Jules Bordet, Ctr Data, B-1000 Brussels, Belgium.
[Rotmensz, N.] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy.
[Cordoba, O.] Hosp Valle De Hebron, Barcelona, Spain.
[Gelber, S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pinto, A.] Univ La Paz, Madrid, Spain.
[Peccatori, F.] European Inst Oncol, Fertil & Procreat Unit, Milan, Italy.
RI Cordoba, Octavi/C-5613-2014
OI Cordoba, Octavi/0000-0002-9591-7430
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S46
EP S46
PG 1
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600035
ER
PT J
AU Baselga, J
Costa, F
Gomez, H
Hudis, C
Rapoport, B
Roche, H
Schwartzberg, LS
Petrenciuc, O
Shan, M
Gradishar, WJ
AF Baselga, J.
Costa, F.
Gomez, H.
Hudis, C.
Rapoport, B.
Roche, H.
Schwartzberg, L. S.
Petrenciuc, O.
Shan, M.
Gradishar, W. J.
TI Design of RESILIENCE: a Phase 3 TRial Comparing CapecitabinE in
Combination with SorafenIb or PLacebo for Treatment of Locally Advanced
or MetastatIc HER2-Negative Breast CancEr
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Baselga, J.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA.
[Costa, F.] Hosp Sirio Libanes, Dept Oncol, Sao Paulo, Brazil.
[Gomez, H.] Inst Nacl Enfermedades Neoplas, Dept Oncol, Lima, Peru.
[Hudis, C.] Mem Sloan Kettering Canc Ctr, Dept Oncol, New York, NY 10021 USA.
[Rapoport, B.] Med Oncol Ctr Rosebank, Dept Oncol, Johannesburg, South Africa.
[Roche, H.] Inst Claudius Regaud, Dept Oncol, Toulouse, France.
[Schwartzberg, L. S.] West Clin, Dept Oncol, Memphis, TN USA.
[Petrenciuc, O.] Bayer HealthCare Pharmaceut, Dept Oncol, Toronto, ON, Canada.
[Shan, M.] Bayer HealthCare Pharmaceut, Dept Oncol, Montville, NJ USA.
[Gradishar, W. J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RI Roche, Henri/O-9211-2014
OI Roche, Henri/0000-0001-7463-205X
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S117
EP S117
PG 1
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600266
ER
PT J
AU Cardoso, F
Winer, E
Norton, L
Gomis, R
Krop, I
Harbeck, N
Costa, A
AF Cardoso, Fatima
Winer, Eric
Norton, Larry
Gomis, Roger
Krop, Ian
Harbeck, Nadia
Costa, Alberto
TI Can an international consensus meeting change the future of advanced
breast cancer patients? Highlights from ABC1 Consensus Meeting
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Cardoso, Fatima] Milan & Champalimaud Canc Ctr, European Sch Oncol, Lisbon, Portugal.
[Winer, Eric] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Norton, Larry] Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, New York, NY 10021 USA.
[Norton, Larry] Mem Sloan Kettering Canc Ctr, Breast Canc Program, New York, NY 10021 USA.
[Gomis, Roger] Inst Res Biomed, Growth Control & Canc Metastasis Programme, Barcelona, Spain.
[Krop, Ian] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA.
[Harbeck, Nadia] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany.
[Costa, Alberto] European Sch Oncol, Milan & Maugeri Fdn Breast Unit, Pavia, Italy.
NR 7
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S13
EP S14
PG 2
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600007
ER
PT J
AU Gnant, M
Hortobagyi, GN
Rugo, H
Burris, HA
Noguchi, S
Pritchard, KI
Baselga, J
Sahmoud, T
Bauly, H
Piccart, M
AF Gnant, M.
Hortobagyi, G. N.
Rugo, H.
Burris, H. A.
Noguchi, S.
Pritchard, K. I.
Baselga, J.
Sahmoud, T.
Bauly, H.
Piccart, M.
TI Everolimus Added to Exemestane Reduced Bone Markers in Postmenopausal
Women with Advanced Breast Cancer (ABC): the BOLERO-2 Trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria.
[Hortobagyi, G. N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Rugo, H.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Burris, H. A.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA.
[Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan.
[Pritchard, K. I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Pritchard, K. I.] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA.
[Sahmoud, T.] Novartis Pharmaceut, Global Oncol Dept, Florham Pk, NJ USA.
[Bauly, H.] Novartis Pharma AG, Biostat, Basel, Switzerland.
[Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S43
EP S43
PG 1
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600026
ER
PT J
AU Ligibel, J
Cirrincione, C
Citron, M
Ingle, J
Gradishar, W
Martino, S
Hudis, C
Winer, E
Berry, D
AF Ligibel, J.
Cirrincione, C.
Citron, M.
Ingle, J.
Gradishar, W.
Martino, S.
Hudis, C.
Winer, E.
Berry, D.
TI Relationship Between Body Mass Index (BMI) and Outcomes in Node-positive
Breast Cancer Patients Receiving Chemotherapy - Results From
CALGB/Intergroup 9741
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Ligibel, J.; Winer, E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cirrincione, C.] Duke Univ, Durham, NC USA.
[Citron, M.] LIJ Sch Med, Lake Success, NY USA.
[Ingle, J.] Mayo Clin, Rochester, MN USA.
[Gradishar, W.] Robert Lurie Comprehens Canc Ctr, Chicago, IL USA.
[Martino, S.] Angels Clin, Los Angeles, CA USA.
[Hudis, C.] Mem Sloane Kettering Canc Ctr, New York, NY USA.
[Berry, D.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S166
EP S167
PG 2
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600421
ER
PT J
AU Rugo, H
Pritchard, KI
Gnant, M
Noguchi, S
Piccart, M
Hortobagyi, GN
Burris, HA
Bauly, H
Sahmoud, T
Baselga, J
AF Rugo, H.
Pritchard, K. I.
Gnant, M.
Noguchi, S.
Piccart, M.
Hortobagyi, G. N.
Burris, H. A.
Bauly, H.
Sahmoud, T.
Baselga, J.
TI Everolimus (EVE) for Postmenopausal Women with Advanced Breast Cancer
(ABC) Refractory to Letrozole or Anastrozole: Long-term Efficacy and
Safety Results of the BOLERO-2 Trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Rugo, H.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Pritchard, K. I.] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Pritchard, K. I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria.
[Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan.
[Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium.
[Hortobagyi, G. N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Burris, H. A.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA.
[Bauly, H.] Novartis Pharma AG, Biostat, Basel, Switzerland.
[Sahmoud, T.] Novartis Pharmaceut, Global Oncol Dev, Florham Pk, NJ USA.
[Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S116
EP S116
PG 1
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600262
ER
PT J
AU Freudenreich, O
Kontos, N
Querques, J
AF Freudenreich, Oliver
Kontos, Nicholas
Querques, John
TI Psychiatric Polypharmacy: A Clinical Approach Based on Etiology and
Differential Diagnosis
SO HARVARD REVIEW OF PSYCHIATRY
LA English
DT Article
DE differential diagnosis; etiology; polypharmacy; professionalism
ID 1ST-EPISODE SCHIZOPHRENIA; ILLNESS BEHAVIOR; MONOTHERAPY; MEDICATION;
METAANALYSIS; PHYSICIANS; OUTCOMES; THERAPY; TRIAL; CARE
AB Polypharmacy is common clinical practice in the United States for many psychiatric conditions and for many reasons. In this article we encourage clinicians to use the familiar practice of differential diagnosis to systematically identify etiological factors contributing to polypharmacy. We offer a clinical approach based on (1) reviewing the four main factors responsible for polypharmacy (the disease, the patient, the physician, and society) and (2) answering two questions about optimizing medication regimens (What can I do without explicit permission from the patient or others? What can I do with permission from them?). We contend that all physicians share a professional responsibility for prescribing medications judiciously because unnecessary prescribing exposes patients to unwarranted risks and squanders valuable and scarce resources. Psychiatrists can ask themselves a Kantian question: would my way of prescribing lead to good, socially acceptable outcomes if followed by all physicians treating similar patients? (HARV REV PSYCHIATRY 2012;20:79-85.)
C1 Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Freudenreich, O (reprint author), Erich Lindemann Mental Hlth Ctr, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA.
EM ofreudenreich@partners.org
NR 39
TC 2
Z9 2
U1 2
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1067-3229
J9 HARVARD REV PSYCHIAT
JI Harv. Rev. Psychiatr.
PD MAR-APR
PY 2012
VL 20
IS 2
BP 79
EP 85
DI 10.3109/10673229.2012.677358
PG 7
WC Psychiatry
SC Psychiatry
GA 927ZJ
UT WOS:000302948900001
PM 22512741
ER
PT J
AU Judge, AM
AF Judge, Abigail M.
TI "Sexting" Among US Adolescents: Psychological and Legal Perspectives
SO HARVARD REVIEW OF PSYCHIATRY
LA English
DT Article
DE adolescent psychology; law; sexting; sexual behavior
ID PARENTAL COMMUNICATION; OBJECTIFICATION THEORY; SELF-OBJECTIFICATION;
SEX; PERFORMANCE; EXPERIENCES; SWIMSUIT; CHILDREN; PEERS; BRAIN
AB This article will discuss the phenomenon of "sexting" (i.e., the exchange of sexually explicit images between adolescents via cell phone) in the United States, with a particular focus on clinical and legal implications. Although sexting is frequently discussed in the popular press, there is virtually no scientific literature available on this topic. In contrast, the legal literature has discussed sexting more comprehensively due to the implications of child pornography statutes for the social response to involved youth. This article will consider sexting from a clinical and legal perspective, and recommend ways to understand and address this practice clinically with adolescent patients. (HARV REV PSYCHIATRY 2012;20:86-96.)
C1 [Judge, Abigail M.] Harvard Univ, Sch Med, Boston, MA USA.
[Judge, Abigail M.] Massachusetts Gen Hosp, Children & Law Program, Boston, MA 02114 USA.
RP Judge, AM (reprint author), 1218 Massachusetts Ave, Cambridge, MA 02138 USA.
EM abigailjudge@abigailjudge.com
NR 59
TC 12
Z9 12
U1 2
U2 19
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1067-3229
J9 HARVARD REV PSYCHIAT
JI Harv. Rev. Psychiatr.
PD MAR-APR
PY 2012
VL 20
IS 2
BP 86
EP 96
DI 10.3109/10673229.2012.677360
PG 11
WC Psychiatry
SC Psychiatry
GA 927ZJ
UT WOS:000302948900002
PM 22512742
ER
PT J
AU Adler, KA
Stark, M
Choi-Kain, LW
Marouf, F
AF Adler, Karen A.
Stark, Martha
Choi-Kain, Lois W.
Marouf, Feyza
TI "Something Is Better Than Nothing": Psychotherapy with an Older Woman
SO HARVARD REVIEW OF PSYCHIATRY
LA English
DT Article
DE aging; personality disorder; psychotherapy
C1 [Adler, Karen A.; Choi-Kain, Lois W.] McLean Hosp, Belmont, MA 02478 USA.
[Adler, Karen A.; Choi-Kain, Lois W.] Harvard Univ, Sch Med, Belmont, MA 02178 USA.
[Stark, Martha] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA.
[Marouf, Feyza] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Adler, KA (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA.
EM kadler@partners.org
NR 8
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1067-3229
J9 HARVARD REV PSYCHIAT
JI Harv. Rev. Psychiatr.
PD MAR-APR
PY 2012
VL 20
IS 2
BP 109
EP 118
DI 10.3109/10673229.2012.677356
PG 10
WC Psychiatry
SC Psychiatry
GA 927ZJ
UT WOS:000302948900004
PM 22512744
ER
PT J
AU Wray, LO
Szymanski, BR
Kearney, LK
McCarthy, JF
AF Wray, Laura O.
Szymanski, Benjamin R.
Kearney, Lisa K.
McCarthy, John F.
TI Implementation of Primary Care-Mental Health Integration Services in the
Veterans Health Administration: Program Activity and Associations with
Engagement in Specialty Mental Health Services
SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS
LA English
DT Article
DE Primary care; Mental health; Engagement; Veterans
ID RISK ALCOHOL-USE; COLLABORATIVE CARE; RANDOMIZED-TRIAL; TERM OUTCOMES;
REFERRAL CARE; OLDER-ADULTS; PRISM-E; DEPRESSION; MANAGEMENT; SYSTEM
AB This paper describes the status of the Veterans Health Administration (VHA) Primary Care-Mental Health Integration (PC-MHI) services implementation and presents an assessment of associations between receipt of PC-MHI services and likelihood of receiving a second specialty mental health (SMH) appointment following an initial SMH encounter. The total PC-MHI service recipients and encounters/month rose substantially between October 2007 and April 2011. Adjusting for important covariates, the likelihood of receiving a second SMH encounter within 3 months of an index SMH appointment was 1.37 times greater among individuals who had received a PC-MHI encounter within 3 months of the initial SMH appointment. Implementation of VHA PC-MHI services has substantially increased VHA capacity to deliver mental health services in primary care and findings indicate that PC-MHI services are associated with greater engagement in SMH treatment. Implementation of VHA PC-MHI services is progressing with new technical assistance strategies being deployed.
C1 [Wray, Laura O.] US Dept Vet Affairs, Ctr Integrated Healthcare, Buffalo, NY 14215 USA.
[Wray, Laura O.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Med, Buffalo, NY 14260 USA.
[Szymanski, Benjamin R.; McCarthy, John F.] US Dept Vet Affairs, Off Mental Hlth Operat, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA.
[Kearney, Lisa K.] US Dept Vet Affairs, Off Mental Hlth Operat, Washington, DC USA.
[Kearney, Lisa K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[McCarthy, John F.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA.
RP Wray, LO (reprint author), US Dept Vet Affairs, Ctr Integrated Healthcare, VAWNYHS 116 N,3495 Bailey Ave, Buffalo, NY 14215 USA.
EM Laura.wray@va.gov
NR 41
TC 36
Z9 36
U1 2
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9583
J9 J CLIN PSYCHOL MED S
JI J. Clin. Psychol. Med. Settings
PD MAR
PY 2012
VL 19
IS 1
BP 105
EP 116
DI 10.1007/s10880-011-9285-9
PG 12
WC Psychology, Clinical
SC Psychology
GA 925PC
UT WOS:000302772300012
PM 22383016
ER
PT J
AU Gruenewald, DA
AF Gruenewald, David A.
TI Can Health Care Rationing Ever Be Rational?
SO JOURNAL OF LAW MEDICINE & ETHICS
LA English
DT Article
ID DECISION-MAKING; MEDICAL-CARE; END; AGE; INFORMATION; CANCER;
PHYSICIANS; REFORM; OLDER
AB Americans' appetite for life-prolonging therapies has led to unsustainable growth in health care costs. It is tempting to target older people for health care rationing based on their disproportionate use of health care resources and lifespan already lived, but aged-based rationing is unacceptable to many. Systems reforms can improve the efficiency of health care and may lessen pressure to ration services, but difficult choices still must be made to limit expensive, marginally beneficial interventions. In the absence of agreement on principles to govern health care resource allocation, a fair, open priority-setting process should be created to allow for reasonable disagreement on principles while being seen as legitimate by all stakeholders. At the patient-care level, careful discussions about the benefits and burdens of medical intervention and support for slow medicine a gentle, family-centered care approach for frail elders can do much to avoid harming these patients with aggressive yet unwanted medical care while reducing wasteful spending.
C1 [Gruenewald, David A.] Univ Washington, Sch Med, Seattle, WA 98195 USA.
[Gruenewald, David A.] VA Puget Sound Hlth Care Syst, Palliat Care & Hosp Serv, Seattle, WA USA.
RP Gruenewald, DA (reprint author), Univ Washington, Sch Med, Seattle, WA 98195 USA.
RI Embrett, Mark/H-4466-2014
OI Embrett, Mark/0000-0002-3969-0219
NR 42
TC 8
Z9 8
U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1073-1105
J9 J LAW MED ETHICS
JI J. Law Med. Ethics
PD SPR
PY 2012
VL 40
IS 1
BP 17
EP 25
DI 10.1111/j.1748-720X.2012.00641.x
PG 9
WC Ethics; Law; Medical Ethics; Medicine, Legal
SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal
Medicine
GA 915ZB
UT WOS:000302065100003
PM 22458458
ER
PT J
AU Rasetshwane, DM
Neely, ST
Allen, JB
Shera, CA
AF Rasetshwane, Daniel M.
Neely, Stephen T.
Allen, Jont B.
Shera, Christopher A.
TI Reflectance of acoustic horns and solution of the inverse problem
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID VOCAL-TRACT SHAPE; IMPEDANCE; PROPAGATION; COEFFICIENT; EQUATION; LINES
AB A method is described for solving the inverse problem of determining the profile of an acoustic horn when time-domain reflectance (TDR) is known only at the entrance. The method involves recasting Webster's horn equation in terms of forward and backward propagating wave variables. An essential feature of this method is a requirement that the backward propagating wave be continuous at the wave-front at all locations beyond the entrance. Derivation of the inverse solution raises questions about the meaning of causality in the context of wave propagation in non-uniform tubes. Exact reflectance expressions are presented for infinite exponential, conical and parabolic horns based on exact solutions of the horn equation. Diameter functions obtained with the inverse solution are a good match to all three horn profiles. (C) 2012 Acoustical Society of America. [DOI: 10.1121/1.3681923]
C1 [Rasetshwane, Daniel M.; Neely, Stephen T.] Boys Town Natl Res Hosp, Omaha, NE 68131 USA.
[Allen, Jont B.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA.
[Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA.
RP Rasetshwane, DM (reprint author), Boys Town Natl Res Hosp, 555 N 30th St, Omaha, NE 68131 USA.
EM daniel.rasetshwane@boystown.org
OI Neely, Stephen/0000-0002-1349-5386
FU NIH [R01 DC08318, R01 DC03687]
FX Research was supported by grants from NIH [R01 DC08318 (S.T.N.) and R01
DC03687 (C.A.S.)] We would like to thank Roger D. Serwy for stimulating
discussions regarding the inverse solution of Caflisch (1981).
NR 25
TC 5
Z9 5
U1 0
U2 3
PU ACOUSTICAL SOC AMER AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0001-4966
J9 J ACOUST SOC AM
JI J. Acoust. Soc. Am.
PD MAR
PY 2012
VL 131
IS 3
BP 1863
EP 1873
DI 10.1121/1.3681923
PN 1
PG 11
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA 911LV
UT WOS:000301719200017
PM 22423684
ER
PT J
AU Chambliss, WG
Carroll, WA
Kennedy, D
Levine, D
Mone, MA
Ried, LD
Shepherd, M
Yelvigi, M
AF Chambliss, Walter G.
Carroll, Wesley A.
Kennedy, Daniel
Levine, Donald
Mone, Michael A.
Ried, L. Douglas
Shepherd, Marv
Yelvigi, Mukund
TI Role of the pharmacist in preventing distribution of counterfeit
medications
SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION
LA English
DT Editorial Material
DE Counterfeiting (drug); drug products; technology; pedigree
AB Objective: To provide an overview of the counterfeit medication problem and recommendations of a joint American Pharmacists Association (APhA) Academy of Pharmaceutical Research and Science and APhA Academy of Pharmacy Practice and Management taskforce.
Date sources: SciFinder and PubMed were searched from 1980 to March 2011 using the following keywords: counterfeit drug product, counterfeit medications, drug product authentication, drug product verification, and track-and-trace. Publications, presentations, and websites of organizations that research the counterfeit medication problem in the United States and other countries were reviewed. A representative from the security division of a pharmaceutical manufacturer and a representative from a supplier of anticounterfeiting technologies gave presentations to the taskforce.
Summary: The taskforce recommends that pharmacists (1) purchase medications from known, reliable sources; (2) warn patients of the dangers of purchasing medications over the Internet; (3) confirm with distributors that products were purchased from manufacturers or other reliable sources; (4) monitor counterfeit product alerts; (5) examine products for suspicious appearance; (6) work with the pharmaceutical industry, distributors, and the Food and Drug Administration (FDA) to close gaps in the supply chain, especially for drugs in short supply; (7) use scanning technology in the pharmacy as part of a prescription verification process; (8) educate themselves, coworkers, and patients about the risks of counterfeit medications; and (9) report suspicious medications to FDA, the distributor, and the manufacturer.
Conclusion: The consequence of a patient receiving a counterfeit medication in the United States could be catastrophic, and pharmacists must play an active role in preventing such an event from occurring.
C1 [Chambliss, Walter G.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA.
[Carroll, Wesley A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Kennedy, Daniel] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Levine, Donald] Merck Consumer Care, World Wide Clin Supply, Memphis, TN USA.
[Mone, Michael A.] Cardinal Hlth, Supply Chain Integr & Senior Regulatory Counsel, Qual & Regulatory Affairs, Dublin, OH USA.
[Ried, L. Douglas] Univ S Florida, Coll Pharm, Tampa, FL USA.
[Shepherd, Marv] Univ Texas Austin, Coll Pharm, Ctr Pharmacoecon Studies, Austin, TX 78712 USA.
[Yelvigi, Mukund] Pfizer Inc, Clin Supply Chain Management, New York, NY USA.
RP Chambliss, WG (reprint author), Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, 100 Barr Hall, University, MS 38677 USA.
EM wchambli@olemiss.edu
NR 24
TC 3
Z9 3
U1 0
U2 14
PU AMER PHARMACEUTICAL ASSOC
PI WASHINGTON
PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA
SN 1544-3191
J9 J AM PHARM ASSOC
JI J. Am. Pharm. Assoc.
PD MAR-APR
PY 2012
VL 52
IS 2
BP 195
EP 199
DI 10.1331/JAPhA.2012.11085
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 927AS
UT WOS:000302877900011
PM 22370383
ER
PT J
AU Eshghi, A
Pinne, M
Haake, DA
Zuerner, RL
Frank, A
Cameron, CE
AF Eshghi, Azad
Pinne, Marija
Haake, David A.
Zuerner, Richard L.
Frank, Ami
Cameron, Caroline E.
TI Methylation and in vivo expression of the surface-exposed Leptospira
interrogans outer-membrane protein OmpL32
SO MICROBIOLOGY-SGM
LA English
DT Article
ID SECONDARY STRUCTURE PREDICTION; HEPARIN-BINDING HEMAGGLUTININ;
ESCHERICHIA-COLI; PATHOGENIC LEPTOSPIRA; RICKETTSIA-PROWAZEKII;
BACTERIAL CHEMOTAXIS; PROTEOMIC ANALYSIS; RELEASE FACTORS; VIRULENCE;
IDENTIFICATION
AB Recent studies have revealed that bacterial protein methylation is a widespread post-translational modification that is required for virulence in selected pathogenic bacteria. In particular, altered methylation of outer-membrane proteins has been shown to modulate the effectiveness of the host immune response. In this study, 2D gel electrophoresis combined with MALDI-TOF MS identified a Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 protein, corresponding to ORF LIC11848, which undergoes extensive and differential methylation of glutamic acid residues. Immunofluorescence microscopy implicated LIC11848 as a surface-exposed outer-membrane protein, prompting the designation OmpL32. Indirect immunofluorescence microscopy of golden Syrian hamster liver and kidney sections revealed expression of OmpL32 during colonization of these organs. Identification of methylated surface-exposed outer-membrane proteins, such as OmpL32, provides a foundation for delineating the role of this post-translational modification in leptospiral virulence.
C1 [Eshghi, Azad; Cameron, Caroline E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada.
[Pinne, Marija] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
[Pinne, Marija; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA.
[Zuerner, Richard L.; Frank, Ami] ARS, Infect Bacterial Dis Res Unit, NADC, USDA, Ames, IA USA.
RP Cameron, CE (reprint author), Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada.
EM caroc@uvic.ca
FU University of Victoria; Pacific Century Graduate Scholarship; Natural
Sciences and Engineering Research Council of Canada [327186]; British
Columbia Proteomics Network; Canada Foundation for Innovation; British
Columbia Knowledge Development Fund; VA; Public Health Service from the
National Institute of Allergy and Infectious Diseases [AI-034431]
FX The authors would like to thank Dr Martin Boulanger, University of
Victoria, Victoria, BC, Canada, for his gift of the pET28a vector and
assistance with construct design, Anna von Rossum and Marcus Barron for
assistance with recombinant protein production, and Dr Christoph
Borchers, Derek Smith, Jen Proc, Leanne Ohlund, Darryl Hardie and the
members of the University of Victoria-Genome BC Proteomics Centre for
their support and guidance with the proteomic analyses. This work was
supported by a University of Victoria Fellowship, Graduate Scholarship
and the Pacific Century Graduate Scholarship (A. E.), a Discovery Grant
from the Natural Sciences and Engineering Research Council of Canada
(327186; C. E. C.), the British Columbia Proteomics Network (C. E. C.),
the Canada Foundation for Innovation (C. E. C.), the British Columbia
Knowledge Development Fund (C. E. C.), VA Medical Research Funds (D. A.
H.), and Public Health Service grant AI-034431 (D. A. H.) from the
National Institute of Allergy and Infectious Diseases. C. E. C. is a
Canada Research Chair in Molecular Pathogenesis and a Michael Smith
Foundation for Health Research Scholar.
NR 71
TC 11
Z9 11
U1 2
U2 17
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 1350-0872
J9 MICROBIOL-SGM
JI Microbiology-(UK)
PD MAR
PY 2012
VL 158
BP 622
EP 635
DI 10.1099/mic.0.054767-0
PN 3
PG 14
WC Microbiology
SC Microbiology
GA 926II
UT WOS:000302824100004
PM 22174381
ER
PT J
AU Reiner, T
Lacy, J
Keliher, EJ
Yang, KS
Ullal, A
Kohler, RH
Vinegoni, C
Weissleder, R
AF Reiner, Thomas
Lacy, Jessica
Keliher, Edmund J.
Yang, Katherine S.
Ullal, Adeeti
Kohler, Rainer H.
Vinegoni, Claudio
Weissleder, Ralph
TI Imaging Therapeutic PARP Inhibition In Vivo through Bioorthogonally
Developed Companion Imaging Agents
SO NEOPLASIA
LA English
DT Article
ID POLY(ADP-RIBOSE) POLYMERASE; BREAST-CANCER; SKIN-FOLD; CHAMBER;
OPTIMIZATION; MICROSCOPY; INVASION; TUMORS; MICE
AB A number of small-molecule poly (ADP-ribose) polymerase (PARP) inhibitors are currently undergoing advanced clinical trials. Determining the distribution and target inhibitory activity of these drugs in individual subjects, however, has proven problematic. Here, we used a PARP agent for positron emission tomography-computed tomography (PET-CT) imaging (F-18-BO), which we developed based on the Olaparib scaffold using rapid bioorthogonal conjugation chemistries. We show that the bioorthogonal F-18 modification of the parent molecule is simple, highly efficient, and well tolerated, resulting in a half maximal inhibitory concentration (IC50) of 17.9 +/- 1.1 nM. Intravital imaging showed ubiquitous distribution of the drug and uptake into cancer cells, with ultimate localization within the nucleus, all of which were inhibitable. Whole-body PET-CT imaging showed tumoral uptake of the drug, which decreased significantly, after a daily dose of Olaparib. Standard F-18-fludeoxyglucose imaging, however, failed to detect such therapy-induced changes. This research represents a step toward developing a more generic approach for the rapid codevelopment of companion imaging agents based on small-molecule therapeutic inhibitors.
C1 [Reiner, Thomas; Lacy, Jessica; Keliher, Edmund J.; Yang, Katherine S.; Ullal, Adeeti; Kohler, Rainer H.; Vinegoni, Claudio; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA.
EM rweissleder@mgh.harvard.edu
FU National Institutes of Health [R01EB010011, P50CA86355, T32-CA79443];
German Academy of Sciences Leopoldina [LPDS 2009-24]
FX This study was funded in part by National Institutes of Health grants
R01EB010011 and P50CA86355 (R. W.). K. S. Yang was supported by a
National Institutes of Health grant T32-CA79443, and T. Reiner was
supported by a grant from the German Academy of Sciences Leopoldina
(LPDS 2009-24). The authors have no conflicts of interest to declare.
The costs of publication of this article were defrayed, in part, by the
payment of page charges. This article must therefore be hereby-marked
advertisement in accordance with 18 U. S. C. Section 1734 solely to
indicate this fact.
NR 25
TC 34
Z9 34
U1 2
U2 14
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD MAR
PY 2012
VL 14
IS 3
BP 169
EP +
DI 10.1593/neo.12414
PG 12
WC Oncology
SC Oncology
GA 922HW
UT WOS:000302539000001
PM 22496617
ER
PT J
AU Bishehsari, F
Sharma, A
Stello, K
Toth, C
O'Connell, MR
Evans, AC
LaRusch, J
Muddana, V
Papachristou, GI
Whitcomb, DC
AF Bishehsari, Faraz
Sharma, Arun
Stello, Kimberly
Toth, Chad
O'Connell, Michael Richard
Evans, Anna C.
LaRusch, Jessica
Muddana, Venkata
Papachristou, Georgios I.
Whitcomb, David C.
TI TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction
syndrome (MODS) in acute pancreatitis
SO PANCREATOLOGY
LA English
DT Article
DE Ystemic inflammatory response syndrome (SIRS); Genetic epidemiology;
Shock; Modeling; Pancreas
ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY RESPONSE SYNDROME; CYTOKINE CASCADE
PROGRESSION; SMALL-MOLECULE INHIBITION; PROMOTER POLYMORPHISM;
5'-FLANKING REGION; CYSTIC-FIBROSIS; UNITED-STATES; SEVERITY;
ASSOCIATION
AB Background/Objectives: Acute pancreatitis (AP) is a complex inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction syndrome (MODS). Tumor necrosis factor alpha (TNF-alpha) is a cytokine that may link inflammation to the systemic inflammatory response syndrome (SIRS), which usually precedes MODS. Small genetic cohort studies of the TNFA promoter in AP produced ambiguous results. We performed a comprehensive evaluation of TNFA promoter variants to assess both susceptibility to AP and risk of progression to MODS.
Methods: We prospectively ascertained 401 controls and 211 patients with AP that were assessed for persistent SIRS (>48 h) and MODS. MODS was defined as failure of >= 2 organ systems (cardiovascular, pulmonary, and/or renal) persisting more than 48 h. Subjects were genotyped by DNA sequencing and analyzed for SNPs at -1031 C/T (rs1799964), -863 A/C (rs1800630), -857 C/T (rs1799724), -308 A/C (rs1800629), and -238 A/C (r5361525).
Results: Twenty-three of 211 AP patients (11%) developed MODS. TNFA promoter variants were not associated with susceptibility to AP. but progression to MODS was associated with the minor allele at -1031C (56.5% vs. 32.4% P = 0.022, OR: 2.7: 95%CI: 1.12-6.51) and -863A (43.5% vs. 21.8% P = 0.022, OR: 2.76: 95%CI: 1.12-6.74).
Conclusion: TNFA promoter variants do not alter susceptibility to AP, but rather the TNF-alpha expression-enhancing -1031C and -863A alleles significantly increased the risk of AP progression to MODS. These data, within the context of previous studies, clarify the risk of specific genetic variants in TNFA and therefore the role of TNF-alpha in the overall AP syndrome. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
C1 [Bishehsari, Faraz; Stello, Kimberly; Toth, Chad; O'Connell, Michael Richard; LaRusch, Jessica; Muddana, Venkata; Papachristou, Georgios I.; Whitcomb, David C.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA.
[Whitcomb, David C.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA 15213 USA.
[Whitcomb, David C.] Univ Pittsburgh, Dept Physiol, Pittsburgh, PA 15213 USA.
[Bishehsari, Faraz; Stello, Kimberly; Toth, Chad; O'Connell, Michael Richard; LaRusch, Jessica; Muddana, Venkata; Papachristou, Georgios I.; Whitcomb, David C.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA.
[Sharma, Arun; Evans, Anna C.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA.
[Papachristou, Georgios I.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
RP Whitcomb, DC (reprint author), UPMC Gastroenterol Hepatol & Nutr Adm, Room 401-4,3708 5th Ave, Pittsburgh, PA 15213 USA.
EM whitcomb@pitt.edu
FU Medical Student Research Training (MSRT [T32DK063922]; [R01 DK061451]
FX The authors gratefully acknowledge the critical review of M Michael
Barmada PhD and the editorial assistance of Michelle Kienholz. Arun
Sharma was supported by Medical Student Research Training (MSRT)
supplement to T32DK063922 (DCW). Jessica LaRusch PhD was supported by
T32DK063922 (DCW). Genotyping was supported by R01 DK061451 (DCW). This
project used the University of Pittsburgh Genomics and Proteomics Core
Laboratory (UL1 RR024153) and the UPCI Clinical Genomics
Immunoproteomics and Sequencing Facility (NIH P30CA047904). The contents
of this publication are solely the responsibility of the authors and do
not necessarily represent the official view of the NCRR or NIH.
NR 41
TC 12
Z9 15
U1 0
U2 3
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1424-3903
J9 PANCREATOLOGY
JI Pancreatology
PD MAR-APR
PY 2012
VL 12
IS 2
BP 113
EP 118
DI 10.1016/j.pan.2012.02.014
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 929NY
UT WOS:000303073800006
PM 22487520
ER
PT J
AU Gaal, EI
Salo, P
Kristiansson, K
Rehnstrom, K
Kettunen, J
Sarin, AP
Niemela, M
Jula, A
Raitakari, OT
Lehtimaki, T
Eriksson, JG
Widen, E
Gunel, M
Kurki, M
Fraunberg, MVZ
Jaaskelainen, JE
Hernesniemi, J
Jarvelin, MR
Pouta, A
Newton-Cheh, C
Salomaa, V
Palotie, A
Perola, M
AF Gaal, Emilia Ilona
Salo, Perttu
Kristiansson, Kati
Rehnstrom, Karola
Kettunen, Johannes
Sarin, Antti-Pekka
Niemela, Mika
Jula, Antti
Raitakari, Olli T.
Lehtimaki, Terho
Eriksson, Johan G.
Widen, Elisabeth
Guenel, Murat
Kurki, Mitja
Fraunberg, Mikael von Und Zu
Jaaskelainen, Juha E.
Hernesniemi, Juha
Jarvelin, Marjo-Riitta
Pouta, Anneli
Newton-Cheh, Christopher
Salomaa, Veikko
Palotie, Aarno
Perola, Markus
CA ICBP-GWAS
TI Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated
Systolic Blood Pressure
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUBARACHNOID HEMORRHAGE; GENETIC-VARIANTS;
CASE-FATALITY; DISEASE RISK; METAANALYSIS; IMPUTATION; PROLIFERATION;
HYPERTENSION; AGE
AB Although genome-wide association studies (GWAS) have identified hundreds of complex trait loci, the pathomechanisms of most remain elusive. Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. Intracranial aneurysms (IA) are rupture-prone pouches at cerebral artery branching sites. IA is a complex disease for which GWAS have identified five loci with strong association and a further 14 loci with suggestive association. To decipher potential underlying disease mechanisms, we tested whether there are IA loci that convey their effect through elevating blood pressure (BP), a strong risk factor of IA. We performed a meta-analysis of four population-based Finnish cohorts (n(FIN) = 11 266) not selected for IA, to assess the association of previously identified IA candidate loci (n = 19) with BP. We defined systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure as quantitative outcome variables. The most significant result was further tested for association in the ICBP-GWAS cohort of 200 000 individuals. We found that the suggestive IA locus at 5q23.2 in PRDM6 was significantly associated with SBP in individuals of European descent (p(FIN) = 3.01E-05, p(ICBP-GWAS) = 0.0007, p(ALL) = 8.13E-07). The risk allele of IA was associated with higher SBP. PRDM6 encodes a protein predominantly expressed in vascular smooth muscle cells. Our study connects a complex disease (IA) locus with a common risk factor for the disease (SBP). We hypothesize that common variants in PRDM6 can contribute to altered vascular wall structure, hence increasing SBP and predisposing to IA. True positive associations often fail to reach genome-wide significance in GWAS. Our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. Further, we demonstrate that common disease loci identified in a population isolate may bear wider significance.
C1 [Gaal, Emilia Ilona; Salo, Perttu; Kristiansson, Kati; Kettunen, Johannes; Sarin, Antti-Pekka; Jula, Antti; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland.
[Gaal, Emilia Ilona; Kristiansson, Kati; Rehnstrom, Karola; Kettunen, Johannes; Sarin, Antti-Pekka; Widen, Elisabeth; Palotie, Aarno; Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Gaal, Emilia Ilona; Niemela, Mika; Hernesniemi, Juha] Univ Helsinki, Cent Hosp, Dept Neurosurg, Helsinki, Finland.
[Rehnstrom, Karola; Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton, England.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Dept Clin Physiol, Turku, Finland.
[Raitakari, Olli T.] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland.
[Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Diabet Unit, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Inst Clin Med, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Guenel, Murat] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA.
[Kurki, Mitja; Fraunberg, Mikael von Und Zu; Jaaskelainen, Juha E.] Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Biostat & Epidemiol, Sch Publ Hlth, Fac Med, London, England.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jarvelin, Marjo-Riitta; Pouta, Anneli] Natl Inst Hlth & Welf, Dept Children Young People & Families, Oulu, Finland.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland.
[Palotie, Aarno] Broad Inst Harvard & MIT, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA.
[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Palotie, Aarno] Univ Cent Hosp, Helsinki, Finland.
[Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
RP Gaal, EI (reprint author), Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland.
EM emilia.gaal@helsinki.fi
RI EHRET, Georg/A-9532-2009; Niemela, Mika/F-2539-2015;
OI EHRET, Georg/0000-0002-5730-0675; Niemela, Mika/0000-0003-1526-0684;
Kristiansson, Kati/0000-0003-4688-107X; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Eriksson, Johan/0000-0002-2516-2060
FU Orion-Farmos Research Foundation; Academy of Finland [250207, 129494,
129322, 129287, 134839, 120315, 129255, 129907, 135072, 114382, 126775,
127437, 129306, 130326, 209072, 210595, 213225, 216374, 126925, 121584,
124282, 129378, 117797, 41071, 104781, 1114194]; Finnish Foundation for
Cardiovascular Research; Sigrid Juselius Foundation; Finnish Diabetes
Research Society; Samfundet Folkhalsan; Juho Vainio Foundation; Novo
Nordisk Foundation; Finska Lakaresallskapet; Paivikki and Sakari
Sohlberg Foundation; Signe and Ane Gyllenberg Foundation; Yrjo Jahnsson
Foundation; Social Insurance Institution of Finland; Kuopio, Tampere,
and Turku University; Paavo Nurmi Foundation; Finnish Foundation of
Cardiovascular Research and Finnish Cultural Foundation; Tampere
Tuberculosis Foundation; Emil Aaltonen Foundation; University Hospital
Oulu, Biocenter [5R01HL087679-02]; University of Oulu, Finland, NHLBI
[HEALTH-F4-2007-201413]; Medical Research Council [G0500539, G0600705];
Wellcome Trust, UK [GR069224]
FX K Kristiansson was supported by the Orion-Farmos Research Foundation and
the Academy of Finland (grant number 250207). V Salomaa and M Perola
were supported by the Academy of Finland (grant numbers 129494 and
129322, respectively), the Finnish Foundation for Cardiovascular
Research, and the Sigrid Juselius Foundation. E Widen was supported by
the Academy of Finland (grants 129287, 134839 and 120315). JG Eriksson
was supported by the Academy of Finland (grants 126775, 129255, 129907,
and 135072). Helsinki Birth Cohort Study has been supported by grants
from the Academy of Finland (project numbers: 114382, 126775, 127437,
129255, 129306, 130326, 209072, 210595, 213225, and 216374), the Finnish
Diabetes Research Society, the Finnish Foundation for Cardiovascular
Research, the Samfundet Folkhalsan, the Juho Vainio Foundation, the Novo
Nordisk Foundation, the Finska Lakaresallskapet, the Paivikki and Sakari
Sohlberg Foundation, the Signe and Ane Gyllenberg Foundation, and the
Yrjo Jahnsson Foundation. The Young Finns Study has been financially
supported by the Academy of Finland (project numbers: 126925, 121584,
124282, 129378, 117797, and 41071), the Social Insurance Institution of
Finland, Kuopio, Tampere, and Turku University Hospital Medical Funds,
the Juho Vainio Foundation, the Paavo Nurmi Foundation, Finnish
Foundation of Cardiovascular Research and Finnish Cultural Foundation,
the Sigrid Juselius Foundation, Tampere Tuberculosis Foundation, and the
Emil Aaltonen Foundation. The Northern Finland Birth Cohort 1966
received financial support from the Academy of Finland (project numbers:
104781, 120315, 1114194, and Center of Excellence in Complex Disease
Genetics), University Hospital Oulu, Biocenter, University of Oulu,
Finland, NHLBI grant 5R01HL087679-02 through the STAMPEED program
(1RL1MH083268-01), ENGAGE project and grant agreement
HEALTH-F4-2007-201413, the Medical Research Council (studentship grant
G0500539, centre grant G0600705), and the Wellcome Trust (project grant
GR069224), UK. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 44
TC 13
Z9 14
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002563
DI 10.1371/journal.pgen.1002563
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800039
PM 22438818
ER
PT J
AU Lill, CM
Roehr, JT
McQueen, MB
Kavvoura, FK
Bagade, S
Schjeide, BMM
Schjeide, LM
Meissner, E
Zauft, U
Allen, NC
Liu, T
Schilling, M
Anderson, KJ
Beecham, G
Berg, D
Biernacka, JM
Brice, A
DeStefano, AL
Do, CB
Eriksson, N
Factor, SA
Farrer, MJ
Foroud, T
Gasser, T
Hamza, T
Hardy, JA
Heutink, P
Hill-Burns, EM
Klein, C
Latourelle, JC
Maraganore, DM
Martin, ER
Martinez, M
Myers, RH
Nalls, MA
Pankratz, N
Payami, H
Satake, W
Scott, WK
Sharma, M
Singleton, AB
Stefansson, K
Toda, T
Tung, JY
Vance, J
Wood, NW
Zabetian, CP
Young, P
Tanzi, RE
Khoury, MJ
Zipp, F
Lehrach, H
Ioannidis, JPA
Bertram, L
AF Lill, Christina M.
Roehr, Johannes T.
McQueen, Matthew B.
Kavvoura, Fotini K.
Bagade, Sachin
Schjeide, Brit-Maren M.
Schjeide, Leif M.
Meissner, Esther
Zauft, Ute
Allen, Nicole C.
Liu, Tian
Schilling, Marcel
Anderson, Kari J.
Beecham, Gary
Berg, Daniela
Biernacka, Joanna M.
Brice, Alexis
DeStefano, Anita L.
Do, Chuong B.
Eriksson, Nicholas
Factor, Stewart A.
Farrer, Matthew J.
Foroud, Tatiana
Gasser, Thomas
Hamza, Taye
Hardy, John A.
Heutink, Peter
Hill-Burns, Erin M.
Klein, Christine
Latourelle, Jeanne C.
Maraganore, Demetrius M.
Martin, Eden R.
Martinez, Maria
Myers, Richard H.
Nalls, Michael A.
Pankratz, Nathan
Payami, Haydeh
Satake, Wataru
Scott, William K.
Sharma, Manu
Singleton, Andrew B.
Stefansson, Kari
Toda, Tatsushi
Tung, Joyce Y.
Vance, Jeffery
Wood, Nick W.
Zabetian, Cyrus P.
Young, Peter
Tanzi, Rudolph E.
Khoury, Muin J.
Zipp, Frauke
Lehrach, Hans
Ioannidis, John P. A.
