FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Freedman, RA
Partridge, AH
AF Freedman, Rachel A.
Partridge, Ann H.
TI Adjuvant therapies for very young women with early stage breast cancer
SO BREAST
LA English
DT Article
DE Young women; Breast cancer; Adjuvant therapy; Chemotherapy; Fertility;
Premature menopause
ID PREMENOPAUSAL PATIENTS; RANDOMIZED-TRIALS; PROGNOSTIC-FACTOR; AGE;
SURVIVAL; TAMOXIFEN; CYCLOPHOSPHAMIDE; FLUOROURACIL; CHEMOTHERAPY;
METHOTREXATE
AB Approximately 16,000-19,000 women aged <= 45 are diagnosed annually with breast cancer in the United States and thousands more are diagnosed worldwide. Compared to older women, young women are more likely to have cancers with aggressive tumor biology and present with higher stage disease, both of which likely lead to their worse outcomes. We review the available evidence for adjuvant systemic therapy as well as treatment considerations for younger women with breast cancer. Although we have begun to appreciate the issues that younger women with breast cancer face, we need a better understanding of how we can optimally prevent disease recurrence while carefully considering their unique physical and emotional needs with regard to diagnosis, treatment, and survivorship. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Freedman, Rachel A.; Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Freedman, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM rafreedman@partners.org; ahpartridge@partners.org
NR 57
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U1 2
U2 3
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD OCT
PY 2011
VL 20
SU 3
BP S146
EP S149
PG 4
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 037CA
UT WOS:000311077400027
PM 22015283
ER
PT J
AU Krop, I
AF Krop, Ian
TI NEW AND FUTURE THERAPIES FOR HER-2+ADVANCED BREAST CANCER
SO BREAST
LA English
DT Meeting Abstract
C1 [Krop, Ian] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD OCT
PY 2011
VL 20
SU 4
BP S16
EP S16
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 037DM
UT WOS:000311082400013
ER
PT J
AU Lim, E
Winer, EP
AF Lim, Elgene
Winer, Eric P.
TI Adjuvant chemotherapy in luminal breast cancers
SO BREAST
LA English
DT Article
DE Luminal breast cancer; Adjuvant chemotherapy
ID GENE-EXPRESSION; RANDOMIZED-TRIALS; ENDOCRINE THERAPY; PROGNOSTIC VALUE;
PREDICTIVE-VALUE; KI67 EXPRESSION; RECEPTOR STATUS; SIGNATURE;
TAMOXIFEN; SUBTYPES
AB Luminal breast cancers are traditionally considered to comprise of tumors expressing estrogen receptor ( ER) and represent the majority of breast cancers. These tumors are characterized by significant heterogeneity in phenotype, molecular signature, relapse patterns and therapeutic response to endocrine and chemotherapy. Whilst adjuvant endocrine therapy is standard of care in patients with tumors that express either ER and/or progesterone receptor ( PR), the indication for adjuvant chemotherapy is less clear-cut. On average, ER-positive breast tumors derive less benefit from chemotherapy compared to ER-negative tumors, however there is still clearly a subset of patients with ER-positive tumors that are chemosensitive. The basis for the addition of chemotherapy to adjuvant endocrine therapy is usually guided by the clinician's estimation of prognosis and assessment of the endocrine sensitivity of the tumor. The use of chemotherapy in this setting, however, is highly variable. There is tremendous value in identifying subgroups of patients who can expect favorable outcomes with endocrine therapy and who may not require any additional therapy. Similarly, it is equally important, if not more important, to characterize patients with ER-positive disease who will derive a substantial benefit from cytotoxic chemotherapy. In this article, we aim to discuss the utility of current biomarkers used to guide decisions regarding chemotherapy in ER-positive, HER2-negative breast cancers. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Lim, Elgene; Winer, Eric P.] Dana Farber Canc Inst, Div Womens Canc, Boston, MA 02115 USA.
RP Lim, E (reprint author), Dana Farber Canc Inst, Div Womens Canc, 450 Brookline Ave, Boston, MA 02115 USA.
EM elgene_lim@dfci.harvard.edu; eric_winer@dfci.harvard.edu
OI Lim, Elgene/0000-0001-8065-8838
FU Genentech
FX E.P. Winer: Consultancy: Novartis; Research support: Genentech. E. Lim
has no conflict of interest to declare.
NR 32
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U1 0
U2 3
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD OCT
PY 2011
VL 20
SU 3
BP S128
EP S131
PG 4
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 037CA
UT WOS:000311077400023
PM 22015279
ER
PT J
AU Mandelblatt, JS
Cronin, KA
Berry, DA
Chang, YJ
de Koning, HJ
Lee, SJ
Plevritis, SK
Schechter, CB
Stout, NK
van Ravesteyn, NT
Zelen, M
Feuer, EJ
AF Mandelblatt, Jeanne S.
Cronin, Kathleen A.
Berry, Donald A.
Chang, Yaojen
de Koning, Harry J.
Lee, Sandra J.
Plevritis, Sylvia K.
Schechter, Clyde B.
Stout, Natasha K.
van Ravesteyn, Nicolien T.
Zelen, Marvin
Feuer, Eric J.
TI Modeling the impact of population screening on breast cancer mortality
in the United States
SO BREAST
LA English
DT Article
DE Mammography; Screening; Modeling
ID SERVICES TASK-FORCE; UPPER AGE LIMIT; RANDOMIZED-TRIALS; OLDER WOMEN;
FOLLOW-UP; MAMMOGRAPHY; RECOMMENDATIONS; CHEMOTHERAPY; BENCHMARKS;
SURVIVAL
AB Objective: Optimal US screening strategies remain controversial. We use six simulation models to evaluate screening outcomes under varying strategies.
Methods: The models incorporate common data on incidence, mammography characteristics, and treatment effects. We evaluate varying initiation and cessation ages applied annually or biennially and calculate mammograms, mortality reduction (vs. no screening), false-positives, unnecessary biopsies and over-diagnosis.
Results: The lifetime risk of breast cancer death starting at age 40 is 3% and is reduced by screening. Screening biennially maintains 81% (range 67% to 99%) of annual screening benefits with fewer false-positives. Biennial screening from 50-74 reduces the probability of breast cancer death from 3% to 2.3%. Screening annually from 40 to 84 only lowers mortality an additional one-half of one percent to 1.8% but requires substantially more mammograms and yields more false-positives and over-diagnosed cases.
Conclusion: Decisions about screening strategy depend on preferences for benefits vs. potential harms and resource considerations. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Mandelblatt, Jeanne S.; Chang, Yaojen] Lombardi Comprehens Canc Ctr, Canc Control Program, Washington, DC 20007 USA.
[Mandelblatt, Jeanne S.; Chang, Yaojen] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Mandelblatt, Jeanne S.; Chang, Yaojen] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.
[Cronin, Kathleen A.; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[de Koning, Harry J.; van Ravesteyn, Nicolien T.] Erasmus MC, Dept Publ Hlth, NL-3015 GE Rotterdam, Netherlands.
[Lee, Sandra J.; Zelen, Marvin] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lee, Sandra J.; Zelen, Marvin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Plevritis, Sylvia K.] Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA.
[Schechter, Clyde B.] Albert Einstein Coll Med, Dept Family & Social Med, Bronx, NY 10461 USA.
[Schechter, Clyde B.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Stout, Natasha K.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA.
[Stout, Natasha K.] Harvard Pilgrim Hlth Care, Boston, MA 02215 USA.
RP Mandelblatt, JS (reprint author), Lombardi Comprehens Canc Ctr, Canc Control Program, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA.
EM mandelbj@georgetown.edu
FU NCI [RC2CA148577, U01CA086076]; BCSC [U01CA63740, U01CA86076,
U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]
FX This work was done under contracts from the Agency for Healthcare
Research and Quality (AHRQ) and NCI and grants from the NCI. The NCI
provided some data and technical assistance and AHRQ reviewed the
manuscript. Model results are the sole responsibility of the
investigators.; By NCI cooperative agreement U01 CA152958-01 and NCI
Grants RC2CA148577 and U01CA086076. Data collection in the BCSC was
supported by NCI-funded BCSC cooperative agreements (U01CA63740,
U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731,
and U01CA70040) and several U.S. state public health departments and
cancer registries. CISNET data management and Web site support were
provided by Cornerstone Systems Northwest (NCI contract
HHSN261200800002C).
NR 37
TC 9
Z9 9
U1 0
U2 4
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD OCT
PY 2011
VL 20
SU 3
BP S75
EP S81
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 037CA
UT WOS:000311077400013
PM 22015298
ER
PT J
AU Robertson, JFR
Lindemann, JPO
Garnett, S
Nicholson, R
Kuter, I
Gee, J
AF Robertson, John F. R.
Lindemann, Justin P. O.
Garnett, Sally
Nicholson, Robert
Kuter, Irene
Gee, Julia
TI FULVESTRANT: ANALYSIS OF TUMOUR BIOMARKER EXPRESSION IN A COMBINED
ANALYSIS OF PRE-SURGICAL STUDIES
SO BREAST
LA English
DT Meeting Abstract
C1 [Robertson, John F. R.] Univ Nottingham, Div Breast Surg, Nottingham NG7 2RD, England.
[Lindemann, Justin P. O.; Garnett, Sally] AstraZeneca, Macclesfield, Cheshire, England.
[Nicholson, Robert; Gee, Julia] Cardiff Univ, Welsh Sch Pharm, Tenovus Ctr Canc Res, Cardiff, S Glam, Wales.
[Kuter, Irene] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 3
TC 0
Z9 0
U1 0
U2 2
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD OCT
PY 2011
VL 20
SU 4
BP S26
EP S26
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 037DM
UT WOS:000311082400039
ER
PT J
AU Schoenfeld, JD
Harris, JR
AF Schoenfeld, Jonathan D.
Harris, Jay R.
TI Abbreviated course of radiotherapy (RT) for breast cancer
SO BREAST
LA English
DT Article
DE Radiation therapy (RT); Hypofractionation; Breast cancer
ID HYPOFRACTIONATED RADIATION-THERAPY; INTENSITY-MODULATED RADIOTHERAPY;
RANDOMIZED CLINICAL-TRIAL; ACCELERATED WHOLE-BREAST; QUALITY-OF-LIFE;
CONSERVING SURGERY; FOLLOW-UP; POSTOPERATIVE RADIOTHERAPY; FRACTIONATION
SCHEDULES; BRACHIAL PLEXOPATHY
AB The use of RT as a component of breast-conserving therapy or after mastectomy has been proven to reduce the risk of local-regional recurrence (LRR) and to improve long-term breast cancer-specific and overall survival. As has been the common practice in the United States and Continental Europe, the majority of studies that demonstrated these benefits utilized daily radiation doses ranging from 1.8-2 Gray (Gy). However, due to geographic limitations, patient preferences and financial considerations, there have been continued attempts to evaluate the efficacy and toxicity of abbreviated courses of breast RT. Two key factors in these attempts have been: (1) advances in radiobiology allowing for a more precise estimation of equivalent dosing; and (2) advances in the delivery of RT that have resulted in substantially improved dose homogeneity in the target volume. As an alternative to approximately five weeks of daily treatment at 1.8-2 Gy, delivering radiobiologically-equivalent total doses in hypofractionated, abbreviated schedules has been evaluated in five randomized controlled trials, as well as many prospective and retrospective experiences. These studies have generally demonstrated equivalent rates of LRR, disease-free survival and overall survival with the use of hypofractionated regimens. Despite theoretical and historic concerns that hypofractionated regimens could increase damage to normal tissue, the rates of acute and long-term toxicities have generally not been increased in most recent series. Some toxicities, however, may take years to decades to manifest.
Questions still remain regarding which patients are appropriate for abbreviated treatment. The majority of patients included in the studies supporting hypofractionated treatment were of older age with early-stage invasive ER+ disease of predominantly lower histological grade. This favorable subset of patients is also the most eligible for other alternative treatment approaches, such as partial-breast irradiation or hormonal therapy alone. Additionally, few to none of the patients included in most studies were treated with mastectomy, lymph node irradiation, a lumpectomy cavity radiation boost, or adjuvant chemotherapy.
The existing evidence prompted the American Society for Radiation Oncology (ASTRO) to convene a task force to issue an evidence-based guideline in 2010 delineating the patients for whom an abbreviated radiation course is most supported by the current evidence [Smith et al. 2010, Int J Radiat Oncol Biol Phys]. Ongoing and future studies will further clarify the suitability of a hypofractionated treatment approach for the patient subgroups underrepresented in available trials. Additionally, alternative abbreviated treatment regimens, including those in which treatment is given once weekly and treatments that include an integrated lumpectomy cavity boost, are actively being investigated. Finally, innovative radiation techniques, such as the use of higher energies, prone treatment, and breathing-adapted therapy have further increased the homogeneity of breast irradiation and minimized dose delivered to nearby critical normal structures. Consequently, increasing experience with these techniques may expand the population of patients amenable to hypofractionated therapy. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Harris, Jay R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
[Harris, Jay R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA.
[Schoenfeld, Jonathan D.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02215 USA.
RP Harris, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,Room D1622, Boston, MA 02215 USA.
EM jschoenfeld@lroc.harvard.edu; jharris@lroc.harvard.edu
NR 114
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U1 0
U2 7
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD OCT
PY 2011
VL 20
SU 3
BP S116
EP S127
PG 12
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 037CA
UT WOS:000311077400022
PM 22015277
ER
PT J
AU Winer, EP
Lin, NU
AF Winer, Eric P.
Lin, Nancy U.
TI STATE OF THE ART TREATMENT OF TRIPLE NEGATIVE BREAST CANCER
SO BREAST
LA English
DT Meeting Abstract
C1 [Winer, Eric P.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Div Womens Canc, Cambridge, MA 02138 USA.
[Lin, Nancy U.] Harvard Univ, Dana Farber Brigham & Womens Canc Ctr, Sch Med, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD OCT
PY 2011
VL 20
SU 4
BP S16
EP S17
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 037DM
UT WOS:000311082400014
ER
PT J
AU Shin, JM
Munson, K
Sachs, G
AF Shin, Jai Moo
Munson, Keith
Sachs, George
TI Gastric H+,K+-ATPase
SO COMPREHENSIVE PHYSIOLOGY
LA English
DT Article
AB The gastric H+, K+-ATPase is responsible for gastric acid secretion. This ATPase is composed of two subunits, the catalytic alpha subunit and the structural beta subunit. The alpha subunit with molecular mass of about 100 kDa has 10 transmembrane domains and is strongly associated with the beta subunit with a single transmembrane segment and a peptide mass of 35 kDa. Its three-dimensional structure is based on homology modeling and site-directed mutagenesis resulting in a proton extrusion and K+ reabsorption model. There are three conserved H3O+-binding sites in the middle of the membrane domain and H3O+ secretion depends on a conformational change involving Lys(791) insertion into the second H3O+ site enclosed by E795, E820, and D824 that allows export of protons at a concentration of 160 mM. K+ countertransport involves binding to this site after the release of protons with retrograde displacement of Lys(791) and then K+ transfer to E343 and exit to the cytoplasm. This ATPase is the major therapeutic target in treatment of acid-related diseases and there are several known luminal inhibitors allowing analysis of the luminal vestibule. One class contains the acid-activated covalent, thiophilic proton pump inhibitors, the most effective of current acid-suppressive drugs. Their binding sites and trypsinolysis allowed identification of all ten transmembrane segments of the ATPase. In addition, various K+-competitive inhibitors of the ATPase are being developed, with the advantage of complete and rapid inhibition of acid secretion independent of pump activity and allowing further refinement of the structure of the luminal vestibule of the E-2 form of this ATPase. (C) 2011 American Physiological Society. Compr Physiol 1: 2141-2153, 2011.
C1 [Shin, Jai Moo; Munson, Keith; Sachs, George] Univ Calif Los Angeles, Dept Med Physiol, Los Angeles, CA 90095 USA.
[Shin, Jai Moo; Munson, Keith; Sachs, George] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Shin, JM (reprint author), Univ Calif Los Angeles, Dept Med Physiol, Los Angeles, CA 90095 USA.
EM jaishin@ucla.edu
FU US VA; NIH/NIDDK [DK053642, DK058333]
FX This work was supported by US VA Merit Grant, NIH/NIDDK grant numbers
DK053642 and DK058333.
NR 110
TC 8
Z9 8
U1 1
U2 8
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2040-4603
J9 COMPR PHYSIOL
JI Compr. Physiol.
PD OCT
PY 2011
VL 1
IS 4
BP 2141
EP 2153
DI 10.1002/cphy.c110010
PG 13
WC Physiology
SC Physiology
GA V27SM
UT WOS:000208632900018
PM 23733700
ER
PT J
AU Mimura, T
Chang, JH
Kim, TI
Onguchi, T
Kojima, T
Sakimoto, T
Azar, DT
AF Mimura, Tatsuya
Chang, Jin-Hong
Kim, Tae-im
Onguchi, Tatsuya
Kojima, Takashi
Sakimoto, Tohru
Azar, Dimitri T.
TI MT1-MMP Cleavage of the Antiangiogenic Proteoglycan Decorin: Role in
Corneal Angiogenesis
SO CORNEA
LA English
DT Article
DE angiogenesis; cornea; decorin; MT1-MMP
AB Purpose: Decorin is a small chondroitin sulfate proteoglycan that inhibits vascular endothelial cell migration and tube formation. Membrane type 1-matrix metalloproteinase (MT1-MMP) has been shown to be an important angiogenic enzyme in the cornea. We evaluated the specific role of MT1-MMP in decorin cleavage in the cornea.
Methods: Western blotting was used to evaluate decorin degradation by MT1-MMP. Aortic ring tube formation assays were used to assay the inhibitory effect of decorin and the stimulatory effect of MT1-MMP on vascular endothelial cells in vitro. Corneal micro-pocket assays using basic fibroblast growth factor (bFGF) were used to assess changes in the levels of decorin and MT1-MMP.
Results: MT1-MMP cleaves decorin in a time-and concentration-dependent manner in vitro. MT1-MMP levels were upregulated after in vivo bFGF pellet implantation in the cornea, and decorin cleavage products were detected in bFGF-implanted corneas but not in normal corneas. MT1-MMP reduced the inhibitory effects of decorin on aortic ring tube formation in vitro.
Conclusion: MT1-MMP may play an essential role in angiogenesis through proteolytic processing of decorin in the cornea.
C1 [Mimura, Tatsuya] Univ Tokyo, Dept Ophthalmol, Grad Sch Med, Tokyo 1138655, Japan.
[Mimura, Tatsuya] Toranomon Gen Hosp, Dept Ophthalmol, Tokyo, Japan.
[Mimura, Tatsuya; Chang, Jin-Hong; Onguchi, Tatsuya; Kojima, Takashi; Azar, Dimitri T.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA.
[Mimura, Tatsuya; Chang, Jin-Hong; Kim, Tae-im; Kojima, Takashi; Sakimoto, Tohru; Azar, Dimitri T.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA.
RP Mimura, T (reprint author), Univ Tokyo, Dept Ophthalmol, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM mimurat-tky@umin.ac.jp
FU National Institutes of Health [EY10101, EY001792, EY14048]; Research to
Prevent Blindness (Department of Ophthalmology and Visual Sciences,
University of Illinois at Chicago)
FX Supported by the National Institutes of Health grants EY10101 and
EY001792 (to D. T. A.) and EY14048 to J.-H. Chang and an unrestricted
departmental grant from Research to Prevent Blindness (Department of
Ophthalmology and Visual Sciences, University of Illinois at Chicago).
NR 21
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-3740
EI 1536-4798
J9 CORNEA
JI Cornea
PD OCT
PY 2011
VL 30
SU 1
BP S45
EP S49
PG 5
WC Ophthalmology
SC Ophthalmology
GA V32LC
UT WOS:000208951700010
PM 21912230
ER
PT J
AU Lakhashe, SK
Silvestri, G
Ruprecht, RM
AF Lakhashe, Samir K.
Silvestri, Guido
Ruprecht, Ruth M.
TI No acquisition: A new ambition for HIV vaccine development?
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLADE C INFECTION; B-CELL RESPONSES;
RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; PROTECTIVE EFFICACY;
IMMUNE-RESPONSES; MONOCLONAL-ANTIBODIES; REPLICATION-COMPETENT;
CHALLENGE VIRUSES
AB Development of a safe and effective prophylactic HIV-1 vaccine presents unique challenges. The pessimism following the failure of two HIV-1 vaccine concepts in clinical trials, HIV-1 gp120 and an adenovirus-based approach to induce only cellular immune responses, has been replaced by cautious optimism engendered by the RV144 trial outcome, the isolation of several new broadly reactive neutralizing monoclonal antibodies, and recent primate model data indicating prevention of viral acquisition by active or passive immunization. Intense efforts are underway to optimize immunogen design, adjuvants, and the tools for preclinical evaluation of candidate vaccines in primates, where correlates of protection can be examined in detail - as proof-of-concept for clinical trials.
C1 [Lakhashe, Samir K.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lakhashe, Samir K.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM ruth_ruprecht@dfci.harvard.edu
RI Lakhashe, Samir/F-1150-2014
FU NIH [P01 AI048240, R37 AI034266, P01 AI082282, P01 AI054558, R56
AI062515]; Bill and Melinda Gates Foundation Collaboration for AIDS
Vaccine Discovery (CAVD) UCL-VDC (Weiss) [38637]; Center for AIDS
Research Immunology Core [P30 AI050409]
FX The work described here was supported by NIH grants P01 AI048240, R37
AI034266, P01 AI082282, P01 AI054558, and R56 AI062515. Support was also
provided by the Bill and Melinda Gates Foundation Collaboration for AIDS
Vaccine Discovery (CAVD) UCL-VDC (Weiss) grant 38637, and by Center for
AIDS Research Immunology Core P30 AI050409.
NR 76
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD OCT
PY 2011
VL 1
IS 4
BP 246
EP 253
DI 10.1016/j.coviro.2011.07.005
PG 8
WC Virology
SC Virology
GA 051FS
UT WOS:000312112200005
PM 22081778
ER
PT J
AU Forster, S
Grimmer, T
Miederer, I
Henriksen, G
Yousefi, BH
Graner, P
Wester, HJ
Forstl, H
Kurz, A
Dickerson, BC
Drzezga, A
AF Foerster, S.
Grimmer, T.
Miederer, I.
Henriksen, G.
Yousefi, B. H.
Graner, P.
Wester, H. J.
Foerstl, H.
Kurz, A.
Dickerson, B. C.
Drzezga, A.
TI Regional expansion of cerebral hypometabolism in AD follows the pattern
of amyloid-deposition with temporal delay and is related to healthy
functional connectivity networks
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Meeting Abstract
C1 [Foerster, S.; Miederer, I.; Henriksen, G.; Yousefi, B. H.; Graner, P.; Wester, H. J.; Drzezga, A.] Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, Munich, Germany.
[Grimmer, T.; Foerstl, H.; Kurz, A.] Univ Munich, Dept Psychiat, Klinikum Rechts Isar, D-80539 Munich, Germany.
[Dickerson, B. C.] Massachusetts Gen Hosp, Dept Neurol, Massachusetts Alzheimers Dis Res Ctr, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Dickerson, B. C.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD OCT
PY 2011
VL 38
SU 2
BP S122
EP S122
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA V27NH
UT WOS:000208619400107
ER
PT J
AU Margey, R
Selzer, F
Quiroz, R
Jneid, H
Marroquin, OC
Mulukutla, SR
Laskey, WK
Jacobs, AK
Maree, AO
AF Margey, R.
Selzer, F.
Quiroz, R.
Jneid, H.
Marroquin, O. C.
Mulukutla, S. R.
Laskey, W. K.
Jacobs, A. K.
Maree, A. O.
TI Impact of Renal Insufficiency on Prescription of Discharge Medication
and 1 year Outcomes After Percutaneous Coronary Intervention
SO IRISH JOURNAL OF MEDICAL SCIENCE
LA English
DT Meeting Abstract
C1 [Margey, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Quiroz, R.; Jacobs, A. K.; Maree, A. O.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA.
[Selzer, F.; Marroquin, O. C.; Mulukutla, S. R.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Jneid, H.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Jneid, H.] Baylor Coll Med, Houston, TX 77030 USA.
[Laskey, W. K.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA.
RI Marroquin, Oscar/F-2214-2015
OI Marroquin, Oscar/0000-0002-0909-0319
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 0021-1265
J9 IRISH J MED SCI
JI Irish J. Med. Sci.
PD OCT
PY 2011
VL 180
SU 11
MA 54
BP S400
EP S400
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA V27YS
UT WOS:000208649100055
ER
PT J
AU Margey, R
Maree, AO
Selzer, F
Adams, B
Patel, N
Jneid, H
Marroquin, OC
Mulukutla, SR
Laskey, WK
Jacobs, AK
AF Margey, R.