Bertram, Lars
CA Genetic Epidemiology Parkinson's
IPDGC
Parkinson's Dis GWAS Consortium
WTCCC2
TI Comprehensive Research Synopsis and Systematic Meta-Analyses in
Parkinson's Disease Genetics: The PDGene Database
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; RISK-FACTORS; MUTATIONS;
VARIANTS; SUSCEPTIBILITY; DATASETS; TRIALS; REGION; VPS35
C1 [Lill, Christina M.; Roehr, Johannes T.; Schjeide, Brit-Maren M.; Schjeide, Leif M.; Meissner, Esther; Zauft, Ute; Liu, Tian; Schilling, Marcel; Lehrach, Hans; Bertram, Lars] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, D-14195 Berlin, Germany.
[Lill, Christina M.; Bagade, Sachin; Allen, Nicole C.; Tanzi, Rudolph E.; Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Lill, Christina M.; Zipp, Frauke] Johannes Gutenberg Univ Mainz, Dept Neurol, Med Ctr, Mainz, Germany.
[Lill, Christina M.; Young, Peter] Univ Hosp, Dept Neurol, Munster, Germany.
[Roehr, Johannes T.; Schilling, Marcel] Free Univ Berlin, Dept Math & Comp Sci, Berlin, Germany.
[McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
[Kavvoura, Fotini K.; Ioannidis, John P. A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Kavvoura, Fotini K.] Royal Berkshire Hosp, Ctr Diabet & Endocrinol, Reading RG1 5AN, Berks, England.
[Kavvoura, Fotini K.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford, England.
[Liu, Tian] Max Planck Inst Human Dev, Berlin, Germany.
[Anderson, Kari J.; Biernacka, Joanna M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Beecham, Gary; Martin, Eden R.; Scott, William K.; Vance, Jeffery] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
[Berg, Daniela; Gasser, Thomas; Sharma, Manu] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany.
[Berg, Daniela; Gasser, Thomas; Sharma, Manu] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany.
[Brice, Alexis] INSERM, UMR S975, Paris, France.
[Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France.
[Brice, Alexis] CNRS, UMR 7225, Paris, France.
[Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Paris, France.
[DeStefano, Anita L.; Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Do, Chuong B.; Eriksson, Nicholas; Tung, Joyce Y.] 23andMe, Mountain View, CA USA.
[Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Farrer, Matthew J.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[Foroud, Tatiana; Pankratz, Nathan] Indiana Univ Sch Med, Indianapolis, IN USA.
[Hamza, Taye; Hill-Burns, Erin M.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Hardy, John A.; Wood, Nick W.] UCL, Dept Mol Neurosci, UCL Inst Neurol, London, England.
[Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands.
[Klein, Christine] Univ Lubeck, Sect Clin & Mol Neurogenet, Dept Neurol, Lubeck, Germany.
[Maraganore, Demetrius M.] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA.
[Martinez, Maria] Fac Med Toulouse, INSERM, UMR 1043, CPTP, F-31073 Toulouse, France.
[Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France.
[Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Satake, Wataru; Toda, Tatsushi] Kobe Univ, Grad Sch Med, Div Neurol Mol Brain Sci, Kobe, Hyogo 657, Japan.
[Wood, Nick W.] UCL, UCL Genet Inst, London, England.
[Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Ioannidis, John P. A.] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
[Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
RP Lill, CM (reprint author), Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, Ihnestr 73, D-14195 Berlin, Germany.
EM lbertram@molgen.mpg.de
RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Traynor,
Bryan/G-5690-2010; Schilling, Marcel/O-3169-2013; Zipp,
Frauke/C-9968-2015; Lill, Christina/J-9449-2015; Bertram,
Lars/K-3889-2015; Martinez, Maria/B-3111-2013; Wood,
Nicholas/C-2505-2009;
OI Zabetian, Cyrus/0000-0002-7739-4306; Schilling,
Marcel/0000-0002-3453-7792; Zipp, Frauke/0000-0002-1231-1928; Lill,
Christina/0000-0002-2805-1307; Bertram, Lars/0000-0002-0108-124X;
Martinez, Maria/0000-0003-2180-4537; Wood, Nicholas/0000-0002-9500-3348;
Latourelle, Jeanne/0000-0002-4218-9572; Myers,
Richard/0000-0002-8365-2674; Burns, Gully/0000-0003-1493-865X
FU Michael J. Fox Foundation for Parkinson's Disease (MJFF); Cure
Alzheimer's Fund (CAF); National Alliance for Research on Schizophrenia
and Depression (NARSAD); Prize4Life; EMD Serono; Deutscher Akademischer
Austauschdienst (DAAD); Fidelity Biosciences Research Initiative (FBRI);
German Ministry for Education and Research (BMBF); Tufts Clinical and
Translational Science Institute (Tufts CTSI); National Institute of
Health/National Center for Research Resources [UL1 RR025752]; Michael J.
Fox Foundation; Edmond J. Safra Michael J. Fox Foundation Global
Genetics Consortium Initiative; NIH [R01 NS 036960, R01CA141668,
R01NS37167, 2R01 ES10751]; National Institute on Aging, National
Institute of Neurological Disorders and Stroke, National Institute of
Environmental Health Sciences, National Human Genome Research Institute,
National Institutes of Health, Department of Health and Human Services
[Z01 AG000949-02, Z01-ES101986]; U.S. Department of Defense
[W81XWH-09-2-0128]; Volkswagen Foundation; Hermann and Lilly Schilling
Foundation; Alnylam Pharmaceuticals; Medtronic; NorthShore University
Health System; Cephalon; Merck-Serono; Novartis; Eisai; Mayo Clinic;
deCODE
FX The main funding for this study was provided by the Michael J. Fox
Foundation for Parkinson's Disease (MJFF) with additional financial
support by the Cure Alzheimer's Fund (CAF), the National Alliance for
Research on Schizophrenia and Depression (NARSAD), Prize4Life, and EMD
Serono (all to L Bertram). CM Lill was supported by a fellowship from
the Deutscher Akademischer Austauschdienst (DAAD) and Fidelity
Biosciences Research Initiative (FBRI). L Bertram is also supported by
the German Ministry for Education and Research (BMBF). JPA Ioannidis was
supported through the Tufts Clinical and Translational Science Institute
(Tufts CTSI) under funding from the National Institute of
Health/National Center for Research Resources (UL1 RR025752). Points of
view or opinions in this paper are those of the authors and do not
necessarily represent the official position or policies of the Tufts
CTSI. M Sharma was supported by the Michael J. Fox Foundation. The
NeuroGenetics Research Consortium GWAS [15] was funded by the Edmond J.
Safra Michael J. Fox Foundation Global Genetics Consortium Initiative
and NIH R01 NS 036960. The work of the International Parkinson's Disease
Genomics Consortium (IPDGC) was supported in part by the Intramural
Research Programs of the National Institute on Aging, National Institute
of Neurological Disorders and Stroke, National Institute of
Environmental Health Sciences, National Human Genome Research Institute,
National Institutes of Health, Department of Health and Human Services:
project numbers Z01 AG000949-02 and Z01-ES101986. In addition the work
of the IPDGC was supported by the U.S. Department of Defense, award
number W81XWH-09-2-0128. Portions of the work of the IPDGC utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the National Institutes of Health, Bethesda, Md.
(http://biowulf.nih.gov). T Foroud received funds from the National
Institutes of Health (R01CA141668 and R01NS37167). C Klein is the
recipient of a career development award from the Volkswagen Foundation
and from the Hermann and Lilly Schilling Foundation. DM Maraganore
acknowledges active funding support from the National Institutes of
Health (2R01 ES10751), Alnylam Pharmaceuticals, Medtronic, and
NorthShore University Health System. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.; CB Do, N Eriksson, and JY Tung are
employed by 23andMe and own stock options in the company. MJ Farrer and
Mayo Foundation received royalties from H. Lundbeck A/S and Isis
Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a
seminar at Genzyme. T Gasser has received consultancy fees from Cephalon
and Merck-Serono, grants from Novartis, payments for lectures including
service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono,
UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has
received consulting fees or honoraria from Eisai and his institute has
received consulting fees or honoraria from Merck-Serono. DM Maraganore
has received extramural research funding support from the National
Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation
(Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra
Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and
Medtronic (observational studies of Parkinson's disease). DM Maraganore
has also received intramural research funding support from the Mayo
Clinic and from NorthShore University Health System. DM Maraganore filed
a provisional patent for a method to predict Parkinson's disease. This
provisional patent is unlicensed. He also filed a provisional patent for
a method to treat neurodegenerative disorders. That provisional patent
has been licensed to Alnylam Pharmaceuticals and DM Maraganore has
received royalty payments in total of less than $20,000. K Stefansson
has received grants from deCODE.
NR 34
TC 224
Z9 226
U1 7
U2 36
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002548
DI 10.1371/journal.pgen.1002548
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800024
PM 22438815
ER
PT J
AU Wu, XY
Shi, Z
Cui, MX
Han, M
Ruvkun, G
AF Wu, Xiaoyun
Shi, Zhen
Cui, Mingxue
Han, Min
Ruvkun, Gary
TI Repression of Germline RNAi Pathways in Somatic Cells by Retinoblastoma
Pathway Chromatin Complexes
SO PLOS GENETICS
LA English
DT Article
ID ELEGANS VULVAL DEVELOPMENT; C-ELEGANS; CAENORHABDITIS-ELEGANS;
TRANSCRIPTIONAL REPRESSION; P GRANULES; LIN-35 RB; GENES ANTAGONIZE;
PROTEIN; INTERFERENCE; EXPRESSION
AB The retinoblastoma (Rb) tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene.
C1 [Wu, Xiaoyun; Shi, Zhen; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Wu, Xiaoyun; Shi, Zhen; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Cui, Mingxue; Han, Min] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
[Cui, Mingxue; Han, Min] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA.
RP Wu, XY (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM ruvkun@molbio.mgh.harvard.edu
FU National Institutes of Health [AG16636, GM47869]; MGH
FX This work was supported by the MGH Fund for Medical Discovery
postdoctoral fellowship to XW and by grants from the National Institutes
of Health (www.nih.gov) to GR (AG16636) and to MH (GM47869). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 76
TC 18
Z9 21
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002542
DI 10.1371/journal.pgen.1002542
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800019
PM 22412383
ER
PT J
AU Morabia, A
Zhang, FF
Kappil, MA
Flory, J
Mirer, FE
Santella, RM
Wolff, M
Markowitz, SB
AF Morabia, Alfredo
Zhang, Fang Fang
Kappil, Maya A.
Flory, Janine
Mirer, Frank E.
Santella, Regina M.
Wolff, Mary
Markowitz, Steven B.
TI Biologic and epigenetic impact of commuting to work by car or using
public transportation: A case-control study
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Transportation; Physical activity; Inflammation; Epigenetic
ID C-REACTIVE PROTEIN; PARTICULATE AIR-POLLUTION; GENOMIC DNA METHYLATION;
CANCER-FREE POPULATION; PHYSICAL-ACTIVITY; INFLAMMATORY MARKERS; ELDERLY
SUBJECTS; BLOOD MARKERS; TRANSIT; OBESITY
AB Background and aims. Commuting by public transportation (PT) entails more physical activity and energy expenditure than by cars, but its biologic consequences are unknown.
Methods. In 2009-2010, we randomly sampled New York adults, usually commuting either by car (n =79) or PT (n = 101). Measures comprised diet and physical activity questionnaires, weight and height, white blood cell (WBC) count, C reactive protein, (CRP) gene-specific methylation (IL-6), and global genomic DNA methylation (LINE-1 methylation).
Results. Compared to the 101 PT commuters, the 79 car drivers were about 9 years older, 2 kg/m(2) heavier, more often non-Hispanic whites, and ate more fruits and more meats. The 2005 guidelines for physical activity were met by more car drivers than PT users (78.5% vs. 65.0%). There were no differences in median levels of CRP (car vs. PT: 0.6 vs. 0.5 mg/dl), mean levels of WBC (car vs. PT: 6.7 vs. 6.5 cells/mm(3)), LINE-1 methylation (car vs. PT: 78.0% vs. 78.3%), and promoter methylation of IL-6 (car vs. PT: 56.1% vs. 58.0%).
Conclusions. PT users were younger and lighter than car drivers, but their commute mode did not translate into a lower inflammatory response or a higher DNA methylation, maybe because, overall, car drivers were more physically active. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Morabia, Alfredo; Markowitz, Steven B.] CUNY, Queens Coll, Ctr Biol Nat Syst, Flushing, NY 11367 USA.
[Morabia, Alfredo; Kappil, Maya A.; Santella, Regina M.] Columbia Univ, New York, NY USA.
[Zhang, Fang Fang] Tufts Univ, Boston, MA 02111 USA.
[Flory, Janine] James J Peters VA Med Ctr, Bronx, NY USA.
[Mirer, Frank E.] CUNY, Hunter Coll, Flushing, NY 11367 USA.
[Flory, Janine; Wolff, Mary] Mt Sinai Sch Med, New York, NY USA.
RP Morabia, A (reprint author), CUNY, Queens Coll, Ctr Biol Nat Syst, 65-30 Kissena Blvd, Flushing, NY 11367 USA.
EM alfredo.morabia@qc.cuny.edu
OI , Maya/0000-0003-2913-2392
FU CUNY; NIEHS Center at Columbia University [1606]; University of North
Texas Health Science Center School of Public Health
FX This COMIR (Commuting Mode and Inflammatory Response) project received
financial support from the CUNY Collaborative Incentive Research Grant
(CIRG) program, round 16, number 1606, from the NIEHS Center ES009089 at
Columbia University, and from the University of North Texas Health
Science Center School of Public Health Seed Program. Results have been
presented orally at the Meeting of the International Society for
Environmental Epidemiology (ISEE, Barcelona, September 14, 2011). The
authors thank Tashia Amstislavski and Steves Vanderpool for their help
in the recruitment and data collection.
NR 36
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U1 3
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD MAR-APR
PY 2012
VL 54
IS 3-4
BP 229
EP 233
DI 10.1016/j.ypmed.2012.01.019
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 923BL
UT WOS:000302593000009
PM 22313796
ER
PT J
AU Weylandt, KH
Chiu, CY
Gomolka, B
Waechter, SF
Wiedenmann, B
AF Weylandt, Karsten H.
Chiu, Cheng-Ying
Gomolka, Beate
Waechter, Simon F.
Wiedenmann, Bertram
TI Omega-3 fatty acids and their lipid mediators: Towards an understanding
of resolvin and protectin formation Omega-3 fatty acids and their
resolvin/protectin mediators
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Review
DE Omega-3; n-3 PUFA; Resolvins; Protectins; 17-HDHA; 18-HEPE
ID N-3 FATTY-ACIDS; EPITHELIAL-CELL SURVIVAL; DAMPENS AIRWAY INFLAMMATION;
CORONARY-HEART-DISEASE; FAT-1 TRANSGENIC MICE; DOCOSAHEXAENOIC ACID;
NEUROPROTECTIN D1; ANTIINFLAMMATORY ACTIONS; OXIDATIVE STRESS; ELEVATED
OMEGA-3-FATTY-ACIDS
AB Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have long been associated with decreased inflammation and are also implicated in the prevention of tumorigenesis. Conventional thinking attributed this mainly to a suppressive effect of these fatty acids on the formation of arachidonic acid-derived prostaglandins and leukotrienes. Recent years have seen the discovery of a new class of inflammation-dampening and resolution-promoting n-3 PUFA-derived lipid mediators called resolvins and protectins. Chemically, these compounds are hydroxylated derivatives of the parent n-3 PUFA eicosapentaenoic acid (EPA) for the E-resolvins, and docosahexaenoic acid (DHA) for the D-resolvins and protectin D1. While a relatively large number of these compounds have been identified and characterized until now, with differences in the positions of the hydroxyl-groups as well as in the chirality at the different carbon atoms, all compounds share common precursor metabolites. 17-hydroperoxydocosahexaenoic acid (17-H(p)DHA) for the DNA-derived compounds and 18-hydroperoxyeicosapentaenoic acid (18-H(p)EPE) for the EPA-derived compounds. In this review we summarize the current knowledge about EPA- and DHA-derived resolvins and protectins and explore the potential use of the pro-resolvins 17-hydroxydocosahexaenoic acid (17-HDHA) and 18-hydroxyeicosapentaenoic acid (18-HEPE) as indicators of anti-inflammatory n-3 PUFA mediator formation. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Weylandt, Karsten H.; Chiu, Cheng-Ying; Gomolka, Beate; Waechter, Simon F.; Wiedenmann, Bertram] Charite, Rudolf Virchow Hosp, Dept Gastroenterol Hepatol & Endocrinol, D-13353 Berlin, Germany.
[Weylandt, Karsten H.; Chiu, Cheng-Ying; Waechter, Simon F.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA.
[Weylandt, Karsten H.; Chiu, Cheng-Ying; Waechter, Simon F.] Harvard Univ, Sch Med, Boston, MA USA.
RP Weylandt, KH (reprint author), Charite, Rudolf Virchow Hosp, Dept Gastroenterol Hepatol & Endocrinol, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM karsten.weylandt@charite.de
FU German Research Council (DFG); German Society for Digestive and
Metabolic Disease (DGVS)
FX Ongoing work in KHW's lab is supported by the German Research Council
(DFG), and KHW has also been the recipient of a Werner-Creutzfeldt
Scholarship from the German Society for Digestive and Metabolic Disease
(DGVS). The fat-1 mice were generously provided by Dr. Jing X. Kang at
the Massachusetts General Hospital, Boston, and lipid mediator analysis
was performed by Dr. Michael Rothe at Lipidomix, Berlin.
NR 115
TC 94
Z9 99
U1 2
U2 37
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD MAR
PY 2012
VL 97
IS 3-4
BP 73
EP 82
DI 10.1016/j.prostaglandins.2012.01.005
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 926SL
UT WOS:000302851300001
PM 22326554
ER
PT J
AU Nath, SB
Wong, YLI
Marcus, SC
Solomon, P
AF Nath, Sara Bressi
Wong, Yin-Ling Irene
Marcus, Steven C.
Solomon, Phyllis
TI Predictors of Health Services Utilization among Persons with Psychiatric
Disabilities Engaged in Supported Independent Housing
SO PSYCHIATRIC REHABILITATION JOURNAL
LA English
DT Article
DE health services utilization; psychiatric rehabilitation; case
management; supported housing
ID SERIOUS MENTAL-ILLNESS; MEDICAL-CARE; DISORDERS; SCHIZOPHRENIA; PEOPLE;
ACCESS
AB Objective: Persons with psychiatric disabilities are at greater risk for medical comorbidity, and prior research suggests these persons may underutilize health services. In response, this study examined the impact of engagement in psychiatric rehabilitation services, including case management, on utilization of general health services among persons with psychiatric disabilities engaged in supported housing, while controlling for demographic and clinical characteristics. Methods: Poisson regression analyses were used to examine the impact of socio-demographic, clinical, and service characteristics on reported utilization of general health services in the past year. Results: Findings indicated supported housing residents receiving case management coupled with weekly contact with residential support services visited a general health practitioner more frequently than those with less support services. Conclusions and Implications: Study results suggest psychiatric rehabilitation services provided to persons in the context of safe and affordable housing may represent an important mechanism for enabling persons with psychiatric disorders to access needed medical care.
C1 [Wong, Yin-Ling Irene; Marcus, Steven C.; Solomon, Phyllis] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
[Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Nath, SB (reprint author), Bryn Mawr Coll, Grad Sch Social Work & Social Res, 300 Airdale Rd, Bryn Mawr, PA 19010 USA.
EM snath@brynmawr.edu
FU NIMH NIH HHS [5-F31-MH67349]
NR 46
TC 1
Z9 1
U1 5
U2 8
PU CENTER PSYCHIATRIC REHABILITATION
PI BOSTON
PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA
SN 1095-158X
J9 PSYCHIATR REHABIL J
JI Psychiatr. Rehabil. J.
PD SPR
PY 2012
VL 35
IS 4
BP 315
EP 323
DI 10.2975/35.4.2012.315.323
PG 9
WC Psychiatry; Rehabilitation
SC Psychiatry; Rehabilitation
GA 928GN
UT WOS:000302971300005
PM 22491371
ER
PT J
AU Ch, AS
Perez, C
Silva, JR
Ruiz-Tagle, A
Mayol, R
Munoz-Neira, C
Nunez-Huasaf, J
AF Slachevsky Ch, Andrea
Perez J, Carolina
Silva A, Jaime R.
Ruiz-Tagle, Amparo
Mayol, Rocio
Munoz-Neira, Carlos
Nunez-Huasaf, Javier
TI Prognostic heterogeneity of attention deficit/hyperactivity disorder in
adults
SO REVISTA MEDICA DE CHILE
LA Spanish
DT Review
DE Achievement; Adult; Deficit Disorder with Hyperactivity; Executive
Function
ID DEFICIT HYPERACTIVITY DISORDER; MENTAL TIME-TRAVEL; DUAL PATHWAY MODEL;
EXECUTIVE FUNCTION; DELAY AVERSION; STRATEGY APPLICATION; LANGUAGE
IMPAIRMENT; ADHD; GRATIFICATION; DYSFUNCTION
AB Attention Deficit/Hyperactivity Disorder (ADHD) is a clinical syndrome characterized by an onset in early life. More than 65% of patients persist with manifestations of ADHD in adulthood. These symptoms may interfere in activities of daily-living, interpersonal relationships and professional and academic achievement. Nevertheless, the observation of an important group of adults with ADHD who do not show significant difficulties in the areas mentioned before puts into evidence the prognostic heterogeneity of this disorder. One of the current, most accepted explanations is the Double-Pathway Model: two double-dissociated deficits (Executive Disorders and Delayed-Reward Processing impairments) are involved in the genesis of ADHD, which explains the existence of different behavioral phenotypes. Moreover, personality traits like tenacity or perseverance are associated with higher levels of achievement in adults. On these grounds, we propose the hypothesis that the neurobiological correlate of tenacity/perseverance is a preserved Delayed-Reward Processing capacity, although further studies are needed to verify this idea. (Rev Med Chile 2012; 140: 379-385).
C1 [Slachevsky Ch, Andrea] Univ Chile, Ctr Invest Avanzada Educ, Fac Med, Dept Farmacol,Inst Ciencias Biomed, Santiago, Chile.
[Slachevsky Ch, Andrea] Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile.
[Slachevsky Ch, Andrea; Munoz-Neira, Carlos] Hosp Salvador, Serv Neurol, Unidad Neurol Cognit & Demencias, Santiago, Chile.
[Slachevsky Ch, Andrea] Clin Alemana, Unidad Neurol, Alemana, Chile.
[Nunez-Huasaf, Javier] Univ Chile, Fac Med, Hosp San Juan Dios, Santiago, Chile.
[Nunez-Huasaf, Javier] Harvard Univ, Massachusetts Gen Hosp, Comp Sci Lab, Cambridge, MA 02138 USA.
RP Ch, AS (reprint author), Univ Chile, Ctr Invest Avanzada Educ, Fac Med, Dept Farmacol,Inst Ciencias Biomed, Periodista Jose Carrasco Tapia N 75, Santiago, Chile.
EM aslachevsky@me.com
NR 55
TC 0
Z9 0
U1 1
U2 9
PU SOC MEDICA SANTIAGO
PI SANTIAGO 9
PA BERNARDA MORIN 488 PROVIDENCIA, CASILLA 168 CORREO 55, SANTIAGO 9,
00000, CHILE
SN 0034-9887
J9 REV MED CHILE
JI Rev. Medica Chile
PD MAR
PY 2012
VL 140
IS 3
BP 379
EP 385
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 927RF
UT WOS:000302927100016
ER
PT J
AU Fishman, JA
Scobie, L
Takeuchi, Y
AF Fishman, Jay A.
Scobie, Linda
Takeuchi, Yasuhiro
TI Xenotransplantation-associated infectious risk: a WHO consultation
SO XENOTRANSPLANTATION
LA English
DT Article
DE Clinical assays; clinical trials; donor; derived infection; infectious
disease; porcine endogenous retrovirus; safety; xenotransplantation
ID PORCINE ENDOGENOUS RETROVIRUS; PATHOGEN-FREE HERD; MINIATURE SWINE;
TRANSMISSION CHARACTERISTICS; REPLICATION-COMPETENT;
REVERSE-TRANSCRIPTASE; NEW-ZEALAND; NO EVIDENCE; PIG; IDENTIFICATION
AB Xenotransplantation carries the potential risk of the transmission of infection with the cells or tissues of the graft. The degree of risk is unknown in the absence of clinical trials. The clinical application of xenotransplantation has important implications for infectious disease surveillance, both at the national and international levels. Preclinical data indicate that infectious disease events associated with clinical xenotransplantation from swine, should they occur, will be rare; data in human trials are limited but have demonstrated no transmission of porcine microorganisms including porcine endogenous retrovirus. Xenotransplantation will necessitate the development of surveillance programs to detect known infectious agents and, potentially, previously unknown or unexpected pathogens. The development of surveillance and safety programs for clinical trials in xenotransplantation is guided by a "Precautionary Principle," with the deployment of appropriate screening procedures and assays for source animals and xenograft recipients even in the absence of data suggesting infectious risk. All assays require training, standardization and validation, and sharing of laboratory methods and expertise to optimize the quality of the surveillance and diagnostic testing. Investigation of suspected xenogeneic infection events (xenosis, xenozoonosis) should be performed in collaboration with an expert data safety review panel and the appropriate public health and competent authorities. It should be considered an obligation of performance of xenotransplantation trials to report outcomes, including any infectious disease transmissions, in the scientific literature. Repositories of samples from source animals and from recipients prior to, and following xenograft transplantation are essential to the investigation of possible infectious disease events. Concerns over any potential hazards associated with xenotransplantation may overshadow potential benefits. Careful microbiological screening of source animals used as xenotransplant donors may enhance the safety of transplantation beyond that of allotransplant procedures. Xenogeneic tissues may be relatively resistant to infection by some human pathogens. Moreover, xenotransplantation may be made available at the time when patients require organ replacement on a clinical basis. Insights gained in studies of the microbiology and immunology of xenotransplantation will benefit transplant recipients in the future. This document summarizes approaches to disease surveillance in individual recipients of nonhuman tissues.
C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Transplantat Infect Dis & Compromised Host Progr, Boston, MA 02114 USA.
[Fishman, Jay A.] Harvard Univ, Sch Med, Boston, MA USA.
[Scobie, Linda] Glasgow Caledonian Univ, Sch Hlth & Life Sci, Glasgow G4 0BA, Lanark, Scotland.
[Takeuchi, Yasuhiro] UCL, Wohl Virion Ctr, Div Infect & Immun, London, England.
RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplantat Infect Dis & Compromised Host Progr, Boston, MA 02114 USA.
EM jfishman@partners.org
FU NIAID [2010A056237, P01AI45897]; European Sixth Framework Programme
(Life Science, Genomics and Biotechnology for Health)
[LSHB-CT-2006-037377]
FX This document was prepared to support discussions at the World Health
Organization Second Global Consultation of Regulatory Requirements for
Xenotransplantation Clinical Trials, Geneva, October 17-19, 2010. The
authors are grateful for the expert editorial assistance of Luc Noel,
Ralf Toenjes, Joachim Denner, Yannick Blanchard, Emanuele Cozzi, and
Takaaki Kobayashi. JAF's research has been supported by NIAID
2010A056237 and P01AI45897. LS's and YT's research has been funded by
the European Sixth Framework Programme (Life Science, Genomics and
Biotechnology for Health) funded project XENOME, LSHB-CT-2006-037377.
NR 51
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U1 2
U2 30
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0908-665X
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD MAR-APR
PY 2012
VL 19
IS 2
BP 72
EP 81
DI 10.1111/j.1399-3089.2012.00693.x
PG 10
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 925XT
UT WOS:000302796400002
PM 22497509
ER
PT J
AU Robinson, EB
Koenen, KC
McCormick, MC
Munir, K
Hallett, V
Happe, F
Plomin, R
Ronald, A
AF Robinson, Elise B.
Koenen, Karestan C.
McCormick, Marie C.
Munir, Kerim
Hallett, Victoria
Happe, Francesca
Plomin, Robert
Ronald, Angelica
TI A Multivariate Twin Study of Autistic Traits in 12-Year-Olds: Testing
the Fractionable Autism Triad Hypothesis
SO BEHAVIOR GENETICS
LA English
DT Article
DE Autistic traits; Autism; Twins; Genetics; Genetic overlap
ID PERVASIVE DEVELOPMENTAL DISORDERS; MULTIPLE-REGRESSION ANALYSIS; CAST
CHILDHOOD ASPERGER; RARE DE-NOVO; GENERAL-POPULATION; SPECTRUM
DISORDERS; ENVIRONMENTAL ETIOLOGIES; INDIVIDUAL-DIFFERENCES; GENETIC
ETIOLOGY; SYMPTOM DOMAINS
AB Autistic traits-social impairment, communication impairment, and restricted and repetitive behaviors and interests-are heritable in the general population. Previous analyses have consistently reported limited genetic and environmental overlap between autistic trait domains in samples assessed in middle childhood. Here we extend this research to parent-report data for 12-year-olds. Data from 5,944 pairs in the Twins Early Development Study were analyzed to explore the domain-specific heritability and degree of shared genetic and environmental influences across different autistic traits in the general population and among individuals scoring in the top 5% of each domain. Sex differences in the etiological estimates were also tested in these analyses. Autistic traits were moderately to highly heritable (0.58-0.88) at age 12. Bivariate genetic correlations in the full sample (0.18-0.40) and the extremes (0.24-0.67), as well as even lower unique environmental correlations, all suggested considerable fractionation of genetic and environmental influences across autistic trait domains, in line with previous findings.
C1 [Robinson, Elise B.; Koenen, Karestan C.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02114 USA.
[Robinson, Elise B.; Munir, Kerim] Harvard Univ, Sch Med, Mental Hlth & Dev Disabil MH DD Program, Div Dev Med,Childrens Hosp, Boston, MA 02114 USA.
[Robinson, Elise B.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02115 USA.
[Koenen, Karestan C.; McCormick, Marie C.] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02114 USA.
[Koenen, Karestan C.] Harvard Univ, Harvard Ctr Developing Child, Cambridge, MA 02138 USA.
[Munir, Kerim] Harvard Univ, Sch Med, Dept Psychiat, Childrens Hosp, Boston, MA 02114 USA.
[Hallett, Victoria; Happe, Francesca; Plomin, Robert; Ronald, Angelica] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, London SE5 8AF, England.
[Hallett, Victoria] Yale Univ, Yale Child Study Ctr, New Haven, CT 06520 USA.
[Ronald, Angelica] Univ London, Ctr Brain & Cognit Dev, Dept Psychol Sci, London WC1E 7HX, England.
RP Robinson, EB (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 185 Cambridge St,6-236, Boston, MA 02114 USA.
EM erobinso@hsph.harvard.edu
RI Happe, Francesca/D-5544-2012; Ronald, Angelica/C-7812-2009; Koenen,
Karestan/K-5402-2014;
OI Ronald, Angelica/0000-0002-9576-2176; Robinson,
Elise/0000-0003-2314-2792; McCormmick, Marie/0000-0002-3938-1707;
Koenen, Karestan/0000-0003-3293-4281; Plomin,
Robert/0000-0002-0756-3629; Happe, Francesca/0000-0001-9226-4000
FU MRC [G0500079]; National Institute of Mental Health/NIH at The
Children's Hospital Boston, Harvard Medical School [MH71286]; Harvard
School of Public Health [T32MH017119]
FX The TEDS is funded by MRC grant G0500079 and has IRB approval. The
research was specifically funded by a National Institute of Mental
Health/NIH Research Fellowship in Mental Health and Developmental
Disabilities (MH/DD) at The Children's Hospital Boston, Harvard Medical
School (MH71286) and the Training Program in Psychiatric Genetics and
Translational Research at the Harvard School of Public Health
(T32MH017119).
NR 51
TC 35
Z9 35
U1 5
U2 29
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD MAR
PY 2012
VL 42
IS 2
BP 245
EP 255
DI 10.1007/s10519-011-9500-3
PG 11
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 924MX
UT WOS:000302697100006
PM 21927971
ER
PT J
AU Srinivasan, VJ
Radhakrishnan, H
Lo, EH
Mandeville, ET
Jiang, JY
Barry, S
Cable, AE
AF Srinivasan, Vivek J.
Radhakrishnan, Harsha
Lo, Eng H.
Mandeville, Emiri T.
Jiang, James Y.
Barry, Scott
Cable, Alex E.
TI OCT methods for capillary velocimetry
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; DOPPLER TOMOGRAPHY;
VELOCITY; MICROVASCULATURE; ANGIOGRAPHY; MICROSCOPY; SPECKLE; MODEL;
BANDWIDTH
AB To date, two main categories of OCT techniques have been described for imaging hemodynamics: Doppler OCT and OCT angiography. Doppler OCT can measure axial velocity profiles and flow in arteries and veins, while OCT angiography can determine vascular morphology, tone, and presence or absence of red blood cell (RBC) perfusion. However, neither method can quantify RBC velocity in capillaries, where RBC flow is typically transverse to the probe beam and single-file. Here, we describe new methods that potentially address these limitations. Firstly, we describe a complex-valued OCT signal in terms of a static scattering component, dynamic scattering component, and noise. Secondly, we propose that the time scale of random fluctuations in the dynamic scattering component are related to red blood cell velocity. Analysis was performed along the slow axis of repeated B-scans to parallelize measurements. We correlate our purported velocity measurements against two-photon microscopy measurements of RBC velocity, and investigate changes during hypercapnia. Finally, we image the ischemic stroke penumbra during distal middle cerebral artery occlusion (dMCAO), where OCT velocimetry methods provide additional insight that is not afforded by either Doppler OCT or OCT angiography. (c) 2012 Optical Society of America
C1 [Srinivasan, Vivek J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Radhakrishnan, Harsha] Penn State Univ, Ctr Neural Engn, University Pk, PA 16802 USA.
[Lo, Eng H.; Mandeville, Emiri T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol & Neurol, Charlestown, MA 02129 USA.
[Jiang, James Y.; Barry, Scott; Cable, Alex E.] Thorlabs Inc, Adv Imaging Grp, Newton, NJ 07860 USA.
RP Srinivasan, VJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM vjsriniv@nmr.mgh.harvard.edu
RI Radhakrishnan, Harsha/K-5557-2012
FU National Institutes of Health [R00NS067050, NS055104, EB001954 R01];
American Heart Association [11IRG5440002]; Glaucoma Research Foundation
Catalyst for a Cure 2
FX We acknowledge support from the National Institutes of Health
(R00NS067050, NS055104, EB001954 R01), the American Heart Association
(11IRG5440002), and the Glaucoma Research Foundation Catalyst for a Cure
2. We thank Maria Angela Franceschini for permission to use the OCT
system.
NR 41
TC 47
Z9 48
U1 0
U2 17
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD MAR 1
PY 2012
VL 3
IS 3
BP 612
EP 629
PG 18
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 925UK
UT WOS:000302787000020
PM 22435106
ER
PT J
AU Auksorius, E
Bromberg, Y
Motiejunaite, R
Pieretti, A
Liu, L
Coron, E
Aranda, J
Goldstein, AM
Bouma, BE
Kazlauskas, A
Tearney, GJ
AF Auksorius, Egidijus
Bromberg, Yaron
Motiejuenaite, Rueta
Pieretti, Alberto
Liu, Linbo
Coron, Emmanuel
Aranda, Jorge
Goldstein, Allan M.
Bouma, Brett E.
Kazlauskas, Andrius
Tearney, Guillermo J.
TI Dual-modality fluorescence and full-field optical coherence microscopy
for biomedical imaging applications
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID STRUCTURED ILLUMINATION; IN-VIVO; TOMOGRAPHY; LIGHT; ANGIOGENESIS;
MOUSE; MODEL
AB Full-field optical coherence microscopy (FFOCM) is a high-resolution interferometric technique that is particularly attractive for biomedical imaging. Here we show that combining it with structured illumination fluorescence microscopy on one platform can increase its versatility since it enables co-localized registration of optically sectioned reflectance and fluorescence images. To demonstrate the potential of this dual modality, a fixed and labeled mouse retina was imaged. Results showed that both techniques can provide complementary information and therefore the system could potentially be useful for biomedical imaging applications. (c) 2012 Optical Society of America
C1 [Auksorius, Egidijus; Bromberg, Yaron; Liu, Linbo; Coron, Emmanuel; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Auksorius, Egidijus; Bromberg, Yaron; Liu, Linbo; Coron, Emmanuel; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Motiejuenaite, Rueta; Aranda, Jorge; Kazlauskas, Andrius] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Motiejuenaite, Rueta; Aranda, Jorge; Kazlauskas, Andrius] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA.
[Motiejuenaite, Rueta] Vilnius Univ, Dept Biochem & Biophys, Vilnius, Lithuania.
[Pieretti, Alberto; Goldstein, Allan M.] Harvard Univ, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA.
[Pieretti, Alberto; Goldstein, Allan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Auksorius, E (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
EM auksorius.egidijus@mgh.harvard.edu
RI Bromberg, Yaron/F-6570-2010; Coron, Emmanuel/K-2415-2015
OI Bromberg, Yaron/0000-0003-2565-7394;
FU Air Force Office of Scientific Research [FA9550-10-1-0537]; NIH
[R01HL076398, R01HL093717, R01CA103769, R01DK091923]
FX We acknowledge financial support from the Air Force Office of Scientific
Research under grant FA9550-10-1-0537 and the NIH under grants
R01HL076398, R01HL093717, R01CA103769, R01DK091923.
NR 23
TC 15
Z9 15
U1 0
U2 6
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD MAR 1
PY 2012
VL 3
IS 3
BP 661
EP 666
PG 6
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 925UK
UT WOS:000302787000024
PM 22435110
ER
PT J
AU Ballen, K
AF Ballen, K.
TI How to manage the transplant question in myelofibrosis
SO BLOOD CANCER JOURNAL
LA English
DT Article
DE transplantation; myelofibrosis; cord blood
ID STEM-CELL TRANSPLANTATION; AGNOGENIC MYELOID METAPLASIA; CORD BLOOD
TRANSPLANTATION; WORLD-HEALTH-ORGANIZATION; MARROW-TRANSPLANTATION;
ESSENTIAL THROMBOCYTHEMIA; POLYCYTHEMIA-VERA; GRUPPO-ITALIANO; SCORING
SYSTEM; MIDOLLO-OSSEO
AB Allogeneic stem cell transplantation remains the only curative therapy for myelofibrosis. Despite advances in transplant, the morbidity and the mortality of the procedure necessitate careful patient selection. In this manuscript, we describe the new prognostic scoring system to help select appropriate patients for transplant and less aggressive therapies. We explore the advances in non-transplant therapy, such as with investigational agents. We review the blossoming literature on results of myeloablative, reduced intensity and alternative donor transplantation. Finally, we make recommendations for which patients are most likely to benefit from transplantation.
C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
RP Ballen, K (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 0 Emerson,Suite 118, Boston, MA 02114 USA.
EM kballen@partners.org
NR 46
TC 12
Z9 12
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD MAR
PY 2012
VL 2
AR e59
DI 10.1038/bcj.2012.3
PG 5
WC Oncology
SC Oncology
GA 925NT
UT WOS:000302768700002
PM 22829254
ER
PT J
AU Ehrlich, S
Walton, E
Roffman, JL
Weiss, D
Puls, I
Doehler, N
Burghardt, R
Lehmkuhl, U
Hillemacher, T
Muschler, M
Frieling, H
AF Ehrlich, Stefan
Walton, Esther
Roffman, Joshua L.
Weiss, Deike
Puls, Imke
Doehler, Nico
Burghardt, Roland
Lehmkuhl, Ulrike
Hillemacher, Thomas
Muschler, Marc
Frieling, Helge
TI Smoking, But Not Malnutrition, Influences Promoter-Specific DNA
Methylation of the Proopiomelanocortin Gene in Patients With and Without
Anorexia Nervosa
SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE
LA English
DT Article
DE proopiomelanocortin; DNA methylation; CpG island; smoking; malnutrition;
anorexia nervosa
ID MESSENGER-RNA EXPRESSION; CPG ISLAND METHYLATION; EATING-DISORDERS;
MELANOCORTIN-4 RECEPTOR; EPIGENETIC REGULATION; ALCOHOL DEPENDENCE;
BIPOLAR DISORDER; TOBACCO-SMOKING; DOWN-REGULATION; DIETARY-FOLATE
AB Objective: Our pilot study evaluates the impact of environmental factors, such as nutrition and smoking status, on epigenetic patterns in a disease-associated gene.
Method: We measured the effects of malnutrition and cigarette smoking on proopiomelanocortin (POMC) promoter-specific DNA methylation in female patients with and without anorexia nervosa (AN). POMC and its derived peptides (alpha melanocyte stimulating hormone and adrenocorticotropic hormone) are implicated in stress and feeding response. Promoter-specific DNA methylation of the POMC gene was determined in peripheral blood mononuclear cells of 54 healthy female control subjects, 40 underweight patients with AN, and 21 weight-restored patients with AN using bisulfite sequencing. Malnutrition was characterized by plasma leptin.
Results: POMC promoter-specific DNA methylation was not affected by diagnosis or nutritional status but significantly negatively associated with cigarette smoking.
Conclusions: Although malnutrition may be expected to reduce DNA methylation through its effects on one-carbon metabolism, our negative results are in line with several in vitro and clinical studies that did not show a direct relation between gene-specific DNA methylation and folate levels. In contrast, smoking has been repeatedly reported to alter DNA methylation of specific genes and should be controlled for in future epigenetic studies.
C1 [Ehrlich, Stefan; Walton, Esther] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, D-01307 Dresden, Germany.
[Ehrlich, Stefan; Weiss, Deike; Doehler, Nico; Burghardt, Roland; Lehmkuhl, Ulrike] Charite, Dept Child & Adolescent Psychiat, D-13353 Berlin, Germany.
[Ehrlich, Stefan; Roffman, Joshua L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Athinoula A Martinos Ctr Biomed Ima, Charlestown, MA USA.
[Puls, Imke] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany.
[Hillemacher, Thomas] Hannover Med Sch, Dept Psychiat Social Psychiat & Psychotherapy, Addict Res Ctr, Hannover, Germany.
[Muschler, Marc; Frieling, Helge] Hannover Med Sch, Dept Psychiat Social Psychiat & Psychotherapy, Mol Neurosci Lab, Hannover, Germany.
[Frieling, Helge] Univ Hosp Erlangen, Dept Psychiat & Psychotherapy, Erlangen, Germany.
RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Fetscherstr 74, D-01307 Dresden, Germany.
EM stefan@nmr.mgh.harvard.edu
RI Hillemacher, Thomas/E-4596-2012; Frieling, Helge/C-5299-2015
OI Hillemacher, Thomas/0000-0002-3362-7868; Frieling,
Helge/0000-0001-5146-9720
FU Charite-Universitatsmedizin Research Fund; German Research Fund
(Deutsche Forschungsgemeinschaft) [EH 367/2-1]; Beyer Vital AG; Astra
Zeneca Germany
FX Funding for our study was provided by the Charite-Universitatsmedizin
Research Fund and the German Research Fund (Deutsche
Forschungsgemeinschaft; grant number EH 367/2-1). Dr Frieling holds
grants from Beyer Vital AG and previously from Astra Zeneca Germany. Dr
Frieling has consulted for Astra Zeneca, Merz, Otsuka, and Servier
Germany. All authors have no conflict of interest.
NR 74
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U1 0
U2 5
PU CANADIAN PSYCHIATRIC ASSOC
PI OTTAWA
PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA
SN 0706-7437
J9 CAN J PSYCHIAT
JI Can. J. Psychiat.-Rev. Can. Psychiat.
PD MAR
PY 2012
VL 57
IS 3
BP 168
EP 176
PG 9
WC Psychiatry
SC Psychiatry
GA 925LC
UT WOS:000302761700006
PM 22398003
ER
PT J
AU Larson, AM
Pfeifer, HH
Thiele, EA
AF Larson, Anna M.
Pfeifer, Heidi H.
Thiele, Elizabeth A.
TI Low glycemic index treatment for epilepsy in tuberous sclerosis complex
SO EPILEPSY RESEARCH
LA English
DT Article
DE Tuberous sclerosis complex; Epilepsy; Low glycemic index treatment;
Ketogenic diet; mTOR pathway
ID NATURAL-HISTORY; KETOGENIC DIET; EFFICACY
AB Retrospective chart review of 15 patients with tuberous sclerosis complex (TSC) who initiated the low glycemic index treatment (LGIT) for epilepsy management at Massachusetts General Hospital over a five-year period. Prior to dietary therapy, this cohort (average age: 8.5 years) had tried an average of 5.8 anti-epileptic drugs with incomplete seizure control. At 6 months on the LGIT, 7/15 (47%) patients experienced >50% reduction in seizure frequency. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Larson, Anna M.; Pfeifer, Heidi H.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Carol & James Herscot Ctr, Dept Neurol, Boston, MA 02114 USA.
RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Carol & James Herscot Ctr, Dept Neurol, Tuberous Sclerosis Complex,175 Cambridge St,Suite, Boston, MA 02114 USA.
EM ethiele@partners.org
FU Herscot Center for Tuberous Sclerosis Complex; Tuberous Sclerosis
Alliance; NIH/NINDS [P01 NS024279]
FX This study was supported by the Herscot Center for Tuberous Sclerosis
Complex, the Tuberous Sclerosis Alliance, and NIH/NINDS P01 NS024279.
NR 9
TC 13
Z9 16
U1 2
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-1211
J9 EPILEPSY RES
JI Epilepsy Res.
PD MAR
PY 2012
VL 99
IS 1-2
BP 180
EP 182
DI 10.1016/j.eplepsyres.2011.10.021
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 920TV
UT WOS:000302431700024
PM 22119636
ER
PT J
AU Chen, CH
Li, JS
Hosseini, A
Gadikota, HR
Gill, TJ
Li, GA
AF Chen, Chih-Hui
Li, Jing-Sheng
Hosseini, Ali
Gadikota, Hemanth R.
Gill, Thomas J.
Li, Guoan
TI Anteroposterior stability of the knee during the stance phase of gait
after anterior cruciate ligament deficiency
SO GAIT & POSTURE
LA English
DT Article
DE Anterior cruciate ligament; Gait; Kinematics
ID FLUOROSCOPIC IMAGING TECHNIQUE; IN-SITU FORCES; ELECTROMYOGRAPHIC
ANALYSIS; TIBIOFEMORAL KINEMATICS; MOTION ANALYSIS; JOINT MOTION;
WALKING; VIVO; RECONSTRUCTION; OSTEOARTHRITIS
AB Quadriceps avoidance and higher flexion strategies have been assumed as effects of ACL deficiency on knee joint function during gait. However, the effect of ACL deficiency on anteroposterior stability of the knee during gait is not well defined. In this study, 10 patients with unilateral acute ACL ruptures and the contralateral side intact performed gait on a treadmill. Flexion angles and anteroposterior translation of the ACL injured and the intact controlateral knees were measured at every 10% of the stance phase of the gait (from heel strike to toe-off) using a combined MRI and dual fluoroscopic imaging system (DFIS). The data indicated that during the stance phase of the gait, the ACL-deficient knees showed higher flexion angles compared to the intact contralateral side, consistent with the assumption of a higher flexion gait strategy. However, the data also :revealed that the ACL-deficient knees had higher anterior tibial translation compared to the intact contralateral side during the stance phase of the gait. The higher flexion gait strategy was not shown to correlate to a reduction of the anterior tibial translation in ACL deficient knees. These data may provide indications for conservative treatment or surgical reconstruction of the ACL injured knees in restoration of the knee kinematics during daily walking activities. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Chen, Chih-Hui; Li, Jing-Sheng; Hosseini, Ali; Gadikota, Hemanth R.; Gill, Thomas J.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA.
[Chen, Chih-Hui; Li, Jing-Sheng; Hosseini, Ali; Gadikota, Hemanth R.; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Chen, Chih-Hui] Taichung Vet Gen Hosp, Dept Orthopaed Surg, Taichung, Taiwan.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.
EM gli1@partners.org
FU National Institute of Health [R01 AR055612]; Department of Orthopaedic
Surgery at Massachusetts General Hospital
FX The authors would like to gratefully acknowledge the financial support
of the National Institute of Health (R01 AR055612) and the Department of
Orthopaedic Surgery at Massachusetts General Hospital.
NR 31
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U1 0
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0966-6362
J9 GAIT POSTURE
JI Gait Posture
PD MAR
PY 2012
VL 35
IS 3
BP 467
EP 471
DI 10.1016/j.gaitpost.2011.11.009
PG 5
WC Neurosciences; Orthopedics; Sport Sciences
SC Neurosciences & Neurology; Orthopedics; Sport Sciences
GA 921BO
UT WOS:000302453200020
PM 22169387
ER
PT J
AU Cashman, EC
Woo, SB
AF Cashman, E. C.
Woo, S. B.
TI Clear cell carcinoma of the major salivary gland: time for a different
approach to management?
SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Letter
C1 [Cashman, E. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Woo, S. B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Cashman, EC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM emma_cashman@dfci.harvard.edu
NR 5
TC 1
Z9 1
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0901-5027
J9 INT J ORAL MAX SURG
JI Int. J. Oral Maxillofac. Surg.
PD MAR
PY 2012
VL 41
IS 3
BP 408
EP 409
DI 10.1016/j.ijom.2011.07.735
PG 2
WC Dentistry, Oral Surgery & Medicine; Surgery
SC Dentistry, Oral Surgery & Medicine; Surgery
GA 921VL
UT WOS:000302506100025
PM 21856122
ER
PT J
AU Hajrasouliha, AR
Funaki, T
Sadrai, Z
Hattori, T
Chauhan, SK
Dana, R
AF Hajrasouliha, Amir R.
Funaki, Toshinari
Sadrai, Zahra
Hattori, Takaaki
Chauhan, Sunil K.
Dana, Reza
TI Vascular Endothelial Growth Factor-C Promotes Alloimmunity by Amplifying
Antigen-Presenting Cell Maturation and Lymphangiogenesis
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RISK CORNEAL TRANSPLANTATION; DRAINING LYMPH-NODES; FACTOR RECEPTOR-3;
DENDRITIC CELLS; GRAFT-SURVIVAL; ANGIOGENESIS; VEGF; MICROENVIRONMENT;
INFLAMMATION; BEVACIZUMAB
AB PURPOSE. To investigate the role of anti-vascular endothelial growth factor (VEGF)-C therapy in corneal graft survival and concomitant suppression of hem-and lymph-angiogenesis.
METHODS. Corneal suture model in BALB/c mice was placed and immunohistochemical staining was performed with CD31/PECAM-1 and LYVE-1 to quantify the level of blood and lymphatic vessels. Corneal transplants were done in BALB/c mice from C57BL/6 mice donors; grafts were subsequently scored for opacity. VEGF-C was blocked in the angiogenesis and transplant model using neutralizing monoclonal anti-VEGF-C (VGX-100) by intraperitoneal injection. To determine the function of VEGF-C in maturation of antigen-presenting cells (APCs), bone marrow-derived dendritic cells were generated and matured in the presence or absence of VEGF-C.
RESULTS. VEGF-C expression was demonstrated to be markedly upregulated in corneal graft rejection. VEGF-C blockade, through administration of a VEGF-C blocking monoclonal antibody, suppresses corneal angiogenic responses, inhibits trafficking and maturation of APCs, and significantly improves allotransplant survival.
CONCLUSIONS. These data suggest VEGF-C as a potentially important target in corneal transplant pharmacotherapy and immunobiology. (Invest Ophthalmol Vis Sci. 2012;53:1244-1250) DOI:10.1167/iovs.11-8668
C1 [Hajrasouliha, Amir R.; Funaki, Toshinari; Sadrai, Zahra; Hattori, Takaaki; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA.
RP Dana, R (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM reza.dana@schepens.harvard.edu
FU National Institutes of Health/National Eye Institute [EY-R01-12963];
Vegenics, Circadian Technologies Ltd. (Melbourne, Australia)
FX Supported in part by National Institutes of Health/National Eye
Institute Grant EY-R01-12963 (RD) and Vegenics, Circadian Technologies
Ltd. (Melbourne, Australia).
NR 39
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U1 1
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2012
VL 53
IS 3
BP 1244
EP 1250
DI 10.1167/iovs.11-8668
PG 7
WC Ophthalmology
SC Ophthalmology
GA 925VT
UT WOS:000302790700023
PM 22281820
ER
PT J
AU Yu, Y
Reynolds, R
Rosner, B
Daly, MJ
Seddon, JM
AF Yu, Yi
Reynolds, Robyn
Rosner, Bernard
Daly, Mark J.
Seddon, Johanna M.
TI Prospective Assessment of Genetic Effects on Progression to Different
Stages of Age-Related Macular Degeneration Using Multistate Markov
Models
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COMPLEMENT FACTOR-H; RISK; VARIANT; SUSCEPTIBILITY; ASSOCIATION; DRUSEN;
POLYMORPHISM; MACULOPATHY; LIPC; AMD
AB PURPOSE. Understanding the effect of genes on progression to different stages of age-related macular degeneration (AMD) may suggest stage-specific therapeutic targets and more precise prediction of the development of this disease.
METHODS. Progression events and time to each stage of AMD were derived from the longitudinal data of 2560 subjects without advanced AMD. SNPs in 12 AMD risk loci were genotyped. A multistate Markov model for progression from normal to intermediate drusen, then to large drusen, and eventually to neovascular disease (NV) or geographic atrophy (GA) was applied to estimate stage-specific hazard ratios for each SNP. The effects of these genetic factors were also estimated by a multivariate multistate Markov model adjusted for baseline age, sex, smoking, body mass index (BMI), education, antioxidant treatment, and the status of AMD in the fellow eye.
RESULTS. Controlling for demographic and behavioral factors and other SNPs, the TT genotype of rs10468017 in LIPC was associated with decreased risk of progression from large drusen to NV (HR = 0.57, P = 0.04) and tended to reduce the risk of progression from normal to intermediate drusen (HR = 0.72, P = 0.07). The SNP rs1883025 (T allele) in ABCA1 was associated with decreased risk of progression from normal to intermediate drusen (HR per allele = 0.82 per allele, P = 9.7 x 10(-3)) and from intermediate drusen to large drusen (HR per allele = 0.77, P = 5.2 x 10(-3)). The genes CFH, C3, CFB, and ARMS2/HTRA1 were associated with progression from intermediate drusen to large drusen and from large drusen to GA or NV.
CONCLUSIONS. Genes in different pathways influence progression to different stages of AMD. (Invest Ophthalmol Vis Sci. 2012;53:1548-1556) DOI:10.1167/iovs.11-8657
C1 [Yu, Yi; Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA.
[Rosner, Bernard] Channing Labs, Boston, MA USA.
[Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
RP Seddon, JM (reprint author), Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, 800 Washington St,450, Boston, MA 02111 USA.
EM jseddon@tuftsmedicalcenter.org
FU National Institutes of Health, Bethesda, MD [R01-EY11309]; Massachusetts
Lions Eye Research Fund, Inc.; Research to Prevent Blindness, Inc., New
York, NY; American Macular Degeneration Foundation, Northampton, MA;
Elizabeth O'Brien Trust; Ophthalmic Epidemiology and Genetics Service,
New England Eye Center, Tufts Medical Center, Tufts University School of
Medicine, Boston, MA; Virginia B. Smith Trust
FX Supported by an anonymous donor (JMS) and in part by Grants R01-EY11309
from the National Institutes of Health, Bethesda, MD; Massachusetts
Lions Eye Research Fund, Inc.; Unrestricted grant from Research to
Prevent Blindness, Inc., New York, NY; the American Macular Degeneration
Foundation, Northampton, MA; Elizabeth O'Brien Trust; Virginia B. Smith
Trust; and the Macular Degeneration Research Fund of the Ophthalmic
Epidemiology and Genetics Service, New England Eye Center, Tufts Medical
Center, Tufts University School of Medicine, Boston, MA.
NR 35
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U1 3
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2012
VL 53
IS 3
BP 1548
EP 1556
DI 10.1167/iovs.11-8657
PG 9
WC Ophthalmology
SC Ophthalmology
GA 925VT
UT WOS:000302790700063
PM 22247473
ER
PT J
AU Iyer, V
Heller, V
Armoundas, AA
AF Iyer, Vivek
Heller, Victoria
Armoundas, Antonis A.
TI Altered spatial calcium regulation enhances electrical heterogeneity in
the failing canine left ventricle: implications for electrical
instability
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE electrophysiological; molecular; EC coupling; calcium; remodeling; heart
failure; arrhythmias
ID INDUCED HEART-FAILURE; TRANSIENT OUTWARD CURRENT; ACTION-POTENTIAL
CHARACTERISTICS; GUINEA-PIG HEARTS; TRANSMURAL HETEROGENEITY; REGIONAL
DIFFERENCES; DILATED CARDIOMYOPATHY; ENDOCARDIAL MYOCYTES; RYANODINE
RECEPTORS; NA+-CA2+ EXCHANGE
AB Iyer V, Heller V, Armoundas AA. Altered spatial calcium regulation enhances electrical heterogeneity in the failing canine left ventricle: implications for electrical instability. J Appl Physiol 112: 944-955, 2012. First published December 22, 2011; doi: 10.1152/japplphysiol.00609.2011.-Myocytes across the left ventricular (LV) wall of the mammalian heart are known to exhibit heterogeneity of electrophysiological properties; however, the transmural variation of cellular electrophysiology and Ca2+ homeostasis in the failing LV is incompletely understood. We studied action potentials (APs), the L-type calcium (Ca2+) current (I-Ca,I-L), and intracellular Ca2+ transients ([Ca2+](i)) of subendocardial (Endo), midmyocardial (Mid), and subepicardial (Epi) tissue layers in the canine normal and tachycardia pacing-induced failing left ventricles. Heart failure (HF) was associated with significant prolongation of the AP duration in Mid myocytes. There were no differences in I-Ca,I-L density in normal Endo, Mid, and Epi myocytes, whereas in the failing heart, I-Ca,I-L density was downregulated by 45% and 26% (at +10 mV) in Endo and Mid myocytes, respectively. The rates of sarcoplasmic reticulum (SR) Ca2+ release and decay of the [Ca2+](i) were slowed, and the amplitude of the [Ca2+](i) was depressed in Endo and Epi myocytes isolated from failing, compared with normal, hearts. Experiments in sodium (Na+)-free solutions showed that Epi and Mid myocytes of the failing ventricle exhibit a greater reliance on the Na+-Ca2+ exchanger to remove cytosolic Ca2+ than myocytes isolated from normal hearts. Simulation studies in Endo, Mid, and Epi canine myocytes demonstrate the importance of L-type current density and SR Ca2+ uptake in modulating the potentially arrhythmogenic repolarization in HF. In conclusion, these results demonstrate that spatially heterogeneous decreases in I-Ca,I-L and defective cytosolic Ca2+ removal contribute to the altered [Ca2+](i) and AP profiles across the canine failing LV. These distinct electrophysiological features in myocytes from a failing heart contribute to a characteristic electrogram arising from increased dispersion of refractoriness across the LV, which may result in significant arrhythmogenic sequellae.
C1 [Heller, Victoria; Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA.
[Iyer, Vivek] Columbia Univ, Dept Med, Div Cardiol, Med Ctr, New York, NY USA.
[Heller, Victoria] Charite, Dept Cardiol & Pulmonol, D-13353 Berlin, Germany.
RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Boston, MA 02129 USA.
EM aarmoundas@partners.org
OI Stary, Victoria/0000-0002-3854-9934
FU American Heart Association [0365304U]
FX Support for this work was provided by an American Heart Association
Beginning Grant-in-Aid (#0365304U) to A. A. Armoundas.
NR 60
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U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD MAR
PY 2012
VL 112
IS 6
BP 944
EP 955
DI 10.1152/japplphysiol.00609.2011
PG 12
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 922GS
UT WOS:000302535900003
PM 22194323
ER
PT J
AU Stuart-Andrews, CR
Kelly, VJ
Sands, SA
Lewis, AJ
Ellis, MJ
Thompson, BR
AF Stuart-Andrews, Christopher R.
Kelly, Vanessa J.
Sands, Scott A.
Lewis, Angela J.
Ellis, Matthew J.
Thompson, Bruce R.
TI Automated detection of the phase III slope during inert gas washout
testing
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE inert gas washout; computer algorithm; alveolar slope
ID VENTILATION HETEROGENEITY; SUSTAINED MICROGRAVITY; SULFUR-HEXAFLUORIDE;
CYSTIC-FIBROSIS; SMALL AIRWAYS; LUNG-DISEASE; ASTHMA; INHOMOGENEITY;
HELIUM; INFLAMMATION
AB Stuart-Andrews CR, Kelly VJ, Sands SA, Lewis AJ, Ellis MJ, Thompson BR. Automated detection of the phase III slope during inert gas washout testing. J Appl Physiol 112: 1073-1081, 2012. First published December 15, 2011; doi:10.1152/japplphysiol.00372.2011.-We describe a method to determine the phase III slope for the purpose of calculating indexes of ventilation heterogeneity, S-acin and S-cond, from the multiple breath nitrogen washout test (MBNW). Our automated method applies a recursive, segmented linear regression technique to each breath of the MBNW test and determines the best point of transition, or breakpoint, between each phase of the washout. A sample set of 50 MBNW tests (controls, asthma, and COPD) was used to establish the conditions in which the phase III slope obtained from the automated technique best matched that obtained by two manual interpreters. We then applied our technique to a test set of 30 subjects (with an even number of subjects in each of the above groups) and compared these results against the manual analysis of a third independent manual interpreter. Indexes of ventilation heterogeneity were determined using both methods and compared. The phase III slopes determined by the automatic technique best matched the manual interpreter when the phase III slope was calculated from the phase II-III transition point plus the addition of 50% of the phase II volume to the end of the expiration. Calculation of the indexes S-acin and S-cond showed no overall difference between analysis methods in either S-acin (P = 0.14) or S-cond (P = 0.59) when the set threshold was applied to our automated analysis. Our analysis method provides an alternate means for rapid quantification of the MBNW test, removing operator dependence without alteration in either S-acin or S-cond.
C1 [Stuart-Andrews, Christopher R.; Kelly, Vanessa J.; Lewis, Angela J.; Ellis, Matthew J.; Thompson, Bruce R.] Alfred Hosp, Dept Allergy Immunol & Resp Med, Serv Physiol, Melbourne, Vic, Australia.
[Kelly, Vanessa J.; Thompson, Bruce R.] Monash Univ, Dept Med Nursing & Hlth Sci, Clayton, Vic, Australia.
[Kelly, Vanessa J.; Thompson, Bruce R.] Cooperat Res Council Asthma & Airways, Glebe, NSW, Australia.
[Kelly, Vanessa J.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Kelly, Vanessa J.; Sands, Scott A.] Harvard Univ, Sch Med, Boston, MA USA.
[Sands, Scott A.] Monash Univ, Ritchie Ctr Baby Hlth Res, Monash Inst Med Res, Clayton, Vic, Australia.
[Sands, Scott A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
RP Stuart-Andrews, CR (reprint author), Alfred Hosp, Dept Allergy Immunol & Resp Med, Serv Physiol, Melbourne, Vic, Australia.
EM C.Stuart-Andrews@alfred.org.au
OI Thompson, Bruce/0000-0002-5885-0652
FU National Health and Medical Research Council of Australia [521808,
486101, 491103]; Cooperative Research Centre for Asthma and Airways
(CRCAA); American Australian Association; American Heart Association
FX Financial support was provided to V. J. Kelly by research grants from
the National Health and Medical Research Council of Australia (Grant
521808), the Cooperative Research Centre for Asthma and Airways (CRCAA),
and the American Australian Association. S. A. Sands received support
from an American Heart Association Post-Doctoral Fellowship. B. R.
Thompson also received financial support through the National Health and
Medical Research Council of Australia (Grants 486101 and 491103).
NR 31
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U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD MAR
PY 2012
VL 112
IS 6
BP 1073
EP 1081
DI 10.1152/japplphysiol.00372.2011
PG 9
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 922GS
UT WOS:000302535900019
PM 22174406
ER
PT J
AU Zwemer, EK
Mahler, HIM
Werchniak, AE
Recklitis, CJ
AF Zwemer, Eric K.
Mahler, Heike I. M.
Werchniak, Andrew E.
Recklitis, Christopher J.
TI Sun exposure in young adult cancer survivors on and off the beach:
results from Project REACH
SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE
LA English
DT Article
DE Cancer survivors; Sun protection behaviors; Incidental exposure;
Radiation therapy
ID HEMATOPOIETIC-CELL TRANSPLANTATION; APPEARANCE-BASED INTERVENTIONS;
BEHAVIORAL RISK-FACTORS; SKIN-CANCER; CHILDHOOD-CANCER; PROTECTION
BEHAVIORS; BASAL-CELL; UNIVERSITY-STUDENTS; IONIZING-RADIATION;
ADOLESCENT CANCER
AB Background Although cancer survivors are at risk for future skin cancers, many do not practice recommended sun protection. Studies have demonstrated poor adherence to specific behaviors (e.g., sunscreen, artificial tanning) during sunbathing, but less is known about survivors' typical amount of sun exposure during activities other than sunbathing.
Methods We conducted a mailed survey of 153 adults (median age=26.1) diagnosed with a non-skin cancer before age 30. Information on recent sunbathing and incidental sun exposures, protective behaviors, and perceived vulnerability was collected. Analyses focused on characterizing survivors with the lowest levels of recommended sun protection.
Results Twenty-nine percent of participants exhibited low sun protection adherence during sunbathing and 31% during incidental exposure. Younger age was associated with low adherence, but this difference was significant only for sunbathing (OR=0.4; 95% CI, 0.2-0.9). Women were more likely than men to have low adherence during sunbathing (34.0% vs. 20.3%; OR=2.44; 95% CI, 1.1-5.5). Survivors treated with radiation did not differ on exposures, adherence, or perceived vulnerability to the sun, despite feeling more susceptible to skin cancers (p=0.03).
Conclusions Despite known skin cancer risks, many young cancer survivors receive significant sun exposure. Assessment of sunbathing alone fails to capture sun exposure behaviors, particularly in men. Survivors treated with radiation may recognize their increased risk of skin cancer, but not the role of sun protection in modifying that risk.
C1 [Zwemer, Eric K.; Recklitis, Christopher J.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Perini Family Survivors Ctr, Boston, MA 02215 USA.
[Werchniak, Andrew E.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA.
[Mahler, Heike I. M.] Univ Calif, Dept Psychol, La Jolla, CA USA.
RP Recklitis, CJ (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Perini Family Survivors Ctr, 450 Brookline Ave,DFCI D321, Boston, MA 02215 USA.
EM Christopher_Recklitis@dfci.harvard.edu
NR 50
TC 5
Z9 5
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD MAR
PY 2012
VL 6
IS 1
BP 63
EP 71
DI 10.1007/s11764-011-0201-y
PG 9
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 920PS
UT WOS:000302419400008
PM 22002547
ER
PT J
AU Burstein, HJ
Griggs, JJ
AF Burstein, Harold J.
Griggs, Jennifer J.
TI Deep Time: The Long and the Short of Adjuvant Endocrine Therapy for
Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; LETROZOLE; TRIAL; RECURRENCE;
SEQUENCE; RELAPSE
C1 [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Griggs, Jennifer J.] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 18
TC 9
Z9 9
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2012
VL 30
IS 7
BP 684
EP 686
DI 10.1200/JCO.2011.40.1455
PG 4
WC Oncology
SC Oncology
GA 923NG
UT WOS:000302625400006
PM 22271478
ER
PT J
AU Meropol, NJ
Kris, MG
Winer, EP
AF Meropol, Neal J.
Kris, Mark G.
Winer, Eric P.
TI The American Society of Clinical Oncology's Blueprint for Transforming
Clinical and Translational Cancer Research
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
C1 [Meropol, Neal J.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Kris, Mark G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Meropol, NJ (reprint author), Case Western Reserve Univ, Case Comprehens Canc Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
OI Kris, Mark/0000-0002-7317-5341
NR 1
TC 9
Z9 10
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2012
VL 30
IS 7
BP 690
EP 691
DI 10.1200/JCO.2011.40.1125
PG 2
WC Oncology
SC Oncology
GA 923NG
UT WOS:000302625400008
PM 22215747
ER
PT J
AU Jin, H
Tu, DS
Zhao, NQ
Shepherd, LE
Goss, PE
AF Jin, Huan
Tu, Dongsheng
Zhao, Naiqing
Shepherd, Lois E.
Goss, Paul E.
TI Longer-Term Outcomes of Letrozole Versus Placebo After 5 Years of
Tamoxifen in the NCIC CTG MA.17 Trial: Analyses Adjusting for Treatment
Crossover
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID EXTENDED ADJUVANT THERAPY; STAGE BREAST-CANCER; RANDOMIZED-TRIAL;
CLINICAL-TRIAL; WOMEN; INFERENCE
AB Purpose
The interim analysis of the National Cancer Institute of Canada Clinical Trials Group MA. 17 trial showed that letrozole was significantly better than placebo in disease-free survival (DFS) for postmenopausal women with hormone receptor-positive breast cancer following about 5 years of tamoxifen therapy. When patients were unblinded, those on placebo were offered letrozole. Longer-term efficacy of letrozole, especially survival, was of particular interest because the median follow-up of the first interim analysis was only 2.5 years. Efficacy was difficult to assess because more than 60% of placebo patients crossed over to letrozole after being unblinded.
Patients and Methods
Two statistical approaches were used to adjust for the potential effects of treatment crossover: one was based on the inverse probability of censoring weighted (IPCW) Cox model and the other on a Cox model with time-dependent covariates.
Results
With a median follow-up of 64 months, the hazard ratios (HRs) of letrozole and placebo from the IPCW analyses were HR of 0.52 (95% CI, 0.45 to 0.61; P < .001) for DFS, HR of 0.51 (95% CI, 0.42 to 0.61; P < .001) for distant disease-free survival (DDFS), and HR of 0.61 (95% CI, 0.52 to 0.71; P , .001) for overall survival (OS). The results from the analyses based on the Cox model with time-dependent covariates were similar for letrozole and placebo: HR of 0.58 (95% CI, 0.47 to 0.72; P < .001) for DFS, HR of 0.68 (95% CI, 0.52 to 0.88; P = .004) for DDFS, and HR of 0.76 (95% CI, 0.60 to 0.96; P = .02) for OS.
Conclusion
Exploratory analyses based on longer follow-up and adjusting for treatment crossover suggest that extended adjuvant letrozole was superior to placebo in DFS, DDFS, and OS. J Clin Oncol 30:718-721. (C) 2011 by American Society of Clinical Oncology
C1 [Tu, Dongsheng] Queens Univ, Canc Res Inst, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada.
[Jin, Huan; Zhao, Naiqing] Fudan Univ, Sch Publ Hlth, Shanghai 200433, Peoples R China.
[Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Tu, DS (reprint author), Queens Univ, Canc Res Inst, NCIC Clin Trials Grp, 10 Stuart St, Kingston, ON K7L 3N6, Canada.
EM dtu@ctg.queensu.ca
FU Naiqing Zhao; Bayer Pharmaceuticals; Novartis
FX Naiqing Zhao, Bayer Pharmaceuticals, Novartis
NR 13
TC 60
Z9 63
U1 0
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2012
VL 30
IS 7
BP 718
EP 721
DI 10.1200/JCO.2010.34.4010
PG 4
WC Oncology
SC Oncology
GA 923NG
UT WOS:000302625400013
PM 22042967
ER
PT J
AU Gildengers, A
Tatsuoka, C
Bialko, C
Cassidy, KA
Al Jurdi, RK
Gyulai, L
Mulsant, BH
Young, RC
Sajatovic, M
AF Gildengers, Ariel
Tatsuoka, Curtis
Bialko, Christopher
Cassidy, Kristin A.
Al Jurdi, Rayan K.
Gyulai, Laszlo
Mulsant, Benoit H.
Young, Robert C.
Sajatovic, Martha
TI Correlates of Treatment Response in Depressed Older Adults With Bipolar
Disorder
SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY
LA English
DT Article
DE bipolar disorder; elderly; geriatric; lamotrigine; mood stabilizer;
anticonvulsant; depression
ID WEEKLY SYMPTOMATIC STATUS; RATING-SCALE; II DISORDER;
ANTIDEPRESSANT-TREATMENT; SUICIDAL-BEHAVIOR; NATURAL-HISTORY; TRIAL;
LIFE; PREVENTION; PLASTICITY
AB Aims: To identify baseline clinical factors associated with acute treatment response in depressed older adults with bipolar disorder (BD) receiving lamotrigine. Methods: Secondary analysis of a multisite, 12-week, open-label, uncontrolled study of add-on lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Cardiometabolic risk was measured with total serum cholesterol and the Cumulative Illness Rating Scale-Geriatric (CIRS-G) item # 13 (endocrine/metabolic burden). Neurocognitive (executive) function was evaluated using the Trail Making Test. Results: Greater reduction in MADRS from baseline was associated with higher baseline cardiometabolic burden at 6 and 9 weeks and lower YMRS scores at 9 weeks. At 12 weeks, improvement in the MADRS from baseline was no longer significantly related to baseline cardiometabolic burden or YMRS scores. A longitudinal mixed model of MADRS scores corroborated these findings with a significant finding of time-by-baseline cholesterol level interaction. In a subset of participants, better baseline executive function was related to greater improvement in the MADRS at 9 weeks but not at 6 or 12 weeks. Among all participants, higher baseline YMRS scores were related to greater likelihood of dropout. Conclusions: Lamotrigine appears to work best in depressed elderly patients with BD who have high cardiometabolic risk and low level of mania. Agents like lamotrigine that act primarily on neuroprogressive pathways involving oxidative stress, neurotrophins, and inflammation may be particularly effective in individuals with BD who have significant cardiometabolic burden because of their effects on shared vulnerability factors in BD and medical illness.
C1 [Gildengers, Ariel] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
[Tatsuoka, Curtis] Case Western Reserve Univ, Sch Med, Dept Neurol, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Bialko, Christopher; Cassidy, Kristin A.; Sajatovic, Martha] Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Al Jurdi, Rayan K.] Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA.
[Gyulai, Laszlo] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA.
[Gyulai, Laszlo] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Mulsant, Benoit H.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Young, Robert C.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA.
RP Gildengers, A (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM gildengersag@upmc.edu
RI Sajatovic, Martha/I-8001-2014;
OI Young, Robert/0000-0002-6380-6314
FU GlaxoSmithKline, Research Triangle Park, North Carolina, USA; Case
Western Reserve University [UL1RR024989]; GlaxoSmithKline; Canadian
Institutes of Health Research; NIH; Bristol-Myers Squibb; Wyeth;
AstraZeneca; Janssen; Pfizer; Merck; Ortho-McNeil Janssen
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This study was
supported by an investigator-initiated research grant from
GlaxoSmithKline, Research Triangle Park, North Carolina, USA, and grant
UL1RR024989 from Case Western Reserve University Clinical and
Translational Science Awards (CTSA). The CTSA is a component of the
National Institute of Health (NIH) and NIH Roadmap for Medical Research.
The contents are solely the responsibility of the authors and do not
necessarily represent the official view of the National Center for
Research Resources or the NIH. Ariel Gildengers, Rayan K. Al-Jurdi,
Laszlo Gyulai, and Robert C. Young received funding for research from
GlaxoSmithKline to conduct this investigator-initiated study. Benoit H.
Mulsant has received funding for research from GlaxoSmithKline, the
Canadian Institutes of Health Research, NIH, Bristol-Myers Squibb, and
Wyeth. Robert C. Young has received funding for research from NIH,
GlaxoSmithKline, AstraZeneca, and Janssen. Martha Sajatovic received
research grants from AstraZeneca, Pfizer, Merck, and Ortho-McNeil
Janssen; is a consultant for Cognition Group and United BioSource
Corporation (Bracket); and receives royalties from Springer Press, Johns
Hopkins University Press, and Oxford Press. All other authors have no
conflicts to report.
NR 42
TC 3
Z9 3
U1 0
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0891-9887
J9 J GERIATR PSYCH NEUR
JI J. Geriatr. Psychiatry Neurol.
PD MAR
PY 2012
VL 25
IS 1
SI SI
BP 37
EP 42
DI 10.1177/0891988712436685
PG 6
WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry
SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry
GA 923NM
UT WOS:000302626000007
PM 22467845
ER
PT J
AU Fox, E
Patel, S
Wathen, JK
Schuetze, S
Chawla, S
Harmon, D
Reinke, D
Chugh, R
Benjamin, RS
Helman, LJ
AF Fox, Elizabeth
Patel, Shreyaskumar
Wathen, J. Kyle
Schuetze, Scott
Chawla, Sant
Harmon, David
Reinke, Denise
Chugh, Rashmi
Benjamin, Robert S.
Helman, Lee J.
TI Phase II Study of Sequential Gemcitabine Followed by Docetaxel for
Recurrent Ewing Sarcoma, Osteosarcoma, or Unresectable or Locally
Recurrent Chondrosarcoma: Results of Sarcoma Alliance for Research
Through Collaboration Study 003
SO ONCOLOGIST
LA English
DT Article
C1 [Fox, Elizabeth] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Patel, Shreyaskumar; Wathen, J. Kyle; Benjamin, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Schuetze, Scott; Reinke, Denise; Chugh, Rashmi] Univ Michigan, Ann Arbor, MI 48109 USA.
[Chawla, Sant] Sarcoma Oncol Ctr, Los Angeles, CA USA.
[Harmon, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fox, Elizabeth; Helman, Lee J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Fox, E (reprint author), Childrens Hosp Philadelphia, Div Oncol, Civ Ctr Blvd,CTRB 4016, Philadelphia, PA 19104 USA.
EM foxe@email.chop.edu
NR 0
TC 31
Z9 34
U1 0
U2 3
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD MAR
PY 2012
VL 17
IS 3
BP 321
EP 321
DI 10.1634/theoncologist.2010-0265
PG 1
WC Oncology
SC Oncology
GA 919YQ
UT WOS:000302368500004
PM 22363068
ER
PT J
AU Delate, T
Witt, DM
Ritzwoller, D
Weeks, JC
Kushi, L
Hornbrook, MC
Bowles, EJA
Schrag, D
AF Delate, Thomas
Witt, Daniel M.
Ritzwoller, Debra
Weeks, Jane C.
Kushi, Lawrence
Hornbrook, Mark C.
Bowles, Erin J. Aiello
Schrag, Deborah
TI Outpatient Use of Low Molecular Weight Heparin Monotherapy for
First-Line Treatment of Venous Thromboembolism in Advanced Cancer
SO ONCOLOGIST
LA English
DT Article
DE Venous thromboembolism; Anticoagulants; Neoplasms; Ambulatory care
ID ANTITHROMBOTIC THERAPY; PALLIATIVE CARE; THROMBOSIS; PROPHYLAXIS;
DISEASE; RISK
AB Background. Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) mono-therapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors.
Methods. Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin, LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed.
Results. Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy.
Conclusions. Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE. The Oncologist 2012; 17: 419-427
C1 [Delate, Thomas] Kaiser Permanente Colorado, Dept Pharm, Clin Pharm Res, Aurora, CO 80011 USA.
[Ritzwoller, Debra] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Weeks, Jane C.; Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kushi, Lawrence] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Hornbrook, Mark C.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
[Bowles, Erin J. Aiello] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
RP Delate, T (reprint author), Kaiser Permanente Colorado, Dept Pharm, Clin Pharm Res, 16601 E Centretech Pkwy, Aurora, CO 80011 USA.
EM tom.delate@kp.org
RI Inov Farmaceutica, Inct/K-2313-2013;
OI Kushi, Lawrence/0000-0001-9136-1175
FU National Cancer Institute [NCI 5U19CA079689, U19CA79689]
FX This study was supported by National Cancer Institute grants NCI
5U19CA079689 (D. R. and J.C.W., MPIs) and U19CA79689 (Wagner, PI). We
acknowledge the contributions of Stephanie Latimer and Addie Clark in
developing the SAS code to extract the necessary data elements from each
site's VDW.
NR 28
TC 14
Z9 16
U1 0
U2 3
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD MAR
PY 2012
VL 17
IS 3
BP 419
EP 427
DI 10.1634/theoncologist.2011-0323
PG 9
WC Oncology
SC Oncology
GA 919YQ
UT WOS:000302368500016
PM 22334451
ER
PT J
AU Price, EL
Bereknyei, S
Kuby, A
Levinson, W
Braddock, CH
AF Price, Erika Leemann
Bereknyei, Sylvia
Kuby, Alma
Levinson, Wendy
Braddock, Clarence Henry, III
TI New elements for informed decision making: A qualitative study of older
adults' views
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Informed decision making; Shared decision making; New elements for
informed decision making; Qualitative analysis; Focus groups; Older
adults
ID HEALTH-CARE; PATIENTS PREFERENCES; PATIENT INVOLVEMENT; CLINICAL
DECISIONS; MEDICAL ENCOUNTER; PARTICIPATION; PHYSICIANS; TIME;
COMMUNICATION; PERCEPTIONS
AB Objective: To explore older adults' views of existing informed decision making (IDM) elements and investigate the need for additional elements.
Methods: We recruited persons 65 and older to participate in six focus groups. Participants completed questionnaires about IDM preferences, and discussed videotapes of idealized patient-physician interactions in light of seven IDM elements: (1) discussion of the patient's role in decision making; (2) discussion of the clinical issue; (3) discussion of alternatives; (4) discussion of benefits/risks; (5) discussion of uncertainties; (6) assessment of patient understanding; and (7) exploration of patient preference. We used a modified grounded theory approach to assess agreement with existing IDM elements and identify new elements.
Results: In questionnaires, 97-100% of 59 participants rated each IDM element as "somewhat" or "very" important. Qualitative analysis supported existing elements and suggested two more: opportunity for input from trusted others, and discussion of decisions' impacts on patients' daily lives. Elements overlapped with global communication themes.
Conclusion: Focus groups affirmed existing IDM elements and suggested two more with particular relevance for older patients. Practice implications: Incorporation of additional IDM elements into clinical practice can enhance informed participation of older adults in decision making. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Price, Erika Leemann] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
[Price, Erika Leemann] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bereknyei, Sylvia; Braddock, Clarence Henry, III] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Kuby, Alma] Univ Chicago, Natl Opin Res Ctr, Chicago, IL 60637 USA.
[Levinson, Wendy] Univ Toronto, Dept Med, Toronto, ON, Canada.
RP Price, EL (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box VAMC-111, San Francisco, CA 94121 USA.
EM erika.price@ucsf.edu
OI Bereknyei Merrell, Sylvia /0000-0002-5525-0379
FU National Institute on Aging, National Institutes of Health [R01
AG18781-02]
FX This study was supported by grant no. R01 AG18781-02 from the National
Institute on Aging, National Institutes of Health. We would like to
thank the National Opinion Research Center and focus group participants
for their contributions.
NR 37
TC 18
Z9 18
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD MAR
PY 2012
VL 86
IS 3
BP 335
EP 341
DI 10.1016/j.pec.2011.06.006
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 924EA
UT WOS:000302672700010
PM 21757315
ER
PT J
AU Peters, JM
Madhavan, VL
Kazacos, KR
Husson, RN
Dangoudoubiyam, S
Soul, JS
AF Peters, Jurriaan M.
Madhavan, Vandana L.
Kazacos, Kevin R.
Husson, Robert N.
Dangoudoubiyam, Sriveny
Soul, Janet S.
TI Good Outcome With Early Empiric Treatment of Neural Larva Migrans Due to
Baylisascaris procyonis
SO PEDIATRICS
LA English
DT Article
DE raccoon; Baylisascaris; larva migrans; meningoencephalitis;
encephalomyelitis
ID EOSINOPHILIC MENINGITIS; ENCEPHALITIS; DISEASE; MENINGOENCEPHALITIS;
TOXOCARIASIS; NEMATODIASIS; CHILDREN; MRI
AB We report a remarkably good outcome in a 14-month-old boy with early clinical diagnosis and aggressive empirical treatment of neural larva migrans caused by the raccoon roundworm Baylisascaris procyonis. He presented with fever, meningismus, lethargy, irritability and asymmetric spastic extremity weakness. Early findings of marked blood and cerebrospinal fluid eosinophilia and of diffuse white matter signal abnormality in the brain and spinal cord on MRI suggested a parasitic encephalomyelitis. Rapid presumptive treatment with albendazole and high-dose steroids halted progression of clinical signs. The diagnosis was confirmed by 2 sequential enzyme-linked immunosorbent assay studies positive for B procyonis serum immunoglobulin G and by Western blot. Field examination with soil sampling yielded infective Baylisascaris eggs. Repeat MRI 3 months later showed atrophy and diffuse, chronic white matter abnormalities, discordant with the marked clinical improvement in this interval. At 10 months, residual neurologic deficits included subtle paraparesis and moderate language delay. This case is the first in which spinal involvement in human Baylisascaris infection was clinically suspected and confirmed by neuroimaging. Importantly, early diagnosis and aggressive treatment of Baylisascaris meningo-encephalitis and myelitis with albendazole and high-dose steroids likely contributed to the good outcome in this patient, in contrast with previous reports. Pediatrics 2012; 129:e806-e811
C1 [Peters, Jurriaan M.; Soul, Janet S.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Husson, Robert N.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Madhavan, Vandana L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Infect Dis Unit, Boston, MA USA.
[Kazacos, Kevin R.; Dangoudoubiyam, Sriveny] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
RP Soul, JS (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA.
EM janet.soul@childrens.harvard.edu
OI Peters, Jurriaan/0000-0002-6725-2814
NR 30
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Z9 6
U1 1
U2 12
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2012
VL 129
IS 3
BP E806
EP E811
DI 10.1542/peds.2011-2078
PG 6
WC Pediatrics
SC Pediatrics
GA 922IQ
UT WOS:000302541000029
PM 22311989
ER
PT J
AU Essig, M
Dinkel, J
Zamecnik, C
AF Essig, M.
Dinkel, J.
Zamecnik, C.
TI Visualization of radiation effects on the central nervous system
SO RADIOLOGE
LA German
DT Article
DE Morbidity; Tumor patients; Magnetic resonance imaging (MRI);
Morphological imaging correlates; Survival time extension
ID INDUCED CAVERNOUS HEMANGIOMAS; CHEMOTHERAPY; THERAPY; BRAIN;
METHOTREXATE; LEUKOENCEPHALOPATHY; ENCEPHALOPATHY; SPECTROSCOPY;
IRRADIATION; LYMPHOMA
AB Therapy-related side effects, which are detectable with magnetic resonance imaging (MRI) at high sensitivity, are one of the most frequent causes of morbidity in cancer patients. They can be observed in the treatment of central nervous system (CNS) diseases as well as in systemic therapy, including whole brain irradiation and chemotherapy and are more often seen due to the better overall survival. This review describes the most frequent acute and chronic therapy-related changes in the CNS and the imaging findings. Acute changes are often reversible while chronic changes can be observed up to several years after treatment.