Maree, A. O.
Selzer, F.
Adams, B.
Patel, N.
Jneid, H.
Marroquin, O. C.
Mulukutla, S. R.
Laskey, W. K.
Jacobs, A. K.
TI Impact of Renal Insufficiency on Bleeding Events in Patients Undergoing
Percutaneous Coronary Intervention
SO IRISH JOURNAL OF MEDICAL SCIENCE
LA English
DT Meeting Abstract
C1 [Margey, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Margey, R.] Harvard Univ, Sch Med, Boston, MA USA.
[Maree, A. O.; Adams, B.; Patel, N.; Jacobs, A. K.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA.
[Selzer, F.; Marroquin, O. C.; Mulukutla, S. R.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Jneid, H.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Jneid, H.] Baylor Coll Med, Houston, TX 77030 USA.
[Laskey, W. K.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA.
RI Marroquin, Oscar/F-2214-2015
OI Marroquin, Oscar/0000-0002-0909-0319
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 0021-1265
J9 IRISH J MED SCI
JI Irish J. Med. Sci.
PD OCT
PY 2011
VL 180
SU 11
MA 16
BP S386
EP S386
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA V27YS
UT WOS:000208649100017
ER
PT J
AU Margey, R
Arzamendi, D
Hynes, B
Elmariah, S
Renfigo-Moreno, P
Schainfeld, R
Jaff, MR
Inglessis, I
Palacios, IP
AF Margey, R.
Arzamendi, D.
Hynes, B.
Elmariah, S.
Renfigo-Moreno, P.
Schainfeld, R.
Jaff, M. R.
Inglessis, I.
Palacios, I. P.
TI Systemic Embolic Events Other than Stroke or TIA from Paradoxical
Embolization via Patent Foramen Ovale
SO IRISH JOURNAL OF MEDICAL SCIENCE
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 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 0021-1265
J9 IRISH J MED SCI
JI Irish J. Med. Sci.
PD OCT
PY 2011
VL 180
SU 11
MA 7
BP S383
EP S383
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA V27YS
UT WOS:000208649100008
ER
PT J
AU Margey, RJP
Sakhuja, R
Gandhi, S
Rogers, RK
Weinberg, I
Jaff, MR
Schainfeld, R
Rosenfield, K
AF Margey, R. J. P.
Sakhuja, R.
Gandhi, S.
Rogers, R. K.
Weinberg, I
Jaff, M. R.
Schainfeld, R.
Rosenfield, K.
TI A Novel Endovenous Approach for Treatment of Massive Central Venous or
Pulmonary Arterial Thrombus, Mass, or Vegetation: The AngioVac Suction
Cannula and Circuit
SO IRISH JOURNAL OF MEDICAL SCIENCE
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 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 0021-1265
J9 IRISH J MED SCI
JI Irish J. Med. Sci.
PD OCT
PY 2011
VL 180
SU 11
MA 12
BP S385
EP S385
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA V27YS
UT WOS:000208649100013
ER
PT J
AU Garg, P
Misra, S
Thakur, JD
Song, J
AF Garg, Pankaj
Misra, Swapna
Thakur, Jai Deep
Song, Jeremy
TI Single incision laparoscopic surgery ovarian cystectomy in large benign
ovarian cysts using conventional instruments
SO JOURNAL OF MINIMAL ACCESS SURGERY
LA English
DT Article
DE Cystectomy; laparoscopy; ovarian; single incision; single incision
laparoscopic surgery
AB We describe a technique for the management of large benign ovarian cysts by single incision laparoscopic surgery (SILS) through the umbilicus. The paucity of intra-abdominal working space in large ovarian cysts poses a technical challenge. Moreover, difficult convergence of operating instruments and competition for operating space outside the abdomen during the SILS makes the procedure quite demanding, especially with the conventional instruments. The concept of providing traction by taking sutures from the abdominal wall, as done in SILS laparoscopic cholecystectomy, was applied for SILS cystectomy in large ovarian cysts. Two sutures taken through the abdominal wall and then through the cyst wall provide excellent traction and "hang" the cyst from the abdominal wall, making it convenient to dissect and operate. This technique demonstrates that SILS ovarian cystectomy is feasible, safe and technically unchallenging even in large benign ovarian cysts.
C1 [Garg, Pankaj; Misra, Swapna] Fortis Super Special Hosp, Dept Minimal Access Surg & Gynaecol, Mohali, Punjab, India.
[Garg, Pankaj] SGHS Hosp, Dept Gen Laparoscop Surg, Mohali, Punjab, India.
[Thakur, Jai Deep] Univ Arkansas Med Sci, Dept Gen Surg, Little Rock, AR 72205 USA.
[Song, Jeremy] Massachusetts Gen Hosp, Dept Sch Med, Simches Res Ctr, Boston, MA 02114 USA.
RP Garg, P (reprint author), 1042,Sect 15, Panchkula, Haryana, India.
EM drgargpankaj@yahoo.com
NR 5
TC 4
Z9 4
U1 0
U2 0
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 0972-9941
J9 J MINIM ACCESS SURG
JI J. Minimal Access Surg.
PD OCT-DEC
PY 2011
VL 7
IS 4
BP 232
EP 235
DI 10.4103/0972-9941.85646
PG 4
WC Surgery
SC Surgery
GA 009RB
UT WOS:000309041800005
PM 22022112
ER
PT J
AU Pugh, MJV
Hanlon, JT
Wang, CP
Semla, T
Burk, M
Amuan, ME
Lowery, A
Good, CB
Berlowitz, DR
AF Pugh, Mary Jo V.
Hanlon, Joseph T.
Wang, Chen-Pin
Semla, Todd
Burk, Muriel
Amuan, Megan E.
Lowery, Ashlei
Good, Chester B.
Berlowitz, Dan R.
TI Trends in Use of High-Risk Medications for Older Veterans: 2004 to 2006
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE inappropriate prescribing; quality of care; aged; pharmacoepidemiology
ID ELDERLY VETERANS; CLAIMS DATABASE; HEALTH; AFFAIRS; FALLS; DRUG; CARE;
NITROFURANTOIN; CRITERIA; PATIENT
AB OBJECTIVES: To examine the change in use of high-risk medications for the elderly (HRME), as defined by the National Committee on Quality Assurance's Healthcare Effectiveness Data and Information Set (HEDIS) quality measure (HEDIS HRME), by older outpatient veterans over a 3-year period and to identify risk factors for HEDIS HRME exposure overall and for the most commonly used drug classes.
DESIGN: Longitudinal retrospective database analysis.
SETTING: Outpatient clinics within the Department of Veterans Affairs (VA).
PARTICIPANTS: Veterans aged 65 by October 1, 2003, and who received VA care at least once each year until September 30, 2006.
MEASUREMENTS: Rates of use of HEDIS HRME overall and according to specific drug classes each year from fiscal year 2004 (FY04) to FY06.
RESULTS: In a cohort of 1,567,467, high-risk medication exposure fell from 13.1% to 12.3% between FY04 and FY06 (P < .001). High-risk antihistamines (e. g., diphenhydramine), opioid analgesics (e. g., propoxyphene), skeletal muscle relaxants (e. g., cyclobenzaprine), psychotropics (e. g., long half-life benzodiazepines), endocrine (e. g., estrogen), and cardiac medications (e. g., short-acting nifedipine) had modest but statistically significant (P < .001) reductions (range -3.8% to -16.0%); nitrofurantoin demonstrated a statistically significant increase (+36.5%; P < .001). Overall HEDIS HRME exposure was more likely for men, Hispanics, those receiving more medications, those with psychiatric comorbidity, and those without prior geriatric care. Exposure was lower for individuals exempt from copayment. Similar associations were seen between ethnicity, polypharmacy, psychiatric comorbidity, access-to-care factors, and use of individual HEDIS HRME classes.
CONCLUSION: HEDIS HRME drug exposure decreased slightly in an integrated healthcare system. Risk factors for exposure were not consistent across drug groups. Future studies should examine whether interventions to further reduce HEDIS HRME use improve health outcomes. J Am Geriatr Soc 59:1891-1898, 2011.
C1 [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst 11C6, VERDICT REAP, Vet Evidence Based Res & Implementat Ctr, San Antonio, TX 78023 USA.
[Pugh, Mary Jo V.; Wang, Chen-Pin] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Lowery, Ashlei] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr Med, Dept Pharm & Therapeut, Pittsburgh, PA USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Div Geriatr Med, Pittsburgh, PA 15261 USA.
[Good, Chester B.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA.
[Hanlon, Joseph T.; Good, Chester B.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
[Hanlon, Joseph T.; Good, Chester B.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Semla, Todd; Burk, Muriel] Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA.
[Semla, Todd; Burk, Muriel] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Semla, Todd; Burk, Muriel; Berlowitz, Dan R.] Northwestern Univ, Dept Psychiat & Behav Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
[Amuan, Megan E.] Ctr Hlth Qual Outcomes & Econ Res, Dept Vet Affairs, Bedford, MA USA.
[Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst 11C6, VERDICT REAP, Vet Evidence Based Res & Implementat Ctr, 7400 Merton Minter, San Antonio, TX 78023 USA.
EM maryjo.pugh2@va.gov
OI Pugh, Mary Jo/0000-0003-4196-7763
FU South Texas Veterans Healthcare System/Audie L. Murphy Division;
Veterans Evidence-based Research and Implementation Center; VA Health
Services Research and Development Service (HSRD) [DHI-09-237,
IIR-06-062, IIR 08-274, SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335,
SHP 08-140, TRX 01-091]; Epilepsy Foundation; Department of Defense
CDMRP [09090014]; NIH [R01-NR010828]; VA Health Services Research
[IIR-06-062]; National Institute of Aging [R01AG027017, P30AG024827, T32
AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health
[R34 MH082682]; National Institute of Nursing Research [R01NR010135];
Agency for Healthcare Research and Quality [R01HS017695]
FX The authors acknowledge and appreciate support from the South Texas
Veterans Healthcare System/Audie L. Murphy Division and the Veterans
Evidence-based Research and Implementation Center. The views expressed
in this article are those of the authors and do not necessarily
represent the views of the VA. We acknowledge the contributions of
Jeffrey Tabares and Ranjani Davalath in assisting with manuscript
preparation.; Dr. Pugh has received research funding from VA Health
Services Research and Development Service (HSRD) DHI-09-237 (PI); VA
HSRD IIR-06-062 PI, Epilepsy Foundation PI, VA HSRD PPO 09-295 PI, VA
HSRD IIR 02-274 PI. Pugh as co-I: VA HSRD IIR 08-274, VA HSRD
SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091
Department of Defense CDMRP 09090014, NIH R01-NR010828,; This study was
supported by a VA Health Services Research grant (IIR-06-062, Dr. Pugh
PI). Dr Hanlon is supported by National Institute of Aging grants
(R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056), a
National Institute of Mental Health grant (R34 MH082682), a National
Institute of Nursing Research grant (R01NR010135), and an Agency for
Healthcare Research and Quality grant (R01HS017695).
NR 39
TC 14
Z9 15
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2011
VL 59
IS 10
BP 1891
EP 1898
DI 10.1111/j.1532-5415.2011.03559.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 840OE
UT WOS:000296449300014
PM 21883108
ER
PT J
AU Nichols, AJ
Evans, CL
AF Nichols, Alexander J.
Evans, Conor L.
TI Video-rate Scanning Confocal Microscopy and Microendoscopy
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Bioengineering; Issue 56; Microscopy; confocal microscopy;
microendoscopy; video-rate; fluorescence; scanning; in vivo imaging
AB Confocal microscopy has become an invaluable tool in biology and the biomedical sciences, enabling rapid, high-sensitivity, and high-resolution optical sectioning of complex systems. Confocal microscopy is routinely used, for example, to study specific cellular targets(1), monitor dynamics in living cells(2-4), and visualize the three dimensional evolution of entire organisms(5,6). Extensions of confocal imaging systems, such as confocal microendoscopes, allow for high-resolution imaging in vivo(7) and are currently being applied to disease imaging and diagnosis in clinical settings(8,9).
Confocal microscopy provides three-dimensional resolution by creating so-called "optical sections" using straightforward geometrical optics. In a standard wide-field microscope, fluorescence generated from a sample is collected by an objective lens and relayed directly to a detector. While acceptable for imaging thin samples, thick samples become blurred by fluorescence generated above and below the objective focal plane. In contrast, confocal microscopy enables virtual, optical sectioning of samples, rejecting out-of-focus light to build high resolution three-dimensional representations of samples.
Confocal microscopes achieve this feat by using a confocal aperture in the detection beam path. The fluorescence collected from a sample by the objective is relayed back through the scanning mirrors and through the primary dichroic mirror, a mirror carefully selected to reflect shorter wavelengths such as the laser excitation beam while passing the longer, Stokes-shifted fluorescence emission. This long-wavelength fluorescence signal is then passed to a pair of lenses on either side of a pinhole that is positioned at a plane exactly conjugate with the focal plane of the objective lens. Photons collected from the focal volume of the object are collimated by the objective lens and are focused by the confocal lenses through the pinhole. Fluorescence generated above or below the focal plane will therefore not be collimated properly, and will not pass through the confocal pinhole(1), creating an optical section in which only light from the microscope focus is visible. (Fig 1). Thus the pinhole effectively acts as a virtual aperture in the focal plane, confining the detected emission to only one limited spatial location.
Modern commercial confocal microscopes offer users fully automated operation, making formerly complex imaging procedures relatively straightforward and accessible. Despite the flexibility and power of these systems, commercial confocal microscopes are not well suited for all confocal imaging tasks, such as many in vivo imaging applications. Without the ability to create customized imaging systems to meet their needs, important experiments can remain out of reach to many scientists.
In this article, we provide a step-by-step method for the complete construction of a custom, video-rate confocal imaging system from basic components. The upright microscope will be constructed using a resonant galvanometric mirror to provide the fast scanning axis, while a standard speed resonant galvanometric mirror will scan the slow axis. To create a precise scanned beam in the objective lens focus, these mirrors will be positioned at the so-called telecentric planes using four relay lenses. Confocal detection will be accomplished using a standard, off-the-shelf photomultiplier tube (PMT), and the images will be captured and displayed using a Matrox framegrabber card and the included software.
C1 [Nichols, Alexander J.; Evans, Conor L.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA.
[Nichols, Alexander J.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Nichols, Alexander J.; Evans, Conor L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02138 USA.
RP Evans, CL (reprint author), Harvard Univ, Program Biophys, Cambridge, MA 02138 USA.
EM Evans.Conor@mgh.harvard.edu
FU ThorLabs; NSF; National Institutes of Health through the NIH Director's
New Innovator Award Program [1 DP2 OD007096-01]
FX The authors would like to thank ThorLabs for their support of this
project. AJN wishes to acknowledge the support of an NSF Graduate
Fellowship.; This work was partially funded by the National Institutes
of Health through the NIH Director's New Innovator Award Program, grant
number 1 DP2 OD007096-01. Information on the New Innovator Award Program
is at http://nihroadmap.nih.gov/newinnovator/. The authors would like to
thank Tom Hayes for use of the Harvard Electronics lab.
NR 10
TC 1
Z9 1
U1 0
U2 3
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD OCT
PY 2011
IS 56
AR UNSP e3252
DI 10.3791/3252
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36PB
UT WOS:000209222400032
ER
PT J
AU Parsons, XH
Teng, YD
Parsons, JF
Snyder, EY
Smotrich, DB
Moore, DA
AF Parsons, Xuejun H.
Teng, Yang D.
Parsons, James F.
Snyder, Evan Y.
Smotrich, David B.
Moore, Dennis A.
TI Efficient Derivation of Human Neuronal Progenitors and Neurons from
Pluripotent Human Embryonic Stem Cells with Small Molecule Induction
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neuroscience; Issue 56; stem cell; human embryonic stem cell; human;
neuronal progenitor; neuron; human pluripotent cell; neuronal
differentiation; small molecule induction; cell culture; cell therapy
AB There is a large unfulfilled need for a clinically-suitable human neuronal cell source for repair or regeneration of the damaged central nervous system (CNS) structure and circuitry in today's healthcare industry. Cell-based therapies hold great promise to restore the lost nerve tissue and function for CNS disorders. However, cell therapies based on CNS-derived neural stem cells have encountered supply restriction and difficulty to use in the clinical setting due to their limited expansion ability in culture and failing plasticity after extensive passaging(1-3). Despite some beneficial outcomes, the CNS-derived human neural stem cells (hNSCs) appear to exert their therapeutic effects primarily by their non-neuronal progenies through producing trophic and neuroprotective molecules to rescue the endogenous cells(1-3). Alternatively, pluripotent human embryonic stem cells (hESCs) proffer cures for a wide range of neurological disorders by supplying the diversity of human neuronal cell types in the developing CNS for regeneration(1,4-7). However, how to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, resulting in inefficient and uncontrollable lineage-commitment that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity(7-10). In addition, undefined foreign/animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic(11-13). To overcome these obstacles, we have resolved the elements of a defined culture system necessary and sufficient for sustaining the epiblast pluripotence of hESCs, serving as a platform for de novo derivation of clinically-suitable hESCs and effectively directing such hESCs uniformly towards clinically-relevant lineages by small molecules(14) (please see a schematic in Fig. 1). Retinoic acid (RA) does not induce neuronal differentiation of undifferentiated hESCs maintained on feeders(1,14). And unlike mouse ESCs, treating hESC-differentiated embryoid bodies (EBs) only slightly increases the low yield of neurons(1,14,15). However, after screening a variety of small molecules and growth factors, we found that such defined conditions rendered retinoic acid (RA) sufficient to induce the specification of neuroectoderm direct from pluripotent hESCs that further progressed to neuroblasts that generated human neuronal progenitors and neurons in the developing CNS with high efficiency (Fig. 2). We defined conditions for induction of neuroblasts direct from pluripotent hESCs without an intervening multi-lineage embryoid body stage, enabling well-controlled efficient derivation of a large supply of human neuronal cells across the spectrum of developmental stages for cell-based therapeutics.
C1 [Parsons, Xuejun H.; Parsons, James F.; Snyder, Evan Y.; Smotrich, David B.; Moore, Dennis A.] San Diego Regenerat Med Inst, San Diego, CA 92109 USA.
[Parsons, Xuejun H.; Parsons, James F.; Snyder, Evan Y.; Smotrich, David B.; Moore, Dennis A.] Xcelthera, San Diego, CA USA.
[Teng, Yang D.] Harvard Univ, Sch Med, Dept Neurosurg, Cambridge, MA 02138 USA.
[Teng, Yang D.] VA Boston Healthcare Syst, Div SCI Res, Jamaica Plain, MA USA.
[Snyder, Evan Y.] Sanford Burnham Med Res Inst, Program Stem Cell & Regenerat Biol, La Jolla, CA USA.
[Smotrich, David B.] La Jolla IVF, La Jolla, CA USA.
RP Parsons, XH (reprint author), San Diego Regenerat Med Inst, San Diego, CA 92109 USA.
EM parsons@SDRMI.org
FU National Institute of Health (NIH) grants from National Institute on
Aging [NIHK01AG024496]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development [NIHR21HD056530]
FX XHP has been supported by National Institute of Health (NIH) grants from
National Institute on Aging (NIHK01AG024496) and The Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NIHR21HD056530).
NR 23
TC 2
Z9 2
U1 0
U2 6
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD OCT
PY 2011
IS 56
AR UNSP e3273
DI 10.3791/3273
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36PB
UT WOS:000209222400036
PM 22064669
ER
PT J
AU Liu, CF
Manning, WG
Burgess, JF
Hebert, PL
Bryson, CL
Fortney, J
Perkins, M
Sharp, ND
Maciejewski, ML
AF Liu, Chuan-Fen
Manning, Willard G.
Burgess, James F., Jr.
Hebert, Paul L.
Bryson, Chris L.
Fortney, John
Perkins, Mark
Sharp, Nancy D.
Maciejewski, Matthew L.
TI Reliance on Veterans Affairs Outpatient Care by Medicare-eligible
Veterans
SO MEDICAL CARE
LA English
DT Article
DE outpatient; veteran; Medicare; primary care; specialty care
ID HEALTH-CARE; DUAL-USE; VA; SERVICES; VHA; TRANSFORMATION; COVERAGE;
ACCESS; SYSTEM
AB Objective: To examine longitudinal changes in Medicare-eligible veterans' reliance on the Department of Veterans Affairs (VA) healthcare system for primary and specialty care over 4 years.
Methods: We merged VA administrative and Medicare claims data to examine outpatient use during fiscal years (FY) 2001 to 2004 by 15,520 Medicare-eligible veterans who used VA primary care in FY2000. Reliance on VA outpatient care was defined as the proportion of total (VA/Medicare) visits received in VA for primary or specialty care.
Results: Of 869,000 primary and specialty care visits in the study period, 39% occurred within VA and 77% were specialty care. Reliance on VA primary care was substantially higher than specialty care (66% vs. 50% in FY2001; P<0.001). Reliance on VA primary and specialty care decreased over time (57% vs. 31% in FY2004; P<0.001). Significant shifts occurred at both extremes of VA reliance. From FY2001 to FY2004, the proportion of patients in the top decile of reliance on VA primary care decreased from 39% to 31%, whereas the proportion in the bottom decile doubled from 8% to 18%. Similarly, the proportion of patients in the top decile of reliance on VA specialty care decreased from 24% to 13%, whereas the proportion in the bottom decile doubled from 22% to 47%.
Conclusions: Reliance on VA primary and specialty care among VA primary care patients decreased substantially over time, particularly for specialty care. Increasing use of non-VA services may complicate VA's implementation of patient-centered medical home models and performance measurement.
C1 [Liu, Chuan-Fen; Hebert, Paul L.; Bryson, Chris L.; Perkins, Mark; Sharp, Nancy D.] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA.
[Liu, Chuan-Fen; Hebert, Paul L.; Sharp, Nancy D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Manning, Willard G.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 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.
[Bryson, Chris L.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA.
[Fortney, John] S Cent Mental Hlth Illness Res & Educ & Clin Ctr, Little Rock, AR USA.
[Fortney, John] Cent Arkansas Vet Healthcare Syst, HSR&D Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA.
[Fortney, John] Univ Arkansas Med Sci, Dept Psychiat & Behav Sci, Div Hlth Serv Res, Little Rock, AR 72205 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 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 fliu@u.washington.edu
OI Burgess, James/0000-0002-6646-7071
FU Health Services Research and Development Service, Office of Research and
Development, Department of Veterans Affairs [IIR 04-292]
FX Supported by the Health Services Research and Development Service,
Office of Research and Development, Department of Veterans Affairs,
project number IIR 04-292.
NR 31
TC 23
Z9 23
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD OCT
PY 2011
VL 49
IS 10
BP 911
EP 917
DI 10.1097/MLR.0b013e31822396c5
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 821EO
UT WOS:000294957900006
PM 21685810
ER
PT J
AU Zhu, JY
Stuver, SO
Epstein, AM
Schneider, EC
Weissman, JS
Weingart, SN
AF Zhu, Junya
Stuver, Sherri O.
Epstein, Arnold M.
Schneider, Eric C.
Weissman, Joel S.
Weingart, Saul N.
TI Can We Rely on Patients' Reports of Adverse Events?
SO MEDICAL CARE
LA English
DT Article
DE patient safety; patient surveys; adverse events; complication
ID PATIENTS TELL US; HOSPITALIZED-PATIENTS; LIKELIHOOD RATIOS; DRUG EVENTS;
MEDICAL PATIENTS; AMBULATORY-CARE; HEALTH-CARE; ERRORS
AB Background: Evidence suggests that patients can report a variety of adverse events (AEs) not captured by traditional methods such as a chart review. Little is known, however, about whether patient reports are useful for measuring patient safety.
Objectives: To examine the degree to which physician reviewers agreed that patient reports of "negative effects" constituted AEs, and to identify questionnaire items that affected reviewers' judgments.
Methods: We surveyed patients discharged from Massachusetts hospitals in 2003 to elicit information about negative effects associated with hospitalization. Physician reviewers judged whether patient-reported negative effects represented AEs, and classified the severity of the event. Likelihood ratios were calculated to assess whether patient responses to questionnaire items affected reviewers' judgments.
Results: Of the 2582 patients surveyed, 753 patients reported 1170 negative effects, and 71.2% of these effects were classified as AEs by physician reviewers. Negative effects most likely to be classified as AEs involved newly prescribed medications and changes to previously prescribed medications. Additional information elicited from follow-up survey questions modestly affected reviewers' classification of serious AEs. Negative effects reported by women, younger patients, those reporting better health status, and those not admitted through the emergency department were more likely to be classified as AEs.
Conclusions: Many patients were able to identify care-related AEs. Patient responses to questions about the sequelae of the events provided limited additional information for physicians to use in gauging the presence and severity of the event. Patient reports complement other incident-detection methods by providing information that is credible and unavailable from other sources.
C1 [Zhu, Junya; Stuver, Sherri O.; Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA.
[Zhu, Junya] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA 02254 USA.
[Epstein, Arnold M.; Schneider, Eric C.; Weissman, Joel S.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA.
[Epstein, Arnold M.; Schneider, Eric C.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA.
[Schneider, Eric C.] RAND Boston, Boston, MA USA.
[Weissman, Joel S.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Weissman, Joel S.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA.
RP Zhu, JY (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA.
EM junya_zhu@dfci.harvard.edu
OI Stuver, Sherri/0000-0002-4027-2663; Schneider, Eric/0000-0002-1132-5084
FU Agency for Healthcare Research and Quality [U18 HS11928]; Center for
Patient Safety at Dana-Farber Cancer Institute
FX Supported by a Cooperative Agreement from the Agency for Healthcare
Research and Quality to the Massachusetts Department of Public Health
[U18 HS11928], and the Center for Patient Safety at Dana-Farber Cancer
Institute.
NR 39
TC 27
Z9 27
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD OCT
PY 2011
VL 49
IS 10
BP 948
EP 955
DI 10.1097/MLR.0b013e31822047a8
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 821EO
UT WOS:000294957900011
PM 21642876
ER
PT J
AU Arora, A
Healy, B
Hayden, D
Ceccarelli, A
Tauhid, S
Neema, M
Bakshi, R
AF Arora, A.
Healy, B.
Hayden, D.
Ceccarelli, A.
Tauhid, S.
Neema, M.
Bakshi, R.
TI Approaches to normalisation of spinal cord volume: application to
multiple sclerosis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Brookline, MA USA.
Brigham & Womens Hosp, Brookline, MA USA.
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 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD OCT
PY 2011
VL 17
SU 10
MA P371
BP S150
EP S150
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V35GA
UT WOS:000209137300300
ER
PT J
AU Gavasso, S
Maroy, T
Gjertsen, BT
Anderssen, E
Myhr, KM
Vedeler, C
AF Gavasso, S.
Maroy, T.
Gjertsen, B. -T.
Anderssen, E.
Myhr, K. -M.
Vedeler, C.
TI Monitoring drug response in patients with signalling pathway-specific
flow cytometry
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
C1 Haukeland Hosp, N-5021 Bergen, Norway.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Gjertsen, Bjorn T/O-1542-2015
OI Gjertsen, Bjorn T/0000-0001-9358-9704
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 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD OCT
PY 2011
VL 17
SU 10
MA P545
BP S236
EP S236
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V35GA
UT WOS:000209137300474
ER
PT J
AU Klawiter, EC
Jackson, JS
Ceccarelli, A
Arora, A
Bakshi, R
Neema, M
AF Klawiter, E. C.
Jackson, J. S.
Ceccarelli, A.
Arora, A.
Bakshi, R.
Neema, M.
TI Magnetic resonance imaging correlates of corpus callosum atrophy in
multiple sclerosis at 3T
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 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 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD OCT
PY 2011
VL 17
SU 10
MA P834
BP S371
EP S371
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V35GA
UT WOS:000209137301200
ER
PT J
AU Xia, Z
Liu, Q
Keenan, B
Berger, C
Kaliszewska, A
Wood, I
Alter, G
De Jager, P
AF Xia, Z.
Liu, Q.
Keenan, B.
Berger, C.
Kaliszewska, A.
Wood, I.
Alter, G.
De Jager, P.
TI Cytometric profiling of natural killer cells as a functional screen of
genetic variants associated with multiple sclerosis susceptibility
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
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 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD OCT
PY 2011
VL 17
SU 10
MA P764
BP S339
EP S339
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V35GA
UT WOS:000209137301130
ER
PT J
AU Wolf, EJ
Miller, MW
Brown, TA
AF Wolf, Erika J.
Miller, Mark W.
Brown, Timothy A.
TI The Structure of Personality Disorders in Individuals With Posttraumatic
Stress Disorder
SO PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT
LA English
DT Article
DE personality disorder; internalizing; externalizing; boundary
disturbances; posttraumatic stress disorder
ID COMMON PSYCHOPATHOLOGICAL SYNDROMES; COMORBIDITY SURVEY REPLICATION;
PROPOSED META-STRUCTURE; DSM-IV; MENTAL-DISORDERS; COMBAT VETERANS;
PSYCHOMETRIC PROPERTIES; GENETIC-STRUCTURE; PTSD CHECKLIST; FIT INDEXES
AB Research on the structure of personality disorders (PDs) has relied primarily on exploratory analyses to evaluate trait-based models of the factors underlying the covariation of these disorders. This study used confirmatory factor analysis to evaluate whether a model that included both PD traits and a general personality dysfunction factor would account for the comorbidity of the PDs better than a trait-only model. It also examined if the internalizing/externalizing model of psychopathology, developed previously through research on the structure of Axis I disorders, might similarly account for the covariation of the Axis II disorders in a sample of 245 veterans and nonveterans with posttraumatic stress disorder. Results indicated that the best fitting model was a modified bifactor structure composed of nine lower-order common factors. These factors indexed pathology ranging from aggression to dependency, with the correlations among them accounted for by higher-order Internalizing and Externalizing factors. Further, a general factor, reflecting a construct that we termed boundary disturbance, accounted for additional variance and covariance across nearly all the indicators. The Internalizing, Externalizing, and Boundary Disturbance factors evidenced differential associations with trauma-related covariates. These findings suggest continuity in the underlying structure of psychopathology across DSM-IV Axes I and II and provide empirical evidence of a pervasive, core disturbance in the boundary between self and other across the PDs.
C1 [Wolf, Erika J.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA.
[Wolf, Erika J.; Brown, Timothy A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
RP Wolf, EJ (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-4,150 S Huntington Ave, Boston, MA 02130 USA.
EM erika.wolf@va.gov
RI Schueter, nicos/A-3625-2014; Miller, Mark/G-7322-2011;
OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435
FU CSRD VA [I01 CX000431]; NIMH NIH HHS [5F31MH074267, F31 MH074267]
NR 51
TC 10
Z9 10
U1 2
U2 4
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1949-2715
EI 1949-2723
J9 PERSONAL DISORD
JI Personal. Disord.
PD OCT
PY 2011
VL 2
IS 4
BP 261
EP 278
DI 10.1037/a0023168
PG 18
WC Psychology, Clinical
SC Psychology
GA 051ZG
UT WOS:000312166900002
PM 22448802
ER
PT J
AU Baker, AM
Haeri, S
Camargo, CA
Stuebe, AM
Boggess, KA
AF Baker, Arthur M.
Haeri, Sina
Camargo, Carlos A., Jr.
Stuebe, Alison M.
Boggess, Kim A.
TI A Nested Case-Control Study of First-Trimester Maternal Vitamin D Status
and Risk for Spontaneous Preterm Birth
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE Preterm birth; vitamin D; 25-hydroxyvitamin D
ID D DEFICIENCY; 25-HYDROXYVITAMIN-D; PREECLAMPSIA; MORTALITY; PREVENTION;
DELIVERY; OUTCOMES; DISEASE
AB We assessed if first-trimester vitamin D deficiency is more prevalent in women who experienced a spontaneous preterm birth compared with women who delivered at term. We conducted a nested case-control study of pregnant women who had previously given blood for first-trimester combined screening for trisomy 21 and subsequently delivered at a tertiary hospital between November 2004 and July 2009. From an overall cohort of 4225 women, 40 cases of spontaneous preterm birth (>= 23 (0)/7 and <= 34 (6)/7 weeks) were matched by race/ethnicity with 120 women delivering at term (>= 37 (0)/7 weeks) with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. The prevalence of first-trimester maternal vitamin D deficiency [25(OH)D < 50 nmol/L] was comparable among women who subsequently delivered preterm compared with controls (7.5% versus 6.7%, p = 0.90). The median 25(OH)D level for all subjects was 89 nmol/L (interquartile range, 73 to 106 nmol/L). Seventy-three percent (117/160) of the cohort had sufficient vitamin D levels [25(OH)D >= 75 nmol/L]. In a cohort of pregnant women with mostly sufficient levels of first-trimester serum 25(OH)D, vitamin D deficiency was not associated with spontaneous preterm birth.
C1 [Baker, Arthur M.; Haeri, Sina; Stuebe, Alison M.; Boggess, Kim A.] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Stuebe, Alison M.] Univ N Carolina, Dept Maternal & Child Hlth, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Ctr D Receptor Activat Res, Boston, MA 02114 USA.
RP Baker, AM (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Gillings Sch Global Publ Hlth, 3010 Old Clin Bldg,CB 7516, Chapel Hill, NC 27599 USA.
EM abaker2@med.unc.edu
FU Bowes/Cefalo Young Researcher Award; Massachusetts General Hospital
Center for D-receptor Activation Research
FX This research was supported, in part, by the Bowes/Cefalo Young
Researcher Award (A.M.B.) and the Massachusetts General Hospital Center
for D-receptor Activation Research (C.A.C.).
NR 21
TC 33
Z9 34
U1 1
U2 2
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD OCT
PY 2011
VL 28
IS 9
BP 667
EP 671
DI 10.1055/s-0031-1276731
PG 5
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 819SV
UT WOS:000294851400001
PM 21500145
ER
PT J
AU Saund, MS
Al Natour, RH
Sharma, AM
Huang, Q
Boosalis, VA
Gold, JS
AF Saund, Mandeep S.
Al Natour, Riad H.
Sharma, Ashish M.
Huang, Qin
Boosalis, Valia A.
Gold, Jason S.
TI Tumor Size and Depth Predict Rate of Lymph Node Metastasis and
Utilization of Lymph Node Sampling in Surgically Managed Gastric
Carcinoids
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID SMALL-CELL; STOMACH; CANCER; GUIDELINES
AB Background. Radical resection with regional lymphadenectomy is recommended for all sporadic gastric carcinoids. Local resection, however, is accepted for some carcinoids from other gastrointestinal sites (i.e., appendix and rectum). We sought to examine the relation of tumor size and depth to lymph node metastasis to determine whether gastric carcinoids can be selected for endoscopic resection. We also sought to quantify the utilization of lymph node sampling.
Methods. 984 patients with localized gastric carcinoids who underwent cancer-directed surgery between 1983 and 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry database.
Results. Tumor size and depth predicted probability of lymph node metastasis. Lymph node metastasis was not seen in intraepithelial (IE) tumors < 2 cm. Of tumors < 1 cm invading into the lamina propria or submucosa (LP/SM), 3.4% had lymph node metastasis. Excluding IE tumors < 2 cm and LP/SM tumors < 1 cm, all other subgroups based on size and depth had rates of lymph node metastasis a parts per thousand yen 8%. Tumor size and depth predicted probability of lymph node sampling. Overall, only 21% of tumors had lymph node sampling. Excluding IE tumors < 2 cm and LP/SM tumors < 1 cm, only 43% of tumors had lymph node sampling.
Conclusions. Tumor size and depth predict lymph node metastasis for gastric carcinoids. Endoscopic resection may be appropriate for intraepithelial (IE) tumors < 2 cm and perhaps tumors < 1 cm invading into the lamina propria or submucosa. Lymph node sampling is underused for gastric carcinoids at high risk for lymph node metastasis.
C1 [Saund, Mandeep S.; Al Natour, Riad H.; Gold, Jason S.] VA Boston Healthcare Syst, Surg Serv, W Roxbury, MA 02132 USA.
[Saund, Mandeep S.; Al Natour, Riad H.; Huang, Qin; Gold, Jason S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Huang, Qin] VA Boston Healthcare Syst, Pathol Serv, W Roxbury, MA USA.
[Sharma, Ashish M.; Boosalis, Valia A.] VA Boston Healthcare Syst, Med Serv, W Roxbury, MA USA.
[Sharma, Ashish M.; Boosalis, Valia A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Saund, MS (reprint author), VA Boston Healthcare Syst, Surg Serv, W Roxbury, MA 02132 USA.
EM jgold4@partners.org
RI Gold, Jason/O-5112-2014
OI Gold, Jason/0000-0002-2925-4755
NR 20
TC 17
Z9 19
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD OCT
PY 2011
VL 18
IS 10
BP 2826
EP 2832
DI 10.1245/s10434-011-1652-0
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA 819JG
UT WOS:000294820600017
PM 21455598
ER
PT J
AU Toi, M
Winer, EP
Inamoto, T
Benson, JR
Forbes, JF
Mitsumori, M
Robertson, JFR
Sasano, H
von Minckwitz, G
Yamauchi, A
Klimberg, VS
AF Toi, Masakazu
Winer, Eric P.
Inamoto, Takashi
Benson, John R.
Forbes, John F.
Mitsumori, Michihide
Robertson, John F. R.
Sasano, Hironobu
von Minckwitz, Gunter
Yamauchi, Akira
Klimberg, V. Suzanne
TI Identifying Gaps in the Locoregional Management of Early Breast Cancer:
Highlights from the Kyoto Consensus Conference
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID SENTINEL NODE BIOPSY; CARCINOMA-IN-SITU; POSTMASTECTOMY RADIATION
IMPROVES; RANDOMIZED CONTROLLED-TRIAL; SURGICAL ADJUVANT BREAST;
LYMPH-NODE; NEOADJUVANT CHEMOTHERAPY; PROGESTERONE-RECEPTOR; CONSERVING
TREATMENT; ESTROGEN-RECEPTOR
AB A consensus conference was held to investigate issues related to the local management of early breast cancer. Here, we highlight the major topics discussed at the conference and propose ideas for future studies. Regarding axillary management, we examined three major issues. First, we discussed whether the use of axillary reverse mapping could clarify the lymphatic system of breast and whether the ipsilateral arm might help avoid lymphedema. Second, the use of an indocyanine green fluorescent navigation system was discussed for intraoperative lymphatic mapping. These new issues should be examined further in practice. Finally, some agreement was reached on the importance of "four-node diagnosis" to aid in the diagnostic accuracy of sentinel nodes. Regarding breast treatment, there was general agreement that the clinical value of surgical margins in predicting local failure was dependent on the tumor's intrinsic biology and subtypes. For patients treated with preoperative chemotherapy, less extensive excision may be feasible in those who respond to systemic therapy in an acceptable manner. Most trials of preoperative chemotherapy lack outcome data on local recurrence. Therefore, there is a need for such data for overview analysis. We also agreed that radiation after mastectomy may be beneficial in node-positive cases where more than four nodes are involved. Throughout the discussions for both invasive and noninvasive disease, the investigation of nomograms was justified for major issues in the decision-making process, such as the presence or absence of microinvasion and the involvement of nonsentinel nodes in sentinel node-positive patients.
C1 [Toi, Masakazu] Kyoto Univ, Grad Sch Med, Dept Surg, Sakyo Ku, Kyoto, Japan.
[Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA.
[Inamoto, Takashi; Yamauchi, Akira] Kitano Hosp, Dept Breast Surg, Osaka, Japan.
[Benson, John R.] Univ Cambridge, Cambridge, England.
[Benson, John R.] Addenbrookes Hosp, Cambridge Breast Unit, Cambridge, England.
[Forbes, John F.] Univ Newcastle, Dept Surg Oncol, Newcastle, NSW 2300, Australia.
[Mitsumori, Michihide] Kyoto Univ, Grad Sch Med, Dept Radiat Oncol & Image Appl Therapy, Kyoto, Japan.
[Robertson, John F. R.] Univ Nottingham, Div Breast Surg, Professorial Surg Unit, Nottingham NG7 2RD, England.
[Sasano, Hironobu] Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 980, Japan.
[von Minckwitz, Gunter] Goethe Univ Frankfurt, Dept Gynecol & Obstet, Frankfurt, Germany.
[Klimberg, V. Suzanne] Univ Arkansas Med Sci, Rockefeller Canc Inst, Div Breast Surg Oncol, Little Rock, AR 72205 USA.
RP Toi, M (reprint author), Kyoto Univ, Grad Sch Med, Dept Surg, Sakyo Ku, Kyoto, Japan.
EM toi@kuhp.kyoto-u.ac.jp
FU Kyoto University Foundation
FX We thank Dr. Masahiro Hiraoka, Chairman of the Department of Radiation
Oncology and Image-applied Therapy at Kyoto University, the executive
advisor to this project. We are also grateful to Dr. Fabrizio
Michelassi, Chairman of the Department of Surgery at New York
Presbyterian Hospital, Weill Cornell Medical Center, for providing
guidance regarding the consensus questionnaire. We thank the Kyoto
University Foundation for their generous donation of funds. The
conference was part of a program, "Raising Proficient Oncologists,'' run
by the Japanese Ministry of Education, Culture, Sports, Science, and
Technology. We acknowledge the kind support of the Japan Breast Cancer
Society. We express sincere thanks to the doctors who completed the
consensus questionnaire. We are grateful to Dr. Hiroshi Ishiguro for his
valuable help and scientific advice. We also thank Ms. Aya Morotomi, Mr.
David Graham, Ms. Mihoko Yamamoto, Ms. Nastajia Burke, Ms. Chisa Takano,
and Ms. Nobuko Yagi for their invaluable support. Moderators: S. K.
Apple (University of California, Los Angeles), J. R. Benson
(Addenbrooke's Hospital and University of Cambridge, Cambridge), W. C.
Chow (UNIMED Medical Institute/Hong Kong University, Hong Kong), J. F.
Forbes (The University of Newcastle, Newcastle), M. Golshan (Dana-Farber
Cancer Institute, Brigham & Women's Cancer Center, Boston), T. Inamoto
(Kitano Hospital, Osaka), V. S. Klimberg (University of Arkansas for
Medical Sciences, Arkansas), M. Mitsumori (Kyoto University, Kyoto), S.
Noguchi (Osaka University, Osaka), J. F. R. Robertson (The University of
Nottingham, Nottingham), D. H. Roukos (University of Ioannina,
Ioannina), H. Sasano (Tohoku University, Sendai), E. A. Strom (The
University of Texas M. D. Anderson Cancer Center, Houston), M. Toi
(Kyoto University, Kyoto), G. Von Minckwitz (The Centre for Gynecology
and Obstetrics at the University of Frankfurt, Frankfurt), E. P. Winer
(Dana-Farber Cancer Institute, Brigham & Women's Cancer Center, Boston),
and A. Yamauchi (Kitano Hospital, Osaka). Discussants and organizers: S.
Akashi-Tanaka (National Cancer Center Hospital, Tokyo), R. Arriagada
(Karolinska institute, Stockholm/ Institut Gustave-Roussy, Paris), J.
Chen (Cancer Hospital of Fudan University, Shanghai), S. C. Chen (Chang
Gung University, Taoyuan), S. W. Ha (Seoul National University Hospital,
Seoul), S. Han (Inje University Sanggye Paik Hospital, Kyungnam), C. S.
Huang and T. Ikeda (Teikyo University, Tokyo), S. Imoto (Kyorin
University, Tokyo), H. Inaji (Osaka Medical Center for Cancer and
Cardiovascular Diseases, Osaka), T. Iwase (The Cancer Institute Hospital
of JFCR, Tokyo), H. Iwata (Aichi Cancer Center, Nagoya), R. V. Jakesz
(University of Vienna, Vienna), H. Jinno (Keio University, Tokyo), H.
Kawabata (Toranomon Hospital, Tokyo), T. Kinoshita (National Cancer
Center Hospital, Tokyo), T. Kitai (Nara Social Insurance Hospital,
Nara), N. Kohno (Tokyo Medical University, Tokyo), I. E. Krop
(Dana-Farber Cancer Institute, Brigham and Women's Cancer Center,
Boston), I. Kunkler (University of Edinburgh, Edinburgh), J. Kurebayashi
(Kawasaki Medical University, Kurashiki), K. Kuroi (Tokyo Metropolitan
Cancer and Infectious Disease Center, Tokyo), E. S. Lee (Korea
University Anam-Hospital, Seoul), S. J. Lee (Yeungnam University,
Gyeongsan), N. Masuda (Osaka National Hospital, Osaka), Y. Mikami (Kyoto
University, Kyoto), S. Nakamura (St. Luke's International Hospital,
Tokyo), D. Y. Noh (Seoul National University, Seoul), S. Ohno (National
Kyushu Cancer Center, Fukuoka), N. S.; Paik (Konkuk University Medical
Center Seoul), M. D. Pegram (University of Miami, Miller School of
Medicine, Miami), T. Saeki (Saitama Medical University, Saitama), M.
Shafir (Mount Sinai Hospital and School of Medicine, New York), H. Takei
(Saitama Cancer Center, Saitama), H. Sonoo (Kawasaki Medical School
Hospital, Kurashiki), T. Sugie (Kyoto University, Kyoto), M. Takada
(Kyoto University, Kyoto), Y. Tanaka (Kyoto University, Kyoto), T. Ueno
(Kyoto University, Kyoto), T. Varughese (Lakeshore Hospital and Research
Centre, Cochin), and K. Yamagami (Shinko Hospital, Kobe).
NR 52
TC 5
Z9 5
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD OCT
PY 2011
VL 18
IS 10
BP 2885
EP 2892
DI 10.1245/s10434-011-1666-7
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 819JG
UT WOS:000294820600025
PM 21431404
ER
PT J
AU Adler, JT
Chen, H
Schaefer, S
Sippel, RS
AF Adler, Joel T.
Chen, Herbert
Schaefer, Sarah
Sippel, Rebecca S.
TI What is the Added Benefit of Cervical Ultrasound to Tc-99m-Sestamibi
Scanning in Primary Hyperparathyroidism?
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID MINIMALLY INVASIVE PARATHYROIDECTOMY; SESTAMIBI-SPECT LOCALIZATION;
SURGEON-PERFORMED ULTRASOUND; QUALITY-OF-LIFE; RADIOGUIDED
PARATHYROIDECTOMY; HYPERPLASTIC GLANDS; BLOCK ANESTHESIA; HORMONE ASSAY;
COMBINATION; ADENOMA
AB Background. Minimally invasive parathyroidectomy for primary hyperparathyroidism depends on accurate preoperative imaging, which is traditionally accomplished by Tc-99m-sestamibi scanning. Cervical ultrasound is gaining in use, but it is unclear how much information it adds to the routine use of Tc-99m-sestamibi scans.
Methods. A prospectively maintained database of patients undergoing parathyroidectomy for primary hyperparathyroidism was queried, and the utility of cervical ultrasound in preoperative planning was analyzed.
Results. Between July 2002 and November 2009, 310 patients with primary hyperparathyroidism underwent both Tc-99m-sestamibi and ultrasound imaging. Ultrasound added new information to Tc-99m-sestamibi in 43 patients (14%) by finding either the correct enlarged gland (n = 40, 88%) or additional enlarged glands (n = 5, 12%). Ultrasound correctly localized glands in 38 of 85 (45%) patients with a negative Tc-99m-sestamibi, allowing for a minimally invasive parathyroidectomy in those patients. However, in the 206 patients (66%) who had a 1-gland positive Tc-99m-sestamibi, ultrasound only added information for 8 patients (4%). When compared with radiology-performed ultrasound, surgeon-performed ultrasound was successful in localizing additional glands in 27 (15%) versus 17 patients (10%) (P < 0.001).
Conclusions. Ultrasound led to additional localization information in 14% of patients, although this benefit was less in patients with a clearly positive 1-gland Tc-99m-sestamibi scan. Cervical ultrasound provides added benefit to Tc-99m-sestamibi scanning in patients with primary hyperparathyroidism, but its greatest utility is when performed by a surgeon in patients with a negative Tc-99m-sestamibi scan.
C1 [Adler, Joel T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Chen, Herbert; Schaefer, Sarah; Sippel, Rebecca S.] Univ Wisconsin, Dept Surg, Madison, WI USA.
RP Adler, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
EM sippel@surgery.wisc.edu
OI Adler, Joel/0000-0001-8190-3444
NR 21
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD OCT
PY 2011
VL 18
IS 10
BP 2907
EP 2911
DI 10.1245/s10434-011-1724-1
PG 5
WC Oncology; Surgery
SC Oncology; Surgery
GA 819JG
UT WOS:000294820600028
PM 21509629
ER
PT J
AU McCann, CK
Growdon, WB
Munro, EG
Del Carmen, MG
Boruta, DM
Schorge, JO
Goodman, A
AF McCann, Christopher K.
Growdon, Whitfield B.