The differentiation of treatment-related from tumor-related changes might be very difficult, although modern imaging modalities such as MR spectroscopy or MR perfusion measurements supply helpful differential diagnostic information.
C1 [Essig, M.] Univ Klinikum Erlangen, Abt Neuroradiol, D-91054 Erlangen, Germany.
[Dinkel, J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Zamecnik, C.] Deutsch Krebsforschungszentrum, Abt Radiol, Heidelberg, Germany.
RP Essig, M (reprint author), Univ Klinikum Erlangen, Abt Neuroradiol, Schwabachanlage 6, D-91054 Erlangen, Germany.
EM mediag@me.com
NR 30
TC 0
Z9 0
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-832X
J9 RADIOLOGE
JI Radiologe
PD MAR
PY 2012
VL 52
IS 3
BP 229
EP 234
DI 10.1007/s00117-011-2197-8
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 919YU
UT WOS:000302368900005
PM 22476705
ER
PT J
AU Long, M
Kalish, LA
Neufeld, EJ
Grace, RF
AF Long, Michelle
Kalish, Leslie A.
Neufeld, Ellis J.
Grace, Rachael F.
TI Trends in anti-D immune globulin for childhood immune thrombocytopenia:
Usage, response rates, and adverse effects
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID PURPURA; CHILDREN
C1 [Long, Michelle; Neufeld, Ellis J.; Grace, Rachael F.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Kalish, Leslie A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA.
[Kalish, Leslie A.; Neufeld, Ellis J.; Grace, Rachael F.] Harvard Univ, Sch Med, Boston, MA USA.
[Neufeld, Ellis J.; Grace, Rachael F.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Grace, RF (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Karp 8, Boston, MA 02115 USA.
EM rachael.grace@childrens.harvard.edu
OI Grace, Fergal/0000-0002-3144-5999
FU NCRR NIH HHS [UL1 RR025758, UL1 RR 025758]; NHLBI NIH HHS [K24 HL004184]
NR 12
TC 8
Z9 8
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD MAR
PY 2012
VL 87
IS 3
BP 315
EP 317
DI 10.1002/ajh.22261
PG 3
WC Hematology
SC Hematology
GA 894TF
UT WOS:000300449100016
PM 22190130
ER
PT J
AU Kamalian, S
Kamalian, S
Konstas, AA
Maas, MB
Payabvash, S
Pomerantz, SR
Schaefer, PW
Furie, KL
Gonzalez, RG
Lev, MH
AF Kamalian, Shervin
Kamalian, Shahmir
Konstas, A. A.
Maas, M. B.
Payabvash, S.
Pomerantz, S. R.
Schaefer, P. W.
Furie, K. L.
Gonzalez, R. G.
Lev, M. H.
TI CT Perfusion Mean Transit Time Maps Optimally Distinguish Benign
Oligemia from True "At-Risk" Ischemic Penumbra, but Thresholds Vary by
Postprocessing Technique
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID ACUTE STROKE PATIENTS; CEREBRAL-BLOOD-FLOW; SINGULAR-VALUE
DECOMPOSITION; INFARCT CORE; COMPUTED-TOMOGRAPHY; LESION VOLUMES;
DIFFUSION; MR; DELAY; VALIDATION
AB BACKGROUND AND PURPOSE: Various CTP parameters have been used to identify ischemic penumbra. The purpose of this study was to determine the optimal CTP parameter and threshold to distinguish true "at-risk" penumbra from benign oligemia in acute stroke patients without reperfusion.
MATERIALS AND METHODS: Consecutive stroke patients were screened and 23 met the following criteria: 1) admission scanning within 9 hours of onset, 2) CTA confirmation of large vessel occlusion, 3) no late clinical or radiographic evidence of reperfusion, 4) no thrombolytic therapy, 5) DWI imaging within 3 hours of CTP, and 6) either CT or MR follow-up imaging. CTP was postprocessed with commercial software packages, using standard and delay-corrected deconvolution algorithms. Relative cerebral blood flow, volume, and mean transit time (rCBF, rCBV and rMTT) values were obtained by normalization to the uninvolved hemisphere. The admission DWI and final infarct were transposed onto the CTP maps and receiver operating characteristic curve analysis was performed to determine optimal thresholds for each perfusion parameter in defining penumbra destined to infarct.
RESULTS: Relative and absolute MTT identified penumbra destined to infarct more accurately than CBF or CBV*CBF (P < .01). Absolute and relative MTT thresholds for defining penumbra were 12s and 249% for the standard and 13.5s and 150% for the delay-corrected algorithms, respectively.
CONCLUSIONS: Appropriately thresholded absolute and relative MTT-CTP maps optimally distinguish "at-risk" penumbra from benign oligemia in acute stroke patients with large-vessel occlusion and no reperfusion. The precise threshold values may vary, however, depending on the postprocessing technique used for CTP map construction.
C1 [Kamalian, Shervin; Kamalian, Shahmir; Konstas, A. A.; Payabvash, S.; Pomerantz, S. R.; Schaefer, P. W.; Gonzalez, R. G.; Lev, M. H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Maas, M. B.; Furie, K. L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol GRB285, POB 9657, Boston, MA 02114 USA.
EM mlev@partners.org
RI Kamalian, Shervin/D-7667-2013;
OI Kamalian, Shervin/0000-0001-8962-4773; Kamalian,
Shahmir/0000-0002-9640-8144
FU Specialized Programs of Translational Research in Acute Stroke
(SPOTRIAS) Network; NIH [1 P50 NS051343-01A2, R01NS050041]; Agency for
Healthcare Research and Quality (AHRQ) [R01 HS11392-01A1]; Massachusetts
General Hospital Clinical Research Center [1 UL1 RR025758-01]; Harvard
Clinical and Translational Science Center, from the National Center for
Research Resources; SPOTRIAS; National Institutes of Health
(NIH/National Institute of Neurological Disorders and Stroke) [one P50
NS051343-01A2]; GE Healthcare; NIH; Penumbra; NIH SPOTRIAS Network [P50
NS051343]; Agency for Healthcare Research and Quality [R01 HS11392]; MGH
Clinical Research Center [one UL1 RR025758-01]
FX This work was supported by the Specialized Programs of Translational
Research in Acute Stroke (SPOTRIAS) Network grant funded by the NIH (1
P50 NS051343-01A2 and R01NS050041), Agency for Healthcare Research and
Quality grant (AHRQ) R01 HS11392-01A1, and Massachusetts General
Hospital Clinical Research Center (No. 1 UL1 RR025758-01), Harvard
Clinical and Translational Science Center, from the National Center for
Research Resources.; Shahmir Kamalian-RELATED: Grant: SPOTRIAS,
Comments: My salary was from Specialized Programs of Translational
Research in Acute Stroke (SPOTRIAS) Network grant funded by the National
Institutes of Health (NIH/National Institute of Neurological Disorders
and Stroke; one P50 NS051343-01A2). Stuart Pornerantz-discloses research
support from GE Healthcare not related to CT perfusion. Ramon
Gonzalez-RELATED: Grant: NIH,* Penumbra;* UNRELATED: Grants/Grants
Pending: NIH,* Penumbra.* Michael Lev-RELATED: Grant: NIH,* GE
Healthcare,* Comments: Research funding from GE Healthcare for relevant
CT scanning hardware, software, and research assistant support; NIH
SPOTRIAS Network grant (P50 NS051343); Agency for Healthcare Research
and Quality grant (R01 HS11392); MGH Clinical Research Center (No. one
UL1 RR025758-01) Harvard Clinical and Translational Science Center
(National Center for Research Resources); UNRELATED.. Consultancy: GE
Healthcare, CoAxia, Millennium Pharmaceuticals; Grants/Grants Pending:
DOD, NBIB Other: Common stock in GE Healthcare < $10K, Honoraria for
various academic Grand Rounds, National Medical/Imaging meetings, <<
$10K.
NR 24
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U1 0
U2 2
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD MAR
PY 2012
VL 33
IS 3
BP 545
EP 549
DI 10.3174/ajnr.A2809
PG 5
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 913II
UT WOS:000301870300030
PM 22194372
ER
PT J
AU Dominguez, I
Fernandez-del Castillo, C
AF Dominguez, Ismael
Fernandez-del Castillo, Carlos
TI Preoperative platelet-lymphocyte ratio in resected pancreatic ductal
carcinoma: is it meaningful?
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Letter
ID ADENOCARCINOMA
C1 [Dominguez, Ismael] Inst Nacl Ciencias Med Nutr Salvador Zubiran, Dept Surg, Mexico City, DF, Mexico.
[Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Dominguez, I (reprint author), Inst Nacl Ciencias Med Nutr Salvador Zubiran, Dept Surg, Mexico City, DF, Mexico.
NR 4
TC 3
Z9 3
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD MAR
PY 2012
VL 203
IS 3
BP 412
EP 412
DI 10.1016/j.amjsurg.2009.05.022
PG 1
WC Surgery
SC Surgery
GA 911GD
UT WOS:000301704400060
PM 20579970
ER
PT J
AU Mengel, M
Sis, B
Haas, M
Colvin, RB
Halloran, PF
Racusen, LC
Solez, K
Cendales, L
Demetris, AJ
Drachenberg, CB
Farver, CF
Rodriguez, ER
Wallace, WD
Glotz, D
AF Mengel, M.
Sis, B.
Haas, M.
Colvin, R. B.
Halloran, P. F.
Racusen, L. C.
Solez, K.
Cendales, L.
Demetris, A. J.
Drachenberg, C. B.
Farver, C. F.
Rodriguez, E. R.
Wallace, W. D.
Glotz, D.
CA Banff Meeting Report Writing Comm
TI Banff 2011 Meeting Report: New Concepts in Antibody-Mediated Rejection
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Allograft rejection; allograft transplantation; antibody-mediated
rejection; Banff classification
ID DONOR-SPECIFIC ANTIBODIES; KIDNEY-TRANSPLANT RECIPIENTS; PROTOCOL
BIOPSIES; RENAL-ALLOGRAFTS; HLA ANTIBODIES; INJURY; GLOMERULOPATHY;
DESENSITIZATION; ALLOANTIBODY; INFLAMMATION
AB The 11th Banff meeting was held in Paris, France, from June 5 to 10, 2011, with a focus on refining diagnostic criteria for antibody-mediated rejection (ABMR). The major outcome was the acknowledgment of C4d-negative ABMR in kidney transplants. Diagnostic criteria for ABMR have also been revisited in other types of transplants. It was recognized that ABMR is associated with heterogeneous phenotypes even within the same type of transplant. This highlights the necessity of further refining the respective diagnostic criteria, and is of particular significance for the design of randomized clinical trials. A reliable phenotyping will allow for definition of robust end-points. To address this unmet need and to allow for an evidence-based refinement of the Banff classification, Banff Working Groups presented multicenter data regarding the reproducibility of features relevant to the diagnosis of ABMR. However, the consensus was that more data are necessary and further Banff Working Group activities were initiated. A new Banff working group was created to define diagnostic criteria for ABMR in kidneys independent of C4d. Results are expected to be presented at the 12th Banff meeting to be held in 2013 in Brazil. No change to the Banff classification occurred in 2011.
C1 [Mengel, M.; Sis, B.; Solez, K.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada.
[Mengel, M.; Sis, B.; Halloran, P. F.] Univ Alberta, Div Nephrol & Immunol, Alberta Transplant Appl Genom Ctr, Dept Med, Edmonton, AB, Canada.
[Haas, M.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA.
[Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Racusen, L. C.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Cendales, L.] Emory Univ, Sch Med, Emory Transplant Ctr, Atlanta, GA USA.
[Cendales, L.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA.
[Demetris, A. J.] Univ Pittsburgh, Dept Pathol, Div Transplantat Pathol, Pittsburgh, PA USA.
[Drachenberg, C. B.] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA.
[Farver, C. F.; Rodriguez, E. R.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA.
[Wallace, W. D.] Univ Calif Los Angeles, Dept Lab Med & Pathol, Los Angeles, CA USA.
[Glotz, D.] Hosp St Louis, Dept Nephrol, Paris, France.
RP Mengel, M (reprint author), Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada.
EM mmengel@ualberta.ca
RI Halloran, Philip/J-1390-2012
OI Halloran, Philip/0000-0003-1371-1947
FU Astellas; Novartis; Roche; Pfizer; One Lambda; CSL Behring; Transpath;
Alexion; Aperio; Philips; Omnyx; University of Alberta; National Kidney
Foundation; Renal Pathology Society; Astellas Canada; Genzyme; ORS
FX The participants of the 11th Banff Conference gratefully acknowledge the
financial support provided by the following companies and institutions:
Astellas, Novartis, Roche, Pfizer, One Lambda, CSL Behring, Transpath,
Alexion, Aperio, Philips, Omnyx, University of Alberta, National Kidney
Foundation and Renal Pathology Society.; Michael Mengel and Banu Sis
received a research grant from Astellas Canada in support for the Banff
Working Group activities. Michael Mengel is a consultant to Novartis
Canada. Denis Glotz received honoraria/speaker's fees from Roche,
Novartis, Pfizer, Genzyme, Alexion, ORS, CSL Behring. None of the other
authors has any conflicts of interest to disclose as described by the
American Journal of Transplantation.
NR 41
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U1 0
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAR
PY 2012
VL 12
IS 3
BP 563
EP 570
DI 10.1111/j.1600-6143.2011.03926.x
PG 8
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 899QZ
UT WOS:000300832500013
PM 22300494
ER
PT J
AU Berry, K
Ioannou, GN
AF Berry, K.
Ioannou, G. N.
TI Are Patients with Child's A Cirrhosis and Hepatocellular Carcinoma
Appropriate Candidates for Liver Transplantation?
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Child's A Cirrhosis; hepatocellular carcinoma; liver transplantation;
posttransplantation survival; survival benefit
ID PERCUTANEOUS RADIOFREQUENCY ABLATION; RANDOMIZED CONTROLLED-TRIAL;
TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; SURGICAL RESECTION; ETHANOL
INJECTION; SURVIVAL BENEFIT; TRANSARTERIAL CHEMOEMBOLIZATION; CONVENIENT
APPROXIMATION; MULTIVARIATE-ANALYSIS; PROGNOSTIC-FACTORS
AB We aimed to estimate the survival benefit derived from transplantation in patients with stage II hepatocellular carcinoma (HCC) and Child's A cirrhosis, defined as the mean lifetime with transplantation minus the mean lifetime with treatments other than transplantation. We calculated the posttransplantation survival of all adult, first-time, deceased-donor, liver transplant recipients in the United States since the introduction of the Model for End-Stage Liver Disease based priority system in February 2002 (n = 36 791). We estimated the posttreatment survival of patients with Child's A cirrhosis and stage II HCC treated by radiofrequency ablation (RFA) +/- transarterial chemoembolization (TACE) or surgical resection by conducting a systematic review of the medical literature. In patients with Child's A cirrhosis and stage II HCC, the estimated median survival benefit of liver transplantation compared to RFA +/- TACE was 1.5 months at 3 years (range -3.5 to 5.6) and 5.7 months at 5 years (range 0.711.4), whereas compared to surgical resection it was 0.7 months at 3 years (range -2.9 to 3) and 2.8 months at 5 years (range -4.4 to 5.7). Liver transplantation in patients with stage II HCC and Child's A cirrhosis results in a very low survival benefit and may not constitute optimal use of scarce liver donor organs.
C1 [Ioannou, G. N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA.
[Berry, K.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Ioannou, G. N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA.
RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA.
EM georgei@medicine.washington.edu
FU Health Resources and Services Administration [231-00-0115]; Office of
Research and Development, Veterans Affairs
FX This research was based on data derived from the United Network for
Organ Sharing (UNOS) on January 21, 2011. This work was supported in
part by Health Resources and Services Administration contract
231-00-0115. G.N.I. was supported by Research Enhancement Award Program,
Office of Research and Development, Veterans Affairs. The content is the
responsibility of the authors alone and does not necessarily reflect the
views or policies of the Department of Health and Human Services.
NR 48
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U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAR
PY 2012
VL 12
IS 3
BP 706
EP 717
DI 10.1111/j.1600-6143.2011.03853.x
PG 12
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 899QZ
UT WOS:000300832500027
PM 22123435
ER
PT J
AU Stagakis, E
Bertsias, G
Verginis, P
Nakou, M
Hatziapostolou, M
Sidiropoulos, P
Goulielmos, G
Iliopoulos, D
Boumpas, DT
AF Stagakis, E.
Bertsias, G.
Verginis, P.
Nakou, M.
Hatziapostolou, Maria
Sidiropoulos, P.
Goulielmos, G.
Iliopoulos, D.
Boumpas, D. T.
TI REGULATION OF T CELL HYPERACTIVITY IN SLE: THE NEGATIVE CO-STIMULATORY
MOLECULE PD-1 REGULATES MIR-21 EXPRESSION IN SLE T LYMPHOCYTES
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
CT 32nd European Workshop for Rheumatology Research
CY FEB 23-25, 2012
CL Stockholm, SWEDEN
C1 [Stagakis, E.; Bertsias, G.; Verginis, P.; Nakou, M.; Boumpas, D. T.] Univ Crete, Sch Med, Lab Autoimmun & Inflammat, Iraklion, Greece.
[Hatziapostolou, Maria; Sidiropoulos, P.; Goulielmos, G.; Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD MAR
PY 2012
VL 71
SU 1
BP A58
EP A58
DI 10.1136/annrheumdis-2011-201236.18
PG 1
WC Rheumatology
SC Rheumatology
GA 919KF
UT WOS:000302323600133
ER
PT J
AU Bernstein, EJ
Isakova, T
Sullivan, ME
Chibnik, LB
Bazari, H
Wolf, MS
Kay, J
AF Bernstein, Elana J.
Isakova, Tamara
Sullivan, Mary E.
Chibnik, Lori B.
Bazari, Hasan
Wolf, Myles S.
Kay, Jonathan
TI HYPOPHOSPHATEMIA IS ASSOCIATED WITH NEPHROGENIC SYSTEMIC FIBROSIS: A
CASE-CONTROL STUDY
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
CT 32nd European Workshop for Rheumatology Research
CY FEB 23-25, 2012
CL Stockholm, SWEDEN
C1 [Bernstein, Elana J.] Hosp Special Surg, New York, NY 10021 USA.
[Isakova, Tamara; Wolf, Myles S.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Sullivan, Mary E.; Bazari, Hasan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chibnik, Lori B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kay, Jonathan] Univ Massachusetts, Sch Med, Worcester, MA 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 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD MAR
PY 2012
VL 71
SU 1
DI 10.1136/annrheumdis-2011-201237.26
PG 1
WC Rheumatology
SC Rheumatology
GA 919KF
UT WOS:000302323600166
ER
PT J
AU Krasoudaki, E
Stagakis, E
Loupasakis, K
Papagianni, A
Alexopoulos, E
Bertsias, G
Iliopoulos, D
Boumpas, DT
AF Krasoudaki, E.
Stagakis, E.
Loupasakis, K.
Papagianni, A.
Alexopoulos, E.
Bertsias, G.
Iliopoulos, D.
Boumpas, D. T.
TI IDENTIFICATION OF A NOVEL MICRORNA-GENE CIRCUIT IN HUMAN LUPUS
NEPHRITIS: EVIDENCE FOR MODULATION OF KALLIKREIN GENES BY MIR-422A
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
CT 32nd European Workshop for Rheumatology Research
CY FEB 23-25, 2012
CL Stockholm, SWEDEN
C1 [Krasoudaki, E.; Stagakis, E.; Bertsias, G.; Boumpas, D. T.] Univ Crete, Sch Med, Lab Autoimmun & Inflammat, Iraklion, Greece.
[Loupasakis, K.; Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Papagianni, A.; Alexopoulos, E.] Aristotle Univ Thessaloniki, Dept Nephrol, Gen Hosp Thessaloniki Hippokrat, GR-54006 Thessaloniki, Greece.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD MAR
PY 2012
VL 71
SU 1
DI 10.1136/annrheumdis-2011-201236.1
PG 1
WC Rheumatology
SC Rheumatology
GA 919KF
UT WOS:000302323600116
ER
PT J
AU Mountz, JD
Li, J
Hsu, HC
AF Mountz, John D.
Li, Jun
Hsu, Hui-Chen
TI Systemic autoimmunity caused by fas deficiency in macrophages: A new
perspective on the first identified autoimmunity gene
SO ARTHRITIS AND RHEUMATISM
LA English
DT Editorial Material
ID CELL-DEATH; MICE; LIGAND; ACTIVATION; APOPTOSIS; DISEASE; ANTIGEN;
DEGRADATION; PREVENTION; ABLATION
C1 [Mountz, John D.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA.
[Mountz, John D.; Hsu, Hui-Chen] Birmingham VA Med Ctr, Birmingham, AL USA.
RP Mountz, JD (reprint author), Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, 701 S 19th St,Room 473 LHRB, Birmingham, AL 35294 USA.
EM jdmountz@uab.edu
FU NIAID NIH HHS [R01-AI-083705-01A2, 1-AI-071110-01A1, R01-AI-71110-02S1]
NR 18
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 609
EP 612
DI 10.1002/art.34321
PG 4
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900003
PM 22139895
ER
PT J
AU Kezic, JM
Davey, MP
Glant, TT
Rosenbaum, JT
Rosenzweig, HL
AF Kezic, Jelena M.
Davey, Michael P.
Glant, Tibor T.
Rosenbaum, James T.
Rosenzweig, Holly L.
TI Interferon-gamma regulates discordant mechanisms of uveitis versus joint
and axial disease in a murine model resembling spondylarthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID PROTEOGLYCAN-INDUCED ARTHRITIS; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS;
ENDOTOXIN-INDUCED UVEITIS; ACUTE ANTERIOR UVEITIS;
ANKYLOSING-SPONDYLITIS; T-CELLS; INTRAVITAL MICROSCOPY; GENETIC-CONTROL;
SYNOVIAL-FLUID; BALB/C MICE
AB Objective The spondylarthritides (such as ankylosing spondylitis) are multisystem inflammatory diseases that frequently result in uveitis. Despite the common co-occurrence of uveitis with arthritis, there has been no explanation for the susceptibility of the eye to inflammation. Using an innovative intravital videomicroscopic approach, we discovered the coexistence of uveitis with axial and peripheral joint inflammation in mice immunized with cartilage proteoglycan (PG). The aim of this study was to elucidate the characteristics of uveitis and test the impact of interferon-? (IFN?) deficiency on the eye versus the joint and spine. Methods. Female T cell receptor (TCR)-transgenic mice or IFN gamma -knockout mice crossed to TCR-transgenic mice were immunized with PG. Uveitis was assessed by intravital videomicroscopy and histology. The clinical and histopathologic severity of arthritis and spondylitis were evaluated. The bone remodeling process within the spine was assessed by whole-body near-infrared imaging. Immunoblotting and immunofluorescence staining were used to examine the expression of PG and ADAMTS-5 and to examine the cellular composition of eyes with uveitis. Results. PG neoepitopes along with the aggrecanase ADAMTS-5 were present in the eye, as they were the joint. Anterior uveitis developed in response to PG immunization. The cellular infiltrate consisted mainly of neutrophils and eosinophils. Unexpectedly, IFN gamma deficiency markedly exacerbated uveitis while ameliorating joint and spine disease, indicating divergent mechanisms that drive diseases in the eye versus the joints and spine. Conclusion. This study provides the first detailed description of a murine disease model in which uveitis coincides with arthritis and spondylitis. Our observations provide a great opportunity for understanding the pathogenesis of a relatively common but poorly understood disease.
C1 [Kezic, Jelena M.; Davey, Michael P.; Rosenbaum, James T.; Rosenzweig, Holly L.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Davey, Michael P.; Rosenzweig, Holly L.] Portland VA Med Ctr, Portland, OR 97239 USA.
[Glant, Tibor T.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
RP Rosenzweig, HL (reprint author), Oregon Hlth & Sci Univ, Mail Stop L 467 AD,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM rosenzwh@ohsu.edu
FU NIH (National Eye Institute) [EY-021733, EY-019020, EY-019604]; William
and Mary Bauman Foundation; Stan and Madelle Rosenfeld Family Trust;
William C. Kuzell Foundation; American College of Rheumatology Research
and Education Foundation; Research to Prevent Blindness Foundation;
Novartis; Amgen
FX Supported by the NIH (National Eye Institute grants EY-021733,
EY-019020, and EY-019604), the William and Mary Bauman Foundation, the
Stan and Madelle Rosenfeld Family Trust, and the William C. Kuzell
Foundation. Dr. Rosenzweig's work was also supported by the American
College of Rheumatology Research and Education Foundation and the
Research to Prevent Blindness Foundation.; Dr. Rosenbaum has received
consulting fees, speaking fees, and/or honoraria from Novartis and Amgen
(less than $10,000 each).
NR 44
TC 7
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 762
EP 771
DI 10.1002/art.33404
PG 10
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900020
PM 21987263
ER
PT J
AU Schumacher, HR
Sundy, JS
Terkeltaub, R
Knapp, HR
Mellis, SJ
Stahl, N
Yancopoulos, GD
Soo, Y
King-Davis, S
Weinstein, SP
Radin, AR
AF Schumacher, H. Ralph, Jr.
Sundy, John S.
Terkeltaub, Robert
Knapp, Howard R.
Mellis, Scott J.
Stahl, Neil
Yancopoulos, George D.
Soo, Yuhwen
King-Davis, Shirletta
Weinstein, Steven P.
Radin, Allen R.
CA 0619 Study Grp
TI Rilonacept (interleukin-1 trap) in the prevention of acute gout flares
during initiation of urate-lowering therapy: Results of a phase II
randomized, double-blind, placebo-controlled trial
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID ALLOPURINOL; ARTHRITIS; MANAGEMENT; CARE; INHIBITION; CRYSTALS;
ANAKINRA; RISK
AB Objective To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy.
Methods. In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained.
Results. Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015).
Conclusion. The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.
C1 [Schumacher, H. Ralph, Jr.] Univ Penn, VA Med Ctr, Philadelphia, PA 19104 USA.
[Schumacher, H. Ralph, Jr.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Sundy, John S.] Duke Univ, Med Ctr, Durham, NC USA.
[Terkeltaub, Robert] Univ Calif San Diego, San Diego, CA 92103 USA.
[Terkeltaub, Robert] San Diego VA Med Ctr, San Diego, CA USA.
[Knapp, Howard R.] Montana State Univ, Billings, MT USA.
[Mellis, Scott J.; Stahl, Neil; Yancopoulos, George D.; Soo, Yuhwen; King-Davis, Shirletta; Weinstein, Steven P.; Radin, Allen R.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
RP Schumacher, HR (reprint author), Univ Penn, VA Med Ctr, 151K,Univ & Woodland Avenues, Philadelphia, PA 19104 USA.
EM schumacr@mail.med.upenn.edu
FU Regeneron Pharmaceuticals, Inc.; Regeneron; Takeda; Savient; Ardea;
Pfizer; Xoma; Novartis; Regeneron through Duke University; URL Pharma
FX Supported by Regeneron Pharmaceuticals, Inc.; Dr. Schumacher has
received consulting fees, speaking fees, and/or honoraria from
Regeneron, Takeda, Savient, Ardea, Pfizer, Xoma, and Novartis (less than
$10,000 each). Dr. Sundy has received consulting fees from Regeneron and
Novartis (less than $10,000 each) and receives sponsored research grants
from Regeneron through Duke University. Dr. Terkeltaub has received
consulting fees, speaking fees, and/or honoraria from Regeneron,
Novartis, and URL Pharma (less than $10,000 each) and has served as a
paid consultant to the investment analysts Guidepoint Global and the
Coleman Group. Drs. Mellis, Stahl, Yancopoulos, Soo, Weinstein, and
Radin and Ms King-Davis own stock in Regeneron. Dr. Mellis holds a
patent, licensed to Regeneron, for the use of interleukin-1 antagonists
to treat gout.
NR 26
TC 43
Z9 45
U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 876
EP 884
DI 10.1002/art.33412
PG 9
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900032
PM 22223180
ER
PT J
AU Gardiner, DM
Holmes, LB
AF Gardiner, David M.
Holmes, Lewis B.
TI Hypothesis: Terminal transverse limb defects with "nubbins" represent a
regenerative process during limb development in human fetuses
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
DE terminal transverse limb defects; nubbins; regeneration
ID FINGERTIP; INJURIES; DAUGHTER; CELLS; MICE
AB BACKGROUND Terminal transverse limb defects with nubbins occur in one arm at one of several levels (distal humerus, proximal forearm, wrist, and at the metacarpal-phalangeal joint in the hand). The associated nubbins contain osteocartilaginous tissue and small nails and are not associated with evidence of amnion disruption. METHODS: We present affected newborn infants whose terminal transverse limb defects are at one of these three levels: proximal forearm, elbow, or metacarpal-phalangeal joint. RESULTS: We hypothesize that the presence of residual digit-like structures reflects a regenerative process that has occurred during limb development in these infants. DISCUSSION: Only limited regeneration of digit-like structures can occur in the human fetus. Birth Defects Research (Part A) 94:129-133, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Holmes, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, Genet Unit,MassGen Hosp Children, Boston, MA 02114 USA.
[Gardiner, David M.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
RP Holmes, LB (reprint author), Harvard Univ, Sch Med, Dept Pediat, Genet Unit,MassGen Hosp Children, 175 Cambridge St,Room 504, Boston, MA 02114 USA.
EM holmes.lewis@mgh.harvard.edu
NR 24
TC 1
Z9 1
U1 0
U2 4
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 MAR
PY 2012
VL 94
IS 3
BP 129
EP 133
DI 10.1002/bdra.22876
PG 5
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 907QX
UT WOS:000301433600002
PM 22287196
ER
PT J
AU Lui, KO
Bu, L
Li, RA
Chan, CW
AF Lui, Kathy O.
Bu, Lei
Li, Ronald A.
Chan, Camie W.
TI Pluripotent Stem Cell-based Heart Regeneration: From the Developmental
and Immunological Perspectives
SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS
LA English
DT Review
DE stem cells; ESC; iPSC; heart development; immunogenicity; regenerative
medicine; transplantation
ID REGULATORY T-CELLS; BHLH TRANSCRIPTION FACTOR; MODIFIED MESSENGER-RNA;
CARDIOVASCULAR PROGENITORS; MYOCARDIAL-INFARCTION; HUMAN FIBROBLASTS;
COSTIMULATION BLOCKADE; CARDIAC MORPHOGENESIS; TOLERANCE INDUCTION;
SMOOTH-MUSCLE
AB Heart diseases such as myocardial infarction cause massive loss of cardiomyocytes, but the human heart lacks the innate ability to regenerate. In the adult mammalian heart, a resident progenitor cell population, termed epicardial progenitors, has been identified and reported to stay quiescent under uninjured conditions; however, myocardial infarction induces their proliferation and de novo differentiation into cardiac cells. It is conceivable to develop novel therapeutic approaches for myocardial repair by targeting such expandable sources of cardiac progenitors, thereby giving rise to new muscle and vasculatures. Human pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells can self-renew and differentiate into the three major cell types of the heart, namely cardiomyocytes, smooth muscle, and endothelial cells. In this review, we describe our current knowledge of the therapeutic potential and challenges associated with the use of pluripotent stem cell and progenitor biology in cell therapy. An emphasis is placed on the contribution of paracrine factors in the growth of myocardium and neovascularization as well as the role of immunogenicity in cell survival and engraftment. (Part C) 96:98-107, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Lui, Kathy O.; Bu, Lei; Li, Ronald A.; Chan, Camie W.] Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Pokfulam, Hong Kong, Peoples R China.
[Lui, Kathy O.; Bu, Lei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Lui, Kathy O.; Bu, Lei] Harvard Stem Cell Inst, Boston, MA 02114 USA.
[Li, Ronald A.] Univ Hong Kong, LKS Fac Med, Dept Med, Pokfulam, Hong Kong, Peoples R China.
[Li, Ronald A.] Univ Hong Kong, LKS Fac Med, Dept Physiol, Pokfulam, Hong Kong, Peoples R China.
[Chan, Camie W.] Univ Hong Kong, LKS Fac Med, Dept Anat, Pokfulam, Hong Kong, Peoples R China.
[Li, Ronald A.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY USA.
RP Chan, CW (reprint author), Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Pokfulam, Hong Kong, Peoples R China.
EM ronald.li@mssm.edu; camchan@hku.hk
RI Lui, Kathy O./E-4883-2015
OI Lui, Kathy O./0000-0002-1616-3643
NR 95
TC 4
Z9 6
U1 2
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1542-975X
J9 BIRTH DEFECTS RES C
JI Birth Defects Res. Part C-Embryo Today-Rev.
PD MAR
PY 2012
VL 96
IS 1
BP 98
EP 108
DI 10.1002/bdrc.21004
PG 11
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 918YO
UT WOS:000302287800008
PM 22457181
ER
PT J
AU Gee, AO
Baker, BM
Silverstein, AM
Montero, G
Esterhai, JL
Mauck, RL
AF Gee, Albert O.
Baker, Brendon M.
Silverstein, Amy M.
Montero, Giana
Esterhai, John L.
Mauck, Robert L.
TI Fabrication and evaluation of biomimetic-synthetic nanofibrous
composites for soft tissue regeneration
SO CELL AND TISSUE RESEARCH
LA English
DT Article
DE Tissue engineering; Mechanical properties; Nanofiber; Scaffolds;
Electrospinning; Mesenchymal stem cells
ID HUMAN ARTICULAR-CARTILAGE; CROSS-LINKING AGENT; ENGINEERING SCAFFOLDS;
IN-VITRO; EXTRACELLULAR-MATRIX; CELLULAR INFILTRATION; ELECTROSPUN
SCAFFOLDS; GELATIN MICROSPHERES; COLLAGEN NANOFIBERS; BIOLOGICAL TISSUE
AB Electrospun scaffolds hold promise for the regeneration of dense connective tissues, given their nanoscale topographies, provision of directional cues for infiltrating cells and versatile composition. Synthetic slow-degrading scaffolds provide long-term mechanical support and nanoscale instructional cues; however, these scaffolds suffer from a poor infiltration rate. Alternatively, nanofibrous constructs formed from natural biomimetic materials (such as collagen) rapidly infiltrate but provide little mechanical support. To take advantage of the positive features of these constructs, we have developed a composite scaffold consisting in both a biomimetic fiber fraction (i.e., Type I collagen nanofibers) together with a traditional synthetic (i.e., poly-[epsilon-caprolactone], PCL) fiber fraction. We hypothesize that inclusion of biomimetic elements will improve initial cell adhesion and eventual scaffold infiltration, whereas the synthetic elements will provide controlled and long-term mechanical support. We have developed a method of forming and crosslinking collagen nanofibers by using the natural crosslinking agent genipin (GP). Further, we have formed composites from collagen and PCL and evaluated the long-term performance of these scaffolds when seeded with mesenchymal stem cells. Our results demonstrate that GP crosslinking is cytocompatible and generates stable nanofibrous type I collagen constructs. Composites with varying fractions of the biomimetic and synthetic fiber families are formed and retain their collagen fiber fractions during in vitro culture. However, at the maximum collagen fiber fractions (20%), cell ingress is limited compared with pure PCL scaffolds. These results provide a new foundation for the development and optimization of biomimetic/synthetic nanofibrous composites for in vivo tissue engineering.
C1 [Gee, Albert O.; Baker, Brendon M.; Silverstein, Amy M.; Montero, Giana; Esterhai, John L.; Mauck, Robert L.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA.
[Baker, Brendon M.; Silverstein, Amy M.; Montero, Giana; Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
[Esterhai, John L.; Mauck, Robert L.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
RP Mauck, RL (reprint author), Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, 424G Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA.
EM lemauck@mail.med.upenn.edu
FU National Institutes of Health [R01 AR056624]; Department of Veterans'
Affairs [I01 RX000174]; Penn Center for Musculoskeletal Disorders [P30
AR050950]; Penn Department of Orthopaedic Surgery; National Science
Foundation
FX This work was supported by the National Institutes of Health (R01
AR056624, RLM), The Department of Veterans' Affairs (I01 RX000174, JLE)
and the Penn Center for Musculoskeletal Disorders (P30 AR050950, RLM).
Additional support was provided by the Penn Department of Orthopaedic
Surgery (AOG) and a graduate fellowship from the National Science
Foundation (BMB).
NR 67
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U1 3
U2 45
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD MAR
PY 2012
VL 347
IS 3
BP 803
EP 813
DI 10.1007/s00441-011-1308-1
PG 11
WC Cell Biology
SC Cell Biology
GA 916YG
UT WOS:000302138500027
PM 22287042
ER
PT J
AU Moriggi, L
Yaseen, MA
Helm, L
Caravan, P
AF Moriggi, Loick
Yaseen, Mohammad A.
Helm, Lothar
Caravan, Peter
TI Serum Albumin Targeted, pH-Dependent Magnetic Resonance Relaxation
Agents
SO CHEMISTRY-A EUROPEAN JOURNAL
LA English
DT Article
DE gadolinium; imaging; imaging agents; second-sphere relaxation; serum
albumin
ID MRI CONTRAST AGENTS; SPHERE WATER-MOLECULES; N-B TRANSITION; TUMOR PH;
O-17 NMR; IN-VIVO; RELAXIVITY; BINDING; COMPLEXES; GADOLINIUM
AB The objective of this work was the synthesis of serum albumin targeted, GdIII-based magnetic resonance imaging (MRI) contrast agents exhibiting a strong pH-dependent relaxivity. Two new complexes (Gd-glu and Gd-bbu) were synthesized based on the DO3A macrocycle modified with three carboxyalkyl substituents a to the three ring nitrogen atoms, and a biphenylsulfonamide arm. The sulfonamide nitrogen coordinates the Gd in a pH-dependent fashion, resulting in a decrease in the hydration state, q, as pH is increased and a resultant decrease in relaxivity (r1). In the absence of human serum albumin (HSA), r1 increases from 2.0 to 6.0 mM-1?s-1 for Gd-glu and from 2.4 to 9.0 mM-1?s-1 for Gd-bbu from pH 5 to 8.5 at 37?degrees C, 0.47 T, respectively. These complexes (0.2 mM) are bound (>98.9?%) to HSA (0.69 mM) over the pH range 58.5. Binding to albumin increases the rotational correlation time and results in higher relaxivity. The r1 increased 120?% (pH 5) and 550?% (pH 8.5) for Gd-glu and 42?% (pH 5) and 260?% (pH 8.5) for Gd-bbu. The increases in r1 at pH 5 were unexpectedly low for a putative slow tumbling q=2 complex. The Gd-bbu system was investigated further. At pH 5, it binds in a stepwise fashion to HSA with dissociation constants Kd1=0.65, Kd2=18, Kd3=1360 mu M. The relaxivity at each binding site was constant. Luminescence lifetime titration experiments with the EuIII analogue revealed that the inner-sphere water ligands are displaced when the complex binds to HSA resulting in lower than expected r1 at pH 5. Variable pH and temperature nuclear magnetic relaxation dispersion (NMRD) studies showed that the increased r1 of the albumin-bound q=0 complexes is due to the presence of a nearby water molecule with a long residency time (12 ns). The distance between this water molecule and the Gd ion changes with pH resulting in albumin-bound pH-dependent relaxivity.
C1 [Moriggi, Loick; Yaseen, Mohammad A.; Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Moriggi, Loick; Yaseen, Mohammad A.; Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Helm, Lothar] Ecole Polytech Fed Lausanne, BCH, Inst Chim Mol & Biol, CH-1015 Lausanne, Switzerland.
RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM caravan@nmr.mgh.harvard.edu
FU Swiss National Science Foundation [PBELP2-130907]; National Institute of
Biomedical Imaging and Bio-engineering [R01EB009062, R21EB009738];
National Institute of Neurological Disorders and Stroke [R01NS057476]
FX L.M. acknowledges the Swiss National Science Foundation for a fellowship
(PBELP2-130907). Fabrice Yerly is thanked for providing the program
VISUALISEUR/OPTIMISEUR, version 2.3.7 (2010) for least-squares fitting
of the NMRD data and the pKa experiment. We thank Zhaoda
Zhang for helpful discussions regarding the synthesis. This work was
supported by the National Institute of Biomedical Imaging and
Bio-engineering (award numbers: R01EB009062 and R21EB009738) and the
National Institute of Neurological Disorders and Stroke (R01NS057476).
NR 61
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U1 1
U2 34
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 0947-6539
EI 1521-3765
J9 CHEM-EUR J
JI Chem.-Eur. J.
PD MAR
PY 2012
VL 18
IS 12
BP 3675
EP 3686
DI 10.1002/chem.201103344
PG 12
WC Chemistry, Multidisciplinary
SC Chemistry
GA 907UR
UT WOS:000301444900028
PM 22328098
ER
PT J
AU Blankstein, R
Ahmed, W
Bamberg, F
Rogers, IS
Schlett, CL
Nasir, K
Fontes, J
Tawakol, A
Brady, TJ
Nagurney, JT
Hoffmann, U
Truong, QA
AF Blankstein, Ron
Ahmed, Waleed
Bamberg, Fabian
Rogers, Ian S.
Schlett, Christopher Lothar
Nasir, Khurram
Fontes, Joao
Tawakol, Ahmed
Brady, Thomas J.
Nagurney, John T.
Hoffmann, Udo
Truong, Quynh A.
TI Comparison of Exercise Treadmill Testing With Cardiac Computed
Tomography Angiography Among Patients Presenting to the Emergency Room
With Chest Pain The Rule Out Myocardial Infarction Using
Computer-Assisted Tomography (ROMICAT) Study
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiovascular CT; exercise testing; coronary artery disease; stress
testing
ID CORONARY-ARTERY-DISEASE; ASSOCIATION TASK-FORCE; 2002 GUIDELINE UPDATE;
HEART-ASSOCIATION; AMERICAN-COLLEGE; CARDIOVASCULAR RISK; DEPARTMENT
PATIENTS; PROGNOSTIC VALUE; TRIAL; CARDIOLOGY
AB Background-The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA.
Methods and Results-The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect >50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a >70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis >50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men <40 years old or women <50 years old or individuals who achieved at least 13 metabolic equivalents on ETT.
Conclusions-Among low-to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of >50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA. (Circ Cardiovasc Imaging. 2012;5:233-242.)
C1 [Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med,Dept Med, Boston, MA 02115 USA.
[Nasir, Khurram] Yale Univ, Sect Cardiovasc Med, New Haven, CT USA.
[Fontes, Joao] NHLBI, Framingham, MA USA.
[Fontes, Joao] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Ahmed, Waleed; Bamberg, Fabian; Rogers, Ian S.; Schlett, Christopher Lothar; Tawakol, Ahmed; Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA.
[Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Tawakol, Ahmed; Brady, Thomas J.; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
[Nagurney, John T.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Blankstein, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med,Dept Med, 75 Francis St,Room Shapiro 5096, Boston, MA 02115 USA.
EM rblankstein@parters.org
FU National Institutes of Health (NIH) [R01 HL080053, T32HL076136,
K23HL098370, L30HL093896]
FX This work was supported by the National Institutes of Health (NIH) (R01
HL080053). Drs Blankstein, Ahmed, Rogers, and Truong received support
from NIH grant T32HL076136. Dr Truong also received support from NIH
grants K23HL098370 and L30HL093896.
NR 26
TC 16
Z9 16
U1 0
U2 4
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 MAR
PY 2012
VL 5
IS 2
BP 233
EP 242
DI 10.1161/CIRCIMAGING.111.969568
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 916SE
UT WOS:000302122700012
PM 22308274
ER
PT J
AU Reynolds, MR
Gunnarsson, CL
Hunter, TD
Ladapo, JA
March, JL
Zhang, MD
Hao, SC
AF Reynolds, Matthew R.