Munro, Elizabeth G.
Del Carmen, Marcela G.
Boruta, David M.
Schorge, John O.
Goodman, Annekathryn
TI Prognostic Significance of Splenectomy as Part of Initial Cytoreductive
Surgery in Ovarian Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID LYMPH-NODE DISSECTION; GYNECOLOGIC-ONCOLOGY-GROUP; PROXIMAL
GASTRIC-CANCER; IV EPITHELIAL OVARIAN; DISTAL PANCREATECTOMY; STAGE-III;
SURGICAL CYTOREDUCTION; FALLOPIAN-TUBE; CARCINOMA; SURVIVAL
AB Purpose. We sought to examine how splenectomy as part of up-front cytoreductive surgery in ovarian cancer influences the postoperative course and affects survival.
Methods. We reviewed cases of ovarian cancer diagnosed at Massachusetts General Hospital from 1994 to 2008 and found 44 patients who had a splenectomy as part of their up-front cytoreductive surgery. These were compared to 171 patients who did not undergo splenectomy. We evaluated age at diagnosis, estimated blood loss, percentage of patients whose disease was optimally cytoreduced (< 1 cm), reason for splenectomy (oncologic vs. surgical), length of stay, time to first chemotherapy treatment, and survival.
Results. In the splenectomy cohort, the mean age at diagnosis was 64 (44-83) years. A total of 37 of 44 (84%) patients were optimally cytoreduced. Mean estimated blood loss was 1326 ml. The purpose of splenectomy was to accomplish an optimal cytoreduction (oncologic) in 82% of cases. Median length of stay was 13 (6-76) days. Median time to first chemotherapy was 13.5 (5-54) days. The median disease-free interval and overall survival of the splenectomy cohort were 8 and 30 months, respectively. The median overall survival for patients whose disease was optimally cytoreduced in the splenectomy cohort compared to the no-splenectomy group was 30 and 45 months (P < 0.045), respectively.
Conclusions. The addition of splenectomy to up-front cytoreductive surgery was feasible and safe. However, it appears to carry with it a shortened survival that is unrelated to postoperative morbidity. Our data raise the questions that splenectomy is needed for optimal cytoreduction in more biologically aggressive disease and that splenectomy may be an independent prognostic factor related to depressed immune function.
C1 [McCann, Christopher K.; Growdon, Whitfield B.; Munro, Elizabeth G.; Del Carmen, Marcela G.; Boruta, David M.; Schorge, John O.; Goodman, Annekathryn] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Div Gynecol Oncol, Boston, MA 02114 USA.
RP McCann, CK (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Div Gynecol Oncol, Boston, MA 02114 USA.
EM cmccann3@partners.org
NR 36
TC 11
Z9 11
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD OCT
PY 2011
VL 18
IS 10
BP 2912
EP 2918
DI 10.1245/s10434-011-1661-z
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA 819JG
UT WOS:000294820600029
PM 21424880
ER
PT J
AU Lovely, RS
Yang, Q
Massaro, JM
Wang, J
D'Agostino, RB
O'Donnell, CJ
Shannon, J
Farrell, DH
AF Lovely, Rehana S.
Yang, Qiong
Massaro, Joseph M.
Wang, Jing
D'Agostino, Ralph B., Sr.
O'Donnell, Christopher J.
Shannon, Jackilen
Farrell, David H.
TI Assessment of Genetic Determinants of the Association of gamma '
Fibrinogen in Relation to Cardiovascular Disease
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE coronary heart disease; epidemiology; fibrin; gene mutations; risk
factors
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; ISCHEMIC-STROKE; SPLICE
VARIANT; CHAIN; RISK; FIBRINOLYSIS; POPULATION; RATIO
AB Objective-gamma ' fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of gamma ' fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort.
Methods and Results-A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for gamma ' fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (P<5.0x10(-8)) for association with gamma ' fibrinogen levels. The top-signal SNP was rs7681423 (P=9.97x10(-110)) in the fibrinogen gene locus near FGG, which encodes the gamma chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, gamma ' fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. gamma ' fibrinogen levels were associated with prevalent CVD (P=0.02), although the top 2 SNPs associated with gamma ' fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly FGB, which encodes the B beta chain.
Conclusion-gamma ' fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus. (Arterioscler Thromb Vasc Biol. 2011;31:2345-2352.)
C1 [Farrell, David H.] Oregon Hlth & Sci Univ, Sch Med, Dept Med, Div Cardiovasc Med, Portland, OR 97239 USA.
[Lovely, Rehana S.] Missouri State Univ, Dept Biomed Sci, Springfield, MO USA.
[Yang, Qiong; Massaro, Joseph M.; Wang, Jing] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Shannon, Jackilen] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA.
RP Farrell, DH (reprint author), Oregon Hlth & Sci Univ, Sch Med, Dept Med, Div Cardiovasc Med, MQ280,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM farrelld@ohsu.edu
RI Yang, Qiong/G-5438-2014;
OI Massaro, Joseph/0000-0002-2682-4812
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; American Heart Association [0865486G]; National Heart,
Lung, and Blood Institute; National Institutes of Health [R21-HL-75006,
R21-HL-097298]; Office of Naval Research [N000140610411]
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195); American
Heart Association Grant 0865486G (to R. S. L.); National Heart, Lung,
and Blood Institute, National Institutes of Health, Grants R21-HL-75006
and R21-HL-097298 (to D. H. F.); and Office of Naval Research Grant
N000140610411 (to D.H.F.).
NR 30
TC 19
Z9 19
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD OCT
PY 2011
VL 31
IS 10
BP 2345
EP U399
DI 10.1161/ATVBAHA.111.232710
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 819QK
UT WOS:000294843700024
PM 21757653
ER
PT J
AU Wang, JM
Zeng, YS
Wu, JL
Li, Y
Teng, YD
AF Wang, Jun-Mei
Zeng, Yuan-Shan
Wu, Jin-Lang
Li, Yan
Teng, Yang D.
TI Cograft of neural stem cells and schwann cells overexpressing TrkC and
neurotrophin-3 respectively after rat spinal cord transection
SO BIOMATERIALS
LA English
DT Article
DE Spinal cord injury; Neurotrophin-3; TrkC; Schwann cells; Neural stem
cells; Transection
ID RECOMBINANT ADENOVIRUS VECTOR; AXONAL REGENERATION; FUNCTIONAL RECOVERY;
TRANSPLANTATION THERAPY; EXCITATORY SYNAPSES; GROWTH-FACTOR; INJURY;
PROMOTES; NEURONS; BDNF
AB Effectively bridging the lesion gap is still an unmet demand for spinal cord repair. In the present study, we tested our hypothesis if cograft of Schwann cells (SCs) and neural stem cells (NSCs) with genetically enhanced expression of neurotrophin-3 (NT-3) and its high affinity receptor TrkC, respectively, could strengthen neural repair through increased NSC survival and neuronal differentiation at the epicenter after complete T10 spinal cord transection in adult rats. Transplantation of NT-3-SCs + TrkC-NSCs in Gelfoam (1 x 10(6)/implant/rat; n = 10) into the lesion gap immediately following injury results in significantly improved relay of the cortical motor evoked potential (CMEP) and cortical somatosensory evoked potential (CSEP) as well as ameliorated hindlimb deficits, relative to controls (treated with LacZ-SCs + LacZ-NSCs, NT-3-SCs + NSCs, NSCs alone, or lesion only; n = 10/group). Further analyses demonstrate that NT-3-SCs + TrkC-NSCs cografting augments levels of neuronal differentiation of NSCs, synaptogenesis (including inhibitory/type II-like synapses) and myelin formation of SCs, in addition to neuroprotection and outgrowth of serotonergic fibers in the lesioned spinal cord. Compared with controls, the treated spinal cords also show elevated expression of laminin, a pro-neurogenic factor, and decreased presence of chondroitin sulfate proteoglycans, major inhibitors of axonal growth and neuroplasticity. Together, our data suggests that coimplantation of neurologically compatible cells with compensatorily overexpressed therapeutic genes may constitute a valuable approach to study, and/or develop therapies for spinal cord injury (SCI). Published by Elsevier Ltd.
C1 [Wang, Jun-Mei; Zeng, Yuan-Shan; Li, Yan] Sun Yat Sen Univ, Div Neurosci, Dept Histol & Embryol, Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China.
[Zeng, Yuan-Shan] Sun Yat Sen Univ, Minist Educ, Key Lab Stem Cells & Tissue Engn, Guangzhou 510080, Guangdong, Peoples R China.
[Zeng, Yuan-Shan] Sun Yat Sen Univ, Inst Spinal Cord Injury, Guangzhou 510120, Guangdong, Peoples R China.
[Wu, Jin-Lang] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Electron Microscope, Guangzhou 510080, Guangdong, Peoples R China.
[Wang, Jun-Mei; Teng, Yang D.] Harvard Univ, Sch Med, Div SCI Res, Dept Neurosurg,VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Wang, Jun-Mei; Teng, Yang D.] Harvard Univ, Sch Med, Div SCI Res, Dept Phys Med & Rehabil,VA Boston Healthcare Syst, Boston, MA 02115 USA.
RP Zeng, YS (reprint author), Sun Yat Sen Univ, Div Neurosci, Dept Histol & Embryol, Zhongshan Sch Med, 74 Zhongshan 2nd Rd, Guangzhou 510080, Guangdong, Peoples R China.
EM zengysh@mail.sysu.edu.cn; yang_teng@hms.harvard.edu
FU Chinese National Natural Science Foundation [30270700, 30771143]; Social
Developmental Foundation of Guangdong Province [2003C33808]; Guangdong
Province Natural Science Foundation [07117373]; HeadNorth Project (La
Jolla, CA, USA); United States Department of Veteran Affairs; U.S.
Department of Defense, OMIT, NIH; State of Massachusetts; HeadNorth
Project; VA; DoD; CIMIT; NIH
FX Research work at the lab of Y.S.Z. was supported by the Chinese National
Natural Science Foundation (30270700, 30771143), the Social
Developmental Foundation of Guangdong Province (2003C33808), and the
Guangdong Province Natural Science Foundation (07117373). HeadNorth
Project (La Jolla, CA, USA) sponsored J.M.W.'s research at Teng Labs.
Teng Labs are additionally supported by the United States Department of
Veteran Affairs (Rehabilitation Research and Development Grant;
Biomedical and Laboratory Research and Development Grant to Y.D.T.),
U.S. Department of Defense, OMIT, NIH, and the State of Massachusetts.;
Y.S.Z. thanks all the grant sponsors for their support to work done in
his lab. Y.D.T. and J.M.W. gratefully acknowledge the instrumental role
of Dr. Evan Y. Snyder in orchestrating research projects sponsored by
HeadNorth Project. Y.D.T. wants to thank VA, DoD, CIMIT, NIH, and the
State of Massachusetts for their grant support to research projects
performed in his labs.
NR 65
TC 33
Z9 42
U1 1
U2 15
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD OCT
PY 2011
VL 32
IS 30
BP 7454
EP 7468
DI 10.1016/j.biomaterials.2011.06.036
PG 15
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 819LW
UT WOS:000294829300017
PM 21783247
ER
PT J
AU Jeong, JY
Silver, M
Parnes, A
Nikiforow, S
Berliner, N
Vanasse, GJ
AF Jeong, Jee-Yeong
Silver, Matthew
Parnes, Aric
Nikiforow, Sarah
Berliner, Nancy
Vanasse, Gary J.
TI Resveratrol ameliorates TNF alpha-mediated suppression of erythropoiesis
in human CD34(+) cells via modulation of NF-kappa B signalling
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE erythropoiesis; anaemia; NF-kappa B; resveratrol; TNF alpha
ID TRANSCRIPTION FACTOR GATA-1; NECROSIS-FACTOR-ALPHA;
ERYTHROID-DIFFERENTIATION; GENE-EXPRESSION; PROINFLAMMATORY STATE;
HEMATOPOIETIC-CELLS; INFLAMMATION; ANEMIA; AGE; APOPTOSIS
AB Overexpression of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF alpha), has been implicated in the pathogenesis of anaemia of inflammation. TNF alpha suppresses erythroid colony formation via both direct and indirect effects on haematopoietic progenitors, often involving activation of nuclear factor (NF-kappa B signalling resulting in downregulation of transcription factors critical for erythropoiesis. There is a dearth of effective and safe therapies for many patients with inflammatory anaemia. Resveratrol is a flavanol found in red wine grapes that possesses potent anti-inflammatory properties, but studies of its impact on human erythropoiesis have proven contradictory. We investigated whether resveratrol ameliorates TNF alpha-mediated suppression of erythropoiesis in human CD34(+) haematopoietic progenitors. We found that resveratrol partially reverses the erythroid suppressive effects of TNF alpha, leading to significant recovery in burst forming unit-erythroid colony formation in human CD34(+) cells. CD34(+) cells preincubated with resveratrol for 72 h in the presence of TNF alpha inhibited NF-kappa B activation via decreased NF-kappa B nuclear localization without altering total NF-kappa B protein levels and independent of I kappa B degradation. Resveratrol also significantly restored the baseline expression of erythroid transcription factors NFE2 and the GATA1/GATA2 ratio in CD34(+) cells treated with TNF alpha. In conclusion, resveratrol may inhibit TNF alpha-mediated NF-kappa B activation and promote erythropoiesis in primary human CD34(+) cells.
C1 [Vanasse, Gary J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Haematol,Dept Med, Boston, MA 02115 USA.
[Nikiforow, Sarah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Vanasse, GJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Haematol,Dept Med, 75 Francis St,Karp 5-216, Boston, MA 02115 USA.
EM gvanasse@partners.org
FU National Institutes of Health [RO1AG29154]
FX This work was supported by National Institutes of Health Grant
RO1AG29154 (N.B.).
NR 37
TC 6
Z9 6
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD OCT
PY 2011
VL 155
IS 1
BP 93
EP 101
DI 10.1111/j.1365-2141.2011.08800.x
PG 9
WC Hematology
SC Hematology
GA 820QE
UT WOS:000294919700009
PM 21762122
ER
PT J
AU Eyler, LT
Prom-Wormley, E
Panizzon, MS
Kaup, AR
Fennema-Notestine, C
Neale, MC
Jernigan, TL
Fischl, B
Franz, CE
Lyons, MJ
Grant, M
Stevens, A
Pacheco, J
Perry, ME
Schmitt, JE
Seidman, LJ
Thermenos, HW
Tsuang, MT
Chen, CH
Thompson, WK
Jak, A
Dale, AM
Kremen, WS
AF Eyler, Lisa T.
Prom-Wormley, Elizabeth
Panizzon, Matthew S.
Kaup, Allison R.
Fennema-Notestine, Christine
Neale, Michael C.
Jernigan, Terry L.
Fischl, Bruce
Franz, Carol E.
Lyons, Michael J.
Grant, Michael
Stevens, Allison
Pacheco, Jennifer
Perry, Michele E.
Schmitt, J. Eric
Seidman, Larry J.
Thermenos, Heidi W.
Tsuang, Ming T.
Chen, Chi-Hua
Thompson, Wesley K.
Jak, Amy
Dale, Anders M.
Kremen, William S.
TI Genetic and Environmental Contributions to Regional Cortical Surface
Area in Humans: A Magnetic Resonance Imaging Twin Study
SO CEREBRAL CORTEX
LA English
DT Article
DE cortex; cortical thickness; heritability
ID HUMAN CEREBRAL-CORTEX; VIETNAM ERA TWIN; MONOZYGOTIC TWINS; BRAIN;
EVOLUTION; THICKNESS; SYSTEM; MRI; HERITABILITY; EXPANSION
AB Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.
C1 [Eyler, Lisa T.; Panizzon, Matthew S.; Kaup, Allison R.; Fennema-Notestine, Christine; Jernigan, Terry L.; Franz, Carol E.; Perry, Michele E.; Tsuang, Ming T.; Chen, Chi-Hua; Thompson, Wesley K.; Jak, Amy; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Eyler, Lisa T.] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA 92161 USA.
[Prom-Wormley, Elizabeth; Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23219 USA.
[Prom-Wormley, Elizabeth; Neale, Michael C.; Schmitt, J. Eric] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23219 USA.
[Kaup, Allison R.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92182 USA.
[Jernigan, Terry L.; Perry, Michele E.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA.
[Fennema-Notestine, Christine; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Fischl, Bruce; Stevens, Allison; Pacheco, Jennifer] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02129 USA.
[Fischl, Bruce; Stevens, Allison; Pacheco, Jennifer] Massachusetts Gen Hosp, Boston, MA 02129 USA.
[Lyons, Michael J.; Grant, Michael] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Seidman, Larry J.; Thermenos, Heidi W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA.
[Tsuang, Ming T.] Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02215 USA.
[Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
[Tsuang, Ming T.; Kremen, William S.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA 92161 USA.
[Tsuang, Ming T.; Jak, Amy] VA San Diego Healthcare Syst, Psychol Serv, San Diego, CA 92161 USA.
[Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
RP Eyler, LT (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,Mail Code 9151B, La Jolla, CA 92093 USA.
EM lteyler@ucsd.edu
OI Prom-Wormley, Elizabeth/0000-0001-9230-9723; Lyons,
Michael/0000-0001-6516-9219; Fennema-Notestine,
Christine/0000-0002-6527-6361
FU National Institutes of Health (NIH) National Institute on Aging [U24
RR021382, R01 AG18386, R01 AG18384, R01 AG22381, R01 AG 22982]; National
Institute for Mental Health [T32 MH20030]; National Institute for Drug
Abuse [R01 DA18673]; VA Desert Pacific Mental Illness Research Education
and Clinical Center; Ellison Medical Foundation; US Department of
Veterans Affairs
FX National Institutes of Health (NIH) National Institute on Aging (U24
RR021382, R01 AG18386, R01 AG18384, R01 AG22381, and R01 AG 22982);
National Institute for Mental Health (T32 MH20030); National Institute
for Drug Abuse (R01 DA18673); and VA Desert Pacific Mental Illness
Research Education and Clinical Center. Additional support was provided
in part by the National Center for Research Resources (P41-RR14075 and
the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National
Institute for Biomedical Imaging and Bioengineering (R01 EB006758), the
National Institute for Neurological Disorders and Stroke (R01
NS052585-01), as well The Autism and Dyslexia Project funded by the
Ellison Medical Foundation. The US Department of Veterans Affairs has
provided support for the development and maintenance of the VET
Registry.
NR 42
TC 44
Z9 44
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD OCT
PY 2011
VL 21
IS 10
BP 2313
EP 2321
DI 10.1093/cercor/bhr013
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 819ES
UT WOS:000294808800012
PM 21378112
ER
PT J
AU Conner, PS
Hyun, J
Wells, BO
Anema, I
Goral, M
Monereau-Merry, MM
Rubino, D
Kuckuk, R
Obler, LK
AF Conner, Peggy S.
Hyun, Jungmoon
Wells, Barbara O'Connor
Anema, Inge
Goral, Mira
Monereau-Merry, Marie-Michelle
Rubino, Daniel
Kuckuk, Raija
Obler, Loraine K.
TI Age-related differences in idiom production in adulthood
SO CLINICAL LINGUISTICS & PHONETICS
LA English
DT Article
DE idioms; older adults; age-related language changes; retrieval
ID THE-TONGUE EXPERIENCES; LEXICAL ACCESS; WORD RETRIEVAL; PROPER-NAMES;
OLDER-ADULTS; SPEECH PRODUCTION; LIFE-SPAN; TIP; MEMORY; YOUNG
AB To investigate whether idiom production was vulnerable to age-related difficulties, we asked 40 younger (ages 18-30) and 40 older healthy adults (ages 60-85) to produce idiomatic expressions in a story-completion task. Younger adults produced significantly more correct idiom responses (73%) than did older adults (60%). When older adults generated partially correct responses, they were less likely than younger participants to eventually produce the complete target idiom (old: 32%; young: 70%); first-word cues after initial failure to retrieve an idiom resulted in more correct idioms for older (24%) than younger (15%) participants. Correlations between age and idiom correctness were positive for the young group and negative for the older group, suggesting mastery of familiar idioms continues into adulthood. Within each group, scores on the Boston Naming Test correlated with performance on the idiom task. Findings for retrieving idiomatic expressions are thus similar to those for retrieving lexical items.
C1 [Conner, Peggy S.; Hyun, Jungmoon; Wells, Barbara O'Connor; Goral, Mira; Monereau-Merry, Marie-Michelle; Kuckuk, Raija; Obler, Loraine K.] CUNY, Grad Ctr, Program Speech Language Hearing Sci, New York, NY 10016 USA.
[Hyun, Jungmoon; Obler, Loraine K.] VA Boston Healthcare Syst, Boston, MA USA.
[Anema, Inge] State Univ New York New Paltz, New Paltz, NY USA.
[Goral, Mira] CUNY, Lehman Coll, Bronx, NY USA.
[Rubino, Daniel] New York Presbyterian Hosp, Weil Cornell Med Coll, Ctr Sleep Med, New York, NY USA.
[Kuckuk, Raija] Univ Freiburg, Deutsch Seminar 1, Freiburg, Germany.
RP Conner, PS (reprint author), CUNY, Grad Ctr, Program Speech Language Hearing Sci, 365 5th Ave, New York, NY 10016 USA.
EM psconner@gmail.com
FU NIA NIH HHS [R01 AG014345, R01-AG 14345]
NR 50
TC 3
Z9 3
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0269-9206
J9 CLIN LINGUIST PHONET
JI Clin. Linguist. Phon.
PD OCT
PY 2011
VL 25
IS 10
BP 899
EP 912
DI 10.3109/02699206.2011.584136
PG 14
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA 819LH
UT WOS:000294826700006
PM 21728830
ER
PT J
AU Yoo, WJ
Kim, YJ
Menezes, NM
Cheon, JE
Jaramillo, D
AF Yoo, Won Joon
Kim, Young-Jo
Menezes, Nina M.
Cheon, Jung-Eun
Jaramillo, Diego
TI Diffusion-weighted MRI Reveals Epiphyseal and Metaphyseal Abnormalities
in Legg-Calv,-Perthes Disease: A Pilot Study
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID CALVE-PERTHES-DISEASE; TERM-FOLLOW-UP; BONE-MARROW; NATURAL-HISTORY;
CLASSIFICATION; SCINTIGRAPHY; DISORDERS; DIAGNOSIS; PERFUSION; SKELETON
AB Background Legg-Calv,-Perthes disease (LCP) is thought to be associated with ischemic events in the femoral head. However, the types and patterns of reperfusion after these ischemic events are unclear.
Purposes We therefore determined whether (1) there would be any age-related diffusion changes; (2) diffusion-weighted MR imaging would reveal ischemic damage; and (3) diffusion changes are correlated with prognostic MR findings in patients with LCP.
Methods We prospectively performed conventional, perfusion, and diffusion-weighted MR imaging studies in 17 children with unilateral LCP. We then measured the apparent diffusion coefficient (ADC) values in the epiphysis and the metaphysis, and compared them with those of the contralateral normal side. Based on perfusion MR imaging, we assessed reperfusion to the epiphysis as either periphyseal or transphyseal. We studied T2-signal intensity changes in the metaphysis and the presence of focal physeal irregularity. We correlated diffusion changes with reperfusion to the epiphysis, T2-signal intensity change, and focal physeal irregularity.
Results Normal diffusion decreased with age. In LCP hips, epiphyseal diffusion increased early and remained elevated through the healing stage. Six of the 17 patients who had a metaphyseal ADC greater than 50% over the normal side had 13 times greater odds of having an association with transphyseal reperfusion to the epiphysis. The increase of metaphyseal ADC also was associated with an increased T2-signal intensity in the metaphysis and presence of focal physeal irregularity.
Conclusions Diffusion-weighted MR imaging can be used as a complimentary modality to evaluate ischemic tissue damage with a potential prognostic value in patients with LCP.
C1 [Kim, Young-Jo] Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
[Yoo, Won Joon] Seoul Natl Univ, Childrens Hosp, Dept Orthopaed Surg, Seoul, South Korea.
[Yoo, Won Joon] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Kim, Young-Jo; Jaramillo, Diego] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Menezes, Nina M.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Menezes, Nina M.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA.
[Cheon, Jung-Eun] Seoul Natl Univ, Childrens Hosp, Dept Radiol, Seoul, South Korea.
[Jaramillo, Diego] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA.
[Jaramillo, Diego] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA.
RP Kim, YJ (reprint author), Childrens Hosp, Dept Orthopaed Surg, 300 Longwood Ave, Boston, MA 02115 USA.
EM young-jo.kim@childrens.harvard.edu
RI Cheon, Jung-Eun/J-5684-2012; Yoo, Wonjoon/J-5552-2012
NR 31
TC 15
Z9 16
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD OCT
PY 2011
VL 469
IS 10
BP 2881
EP 2888
DI 10.1007/s11999-011-1931-x
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 819KA
UT WOS:000294822600024
PM 21660596
ER
PT J
AU Pratchett, LC
Daly, K
Bierer, LM
Yehuda, R
AF Pratchett, Laura C.
Daly, Kelly
Bierer, Linda M.
Yehuda, Rachel
TI New approaches to combining pharmacotherapy and psychotherapy for
posttraumatic stress disorder
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Review
DE evidence-based psychotherapy; pharmacologic augmentation of
psychotherapy; pharmacotherapy; posttraumatic stress disorder; treatment
ID RANDOMIZED CONTROLLED-TRIAL; EYE-MOVEMENT DESENSITIZATION;
COGNITIVE-BEHAVIOR-THERAPY; REALITY EXPOSURE THERAPY; VIETNAM COMBAT
VETERANS; BRIEF ECLECTIC PSYCHOTHERAPY; AFRICAN REFUGEE SETTLEMENT;
PLACEBO-CONTROLLED TRIAL; SOCIAL ANXIETY DISORDER; CHILDHOOD
SEXUAL-ABUSE
AB Introduction: Posttraumatic stress disorder (PTSD) is a complex disorder associated with an intricate biological and psychological symptom profile and various common comorbidities. Despite an existing myriad of evidence-based and experimental treatments, PTSD is often difficult to treat. This reality necessitates a discussion of the potential of emerging treatments.
Areas covered: A literature search using PubMed and PsychInfo was done using the following keywords: randomized clinical trials, treatment guidelines, pharmacotherapy and psychotherapy, all in addition to PTSD. A comprehensive treatment review establishes that early intervention approaches have not yet been found to prevent PTSD in trauma survivors. However, psychotherapy research provides substantial support for cognitive behavioral therapies and eye movement desensitization and reprocessing for chronic PTSD, and psychopharmacological approaches are myriad - although at present there is FDA approval only for sertraline and paroxetine. However, the efficacy of these treatments varies and, unfortunately, not everyone will achieve remission.
Expert opinion: So far, the mental health field has tended to focus on either biological or psychological targets. We propose that maximizing treatment success may require an integrated approach that does not dichotomize biological and psychological aspects. Exciting new developments reflecting this perspective include psychopharmacologic augmentation strategies that enhance the mechanisms of psychotherapy.
C1 [Pratchett, Laura C.; Bierer, Linda M.; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
[Daly, Kelly] Bronx Vet Med Res Fdn, Traumat Stress Studies Div, Bronx, NY 10468 USA.
[Pratchett, Laura C.; Bierer, Linda M.; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
RP Pratchett, LC (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
EM Laura.pratchett@va.gov
NR 195
TC 17
Z9 18
U1 12
U2 30
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-6566
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD OCT
PY 2011
VL 12
IS 15
BP 2339
EP 2354
DI 10.1517/14656566.2011.604030
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 820MC
UT WOS:000294909000006
PM 21819273
ER
PT J
AU Gonzalez, JS
Batchelder, AW
Psaros, C
Safren, SA
AF Gonzalez, Jeffrey S.
Batchelder, Abigail W.
Psaros, Christina
Safren, Steven A.
TI Depression and HIV/AIDS Treatment Nonadherence: A Review and
Meta-analysis
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE adherence; compliance; depression; HIV/AIDS; meta-analysis
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS;
POSTTRAUMATIC-STRESS-DISORDER; HIV-INFECTED INDIVIDUALS; MULTICENTER
AIDS COHORT; MEDICATION ADHERENCE; VIRAL LOAD; SOCIAL SUPPORT;
MENTAL-HEALTH; PSYCHOSOCIAL FACTORS
AB We meta-analyzed the relationship between depression and HIV medication nonadherence to calculate the overall effect size and examine potential moderators. Overall, across 95 independent samples, depression was significantly (P < 0.0001) associated with nonadherence (r = 0.19; 95% confidence interval = 0.14 to 0.25). Studies evaluating medication adherence via interview found significantly larger effects than those using self-administered questionnaires. Studies measuring adherence along a continuum found significantly stronger effects than studies comparing dichotomies. Effect size was not significantly related to other aspects of adherence or depression measurement, assessment interval (ie, cross-sectional vs. longitudinal), sex, IV drug use, sexual orientation, or study location. The relationship between depression and HIV treatment nonadherence is consistent across samples and over time, is not limited to those with clinical depression, and is not inflated by self-report bias. Our results suggest that interventions aimed at reducing depressive symptom severity, even at subclinical levels, should be a behavioral research priority.
C1 [Gonzalez, Jeffrey S.] Albert Einstein Coll Med, Ferkauf Grad Sch Psychol, Dept Med, Bronx, NY 10461 USA.
[Gonzalez, Jeffrey S.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Gonzalez, Jeffrey S.; Batchelder, Abigail W.] Yeshiva Univ, Dept Med, Ferkauf Grad Sch Psychol, Bronx, NY 10461 USA.
[Gonzalez, Jeffrey S.; Batchelder, Abigail W.] Yeshiva Univ, Dept Epidemiol & Populat Hlth, Ferkauf Grad Sch Psychol, Bronx, NY 10461 USA.
[Gonzalez, Jeffrey S.; Psaros, Christina; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Psaros, Christina; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Gonzalez, JS (reprint author), Albert Einstein Coll Med, Ferkauf Grad Sch Psychol, Dept Med, 1300 Morris Pk Ave,Rousso Bldg, Bronx, NY 10461 USA.
EM jeffrey.gonzalez@einstein.yu.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), DK [020541]; [DA018603]; [MH084757]
FX Funding for investigator time was supported by grants DA018603 and
MH084757 awarded to Dr S.A.S. Dr J.S.G. is supported in part by National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), DK
020541.
NR 69
TC 187
Z9 188
U1 15
U2 54
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD OCT 1
PY 2011
VL 58
IS 2
BP 181
EP 187
DI 10.1097/QAI.0B013E31822D490A
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 821AL
UT WOS:000294947100021
PM 21857529
ER
PT J
AU Whitton, JP
Polley, DB
AF Whitton, Jonathon P.
Polley, Daniel B.
TI Evaluating the Perceptual and Pathophysiological Consequences of
Auditory Deprivation in Early Postnatal Life: A Comparison of Basic and
Clinical Studies
SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
LA English
DT Review
DE otitis media; conductive hearing loss; auditory deprivation;
development; plasticity; auditory cortex; binaural; dichotic; language;
hearing; listening; amblyopia; visual cortex; experience; neural circuit
ID CONDUCTIVE HEARING-LOSS; 1ST 3 YEARS; PERSISTENT OTITIS-MEDIA; MASKING
LEVEL DIFFERENCES; BRAIN-STEM-RESPONSE; DEVELOPMENTAL OUTCOMES;
TYMPANOSTOMY TUBES; BINAURAL HEARING; EARLY-CHILDHOOD;
LANGUAGE-DEVELOPMENT
AB Decades of clinical and basic research in visual system development have shown that degraded or imbalanced visual inputs can induce a long-lasting visual impairment called amblyopia. In the auditory domain, it is well established that inducing a conductive hearing loss (CHL) in young laboratory animals is associated with a panoply of central auditory system irregularities, ranging from cellular morphology to behavior. Human auditory deprivation, in the form of otitis media (OM), is tremendously common in young children, yet the evidence linking a history of OM to long-lasting auditory processing impairments has been equivocal for decades. Here, we review the apparent discrepancies in the clinical and basic auditory literature and provide a meta-analysis to show that the evidence for human amblyaudia, the auditory analog of amblyopia, is considerably more compelling than is generally believed. We argue that a major cause for this discrepancy is the fact that most clinical studies attempt to link central auditory deficits to a history of middle ear pathology, when the primary risk factor for brain-based developmental impairments such as amblyopia and amblyaudia is whether the afferent sensory signal is degraded during critical periods of brain development. Accordingly, clinical studies that target the subset of children with a history of OM that is also accompanied by elevated hearing thresholds consistently identify perceptual and physiological deficits that can endure for years after peripheral hearing is audiometrically normal, in keeping with the animal studies on CHL. These studies suggest that infants with OM severe enough to cause degraded afferent signal transmission (e.g., CHL) are particularly at risk to develop lasting central auditory impairments. We propose some practical guidelines to identify at-risk infants and test for the positive expression of amblyaudia in older children.
C1 [Whitton, Jonathon P.; Polley, Daniel B.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA.
[Whitton, Jonathon P.; Polley, Daniel B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Polley, Daniel B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Whitton, JP (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA.
EM jpwhit05@mit.edu
OI Polley, Daniel/0000-0002-5120-2409
FU NIDCD NIH HHS [R01 DC009836]
NR 97
TC 32
Z9 33
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1525-3961
J9 JARO-J ASSOC RES OTO
JI JARO
PD OCT
PY 2011
VL 12
IS 5
BP 535
EP 547
DI 10.1007/s10162-011-0271-6
PG 13
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 820MK
UT WOS:000294909800001
PM 21607783
ER
PT J
AU Amatuzzi, M
Liberman, MC
Northrop, C
AF Amatuzzi, Monica
Liberman, M. Charles
Northrop, Clarinda
TI Selective Inner Hair Cell Loss in Prematurity: A Temporal Bone Study of
Infants from a Neonatal Intensive Care Unit
SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
LA English
DT Article
DE auditory neuropathy; deafness; cochlea; histopathology
ID AUDITORY NEUROPATHY; CARBOPLATIN; CHILDREN; HEARING; NERVE; RISK;
DEGENERATION; OTOTOXICITY; EXOCYTOSIS; OTOFERLIN
AB Premature birth is a well-known risk factor for sensorineural hearing loss in general and auditory neuropathy in particular. However, relatively little is known about the underlying causes, in part because there are so few relevant histopathological studies. Here, we report on the analysis of hair cell loss patterns in 54 temporal bones from premature infants and a control group of 46 bones from full-term infants, all of whom spent time in the neonatal intensive care unit at the Hospital de Nios in San Jose, Costa Rica, between 1977 and 1993. The prevalence of significant hair cell loss was higher in the preterm group than the full-term group (41% vs. 28%, respectively). The most striking finding was the frequency of selective inner hair cell loss, an extremely rare histopathological pattern, in the preterm vs. the full-term babies (27% vs. 3%, respectively). The findings suggest that a common cause of non-genetic auditory neuropathy is selective loss of inner hair cells rather than primary damage to the cochlear nerve.
C1 [Liberman, M. Charles; Northrop, Clarinda] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Amatuzzi, Monica] Univ Sao Paulo, Dept Otorhinolaryngol, Sao Paulo, Brazil.
[Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Northrop, Clarinda] Temporal Bone Fdn, Boston, MA USA.
RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM charles_liberman@meei.harvard.edu
FU NIH [R01 DC0188, P30 DC5029]; Temporal Bone Foundation
FX This work was supported by NIH Grants: R01 DC0188 (MCL and P30 DC5029
(MCL) and from a grant from the Temporal Bone Foundation. We are
grateful to Prof. Jorge Pizza from the Pathology Department of the
Hospital de Ninos in San Jose, Costa Rica, for granting access to obtain
material for this research.
NR 35
TC 12
Z9 16
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1525-3961
J9 JARO-J ASSOC RES OTO
JI JARO
PD OCT
PY 2011
VL 12
IS 5
BP 595
EP 604
DI 10.1007/s10162-011-0273-4
PG 10
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 820MK
UT WOS:000294909800005
PM 21674215
ER
PT J
AU Lin, HW
Furman, AC
Kujawa, SG
Liberman, MC
AF Lin, Harrison W.
Furman, Adam C.
Kujawa, Sharon G.
Liberman, M. Charles
TI Primary Neural Degeneration in the Guinea Pig Cochlea After Reversible
Noise-Induced Threshold Shift
SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
LA English
DT Article
DE acoustic injury; excitotoxicity; inner ear
ID AUDITORY-NERVE FIBERS; INDUCED HEARING-LOSS; INNER HAIR-CELLS; MAMMALIAN
COCHLEA; CAT; EXCITOTOXICITY; TRAUMA; REPAIR; SYNAPSES; NEURONS
AB Recent work in mouse showed that acoustic overexposure can produce a rapid and irreversible loss of cochlear nerve peripheral terminals on inner hair cells (IHCs) and a slow degeneration of spiral ganglion cells, despite full recovery of cochlear thresholds and no loss of inner or outer hair cells (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). This contrasts with earlier ultrastructural work in guinea pig suggesting that acute noise-induced neural degeneration is followed by full regeneration of cochlear nerve terminals in the IHC area (Puel et al., Neuroreport 9:2109-2114, 1998; Pujol and Puel, Ann N Y Acad Sci 884:249-254, 1999). Here, we show that the same patterns of primary neural degeneration reported for mouse are also seen in the noise-exposed guinea pig, when IHC synapses and cochlear nerve terminals are counted 1 week post-exposure in confocal images from immunostained whole mounts and that the same slow degeneration of spiral ganglion cells occurs despite no loss of IHCs and apparent recovery of cochlear thresholds. The data cast doubt on prior claims that there is significant neural regeneration and synaptogenesis in the adult cochlea and suggest that denervation of the inner hair cell is an important sequela of "reversible" noise-induced hearing loss, which likely applies to the human ear as well.
C1 [Lin, Harrison W.; Furman, Adam C.; Kujawa, Sharon G.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Lin, Harrison W.; Kujawa, Sharon G.; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA.
[Furman, Adam C.; Kujawa, Sharon G.; Liberman, M. Charles] Harvard MIT, Program Speech & Hearing Biosci & Technol, Cambridge, MA USA.
RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM charles_liberman@meei.harvard.edu
FU National Institute on Deafness and other Communication Disorders [R01
DC0188, R01 DC8577, T32 DC0038, P30 DC5029]
FX This work was supported by grants from the National Institute on
Deafness and other Communication Disorders: R01 DC0188, R01 DC8577, T32
DC0038, and P30 DC5029.
NR 34
TC 163
Z9 167
U1 7
U2 49
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1525-3961
J9 JARO-J ASSOC RES OTO
JI JARO
PD OCT
PY 2011
VL 12
IS 5
BP 605
EP 616
DI 10.1007/s10162-011-0277-0
PG 12
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 820MK
UT WOS:000294909800006
PM 21688060
ER
PT J
AU Favorov, A
Lvovs, D
Speier, W
Parmigiani, G
Ochs, MF
AF Favorov, Alexander
Lvovs, Dmitrijs
Speier, William
Parmigiani, Giovanni
Ochs, Michael F.
TI OnionTree XML: A Format to Exchange Gene-Related Probabilities
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Letter
ID MICROARRAY DATA; HUMAN GENOME; SYSTEMS BIOLOGY; IDENTIFICATION;
BIOCONDUCTOR; PREDICTION; SEQUENCES; SOFTWARE; LANGUAGE; MODELS
C1 [Favorov, Alexander; Speier, William; Ochs, Michael F.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
[Favorov, Alexander; Lvovs, Dmitrijs] Russian Federat Res Inst Genet & Select Ind Micro, Ctr Sci, Bioinformat Lab, Moscow 117545, Russia.
[Favorov, Alexander] RAS, Vavilov Inst Gen Genet, Moscow 119991, Russia.
[Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Favorov, A (reprint author), Sidney Kimmel Comprehens Canc Ctr, 550 North Broadway,Suite 1103, Baltimore, MD 21205 USA.
EM favorov@sensi.org
FU NCI NIH HHS [P30 CA006973]; NLM NIH HHS [R03 LM008932, LM008932]
NR 32
TC 0
Z9 0
U1 0
U2 1
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD OCT
PY 2011
VL 29
IS 2
BP 417
EP 423
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 820CV
UT WOS:000294884000016
PM 21875159
ER
PT J
AU Hoeppner, BB
Kelly, JF
Urbanoski, KA
Slaymaker, V
AF Hoeppner, Bettina B.
Kelly, John F.
Urbanoski, Karen A.
Slaymaker, Valerie
TI Comparative utility of a single-item versus multiple-item measure of
self-efficacy in predicting relapse among young adults
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Self-efficacy; Substance use relapse; Young adults; Psychometrics
ID JOB-SATISFACTION; ALCOHOL; BEHAVIOR; CONSTRUCTS; MOTIVATION; VALIDITY;
SMOKING; SCALES; MODEL
AB Single-item measures of psychological experiences are often viewed as psychometrically suspect. The purpose of this study was to evaluate the validity and utility of a single-item measure of self-efficacy in a clinical sample of treatment-seeking young adults. Inpatient young adults (N = 303, age = 18-24, 26% female) were assessed at intake to residential treatment, end of treatment, and at 1, 3, and 6 months following discharge. The single-item measure of self-efficacy consistently correlated positively with a well-established 20-item measure of self-efficacy and negatively with temptation scores from the same scale, demonstrating convergent and discriminant validity. It also consistently predicted relapse to substance use at 1-, 3-, and 6-month assessments postdischarge, even after controlling for other predictors of relapse (e.g., controlled environment), whereas global or subscale scores of the 20-item scale did not. Based on these findings, we encourage the use of this single-item measure of self-efficacy in research and clinical practice. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Hoeppner, Bettina B.; Kelly, John F.; Urbanoski, Karen A.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA.
[Slaymaker, Valerie] Hazelden Fdn Butler Ctr Res, Ctr City, MN 55012 USA.
RP Hoeppner, BB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA.
EM bhoeppner@partners.org; jkelly11@partners.org; kurbanoski@partners.org;
VSlaymaker@Hazelden.org
OI Urbanoski, Karen/0000-0001-7287-7176
FU NIAAA NIH HHS [R21 AA018185, R21 AA018185-01A2, R21AA018185]; NIDA NIH
HHS [K01 DA027097, K01 DA027097-02, K01DA027097, L30 DA025511, L30
DA025511-02]
NR 33
TC 43
Z9 44
U1 5
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD OCT
PY 2011
VL 41
IS 3
BP 305
EP 312
DI 10.1016/j.jsat.2011.04.005
PG 8
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 821NQ
UT WOS:000294982100012
PM 21700411
ER
PT J
AU Spina, JR
Glassman, PA
Simon, B
Lanto, A
Lee, M
Cunningham, F
Good, CB
AF Spina, Jeffrey R.
Glassman, Peter A.
Simon, Barbara
Lanto, Andrew
Lee, Martin
Cunningham, Francesca
Good, Chester B.
TI Potential Safety Gaps in Order Entry and Automated Drug Alerts A
Nationwide Survey of VA Physician Self-Reported Practices With
Computerized Order Entry
SO MEDICAL CARE
LA English
DT Article
DE medication safety; clinical decision support systems; drug interactions;
medication errors; attitude of health personnel
ID CLINICAL DECISION-SUPPORT; PRIMARY-CARE; MEDICATION SAFETY;
AMBULATORY-CARE
AB Objective: Understanding provider perceptions of and experiences with order entry and order checks (drug alerts) in an electronic prescribing system may help improve medication safety technology.
Design: Cross-sectional, national survey of Veterans Administration physicians practicing in various specialties.
Measurement: Thirty-five question instrument was divided into 4 content domains. Response options included dichotomous, numeric, multiple choices, and Likert-like scales. Statistical methods included logistic regression.
Results: The adjusted response rate was 1543 of 3588 (43%). Almost all providers (90%) felt that the VA electronic prescribing system, including its order checks, improved prescribing safety to some degree. Most respondents (72%) reported that they always or almost always document outside medications in a clinic note, although only 44% always or almost always entered outside medications in the non-VA medication data field. Most physicians (88%) who encountered serious allergic or adverse drug reactions reported either notifying a pharmacist or entering the information in the allergies/adverse reactions field. Generalists and physicians with higher numbers of prescriptions were more likely to enter relevant data into the electronic medical record (or notify a pharmacist, in the case of adverse reactions). In addition, 48% of providers described critical drug-drug interaction alerts as very useful; medical specialists found these less useful, whereas surgical specialists found these more useful when compared with generalists.
Limitations: Survey was conducted within a single healthcare system.
Conclusion: Computerized provider order entry and related order checks are perceived to improve prescribing safety; however, provider entry of some relevant information into the appropriate electronic fields may not be optimal.
C1 [Spina, Jeffrey R.; Glassman, Peter A.; Simon, Barbara; Lanto, Andrew; Lee, Martin] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Spina, Jeffrey R.; Glassman, Peter A.; Lee, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Glassman, Peter A.; Simon, Barbara; Lanto, Andrew; Lee, Martin] VA HSR&D Ctr Study Healthcare Provider Behav, Hines, IL USA.
[Glassman, Peter A.; Cunningham, Francesca; Good, Chester B.] VA Ctr Medicat Safety, Hines, IL USA.
[Lee, Martin] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Cunningham, Francesca] VA Pharm Benefits Management Serv, Hines, IL USA.
[Good, Chester B.] Pittsburgh VA Med Ctr, Pittsburgh, PA USA.
RP Spina, JR (reprint author), 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM Jeffrey.Spina@va.gov
NR 23
TC 6
Z9 6
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD OCT
PY 2011
VL 49
IS 10
BP 904
EP 910
DI 10.1097/MLR.0b013e318222a6f5
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 821EO
UT WOS:000294957900005
PM 21666510
ER
PT J
AU Lee, JM
Rhee, K
O'Grady, MJ
Basu, A
Winn, A
John, P
Meltzer, DO
Kollman, C
Laffel, LM
Lawrence, JM
Tamborlane, WV
Wysocki, T
Xing, DY
Huang, ES
AF Lee, Joyce M.
Rhee, Kirsten
O'Grady, Michael J.
Basu, Anirban
Winn, Aaron
John, Priya
Meltzer, David O.
Kollman, Craig
Laffel, Lori M.
Lawrence, Jean M.
Tamborlane, William V.
Wysocki, Tim
Xing, Dongyuan
Huang, Elbert S.
CA JDRF Continuous Glucose Monitoring
TI Health Utilities for Children and Adults With Type 1 Diabetes
SO MEDICAL CARE
LA English
DT Article
DE diabetes; health utilities; quality of life
ID QUALITY-OF-LIFE; LONG-TERM COMPLICATIONS; INTENSIVE TREATMENT;
PREFERENCES; MELLITUS; INDEX; POPULATION; OUTCOMES; PATIENT; CARE
AB Objective: We studied health utilities in patients with type 1 diabetes to understand potential differences in health utilities as function of age, type of respondent (self report vs. proxy report), and method of assessment (direct vs. indirect).
Research Design and Methods: We elicited self-reported health utilities for adults (n = 213) and children (n = 238) with type 1 diabetes, and by parent proxy report (n = 223) for overall quality of life [Health Utilities Index (HUI) Mark 3 and experienced time-trade-off (TTO) questions] and hypothetical complication states (TTO questions).
Results: Mean health utilities for overall quality of life (QOL) ranged from 0.81 to 0.91. Children had significantly higher overall QOL compared with adults (0.89 vs. 0.85, P<0.01) by HUI, but had no significant difference in QOL by TTO. There were no significant differences in QOL between child self report and parent proxy report. Utilities were higher for HUI versus TTO for parent proxy report (P<0.01) but not for adult or child self report. Utilities for hypothetical complication states were lower than for current QOL. Values were lower for stroke (0.34 to 0.53), end stage renal disease (0.47 to 0.55), and blindness (0.52 to 0.69) than for amputation (0.73 to 0.82) and angina (0.74 to 0.80). Complication utilities for parent proxy report were higher compared with adult self report for most hypothetical complication states.
Conclusions: Individuals with type 1 diabetes with few complications report a relatively high QOL; however, future end stage complications are rated as having a significant impact on QOL. Differences in utilities by age, self report versus proxy report, and method raise important questions about whose utilities should be used in economic analyses.
C1 [Lee, Joyce M.] Univ Michigan, Pediat Endocrinol & Hlth Serv Res, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA.
[Lee, Joyce M.] Univ Michigan, Child Hlth Evaluat & Res CHEAR Unit, Ann Arbor, MI 48109 USA.
[Rhee, Kirsten] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[O'Grady, Michael J.] Univ Chicago, Natl Opin Res Ctr, Chicago, IL 60637 USA.
[Basu, Anirban] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
[Winn, Aaron] Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA.
[John, Priya; Meltzer, David O.; Huang, Elbert S.] Univ Chicago, Sect Hosp Med, Chicago, IL 60637 USA.
[Kollman, Craig; Xing, Dongyuan] Jaeb Ctr Hlth Res, Tampa, FL USA.
[Laffel, Lori M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA.
[Lawrence, Jean M.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA.
[Tamborlane, William V.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Wysocki, Tim] Nemours Childrens Clin, Jacksonville, FL USA.