Gunnarsson, Candace L.
Hunter, Tina D.
Ladapo, Joseph A.
March, Jamie L.
Zhang, Mingdong
Hao, Steven C.
TI Health Outcomes With Catheter Ablation or Antiarrhythmic Drug Therapy in
Atrial Fibrillation Results of a Propensity-Matched Analysis
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE fibrillation; catheter ablation; stroke; heart failure; antiarrhythmia
agents
ID QUALITY-OF-LIFE; HEART-FAILURE; RISK-FACTORS; RADIOFREQUENCY ABLATION;
LONG-TERM; FOLLOW-UP; STROKE; ANTICOAGULATION; PREVALENCE; MORTALITY
AB Background-Patients with atrial fibrillation (AF) face significant risks of stroke and heart failure. The objective of this study was to determine whether AF ablation reduces the long-term risk of stroke or heart failure compared with antiarrhythmic drug therapy.
Methods and Results-A coding algorithm was used to identify AF patients treated with catheter ablation (n=3194) or antiarrhythmic drugs without ablation (n=6028) between 2005 and 2009 using The MarketScan Research Database from Thomson Reuters From this sample, 801 pairs were propensity matched, based on 15 demographic and clinical characteristics and baseline medication use. Rates of stroke/transient ischemic attack (TIA) and heart failure hospitalizations for up to 3 years were examined. Patients treated with catheter ablation had a significantly lower rate of stroke or TIA (3.4% per year) than a group of patients with AF managed with antiarrhythmic drugs only (5.5% per year), with an unadjusted hazard ratio of 0.62 (95% CI, 0.44-0.86; P=0.005). The rates for heart failure hospitalization were 1.5% per year in the ablation group and 2.2% per year in the antiarrhythmic drug group, with an unadjusted hazard ratio of 0.69 (95% CI, 0.42-1.15; P=0.158). These results were minimally altered in Cox proportional hazards models, which further adjusted for potential confounders not well balanced by the propensity matching.
Conclusions-In a large propensity-matched community sample, AF ablation was associated with a reduced risk of stroke/TIA and no significant difference in heart failure hospitalizations compared with antiarrhythmic drug therapy. These findings require confirmation with randomized study designs. (Circ Cardiovasc Qual Outcomes. 2012;5:171-181.)
C1 [Reynolds, Matthew R.] Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA.
[Reynolds, Matthew R.] VA Boston Healthcare Syst, Boston, MA USA.
[Gunnarsson, Candace L.; Hunter, Tina D.] S2 Stat Solut Inc, Cincinnati, OH 45241 USA.
[Ladapo, Joseph A.] NYU, Sch Med, Dept Med, New York, NY USA.
[March, Jamie L.; Zhang, Mingdong] Biosense Webster Inc, Diamond Bar, CA USA.
[Hao, Steven C.] Sutter Pacific Med Fdn, San Francisco, CA USA.
RP Gunnarsson, CL (reprint author), S2 Stat Solut Inc, 11176 Main St, Cincinnati, OH 45241 USA.
EM candaceg@s2stats.com
OI Ladapo, Joseph/0000-0002-8518-4800
FU Biosense Webster, Inc, Diamond Bar, CA; Biosense Webster, Inc; Sanofi
Aventis; St Jude Medical; Medtronic, Inc.
FX This study was funded by Biosense Webster, Inc, Diamond Bar, CA.; Dr
Reynolds has received research grant support from Biosense Webster, Inc,
and Sanofi Aventis; and consulting fees from Biosense Webster, Inc,
Sanofi Aventis, St Jude Medical, and Medtronic, Inc. Drs Gunnarsson and
Hunter are employed by and Dr Ladapo is a paid consultant to
S2 Statistical Solutions, Inc, which is a paid consultant
firm to Biosense Webster, Inc. Ms March and Dr Zhang are employees of
Biosense Webster, Inc. Dr Hao has received consulting fees from Biosense
Webster, Inc, and Medtronic, Inc.
NR 25
TC 35
Z9 37
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2012
VL 5
IS 2
BP 171
EP U71
DI 10.1161/CIRCOUTCOMES.111.963108
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RG
UT WOS:000302120300010
PM 22373904
ER
PT J
AU Yeh, RW
Normand, SLT
Wang, Y
Barr, CD
Dominici, F
AF Yeh, Robert W.
Normand, Sharon-Lise T.
Wang, Yun
Barr, Christopher D.
Dominici, Francesca
TI Geographic Disparities in the Incidence and Outcomes of Hospitalized
Myocardial Infarction Does a Rising Tide Lift All Boats?
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE myocardial infarction; Medicare; trends; disparities
ID FEE-FOR-SERVICE; UNITED-STATES; REGIONAL-VARIATION;
CARDIOVASCULAR-DISEASE; CORONARY-ANGIOGRAPHY; MORTALITY-RATES;
HEART-DISEASE; SMOKING BAN; US ADULTS; TRENDS
AB Background-Improvements in prevention have led to declines in incidence and mortality of myocardial infarction (MI) in selected populations. However, no studies have examined regional differences in recent trends in MI incidence, and few have examined whether known regional disparities in MI care have narrowed over time.
Methods and Results-We compared trends in incidence rates of MI, associated procedures and mortality for all US Census Divisions (regions) in Medicare fee-for-service patients between 2000-2008 (292 773 151 patient-years). Two-stage hierarchical models were used to account for patient characteristics and state-level random effects. To assess trends in geographic disparities, we calculated changes in between-state variance for outcomes over time. Although the incidence of MI declined in all regions (P<0.001 for trend for each) between 2000-2008, adjusted rates of decline varied by region (annual declines ranging from 2.9-6.1%). Widening geographic disparities, as measured by percent change of between-state variance from 2000-2008, were observed for MI incidence (37.6% increase, P=0.03) and percutaneous coronary intervention rates (31.4% increase, P=0.06). Significant declines in risk-adjusted 30-day mortality were observed in all regions, with the fastest declines observed in states with higher baseline mortality rates.
Conclusions-In a large contemporary analysis of geographic trends in MI epidemiology, the incidence of MI and associated mortality declined significantly in all US Census Divisions between 2000-2008. Although geographic disparities in MI incidence may have increased, regional differences in MI-associated mortality have narrowed. (Circ Cardiovasc Qual Outcomes. 2012;5:197-204.)
C1 [Yeh, Robert W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02114 USA.
[Normand, Sharon-Lise T.; Barr, Christopher D.; Dominici, Francesca] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.; Wang, Yun] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Barr, Christopher D.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA.
RP Yeh, RW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, GRB8-843,55 Fruit St, Boston, MA 02114 USA.
EM ryeh@partners.org
FU National Institute of Environmental Health Sciences [R01ES012054];
Environmental Protection Agency [EPA RD83479801, EPA RD83489401]
FX This project was supported by Award No. R01ES012054 from the National
Institute of Environmental Health Sciences and Award Nos. EPA RD83479801
and EPA RD83489401 from the Environmental Protection Agency.
NR 30
TC 15
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2012
VL 5
IS 2
BP 197
EP U103
DI 10.1161/CIRCOUTCOMES.111.962456
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RG
UT WOS:000302120300013
PM 22354937
ER
PT J
AU Roe, MT
White, JA
Kaul, P
Tricoci, P
Lokhnygina, Y
Miller, CD
van't Hof, AW
Montalescot, G
James, SK
Saucedo, J
Ohman, EM
Pollack, CV
Hochman, JS
Armstrong, PW
Giugliano, RP
Harrington, RA
Van de Werf, F
Califf, RM
Newby, LK
AF Roe, Matthew T.
White, Jennifer A.
Kaul, Padma
Tricoci, Pierluigi
Lokhnygina, Yuliya
Miller, Chadwick D.
van't Hof, Arnoud W.
Montalescot, Gilles
James, Stefan K.
Saucedo, Jorge
Ohman, E. Magnus
Pollack, Charles V., Jr.
Hochman, Judith S.
Armstrong, Paul W.
Giugliano, Robert P.
Harrington, Robert A.
Van de Werf, Frans
Califf, Robert M.
Newby, L. Kristin
TI Regional Patterns of Use of a Medical Management Strategy for Patients
With Non-ST-Segment Elevation Acute Coronary Syndromes Insights From the
EARLY ACS Trial
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE non-ST-segment elevation acute coronary syndrome; medical management;
coronary artery disease; mortality
ID UNSTABLE ANGINA; CARDIAC-CATHETERIZATION; MYOCARDIAL-INFARCTION;
OUTCOMES; PREDICTORS; DEATH
AB Background-Regional differences in the profile and prognosis of non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients treated with medical management after angiography remain uncertain.
Methods and Results-Using data from the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndromes (EARLY ACS) trial, we examined regional variations in the use of an in-hospital medical management strategy in NSTE ACS patients who had significant coronary artery disease (CAD) identified during angiography, factors associated with the use of a medical management strategy, and 1-year mortality rates. Of 9406 patients, 8387 (89%) underwent angiography and had significant CAD; thereafter, 1766 (21%) were treated solely with a medical management strategy (range: 18% to 23% across 4 major geographic regions). Factors most strongly associated with a medical management strategy were negative baseline troponin values, prior coronary artery bypass grafting, lower baseline hemoglobin values, and greater number of diseased vessels; region was not a significant factor. One-year mortality was higher among patients treated with a medical management strategy compared with those who underwent revascularization (7.8% versus 3.6%; adjusted hazard ratio, 1.46; 95% CI, 1.21-1.76), with no significant interaction by region (interaction probability value=0.42).
Conclusions-Approximately 20% of NSTE ACS patients with significant CAD in an international trial were treated solely with an in-hospital medical management strategy after early angiography, with no regional differences in factors associated with medical management or the risk of 1-year mortality. These findings have important implications for the conduct of future clinical trials, and highlight global similarities in the profile and prognosis of medically managed NSTE ACS patients.
C1 [Roe, Matthew T.; White, Jennifer A.; Kaul, Padma; Lokhnygina, Yuliya; Ohman, E. Magnus; Harrington, Robert A.; Califf, Robert M.; Newby, L. Kristin] Duke Clin Res Inst, Durham, NC 27705 USA.
[Kaul, Padma; Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada.
[Miller, Chadwick D.] Wake Forest Univ, Bowman Gray Sch Med, Dept Emergency Med, Winston Salem, NC USA.
[van't Hof, Arnoud W.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands.
[Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, Paris, France.
[James, Stefan K.] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
[Saucedo, Jorge] Univ Oklahoma, Med Ctr, Div Cardiol, Oklahoma City, OK USA.
[Pollack, Charles V., Jr.] Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA.
[Hochman, Judith S.] NYU, Sch Med, Dept Med, New York, NY USA.
[Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
[Van de Werf, Frans] Gasthuisberg Univ Hosp Leuven, Dept Cardiovasc Dis, Louvain, Belgium.
RP Roe, MT (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 7035, Durham, NC 27705 USA.
EM matthew.roe@duke.edu
OI Van de Werf, Frans/0000-0001-9479-7767; Hochman,
Judith/0000-0002-5889-5981
FU Schering-Plough Corporation; Merck Co, Inc.; Merck;
Schering-Plough/Merck; Schering-Plough
FX The EARLY ACS trial was funded by Schering-Plough Corporation. These
analyses were funded by research grant support from Merck & Co, Inc.; Dr
Roe has received prior research support from Merck/Schering-Plough and
compensation from Merck for clinical end point adjudication activities.
Dr Tricoci has received advisory board and research support from Merck.
Dr Miller has received research support from Schering-Plough/Merck. Dr
van't Hof has received lecture fees and unrestricted grants from
Schering Plough/Merck. Dr Montalescot has received consulting/lecture
fees from Schering-Plough/Merck. Dr James has received research support
and speaker fees from Schering-Plough. Dr Ohman is a principal
investigator for Schering-Plough, now Merck. Dr Pollack has received
research support from Schering-Plough. Dr Hochman is on the advisory
board for Schering-Plough/Merck. Dr Armstrong has done consulting for
Merck Frosst Canada Ltd. and receives research support from
Schering-Plough/Merck. Dr Giugliano has received research support,
advisory board, and honoraria for CME lectures from
Schering-Plough/Merck. Dr Harrington has received research support and
consulting with Schering-Plough/Merck. Dr Van de Werf has received
research support, advisory board, and speaker fee from
Schering-Plough/Merck. Dr Califf has received research funding and
consulting with Schering-Plough, now Merck (all consulting funds donated
to not-for-profits). Dr Saucedo has received research support, advisory
board, and honoraria for lectures from Schering-Plough/Merck. Dr Newby
has received research support from Schering-Plough/Merck. Ms White and
Drs Lokhnygina and Kaul have no conflicts to disclose.
NR 14
TC 15
Z9 15
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2012
VL 5
IS 2
BP 205
EP 213
DI 10.1161/CIRCOUTCOMES.111.962332
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RG
UT WOS:000302120300014
PM 22373905
ER
PT J
AU Afilalo, J
Mottillo, S
Eisenberg, MJ
Alexander, KP
Noiseux, N
Perrault, LP
Morin, JF
Langlois, Y
Ohayon, SM
Monette, J
Boivin, JF
Shahian, DM
Bergman, H
AF Afilalo, Jonathan
Mottillo, Salvatore
Eisenberg, Mark J.
Alexander, Karen P.
Noiseux, Nicolas
Perrault, Louis P.
Morin, Jean-Francois
Langlois, Yves
Ohayon, Samuel M.
Monette, Johanne
Boivin, Jean-Francois
Shahian, David M.
Bergman, Howard
TI Addition of Frailty and Disability to Cardiac Surgery Risk Scores
Identifies Elderly Patients at High Risk of Mortality or Major Morbidity
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE cardiac surgery; outcomes; aging; frailty; disability; elderly; heart
valve surgery
ID LONG-TERM SURVIVAL; BYPASS-GRAFTING SURGERY; IN-HOSPITAL MORTALITY;
OLDER-ADULTS; FUNCTIONAL STATUS; VALVE SURGERY; GAIT SPEED; MODELS;
EUROSCORE; STRATIFICATION
AB Background-Cardiac surgery risk scores perform poorly in elderly patients, in part because they do not take into account frailty and disability which are critical determinants of health status with advanced age. There is an unmet need to combine established cardiac surgery risk scores with measures of frailty and disability to provide a more complete model for risk prediction in elderly patients undergoing cardiac surgery.
Methods and Results-This was a prospective, multicenter cohort study of elderly patients (>= 70 years) undergoing coronary artery bypass and/or valve surgery in the United States and Canada. Four different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores were measured in all patients. The primary outcome was the STS composite end point of in-hospital postoperative mortality or major morbidity. A total of 152 patients were enrolled, with a mean age of 75.9+/-4.4 years and 34% women. Depending on the scale used, 20-46% of patients were found to be frail, and 5-76% were found to have at least 1 disability. The most predictive scale in each domain was: 5-meter gait speed >= 6 seconds as a measure of frailty (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.17-5.90), >= 3 impairments in the Nagi scale as a measure of disability (OR, 2.98; 95% CI, 1.35-6.56) and either the Parsonnet score (OR, 1.08; 95% CI, 1.04-1.13) or Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI, 1.01-1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or STS-PROMM alone, (area under the curve, 0.68-0.72), addition of frailty and disability provided incremental value and improved model discrimination (area under the curve, 0.73-0.76).
Conclusions-Clinicians should use an integrative approach combining frailty, disability, and risk scores to better characterize elderly patients referred for cardiac surgery and identify those that are at increased risk. (Circ Cardiovasc Qual Outcomes. 2012;5:222-228.)
C1 [Afilalo, Jonathan; Eisenberg, Mark J.] McGill Univ, SMBD Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada.
[Afilalo, Jonathan; Mottillo, Salvatore; Eisenberg, Mark J.; Boivin, Jean-Francois] McGill Univ, SMBD Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada.
[Morin, Jean-Francois; Langlois, Yves; Ohayon, Samuel M.] McGill Univ, SMBD Jewish Gen Hosp, Div Cardiac Surg, Montreal, PQ H3T 1E2, Canada.
[Monette, Johanne; Bergman, Howard] McGill Univ, SMBD Jewish Gen Hosp, Div Geriatr Med, Montreal, PQ H3T 1E2, Canada.
[Alexander, Karen P.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Noiseux, Nicolas] Univ Montreal, Ctr Hosp Univ Montreal, Ctr Rech, Div Cardiac Surg, Montreal, PQ, Canada.
[Perrault, Louis P.] Univ Montreal, Montreal Heart Inst, Div Cardiac Surg, Montreal, PQ, Canada.
[Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA.
[Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02115 USA.
RP Afilalo, J (reprint author), McGill Univ, SMBD Jewish Gen Hosp, Div Cardiol, 3755 Cote Sainte Catherine Rd, Montreal, PQ H3T 1E2, Canada.
EM jonathan@afilalo.com
FU Fonds de la Recherche en Sante du Quebec; Royal College of Physicians
and Surgeons of Canada
FX Dr Afilalo is supported by the Fonds de la Recherche en Sante du Quebec
and the Royal College of Physicians and Surgeons of Canada Detweiller
Grant.
NR 47
TC 100
Z9 100
U1 1
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2012
VL 5
IS 2
BP 222
EP U140
DI 10.1161/CIRCOUTCOMES.111.963157
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RG
UT WOS:000302120300016
PM 22396586
ER
PT J
AU Vivo, RP
Krim, SR
Krim, NR
Zhao, X
Hernandez, AF
Peterson, ED
Pina, IL
Bhatt, DL
Schwamm, LH
Fonarow, GC
AF Vivo, Rey P.
Krim, Selim R.
Krim, Nassim R.
Zhao, Xin
Hernandez, Adrian F.
Peterson, Eric D.
Pina, Ileana L.
Bhatt, Deepak L.
Schwamm, Lee H.
Fonarow, Gregg C.
TI Care and Outcomes of Hispanic Patients Admitted With Heart Failure With
Preserved or Reduced Ejection Fraction Findings From Get With The
Guidelines-Heart Failure
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE congestive heart failure; contractile function; health policy and
outcome research
ID ACUTE MYOCARDIAL-INFARCTION; NATIONAL REGISTRY ADHERE; QUALITY-OF-CARE;
SYSTOLIC FUNCTION; INSULIN-RESISTANCE; ETHNIC-DIFFERENCES; RISK-FACTORS;
OPTIMIZE-HF; AMERICANS; DISEASE
AB ackground-Although individuals of Hispanic ethnicity are at high risk for developing heart failure (HF), little is known about differences between Hispanic HF patients stratified by left ventricular ejection fraction (EF). We compared characteristics, quality of care, and outcomes between Hispanic and non-Hispanic white patients hospitalized for HF with preserved EF (PEF) or reduced EF (REF).
Methods and Results-From 247 hospitals in Get With The Guidelines-Heart Failure between 2005-2010, 6117 Hispanics were compared with 71 859 non-Hispanic whites. Forty-six percent of Hispanics had PEF (EF > 40%), whereas 54% had REF (EF <40%); 55% and 45% of non-Hispanic whites had PEF and REF, respectively. Relative to non-Hispanic whites, Hispanics with PEF or REF were more likely to be younger and to have diabetes, hypertension, and overweight/obesity. In multivariate analysis, a lower mortality risk was observed among Hispanics with PEF (odds ratio, 0.50; 95% confidence interval, 0.31-0.81; P=0.005) but not in Hispanics with REF (odds ratio, 0.94; 95% confidence interval, 0.62-1.43; P=0.784) compared with non-Hispanic whites. In all groups, composite performance improved within the study period (Hispanics PEF: 75.2-95.1%; non-Hispanic whites PEF: 79.0-92.7%; Hispanics REF: 67.7-88.4%; non-Hispanic whites REF: 60.8-85.6%, P<0.0001).
Conclusions-Hispanic HF patients with PEF had better in-hospital survival than non-Hispanic whites with PEF. Inpatient mortality was similar between groups with REF. Quality of care was similar and improved over time irrespective of ethnicity, highlighting the potential benefit of performance improvement programs in promoting equitable care. (Circ Heart Fail. 2012; 5: 167-175.)
C1 [Vivo, Rey P.] Univ Texas Galveston, Med Branch, Div Cardiol, Galveston, TX 77555 USA.
[Vivo, Rey P.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA.
[Krim, Selim R.] Ochsner Heart & Vasc Inst, New Orleans, LA USA.
[Krim, Nassim R.] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Zhao, Xin; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA.
[Pina, Ileana L.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Pina, Ileana L.] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA.
RP Vivo, RP (reprint author), Univ Texas Galveston, Med Branch, Div Cardiol, 301 Univ Blvd, Galveston, TX 77555 USA.
EM rpvivo@gmail.com
RI Hernandez, Adrian F./A-7818-2016
OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian
F./0000-0003-3387-9616
FU Council of Clinical Cardiology of the AHA; Medtronic; Ortho-McNeil; AHA
Pharmaceutical Roundtable; GlaxoSmithKline; Johnson Johnson;
Bristol-Meyers Squibb; Sanofi; Merck; Schering-Plough; Lilly; Amarin;
Astra Zeneca; Eisai; Ethicon; Sanofi Aventis; National Heart, Lung, and
Blood Institute; Medicines Company
FX This study was supported in part by a Young Investigator database
research seed grant from the Council of Clinical Cardiology of the AHA.
The GWTG-HF program is provided by the AHA and is currently supported in
part by Medtronic, Ortho-McNeil, and the AHA Pharmaceutical Roundtable.
GWTG-HF has been funded in the past through support from
GlaxoSmithKline.; Dr Hernandez reports receiving research grants from
Johnson & Johnson and honoraria from Medtronic, Amgen, and Astra Zeneca.
Dr Peterson serves as the Principal Investigator of the Data Analytic
Center for the GWTG of the AHA. He reports receiving research support
from Bristol-Meyers Squibb, Sanofi, Merck, Schering-Plough, Lilly, and
Johnson & Johnson. Dr Bhatt reports receiving grants from Amarin, Astra
Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis,
and The Medicines Company (significant); he serves as the Chair of the
AHA GWTG Science Subcommittee. Dr Schwamm serves as Chair of the GWTG
Steering Committee of the AHA. Dr Fonarow served as former Chair of the
AHA GWTG Steering Committee. He reports receiving research grants from
National Heart, Lung, and Blood Institute (significant); receiving
honoraria from Medtronic (modest); and serving as a consultant for
Novartis (significant). The remaining authors report no conflicts of
interest. The authors are solely responsible for the design and conduct
of this study, all analyses, and the drafting and editing of the article
and its final contents.
NR 29
TC 10
Z9 11
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAR
PY 2012
VL 5
IS 2
BP 167
EP U118
DI 10.1161/CIRCHEARTFAILURE.111.963546
PG 25
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RL
UT WOS:000302120800016
PM 22414939
ER
PT J
AU Chae, CU
Albert, CM
Moorthy, MV
Lee, IM
Buring, JE
AF Chae, Claudia U.
Albert, Christine M.
Moorthy, M. V.
Lee, I-Min
Buring, Julie E.
TI Vitamin E Supplementation and the Risk of Heart Failure in Women
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE antioxidants; epidemiology; heart failure; prevention; women
ID RANDOMIZED CONTROLLED-TRIAL; PRESERVED EJECTION FRACTION; LOW-DOSE
ASPIRIN; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION;
VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; DIAGNOSTIC-CRITERIA;
HEALTH
AB Background-Oxidative stress may contribute to the development of heart failure (HF); however, an increased risk of HF has been observed with antioxidant therapy in secondary prevention trials. No large clinical trials have addressed the role of antioxidant therapy in the primary prevention of HF.
Methods and Results-We examined the effect of vitamin E and HF risk in 39 815 initially healthy women, aged at least 45 years at baseline, who were enrolled in the Women's Health Study, a randomized, double-blind, placebo-controlled trial of vitamin E (600 IU every other day). Over a median follow-up of 10.2 years, there were 220 incident HF events. In proportional hazards models, adjusting for age and randomized aspirin and beta carotene treatment, vitamin E assignment did not significantly affect HF risk (hazards ratio [HR], 0.93; 95% CI, 0.71-1.21; P=0.59). These results did not change with multivariate adjustment for other risk factors, including interim myocardial infarction. In a prespecified subgroup analysis, vitamin E was inversely related to developing HF with normal ejection fraction (>= 50%) with HR 0.59 (95% CI, 0.38-0.92; P=0.02), but there was no statistically significant effect on the risk of developing systolic HF (HR, 1.26; 95% CI, 0.84-1.89; P=0.26).
Conclusions-In this population of apparently healthy women, vitamin E did not affect the overall risk of HF. The possible benefit on diastolic HF requires confirmation in larger populations.
C1 [Chae, Claudia U.] Massachusetts Gen Hosp, Div Cardiol, YAW 5800, Boston, MA 02114 USA.
[Chae, Claudia U.; Albert, Christine M.; Moorthy, M. V.; Lee, I-Min; Buring, Julie E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Albert, Christine M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Boston, MA 02115 USA.
[Albert, Christine M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Lee, I-Min; Buring, Julie E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Chae, CU (reprint author), Massachusetts Gen Hosp, Div Cardiol, YAW 5800, 55 Fruit St, Boston, MA 02114 USA.
EM cchae@partners.org
FU Massachusetts General Hospital; Donald W. Reynolds Foundation; National
Heart, Lung, and Blood Institute [HL-043851, HL-080467]; National Cancer
Institute [CA-047988]
FX This work was supported by the Elizabeth Anne and Karen Barlow Corrigan
Women's Heart Health Program at Massachusetts General Hospital, the
Donald W. Reynolds Foundation, and grants HL-043851 and HL-080467 from
the National Heart, Lung, and Blood Institute and CA-047988 from the
National Cancer Institute.
NR 37
TC 9
Z9 11
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAR
PY 2012
VL 5
IS 2
BP 176
EP 182
DI 10.1161/CIRCHEARTFAILURE.111.963793
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RL
UT WOS:000302120800017
PM 22438520
ER
PT J
AU Rector, TS
Carson, PE
Anand, IS
McMurray, JJ
Zile, MR
McKelvie, RS
Komajda, M
Kuskowski, M
Massie, BM
AF Rector, Thomas S.
Carson, Peter E.
Anand, Inder S.
McMurray, John J.
Zile, Michael R.
McKelvie, Robert S.
Komajda, Michel
Kuskowski, Michael
Massie, Barry M.
CA I-PRESERVE Trial Investigators
TI Assessment of Long-Term Effects of Irbesartan on Heart Failure With
Preserved Ejection Fraction as Measured by the Minnesota Living With
Heart Failure Questionnaire in the Irbesartan in Heart Failure With
Preserved Systolic Function (I-PRESERVE) Trial
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE diastolic heart failure; ARBs; quality of life
ID QUALITY-OF-LIFE; CLINICAL CHARACTERISTICS; RANDOMIZED-TRIAL;
DOUBLE-BLIND; DYSFUNCTION; PLACEBO; RELIABILITY; PREVALENCE; VALIDITY
AB Background-The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used in a large, multinational, randomized, placebo-controlled trial to measure adverse effects of heart failure with preserved ejection fraction (HF-PEF) on patients' lives and the effects of irbesartan.
Methods and Results-Patients with symptomatic HF-PEF were randomly assigned to irbesartan (up to 300 mg daily) or placebo. The MLHFQ was administered at baseline (n=3605), month 6 (n=3137), month 14 (n=2904), and the end of study (median, 56 months, n=2205). Baseline MLHFQ scores of 43 +/- 21 indicated that HF-PEF had a substantial adverse effects. Estimated retest reliability was 0.80. Baseline MLHFQ scores were associated with other measures of the severity of heart failure including symptoms, signs of congestion, cardiac structure, and time to hospitalizations or deaths attributed to heart failure. Slight improvement in shortness of breath or fatigue was associated with significant improvement in MLHFQ scores (-5.9 and -5.0, P<0.0001). Compared with placebo, further improvement in MLHFQ scores was not observed with irbesartan after 6 months (mean adjusted difference, 0.4; 95% confidence interval, -0.8 to 1.7), 14 months (0.5; 95% confidence interval, -0.9 to 1.8), or the end of study (2.0; 95% confidence interval, -4.1 to 0.01).
Conclusions-The MLHFQ scores are a reliable, valid, and sensitive measure of the adverse impact of HF-PEF on patients' lives. Irbesartan did not substantially improve MLHFQ scores during a long period of follow-up.
C1 [Rector, Thomas S.; Anand, Inder S.] Univ Minnesota, Dept Vet Affairs Hlth Care Syst, Minneapolis, MN USA.
[Rector, Thomas S.; Anand, Inder S.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Carson, Peter E.] Dept Vet Affairs Hlth Care Syst, Washington, DC USA.
[Carson, Peter E.] Georgetown Univ Hosp, Washington, DC 20007 USA.
[McMurray, John J.] Univ Glasgow, British Heart Fdn, Cardiovasc Res Ctr, Glasgow G12 8QQ, Lanark, Scotland.
[Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA.
[Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA.
[McKelvie, Robert S.] Populat Hlth Res Inst, Hamilton, ON, Canada.
[McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada.
[Kuskowski, Michael] Hop La Pitie Salpetriere, Dept Cardiol, Paris, France.
[Komajda, Michel] Univ Paris 06, Paris, France.
[Komajda, Michel] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
[Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Massie, Barry M.] San Francisco Dept Vet Affairs Hlth Care Syst, San Francisco, CA USA.
RP Rector, TS (reprint author), Minneapolis VA Hlth Care Syst, 1 Vet Dr, Minneapolis, MN 55417 USA.
EM thomas.rector@va.gov
FU Bristol-Myers Squibb; Sanofi-Aventis; Veterans Health Administration
[HFP-98-001]; Servier
FX The I-PRESERVE Trial was funded by Bristol-Myers Squibb and
Sanofi-Aventis. Dr Rector was supported by the Veterans Health
Administration [Health Services Research and Development grant
HFP-98-001. All expressed views and conclusions are the authors' and do
not necessarily represent the Veterans Health Administration.; Drs
Anand, Carson, and Zile received consulting fees from Bristol-Myers
Squibb and/or Sanofi-Aventis. Dr McMurray received support from
Bristol-Myers Squibb (to Glasgow University) for his work on this trial.
Dr Komajda received consulting fees from Bristol-Myers Squibb and
Servier and lecture fees from Sanofi-Aventis. Dr McKelvie received
consulting fees and lecture fees from Bristol-Myers Squibb and
Sanofi-Aventis. Dr Massie received grant support and consulting fees
from Bristol-Myers Squibb and Sanofi-Aventis. Drs Rector and Kuskowski
have no industry relationships to disclose. Dr Rector receives royalty
payments from the University of Minnesota for licensed use of the
Minnesota Living with Heart Failure Questionnaire.
NR 24
TC 16
Z9 17
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAR
PY 2012
VL 5
IS 2
BP 217
EP 225
DI 10.1161/CIRCHEARTFAILURE.111.964221
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RL
UT WOS:000302120800022
PM 22267751
ER
PT J
AU Singh, TP
Almond, CS
Semigran, MJ
Piercey, G
Gauvreau, K
AF Singh, Tajinder P.
Almond, Christopher S.
Semigran, Marc J.
Piercey, Gary
Gauvreau, Kimberlee
TI Risk Prediction for Early In-Hospital Mortality Following Heart
Transplantation in the United States
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE transplantation; survival; risk factors; decision support techniques;
heart failure
ID GLOMERULAR-FILTRATION-RATE; VENTRICULAR ASSIST DEVICE; GLOBAL
CARDIOVASCULAR RISK; SERUM CREATININE VALUES; INTERNATIONAL SOCIETY;
LUNG TRANSPLANTATION; RENAL-DISEASE; VALIDATION; EQUATION; SURVIVAL
AB Background-Risk factors for early mortality after heart transplant (HT) have not been used for quantitative risk prediction. We sought to develop and validate a risk prediction model for posttransplant in-hospital mortality in HT recipients.
Methods and Results-We derived the model in subjects aged >= 18 years who underwent primary HT in the United States from January 2007 to June 2009 (n=4248) and validated it internally using a bootstrapping technique (200 random samples, n=4248). We then assessed the model's performance in patients receiving an HT from July 2009 to October 2010 (external validation cohort, n=2346). Posttransplant in-hospital mortality was 4.7% in the model derivation cohort. The best-fitting model based on recipient characteristics at transplant had 6 variables: age, diagnosis, type of mechanical support, ventilator support, estimated glomerular filtration rate, and total serum bilirubin. Model discrimination for survivors versus nonsurvivors was acceptable during derivation and internal validation (C statistic, 0.722 and 0.731, respectively) as was model calibration during derivation (Hosmer Lemeshow [HL] P=0.47). Model performance was reasonable in the external validation cohort (predicted mortality, 4.9%; actual mortality, 4.3%; R-2=0.95; C statistic, 0.68; HL P=0.48). Adding the donor-related variables of age and ischemic time to the model improved its performance in both the model derivation (C statistic, 0.742; HL P=0.70) and the external validation (C statistic, 0.695; HL P=0.42) cohorts.
Conclusions-The proposed model allows risk stratification of HT candidates for early posttransplant mortality and may be useful in counseling patients with regard to their posttransplant prognosis. The model with additional donor-related variables may be useful during donor selection. (Circ Heart Fail. 2012;5:259-266.)
C1 [Singh, Tajinder P.; Almond, Christopher S.; Piercey, Gary; Gauvreau, Kimberlee] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Semigran, Marc J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
[Singh, Tajinder P.; Almond, Christopher S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Semigran, Marc J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Gauvreau, Kimberlee] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Singh, TP (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA.
EM TP.Singh@cardio.chboston.org
FU Department of Cardiology, Children's Hospital Boston, Boston,
Massachusetts; Health Resources and Services Administration
[234-2005-370011C]
FX This study was supported by the Heart Transplant Research and Education
Fund, Department of Cardiology, Children's Hospital Boston, Boston,
Massachusetts, and in part by Health Resources and Services
Administration contract 234-2005-370011C.
NR 30
TC 13
Z9 13
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAR
PY 2012
VL 5
IS 2
BP 259
EP U239
DI 10.1161/CIRCHEARTFAILURE.111.965996
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RL
UT WOS:000302120800027
PM 22308287
ER
PT J
AU Karaosmanoglu, AD
Blake, MA
AF Karaosmanoglu, Ali Devrim
Blake, Michael A.
TI Applications of PET-CT in patients with esophageal cancer
SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
DE PET scan; cancer; esophagus
ID POSITRON-EMISSION-TOMOGRAPHY; SQUAMOUS-CELL CARCINOMA; ECTOPIC
GASTRIC-MUCOSA; ESOPHAGOGASTRIC JUNCTION; BARRETTS-ESOPHAGUS;
RISK-FACTORS; TUMOR RESPONSE; LYMPH-NODES; FDG PET; ADENOCARCINOMA
AB Although esophageal cancer is not among the common cancers as prostate, lung, breast, or colon malignancies, it has an exceedingly high mortality rate, with its incidence close to the cancer-specific mortality. Currently, the only potentially curative treatment is surgery. Unfortunately, surgical treatment is extensive and may have significant morbidity and mortality related with it. Given these facts, selection of patients who are amenable to surgical treatment is of utmost importance. Conventional morphology based cross-sectional imaging modalities are extremely helpful for pre-surgical evaluation and follow-up of these patients, however, they have very well-known limitations. Positron emission tomography-computed tomography (PET-CT) is a relatively new, highly promising molecular imaging technique which may overcome some of the fundemental limitations of these conventional cross-sectional modalities in the pre-surgical evaluation and follow-up of these patients. In this review, we evaluated the applications of PET-CT in patients with esophageal cancer.
C1 [Karaosmanoglu, Ali Devrim] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02115 USA.
RP Karaosmanoglu, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02115 USA.
EM alidevrim76@yahoo.com
RI Karaosmanoglu, Ali/D-8624-2015
OI Karaosmanoglu, Ali/0000-0003-0027-9593
NR 48
TC 8
Z9 8
U1 0
U2 4
PU TURKISH SOC RADIOLOGY
PI ANKARA
PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY
SN 1305-3825
J9 DIAGN INTERV RADIOL
JI Diagn. Interv. Radiol.
PD MAR-APR
PY 2012
VL 18
IS 2
BP 171
EP 182
DI 10.4261/1305-3825.DIR.4309-11.1
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 917VI
UT WOS:000302206300006
PM 22198910
ER
PT J
AU Abbott, AL
Adelman, MA
Alexandrov, AV
Barnett, HJM
Beard, J
Bell, P
Bjorck, M
Blacker, D
Buckley, CJ
Cambria, RP
Comerota, AJ
Connolly, ES
Davies, AH
Eckstein, HH
Faruqi, R
Fraedrich, G
Gloviczki, P
Hankey, GJ
Harbaugh, RE
Heldenberg, E
Kittner, SJ
Kleinig, TJ
Mikhailidis, DP
Moore, WS
Naylor, R
Nicolaides, A
Paraskevas, KI
Pelz, DM
Prichard, JW
Purdie, G
Ricco, JB
Riles, T
Rothwell, P
Sandercock, P
Sillesen, H
Spence, JD
Spinelli, F
Tan, A
Thapar, A
Veith, FJ
Zhou, W
AF Abbott, A. L.
Adelman, M. A.
Alexandrov, A. V.
Barnett, H. J. M.
Beard, J.
Bell, P.
Bjorck, M.
Blacker, D.
Buckley, C. J.
Cambria, R. P.
Comerota, A. J.
Connolly, E. S., Jr.
Davies, A. H.
Eckstein, H. H.
Faruqi, R.
Fraedrich, G.
Gloviczki, P.
Hankey, G. J.
Harbaugh, R. E.
Heldenberg, E.
Kittner, S. J.
Kleinig, T. J.
Mikhailidis, D. P.
Moore, W. S.
Naylor, R.
Nicolaides, A.
Paraskevas, K. I.
Pelz, D. M.
Prichard, J. W.
Purdie, G.
Ricco, J. B.
Riles, T.
Rothwell, P.
Sandercock, P.
Sillesen, H.
Spence, J. D.
Spinelli, F.
Tan, A.
Thapar, A.
Veith, F. J.
Zhou, W.
TI Why the United States Center for Medicare and Medicaid Services (CMS)
Should not Extend Reimbursement Indications for Carotid Artery
Angioplasty/Stenting
SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
LA English
DT Letter
ID RANDOMIZED CONTROLLED-TRIAL; STROKE PREVENTION; ENDARTERECTOMY;
STENOSIS; RISK; REVASCULARIZATION; PROFESSIONALS; ASSOCIATION;
GUIDELINES; THERAPY
C1 [Abbott, A. L.] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia.
[Abbott, A. L.] Florey Neurosci Inst, Melbourne, Vic, Australia.
[Adelman, M. A.] NYU, Langone Med Ctr, New York, NY 10003 USA.
[Alexandrov, A. V.] Univ Alabama Hosp & Clin, Birmingham, AL USA.
[Barnett, H. J. M.] Univ Western Ontario, Robarts Res Inst, Toronto, ON, Canada.
[Beard, J.] No Gen Hosp, Sheffield Vasc Inst, Sheffield S5 7AU, S Yorkshire, England.
[Bell, P.] Univ Leicester, Leicester, Leics, England.
[Bell, P.] Univ Leicester Hosp, Leicester, Leics, England.
[Bjorck, M.] Uppsala Univ, Uppsala, Sweden.
[Blacker, D.] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia.
[Cambria, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cambria, R. P.] Harvard Univ, Sch Med, Boston, MA USA.
[Comerota, A. J.] Toledo Hosp, Jobst Vasc Inst, Toledo, OH USA.
[Connolly, E. S., Jr.] Columbia Univ, New York, NY 10027 USA.
[Davies, A. H.] Charing Cross Hosp, Imperial Coll Sch Med, London, England.
[Eckstein, H. H.] Tech Univ Munich, Klinikum Rechts Isar, D-8000 Munich, Germany.
[Faruqi, R.] Stanford Univ, Kaiser Permanente Med Ctr, Stanford, CA 94305 USA.
[Fraedrich, G.] Med Univ, Innsbruck, Austria.
[Gloviczki, P.] Mayo Clin, Rochester, MN USA.
[Hankey, G. J.] Royal Perth Hosp, Perth, WA, Australia.
[Harbaugh, R. E.] Penn State Univ, Penn State Inst Neurosci, Hershey, PA USA.
[Heldenberg, E.] Assaf Harofeh Med Ctr, IL-70300 Zerifin, Israel.
[Kittner, S. J.] Univ Maryland, Sch Med, Baltimore, MD USA.
[Kleinig, T. J.] Univ Adelaide, Royal Adelaide Hosp, Adelaide, SA, Australia.
[Kittner, S. J.; Tan, A.] Univ Adelaide, Lyell McEwin Hosp, Adelaide, SA, Australia.
[Mikhailidis, D. P.] UCL, Sch Med, London W1N 8AA, England.
[Moore, W. S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Naylor, R.] Leicester Royal Infirm, Leicester, Leics, England.
[Nicolaides, A.] Univ London Imperial Coll Sci Technol & Med, Vasc Diagnost Ctr, London, England.
[Paraskevas, K. I.] Klinikum Nurnberg Sud, Nurnberg, Germany.
[Pelz, D. M.] Univ Western Ontario, London, ON, Canada.
[Prichard, J. W.] Yale Med Sch, New Haven, CT USA.
[Purdie, G.; Tan, A.] Queen Elizabeth Hosp, Adelaide, SA, Australia.
[Ricco, J. B.] Univ Poitiers, Poitiers, France.
[Rothwell, P.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England.
[Sandercock, P.] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland.
[Sillesen, H.] Univ Copenhagen, DK-1168 Copenhagen, Denmark.
[Spence, J. D.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada.
[Spinelli, F.] Univ Messina, Messina, Italy.
[Zhou, W.] Stanford Univ, Palo Alto VA Hlth Care Syst, Stanford, CA 94305 USA.
[Veith, F. J.] NYU, Sch Med, Cleveland Clin, New York, NY 10003 USA.
[Veith, F. J.] Case Western Reserve Univ, Lerner Sch Med, Cleveland, OH 44106 USA.
RP Abbott, AL (reprint author), Baker IDI Heart & Diabet Inst, 75 Commercial Rd, Melbourne, Vic 3004, Australia.
EM Annet.L.Abbott@gmail.com.au; Mark.Adelman@nyumc.org;
avalexandrov@att.net; hjmb@bell.net; j.d.beard@btinternet.com;
peterrfbell@googlemail.com; martin@bjorck.pp.se;
David.Blacker@health.wa.gov.au; Clifford.Buckley@VA.GOV;
RCAMBRIA@PARTNERS.ORG; anthony.comerotamd@promedica.org;
esc5@columbia.edu; a.h.davies@imperial.ac.uk; HHEckstein@web.de;
Rishad.Faruqi@kp.org; gustav.fraedrich@i-med.ac.at;
gloviczki.peter@mayo.edu; gjhankey@cyllene.uwa.edu.au;
rharbaugh@psu.edu; eitanh@asaf.health.gov.il; skittner@umaryland.edu;
tkleinig@hotmail.com; MIKHAILIDIS@aol.com; WMoore@mednet.ucla.edu;
ross.naylor@uhl-tr.nhs.uk; anicolaides1@gmail.com;
paraskevask@hotmail.com; Pelz@uwo.ca; james.prichard@yale.edu;
Grant.Purdie@health.sa.gov.au; jeanbaptistericco@gmail.com;
Thomas.Riles@nyumc.org; peter.rothwell@clneuro.ox.ac.uk;
Peter.sandercock@ed.ac.uk; sillesen@mac.com; dspence@robarts.ca;
f.spinelli@mac.com; Aaron.Tan@health.sa.gov.au;
a.thapar09@imperial.ac.uk; fjvmd@msn.com; weizhou@stanford.edu
RI Mikhailidis, Dimitri/A-1869-2013; Bjorck, Martin/A-4104-2008; Hankey,
Graeme /H-4968-2014; Spence, J. David/K-6396-2013;
OI Hankey, Graeme /0000-0002-6044-7328; Spence, J.