RP Lee, JM (reprint author), Univ Michigan, Pediat Endocrinol & Hlth Serv Res, Child Hlth Evaluat & Res Unit, 300 NIB,Room 6E18,Campus Box 5456, Ann Arbor, MI 48109 USA.
EM joyclee@umich.edu
RI Meltzer, David/C-2926-2009
OI Meltzer, David/0000-0003-2790-7393
FU NIDDK NIH HHS [K08 DK082386, K08 DK082386-02, P30 DK092949]
NR 32
TC 12
Z9 12
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD OCT
PY 2011
VL 49
IS 10
BP 924
EP 931
DI 10.1097/MLR.0b013e318216592c
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 821EO
UT WOS:000294957900008
PM 21544001
ER
PT J
AU Kautz, SA
Bowden, MG
Clark, DJ
Neptune, RR
AF Kautz, Steven A.
Bowden, Mark G.
Clark, David J.
Neptune, Richard R.
TI Comparison of Motor Control Deficits During Treadmill and Overground
Walking Poststroke
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE walking; stroke; motor control; treadmill; overground
ID GROUND REACTION FORCES; MUSCLE SYNERGIES; GAIT PATTERN; LOCOMOTION;
STROKE; SPEED; COORDINATION; HEMIPARESIS; PERFORMANCE
AB Background. Force-sensing split-belt treadmills (TMs) provide an alternative to the conventional overground (OG) setting and allow new avenues for analyzing the biomechanics and motor control of walking. However, walking control may differ on a TM compared with walking OG. Objective. To compare spatiotemporal, kinematic, and EMG-based measures of motor control between TM and OG walking at self-selected and fastest comfortable speeds in persons with poststroke hemiparesis. Methods. Individuals with chronic hemiparesis (56) and similarly aged healthy individuals (17) walked over an instrumented walkway and on an instrumented split-belt TM; 16 channels of EMG recorded bilateral muscle activity, and a 12-camera motion capture system collected bilateral 3D kinematics. The authors applied a nonnegative matrix factorization (NNMF) algorithm to examine the underlying patterns of motor control. Results. Self-selected walking patterns differed on the TM versus OG in controls: speed decreased, stride length decreased, stance percentage increased, and double-support percentage increased. Poststroke, responses were similar, but cadence also decreased, and step length asymmetry increased. Kinematic patterns were similar except those associated with slower walking speeds. NNMF demonstrated similar EMG variance in the 2 environments. Conclusion. Persons, both healthy and poststroke, walk with different gait parameters on the TM. Although measures of motor control were mostly similar between the 2 environments, the TM induced step length asymmetry in 30% of participants (60% of whom took longer paretic steps). TM walking, therefore, is a valid method for detecting motor control deficits.
C1 [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[Kautz, Steven A.; Bowden, Mark G.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Clark, David J.] Malcom Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA.
[Neptune, Richard R.] Univ Texas Austin, Austin, TX 78712 USA.
RP Kautz, SA (reprint author), Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
EM kautz@musc.edu
RI Clark, David/A-4916-2013;
OI Kautz, Steven/0000-0003-3151-8235
FU NIH [R01 HD46820]; VA Rehabilitation R&D Center of Excellence [F2182C];
Office of Research and Development, Rehabilitation R & D Service,
Department of Veterans Affairs (VA); Malcom Randall VA Medical Center,
Gainesville, FL
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was funded by NIH R01 HD46820 and VA Rehabilitation R&D Center of
Excellence Grant F2182C. This material is the result of work supported
in part by the Office of Research and Development, Rehabilitation R & D
Service, Department of Veterans Affairs (VA), and the Malcom Randall VA
Medical Center, Gainesville, FL. The contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the NIH, National Institute of Child Health and Human
Development (NICHHD), or VA.
NR 30
TC 32
Z9 33
U1 0
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD OCT
PY 2011
VL 25
IS 8
BP 756
EP 764
DI 10.1177/1545968311407515
PG 9
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 820ID
UT WOS:000294898000008
PM 21636831
ER
PT J
AU Francis, HW
Makary, C
Halpin, C
Crane, BT
Merchant, SN
AF Francis, Howard W.
Makary, Chadi
Halpin, Christopher
Crane, Benjamin T.
Merchant, Saumil N.
TI Temporal Bone Findings in a Case of Susac's Syndrome
SO OTOLOGY & NEUROTOLOGY
LA English
DT Article
DE Otopathology; Sensorineural hearing loss; Susac's syndrome; Temporal
bone histopathology
ID CLINICAL-IMPLICATIONS; MICROEMBOLISM; COCHLEA; SPEECH; ARTERY
AB Objective: To describe the histopathologic findings in the temporal bones of a patient with Susac's syndrome (SS).
Background: The key clinical features of SS consist of symptoms of encephalopathy, visual defects due to occlusion of branches of the retinal artery, and sensorineural hearing loss. The otopathology in SS has not been described.
Materials and Methods: A 51-year-old woman was hospitalized with severe headache, rapidly progressive encephalopathy, and bilateral low-frequency sensorineural hearing loss. Magnetic resonance imaging showed lesions of the corpus callosum. Fluorescein angiography of the eyes showed focal areas of irregular retinal artery caliber and leakage from small vessels. SS was diagnosed. She died of a pulmonary embolus 1 month after onset of symptoms. Both temporal bones were prepared in celloidin and examined using light microscopy.
Results: Findings were nearly identical in both temporal bones. The apical halves of both cochleae showed widespread atrophy of structures of the cochlear duct (inner and outer hair cells, tectorial membranes, striae vasculares, spiral ligaments, and spiral limbi). The apical parts of both cochleae also showed apparent occlusion of capillaries within the stria vascularis and related areas of the cochlear duct. Cochlear neurons were present in normal numbers. There was no endolymphatic hydrops. The vestibular sense organs were normal for age.
Conclusion: This first reported otopathologic case of SS with hearing loss showed atrophy and degeneration involving the apical halves of the cochlear duct without inflammation or infection. The findings were consistent with capillary occlusion as being responsible for the atrophy.
C1 [Makary, Chadi; Halpin, Christopher; Merchant, Saumil N.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Makary, Chadi; Halpin, Christopher; Merchant, Saumil N.] Harvard Univ, Sch Med, Boston, MA USA.
[Francis, Howard W.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Crane, Benjamin T.] Univ Rochester, Rochester, NY USA.
RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM saumil_merchant@meei.harvard.edu
FU National Institutes of Health [U24 DC011943]
FX This work was supported by National Institutes of Health grant U24
DC011943.
NR 17
TC 4
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1531-7129
J9 OTOL NEUROTOL
JI Otol. Neurotol.
PD OCT
PY 2011
VL 32
IS 8
BP 1198
EP 1204
DI 10.1097/MAO.0b013e31822e9665
PG 7
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 821BD
UT WOS:000294948900006
PM 21897318
ER
PT J
AU McCall, AA
McKenna, MJ
Merchant, SN
Curtin, HD
Lee, DJ
AF McCall, Andrew A.
McKenna, Michael J.
Merchant, Saumil N.
Curtin, Hugh D.
Lee, Daniel J.
TI Superior Canal Dehiscence Syndrome Associated With the Superior Petrosal
Sinus in Pediatric and Adult Patients
SO OTOLOGY & NEUROTOLOGY
LA English
DT Article
DE Adult; Canal plugging; Dizziness; Pediatric; Superior canal dehiscence;
Superior petrosal sinus; Vascular; Vertigo
ID EVOKED MYOGENIC POTENTIALS; INNER-EAR; COMPUTED-TOMOGRAPHY; SYMPTOMS;
HEARING; VERTIGO; REPAIR
AB Objective: To determine whether pediatric and adult patients with superior canal dehiscence (SCD) at the superior petrosal sinus (SPS) develop superior canal dehiscence syndrome (SCDS).
Study Design: Retrospective review.
Setting: Tertiary care academic medical center.
Patients: Pediatric and adult patients with SPS-associated SCD were identified from a database of 131 patients with SCD based on high-resolution temporal bone computed tomography.
Intervention: One pediatric patient experienced incapacitating exercise-induced vertigo, and this patient's superior semicircular canal defect was plugged via a transmastoid approach. The 11 remaining patients were managed by observation.
Main Outcome Measure: Clinical symptoms and signs, audiologic testing, vestibular evoked myogenic potentials, and radiologic data.
Results: Twelve patients, aged 15 to 84 years, with SCD caused by the SPS contacting the superior semicircular canal were identified. The most characteristic clinical feature in this population (5/12) was dizziness related to exercise and exertion. Bilateral SCD was observed in 3 patients. Eleven patients did not have severe symptoms and were managed conservatively. One patient, aged 15, required surgical intervention for incapacitating vertigo and experienced relief of symptoms with reversal of diagnostic indicators postoperatively. This is the first reported surgical repair of SCDS in a pediatric patient.
Conclusion: This is the first series of patients who have SCDS due to contact of the SPS with the superior semicircular canal. Exercise and exertion-related symptoms are common in patients who have SCD owing to this cause. Transmastoid superior canal plugging is feasible and successful in treating SCDS in the pediatric patient.
C1 [McCall, Andrew A.; McKenna, Michael J.; Merchant, Saumil N.; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[McCall, Andrew A.; McKenna, Michael J.; Merchant, Saumil N.; Lee, Daniel J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Curtin, Hugh D.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA.
[Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM daniel_lee@meei.harvard.edu
NR 29
TC 16
Z9 16
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1531-7129
J9 OTOL NEUROTOL
JI Otol. Neurotol.
PD OCT
PY 2011
VL 32
IS 8
BP 1312
EP 1319
DI 10.1097/MAO.0b013e31822e5b0a
PG 8
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 821BD
UT WOS:000294948900025
PM 21918420
ER
PT J
AU Szmulewicz, DJ
Merchant, SN
Halmagyi, GM
AF Szmulewicz, David J.
Merchant, Saumil N.
Halmagyi, Gabor Michael
TI Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia
Syndrome: A Histopathologic Case Report
SO OTOLOGY & NEUROTOLOGY
LA English
DT Editorial Material
C1 [Szmulewicz, David J.] Alfred Hosp, Dept Neurosci, Prahran, Vic, Australia.
[Merchant, Saumil N.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA.
[Halmagyi, Gabor Michael] Royal Prince Alfred Hosp, Dept Neurol, Camperdown, NSW, Australia.
RP Szmulewicz, DJ (reprint author), Alfred Hosp, Dept Neurosci, Prahran, Vic, Australia.
EM dsz@me.com
FU NIDCD NIH HHS [U24 DC008559, U24 DC008559-04]
NR 5
TC 12
Z9 12
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1531-7129
J9 OTOL NEUROTOL
JI Otol. Neurotol.
PD OCT
PY 2011
VL 32
IS 8
BP E63
EP E65
DI 10.1097/MAO.0b013e318210b719
PG 3
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 821BD
UT WOS:000294948900004
PM 21451431
ER
PT J
AU Zou, L
Feng, Y
Zhang, M
Li, Y
Chao, W
AF Zou, Lin
Feng, Yan
Zhang, Ming
Li, Yan
Chao, Wei
TI NONHEMATOPOIETIC TOLL-LIKE RECEPTOR 2 CONTRIBUTES TO NEUTROPHIL AND
CARDIAC FUNCTION IMPAIRMENT DURING POLYMICROBIAL SEPSIS
SO SHOCK
LA English
DT Article
DE Sepsis; phagocytosis; cytokine; innate immunity; toll-like receptors;
cardiac dysfunction
ID PEPTIDOGLYCAN-ASSOCIATED LIPOPROTEIN; MYOCARDIAL DYSFUNCTION;
UNITED-STATES; SURVIVAL; MICE; INJURY; MYD88; RECOGNITION; TLR4;
LIPOPOLYSACCHARIDE
AB Toll-like receptor 2 (TLR2) has been implicated in neutrophil and cardiac dysfunction during sepsis. Here we tested the hypothesis that nonhematopoietic (parenchymal) and hematopoietic TLR2 play distinct roles in sepsis pathogenesis. To achieve this, we generated two groups of chimeric mice with TLR2 deletions either in nonhematopoietic cells (knockout [KO] mice with wildtype [WT] bone marrow [BM]) or in BM cells (WT mice with KOBM). Polymicrobial sepsis was created by cecal ligation and puncture (CLP). Neutrophil functions, cytokine production, and bacterial clearance were investigated following CLP or sham procedures. Cardiac contractile function was measured in a Langendorff apparatus. Intracellular reactive oxygen species (ROS) were measured using redoxsensitive dye and flow cytometry. Cecal ligation and puncture mice had markedly increased peritoneal neutrophil recruitment compared with the shamoperated mice. Toll-like receptor 2 KO mice, regardless their TLR2 phenotypes (WT vs. KO) in their BM-derived hematopoietic cells, had markedly increased neutrophil migration as well as phagocytosis and reduced cytokine productions compared with TLR2 WT mice following polymicrobial peritonitis. These changes in the chimeric TLR2 KO mice were associated with enhanced blood bacterial clearance and markedly improved cardiac contractile function. Moreover, CLP induced a robust ROS production in the peritoneal leukocytes isolated from WT mice but not from TLR2 KO mice. Taken together, these data indicate that TLR2, particularly that of nonhematopoietic cells, plays a major role in sepsis pathogenesis by impairing neutrophil migratory and phagocytic function, promoting cytokine production, and mediating cardiac contractile dysfunction during polymicrobial sepsis. Toll-like receptor 2 also mediates critical ROS production during polymicrobial sepsis.
C1 [Zou, Lin; Feng, Yan; Zhang, Ming; Li, Yan; Chao, Wei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA.
RP Chao, W (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,Room 4-212, Charlestown, MA 02129 USA.
EM wchao@partners.org
RI Feng, Yan/H-5808-2012
FU National Institutes of Health [GM-080906]; American Heart Association
[0755890T]
FX This work was supported by National Institutes of Health grant GM-080906
and American Heart Association grant 0755890T.
NR 44
TC 18
Z9 18
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1073-2322
J9 SHOCK
JI Shock
PD OCT
PY 2011
VL 36
IS 4
BP 370
EP 380
DI 10.1097/SHK.0b013e3182279868
PG 11
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA 821CF
UT WOS:000294951700009
PM 21701420
ER
PT J
AU Sharpless, BA
Barber, JP
AF Sharpless, Brian A.
Barber, Jacques P.
TI Lifetime prevalence rates of sleep paralysis: A systematic review
SO SLEEP MEDICINE REVIEWS
LA English
DT Review
DE Sleep paralysis; Isolated sleep paralysis; Anxiety; Fear; Parasomnia;
Prevalence
ID CHILDHOOD SEXUAL-ABUSE; GENERAL-POPULATION; MEDICAL-STUDENTS; PANIC
DISORDER; COLLEGE-STUDENTS; HALLUCINATIONS; SYMPTOMATOLOGY; KANASHIBARI;
OUTPATIENTS; FREQUENCY
AB Objective: To determine lifetime prevalence rates of sleep paralysis.
Data sources: Keyword term searches using "sleep paralysis", "isolated sleep paralysis", or "parasomnia not otherwise specified" were conducted using MEDLINE (1950-present) and PsychINFO (1872-present). English and Spanish language abstracts were reviewed, as were reference lists of identified articles.
Study selection: Thirty five studies that reported lifetime sleep paralysis rates and described both the assessment procedures and sample utilized were selected.
Data extraction: Weighted percentages were calculated for each study and, when possible, for each reported subsample.
Data synthesis: Aggregating across studies (total N = 36,533), 7.6% of the general population, 28.3% of students, and 31.9% of psychiatric patients experienced at least one episode of sleep paralysis. Of the psychiatric patients with panic disorder, 34.6% reported lifetime sleep paralysis. Results also suggested that minorities experience lifetime sleep paralysis at higher rates than Caucasians.
Conclusions: Sleep paralysis is relatively common in the general population and more frequent in students and psychiatric patients. Given these prevalence rates, sleep paralysis should be assessed more regularly and uniformly in order to determine its impact on individual functioning and better articulate its relation to psychiatric and other medical conditions. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Sharpless, Brian A.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
[Barber, Jacques P.] Univ Penn, Ctr Psychotherapy Res, Dept Psychiat, Philadelphia, PA 19104 USA.
[Barber, Jacques P.] Univ Philadelphia, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
RP Sharpless, BA (reprint author), Penn State Univ, Dept Psychol, 317 Moore Bldg, University Pk, PA 16802 USA.
EM bas171@psu.edu; barberj@mail.med.upenn.edu
FU NIMH [R01 MH 070664]
FX We would like to thank the authors who responded to our emails with
additional clarifications on their published studies as well as the
anonymous reviewers. This work was supported in part by a grant (NIMH
R01 MH 070664) held by Jacques P. Barber.
NR 49
TC 22
Z9 23
U1 3
U2 28
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1087-0792
J9 SLEEP MED REV
JI Sleep Med. Rev.
PD OCT
PY 2011
VL 15
IS 5
BP 311
EP 315
DI 10.1016/j.smrv.2011.01.007
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 820YL
UT WOS:000294941900005
PM 21571556
ER
PT J
AU Adluri, RS
Thirunavukkarasu, M
Dunna, NR
Zhan, LJ
Oriowo, B
Takeda, K
Sanchez, JA
Otani, H
Maulik, G
Fong, GH
Maulik, N
AF Adluri, Ram Sudheer
Thirunavukkarasu, Mahesh
Dunna, Nageswara Rao
Zhan, Lijun
Oriowo, Babatunde
Takeda, Kotaro
Sanchez, Juan A.
Otani, Hajime
Maulik, Gautam
Fong, Guo-Hua
Maulik, Nilanjana
TI Disruption of Hypoxia-Inducible Transcription Factor-Prolyl Hydroxylase
Domain-1 (PHD-1(-/-)) Attenuates Ex Vivo Myocardial Ischemia/Reperfusion
Injury Through Hypoxia-Inducible Factor-1 alpha Transcription Factor and
Its Target Genes in Mice
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID ISCHEMIA-REPERFUSION INJURY; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE;
FACTOR-I; INDUCED APOPTOSIS; OXYGEN SENSORS; FACTOR-ALPHA; ANGIOGENESIS;
INHIBITION; RAT
AB Hypoxia-inducible transcription factor (HIF)-prolyl hydroxylases domain (PHD-1-3) are oxygen sensors that regulate the stability of the HIFs in an oxygen-dependent manner. Suppression of PHD enzymes leads to stabilization of HIFs and offers a potential treatment option for many ischemic disorders, such as peripheral artery occlusive disease, myocardial infarction, and stroke. Here, we show that homozygous disruption of PHD-1 (PHD-1(-/-)) could facilitate HIF-1 alpha-mediated cardioprotection in ischemia/reperfused (I/R) myocardium. Wild-type (WT) and PHD-1(-/-) mice were randomized into WT time-matched control (TMC), PHD-1(-/-) TMC (PHD1TMC), WT I/R, and PHD-1(-/-) I/R (PHD1IR). Isolated hearts from each group were subjected to 30 min of global ischemia followed by 2h of reperfusion. TMC hearts were perfused for 2h 30 min without ischemia. Decreased infarct size (35% +/- 0.6% vs. 49% +/- 0.4%) and apoptotic cardiomyocytes (106 +/- 13 vs. 233 +/- 21 counts/100 high-power field) were observed in PHD1IR compared to wild-type ischemia/reperfusion (WTIR). Protein expression of HIF-1 alpha was significantly increased in PHD1IR compared to WTIR. mRNA expression of beta-catenin (1.9-fold), endothelial nitric oxide synthase (1.9-fold), p65 (1.9-fold), and Bcl-2 (2.7-fold) were upregulated in the PHD1IR compared withWTIR, which was studied by real-time quantitative polymerase chain reaction. Further, gel-shift analysis showed increased DNA binding activity of HIF-1 alpha and nuclear factor-kappaB in PHD1IR compared to WTIR. In addition, nuclear translocation of beta-catenin was increased in PHD1IR compared with WTIR. These findings indicated that silencing of PHD-1 attenuates myocardial I/R injury probably by enhancing HIF-1 alpha/beta-catenin/endothelial nitric oxide synthase/nuclear factor-kappaB and Bcl-2 signaling pathway. Antioxid. Redox Signal. 15, 1789-1797.
C1 [Adluri, Ram Sudheer; Thirunavukkarasu, Mahesh; Dunna, Nageswara Rao; Zhan, Lijun; Oriowo, Babatunde; Maulik, Nilanjana] Univ Connecticut, Sch Med, Mol Cardiol & Angiogenesis Lab, Dept Surg, Farmington, CT 06032 USA.
[Oriowo, Babatunde; Sanchez, Juan A.] St Marys Hosp, Dept Surg, Waterbury, CT USA.
[Takeda, Kotaro; Fong, Guo-Hua] Univ Connecticut, Sch Med, Dept Cell Biol, Farmington, CT 06032 USA.
[Otani, Hajime] Kansai Med Univ, Dept Thorac & Cardiovasc Surg 2, Moriguchi, Osaka 570, Japan.
[Maulik, Gautam] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Maulik, N (reprint author), Univ Connecticut, Sch Med, Mol Cardiol & Angiogenesis Lab, Dept Surg, 263 Farmington Ave, Farmington, CT 06032 USA.
EM nmaulik@neuron.uchc.edu
RI Sanchez, Juan/I-1936-2016
OI Sanchez, Juan/0000-0002-6789-3208
FU [HL-85804]; [5R01EY019721]
FX This study was supported by the grant HL-85804 (N. Maulik) and also
5R01EY019721 (G.-H. Fong).
NR 39
TC 28
Z9 30
U1 0
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD OCT
PY 2011
VL 15
IS 7
BP 1789
EP 1797
DI 10.1089/ars.2010.3769
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 818QY
UT WOS:000294770900004
PM 21083501
ER
PT J
AU Yao, JK
Reddy, R
AF Yao, Jeffrey K.
Reddy, Ravinder
TI Oxidative Stress in Schizophrenia: Pathogenetic and Therapeutic
Implications
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Editorial Material
ID SYSTEM; BRAIN; ABNORMALITIES
AB Over a century, a wide-ranging variety of pathophysiological models and causal hypotheses have been conceptualized for schizophrenia. One among these is the role for free radical-mediated pathology in schizophrenia, indicating impaired antioxidant defense system (AODS) and presence of oxidative stress in patients with schizophrenia. For the past two decades, the whole investigative domain of AODS and oxidative stress has broadened to include the wider AODS components, direct central nervous system assays of AODS, chemical imaging studies, proteomics, genetics of AODS, and, of importance to sufferers of schizophrenia, antioxidant therapeutics. These are some of the perspectives that are reviewed by several articles in this Forum. Overall, there has been growing recognition of the importance of oxidative stress in the pathophysiology of schizophrenia and in treatment-related side effects. The totality of the evidence from biochemistry, metabolomics, proteomics, genetics, and in vivo brain imaging points to the presence of multifarious abnormalities in the AODS and redox signaling in schizophrenia. Antioxid. Redox Signal. 15, 1999-2002.
C1 [Yao, Jeffrey K.; Reddy, Ravinder] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA 15206 USA.
[Yao, Jeffrey K.; Reddy, Ravinder] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Med Res Serv, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM jkyao@pitt.edu
FU NIMH NIH HHS [MH58141]
NR 33
TC 38
Z9 39
U1 1
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD OCT
PY 2011
VL 15
IS 7
BP 1999
EP 2002
DI 10.1089/ars.2010.3646
PG 4
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 818QY
UT WOS:000294770900016
PM 21194354
ER
PT J
AU Yao, JK
Keshavan, MS
AF Yao, Jeffrey K.
Keshavan, Matcheri S.
TI Antioxidants, Redox Signaling, and Pathophysiology in Schizophrenia: An
Integrative View
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID NITRIC-OXIDE SYNTHASE; POLYUNSATURATED FATTY-ACIDS;
MAGNETIC-RESONANCE-SPECTROSCOPY; SERUM URIC-ACID; MEMBRANE
PHOSPHOLIPID-METABOLISM; PERFORMANCE LIQUID-CHROMATOGRAPHY;
SUPEROXIDE-DISMUTASE ACTIVITY; LIPID-PEROXIDATION PRODUCTS;
NEVER-MEDICATED 1ST-EPISODE; MULTIPLE-SCLEROSIS PATIENTS
AB Schizophrenia (SZ) is a brain disorder that has been intensively studied for over a century; yet, its etiology and multifactorial pathophysiology remain a puzzle. However, significant advances have been made in identifying numerous abnormalities in key biochemical systems. One among these is the antioxidant defense system (AODS) and redox signaling. This review summarizes the findings to date in human studies. The evidence can be broadly clustered into three major themes: perturbations in AODS, relationships between AODS alterations and other systems (i.e., membrane structure, immune function, and neurotransmission), and clinical implications. These domains of AODS have been examined in samples from both the central nervous system and peripheral tissues. Findings in patients with SZ include decreased nonenzymatic antioxidants, increased lipid peroxides and nitric oxides, and homeostatic imbalance of purine catabolism. Reductions of plasma antioxidant capacity are seen in patients with chronic illness as well as early in the course of SZ. Notably, these data indicate that many AODS alterations are independent of treatment effects. Moreover, there is burgeoning evidence indicating a link among oxidative stress, membrane defects, immune dysfunction, and multineurotransmitter pathologies in SZ. Finally, the body of evidence reviewed herein provides a theoretical rationale for the development of novel treatment approaches. Antioxid. Redox Signal. 15, 2011-2035.