David/0000-0001-7478-1098; Spinelli, Francesco/0000-0001-6527-1993;
Alexandrov, Andrei V/0000-0001-8871-1023; Adelman,
Mark/0000-0001-9276-6131
FU The Dunhill Medical Trust [RCS/DMT 3RD ROUND (3)]
NR 57
TC 12
Z9 12
U1 0
U2 8
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1078-5884
J9 EUR J VASC ENDOVASC
JI Eur. J. Vasc. Endovasc. Surg.
PD MAR
PY 2012
VL 43
IS 3
BP 247
EP 251
DI 10.1016/j.ejvs.2011.12.006
PG 5
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 917SY
UT WOS:000302200100001
PM 22226698
ER
PT J
AU Beck, D
Niessner, H
Kulms, D
Flaherty, K
Schaller, M
Garbe, C
Meier, F
AF Beck, D.
Niessner, H.
Kulms, D.
Flaherty, K.
Schaller, M.
Garbe, C.
Meier, F.
TI The BRAFV600E kinase inhibitor vemurafenib induces apoptosis through a
process involving induction of endoplasmic reticulum stress in melanoma
cells
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
(ADF)
CY MAR 01-03, 2012
CL Marburg, GERMANY
SP Arbeitsgemeinsch Dermatol Forsch (ADF)
C1 [Beck, D.; Niessner, H.; Schaller, M.; Garbe, C.; Meier, F.] Univ Tubingen, Dept Dermatol, Tubingen, Germany.
[Kulms, D.] Univ Stuttgart, Inst Cell Biol & Immunol, Stuttgart, Germany.
[Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RI Kulms, Dagmar/H-1653-2014
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 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2012
VL 21
IS 3
BP e12
EP e12
PG 1
WC Dermatology
SC Dermatology
GA 900ZP
UT WOS:000300931700068
ER
PT J
AU Eberle, FC
Song, JY
Xi, L
Raffeld, M
Harris, NL
Wilson, WH
Pittaluga, S
Jaffe, ES
AF Eberle, F. C.
Song, J. Y.
Xi, L.
Raffeld, M.
Harris, N. L.
Wilson, W. H.
Pittaluga, S.
Jaffe, E. S.
TI Transformed cutaneous CD30 positive T-cell lymphoma of the lymph node
mimicking classical Hodgkin lymphoma
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
(ADF)
CY MAR 01-03, 2012
CL Marburg, GERMANY
SP Arbeitsgemeinsch Dermatol Forsch (ADF)
C1 [Eberle, F. C.] Univ Tubingen, Dept Dermatol, D-72074 Tubingen, Germany.
[Eberle, F. C.; Song, J. Y.; Xi, L.; Raffeld, M.; Pittaluga, S.; Jaffe, E. S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Harris, N. L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Harris, N. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Wilson, W. H.] NCI, Metab Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2012
VL 21
IS 3
BP e19
EP e20
PG 2
WC Dermatology
SC Dermatology
GA 900ZP
UT WOS:000300931700114
ER
PT J
AU Yoon, WJ
Brugge, WR
AF Yoon, Won Jae
Brugge, William R.
TI Pancreatic Cystic Neoplasms: Diagnosis and Management
SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Pancreatic cystic neoplasm; Intraductal papillary mucinous neoplasm;
Mucinous cystic neoplasm; Serous cystic neoplasm; Solid-pseudopapillary
neoplasm
ID PAPILLARY MUCINOUS NEOPLASMS; FINE-NEEDLE-ASPIRATION; SOLID
PSEUDOPAPILLARY NEOPLASM; OPTICAL COHERENCE TOMOGRAPHY; OVARIAN-TYPE
STROMA; SEROUS-CYSTADENOMA; CLINICOPATHOLOGICAL FEATURES; PATHOLOGICAL
CORRELATION; DIFFERENTIAL-DIAGNOSIS; ENDOSCOPIC ULTRASOUND
AB Pancreatic cystic neoplasms are detected with increasing frequency. The management of such lesions is frequently hampered by limitations of current imaging techniques, difficulty in tissue acquisition, and the morbidity and mortality associated with pancreatic resection. Despite recent development in our understanding of the premalignant nature of mucinous lesions, the indications and timing of surgery remain controversial. More effort is needed to improve our diagnostic and treatment ability of pancreatic cystic neoplasms.
C1 [Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
[Yoon, Won Jae] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Brugge, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
EM wbrugge@partners.org
NR 100
TC 22
Z9 25
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 0889-8553
J9 GASTROENTEROL CLIN N
JI Gastroenterol. Clin. North Am.
PD MAR
PY 2012
VL 41
IS 1
BP 103
EP +
DI 10.1016/j.gtc.2011.12.016
PG 17
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 914YH
UT WOS:000301989100008
PM 22341252
ER
PT J
AU Halperin, DM
Kulke, MH
AF Halperin, Daniel M.
Kulke, Matthew H.
TI Management of Pancreatic Neuroendocrine Tumors
SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Neuroendocrine tumor; Pancreatic neuroendocrine tumor; Islet cell tumor;
Diagnosis; Prognosis; Management
ID ZOLLINGER-ELLISON-SYNDROME; ISLET-CELL-CARCINOMA; SOMATOSTATIN RECEPTOR
SCINTIGRAPHY; DUODX AFFECT RATE; PHASE-II; LIVER METASTASES; ENDOCRINE
TUMOR; CUSHINGS-SYNDROME; CHROMOGRANIN-A; INSULINOMA
AB Pancreatic neuroendocrine tumors secrete hormones that can result in characteristic clinical syndromes; however, most remain clinically silent and are diagnosed at a late stage. Tumor stage and histologic grade are associated with prognosis and help guide therapeutic decisions. Surgical resection is generally attempted in patients with localized disease. In patients with surgically unresectable disease, treatment with somatostatin analogs, hepatic embolization, or cytotoxic chemotherapy may be recommended. Newer targeted therapies have been shown to improve progression-free survival durations and were recently approved for use in patients with advanced pancreatic neuroendocrine tumors, further expanding treatment options for patients with this disease.
C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Carcinoid & Pancreat Neuroendocrine Tumor Program, Boston, MA 02115 USA.
[Halperin, Daniel M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kulke, Matthew H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Carcinoid & Pancreat Neuroendocrine Tumor Program, 44 Binney St, Boston, MA 02115 USA.
EM Matthew_Kulke@dfci.harvard.edu
RI Halperin, Daniel M/I-1944-2013
OI Halperin, Daniel M/0000-0002-3113-930X
NR 68
TC 6
Z9 6
U1 2
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8553
EI 1558-1942
J9 GASTROENTEROL CLIN N
JI Gastroenterol. Clin. North Am.
PD MAR
PY 2012
VL 41
IS 1
BP 119
EP +
DI 10.1016/j.gtc.2011.12.003
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 914YH
UT WOS:000301989100009
PM 22341253
ER
PT J
AU Doi, H
Iyer, TK
Carpenter, E
Li, H
Chang, KM
Vonderheide, RH
Kaplan, DE
AF Doi, Hiroyoshi
Iyer, Tara K.
Carpenter, Erica
Li, Hong
Chang, Kyong-Mi
Vonderheide, Robert H.
Kaplan, David E.
TI Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C
infection associated with disappearance of CD27-Positive B-cell
population
SO HEPATOLOGY
LA English
DT Article
ID SOLUBLE CD14; VIRUS-INFECTION; MICROBIAL TRANSLOCATION;
LIVER-TRANSPLANTATION; IMMUNE ACTIVATION; LYMPHOCYTES; EXPRESSION;
SERUM; INDIVIDUALS; COMPARTMENT
AB Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Both advanced solid tumors and HCV have previously been associated with memory B-cell dysfunction. In this study, we sought to dissect the effect of viral infection, cirrhosis, and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Peripheral blood from healthy donors, HCV-infected patients with F1-F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related HCC, and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B cells were stimulated with anticluster of differentiation (CD)40 antibodies and Toll-like receptor (TLR)9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin (Ig) production, and CD4+ T-cell allostimulatory capacity. CD27+ memory B cells and, more specifically, CD27+IgM+ B cells were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B cells in cirrhotics were hyporesponsive to CD40/TLR9 activation, as characterized by CD70 up-regulation, tumor necrosis factor beta secretion, IgG production, and T-cell allostimulation. Last, blockade of TLR4 and TLR9 signaling abrogated the activation of healthy donor B cells by cirrhotic plasma, suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis. Conclusion: Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of HCV infection. These B-cell defects may explain, in part, the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population. (HEPATOLOGY 2012)
C1 [Chang, Kyong-Mi; Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA.
[Doi, Hiroyoshi; Iyer, Tara K.; Li, Hong; Chang, Kyong-Mi; Kaplan, David E.] Univ Penn, Div Gastroenterol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Carpenter, Erica; Vonderheide, Robert H.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Vonderheide, Robert H.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Vonderheide, Robert H.] Univ Penn, Div Hematol Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Med & Res Serv, Res Bldg 21,A402A,3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM dakaplan@mail.med.upenn.edu
OI Kaplan, David E./0000-0002-3839-336X
FU NCI NIH HHS [R21 CA149908, R21 CA149908-01, T32 CA009140]; NIAAA NIH HHS
[AA12849, R01 AA012849, R01 AA012849-05]; NIAID NIH HHS [AI47519, R01
AI047519, R01 AI047519-12]; NIDDK NIH HHS [L30 DK069063, L30
DK069063-01, P30 DK050306, P30 DK050306-15, P30-DK050306]
NR 45
TC 21
Z9 22
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAR
PY 2012
VL 55
IS 3
BP 709
EP 719
DI 10.1002/hep.24689
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 897YS
UT WOS:000300699900008
PM 21932384
ER
PT J
AU Rosen, RC
Marx, BP
Maserejian, NN
Holowka, DW
Gates, MA
Sleeper, LA
Vasterling, JJ
Kang, HK
Keane, TM
AF Rosen, Raymond C.
Marx, Brian P.
Maserejian, Nancy N.
Holowka, Darren W.
Gates, Margaret A.
Sleeper, Lynn A.
Vasterling, Jennifer J.
Kang, Han K.
Keane, Terence M.
TI Project VALOR: design and methods of a longitudinal registry of
post-traumatic stress disorder (PTSD) in combat-exposed Veterans in the
Afghanistan and Iraqi military theaters of operations
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE post-traumatic stress disorder (PTSD); study design; disease registry;
combat-exposed Veterans; psychosocial outcomes
ID TRAUMATIC BRAIN-INJURY; STRUCTURED CLINICAL INTERVIEW; HARMFUL
ALCOHOL-CONSUMPTION; MENTAL-HEALTH PROBLEMS; WAR VETERANS; PRIMARY-CARE;
LIFE EVENTS; DEPLOYMENT; SYMPTOMS; THERAPY
AB Few studies have investigated the natural history of post-traumatic stress disorder (PTSD). Project VALOR (Veterans' After-discharge Longitudinal Registry) was designed as a longitudinal patient registry assessing the course of combat-related PTSD among 1600 male and female Veterans who served in Operation Enduring Freedom (OEF) in Afghanistan or Operation Iraqi Freedom (OIF). Aims of the study include investigating patterns and predictors of progression or remission of PTSD and treatment utilization. The study design was based on recommendations from the Agency for Healthcare Quality and Research for longitudinal disease registries and used a pre-specified theoretical model to select the measurement domains for data collection and interpretation of forthcoming results. The registry will include 1200 male and female Veterans with a recent diagnosis of PTSD in the Department of Veteran Affairs (VA) electronic medical record and a comparison group of 400 Veterans without a medical record-based PTSD diagnosis, to also allow for case-control analyses. Data are collected from administrative databases, electronic medical records, a self-administered questionnaire, and a semi-structured diagnostic telephone interview. Project VALOR is a unique and timely registry study that will evaluate the clinical course of PTSD, psychosocial correlates, and health outcomes in a carefully selected cohort of returning OEF/OIF Veterans. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Rosen, Raymond C.; Maserejian, Nancy N.; Gates, Margaret A.; Sleeper, Lynn A.] New England Res Inst Inc, Watertown, MA 02472 USA.
[Marx, Brian P.; Holowka, Darren W.; Vasterling, Jennifer J.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Marx, Brian P.; Holowka, Darren W.; Vasterling, Jennifer J.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Kang, Han K.] Environm Epidemiol Serv, Dept Vet Affairs, Washington, DC USA.
RP Rosen, RC (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA.
EM rrosen@neriscience.com
RI Schueter, nicos/A-3625-2014
FU US Department of Defense [W81XWH-08-2-0102, W81XWH-08-2-0100]
FX This work was funded by the US Department of Defense Awards
W81XWH-08-2-0102 and W81XWH-08-2-0100.
NR 44
TC 13
Z9 13
U1 3
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1049-8931
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD MAR
PY 2012
VL 21
IS 1
BP 5
EP 16
DI 10.1002/mpr.355
PG 12
WC Psychiatry
SC Psychiatry
GA 907QI
UT WOS:000301432000004
PM 22095917
ER
PT J
AU Maes, C
Araldi, E
Haigh, K
Khatri, R
Van Looveren, R
Giaccia, AJ
Haigh, JJ
Carmeliet, G
Schipani, E
AF Maes, Christa
Araldi, Elisa
Haigh, Katharina
Khatri, Richa
Van Looveren, Riet
Giaccia, Amato J.
Haigh, Jody J.
Carmeliet, Geert
Schipani, Ernestina
TI VEGF-independent cell-autonomous functions of HIF-1a regulating oxygen
consumption in fetal cartilage are critical for chondrocyte survival
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE ENDOCHONDRAL OSSIFICATION; CARTILAGE; CHONDROCYTE SURVIVAL; HYPOXIA; HIF
ID HYPOXIA-INDUCIBLE FACTOR-1; ENDOTHELIAL GROWTH-FACTOR; ENDOCHONDRAL
BONE-FORMATION; GENE-EXPRESSION; EPIPHYSEAL CHONDROCYTES; DIFFERENTIAL
ROLES; O-2 HOMEOSTASIS; MULTIPLE ROLES; HIF-1-ALPHA; ANGIOGENESIS
AB Fetal growth plate cartilage is nonvascularized, and chondrocytes largely develop in hypoxic conditions. We previously found that mice lacking the hypoxia-inducible transcription factor HIF-1a in cartilage show massive death of centrally located, hypoxic chondrocytes. A similar phenotype was observed in mice with genetic ablation of either all or specifically the diffusible isoforms of vascular endothelial growth factor (VEGF), a prime angiogenic target of HIF-1a. Here, we assessed whether VEGF is a critical downstream component of the HIF-1adependent survival pathway in chondrocytes. We used a genetic approach to conditionally overexpress VEGF164 in chondrocytes lacking HIF-1a, evaluating potential rescuing effects. The effectiveness of the strategy was validated by showing that transgenic expression of VEGF164 in Col2-Cre;VEGFf/f mice stimulated angiogenesis in the perichondrium, fully corrected the excessive hypoxia of VEGF-deficient chondrocytes, and completely prevented chondrocyte death. Yet, similarly crossed double-mutant embryos lacking HIF-1a and overexpressing VEGF164 in the growth plate cartilage still displayed a central cell death phenotype, albeit slightly delayed and less severe compared with mice exclusively lacking HIF-1a. Transgenic VEGF164 induced massive angiogenesis in the perichondrium, yet this only partially relieved the aberrant hypoxia present in HIF-1adeficient cartilage and thereby likely inflicted only a partial rescue effect. In fact, excessive hypoxia and failure to upregulate phosphoglycerate-kinase 1 (PGK1), a key enzyme of anaerobic glycolytic metabolism, were among the earliest manifestations of HIF-1a deficiency in cartilaginous bone templates, and reduced PGK1 expression was irrespective of transgenic VEGF164. These findings suggest that HIF-1a activates VEGF-independent cell-autonomous mechanisms to sustain oxygen levels in the challenged avascular cartilage by reducing oxygen consumption. Hence, regulation of the metabolic pathways by HIF-1a and VEGF-dependent regulation of angiogenesis coordinately act to maintain physiological cartilage oxygenation. We conclude that VEGF and HIF-1a are critical preservers of chondrocyte survival by ensuring an adequate balance between availability and handling of oxygen in developing growth cartilage. (c) 2012 American Society for Bone and Mineral Research
C1 [Maes, Christa; Van Looveren, Riet; Carmeliet, Geert] KULeuven, Lab Expt Med & Endocrinol, Louvain, Belgium.
[Araldi, Elisa; Khatri, Richa; Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
[Haigh, Katharina; Haigh, Jody J.] VIB, Dept Mol Biomed Res, Vasc Cell Biol Unit, Ghent, Belgium.
[Haigh, Katharina; Haigh, Jody J.] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium.
[Giaccia, Amato J.] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA.
RP Schipani, E (reprint author), Indiana Univ, Dept Med, Indianapolis, IN 46202 USA.
EM geert.carmeliet@med.kuleuven.be; eschipan@iupui.edu
FU National Institutes of Health [RO1 AR048191-06]; Fund for Scientific
Research (FWO)-Flanders [G.0569.07, G.0500.08, G.0982.11]
FX We thank Dr Henry M Kronenberg for helpful discussions, and Kim Atkin
(Histology Core, Endocrine Unit, MGH), Karen Moermans, Ingrid Stockmans,
and Sophie Torrekens (Legendo, KULeuven) for excellent technical help.
We thank Napoleone Ferrara and Andras Nagy for the VEGF floxed and
Rosa26-VEGF164 Tg mice used in this study. This work was supported by
National Institutes of Health RO1 AR048191-06 (to ES) and Fund for
Scientific Research (FWO)-Flanders G.0569.07 (to GC and JH) and
G.0500.08 and G.0982.11 (to GC).
NR 51
TC 28
Z9 28
U1 0
U2 8
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 MAR
PY 2012
VL 27
IS 3
BP 596
EP 609
DI 10.1002/jbmr.1487
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897UG
UT WOS:000300682500010
PM 22162090
ER
PT J
AU Schwartz, AV
Johnson, KC
Kahn, SE
Shepherd, JA
Nevitt, MC
Peters, AL
Walkup, MP
Hodges, A
Williams, CC
Bray, GA
AF Schwartz, Ann V.
Johnson, Karen C.
Kahn, Steven E.
Shepherd, John A.
Nevitt, Michael C.
Peters, Anne L.
Walkup, Michael P.
Hodges, Amelia
Williams, Carrie C.
Bray, George A.
CA Look AHEAD Res Grp
TI Effect of 1 year of an intentional weight loss intervention on bone
mineral density in type 2 diabetes: Results from the look AHEAD
randomized trial
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE BONE MINERAL DENSITY; WEIGHT LOSS; TYPE 2 DIABETES; OBESITY; GLYCEMIC
CONTROL; PHYSICAL FITNESS
ID OVERWEIGHT POSTMENOPAUSAL WOMEN; LIFE-STYLE INTERVENTION; X-RAY
ABSORPTIOMETRY; FRACTURE RISK; CARDIOVASCULAR-DISEASE; HIP FRACTURE;
OLDER WOMEN; BODY-WEIGHT; MASS; ADULTS
AB Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared with diabetes support and education (DSE) on changes in bone mineral density (BMD) over 12 months. Overweight and obese adults with type 2 diabetes were randomly assigned to ILI or DSE. In a substudy of BMD conducted at 5 of 16 clinical centers, hip, spine, and whole body dual X-ray absorptiometry scans were obtained at baseline and 1-year later on 642 of 739 ILI and 632 of 740 DSE participants. At baseline, mean age was 58.4 years, and average body mass index was 35.2?kg/m2. Total hip BMD T-score was <-2.5 in 1% and <-1.0 in 8%. At 1 year, weight loss was greater in ILI than DSE (-8.6% versus -0.7%), and glycemic control and fitness were also improved. Bone loss over 1 year was greater in ILI at the total hip (-1.4% versus -0.4%; p?0.001) and femoral neck (-1.5% versus -0.8%; p?=?0.009), but change in BMD for the lumbar spine and whole body did not differ between groups. In ILI, bone loss at the total hip was independently associated with weight loss in men and women and with poorer glycemic control in men, but was not associated with changes in fitness. One year of an intensive lifestyle intervention in adults with type 2 diabetes, resulting in weight loss, was associated with a modest increase in hip bone loss despite improved fitness and glycemic control. (c) 2012 American Society for Bone and Mineral Research
C1 [Schwartz, Ann V.; Nevitt, Michael C.] Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94107 USA.
[Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA.
[Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
[Shepherd, John A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94107 USA.
[Peters, Anne L.] Keck Sch Med USC, Div Endocrinol, Dept Med, Los Angeles, CA USA.
[Walkup, Michael P.; Hodges, Amelia; Williams, Carrie C.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
RP Schwartz, AV (reprint author), Univ Calif San Francisco, Dept Biostat & Epidemiol, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA.
EM aschwartz@psg.ucsf.edu
OI Peters, Anne/0000-0003-0520-0776; Kahn, Steven/0000-0001-7307-9002
FU Department of Health and Human Services through National Institutes of
Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182,
DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135,
DK56992]; National Institute of Diabetes and Digestive and Kidney
Diseases; National Heart, Lung, and Blood Institute; National Institute
of Nursing Research; National Center on Minority Health and Health
Disparities; Office of Research on Women's Health; Centers for Disease
Control and Prevention; Department of Veterans Affairs; Johns Hopkins
Medical Institutions Bayview General Clinical Research Center
[M01RR02719]; Massachusetts General Hospital Mallinckrodt General
Clinical Research Center [M01RR01066]; University of Colorado Health
Sciences Center General Clinical Research Center [M01RR00051]; Clinical
Nutrition Research Unit [P30 DK48520]; University of Tennessee at
Memphis General Clinical Research Center [M01RR0021140]; University of
Pittsburgh General Clinical Research Center [M01RR000056 44]; NIH [DK
046204]; VA Puget Sound Health Care System/University of Washington,
Medical Research Service, Department of Veterans Affairs; Frederic C.
Bartter General Clinical Research Center [M01RR01346]
FX This study is supported by the Department of Health and Human Services
through the following cooperative agreements from the National
Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171,
DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219,
DK57008, DK57135, and DK56992. The following federal agencies have
contributed support: National Institute of Diabetes and Digestive and
Kidney Diseases; National Heart, Lung, and Blood Institute; National
Institute of Nursing Research; National Center on Minority Health and
Health Disparities; Office of Research on Women's Health; the Centers
for Disease Control and Prevention; and the Department of Veterans
Affairs. This research was supported in part by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases. Additional support was received from The Johns Hopkins Medical
Institutions Bayview General Clinical Research Center (M01RR02719); the
Massachusetts General Hospital Mallinckrodt General Clinical Research
Center (M01RR01066); the University of Colorado Health Sciences Center
General Clinical Research Center (M01RR00051) and Clinical Nutrition
Research Unit (P30 DK48520); the University of Tennessee at Memphis
General Clinical Research Center (M01RR0021140); the University of
Pittsburgh General Clinical Research Center (M01RR000056 44) and NIH
Grant (DK 046204); and the VA Puget Sound Health Care System/University
of Washington, Medical Research Service, Department of Veterans Affairs;
Frederic C. Bartter General Clinical Research Center (M01RR01346).
NR 28
TC 29
Z9 29
U1 0
U2 9
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 MAR
PY 2012
VL 27
IS 3
BP 619
EP 627
DI 10.1002/jbmr.1483
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897UG
UT WOS:000300682500012
PM 22354851
ER
PT J
AU White, BA
Brown, DFM
Sinclair, J
Chang, YC
Carignan, S
McIntyre, J
Biddinger, PD
AF White, Benjamin A.
Brown, David F. M.
Sinclair, Julia
Chang, Yuchiao
Carignan, Sarah
McIntyre, Joyce
Biddinger, Paul D.
TI SUPPLEMENTED TRIAGE AND RAPID TREATMENT (START) IMPROVES PERFORMANCE
MEASURES IN THE EMERGENCY DEPARTMENT
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE ED crowding; triage; triage physician; ED LOS; LWCA; ED performance
ID MYOCARDIAL-INFARCTION; SEVERE PAIN; POOR CARE; THROUGHPUT; ASSOCIATION;
IMPACT; CONSEQUENCES; MANAGEMENT; PNEUMONIA; PHYSICIAN
AB Background: Emergency Department (ED) crowding is well recognized, and multiple studies have demonstrated its negative effect on patient care. Study Objectives: This study aimed to assess the effect of an intervention, Supplemented Triage and Rapid Treatment (START), on standard ED performance measures. The START program complemented standard ED triage with a team of clinicians who initiated the diagnostic work-up and selectively accelerated disposition in a subset of patients. Methods: This retrospective before after study compared performance measures over two 3-month periods (September-November 2007 and 2008) in an urban, academic tertiary care ED. Data from an electronic patient tracking system were queried over 12,936 patients pre-intervention, and 14,220 patients post-intervention. Primary outcomes included: 1) overall length of stay (LOS), 2) LOS for discharged and admitted patients, and 3) the percentage of patients who left without complete assessment (LWCA). Results: In the post-intervention period, patient volume increased 9% and boarder hours decreased by 1.3%. Median overall ED LOS decreased by 29 min (8%, 361 min pre-intervention, 332 min post-intervention; p < 0.001). Median LOS for discharged patients decreased by 23 min (7%, 318 min pre-intervention, 295 min post-intervention; p < 0.001), and by 31 min (7%, 431 min pre-intervention, 400 min post-intervention) for admitted patients. LWCA was decreased by 1.7% (4.1% pre-intervention, 2.4% post-intervention; p < 0.001). Conclusions: In this study, a comprehensive screening and clinical care program was associated with a significant decrease in overall ED LOS, LOS for discharged and admitted patients, and rate of LWCA, despite an increase in ED patient volume. (C) 2012 Elsevier Inc.
C1 [White, Benjamin A.; Brown, David F. M.; Sinclair, Julia; Chang, Yuchiao; Carignan, Sarah; McIntyre, Joyce; Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP White, BA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl 3B, Boston, MA 02114 USA.
NR 29
TC 7
Z9 7
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0736-4679
J9 J EMERG MED
JI J. Emerg. Med.
PD MAR
PY 2012
VL 42
IS 3
BP 322
EP 328
DI 10.1016/j.jemermed.2010.04.022
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA 918SX
UT WOS:000302272500022
PM 20554420
ER
PT J
AU Nielsen, AS
Kinkel, RP
Tinelli, E
Benner, T
Cohen-Adad, J
Mainero, C
AF Nielsen, A. Scott
Kinkel, R. Philip
Tinelli, Emanuele
Benner, Thomas
Cohen-Adad, Julien
Mainero, Caterina
TI Focal cortical lesion detection in multiple sclerosis: 3 tesla DIR
versus 7 tesla FLASH-T2*
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE multiple sclerosis; magnetic resonance imaging; Ultra-high field;
cerebral cortex; demyelination; MAGNIMS consensus guidelines
ID DEMYELINATION; IMPAIRMENT; MPRAGE; COIL
AB Purpose: To evaluate the inter-rater agreement of cortical lesion detection using 7 Tesla (T) FLASH-T2* and 3T DIR sequences.
Materials and Methods: Twenty-six patients with multiple sclerosis were scanned on a human 7T (Siemens) and 3T MRI (TIM Trio, Siemens) to acquire 3T DIR/MEMPR and 7T FLASH-T2* sequences. Four independent reviewers scored and categorized cortical lesions in the bilateral precentral gyri (motor strips) as leukocortical, intracortical, or subpial. Inter-rater agreement was assessed according to lesion category using the kappa statistic. The sensitivity of recent MAGNIMS consensus guidelines for cortical lesion detection using 3T DIR was assessed with 7T FLASH-T2* as the reference gold standard.
Results: Inter-rater agreement at 7T was excellent compared with 3T (k 0.97 versus 0.12). FLASH-T2* at 7T detected subpial lesions while 3T DIR did not. The predicted sensitivity of 3T DIR sequence for cortical lesions in vivo is modest (range of 13.6 to 18.3%).
Conclusion: The 7T FLASH-T2* detects more corticalparticularly subpial-lesions compared with 3T DIR. In the absence of DIR/postmortem data, 7T FLASH-T2* is a suitable gold-standard instrument and should be incorporated into future consensus guidelines.
C1 [Mainero, Caterina] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Nielsen, A. Scott; Kinkel, R. Philip] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Nielsen, A. Scott; Kinkel, R. Philip; Cohen-Adad, Julien; Mainero, Caterina] Harvard Univ, Sch Med, Boston, MA USA.
[Tinelli, Emanuele] Univ Rome, Dept Neurol & Psychiat, La Sapienza, Italy.
RP Mainero, C (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM caterina@nmr.mgh.harvard.edu
FU National Multiple Sclerosis Society [RG 4281-A-1, FP 1770A1]; National
Center for Research Resources [P41-RR14075]; BIRN Morphometric [U24
RR021382]; National Institutes of Health [KL2 RR025757-01]
FX Contract grant sponsor: National Multiple Sclerosis Society; Contract
grant number: RG 4281-A-1; Contract grant sponsor: the National Center
for Research Resources; Contract grant number: P41-RR14075; Contract
grant sponsor: BIRN Morphometric, Project BIRN002; Contract grant
number: U24 RR021382; Contract grant sponsor: National Institutes of
Health; Contract grant number: KL2 RR025757-01; Contract grant sponsor:
National Multiple Sclerosis Society; Contract grant number: FP 1770A1.
NR 28
TC 33
Z9 33
U1 1
U2 5
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 MAR
PY 2012
VL 35
IS 3
BP 537
EP 542
DI 10.1002/jmri.22847
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 897WH
UT WOS:000300690400006
PM 22045554
ER
PT J
AU Bansal, AK
Truccolo, W
Vargas-Irwin, CE
Donoghue, JP
AF Bansal, Arjun K.
Truccolo, Wilson
Vargas-Irwin, Carlos E.
Donoghue, John P.
TI Decoding 3D reach and grasp from hybrid signals in motor and premotor
cortices: spikes, multiunit activity, and local field potentials
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE motor cortex; neural signals; neural coding; brain-machine interfaces;
neural prosthesis
ID POSTERIOR PARIETAL CORTEX; MOVEMENT TRAJECTORIES; MACAQUE MONKEY; HAND
MOVEMENTS; NEURONS; PREDICTION; HUMANS; ORGANIZATION; POPULATIONS;
KINEMATICS
AB Bansal AK, Truccolo W, Vargas-Irwin CE, Donoghue JP. Decoding 3D reach and grasp from hybrid signals in motor and premotor cortices: spikes, multiunit activity, and local field potentials. J Neurophysiol 107: 1337-1355, 2012. First published December 7, 2011; doi: 10.1152/jn.00781.2011.-Neural activity in motor cortex during reach and grasp movements shows modulations in a broad range of signals from single-neuron spiking activity (SA) to various frequency bands in broadband local field potentials (LFPs). In particular, spatiotemporal patterns in multiband LFPs are thought to reflect dendritic integration of local and interareal synaptic inputs, attentional and preparatory processes, and multiunit activity (MUA) related to movement representation in the local motor area. Nevertheless, the relationship between multiband LFPs and SA, and their relationship to movement parameters and their relative value as brain-computer interface (BCI) control signals, remain poorly understood. Also, although this broad range of signals may provide complementary information channels in primary (MI) and ventral premotor (PMv) areas, areal differences in information have not been systematically examined. Here, for the first time, the amount of information in SA and multiband LFPs was compared for MI and PMv by recording from dual 96-multielectrode arrays while monkeys made naturalistic reach and grasp actions. Information was assessed as decoding accuracy for 3D arm end point and grip aperture kinematics based on SA or LFPs in MI and PMv, or combinations of signal types across areas. In contrast with previous studies with <= 16 simultaneous electrodes, here ensembles of > 16 units (on average) carried more information than multiband, multichannel LFPs. Furthermore, reach and grasp information added by various LFP frequency bands was not independent from that in SA ensembles but rather typically less than and primarily contained within the latter. Notably, MI and PMv did not show a particular bias toward reach or grasp for this task or for a broad range of signal types. For BCIs, our results indicate that neuronal ensemble spiking is the preferred signal for decoding, while LFPs and combined signals from PMv and MI can add robustness to BCI control.
C1 [Bansal, Arjun K.; Truccolo, Wilson; Vargas-Irwin, Carlos E.; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Truccolo, Wilson; Donoghue, John P.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA.
[Truccolo, Wilson] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Truccolo, Wilson; Donoghue, John P.] Dept Vet Affairs Med Ctr, Rehabil Res & Dev Serv, Providence, RI USA.
RP Bansal, AK (reprint author), 3 Blackfan Circle,CLS 13th Floor 13077, Boston, MA 02115 USA.
EM arjun.bansal@childrens.harvard.edu
FU National Institutes of Health [National Institute of Neurological
Disorders and Stroke (NINDS)] [F32-NS-061483, NS-25074,
RO1-EB-007401-01]; National Center for Research Resources (NCRR)
[C06-16549-01A1]; National Science Foundation [IIS-0534858]; Office of
Naval Research [N00014-07-1-0803, N00014-16-1-0692]; NINDS
[5K01-NS-057389]; DARPA [N66001-10-C-2010]; Katie Samson Foundation;
Dana Foundation; Office of Research and Development, Rehabilitation R &
D Service, Department of Veterans Affairs
FX This research project was supported by the National Institutes of Health
[National Institute of Neurological Disorders and Stroke (NINDS)
F32-NS-061483, NS-25074, RO1-EB-007401-01] the National Center for
Research Resources (NCRR C06-16549-01A1), the National Science
Foundation (IIS-0534858), the Office of Naval Research
(N00014-07-1-0803, award N00014-16-1-0692), NINDS Career Award
5K01-NS-057389 (W. Truccolo), DARPA (N66001-10-C-2010), the Katie Samson
Foundation, Dana Foundation, Brown Brain Science Fellowship (A. K.
Bansal), and the Office of Research and Development, Rehabilitation R &
D Service, Department of Veterans Affairs.
NR 56
TC 62
Z9 63
U1 0
U2 16
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD MAR
PY 2012
VL 107
IS 5
BP 1337
EP 1355
DI 10.1152/jn.00781.2011
PG 19
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 916TQ
UT WOS:000302126500008
PM 22157115
ER
PT J
AU Williams, EC
McFarland, LV
Nelson, KM
AF Williams, Emily C.
McFarland, Lynne V.
Nelson, Karin M.
TI Alcohol Consumption Among Urban, Suburban, and Rural Veterans Affairs
Outpatients
SO JOURNAL OF RURAL HEALTH
LA English
DT Article
DE alcohol abuse; health services research; health disparities; rural;
veterans
ID PRIMARY-CARE PATIENTS; BEHAVIORAL-COUNSELING INTERVENTIONS;
IDENTIFICATION TEST AUDIT; HEALTH-STATUS; PREVENTIVE-SERVICES; DRINKING
PATTERNS; SCREENING-TEST; RISK DRINKING; USE DISORDERS; MISUSE
AB Purpose: United States rural residents tend toward poorer health than urban residents. Although alcohol use is associated with multiple medical conditions and can be reduced via brief primary care-based interventions, it is unknown whether alcohol consumption differs by rurality among primary care patients. We sought to describe alcohol consumption among urban, suburban, and rural Veterans Affairs (VA) outpatients.
Methods: Outpatients from 7 VA facilities responded to mailed surveys that included the validated Alcohol Use Disorders Identification Test Consumption (AUDIT-C) screening questionnaire. The ZIP code approximation of the US Department of Agriculture's rural-urban commuting area (RUCA) codes classified participants into urban, suburban, and rural areas. For each area, adjusted logistic regression models estimated the prevalence of past-year abstinence among all participants and unhealthy alcohol use (AUDIT-C = 3 for women and = 4 for men) among drinkers.
Findings: Among 33,883 outpatients, 14,967 (44%) reported abstinence. Among 18,916 drinkers, 8,524 (45%) screened positive for unhealthy alcohol use. The adjusted prevalence of abstinence was lowest in urban residents (43%, 95% CI 42%-43%) with significantly higher rates in both suburban and rural residents [ 45% (44%-46%) and 46% (45%-47%), respectively]. No significant differences were observed in the adjusted prevalence of unhealthy alcohol use among drinkers.
Conclusions: Abstinence is slightly more common among rural and suburban than urban VA outpatients, but unhealthy alcohol use does not vary by rurality. As the VA and other health systems implement evidence-based care for unhealthy alcohol use, more research is needed to identify whether preventive strategies targeted to high-risk areas are needed.
C1 [Williams, Emily C.; McFarland, Lynne V.; Nelson, Karin M.] Vet Affairs VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, Seattle, WA USA.
[Nelson, Karin M.] Vet Affairs VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA.
[Williams, Emily C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA.
RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM emily.williams3@va.gov
FU US Department of Veterans Affairs, Office of Research and Development,
VA Health Services [IIR 04-436-3]; Seattle Epidemiologic Research and
Information Center; VA HSRD [SDR96-002, IIR99-376]
FX This material is based upon work supported by the US Department of
Veterans Affairs, Office of Research and Development, VA Health Services
Research and Development Program (IIR 04-436-3), and the Seattle
Epidemiologic Research and Information Center. The parent study, the VA
Ambulatory Care Quality Improvement Project (ACQUIP), was funded by VA
HSR&D Grants #SDR96-002 and IIR99-376. Views expressed in this article
are those of the authors and do not necessarily represent the views of
the Department of Veterans Affairs or the University of Washington. For
further information, contact: Emily C. Williams, PhD, MPH; VA Puget
Sound Health Care System; 1100 Olive Way, Suite 1400; Seattle, WA 98101;
e-mail emily.williams3@va.gov.
NR 49
TC 5
Z9 5
U1 2
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0890-765X
J9 J RURAL HEALTH
JI J. Rural Health
PD SPR
PY 2012
VL 28
IS 2
BP 202
EP 210
DI 10.1111/j.1748-0361.2011.00389.x
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 916BI
UT WOS:000302071200011
PM 22458321
ER
PT J
AU Kuye, IO
Jain, NB
Warner, L
Herndon, JH
Warner, JJP
AF Kuye, Ifedayo O.
Jain, Nitin B.
Warner, Lauren
Herndon, James H.
Warner, Jon J. P.
TI Economic evaluations in shoulder pathologies: a systematic review of the
literature
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Review
DE Shoulder surgery; shoulder pathology; cost-effectiveness; economic
evaluation; cost-utility; cost-minimization; health economics
ID ROTATOR CUFF REPAIR; COST-EFFECTIVENESS ANALYSIS; OPEN BANKART REPAIR;
HEALTH-CARE; ARTHROSCOPIC ACROMIOPLASTY; IMPINGEMENT SYNDROME; ADHESIVE
CAPSULITIS; RANDOMIZED-TRIAL; BENEFIT ANALYSES; THERAPY PROGRAM
AB Background: Economic evaluations provide decision makers with a tool for reducing health care costs because they assess both the costs and consequences of health care interventions. This study reviewed the quality of published economic evaluations for shoulder pathologies.
Materials and method: A MEDLINE search was conducted to identify articles published from 1980 to 2010 that contained "cost" or "economic" combined with terms for several shoulder disorders and treatments. We selected studies that fit the definition of 1 of the 4 routinely performed economic evaluations: cost-minimization, cost-effectiveness, cost-utility, and cost-benefit analyses. Study quality was determined by measuring adherence to 6 established health economic principles, as described in the literature.
Results: The search retrieved 942 studies. Of these, 32 were determined to be economic evaluations, and 53% of the economic evaluations were published from 2005 to 2010. Only 8 of the 32 studies (25%) adhered to all 6 health economic principles. Publication in a nonsurgical journal (P < .05) or in more recent years (P < .01) was significantly associated with higher quality.
Conclusion: Future health care resource allocation will likely be based on the economic feasibility of treatments. Although the number and quality of economic evaluations of shoulder disorders have risen in recent years, the current state of the literature is poor. Given that availability of such data may factor in private and public reimbursement decisions, there is a clear demand for more rigorous economic evaluations.
Level of evidence: Level IV, Systematic Review of Economic and Decision Analyses. (C) 2012 Journal of Shoulder and Elbow Surgery Board of Trustees.
C1 [Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Dept Orthoped, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA.
[Jain, Nitin B.] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA.
[Jain, Nitin B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Jain, Nitin B.] Harvard Univ, Sch Med, Boston, MA USA.
[Warner, Lauren] Colgate Univ, Hamilton, NY 13346 USA.
RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, Dept Orthoped, Yawkey Ctr Outpatient Care, 55 Fruit St,Ste 3200,3G,Rm 3-046, Boston, MA 02114 USA.
EM jwarner@partners.org
FU National institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) [1K23AR059199]; Foundation for PMR; Biomedical Research
Institute at Brigham and Women's Hospital
FX Dr Jain is supported by funding from the National institute of Arthritis
and Musculoskeletal and Skin Diseases (NIAMS; project no. 1K23AR059199),
the Foundation for PM&R, and the Biomedical Research Institute at
Brigham and Women's Hospital. The remaining authors, their immediate
families, and any research foundations with which they are affiliated
have not received any financial payments or other benefits from any
commercial entity related to the subject of this article.
NR 54
TC 6
Z9 6
U1 1
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1058-2746
J9 J SHOULDER ELB SURG
JI J. Shoulder Elbow Surg.
PD MAR
PY 2012
VL 21
IS 3
BP 367
EP 375
DI 10.1016/j.jse.2011.05.019
PG 9
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA 919AD
UT WOS:000302292100018
PM 21865060
ER
PT J
AU Ring, D
AF Ring, David
TI Regarding the "Editor's Note"
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Letter
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1058-2746
J9 J SHOULDER ELB SURG
JI J. Shoulder Elbow Surg.
PD MAR
PY 2012
VL 21
IS 3
BP E21
EP E22
DI 10.1016/j.jse.2011.10.025
PG 3
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA 919AD
UT WOS:000302292100006
PM 22420044
ER
PT J
AU Taylor, JS
DeMers, SM
Vig, EK
Borson, S
AF Taylor, Janelle S.
DeMers, Shaune M.
Vig, Elizabeth K.
Borson, Soo
TI The Disappearing Subject: Exclusion of People with Cognitive Impairment
and Dementia from Geriatrics Research
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE exclusion criteria; research methodologies
ID DECISION-MAKING CAPACITY; RESEARCH CONSENT CAPACITY; NURSING-HOME
RESIDENTS; QUALITY-OF-LIFE; OLDER-ADULTS; AGING RESEARCH; INCONTINENCE;
INDIVIDUALS; MEDICATION; STRATEGIES
AB OBJECTIVES: To evaluate exclusion of persons with cognitive impairment from research in geriatrics by determining its frequency, method, and rationale and treatment in the resulting publications.
DESIGN: All original research articles published in 2008 and 2009 in the Journal of the American Geriatrics Society (n = 434) were reviewed using a structured data collection tool.
SETTING: The Journal of the American Geriatrics Society.
PARTICIPANTS: There were no participants in this study.
MEASUREMENTS: Data captured included recruitment method, explicit criterion for exclusion of persons with cognitive impairment, justification of exclusion criterion, reason given for exclusion, percentage of individuals excluded, and mention of exclusion as a possible limitation.
RESULTS: Of 434 articles examined, 16% used recruitment methods likely to reduce participation by persons with cognitive impairment. At least 29% of studies (n = 127) employed explicit exclusion criteria. Half used the Folstein Mini-Mental State Examination (MMSE), with variable cut points (10, 12, 17, 18, 23, 26), and 19% excluded individuals for "having dementia" without specifying how this was determined. Few (6%) provided any justification for exclusion criteria used, only 43% gave any reason for exclusion, and only 14% discussed exclusion as a possible limitation.
CONCLUSION: Persons with cognitive impairment are frequently excluded from research, often without rationale or mention of exclusion as a limitation or any discussion of its potential effect on the evidence base in geriatrics. When necessary, exclusion should be done thoughtfully and with awareness that this may reduce the clinical utility of study findings. J Am Geriatr Soc 60:413-419, 2012.
C1 [Taylor, Janelle S.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA.
[DeMers, Shaune M.; Borson, Soo] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Vig, Elizabeth K.] Univ Washington, Dept Geriatr, Seattle, WA 98195 USA.
[Vig, Elizabeth K.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Taylor, JS (reprint author), Univ Washington, Dept Anthropol, Box 353100, Seattle, WA 98195 USA.
EM jstaylor@uw.edu
NR 37
TC 21
Z9 21
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2012
VL 60
IS 3
BP 413
EP 419
DI 10.1111/j.1532-5415.2011.03847.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 906KM
UT WOS:000301344000002
PM 22288835
ER
PT J
AU Stineman, MG
Xie, DW
Pan, Q
Kurichi, JE
Zhang, Z
Saliba, D
Henry-Sanchez, JT
Streim, J
AF Stineman, Margaret G.
Xie, Dawei
Pan, Qiang
Kurichi, Jibby E.
Zhang, Zi
Saliba, Debra
Henry-Sanchez, John T.
Streim, Joel
TI All-Cause 1-, 5-, and 10-Year Mortality in Elderly People According to
Activities of Daily Living Stage
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE activities of daily living; staging; mortality; risk factors
ID CASE-MIX; PHYSICAL INDEPENDENCE; FUNCTIONAL STATUS; OLDER-ADULTS;
HEALTH; VALIDATION; DISABILITY; INDEX; LIFE; HOSPITALIZATION
AB OBJECTIVES: To examine the independent association between five stages of activities of daily living (ADLs) and mortality after accounting for known diagnostic and sociodemographic risk factors.
DESIGN: For five stages of ADLs (0 to IV), determined according to the severity and pattern of ADL limitations, unadjusted life expectancies and adjusted associations with mortality were estimated using a Cox proportional hazards regression model.
SETTING: Community,
PARTICIPANTS: Nine thousand four hundred forty-seven participants aged 70 and older from the second Longitudinal Study of Aging.
MEASUREMENTS: One-, 5-, and 10-year survival and time to death.
RESULTS: Median life expectancy was 10.6 years for participants with no ADL limitations and 6.5, 5.1, 3.8, and 1.6 years for those at ADL stages I, II, III, and IV, respectively. The sociodemographic-and diagnosticadjusted hazard of death at 1 year was five times as great at stage IV as at stage 0 (hazard ratio = 5.6, 95% confidence interval = 3.8-8.3). The associations between ADL stage and mortality declined over time but remained statistically significant at 5 and 10 years.
CONCLUSION: ADL stage continued to explain mortality risk after adjusting for known risk factors including advanced age, stroke, and cancer. ADL stages might aid clinical care planning and policy as a powerful prognostic indicator particularly of short-term mortality, improving on current ADL measures by profiling activity limitations of relevance to determining community support needs. J Am Geriatr Soc 60:485-492, 2012.
C1 [Stineman, Margaret G.; Xie, Dawei; Pan, Qiang; Kurichi, Jibby E.; Zhang, Zi] Univ Calif Los Angeles, Dept Biostat & Epidemiol, JH Borun Ctr Gerontol Res, Ctr Clin Epidemiol & Biostat, Los Angeles, CA USA.
[Stineman, Margaret G.] Univ Calif Los Angeles, Dept Phys Med & Rehabil, JH Borun Ctr Gerontol Res, Perelman Sch Med, Los Angeles, CA USA.
[Saliba, Debra] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Geriatr Res Educ, JH Borun Ctr Gerontol Res, Los Angeles, CA USA.
[Saliba, Debra] RAND Corp, Santa Monica, CA USA.
[Henry-Sanchez, John T.] Hosp La Concepc, San German, PR USA.
[Streim, Joel] Univ Penn, Geriatr Psychiat Sect, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Streim, Joel] Philadelphia Vet Affairs Med Ctr, Vet Integrated Serv Network Mental Illness Res Ed, Philadelphia, PA USA.
RP Stineman, MG (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Geriatr Psychiat Sect, Dept Psychiat,Perelman Sch Med, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM mstinema@exchange.upenn.edu
FU National Institutes of Health [AG032420 -01A1]; National Institute of
Child Health and Human Development, National Center for Medical
Rehabilitation Research [T32-HD-007425]
FX The research for this manuscript was supported by the National
Institutes of Health (AG032420 -01A1) and a Post-Doctoral Fellowship for
Dr. Henry-Sanchez (T32-HD-007425) awarded to the University of
Pennsylvania from the National Institute of Child Health and Human
Development, National Center for Medical Rehabilitation Research.
NR 42
TC 33
Z9 33
U1 3
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2012
VL 60
IS 3
BP 485
EP 492
DI 10.1111/j.1532-5415.2011.03867.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 906KM
UT WOS:000301344000012
PM 22352414
ER
PT J
AU King, J
Yourman, L
Ahalt, C
Eng, C
Knight, SJ
Perez-Stable, EJ
Smith, AK
AF King, Jennifer
Yourman, Lindsey
Ahalt, Cyrus
Eng, Catherine
Knight, Sara J.
Perez-Stable, Eliseo J.
Smith, Alexander K.
TI Quality of Life in Late-Life Disability: "I Don't Feel Bitter Because I
Am in a Wheelchair"
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE ethnicity; quality of life; disability
ID OLDER AGES; LAST YEAR; HEALTH; MODEL; TRAJECTORIES; CHALLENGE; DECLINE;
FRAIL; CARE
AB OBJECTIVES: To determine perceived quality of life in a diverse population of elderly adults with late-life disability.
DESIGN: Qualitative cross-sectional study.
SETTING: Community-dwelling participants were recruited from San Francisco's On Lok Lifeways program, the first Program of All-inclusive Care for the Elderly. On Lok enrollees meet Medicaid criteria for nursing home placement.
PARTICIPANTS: Sixty-two elderly adults with a mean age of 78 and a mean 2.4 activity of daily living dependencies and 6.6 instrumental activity of daily living dependencies were interviewed. Respondents were 63% female, 24% white, 19% black, 18% Latino, 32% Chinese American, and 6% other race.
MEASUREMENTS: Elderly adults who scored higher than 17 points on the Mini-Mental State Examination were interviewed. Interviews were conducted in English, Spanish, and Cantonese. Respondents were asked to rate their overall quality of life on a 5-point scale. Open-ended questions explored positive and negative aspects of participants' daily experiences. Interviews were analyzed using modified grounded theory and digital coding software. RESULTS: Eighty-seven percent of respondents rated their quality of life in the middle range of the quality-of-life spectrum (fair to very good). Themes were similar across ethnic groups. Most themes could be grouped into four domains that dependent elderly adults considered important to their quality of life: physical (e.g., pain), psychological (e.g., depression), spiritual or religious (e.g., religious coping), and social (e.g., life-space). Dignity and a sense of control were identified as themes that are the most closely tied to overall quality of life.
CONCLUSION: Factors that influence quality of life in late-life disability were similar across ethnic groups. As the number of elderly adults from diverse backgrounds with late life disability increases in the United States, interventions should be targeted to maximize daily sense of control and dignity. J Am Geriatr Soc 60:569-576, 2012.
C1 [Yourman, Lindsey; Ahalt, Cyrus; Eng, Catherine; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94121 USA.
[Perez-Stable, Eliseo J.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94121 USA.
[Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
Univ Calif San Francisco, Dept Urol, San Francisco, CA 94121 USA.
[Perez-Stable, Eliseo J.] Univ Calif San Francisco, Med Effectiveness Res Ctr Div Populat, San Francisco, CA 94121 USA.
[King, Jennifer] Univ Calif San Francisco, Sch Med, San Francisco, CA 94121 USA.
[Ahalt, Cyrus; Knight, Sara J.; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Eng, Catherine; Knight, Sara J.] Lok Lifeways, San Francisco, CA USA.
RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 4150 Clement St,181G, San Francisco, CA 94121 USA.
EM aksmith@ucsf.edu
FU Resource Centers for Minority Aging Research [P30-AG15272]; National
Institute on Aging, National Institutes of Health; National Center for
Research Resources UCSF-CTSI [UL1 RR024131]; Atlantic Philanthropies;
Society of General Internal Medicine; John A. Hartford Foundation;
Association of Specialty Professors
FX Dr. Smith was supported by Grant P30-AG15272 of the Resource Centers for
Minority Aging Research program funded by the National Institute on
Aging, National Institutes of Health. Additional support provided by the
National Center for Research Resources UCSF-CTSI (UL1 RR024131),
Atlantic Philanthropies, the Society of General Internal Medicine, the
John A. Hartford Foundation, and the Association of Specialty
Professors. An early version of this paper was presented in abstract
form at the 2011 Annual Meetings of the American Geriatrics Society,
National Harbor, Maryland, and the Society of General Internal Medicine,
Phoenix, Arizona.
NR 26
TC 16
Z9 16
U1 3
U2 24
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2012
VL 60
IS 3
BP 569
EP 576
DI 10.1111/j.1532-5415.2011.03844.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 906KM
UT WOS:000301344000024
PM 22288767
ER
PT J
AU Noble, VE
AF Noble, Vicki E.
TI Think Ultrasound When Evaluating for Pneumothorax
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Editorial Material
ID TRAUMATIC PNEUMOTHORAX; BEDSIDE ULTRASOUND; CHEST RADIOGRAPHY
C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Noble, VE (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson,3B,55 Fruit St, Boston, MA 02114 USA.
EM vnoble@partners.org
NR 7
TC 5
Z9 5
U1 0
U2 0
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 MAR
PY 2012
VL 31
IS 3
BP 501
EP 504
PG 4
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 905ZZ
UT WOS:000301316000019
PM 22368142
ER
PT J
AU Kam, WWY
Wu, X
Chan, ST
AF Kam, Winnie Wai-Ying
Wu, Xing
Chan, Suk-Tak
TI The feasibility of 2-back task with alphabets and functional
transcranial Doppler sonography in assessing hemispheric lateralization
of working memory in Chinese
SO NEUROLOGY ASIA
LA English
DT Article
ID FLOW-VELOCITY CHANGES; CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; LANGUAGE
LATERALIZATION; PREFRONTAL CORTEX; COGNITIVE TASKS; WADA TEST; BRAIN
ACTIVATION; MRI; CHARACTERS
AB Background: Hemispheric asymmetry studies of working memory are mainly carried out in western countries. Data on Chinese is limited in this area of research. On the other hand, working memory assessment can be limited by the temporal resolution of the imaging modality as well as the design of the cognitive paradigm. These methodological limitations influence result interpretation hence hinder cross study comparison. Hemispheric study of memory using a pure working memory paradigm on native Chinese speakers, using a hemodynamic technique with high temporal resolution is thus mandatory. Objective: We aimed to investigate the feasibility of the functional transcranial Doppler sonography (fTCD) and 2-back task with alphabets in assessing the hemispheric lateralization of memory in healthy right-handed Chinese. Methods: Thirteen healthy right-handed Chinese subjects (7 males and 6 females, 19-22 years old) were included. Bilateral monitoring of the cerebral blood flow velocity (CFBV) changes in their left and right middle cerebral arteries (MCAs) was performed using fTCD during their performance of a 2-back working memory task with alphabets. Differences of CBFV change between left and right MCAs were analyzed, and the laterality index (LI) was determined. Results: Left lateralization was found in all subjects, with females performed better than males (p < 0.05). No difference in age, response time and LI between the male and female subjects could be observed (p > 0.05). A weak correlation was found between performance accuracy/response time and LI (r(2) = 0.12).
Conclusion: To the best of our knowledge, this is the first report on the use of fTCD in memory function assessment in Chinese. The consistency of our results with previous studies demonstrates the feasibility as well as the potential application of the 2-back task with alphabets and fTCD, as a bedside assessment system of memory function in native Chinese speaking population.
C1 [Kam, Winnie Wai-Ying] Australian Nucl Sci & Technol Org, Lucas Heights, NSW 2234, Australia.
[Wu, Xing] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
[Chan, Suk-Tak] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Kam, WWY (reprint author), Australian Nucl Sci & Technol Org, Lucas Heights, NSW 2234, Australia.
EM wik@ansto.gov.au
RI Kam, Winnie/B-7407-2013; Chan, Suk-tak/G-5846-2015
OI Kam, Winnie/0000-0002-5508-2432;
NR 50
TC 0
Z9 0
U1 0
U2 6
PU ASEAN NEUROLOGICAL ASSOC
PI KUALA LUMPUR
PA UNIV MALAYA MEDICAL CENTRE, NEUROLOGY LABORATORY, KUALA LUMPUR, 59100,
MALAYSIA
SN 1823-6138
J9 NEUROL ASIA
JI Neurol. Asia
PD MAR
PY 2012
VL 17
IS 1
BP 39
EP 48
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 917GI
UT WOS:000302160400006
ER
PT J
AU Manchikanti, L
Singh, V
Hirsch, JA
AF Manchikanti, Laxmaiah
Singh, Vijay
Hirsch, Joshua A.
TI Saga of Payment Systems of Ambulatory Surgery Centers for Interventional
Techniques: An Update
SO PAIN PHYSICIAN
LA English
DT Review
DE Outpatient prospective payment system; ambulatory surgery center payment
system; Government Accountability Office; Medicare Modernization and
Improvement Act; interventional techniques
ID EPIDURAL STEROID INJECTIONS; LOW-BACK-PAIN; CHRONIC SPINAL PAIN; ACTIVE
CONTROLLED-TRIAL; LUMBAR DISC HERNIATION; AFFORDABLE CARE ACT;
DOUBLE-BLIND TRIAL; EQUIVALENCE CONTROLLED-TRIAL; CLINICAL-PRACTICE
GUIDELINES; DRUG-MONITORING PROGRAMS
AB The health care system in the United States has been criticized for skyrocketing expenditures and quality deficits. Simultaneously, health care providers and systems are under pressure to provide better and more proficient care. The landscape of the US health care system is shaped by federal and private payers which continue to develop initiatives designed to curtail costs. These include value-based reimbursement programs; cost-shifting expenses to the consumer and reducing reimbursement of providers and facilities. Moreover, there is an underlying thought to steer provision of health care to theoretically more efficient settings. Many of these initiatives are based on affordable health care reform.
The major aspects of curtailing health care costs include hospital and other facility payments as well as physician payments and reductions in the approved services. Consequently, ambulatory surgery centers (ASCs) are not immune to these changes. Until 1970, all surgery was performed in hospitals The development of ASCs and site of service differential payments for in-office procedures have changed the dynamics of surgical trends with outpatient surgeries outpacing inpatient surgeries by as early as 1989. By 2008, approximately 65% of procedures were performed in all outpatient settings including hospital outpatient departments. ASCs claim that improved efficiency in health care delivery allows patients to spend less time in the health care setting with quicker turn over, improving the productivity of the health care team. However, since the majority of the ASCs are owned, in part, by the physicians who staff them, the financial incentives related to ownership have been alleged to potentially alter provider behavior.
The number of Medicare certified ASCs and total Medicare payments from 1999 to 2010 increased significantly, but more recent year-to-year changes are far less substantial when compared to previous years. Net percent revenue growth from 2008 to 2009 was 3.2% and from 2009 to 2010 was 6.2% with an overall increase from 1999 of 183% over a period of 11 years. Similarly, the number of Medicare certified ASCs increased from 2,786 in 1999 to 5,316 in 2010, 1.1% increased from 2009 to 2010, however, a 91% increase from 1999 over a period of 11 years.
Interventional pain management is one of the fastest growing specialties with a footprint in multiple disciplines. Interventional pain management in ASC settings has come a long way since June 1998 proposed Health Care Financing Administration's ASC rule which seriously compromised interventional pain management in the ASC setting. There are many payment challenges facing interventional pain management (IPM) in 2012. Significant changes continue to occur in the payment systems with policies of paying a certain percent of hospital outpatient department payments to ASCs which declined from 63% in 2008 to 56% in 2011, with substantial reductions for add-on codes. The Centers for Medicare and Medicaid Services (CMS) evaluation of IPM codes also consists of multiple misvalued codes.
In conclusion, overall the future of ASCs may appear optimistic, but in the near perspective, specifically in 2012 to 2014, there will be challenging times specifically for interventional pain management centers with the regulatory environment and rapid changes taking place with or without implementation of Affordable Care Act.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 148
TC 16
Z9 16
U1 5
U2 8
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAR-APR
PY 2012
VL 15
IS 2
BP 109
EP 130
PG 22
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 913ZY
UT WOS:000301917800011
PM 22430649
ER
PT J
AU Hirsch, JA
Falco, F
Manchikanti, L
AF Hirsch, Joshua A.
Falco, Frank
Manchikanti, Laxmaiah
TI Necessity and Implications of ICD-10: Facts and Fallacies
SO PAIN PHYSICIAN
LA English
DT Letter
C1 [Hirsch, Joshua A.] Mass Gen Hosp, Boston, MA 02114 USA.
[Falco, Frank] Mid Atlantic Spine, Newark, DE 19713 USA.
[Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA.
RP Hirsch, JA (reprint author), Mass Gen Hosp, GRB 241, Boston, MA 02114 USA.
EM HIrsch@snisonline.org; cssm01@aol.com; drlm@thepainmd.com
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAR-APR
PY 2012
VL 15
IS 2
BP E153
EP E153
PG 1
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 913ZY
UT WOS:000301917800005
PM 22430662
ER
PT J
AU Martel, JM
Toner, M
AF Martel, Joseph M.
Toner, Mehmet
TI Inertial focusing dynamics in spiral microchannels
SO PHYSICS OF FLUIDS
LA English
DT Article
ID CELL-SEPARATION; POISEUILLE FLOW; MICROFLUIDIC SYSTEMS; REYNOLDS-NUMBER;
PARTICLE; FILTRATION; MIGRATION; DEVICE
AB This report details a comprehensive study of inertial focusing dynamics and particle behavior in low aspect ratio (h/w similar to 1/1 to 1/8) spiral microchannels. A continuum of particle streak behavior is shown with longitudinal, cross-sectional, and velocity resolution, yielding a large analyzed parameter space. The dataset is then summarized and compared to prior results from both straight microchannels and other low aspect ratio spiral microchannel designs. Breakdown of focusing into a primary and secondary fluorescent streak is observed in the lowest aspect ratio channels at high average downstream velocities. Streak movement away from the theoretically predicted near inner wall equilibrium position towards the center of the channel at high average downstream velocities is also detailed as a precursor to breakdown. State diagrams detail the overall performance of each device including values of the required channel lengths and the range of velocities over which quality focusing can be achieved. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3681228]
C1 [Martel, Joseph M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Martel, Joseph M.; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA.
[Martel, Joseph M.; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Martel, JM (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM joseph.m.martel@gmail.com
FU National Institute of Biomedical Imaging and Bioengineering (BioMEMS
Resource Center) [P41 EB002503]
FX Joseph M. Martel is a National Science Foundation Graduate Research
Fellow. This work was supported in part by the National Institute of
Biomedical Imaging and Bioengineering (BioMEMS Resource Center, P41
EB002503). The authors thank Octavio Hurtado for microfabrication
training, Bryan Hassel for his help generating straightened images, as
well as Anh Hoang, Ian Wong, Daniel Irimia, and Dino Di Carlo for their
assistance in editing the paper.
NR 33
TC 44
Z9 44
U1 4
U2 46
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 1070-6631
J9 PHYS FLUIDS
JI Phys. Fluids
PD MAR
PY 2012
VL 24
IS 3
AR 032001
DI 10.1063/1.3681228
PG 13
WC Mechanics; Physics, Fluids & Plasmas
SC Mechanics; Physics
GA 918BT
UT WOS:000302224600004
PM 22454556
ER
PT J
AU Shimazaki, H
Amari, S
Brown, EN
Grun, S
AF Shimazaki, Hideaki
Amari, Shun-ichi
Brown, Emery N.
Gruen, Sonja
TI State-Space Analysis of Time-Varying Higher-Order Spike Correlation for
Multiple Neural Spike Train Data
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID CELL ASSEMBLIES; UNITARY EVENTS; NEURONAL INTERACTIONS; SOMATOSENSORY
CORTEX; INFORMATION GEOMETRY; MAXIMUM-LIKELIHOOD; BOLTZMANN MACHINES;
PREFRONTAL CORTEX; CORTICAL NETWORKS; DYNAMIC-ANALYSIS
AB Precise spike coordination between the spiking activities of multiple neurons is suggested as an indication of coordinated network activity in active cell assemblies. Spike correlation analysis aims to identify such cooperative network activity by detecting excess spike synchrony in simultaneously recorded multiple neural spike sequences. Cooperative activity is expected to organize dynamically during behavior and cognition; therefore currently available analysis techniques must be extended to enable the estimation of multiple time-varying spike interactions between neurons simultaneously. In particular, new methods must take advantage of the simultaneous observations of multiple neurons by addressing their higher-order dependencies, which cannot be revealed by pairwise analyses alone. In this paper, we develop a method for estimating time-varying spike interactions by means of a state-space analysis. Discretized parallel spike sequences are modeled as multi-variate binary processes using a log-linear model that provides a well-defined measure of higher-order spike correlation in an information geometry framework. We construct a recursive Bayesian filter/smoother for the extraction of spike interaction parameters. This method can simultaneously estimate the dynamic pairwise spike interactions of multiple single neurons, thereby extending the Ising/spin-glass model analysis of multiple neural spike train data to a nonstationary analysis. Furthermore, the method can estimate dynamic higher-order spike interactions. To validate the inclusion of the higher-order terms in the model, we construct an approximation method to assess the goodness-of-fit to spike data. In addition, we formulate a test method for the presence of higher-order spike correlation even in nonstationary spike data, e. g., data from awake behaving animals. The utility of the proposed methods is tested using simulated spike data with known underlying correlation dynamics. Finally, we apply the methods to neural spike data simultaneously recorded from the motor cortex of an awake monkey and demonstrate that the higher-order spike correlation organizes dynamically in relation to a behavioral demand.
C1 [Shimazaki, Hideaki; Amari, Shun-ichi; Gruen, Sonja] RIKEN Brain Sci Inst, Wako, Saitama, Japan.
[Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Brown, Emery N.] Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Gruen, Sonja] Forschungszentrum Julich, Inst Neurosci & Med INM 6, D-52425 Julich, Germany.
[Gruen, Sonja] Rhein Westfal TH Aachen, Aachen, Germany.
RP Shimazaki, H (reprint author), RIKEN Brain Sci Inst, Wako, Saitama, Japan.
EM shimazaki@brain.riken.jp
RI Shimazaki, Hideaki/C-8606-2009; Grun, Sonja/I-6321-2013; Amari,
Shun-ichi/A-5901-2016
OI Shimazaki, Hideaki/0000-0001-7794-3064; Grun, Sonja/0000-0003-2829-2220;
FU JSPS; RIKEN; [R01 MH59733]; [DP1 OD003646]; [R01 MH071847]
FX This work was supported in part by JSPS Research Fellowships for Young
Scientists (HS), R01 MH59733 (ENB), DP1 OD003646 (ENB), R01 MH071847
(ENB), and RIKEN Strategic Programs for R&D (SG). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 111
TC 33
Z9 33
U1 1
U2 16
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 MAR
PY 2012
VL 8
IS 3
AR e1002385
DI 10.1371/journal.pcbi.1002385
PG 27
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 918IY
UT WOS:000302244000002
PM 22412358
ER
PT J
AU Henn, MR
Boutwell, CL
Charlebois, P
Lennon, NJ
Power, KA
Macalalad, AR
Berlin, AM
Malboeuf, CM
Ryan, EM
Gnerre, S
Zody, MC
Erlich, RL
Green, LM
Berical, A
Wang, YY
Casali, M
Streeck, H
Bloom, AK
Dudek, T
Tully, D
Newman, R
Axten, KL
Gladden, AD
Battis, L
Kemper, M
Zeng, QD
Shea, TP
Gujja, S
Zedlack, C
Gasser, O
Brander, C
Hess, C
Gunthard, HF
Brumme, ZL
Brumme, CJ
Bazner, S
Rychert, J
Tinsley, JP
Mayer, KH
Rosenberg, E
Pereyra, F
Levin, JZ
Young, SK
Jessen, H
Altfeld, M
Birren, BW
Walker, BD
Allen, TM
AF Henn, Matthew R.
Boutwell, Christian L.
Charlebois, Patrick
Lennon, Niall J.
Power, Karen A.
Macalalad, Alexander R.
Berlin, Aaron M.
Malboeuf, Christine M.
Ryan, Elizabeth M.
Gnerre, Sante
Zody, Michael C.
Erlich, Rachel L.
Green, Lisa M.
Berical, Andrew
Wang, Yaoyu
Casali, Monica
Streeck, Hendrik
Bloom, Allyson K.
Dudek, Tim
Tully, Damien
Newman, Ruchi
Axten, Karen L.
Gladden, Adrianne D.
Battis, Laura
Kemper, Michael
Zeng, Qiandong
Shea, Terrance P.
Gujja, Sharvari
Zedlack, Carmen
Gasser, Olivier
Brander, Christian
Hess, Christoph
Guenthard, Huldrych F.
Brumme, Zabrina L.
Brumme, Chanson J.
Bazner, Suzane
Rychert, Jenna
Tinsley, Jake P.
Mayer, Ken H.
Rosenberg, Eric
Pereyra, Florencia
Levin, Joshua Z.
Young, Sarah K.
Jessen, Heiko
Altfeld, Marcus
Birren, Bruce W.
Walker, Bruce D.
Allen, Todd M.
TI Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor
Variants Upon Immune Recognition During Acute Infection
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE ESCAPE; CELL RESPONSES;
REVERSE-TRANSCRIPTASE; DRUG-RESISTANCE; VACCINE DESIGN; IN-VIVO; GAG;
MUTATIONS; TRANSMISSION
AB Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained regions of the virus in order to ensure the maintenance of immunodominant CD8 responses and the sustained decline of early viremia.
C1 [Henn, Matthew R.; Charlebois, Patrick; Lennon, Niall J.; Macalalad, Alexander R.; Berlin, Aaron M.; Malboeuf, Christine M.; Ryan, Elizabeth M.; Gnerre, Sante; Zody, Michael C.; Erlich, Rachel L.; Green, Lisa M.; Casali, Monica; Newman, Ruchi; Zeng, Qiandong; Shea, Terrance P.; Gujja, Sharvari; Levin, Joshua Z.; Young, Sarah K.; Birren, Bruce W.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Boutwell, Christian L.; Power, Karen A.; Berical, Andrew; Wang, Yaoyu; Streeck, Hendrik; Bloom, Allyson K.; Dudek, Tim; Tully, Damien; Axten, Karen L.; Gladden, Adrianne D.; Battis, Laura; Kemper, Michael; Brumme, Zabrina L.; Brumme, Chanson J.; Pereyra, Florencia; Altfeld, Marcus; Walker, Bruce D.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Zedlack, Carmen; Jessen, Heiko] HIV Clin Praxis Jessen, Berlin, Germany.
[Gasser, Olivier; Hess, Christoph] Univ Basel Hosp, Dept Biomed, Immunobiol Lab, CH-4031 Basel, Switzerland.
[Brander, Christian] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain.
[Brander, Christian] Hosp Badalona Germans Trias & Pujol, Irsicaixa AIDS Res Inst HIVACAT, Badalona, Spain.
[Guenthard, Huldrych F.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, CH-8006 Zurich, Switzerland.
[Bazner, Suzane; Rychert, Jenna; Rosenberg, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bazner, Suzane; Rychert, Jenna; Rosenberg, Eric] Harvard Univ, Sch Med, Boston, MA USA.
[Tinsley, Jake P.; Mayer, Ken H.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Henn, MR (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.
EM tallen2@partners.org
RI gunthard, huldrych/F-1724-2011; Gasser, Olivier/I-3663-2013;
Infektiologie, USZ/A-6921-2011; SHCS, all/G-4072-2011; SHCS, int. coll.
A/G-4083-2011; Allen, Todd/F-5473-2011;
OI gunthard, huldrych/0000-0002-1142-6723; Brander,
Christian/0000-0002-0548-5778; Brumme, Chanson/0000-0003-2722-5288
FU Bill and Melinda Gates Foundation; National Institute of Allergy and
Infectious Disease; National Institutes of Health; Department of Health
and Human Services [NIAID P01-AI074415, NIAID T32-AI07245,
HHSN272200900018C, HHSN272200900006C]; Ragon Institute of MGH, MIT and
Harvard; Swiss HIV Cohort Study (SHCS) [535]; Swiss National Science
Foundation (SNF) [33CSC0-108787]
FX This project was funded in part with Federal funds from the Bill and
Melinda Gates Foundation (BDW, TMA), the National Institute of Allergy
and Infectious Disease, the National Institutes of Health, and the
Department of Health and Human Services under grants NIAID P01-AI074415
(TMA, MA), NIAID T32-AI07245 (CLB), and contracts no. HHSN272200900018C
(BWB) and HHSN272200900006C (BWB), as well as by an Innovation Award
from the Ragon Institute of MGH, MIT and Harvard (TMA and MRH) and by
the Swiss HIV Cohort Study (SHCS) project No. 535 (OG, CH, and HFG). We
also thank the International HIV Controllers Study and the SHCS,
supported by the Swiss National Science Foundation (SNF # 33CSC0-108787)
for collaboration.
NR 65
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U1 1
U2 33
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 MAR
PY 2012
VL 8
IS 3
AR e1002529
DI 10.1371/journal.ppat.1002529
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 918CC
UT WOS:000302225600005
PM 22412369
ER
PT J
AU Pfeiffer, PN
Valenstein, M
AF Pfeiffer, Paul N.
Valenstein, Marcia
TI Assessing the Costs of Second-Generation Antipsychotics
SO PSYCHIATRIC SERVICES
LA English
DT Editorial Material
C1 [Pfeiffer, Paul N.] Univ Michigan, US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI 48109 USA.
Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Pfeiffer, PN (reprint author), Univ Michigan, US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI 48109 USA.
NR 0
TC 0
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U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD MAR
PY 2012
VL 63
IS 3
BP 199
EP 199
PG 1
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 917NV
UT WOS:000302185600001
PM 22388524
ER
PT J
AU Kilbourne, AM
Neumann, MS
Waxmonsky, J
Bauer, MS
Kim, HM
Pincus, HA
Thomas, M
AF Kilbourne, Amy M.
Neumann, Mary Spink
Waxmonsky, Jeanette
Bauer, Mark S.
Kim, Hyungin Myra
Pincus, Harold Alan
Thomas, Marshall
TI Evidence-Based Implementation: The Role of Sustained Community-Based
Practice and Research Partnerships
SO PSYCHIATRIC SERVICES
LA English
DT Editorial Material
ID HEALTH-SERVICES RESEARCH; SCIENCE
AB This column describes a process for adapting an evidence-based practice in community clinics in which researchers and community providers participated and the resulting framework for implementation of the practice Replicating Effective Programs Facilitation. A two-day meeting for the Recovery-Oriented Collaborative Care study was conducted to elicit input from more than 50 stakeholders, including community providers, health care administrators, and implementation researchers. The process illustrates an effective researcher-community partnership in which stakeholders worked together not only to adapt the evidence-based practice to the needs of the clinical settings but also to develop the implementation strategy. (Psychiatric Services 63:205 207, 2012; doi: 10.1176/appi.ps.201200032)
C1 [Kilbourne, Amy M.; Kim, Hyungin Myra] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48105 USA.
[Kilbourne, Amy M.; Kim, Hyungin Myra] US Dept Vet Affairs, Ann Arbor Ctr Clin Management Res, Ann Arbor, MI 48105 USA.
[Neumann, Mary Spink] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA.
[Waxmonsky, Jeanette; Thomas, Marshall] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80202 USA.
[Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Pincus, Harold Alan] Columbia Univ, Sch Med, Dept Psychiat, New York, NY USA.
RP Kilbourne, AM (reprint author), Univ Michigan, Dept Psychiat, 11H,2215 Fuller Rd, Ann Arbor, MI 48105 USA.
EM amykilbo@umich.edu
RI Waxmonsky, Jeanette/L-4739-2013
FU NIMH NIH HHS [R01 MH 79994, R01 MH 74509]
NR 5
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U1 0
U2 9
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD MAR
PY 2012
VL 63
IS 3
BP 205
EP 207
DI 10.1176/appi.ps.201200032
PG 3
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 917NV
UT WOS:000302185600003
PM 22388527
ER
PT J
AU Copeland, LA
Pugh, MJ
Hicks, PB
Noel, PH
AF Copeland, Laurel Anne
Pugh, Mary Jo
Hicks, Paul B.
Noel, Polly Hitchcock
TI Use of Obesity Related Care by Psychiatric Patients
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID HEALTH-SERVICES RESEARCH; SEVERE MENTAL-DISORDERS; QUALITY-OF-LIFE;
ANTIPSYCHOTIC MEDICATIONS; WEIGHT-MANAGEMENT; VETERANS-AFFAIRS;
CONTROLLED-TRIAL; SCHIZOPHRENIA; OVERWEIGHT; PATTERNS
AB Objective: The objective of this study was to assess receipt of obesity care by patients with and without mental illness. Methods: The sample consisted of 254,051 obese primary care patients surviving through fiscal year (FY) 2006. Administrative data for Veterans Health Administration (VHA) patients who were obese in FY 2002 (body mass index >= 30) and received primary care in one of six selected VHA regions were included. Outcomes were receipt of obesity care and weight loss during FY 2002 FY 2006. Covariates included baseline mental illness (major depression, posttraumatic stress disorder, and substance use disorders; ICD-9-CM codes 290-311); psychotropic medications associated with weight gain; comorbidity; and demographic characteristics. Results: Most patients were male (95%), non-Hispanic white (80%), older than 50 (mean +/- SD=61 +/- 12) with comorbid hypertension (65%) and dyslipidemia (50%). One-fifth (20%) had mental illness, primarily depression (8%) or posttraumatic stress disorder (6%). Ten percent of the sample lost weight, and 7% gained >= 10% from baseline weight). Although one-third (34%) received obesity care during the study period, receipt of this care was more common among patients with psychiatric diagnoses (46% versus 31%). In multivariable analysis, psychiatric patients prescribed obesogenic psychotropic medications were more likely than other patients to receive obesity care (interaction effect). Conclusions: VITA efforts to help obese patients manage their weight appeared more common for patients prescribed obesogenic psychotropic medication, especially those with psychiatric diagnoses. The results of this study represent an unusual example in which psychiatric patients were relatively more likely to receive care addressing cardiometabolic risk factors. (Psychiatric Services 63:230-236, 2012; doi: 10.1176/appi.ps.201100221)
C1 [Copeland, Laurel Anne] Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, Temple, TX 76502 USA.
[Hicks, Paul B.] Cent Texas Vet Hlth Care Syst, Dept Med, Temple, TX 76502 USA.
[Copeland, Laurel Anne] Scott & White Healthcare, Temple, TX USA.
[Pugh, Mary Jo; Noel, Polly Hitchcock] S Texas Vet Hlth Care Syst, VERDICT Res, San Antonio, TX USA.
[Pugh, Mary Jo] UT Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX USA.
[Noel, Polly Hitchcock] UT Hlth Sci Ctr San Antonio, Div Clin Epidemiol, San Antonio, TX USA.
RP Copeland, LA (reprint author), Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, 2102 Birdcreek Dr, Temple, TX 76502 USA.
EM laurelacopeland@gmail.com
OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209
FU U.S. Department of Veterans Affairs (VA), Health Services Research and
Development Services [IIR-05-121]; Central Texas Veterans Health Care
System; Scott and White Healthcare (Temple, Texas); VERDICT Research at
South Texas Veterans Health Care System; University of Texas Health
Science Center San Antonio
FX This work was supported by the U.S. Department of Veterans Affairs (VA),
Health Services Research and Development Services IIR-05-121, with
additional support from Central Texas Veterans Health Care System, Scott
and White Healthcare (Temple, Texas), VERDICT Research at the South
Texas Veterans Health Care System, and the University of Texas Health
Science Center San Antonio. The views expressed in this article are
those of the authors and do not necessarily represent the views of the
VA.
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U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD MAR
PY 2012
VL 63
IS 3
BP 230
EP 236
DI 10.1176/appi.ps.201100221
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 917NV
UT WOS:000302185600007
PM 22307880
ER
PT J
AU Yang, S
Mulvey, EP
Loughran, TA
Hanusa, BH
AF Yang, Suzanne
Mulvey, Edward P.
Loughran, Thomas A.
Hanusa, Barbara H.
TI Psychiatric Symptoms and Alcohol Use in Community Violence by Persons
With a Psychotic Disorder or Depression
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID NATIONAL EPIDEMIOLOGIC SURVEY; RATING-SCALE; SUBSTANCE-ABUSE;
MENTAL-DISORDER; RISK-ASSESSMENT; BEHAVIOR; SCHIZOPHRENIA; OTHERS;
METAANALYSIS; MEDICATION
AB Objective: Prior studies have shown a significant but modest association between mental disorders and violence and an increased risk in the presence of co-occurring substance use disorders. Categorical diagnoses, however, have limited utility when assessing dynamic risk state over time. This study used data from the MacArthur Violence Risk Assessment Study to examine the relationship of symptom levels and alcohol use to violence in repeated observations within two diagnostic groups. Methods: Participants with a primary categorical diagnosis of depression (N=386) or a psychotic disorder (N=201) were identified. Subscale scores for affective or positive symptoms from the Brief Psychiatric Rating Scale and self-reported alcohol consumption were tested in panel logistic models over five ten-week intervals for their concurrent and lagged relationship to violence. An interaction term between each type of symptom and alcohol use was also tested. Results: In models including the amount of alcohol consumed and symptom levels, a high level of affective symptoms was associated with violence during the next follow-up period only for participants with depression. There was a significant interaction between alcohol use and affective symptoms for participants with depression. Conclusions: The relationship of symptoms and alcohol use to community violence should be considered in the context of the individual's primary diagnosis. Further characterization of interactions between symptoms and substance use in relation to violent behavior may allow for more effective assessment of risk state and interventions for violence prevention. (Psychiatric Services 63:262-269, 2012; doi: 10.1176/appi.ps.201100354)
C1 [Yang, Suzanne] VA Pittsburgh Healthcare Syst, Vet Integrated Serv Network VISN Mental Illness R, Pittsburgh, PA 15206 USA.
[Yang, Suzanne] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA.
[Yang, Suzanne] Univ Pittsburgh, Law & Psychiat Program, Pittsburgh, PA 15260 USA.
[Mulvey, Edward P.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
[Loughran, Thomas A.] Univ Maryland, Dept Criminol, College Pk, MD 20742 USA.
[Hanusa, Barbara H.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Hanusa, Barbara H.] VA Pittsburgh Healthcare Syst, VISN MIRECC 4, Pittsburgh, PA 15206 USA.
RP Yang, S (reprint author), VA Pittsburgh Healthcare Syst, Vet Integrated Serv Network VISN Mental Illness R, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM yangs@upmc.edu
FU National Institute of Mental Health [T32 MH16804]; U.S. Department of
Veterans Affairs (VA), Office of Academic Affiliations
FX During the preparation of the manuscript, Dr. Yang was supported by
grant T32 MH16804 from the National Institute of Mental Health and by
the U.S. Department of Veterans Affairs (VA), Office of Academic
Affiliations, Advanced Fellowship Program in Mental Illness Research and
Treatment. Contents do not represent the views of the VA or the U.S.
government. Dr. Yang thanks Kevin Kim, Ph.D., Candice Odgers, Ph.D., and
Ada Youk, Ph.D., for valuable advice during data analysis and Bruno
Falissard, M.D., Ph.D., for insightful comments on the manuscript.
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PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD MAR
PY 2012
VL 63
IS 3
BP 262
EP 269
DI 10.1176/appi.ps.201100354
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 917NV
UT WOS:000302185600012
PM 22388531
ER
PT J
AU Chang, G
Weiss, A
Kosowsky, JM
Orav, EJ
Smallwood, JA
Rauch, SL
AF Chang, Grace
Weiss, Anthony
Kosowsky, Joshua M.
Orav, Endel John
Smallwood, Jennifer A.
Rauch, Scott L.
TI Characteristics of Adult Psychiatric Patients With Stays of 24 Hours or
More in the Emergency Department
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID CARE
AB Objective: This study identified characteristics of adult psychiatric patients who remained for 24 or more hours in the emergency departments of general hospitals in Massachusetts. Methods: Data were collected starting in June 2008 on a prospective cohort of 1,076 patients who presented for emergency psychiatric evaluation at one of five hospitals. Results: A total of 90 patients (8%) stayed 24 or more hours (median=31 hours). More than 90% (N=1,018) of all patients had health insurance. Characteristics associated with extended stays included homelessness, transfer to another hospital, public insurance, and use of restraints or sitters (p<.05). The two academic medical centers had higher proportions of extended-stay patients than the three community hospitals (12% and 15% versus 1%, 7%, and 7%, respectively; p<.001). Conclusions: Despite overall high rates of health insurance coverage, publicly insured patients waited longer than those with private insurance. Future reforms of Massachusetts' mandatory health insurance program should consider treatment capacity as well. (Psychiatric Services 63:283-286, 2012; doi: 10.1176/appi.ps.201000563)
C1 [Chang, Grace] Boston Hlth Care Syst, Dept Vet Affairs, Dept Psychiat, Brockton, MA 02301 USA.
[Weiss, Anthony] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Kosowsky, Joshua M.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Orav, Endel John] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Smallwood, Jennifer A.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA.
[Chang, Grace; Weiss, Anthony; Kosowsky, Joshua M.; Orav, Endel John; Rauch, Scott L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Chang, G (reprint author), Boston Hlth Care Syst, Dept Vet Affairs, Dept Psychiat, 940 Belmont St, Brockton, MA 02301 USA.
EM grace.chang2@va.gov
FU Partners Psychiatry and Mental Health Division of Health Services
Research from National Institute on Alcohol Abuse and Alcoholism
[K-24-AA000289]
FX This study was supported by the Partners Psychiatry and Mental Health
Division of Health Services Research and grant K-24-AA000289 to Dr.
Chang from the National Institute on Alcohol Abuse and Alcoholism. The
authors thank Kenneth J. Sklar, Ed.D.
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U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD MAR
PY 2012
VL 63
IS 3
BP 283
EP 286
DI 10.1176/appi.ps.201000563
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 917NV
UT WOS:000302185600017
PM 22267250
ER
PT J
AU Dubovsky, AN
Arvikar, S
Stern, TA
Axelrod, L
AF Dubovsky, Amelia N.
Arvikar, Sheila
Stern, Theodore A.