C1 [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA.
[Yao, Jeffrey K.; Keshavan, Matcheri S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Keshavan, Matcheri S.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA.
[Keshavan, Matcheri S.] Harvard Univ, Boston, MA 02115 USA.
RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst 151U H, Med Res Serv, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM jkyao@pitt.edu
FU Department of Veterans Affairs; Veterans Health Administration; Office
of Research and Development; Biomedical Laboratory RD; VA Pittsburgh
Healthcare System; National Institute of Health [MH58141, MH45203]
FX This material is based upon work supported in part by the grants from
the Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development, Biomedical Laboratory R&D (Merit
Reviews and Senior Research Career Scientist Award), VA Pittsburgh
Healthcare System, and National Institute of Health [MH58141 (J.K.Y.),
and MH45203 (M.S.K.)]. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
article. The contents of this article do not represent the views of the
Department of Veterans Affairs or the U.S. Government.
NR 308
TC 101
Z9 103
U1 3
U2 23
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD OCT
PY 2011
VL 15
IS 7
BP 2011
EP 2035
DI 10.1089/ars.2010.3603
PG 25
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 818QY
UT WOS:000294770900018
PM 21126177
ER
PT J
AU Reddy, R
Reddy, R
AF Reddy, Ravinder
Reddy, Rajiv
TI Antioxidant Therapeutics for Schizophrenia
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID VITAMIN-E TREATMENT; POLYUNSATURATED FATTY-ACIDS; TERM
TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; OXIDATIVE STRESS; ATYPICAL
ANTIPSYCHOTICS; OPEN-LABEL; SUPPLEMENTATION; OMEGA-3-FATTY-ACIDS;
METAANALYSIS
AB Pharmaceutical treatment for millions worldwide who have schizophrenia is limited to a handful of antipsychotics. Despite the proven efficacy of these drugs, the overall outcome for schizophrenia remains suboptimal. Thus, alternative treatment options are urgently needed. One possible approach may be antioxidant therapy. The extant evidence for the role of oxidative stress in the pathophysiology of schizophrenia offers a hypothesis-derived therapeutic approach in the form of antioxidants. Vitamins C and E, for example, are suitable for human clinical trials because they are readily available, inexpensive, and relatively safe. Research into the therapeutic use of antioxidants in schizophrenia can be grouped into two main clusters: for psychopathology and for side effects. Of these studies, some have been carefully conducted, but majority are open label. Use of antioxidants for treatment-related side effects has been more extensively investigated. The totality of the evidence to date suggests that specific antioxidants, such as N-acetyl cysteine, may offer tangible benefits for the clinical syndrome of schizophrenia, and vitamin E may offer salutary effects on glycemic effects of antipsychotics. However, a great deal of fundamental clinical research remains to be done before antioxidants can be routinely used therapeutically for schizophrenia and treatment-related complications. Antioxid. Redox Signal. 15, 2047-2055.
C1 [Reddy, Ravinder] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Reddy, Ravinder] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Reddy, Rajiv] Univ Toledo, Sch Med, Toledo, OH 43606 USA.
RP Reddy, R (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM reddyr@upmc.edu
NR 55
TC 17
Z9 17
U1 1
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD OCT
PY 2011
VL 15
IS 7
BP 2047
EP +
DI 10.1089/ars.2010.3571
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 818QY
UT WOS:000294770900020
PM 20977337
ER
PT J
AU Marzia, M
Guaiquil, V
Horne, WC
Blobel, CP
Baron, R
Chiusaroli, R
AF Marzia, Marilena
Guaiquil, Victor
Horne, William C.
Blobel, Carl P.
Baron, Roland
Chiusaroli, Riccardo
TI Lack of ADAM15 in mice is associated with increased osteoblast function
and bone mass
SO BIOLOGICAL CHEMISTRY
LA English
DT Article
DE ADAM15; beta-catenin; disintegrin; metalloprotease; osteoblast; skeletal
homeostasis
ID N-CADHERIN; METALLOPROTEASE-DISINTEGRINS; CELL-ADHESION; EXPRESSION;
ACTIVATION; CLEAVAGE; BETA; PHOSPHORYLATION; DIFFERENTIATION; PHENOTYPE
AB The ADAMs (a disintegrin and metalloprotease) contribute to various biological functions including the development of tissues by taking part in cell-cell and cell-matrix interactions. We previously found that ADAM15 is prominently expressed in osteoblasts and to a lesser extent in osteoclasts. The aim of this study was to investigate a possible function of ADAM15 in bone. Adult ADAM15(-/-) mice displayed an increase in bone volume and thickness with an increase in the number and activity of osteoblasts, whereas osteoclasts were apparently unaffected. We found an increase in proliferation, alkaline phosphatase (ALP) staining and nodule deposition, and mineralization in cultures of ADAM15(-/-) osteoblasts compared to wild-type osteoblasts. We also observed an increase in beta-catenin immunoreactivity in the nucleus of ADAM15(-/-) osteoblasts compared to wild-type, whereas beta-catenin in the membrane/cytoplasm compartment appeared to undergo increased degradation. Furthermore, cyclin D1 and c-Jun, known downstream targets of beta-catenin and effectors of cell activation, were found up-regulated in absence of ADAM15. This study indicates that ADAM15 is required for normal skeletal homeostasis and that its absence causes increased nuclear translocation of beta-catenin in osteoblasts leading to increased osteoblast proliferation and function, which results in higher trabecular and cortical bone mass.
C1 [Marzia, Marilena; Baron, Roland; Chiusaroli, Riccardo] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA.
[Marzia, Marilena; Baron, Roland; Chiusaroli, Riccardo] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Marzia, Marilena; Horne, William C.; Baron, Roland; Chiusaroli, Riccardo] Yale Univ, Sch Med, Dept Orthoped & Rehabil, New Haven, CT 06510 USA.
[Horne, William C.; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Guaiquil, Victor; Blobel, Carl P.] Cornell Univ, Arthrit & Tissue Degenerat Program, Hosp Special Surg, New York, NY 10021 USA.
[Chiusaroli, Riccardo] Rottapharm R&D, Preclin Pharmacol Pharmacol & Toxicol Dept, I-20052 Monza, Italy.
RP Chiusaroli, R (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA.
EM riccardo.chiusaroli@rottapharm.com
FU National Institutes of Health [ADE-04724, RO1 GM58668]; Rottapharm
S.p.A. (Monza, Italy)
FX This work was funded by ADE-04724 (to R. B.) from the National
Institutes of Health, RO1 GM58668 (to C. P. B.) from National Institutes
of Health grant, and by a grant from Rottapharm S.p.A. (Monza, Italy).
However, the Rottapharm group as a corporate entity had no role in the
conduct of the study; in the collection, analysis and interpretation of
data; in the writing of the report; and in the decision to submit the
paper for publication.
NR 34
TC 6
Z9 6
U1 0
U2 3
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 1431-6730
J9 BIOL CHEM
JI Biol. Chem.
PD OCT
PY 2011
VL 392
IS 10
BP 877
EP 885
DI 10.1515/BC.2011.080
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 816NU
UT WOS:000294609900005
PM 21801086
ER
PT J
AU Chernigovskaya, E
Atochin, D
Yamova, L
Huang, P
Glazova, M
AF Chernigovskaya, E.
Atochin, D.
Yamova, L.
Huang, P.
Glazova, M.
TI Immunohistochemical expression of Bcl-2, p53 and caspase-9 in
hypothalamus magnocellular centers of nNOS knockout mice following water
deprivation
SO BIOTECHNIC & HISTOCHEMISTRY
LA English
DT Article
DE apoptosis regulator proteins; hypothalamus; magnocellular neurons;
nitric oxide synthase; water deprivation
ID NITRIC-OXIDE SYNTHASE; CELL-DEATH; PARAVENTRICULAR NUCLEUS;
NERVOUS-SYSTEM; NEURONS; RAT; VASOPRESSIN; BRAIN; MECHANISMS; PITUITARY
AB We studied the interactions between apoptosis regulator proteins (Bcl-2, p53 and caspase-9) and neuronal nitric oxide in vasopressinergic magnocellular centers of the hypothalamus using neuronal nitric oxide synthase (nNOS) gene knockout mice. nNOS gene deletion resulted in accumulation of Bcl-2, p53 and caspase-9 in the paraventricular (PVN) and supraoptic (SON) nuclei in controls. Dehydration increased the levels of all three apoptosis regulator proteins studied in nuclei of wild type mice. In the hypothalamus magnocellular centers of nNOS knockout mice, however, expression of Bcl-2, p53 and caspase-9 was unchanged after dehydration. The number of magnocellular neurons did not change in the SON and PVN of nNOS deficient mice compared to wild type, and after dehydration, cell death was not observed in either nucleus of wild type or knockout mice despite activation of apoptosis regulator protein expression. Thus, we demonstrated that gene disruption of nNOS prevents activation of Bcl-2, p53 and caspase-9 expression during water deprivation, and that nNOS deficiency did not affect survival of magnocellular neurons of the hypothalamus.
C1 [Chernigovskaya, E.; Atochin, D.; Yamova, L.; Glazova, M.] Russian Acad Sci, IM Sechenov Evolut Physiol & Biochem Inst, St Petersburg 194223, Russia.
[Atochin, D.; Huang, P.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
RP Glazova, M (reprint author), Russian Acad Sci, IM Sechenov Evolut Physiol & Biochem Inst, 44 Thorez Pr, St Petersburg 194223, Russia.
EM mglazova@hotmail.com
RI Atochin, Dmitriy/Q-3150-2016; Glazova, Margarita/Q-8597-2016
OI Glazova, Margarita/0000-0001-6617-3404
FU PHS [NS33335]; American Heart Association [0835344N]; Russian Foundation
for Fundamental Research [RFBR 08-04-00028-a]
FX This work was supported by PHS NS33335 to PLH, American Heart
Association Scientist Development Grant 0835344N to DNA, and RFBR
08-04-00028-a from the Russian Foundation for Fundamental Research.
NR 33
TC 2
Z9 3
U1 0
U2 2
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1052-0295
J9 BIOTECH HISTOCHEM
JI Biotech. Histochem.
PD OCT
PY 2011
VL 86
IS 5
BP 333
EP 339
DI 10.3109/10520295.2010.501706
PG 7
WC Biotechnology & Applied Microbiology; Cell Biology
SC Biotechnology & Applied Microbiology; Cell Biology
GA 818UT
UT WOS:000294782000005
PM 20662604
ER
PT J
AU Wang, YN
Lee, K
Pai, S
Ledoux, WR
AF Wang, Y. N.
Lee, K.
Pai, S.
Ledoux, W. R.
TI Histomorphometric comparison after fixation with formaldehyde or glyoxal
SO BIOTECHNIC & HISTOCHEMISTRY
LA English
DT Article
DE formaldehyde; glyoxal; heel pad; plantar soft tissue; stereology;
structural properties
ID STEREOLOGICAL METHODS; VERTICAL SECTIONS; TISSUE-SECTIONS; SURFACE-AREA;
SPECIMENS; THICKNESS; HISTOLOGY; BIOLOGY; SKIN
AB Formaldehyde has long been the fixative of choice for histological examination of tissue. The use of alternatives to formaldehyde has grown, however, owing to the serious hazards associated with its use. Companies have striven to maintain the morphological characteristics of formaldehyde-fixed tissue when developing alternatives. Glyoxal-based fixatives now are among the most popular formaldehyde alternatives. Although there are many studies that compare staining quality and immunoreactivity, there have been no studies that quantify possible structural differences. Histomorphometric analysis commonly is used to evaluate diseased tissue. We compared fixation with formaldehyde and glyoxal with regard to the histomorphological properties of plantar foot tissue using a combination of stereological methods and quantitative morphology. We measured skin thickness, interdigitation index, elastic septa thickness, and adipocyte area and diameter. No significant differences were observed between formaldehyde and glyoxal fixation for any feature measured. The glyoxal-based fixative used therefore is a suitable fixative for structural evaluation of plantar soft tissue. Measurements obtained from the glyoxal-fixed tissue can be combined with data obtained from formalin-fixed for analysis.
C1 [Wang, Y. N.; Lee, K.; Pai, S.; Ledoux, W. R.] Univ Washington, VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Dept Vet Affairs, Seattle, WA 98195 USA.
[Wang, Y. N.] Univ Washington, Appl Phys Lab, Seattle, WA 98195 USA.
[Pai, S.; Ledoux, W. R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA.
[Ledoux, W. R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
RP Ledoux, WR (reprint author), VA Puget Sound, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA.
EM wrledoux@u.washington.edu
RI Ledoux, William/K-6815-2015
OI Ledoux, William/0000-0003-4982-7714
FU NIH [R01DK75633-03, P30DK017047]; Department of Veterans Affairs, RRD
Service [A4843C]
FX This study was supported by NIH grants R01DK75633-03 and P30DK017047 and
the Department of Veterans Affairs, RR&D Service grant A4843C.
NR 21
TC 4
Z9 5
U1 0
U2 9
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1052-0295
J9 BIOTECH HISTOCHEM
JI Biotech. Histochem.
PD OCT
PY 2011
VL 86
IS 5
BP 359
EP 365
DI 10.3109/10520295.2010.520275
PG 7
WC Biotechnology & Applied Microbiology; Cell Biology
SC Biotechnology & Applied Microbiology; Cell Biology
GA 818UT
UT WOS:000294782000009
PM 20854226
ER
PT J
AU Misra, D
Xie, WL
Regan, MM
Ross, RW
Lee, GS
Germain, D
Kantoff, PW
Oh, WK
AF Misra, Dipika
Xie, Wanling
Regan, Meredith M.
Ross, Robert W.
Lee, Gwo-shu
Germain, Doris
Kantoff, Philip W.
Oh, William K.
TI Germline CAG repeat length of the androgen receptor and time to
progression in patients with prostate cancer treated with androgen
deprivation therapy
SO BJU INTERNATIONAL
LA English
DT Article
DE androgen receptor; prostate cancer; androgen deprivation therapy;
polymorphisms
ID ENDOCRINE THERAPY; GENE; RISK; POLYMORPHISMS; ASSOCIATION; GLUTAMINE;
EFFICACY; MEN; AGE
AB OBJECTIVES
Germline CAG repeat polymorphisms in the androgen receptor (AR-CAG) have been shown to influence the activity of the AR.
The purpose of the present study was to determine if AR-CAG repeat length correlates with time to progression on androgen deprivation therapy (ADT).
PATIENTS AND METHODS
Germline AR-CAG repeat lengths were determined in a cohort of 480 patients with recurrent or metastatic prostate cancer treated at a single tertiary care institution and correlated to time to progression (TTP) and overall survival. RESULTS
There was no significant correlation between differences in the AR-CAG repeat lengths and TTP or overall survival in patients with prostate cancer receiving ADT.
AR-CAG repeat lengths did not significantly correlate with age, prostate-specific antigen (PSA), Gleason score or clinical stage at diagnosis.
In patients with metastatic disease, longer AR-CAG repeat lengths (>23 vs <= 23) were associated with a longer TTP on ADT, but this finding was of borderline significance (median TTP 18.3 vs 15.5 months, P = 0.09; adjusted HR = 0.76, 95% confidence interval = 0.54-1.09).
CONCLUSIONS
This is the largest published study to date investigating the association of germline AR-CAG repeat lengths and efficacy of ADT in prostate cancer.
Germline AR-CAG repeat lengths do not predict response to ADT.
C1 [Misra, Dipika; Germain, Doris; Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, New York, NY 10029 USA.
[Xie, Wanling; Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Ross, Robert W.; Lee, Gwo-shu; Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Oh, WK (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, 1 Gustave L Levy Pl,Box 1079, New York, NY 10029 USA.
EM william.oh@mssm.edu
RI Oh, William/B-9163-2012
OI Oh, William/0000-0001-5113-8147
NR 17
TC 6
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD OCT
PY 2011
VL 108
IS 7
BP 1086
EP 1091
DI 10.1111/j.1464-410X.2010.10037.x
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 819WS
UT WOS:000294865100010
PM 21410629
ER
PT J
AU McGinnis, SM
Brickhouse, M
Pascual, B
Dickerson, BC
AF McGinnis, Scott M.
Brickhouse, Michael
Pascual, Belen
Dickerson, Bradford C.
TI Age-Related Changes in the Thickness of Cortical Zones in Humans
SO BRAIN TOPOGRAPHY
LA English
DT Article
DE Magnetic resonance imaging; Morphometry; Cortex; Aging
ID HUMAN CEREBRAL-CORTEX; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS;
ALZHEIMERS-DISEASE; OLDER-ADULTS; HUMAN BRAIN; COGNITIVE CONTROL;
WHITE-MATTER; LIFE-SPAN; REGIONAL DIFFERENCES
AB Structural neuroimaging studies have demonstrated that all regions of the cortex are not affected equally by aging, with frontal regions appearing especially susceptible to atrophy. The "last in, first out" hypothesis posits that aging is, in a sense, the inverse of development: late-maturing regions of the brain are preferentially vulnerable to age-related loss of structural integrity. We tested this hypothesis by analyzing age-related changes in regional cortical thickness via three methods: (1) an exploratory linear regression of cortical thickness and age across the entire cortical mantle (2) an analysis of age-related differences in the thickness of zones of cortex defined by functional/cytoarchitectural affiliation (including primary sensory/motor, unimodal association, heteromodal association, and paralimbic zones), and (3) an analysis of age-related differences in the thickness of regions of cortex defined by surface area expansion in the period between birth and early adulthood. Subjects were grouped as young (aged 18-29, n = 138), middle-aged (aged 30-59, n = 80), young-old (aged 60-79, n = 60), and old-old (aged 80+, n = 38). Thinning of the cortex between young and middle-aged adults was greatest in heteromodal association cortex and regions of high postnatal surface area expansion. In contrast, thinning in old-old age was greatest in primary sensory/motor cortices and regions of low postnatal surface area expansion. In sum, these results lead us to propose a sequential "developmental-sensory" model of aging, in which developmental factors influence cortical vulnerability relatively early in the aging process, whereas later-in more advanced stages of aging-factors specific to primary sensory and motor cortices confer vulnerability. This model offers explicitly testable hypotheses and suggests the possibility that normal aging may potentially allow for multiple opportunities for intervention to promote the structural integrity of the cerebral cortex.
C1 [McGinnis, Scott M.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA.
[McGinnis, Scott M.; Brickhouse, Michael; Pascual, Belen; Dickerson, Bradford C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Frontotemporal Dementia Unit, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
[McGinnis, Scott M.; Dickerson, Bradford C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Athinoula A Martinos Ctr Biomed Imagi, Boston, MA USA.
[McGinnis, Scott M.; Dickerson, Bradford C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Massachusetts Alzheimers Dis Res Ctr, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
[Brickhouse, Michael; Dickerson, Bradford C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Athinoula A Martinos Ctr Biomed Ima, Boston, MA USA.
RP McGinnis, SM (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, 221 Longwood Ave, Boston, MA 02115 USA.
EM smmcginnis@partners.org
FU NIA [R01-AG29411, R21-AG29840, P50-AG005134]; NCRR [P41-RR14075,
U24-RR021382]; Harvard NeuroDiscovery Center; Alzheimer's Association
FX This study was supported by grants from the NIA R01-AG29411,
R21-AG29840, P50-AG005134, and NCRR P41-RR14075, U24-RR021382, Harvard
NeuroDiscovery Center, and the Alzheimer's Association.
NR 88
TC 32
Z9 32
U1 1
U2 17
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0896-0267
J9 BRAIN TOPOGR
JI Brain Topogr.
PD OCT
PY 2011
VL 24
IS 3-4
SI SI
BP 279
EP 291
DI 10.1007/s10548-011-0198-6
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 819HC
UT WOS:000294815000012
PM 21842406
ER
PT J
AU Pascual-Leone, A
Freitas, C
Oberman, L
Horvath, JC
Halko, M
Eldaief, M
Bashir, S
Vernet, M
Shafi, M
Westover, B
Vahabzadeh-Hagh, AM
Rotenberg, A
AF Pascual-Leone, Alvaro
Freitas, Catarina
Oberman, Lindsay
Horvath, Jared C.
Halko, Mark
Eldaief, Mark
Bashir, Shahid
Vernet, Marine
Shafi, Mouhshin
Westover, Brandon
Vahabzadeh-Hagh, Andrew M.
Rotenberg, Alexander
TI Characterizing Brain Cortical Plasticity and Network Dynamics Across the
Age-Span in Health and Disease with TMS-EEG and TMS-fMRI
SO BRAIN TOPOGRAPHY
LA English
DT Article
DE Cortical brain plasticity; Transcranial magnetic stimulation;
Electroencephalography; Functional magnetic resonance imaging; Lifespan
ID TRANSCRANIAL MAGNETIC STIMULATION; THETA-BURST-STIMULATION; COGNITIVE
RESERVE HYPOTHESIS; NEUROTROPHIC FACTOR GENE; LONG-TERM POTENTIATION;
HUMAN MOTOR CORTEX; BDNF VAL66MET POLYMORPHISM; GRAPH-THEORETICAL
ANALYSIS; TEMPORAL-LOBE EPILEPSY; ALZHEIMERS-DISEASE
AB Brain plasticity can be conceptualized as nature's invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable 'starting-points' and different 'slopes of change' defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer's disease.
C1 [Pascual-Leone, Alvaro; Freitas, Catarina; Oberman, Lindsay; Horvath, Jared C.; Halko, Mark; Eldaief, Mark; Bashir, Shahid; Vernet, Marine; Shafi, Mouhshin; Westover, Brandon; Vahabzadeh-Hagh, Andrew M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Div Cognit Neurol,Dept Neurol,Med Sch, Boston, MA 02215 USA.
[Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Inst Univ Neurorehabil Guttmann, E-08193 Barcelona, Spain.
[Shafi, Mouhshin; Westover, Brandon] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Partners Neurol Program, Boston, MA 02215 USA.
[Vahabzadeh-Hagh, Andrew M.; Rotenberg, Alexander] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
RP Pascual-Leone, A (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Div Cognit Neurol,Dept Neurol,Med Sch, 330 Brookline Ave, Boston, MA 02215 USA.
EM apleone@bidmc.harvard.edu
RI Bashir, Shahid/E-7212-2014; Halko, Mark/G-8633-2016
OI Halko, Mark/0000-0002-7427-0789
FU National Center for Research Resources: Harvard-Thorndike General
Clinical Research Center at BIDMC [NCRR MO1 RR01032]; Harvard Clinical
and Translational Science Center [UL1 RR025758]; NIH [K24 RR018875,
F32MH080493, 1KL2RR025757-01]; Center for Integration of Medicine and
Innovative Technology (CIMIT); Foundation for Science and Technology,
Portugal [SFRH/BPD/66846/2009]; European Social Fund; Neuronix; Nexstim
FX Work on this study was supported by grants from the National Center for
Research Resources: Harvard-Thorndike General Clinical Research Center
at BIDMC (NCRR MO1 RR01032) and Harvard Clinical and Translational
Science Center (UL1 RR025758), NIH grant K24 RR018875, Center for
Integration of Medicine and Innovative Technology (CIMIT), Neuronix and
Nexstim to APL. CF was supported by a post-doctoral grant from the
Foundation for Science and Technology, Portugal (SFRH/BPD/66846/2009),
co-funded by the European Social Fund. LO was supported by NIH
fellowship F32MH080493 and 1KL2RR025757-01. APL serves on the scientific
advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Allied
Mind, Neosync, and Novavision, and is an inventor on patents and patent
applications related to noninvasive brain stimulation and the real-time
integration of transcranial magnetic stimulation with
electroencephalography and magnetic resonance imaging.
NR 136
TC 83
Z9 88
U1 5
U2 58
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0896-0267
EI 1573-6792
J9 BRAIN TOPOGR
JI Brain Topogr.