Axelrod, Lloyd
TI The Neuropsychiatric Complications of Glucocorticoid Use: Steroid
Psychosis Revisited
SO PSYCHOSOMATICS
LA English
DT Review
ID RECEIVING CORTICOSTEROID-THERAPY; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
WITHDRAWAL SYNDROME; MAJOR DEPRESSION; CUSHINGS-DISEASE; MOOD DISORDERS;
INDUCED MANIA; PREDNISONE; MEMORY; COGNITION
AB Background: Glucocorticoids are widely prescribed for a variety of diseases and are known to cause neuropsychiatric as well as somatic side effects. Objective: This article will review the incidence, clinical characteristics, course, and treatment of neuropsychiatric effects of glucocorticoids. Methods: We performed a literature review of the neuropsychiatric complications of glucocorticoids using the PubMed database. Results: The neuropsychiatric effects of glucocorticoids involve affective, behavioral, and cognitive manifestations. Serious neuropsychiatric effects occur in about 6% of patients who receive steroids. Although the effects of glucocorticoids are unpredictable, the administered dose is the most significant risk factor for the development of neuropsychiatric symptoms. Dosage reduction typically results in clinical recovery. Although evidence from controlled trials is sparse, administration of antipsychotics or mood stabilizers may be beneficial in the prevention and treatment of neuropsychiatric effects of steroids. Conclusion: The neuropsychiatric effects of glucocorticoids are more diverse than the often-misleading term "steroid psychosis" suggests. This label should be limited to those patients who are truly psychotic, and specific designations applied to patients with other effects. The adverse neuropsychiatric effects of glucocorticoids remain poorly characterized in the literature (which consists largely of case reports and case series). Reliable risk factors (other than dose) that identify individuals at risk are lacking; guidelines for the prevention of neuropsychiatric effects are not evidence-based. Further controlled clinical studies are needed to elucidate the optimal management of glucocorticoid-induced neuropsychiatric symptoms. (Psychosomatics 2012; 53:103-115)
C1 [Dubovsky, Amelia N.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Arvikar, Sheila] Dept Rheumatol Allergy & Immunol, Boston, MA USA.
[Axelrod, Lloyd] Massachusetts Gen Hosp, Dept Med, Div Endocrine, Boston, MA 02114 USA.
RP Dubovsky, AN (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,55 Fruit St, Boston, MA 02114 USA.
EM ADUBOVSKY@PARTNERS.ORG
NR 90
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U1 2
U2 11
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD MAR-APR
PY 2012
VL 53
IS 2
BP 103
EP 115
PG 13
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 915BO
UT WOS:000301998100001
PM 22424158
ER
PT J
AU Wodchis, WP
Bhatia, RS
Leblanc, K
Meshkat, N
Morra, D
AF Wodchis, Walter P.
Bhatia, R. Sacha
Leblanc, Kori
Meshkat, Nazanin
Morra, Dante
TI A Review of the Cost of Atrial Fibrillation
SO VALUE IN HEALTH
LA English
DT Review
DE atrial fibrillation; cost analysis; cost of illness; direct cost;
systematic review
ID CATHETER ABLATION; UNITED-STATES; ANTIARRHYTHMIC-DRUGS;
ECONOMIC-EVALUATION; STROKE PREVENTION; WARFARIN THERAPY;
RHYTHM-CONTROL; RISK-FACTORS; CARE; ANTICOAGULATION
AB Objectives: To systematically review and synthesize the literature on the costs of atrial fibrillation (AF) with attention to study design and costing methods, geography, and intervention approaches. Methods: A systematic search for previously published studies reporting the costs for AF patients was conducted. Data were analyzed in three steps: first by evaluating overall system costs; second by evaluating the relative contribution of specific cost components; and third by examining variations across study designs, across primary treatment approach, and by geography. Finally, a specific review of the treatment costs associated with anticoagulation treatment was examined given the clinical importance and attention given to these costs in the literature. Results: The literature search resulted in 115 articles. On review of the abstracts or full text of these articles, 21 articles met all study criteria and reported on health system AF-related direct costs. A further six articles focused exclusively on anticoagulation costs for patients with AF. The overall average annual system cost across 27 esti-mates obtained from the literature was $5450 (SD = $3624) in 2010 Canadian dollars and ranged from a low of $1,632 to a high of $21,099. About one-third of these costs could be attributed to anticoagulation management. The largest cost component was acute care, followed by outpatient and physician and then medication-related costs. Conclusion: AF-related medical costs are high, reflecting resource-intensive and long-term treatments including anticoagulation treatment. These costs, accompanied with increasing prevalence, justify increased attention to the management of patients with AF. Future studies of AF cost should ensure a broad assessment of the incremental direct medical and societal cost associated with this diagnosis.
C1 [Wodchis, Walter P.] Univ Toronto, Fac Med, Toronto, ON M5T 3M6, Canada.
[Wodchis, Walter P.] Toronto Rehabil Inst, Toronto, ON, Canada.
[Bhatia, R. Sacha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Leblanc, Kori] Univ Toronto, Ctr Innovat & Complex Care, Univ Hlth Network, Fac Pharm, Toronto, ON, Canada.
[Leblanc, Kori] Univ Toronto, Dept Pharm, Toronto, ON, Canada.
[Meshkat, Nazanin; Morra, Dante] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Meshkat, Nazanin] Univ Hlth Network, Div Emergency Med, Toronto, ON, Canada.
[Morra, Dante] Univ Hlth Network, Ctr Innovat Complex Care, Toronto, ON, Canada.
RP Wodchis, WP (reprint author), Univ Toronto, Fac Med, 155 Coll St,4th Floor, Toronto, ON M5T 3M6, Canada.
EM walter.wodchis@utoronto.ca
FU Boehringer Ingelheim
FX The Center for Innovation in Complex Care is supported in part by
Boehringer Ingelheim. The study was carried out independently of the
funder. The publication of this study's results was not reviewed by or
contingent on the approval or censorship of any affiliated sponsor.
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U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD MAR-APR
PY 2012
VL 15
IS 2
BP 240
EP 248
DI 10.1016/j.jval.2011.09.009
PG 9
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 914DZ
UT WOS:000301930600004
PM 22433754
ER
PT J
AU Renaud, B
Brun-Buisson, C
Santin, A
Coma, E
Noyez, C
Fine, MJ
Yealy, DM
Labarere, J
AF Renaud, Bertrand
Brun-Buisson, Christian
Santin, Aline
Coma, Eva
Noyez, Cecile
Fine, Michael J.
Yealy, Donald M.
Labarere, Jose
TI Outcomes of Early, Late, and No Admission to the Intensive Care Unit for
Patients Hospitalized with Community-acquired Pneumonia
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID INFECTIOUS-DISEASES-SOCIETY; PREDICTION RULE; EMERGENCY-DEPARTMENT;
CONTROLLED-TRIAL; SEVERITY-INDEX; RISK-FACTORS; VALIDATION; GUIDELINES;
MORTALITY; CRITERIA
AB Objectives: The objective was to compare outcomes associated with early, late, and no admission to the intensive care unit (ICU) for patients hospitalized with community-acquired pneumonia (CAP). Methods: This was a post hoc analysis of the original data from the Emergency Department Community-Acquired Pneumonia (EDCAP) and Pneumocom-1 prospective multicenter cohort studies of adult patients hospitalized with CAP. Propensity scoreadjusted analysis was used to compare 28-day mortality and hospital length of stay (LOS) for 199, 144, and 2,215 patients with early (i.e., ICU admission on the day of emergency department [ED] presentation), late, and no ICU admission. Results: Unadjusted 28-day mortality rates were 13.1, 19.4, and 5.7% for early, late, and no ICU admissions, respectively (p < 0.001). After adjusting for quintile of propensity score, the odds of 28-day mortality were higher for late ICU admissions relative to early ICU admissions (odds ratio [OR] = 2.63; 95% confidence interval [CI] = 1.42 to 4.90), and no ICU admissions (OR = 3.40; 95% CI = 2.11 to 5.48), but did not differ between early and no ICU admissions (OR = 1.29; 95% CI = 0.79 to 2.09). The median hospital LOS was 10 days for early (interquartile range [IQR] = 7 to 18), 15 days for late (IQR 9 to 23), and 6 days (IQR 4 to 9) for no ICU admissions (p < 0.001). Conclusions: This study suggests that late but not early admission to the ICU is associated with higher 28-day mortality for patients hospitalized with CAP. Patients admitted to the ICU have longer hospital LOS in comparison to those managed on the wards, particularly if they are admitted late to the ICU. ACADEMIC EMERGENCY MEDICINE 2012; 19:## (C) 2012 by the Society for Academic Emergency Medicine
C1 [Renaud, Bertrand; Santin, Aline] Grp Hosp Henri Mondor Albert Chenevier, AP HP, Serv Urgence, Creteil, France.
[Renaud, Bertrand; Brun-Buisson, Christian; Santin, Aline] Univ Paris 12, Fac Med, Creteil, France.
[Coma, Eva] Hosp Duran & Reynals, Inst Catala Oncol, Serv Atencio Continuada USAC, Barcelona 08907, Spain.
[Noyez, Cecile] Ctr Hosp Montauban, Emergency Dept, Montauban, France.
[Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA.
[Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA USA.
[Labarere, Jose] CHU Grenoble, Qual Care Unit, F-38043 Grenoble, France.
[Labarere, Jose] Univ Grenoble 1, TIMC UMR CNRS 5525, Grenoble, France.
RP Renaud, B (reprint author), Grp Hosp Henri Mondor Albert Chenevier, AP HP, Serv Urgence, Creteil, France.
EM bertrand.renaud@hmn.aphp.fr
RI Labarere, Jose/N-1688-2014;
OI Labarere, Jose/0000-0001-7621-6586
FU Direction de la Recherche Clinique d'Ile de France [AOM 89-145];
Departement de la Formation Continue des Medecins de l'Assistance
Publique des Hopitaux de Paris (AP-HP); l'ARMUR (Association de
Recherche en Medecine d'Urgence, Henri Mondor, Creteil) France; AQUARE
(Association pour la QUAlite, la Recherche et l'Enseignement a l'Hopital
Saint-Joseph (Paris)); GlaxoSmithKline France; Direction de la Recherche
Clinique du Centre Hospitalier Universitaire de Grenoble
FX This study was funded by the Direction de la Recherche Clinique d'Ile de
France as part of the Programme Hospitalier de Recherche Clinique (Grant
No. AOM 89-145). B. Renaud was supported by the Departement de la
Formation Continue des Medecins de l'Assistance Publique des Hopitaux de
Paris (AP-HP), by l'ARMUR (Association de Recherche en Medecine
d'Urgence, Henri Mondor, Creteil) France; by AQUARE (Association pour la
QUAlite, la Recherche et l'Enseignement a l'Hopital Saint-Joseph
(Paris)); and by GlaxoSmithKline France. J. Labarere was supported by
the Direction de la Recherche Clinique du Centre Hospitalier
Universitaire de Grenoble.
NR 36
TC 7
Z9 8
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD MAR
PY 2012
VL 19
IS 3
BP 294
EP 303
DI 10.1111/j.1553-2712.2012.01301.x
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA 912EE
UT WOS:000301776700007
PM 22435862
ER
PT J
AU Ikonomovic, MD
Abrahamson, EE
Price, JC
Hamilton, RL
Mathis, CA
Paljug, WR
Debnath, ML
Cohen, AD
Mizukami, K
DeKosky, ST
Lopez, OL
Klunk, WE
AF Ikonomovic, Milos D.
Abrahamson, Eric E.
Price, Julie C.
Hamilton, Ronald L.
Mathis, Chester A.
Paljug, William R.
Debnath, Manik L.
Cohen, Anne D.
Mizukami, Katsuyoshi
DeKosky, Steven T.
Lopez, Oscar L.
Klunk, William E.
TI Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging,
biochemical, and immunohistochemical study
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Alzheimer's disease; Brain amyloidosis; Pittsburgh Compound B; Plaques;
Imaging
ID PITTSBURGH COMPOUND-B; POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE;
SENILE PLAQUES; NEUROPATHOLOGIC ASSESSMENT; NEUROFIBRILLARY TANGLES;
REGIONAL-DISTRIBUTION; BETA PROTEIN; PET; BRAIN
AB Amyloid-beta (A beta) deposits are detectable in the brain in vivo using positron emission tomography (PET) and [C-11]-labeled Pittsburgh Compound B ([C-11]PiB); however, the sensitivity of this technique is not well understood. In this study, we examined A beta pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer's disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(-)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(-) case, A beta plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, A beta plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-11]PiB(-) case had low levels of [H-3]PiB binding (<100 pmol/g) and A beta 1-42 (<500 pmol/g) concentration except in the frontal cortex where A beta 1-42 values (788 pmol/g) approached cortical values in the [C-11]PiB(+) case (800-1,700 pmol/g). In several cortical regions of the [C-11]PiB(-) case, A beta 1-40 levels were within the range of cortical A beta 1-40 values in the [C-11]PiB(+) case. Antemortem [C-11]PiB DVR values correlated well with region-matched postmortem measures of A beta 1-42 and A beta 1-40 in the [C-11]PiB(+), and with A beta 1-42 only in the [C-11]PiB(-) case. The low ratios of [H-3]PiB binding levels to Ab concentrations and 6-CN-PiB to Ab plaque loads in the [C-11]PiB(-) case indicate that Ab pathology in the brain may be associated with low or undetectable levels of [C-11]PiB retention. Studies in greater numbers of [C-11]PiB PET autopsy cases are needed to define the Ab concentration and [H-3]PiB binding levels required to produce a positive [C-11]PiB PET signal.
C1 [Ikonomovic, Milos D.; Abrahamson, Eric E.; Paljug, William R.; Lopez, Oscar L.; Klunk, William E.] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15213 USA.
[Ikonomovic, Milos D.; Debnath, Manik L.; Cohen, Anne D.; Klunk, William E.] Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA.
[Price, Julie C.; Mathis, Chester A.] Univ Pittsburgh, Dept Radiol, Sch Med, Pittsburgh, PA 15213 USA.
[Hamilton, Ronald L.] Univ Pittsburgh, Dept Neuropathol, Sch Med, Pittsburgh, PA 15213 USA.
[Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Mizukami, Katsuyoshi] Univ Tsukuba, Inst Clin Med, Dept Psychiat, Tsukuba, Ibaraki 305, Japan.
[DeKosky, Steven T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA.
[DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA.
RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, Sch Med, 200 Lothrop St,BST S521, Pittsburgh, PA 15213 USA.
EM ikonomovicmd@upmc.edu
OI Klunk, William/0000-0001-5512-0251
FU National Institutes of Health [AG025204, AG025516, AG005133, AG014449,
AG033042]; GE Healthcare; Phillip V. and Anna S. Brown Foundation;
Snee-Reinhardt Charitable Foundation
FX We gratefully acknowledge the technical expertise of Suganya Srinivasan,
Lan Shao, Hui Wang, and Jonette Werley. We thank the staff at the
University of Pittsburgh Alzheimer's Disease Research Center and PET
facility for their efforts in conducting and analyzing these studies. We
are indebted to our subjects and their families for the selfless
contributions that made this work possible. This work was supported by
the National Institutes of Health grants AG025204, AG025516, AG005133,
AG014449, and AG033042, GE Healthcare, The Phillip V. and Anna S. Brown
Foundation, and the Snee-Reinhardt Charitable Foundation.
NR 52
TC 41
Z9 41
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD MAR
PY 2012
VL 123
IS 3
BP 433
EP 447
DI 10.1007/s00401-012-0943-2
PG 15
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 913EJ
UT WOS:000301856300009
PM 22271153
ER
PT J
AU Drye, LT
Ismail, Z
Porsteinsson, AP
Rosenberg, PB
Weintraub, D
Marano, C
Pelton, G
Frangakis, C
Rabins, PV
Munro, CA
Meinert, CL
Devanand, DP
Yesavage, J
Mintzer, JE
Schneider, LS
Pollock, BG
Lyketsos, CG
AF Drye, Lea T.
Ismail, Zahinoor
Porsteinsson, Anton P.
Rosenberg, Paul B.
Weintraub, Daniel
Marano, Christopher
Pelton, Gregory
Frangakis, Constantine
Rabins, Peter V.
Munro, Cynthia A.
Meinert, Curtis L.
Devanand, D. P.
Yesavage, Jerome
Mintzer, Jacobo E.
Schneider, Lon S.
Pollock, Bruce G.
Lyketsos, Constantine G.
CA CitAD Res Grp
TI Citalopram for agitation in Alzheimer's disease: Design and methods
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Alzheimer dementia; Citalopram; Agitation; Randomized trial
ID PLACEBO-CONTROLLED TRIAL; NEUROPSYCHIATRIC-SYMPTOMS; ELDERLY-PATIENTS;
NURSING-HOME; DOUBLE-BLIND; BEHAVIORAL DISTURBANCES; SEROTONIN
TRANSPORTER; DEMENTED PATIENTS; DEPRESSION; ASSOCIATION
AB Background: Agitation is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer's disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms.
Methods: CitAD is a randomized, double-masked, placebo-controlled multicenter clinical trial, with two parallel treatment groups assigned in a 1:1 ratio and randomization stratified by clinical center. The study included eight recruiting clinical centers, a chair's office, and a coordinating center located in university settings in the United States and Canada. A total of 200 individuals having probable AD with clinically significant agitation and without major depression were recruited for this study. Patients were randomized to receive citalopram (target dose of 30 mg/d) or matching placebo. Caregivers of patients in both treatment groups received a structured psychosocial therapy. Agitation was compared between treatment groups using the NeuroBehavioral Rating Scale and the AD Cooperative Study- Clinical Global Impression of Change, which are the primary outcomes. Functional performance, cognition, caregiver distress, and rates of adverse and serious adverse events were also measured.
Conclusion: The authors believe the design elements in CitAD are important features to he included in trials assessing the safety and efficacy of psychotropic medications for clinically significant agitation in AD. (C) 2012 The Alzheimer's Association. All rights reserved.
C1 [Drye, Lea T.; Frangakis, Constantine; Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Drye, Lea T.; Frangakis, Constantine; Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Ismail, Zahinoor; Pollock, Bruce G.] Univ Toronto, Div Geriatr Psychiat, Toronto, ON, Canada.
[Porsteinsson, Anton P.] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA.
[Rosenberg, Paul B.; Marano, Christopher; Rabins, Peter V.; Munro, Cynthia A.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Rosenberg, Paul B.; Marano, Christopher; Rabins, Peter V.; Munro, Cynthia A.; Lyketsos, Constantine G.] Johns Hopkins Bayview Med Ctr, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD USA.
[Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Pelton, Gregory; Devanand, D. P.] Columbia Univ, Div Geriatr Psychiat, New York State Psychiat Inst, New York, NY USA.
[Pelton, Gregory; Devanand, D. P.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Yesavage, Jerome] Stanford Univ, Sch Med,Dept Vet Affairs, Med Res Serv Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA 94304 USA.
[Yesavage, Jerome] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Mintzer, Jacobo E.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA.
[Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA.
[Schneider, Lon S.] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90033 USA.
RP Drye, LT (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
EM ldrye@jhsph.edu
OI Drye, Lea/0000-0002-2964-1878
FU National Institute on Aging; National Institute of Mental Health
[R01AG031348]
FX Grant funding: National Institute on Aging and National Institute of
Mental Health, R01AG031348.
NR 59
TC 20
Z9 20
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD MAR
PY 2012
VL 8
IS 2
BP 121
EP 130
DI 10.1016/j.jalz.2011.01.007
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 914ZE
UT WOS:000301991600005
PM 22301195
ER
PT J
AU Funke, M
Zhao, ZW
Xu, Y
Chun, J
Tager, AM
AF Funke, Manuela
Zhao, Zhenwen
Xu, Yan
Chun, Jerold
Tager, Andrew M.
TI The Lysophosphatidic Acid Receptor LPA(1) Promotes Epithelial Cell
Apoptosis after Lung Injury
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE pulmonary fibrosis; apoptosis; epithelial cells, lysophosphatidic acid;
LPA(1)
ID IDIOPATHIC PULMONARY-FIBROSIS; GROWTH-FACTOR BETA(1); MESSENGER-RNA;
EXPRESSION; ANOIKIS; ACTIVATION; BLEOMYCIN; MICE; DEATH; FIBROBLASTS
AB Increased epithelial cell apoptosis in response to lung injury has been implicated in the development of idiopathic pulmonary fibrosis (IPF), but the molecular pathways promoting epithelial cell apoptosis in this disease have yet to be fully identified. Lysophosphatidic acid (LPA), which we have previously demonstrated to mediate bleomycin lung injury-induced fibroblast recruitment and vascular leak in mice and fibroblast recruitment in patients with IPF, is an important regulator of survival and apoptosis in many cell types. We now show that LPA signaling through its receptor LPA(1) promotes epithelial cell apoptosis induced by bleomycin injury. The number of apoptotic cells present in the alveolar and bronchial epithelia of LPA(1)-deficient mice was significantly reduced compared with wild-type mice at Day 3 after bleomycin challenge, as was lung caspase3 activity. Consistent with these in vivo results, we found that LPA signaling through LPA(1) induced apoptosis in normal human bronchial epithelial cells in culture. LPA-LPA(1) signaling appeared to specifically mediate anoikis, the apoptosis of anchorage-dependent cells induced by their detachment. Similarly, LPA negatively regulated attachment of R3/1 rat alveolar epithelial cell line cells. In contrast, LPA signaling through LPA(1) promoted the resistance of lung fibroblasts to apoptosis, which has also been implicated in IPF. The ability of LPA-LPA(1) signaling to promote epithelial cell apoptosis and fibroblast resistance to apoptosis may therefore contribute to the capacity of this signaling pathway to regulate the development of pulmonary fibrosis after lung injury.
C1 [Zhao, Zhenwen; Xu, Yan] Indiana Univ Sch Med, Dept Obstet & Gynecol, Indianapolis, IN USA.
[Chun, Jerold] Scripps Res Inst, Dept Mol Biol, Dorris Neurosci Ctr, La Jolla, CA 92037 USA.
[Funke, Manuela; Tager, Andrew M.] Harvard Univ, Pulm & Crit Care Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
[Funke, Manuela; Tager, Andrew M.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RP Tager, AM (reprint author), Harvard Univ, Pulm & Crit Care Unit, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp,Med Sch, 149 13th St,Room 8301, Charlestown, MA 02129 USA.
EM amtager@partners.org
FU NIH [R01-HL095732, R01-HL108975, R01-CA095042]; Pulmonary Fibrosis
Foundation; Coalition for Pulmonary Fibrosis/American Thoracic Society;
Nirenberg Center for Advanced Lung Disease; Swiss National Foundation;
Swiss Society of Pulmonology; Fondation pour la Recherche et le
Traitement des Maladies Respiratoires; [NIH-HD050685]; [NIH-DA019674]
FX This work was supported by NIH R01-HL095732 and R01-HL108975, a
Pulmonary Fibrosis Foundation grant, a Coalition for Pulmonary
Fibrosis/American Thoracic Society grant, and a Nirenberg Center for
Advanced Lung Disease Grant (A.M.T); by a Swiss National Foundation
grant, a Swiss Society of Pulmonology grant, and a grant from the
Fondation pour la Recherche et le Traitement des Maladies Respiratoires
(M.F.); by NIH grant R01-CA095042 (Y.X.); and by grants NIH-HD050685 and
NIH-DA019674 (J.C.).
NR 50
TC 46
Z9 48
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 MAR
PY 2012
VL 46
IS 3
BP 355
EP 364
DI 10.1165/rcmb.2010-0155OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 901HD
UT WOS:000300953800010
PM 22021336
ER
PT J
AU Pankratz, N
Beecham, GW
DeStefano, AL
Dawson, TM
Doheny, KF
Factor, SA
Hamza, TH
Hung, AY
Hyman, BT
Ivinson, AJ
Krainc, D
Latourelle, JC
Clark, LN
Marder, K
Martin, ER
Mayeux, R
Ross, OA
Scherzer, CR
Simon, DK
Tanner, C
Vance, JM
Wszolek, ZK
Zabetian, CP
Myers, RH
Payami, H
Scott, WK
Foroud, T
AF Pankratz, Nathan
Beecham, Gary W.
DeStefano, Anita L.
Dawson, Ted M.
Doheny, Kimberly F.
Factor, Stewart A.
Hamza, Taye H.
Hung, Albert Y.
Hyman, Bradley T.
Ivinson, Adrian J.
Krainc, Dmitri
Latourelle, Jeanne C.
Clark, Lorraine N.
Marder, Karen
Martin, Eden R.
Mayeux, Richard
Ross, Owen A.
Scherzer, Clemens R.
Simon, David K.
Tanner, Caroline
Vance, Jeffery M.
Wszolek, Zbigniew K.
Zabetian, Cyrus P.
Myers, Richard H.
Payami, Haydeh
Scott, William K.
Foroud, Tatiana
CA PD GWAS Consortium
TI Meta-analysis of Parkinson's Disease: Identification of a novel locus,
RIT2
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; RISK-FACTORS; CALMODULIN;
SNCA; SUSCEPTIBILITY; HAPLOTYPES; VARIANTS; SEQUENCE; GENETICS
AB Objective: Genome-wide association (GWAS) methods have identified genes contributing to Parkinson's disease (PD); we sought to identify additional genes associated with PD susceptibility.
C1 [Pankratz, Nathan; Foroud, Tatiana] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Beecham, Gary W.; Martin, Eden R.; Vance, Jeffery M.; Scott, William K.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[DeStefano, Anita L.; Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Dawson, Ted M.; Doheny, Kimberly F.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Factor, Stewart A.] Emory Univ, Atlanta, GA 30322 USA.
[Hamza, Taye H.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Hung, Albert Y.; Hyman, Bradley T.; Krainc, Dmitri] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hyman, Bradley T.; Ivinson, Adrian J.; Scherzer, Clemens R.] Harvard Univ, Sch Med, Biomarker Program, Harvard NeuroDiscovery Ctr, Boston, MA USA.
[Clark, Lorraine N.; Marder, Karen; Mayeux, Richard] Columbia Univ, Coll Phys & Surg, Sch Med, New York, NY USA.
[Ross, Owen A.; Wszolek, Zbigniew K.] Mayo Clin, Jacksonville, FL 32224 USA.
[Scherzer, Clemens R.] Partners Parkinson Ctr, Boston, MA USA.
[Scherzer, Clemens R.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Simon, David K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA.
[Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Zabetian, Cyrus P.] Univ Washington, Seattle, WA 98195 USA.
RP Foroud, T (reprint author), Indiana Univ Sch Med, 410 W 10th St HS 4000, Indianapolis, IN 46202 USA.
EM tforoud@iupui.edu
RI Kowall, Neil/G-6364-2012; Haines, Jonathan/C-3374-2012; Ross,
Owen/D-7573-2013; Ottman, Ruth/O-2371-2013;
OI Kowall, Neil/0000-0002-6624-0213; Latourelle,
Jeanne/0000-0002-4218-9572; Hirschberger, Johannes/0000-0002-1382-6114;
Myers, Richard/0000-0002-8365-2674; Zabetian, Cyrus/0000-0002-7739-4306;
Goldwurm, Stefano/0000-0002-1651-567X
FU Indiana CTSI CRC [M01RR00750/ RR025761, R01NS36960, P50NS39764,
R01NS064155, U10NS44482, 1RC2NS070276, R01NS057567, P50NS072187, IH
NS36630, UL1 RR024156, NS050487, R01NS060113, U24AG026395, 1I01BX000531,
R01NS36711]; Harvard NeuroDiscovery Center; Michael J. Fox Foundation;
Michael J. Fox Foundation Edmond J Safra Michael J Fox Foundation Global
Genetic Consortium Initiative; Bumpus Foundation; Robert P. and Judith
N. Goldberg Foundation; National Parkinson Foundation; Parkinson's
Disease Foundation; Mayo Clinic Florida (MCF) Research Committee
[90052018, 90052030]; Dystonia Medical Research Foundation; National
Institute on Aging [P30 AG19610]; Arizona Department of Health Services
[211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901];
Prescott Family Initiative of the Michael J. Fox Foundation for
Parkinson's Research; Harvard Brain Tissue Resource Center; PHS [R24 MH
068855]; Human Brain and Spinal Fluid Resource Center VA West Los
Angeles Healthcare Center; NINDS/NIMH, National Multiple Sclerosis
Society, Department of Veterans; [R01CA141668]; [R01NS37167];
[R01NS065070]; [R56NS037167]; [90052031/PAU #90052]
FX This project was supported by R01CA141668 (TF), R01NS37167 (TF),
R01NS065070 (CPZ), R56NS037167 (TF), Indiana CTSI CRC (M01RR00750/
RR025761 - TF), R01NS36960 (HP), P50NS39764 (WKS), R01NS064155 (CRS),
U10NS44482 (DS), 1RC2NS070276 (ZKW, OAR), R01NS057567 (ZKW), P50NS072187
(ZKW, OAR), IH NS36630 (KSM), UL1 RR024156 (KSM), NS050487 (LNC),
R01NS060113 (LNC), U24AG026395 (RM), 1I01BX000531 (CPZ), R01NS36711
(RHM), Harvard NeuroDiscovery Center (CRS), The Michael J. Fox
Foundation (CRS), The Michael J. Fox Foundation Edmond J Safra Michael J
Fox Foundation Global Genetic Consortium Initiative (HP), Bumpus
Foundation (RHM), Robert P. and Judith N. Goldberg Foundation (RHM),
National Parkinson Foundation; Parkinson's Disease Foundation (KSM, LNC,
DK, AYH) Joseph R. Mazzulli and Grace Bwala (DK, AYH), Mayo Clinic
Florida (MCF) Research Committee CR programs (MCF #90052018 and MCF
#90052030) (ZKW), and the gift from Carl Edward Bolch, Jr., and Susan
Bass Bolch (MCF #90052031/PAU #90052) (ZKW, OAR), and Dystonia Medical
Research Foundation (ZKW).; Control samples and clinical data were
provided from the National Cell Repository for Alzheimer's Disease (U24
AG021886; TF) and the NINDS Human Genetics Resource Center DNA and Cell
Line Repository (http://ccr.coriell.org/ninds). PD and control brain
samples provided by the Sun Health Research Institute in Sun City,
Arizona, which is supported by the National Institute on Aging (P30
AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department
of Health Services (contract 211002, Arizona Alzheimer's Research
Center), the Arizona Biomedical Research Commission (contracts 4001,
0011 and 05-901 to the Arizona Parkinson's Disease Consortium) and the
Prescott Family Initiative of the Michael J. Fox Foundation for
Parkinson's Research; the Harvard Brain Tissue Resource Center, which is
supported in part by PHS grant number R24 MH 068855, and the Human Brain
and Spinal Fluid Resource Center VA West Los Angeles Healthcare Center,
11301 Wilshire Blvd. Los Angeles, CA 90073, which is sponsored by
NINDS/NIMH, National Multiple Sclerosis Society, Department of Veterans.
NR 25
TC 102
Z9 102
U1 0
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2012
VL 71
IS 3
BP 370
EP 384
DI 10.1002/ana.22687
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 914BD
UT WOS:000301922800012
PM 22451204
ER
PT J
AU Lichtman, SM
Hurria, A
Cirrincione, CT
Seidman, AD
Winer, E
Hudis, C
Cohen, HJ
Muss, HB
AF Lichtman, S. M.
Hurria, A.
Cirrincione, C. T.
Seidman, A. D.
Winer, E.
Hudis, C.
Cohen, H. J.
Muss, H. B.
CA Canc Leukemia Grp B
TI Paclitaxel efficacy and toxicity in older women with metastatic breast
cancer: combined analysis of CALGB 9342 and 9840
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE breast cancer; elderly; geriatric oncology; geriatrics; neurotoxicity;
paclitaxel
ID ELDERLY-PATIENTS; ADJUVANT CHEMOTHERAPY; 1ST-LINE CHEMOTHERAPY;
RANDOMIZED-TRIAL; EXPERIENCE; ONCOLOGY; TABLES; LIFE; AGE
AB Background: Two Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer.
Patients and methods: CALGB 9840 evaluated weekly paclitaxel (80 mg/m(2)) versus paclitaxel every 3 weeks (175 mg/m(2)); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m(2) each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55-64 years (29%), and (iii) >= 65 years (26%).
Results: Tumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade >= 3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity.
Conclusions: Older women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects.
C1 [Lichtman, S. M.; Seidman, A. D.; Hudis, C.] Mem Sloan Kettering Canc Ctr, Dept Med, Commack, NY 11725 USA.
[Hurria, A.] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA.
[Hurria, A.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA.
[Cirrincione, C. T.] CALGB Stat Ctr, Durham, NC USA.
[Winer, E.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA.
[Cohen, H. J.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC 27706 USA.
[Muss, H. B.] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA.
RP Lichtman, SM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 650 Commack Rd, Commack, NY 11725 USA.
EM lichtmas@mskcc.org
FU National Cancer Institute [CA31946, CA33601, CA45418, CA32291, CA77597,
CA11028, CA12449, CA03927, CA77651, CA45564, CA04457, CA35421, CA35279,
CA08025, CA02599, CA45808, CA21060, CA45389, CA77658, CA47545, CA11789,
CA60138, CA41287, CA74811, CA47642, CA31983, CA37135]; the National
Cancer Institute [CA16450, CA12046, CA77298, CA47559, CA47555, CA77406,
CA26806, CA77440, CA07968]
FX The research for CALGB 9342 and 9840 was supported, in part, by grants
from the National Cancer Institute (CA31946) to the Cancer and Leukemia
Group B (Monica M. Bertagnolli) and to the CALGB Statistical Center
(Daniel J. Sargent, CA33601). The following institutions participated in
this study: CALGB Statistical Office, Durham, NC. Stephen George,
supported by CA33601; Christiana Care Health Services, Inc CCOP,
Wilmington, DE. Stephen Grubbs, supported by CA45418; Dana-Farber Cancer
Institute, Boston, MA. George P. Canellos, supported by CA32291;
Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH. Marc
S. Ernstoff, supported by Georgetown University Medical Center,
Washington, DC. Edward Gelmann, supported by CA77597; Long Island Jewish
Medical Center, Lake Success, NY. Marc Citron, supported by CA11028;
Massachusetts General Hospital, Boston, MA. Michael L. Grossbard,
supported by CA12449; Medical University of South Carolina, Charleston,
SC. Mark Green, supported by CA03927; Memorial Sloan-Kettering Cancer
Center, New York, NY. Clifford Hudis, supported by CA77651; Missouri
Baptist Medical Center, St Louis, MO. Alan P. Lyss, Mount Sinai Medical
Center, Miami, FL. Rogerio Lilenbaum, supported by CA45564; Mount Sinai
School of Medicine, New York, NY. Lewis R. Silverman, supported by
CA04457; Nevada Cancer Research Foundation CCOP, Las Vegas, NV. John
Ellerton, supported by CA35421; New Hampshire Oncology-Hematology P. A.,
Hooksett, NH. Douglas J. Weckstein, North Shore, Long Island Jewish
Medical Center, Manhasset, NY. Daniel R. Budman, supported by CA35279;
Rhode Island Hospital, Providence, RI. Louis A. Leone, supported by
CA08025; Roswell Park Cancer Institute, Buffalo, NY. Ellis Levine,
supported by CA02599; Southeast Cancer Control Consortium Inc CCOP,
Goldsboro, NC. James N. Atkins, supported by CA45808; State University
of New York Upstate Medical University, Syracuse, NY. Stephen L.
Graziano, supported by CA21060; Syracuse Hematology-Oncology Assoc.
CCOP, Syracuse, NY. Jeffrey Kirshner, supported by CA45389; The Ohio
State University Medical Center, Columbus, OH. Clara D. Bloomfield,
supported by CA77658; University of Alabama Birmingham, Birmingham, AL.
Robert Diasio, supported by CA47545; University of California at San
Diego, San Diego, CA. Joanne Mortimer, supported by CA11789; University
of California at San Francisco, San Francisco, CA. Alan P. Venook,
supported by CA60138; University of Chicago Medical Center, Chicago, IL.
Gini Fleming, supported by CA41287; University of Illinois at Chicago,
Chicago, IL. David Gustin, supported by CA74811; University of Iowa,
Iowa City, IA. Gerald Clamon, supported by CA47642; University of
Maryland Cancer Center, Baltimore, MD. David Van Echo, supported by
CA31983; University of Massachusetts Medical Center, Worcester, MA. Mary
Ellen Taplin, supported by CA37135; University of Minnesota,
Minneapolis, MN. Bruce A. Peterson, supported by CA16450; University of
Missouri/Ellis Fischel Cancer Ctr., Columbia, MO. Michael C. Perry,
supported by CA12046; University of Nebraska Medical Center, Omaha, NE.
Anne Kessinger, supported by CA77298; University of North Carolina at
Chapel Hill, Chapel Hill, NC. Thomas C. Shea, supported by CA47559;
University of Tennessee Memphis, Memphis, TN. Harvey B. Niell, supported
by CA47555; Vermont Cancer Center, Burlington, VT. Hyman B. Muss,
supported by CA77406; Wake Forest University School of Medicine,
Winston-Salem, NC. David D. Hurd; supported by CA03927; Walter Reed Army
Medical Center, Washington, DC. John C.; Byrd, supported by CA26806;
Washington University, St Louis, MO. Nancy Bartlett, supported by
CA77440; Weill Medical College of Cornell University, New York, NY.
Michael Schuster, supported by CA07968.
NR 20
TC 18
Z9 21
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
IS 3
BP 632
EP +
DI 10.1093/annonc/mdr297
PG 7
WC Oncology
SC Oncology
GA 898HV
UT WOS:000300733300014
PM 21693770
ER
PT J
AU Gronchi, A
Bui, BN
Bonvalot, S
Pilotti, S
Ferrari, S
Hohenberger, P
Hohl, RJ
Demetri, GD
Le Cesne, A
Lardelli, P
Perez, I
Nieto, A
Tercero, JC
Alfaro, V
Tamborini, E
Blay, JY
AF Gronchi, A.
Bui, B. N.
Bonvalot, S.
Pilotti, S.
Ferrari, S.
Hohenberger, P.
Hohl, R. J.
Demetri, G. D.
Le Cesne, A.
Lardelli, P.
Perez, I.
Nieto, A.
Tercero, J. C.
Alfaro, V.
Tamborini, E.
Blay, J. Y.
TI Phase II clinical trial of neoadjuvant trabectedin in patients with
advanced localized myxoid liposarcoma
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE chemotherapy; liposarcoma; neoadjuvant; soft tissue sarcoma; surgery
ID SOFT-TISSUE SARCOMA; PRIMARY EXTREMITY LIPOSARCOMA; OVARIAN-CANCER;
CHEMOTHERAPY; ECTEINASCIDIN-743; ET-743; IMPACT; SCHEDULES; SURVIVAL;
EFFICACY
AB Background: To evaluate neoadjuvant trabectedin (1.5 mg/m(2) 24-h i.v. infusion every 3 weeks; three to six cycles) in patients with locally advanced myoxid liposarcoma (ML) previously untreated with chemotherapy or radiation.
Patients and methods: Primary efficacy end point was pathological complete response (pCR) or tumoral regression rate. Objective response according to RECIST (v.1.0) was a secondary end point.
Results: Three of 23 assessable patients had pCR [13%; 95% confidence interval (CI), 3% to 34%]. Furthermore, very good and moderate histological responses were observed in another 2 and 10 patients, respectively. Histological decrement in the cellular and vascular tumor component and maturation of tumor cells to lipoblasts were observed in both myoxid and myoxid/round cell variants. Seven patients had partial response according to RECIST (objective response rate of 24%; 95% CI, 10% to 44%). No disease progression was reported. Neoadjuvant trabectedin was usually well tolerated, with a safety profile similar to that described in patients with soft tissue sarcoma or other tumor types.
Conclusion: Trabectedin 1.5 mg/m(2) given as a 24-h i.v. infusion every 3 weeks is a therapeutic option in the neoadjuvant setting of ML.
C1 [Gronchi, A.; Pilotti, S.; Tamborini, E.] Natl Canc Inst, Dept Surg, I-20133 Milan, Italy.
[Bui, B. N.] Inst Bergonie, Dept Med Oncol, Bordeaux, France.
[Bonvalot, S.; Le Cesne, A.] Inst Gustave Roussy, Dept Surg, Paris, France.
[Bonvalot, S.; Le Cesne, A.] Inst Gustave Roussy, Dept Med Oncol, Paris, France.
[Ferrari, S.] Orthoped Inst Rizzoli, Dept Chemotherapy, Bologna, Italy.
[Hohenberger, P.] Heidelberg Univ, Mannheim Univ Med Ctr, Div Surg Oncol & Thorac Surg, D-6900 Heidelberg, Germany.
[Demetri, G. D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lardelli, P.; Perez, I.; Nieto, A.; Tercero, J. C.; Alfaro, V.] PharmaMar, Dept Clin R&D, Madrid, Spain.
[Blay, J. Y.] Leon Berard Canc Ctr, Dept Med Oncol, Lyon, France.
RP Gronchi, A (reprint author), Natl Canc Inst, Dept Surg, Via G Venezian 1, I-20133 Milan, Italy.
EM alessandro.gronchi@istitutotumori.mi.it
RI Blay, Jean-Yves/N-3966-2016; Tamborini, Elena/C-3307-2017;
OI Blay, Jean-Yves/0000-0001-7190-120X; Tamborini,
Elena/0000-0002-3819-8687; Gronchi, Alessandro/0000-0002-4703-3534
FU PharmaMar S.A., Sociedad Unipersonal [NCT00579501]; Novartis; Pfizer;
Roche; PharmaMar; Amgen; Ariad; Daiichi-Sankyo; Infinity
Pharmaceuticals; Johnson Johnson; PhamaMar
FX PharmaMar S.A., Sociedad Unipersonal (ClinicalTrials.gov number,
NCT00579501).; BNB (GlaxoSmithKline, Imclone, Novartis, Pfizer,
PharmaMar, Roche, MSD), PH (PharmaMar), GDD (Amgen, Ariad, ArQule,
Champions Biotechnology, Daiichi-Sankyo, EMD-Serono, Enzon, Genentech,
GlaxoSmithKline, Infinity Pharmaceuticals, Johnson & Johnson, Koltan
Phamaceuticals, Millenium/Takeda, N-of-One, Novartis, Pfizer, PharmaMar,
Plekkixon, Ziopharm), ALC (PharmaMar) and JYB (PhamaMar) were
compensated as consultants or advisors. BNB (GlaxoSmithKline, Imclone,
MSD, Novartis, Pfizer, Roche), SB (Novartis), PH (PharmaMar), GDD
(Novartis, Pfizer), ALC (PharmaMar) and JYB (PhamaMar) received
honoraria. BNB (Novartis, Pfizer, Roche), SB (Novartis), RJH
(PharmaMar), SF (PharmaMar), GDD (Amgen, Ariad, Daiichi-Sankyo, Infinity
Pharmaceuticals, Johnson & Johnson, Novartis, Pfizer, PhamaMar) and JYB
(PhamaMar) received research funding. GDD (Ariad, Inifinity
Pharmaceuticals, Johnson & Johnson, PharmaMar, Ziopharm) gave expert
testimony. AG received remuneration from PharmaMar. PL, IP, AN, JCT and
VA are employees in PharmaMar. PL (Zeltia), IP (Zeltia), AN (Zeltia) and
JCT (Zeltia) are stock ownership.
NR 25
TC 62
Z9 62
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
IS 3
BP 771
EP 776
DI 10.1093/annonc/mdr265
PG 6
WC Oncology
SC Oncology
GA 898HV
UT WOS:000300733300035
PM 21642514
ER
PT J
AU Lenihan, D
Suter, T
Brammer, M
Neate, C
Ross, G
Baselga, J
AF Lenihan, D.
Suter, T.
Brammer, M.