PD OCT
PY 2011
VL 24
IS 3-4
SI SI
BP 302
EP 315
DI 10.1007/s10548-011-0196-8
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 819HC
UT WOS:000294815000014
PM 21842407
ER
PT J
AU Smeets, A
Daemen, A
Vanden Bempt, I
Gevaert, O
Claes, B
Wildiers, H
Drijkoningen, R
Van Hummelen, P
Lambrechts, D
De Moor, B
Neven, P
Sotiriou, C
Vandorpe, T
Paridaens, R
Christiaens, MR
AF Smeets, A.
Daemen, A.
Vanden Bempt, I.
Gevaert, O.
Claes, B.
Wildiers, H.
Drijkoningen, R.
Van Hummelen, P.
Lambrechts, D.
De Moor, B.
Neven, P.
Sotiriou, C.
Vandorpe, T.
Paridaens, R.
Christiaens, M. R.
TI Prediction of lymph node involvement in breast cancer from primary tumor
tissue using gene expression profiling and miRNAs
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Microarrays; miRNA; Lymph node; Prediction
ID GROWTH-FACTOR RECEPTOR-1; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER;
METASTASIS; PROGRESSION; MICROARRAY; CELLS; CLASSIFIERS; SURVIVAL;
MARKERS
AB The aim of this study was to investigate whether lymph node involvement in breast cancer is influenced by gene or miRNA expression of the primary tumor. For this purpose, we selected a very homogeneous patient population to minimize heterogeneity in other tumor and patient characteristics. First, we compared gene expression profiles of primary tumor tissue from a group of 96 breast cancer patients balanced for lymph node involvement using Affymetrix Human U133 Plus 2.0 microarray chip. A model was built by weighted Least-Squares Support Vector Machines and validated on an internal and external dataset. Next, miRNA profiling was performed on a subset of 82 tumors using Human MiRNA-microarray chips (Illumina). Finally, for each miRNA the number of significant inverse correlated targets was determined and compared with 1000 sets of randomly chosen targets. A model based on 241 genes was built (AUC 0.66). The AUC for the internal dataset was 0.646 and 0. 651 for the external datasets. The model includes multiple kinases, apoptosis-related, and zinc ion-binding genes. Integration of the microarray and miRNA data reveals ten miRNAs suppressing lymph node invasion and one miRNA promoting lymph node invasion. Our results provide evidence that measurable differences in gene and miRNA expression exist between node negative and node positive patients and thus that lymph node involvement is not a genetically random process. Moreover, our data suggest a general deregulation of the miRNA machinery that is potentially responsible for lymph node invasion.
C1 [Smeets, A.; Wildiers, H.; Neven, P.; Vandorpe, T.; Paridaens, R.; Christiaens, M. R.] Multidisciplinary Breast Ctr Univ Hosp, B-3000 Louvain, Belgium.
[Daemen, A.; Gevaert, O.; De Moor, B.] Univ Leuven, Dept Elect Engn, Louvain, Belgium.
[Vanden Bempt, I.] Univ Antwerp, Dept Microbiol, B-2020 Antwerp, Belgium.
[Gevaert, O.] Stanford Univ, Dept Radiol, Sch Med, Stanford, CA 94305 USA.
[Claes, B.; Lambrechts, D.] VIB, Vesalius Res Ctr, Louvain, Belgium.
[Drijkoningen, R.] Jessa Hosp, Dept Pathol, Hasselt, Belgium.
[Van Hummelen, P.] Dana Farber Canc Inst, Ctr Canc Genome Discovery CCGD, Boston, MA 02115 USA.
[Sotiriou, C.] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium.
RP Smeets, A (reprint author), Multidisciplinary Breast Ctr Univ Hosp, Herestr 49, B-3000 Louvain, Belgium.
EM ann.smeets@uzleuven.be
RI Verdrengh, Evelien/H-4571-2012;
OI Gevaert, Olivier/0000-0002-9965-5466
FU Research Foundation Flanders (FWO); Pfizer Oncology
FX AS is supported by a grant from Research Foundation Flanders (FWO) and
Pfizer Oncology.
NR 50
TC 16
Z9 17
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD OCT
PY 2011
VL 129
IS 3
BP 767
EP 776
DI 10.1007/s10549-010-1265-5
PG 10
WC Oncology
SC Oncology
GA 817NK
UT WOS:000294680600010
PM 21116709
ER
PT J
AU Thomenius, M
Freel, CD
Horn, S
Krieser, R
Abdelwahid, E
Cannon, R
Balasundaram, S
White, K
Kornbluth, S
AF Thomenius, M.
Freel, C. D.
Horn, S.
Krieser, R.
Abdelwahid, E.
Cannon, R.
Balasundaram, S.
White, K.
Kornbluth, S.
TI Mitochondrial fusion is regulated by Reaper to modulate Drosophila
programmed cell death
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE apoptosis; Drosophila; mitochondria; reaper; mitofusins; dMFN
ID STRESS-INDUCED APOPTOSIS; CYTOCHROME-C; CASPASE ACTIVATION;
MAMMALIAN-CELLS; IAP DEGRADATION; PROTEINS; FISSION; PATHWAY; DOMAIN;
BAX
AB In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or gamma-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die. Cell Death and Differentiation (2011) 18, 1640-1650; doi:10.1038/cdd.2011.26; published online 8 April 2011
C1 [Thomenius, M.; Freel, C. D.; Horn, S.; Kornbluth, S.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Krieser, R.; Abdelwahid, E.; Cannon, R.; Balasundaram, S.; White, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
RP Kornbluth, S (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
EM kornb001@mc.duke.edu
RI White, Kristin/D-7936-2013
FU NIH [RO1 GM080333, GM55568, GM55568-S1]; MGH Fund for Medical Discovery
FX This work was funded by NIH grants RO1 GM080333 (SK), GM55568 (KW), a
supplement for collaborative research GM55568-S1 (KW and SAK), and an
MGH Fund for Medical Discovery (EA).
NR 40
TC 17
Z9 17
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD OCT
PY 2011
VL 18
IS 10
BP 1640
EP 1650
DI 10.1038/cdd.2011.26
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 818ND
UT WOS:000294757800011
PM 21475305
ER
PT J
AU Eschler, DC
Hasham, A
Tomer, Y
AF Eschler, Deirdre Cocks
Hasham, Alia
Tomer, Yaron
TI Cutting Edge: The Etiology of Autoimmune Thyroid Diseases
SO CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
LA English
DT Review
DE Thyroid genetics; Autoimmune thyroid disorders epigenetics
ID SINGLE-NUCLEOTIDE POLYMORPHISM; CHRONIC HEPATITIS-C; II PEPTIDE-BINDING;
GRAVES-DISEASE; INTERFERON-ALPHA; GENETIC SUSCEPTIBILITY; CD40 GENE;
THYROGLOBULIN; AMIODARONE; EPIDEMIOLOGY
AB Significant progress has been made in our understanding of the mechanisms leading to autoimmune thyroid diseases (AITD). For the first time, we are beginning to unravel these mechanisms at the molecular level. AITD, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune diseases affecting the thyroid. They have a complex etiology that involves genetic and environmental influences. Seven genes have been shown to contribute to the etiology of AITD. The first AITD gene discovered, HLA-DR3, is associated with both GD and HT. More recently, this association was dissected at the molecular level when it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide binding pocket is the specific sequence change causing AITD. Non-MHC genes that confer susceptibility to AITD can be classified into two groups: (1) immune-regulatory genes (e.g., CD40, CTLA-4, and PTPN22); (2) thyroid-specific genes-thyroglobulin and TSH receptor genes. These genes interact with environmental factors, such as infection, likely through epigenetic mechanisms to trigger disease. In this review, we summarize the latest findings on disease susceptibility and modulation by environmental factors.
C1 [Eschler, Deirdre Cocks; Hasham, Alia; Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA.
[Tomer, Yaron] James J Peters VA Med Ctr, New York, NY 10029 USA.
RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, 1 Gustave L Levy Pl,Box 1118, New York, NY 10029 USA.
EM Yaron.Tomer@mssm.edu
FU NIDDK [DK061659, DK067555, DK073681]
FX This work was supported in part by grants DK061659, DK067555, and
DK073681 from NIDDK.
NR 63
TC 30
Z9 32
U1 2
U2 27
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1080-0549
J9 CLIN REV ALLERG IMMU
JI Clin. Rev. Allergy Immunol.
PD OCT
PY 2011
VL 41
IS 2
BP 190
EP 197
DI 10.1007/s12016-010-8245-8
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 819KB
UT WOS:000294822700008
PM 21234711
ER
PT J
AU Quesnel, AM
McKenna, MJ
AF Quesnel, Alicia M.
McKenna, Michael J.
TI Current strategies in management of intracanalicular vestibular
schwannoma
SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY
LA English
DT Article
DE acoustic neuroma; intracanalicular; management; vestibular schwannoma
ID ACOUSTIC NEUROMA SURGERY; TERM HEARING PRESERVATION; GAMMA-KNIFE
RADIOSURGERY; QUALITY-OF-LIFE; FACIAL-NERVE FUNCTION; MIDDLE FOSSA
APPROACH; STEREOTACTIC RADIOSURGERY; RETROSIGMOID APPROACH; CLINICAL
ARTICLE; CONSERVATIVE MANAGEMENT
AB Purpose of review
The current practitioner is more often managing intracanalicular vestibular schwannomas than in the past, as improved imaging and heightened awareness leads to earlier diagnosis of these tumors. The role of observation, microsurgery, and radiation treatment in the management of intracanalicular tumors continues to evolve. The goal of this article is to evaluate and summarize recent literature pertaining to the management of intracanalicular vestibular schwannomas.
Recent findings
Watchful waiting is an important management option for patients with minimal symptoms. The literature on the natural history of small vestibular schwannomas continues to expand, with particular emphasis on the expected hearing outcomes. Microsurgical techniques also focus on hearing preservation. Presence of fundal fluid and good or normal hearing preoperatively are positive predictors of hearing preservation after surgery. Long-term follow-up after radiation therapy for vestibular schwannomas continues to demonstrate excellent tumor control rates, although hearing preservation rates are modest.
Summary
Multiple factors, including status of hearing, presence of vestibular symptoms, patient age, medical comorbidities, institutional outcomes, and patient preferences, help determine the management strategy for patients with an intracanalicular vestibular schwannoma.
C1 [Quesnel, Alicia M.; McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Quesnel, Alicia M.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM michael_mckenna@meei.harvard.edu
NR 62
TC 10
Z9 11
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1068-9508
EI 1531-6998
J9 CURR OPIN OTOLARYNGO
JI Curr. Opin. Otolaryngol. Head Neck Surg.
PD OCT
PY 2011
VL 19
IS 5
BP 335
EP 340
DI 10.1097/MOO.0b013e32834a3fa7
PG 6
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 817MQ
UT WOS:000294678100003
PM 22552696
ER
PT J
AU Majithia, AR
Jablonski, KA
McAteer, JB
Mather, KJ
Goldberg, RB
Kahn, SE
Florez, JC
AF Majithia, A. R.
Jablonski, K. A.
McAteer, J. B.
Mather, K. J.
Goldberg, R. B.
Kahn, S. E.
Florez, J. C.
CA DPP Res Grp
TI Association of the SLC30A8 missense polymorphism R325W with proinsulin
levels at baseline and after lifestyle, metformin or troglitazone
intervention in the Diabetes Prevention Program
SO DIABETOLOGIA
LA English
DT Article
DE Diabetes Prevention Program; Genetic association; Proinsulin; Single
nucleotide polymorphisms; SLC30A8; Zinc transporter
ID GENOME-WIDE ASSOCIATION; INSULIN-RELEASE; TYPE-2; PREDICT; VARIANT; LOCI
AB Individuals with impaired glucose tolerance have increased proinsulin levels, despite normal glucose or C-peptide levels. In the Diabetes Prevention Program (DPP), increased proinsulin levels predicted type 2 diabetes and proinsulin levels were significantly reduced following treatment with metformin, lifestyle modification or troglitazone compared with placebo. Genetic and physiological studies suggest a role for the zinc transporter gene SLC30A8 in diabetes risk, possibly through effects on insulin-processing in beta cells. We hypothesised that the risk allele at the type 2 diabetes-associated missense polymorphism rs13266634 (R325W) in SLC30A8 would predict proinsulin levels in individuals at risk of type 2 diabetes and may modulate response to preventive interventions.
We genotyped rs13266634 in 3,007 DPP participants and examined its association with fasting proinsulin and fasting insulin at baseline and at 1 year post-intervention.
We found that increasing dosage of the C risk allele at SLC30A8 rs13266634 was significantly associated with higher proinsulin levels at baseline (p = 0.002) after adjustment for baseline insulin. This supports the hypothesis that risk alleles at SLC30A8 mark individuals with insulin-processing defects. At the 1 year analysis, proinsulin levels decreased significantly in all groups receiving active intervention and were no longer associated with SLC30A8 genotype (p = 0.86) after adjustment for insulin at baseline and 1 year. We found no genotype x treatment interactions at 1 year.
In prediabetic individuals, genotype at SLC30A8 predicts baseline proinsulin levels independently of insulin levels, but does not predict proinsulin levels after amelioration of insulin sensitivity at 1 year.
C1 [Florez, J. C.] George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA.
[Majithia, A. R.; McAteer, J. B.; Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Majithia, A. R.; McAteer, J. B.; Florez, J. C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Majithia, A. R.; McAteer, J. B.; Florez, J. C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Majithia, A. R.; Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Goldberg, R. B.] Univ Miami, Leonard M Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL USA.
[Kahn, S. E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA.
[Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA.
RP Florez, JC (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA.
EM dppmail@biostat.bsc.gwu.edu
OI Kahn, Steven/0000-0001-7307-9002
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health; NIDDK; Indian Health Service;
Office of Research on Minority Health; National Institute of Child
Health and Human Development; National Institute on Aging; Office of
Research on Women's Health; Centers for Disease Control and Prevention;
American Diabetes Association; Department of Veterans Affairs;
Massachusetts General Hospital; Doris Duke Charitable Foundation; [R01
DK072041]
FX The investigators gratefully acknowledge the commitment and dedication
of the participants of the DPP. The National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) of the National Institutes of
Health provided funding to the clinical centres and the Coordinating
Center for the design and conduct of the study, and for collection,
management, analysis and interpretation of the data. The Southwestern
American Indian Centers were supported directly by the NIDDK and the
Indian Health Service. The General Clinical Research Center Program,
National Center for Research Resources and the Department of Veterans
Affairs supported data collection at many of the clinical centres.
Funding for data collection and participant support was also provided by
the Office of Research on Minority Health, the National Institute of
Child Health and Human Development, the National Institute on Aging, the
Office of Research on Women's Health, the Centers for Disease Control
and Prevention and the American Diabetes Association. Bristol-Myers
Squibb and Parke-Davis provided medication. This research was also
supported, in part, by the intramural research programme of the NIDDK.
LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed
Care, Merck, Nike Sports Marketing, Slim Fast Foods and Quaker Oats
donated materials, equipment or medicines for concomitant conditions.
McKesson BioServices, Matthews Media Group and the Henry M. Jackson
Foundation provided support services under subcontract with the
Coordinating Center. The opinions expressed are those of the
investigators and do not necessarily reflect the views of the Indian
Health Service or other funding agencies. A complete list of centres,
investigators and staff can be found in the ESM. This work was supported
in part by R01 DK072041 to J. C. Florez and K. A. Jablonski. S. E. Kahn
is supported in part by the Department of Veterans Affairs. J. C. Florez
is supported by a Physician Scientist Development Award by the
Massachusetts General Hospital and a Clinical Scientist Development
Award from the Doris Duke Charitable Foundation. We also thank the late
A. F. Moore for his intellectual contribution to the genesis of this
project.
NR 10
TC 12
Z9 14
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD OCT
PY 2011
VL 54
IS 10
BP 2570
EP 2574
DI 10.1007/s00125-011-2234-1
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 817OF
UT WOS:000294683000013
PM 21779873
ER
PT J
AU Martinez, HG
Quinones, MP
Jimenez, F
Estrada, CA
Clark, K
Muscogiuri, G
Sorice, G
Musi, N
Reddick, RL
Ahuja, SS
AF Martinez, H. G.
Quinones, M. P.
Jimenez, F.
Estrada, C. A.
Clark, K.
Muscogiuri, G.
Sorice, G.
Musi, N.
Reddick, R. L.
Ahuja, S. S.
TI Critical role of chemokine (C-C motif) receptor 2 (CCR2) in the KKAy (+)
Apoe (-/-) mouse model of the metabolic syndrome
SO DIABETOLOGIA
LA English
DT Article
DE Animal-mouse; Basic science; Cardiac complications; Experimental
immunology; KO mice; Metabolic syndrome; Nephropathy
ID GLYCOGEN-SYNTHASE KINASE-3; TYPE-2 DIABETES-MELLITUS;
INSULIN-RESISTANCE; APOLIPOPROTEIN-E; HEPATIC STEATOSIS;
SKELETAL-MUSCLE; DENDRITIC CELLS; ADIPOSE-TISSUE; KNOCKOUT MICE;
HIGH-FAT
AB Chemokines and their receptors such as chemokine (C-C motif) receptor 2 (CCR2) may contribute to the pathogenesis of the metabolic syndrome via their effects on inflammatory monocytes. Increased accumulation of CCR2-driven inflammatory monocytes in epididymal fat pads is thought to favour the development of insulin resistance. Ultimately, the resulting hyperglycaemia and dyslipidaemia contribute to development of the metabolic syndrome complications such as cardiovascular disease and diabetic nephropathy. Our goal was to elucidate the role of CCR2 and inflammatory monocytes in a mouse model that resembles the human metabolic syndrome.
We generated a model of the metabolic syndrome by backcrossing KKAy (+) with Apoe (-/-) mice (KKAy (+) Apoe (-/-) ) and studied the role of CCR2 in this model system.
KKAy (+) Apoe (-/-) mice were characterised by the presence of obesity, insulin resistance, dyslipidaemia and increased systemic inflammation. This model also manifested two complications of the metabolic syndrome: atherosclerosis and diabetic nephropathy. Inactivation of Ccr2 in KKAy (+) Apoe (-/-) mice protected against the metabolic syndrome, as well as atherosclerosis and diabetic nephropathy. This protective phenotype was associated with a reduced number of inflammatory monocytes in the liver and muscle, but not in the epididymal fat pads; circulating levels of adipokines such as leptin, resistin and adiponectin were also not reduced. Interestingly, the proportion of inflammatory monocytes in the liver, pancreas and muscle, but not in the epididymal fat pads, correlated significantly with peripheral glucose levels.
CCR2-driven inflammatory monocyte accumulation in the liver and muscle may be a critical pathogenic factor in the development of the metabolic syndrome.
C1 [Martinez, H. G.; Jimenez, F.; Estrada, C. A.; Clark, K.; Muscogiuri, G.; Sorice, G.; Musi, N.; Ahuja, S. S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC 7870, San Antonio, TX 78229 USA.
[Martinez, H. G.; Jimenez, F.; Ahuja, S. S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA.
[Quinones, M. P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Reddick, R. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
RP Ahuja, SS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med MC 7870, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM ahuja@uthscsa.edu
FU Fraternal Order of Eagles; Veterans' Administration Merit Award; NIH
[RO1 AR 052755]
FX We thank Y. Patel (Department of Pathology, UTHSCSA) for help with HPLC
measurement of creatinine. This work was supported by grants from
Fraternal Order of Eagles, a Veterans' Administration Merit Award, and
NIH RO1 AR 052755 to S. S. Ahuja.
NR 40
TC 8
Z9 8
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD OCT
PY 2011
VL 54
IS 10
BP 2660
EP 2668
DI 10.1007/s00125-011-2248-8
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 817OF
UT WOS:000294683000022
PM 21779871
ER
PT J
AU Patard, JJ
Pignot, G
Escudier, B
Eisen, T
Bex, A
Sternberg, C
Rini, B
Roigas, J
Choueiri, T
Bukowski, R
Motzer, R
Kirkali, Z
Mulders, P
Bellmunt, J
AF Patard, Jean-Jacques
Pignot, Geraldine
Escudier, Bernard
Eisen, Tim
Bex, Axel
Sternberg, Cora
Rini, Brian
Roigas, Jan
Choueiri, Toni
Bukowski, Ronald
Motzer, Robert
Kirkali, Ziya
Mulders, Peter
Bellmunt, Joaquim
TI ICUD-EAU International Consultation on Kidney Cancer 2010: Treatment of
Metastatic Disease
SO EUROPEAN UROLOGY
LA English
DT Review
DE Renal cell carcinoma; First-line; Second-line; Treatment algorithms;
VEGF-targeted therapy; mTOR inhibitors
ID RENAL-CELL CARCINOMA; PHASE-III TRIAL; SORAFENIB PLUS
INTERFERON-ALPHA-2B; COMBINATION TARGETED THERAPY; PULMONARY RESECTION;
PROGNOSTIC-FACTORS; ANTITUMOR-ACTIVITY; DOUBLE-BLIND; BEVACIZUMAB;
SUNITINIB
AB Context: Until the development of novel targeted agents directed against angiogenesis and tumour growth, few treatment options have been available for the treatment of metastatic renal-cell carcinoma (mRCC).
Objective: This review discusses current targeted therapies for mRCC and provides consensus statements regarding treatment algorithms.
Evidence acquisition: Medical literature was retrieved from PubMed up to April 2011. Additional relevant articles and abstract reviews were included from the bibliographies of the retrieved literature.
Evidence synthesis: Targeted treatment for mRCC can be categorized for the following patient groups: previously untreated patients, those refractory to immunotherapy, and those refractory to vascular endothelial growth factor (VEGF)-targeted therapy. Sunitinib and bevacizumab combined with interferon alpha are generally considered first-line treatment options in patients with favourable or intermediate prognoses. Temsirolimus is considered a first-line treatment option for poor-risk patients. Either sorafenib or sunitinib may be valid second-line treatments for patients who have failed prior cytokine-based therapies. For patients refractory to treatment with VEGF-targeted therapy, everolimus is now recommended. Pazopanib is a new treatment option in the first-and second-line setting (after cytokine failure). Sequential and combination approaches, and the roles of nephrectomy and tumour metastasectomy will also be discussed.
Conclusions: Increasing clinical evidence is clarifying appropriate first-and second-line treatments with targeted agents for patients with mRCC. Based on phase 2 and 3 trials, a sequential approach is most promising, while combination therapy is still investigational. The role of nephrectomy in mRCC is being evaluated in ongoing phase 3 clinical trials. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Patard, Jean-Jacques] Univ Paris 11, Bicetre Hosp, Dept Urol, Le Kremlin Bicetre, France.
[Pignot, Geraldine] Univ Paris 05, Cochin Hosp, Dept Urol, Paris, France.
[Escudier, Bernard] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France.
[Eisen, Tim] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge CB2 2QQ, England.
[Bex, Axel] Netherlands Canc Inst, Div Surg Oncol, Dept Urol, Amsterdam, Netherlands.
[Sternberg, Cora] San Camillo Forlanini Hosp, Dept Med Oncol, Rome, Italy.
[Rini, Brian; Bukowski, Ronald] Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA.
[Roigas, Jan] Univ Hosp Charite, Dept Urol, Berlin, Germany.
[Choueiri, Toni] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA.
[Motzer, Robert] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA.
[Kirkali, Ziya] Dokuz Eylul Univ, Sch Med, Izmir, Turkey.
[Mulders, Peter] Univ Med Ctr Nijmegen, St Radboud, Netherlands.
[Bellmunt, Joaquim] Univ Hosp del Mar, Med Oncol Serv, Barcelona 08003, Spain.
RP Patard, JJ (reprint author), Univ Paris 11, Bicetre Hosp, Dept Urol, Le Kremlin Bicetre, France.
EM jean-jacques.patard@live.fr; jbellmunt@parcdesalutmar.cat
RI Mulders, Peter/H-8076-2014
NR 50
TC 46
Z9 47
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD OCT
PY 2011
VL 60
IS 4
BP 684
EP 690
DI 10.1016/j.eururo.2011.06.017
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 812OZ
UT WOS:000294304100015
PM 21704448
ER
PT J
AU Purwaha, P
Gu, Y
Kelavkar, U
Kang, JX
Law, B
Wu, EX
Qian, SY
AF Purwaha, Preeti
Gu, Yan
Kelavkar, Uddhav
Kang, Jing X.
Law, Benedict
Wu, Erxi
Qian, Steven Y.
TI LC/ESR/MS study of pH-dependent radical generation from 15-LOX-catalyzed
DPA peroxidation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE ESR spin trapping; DPA-derived radicals; 15-LOX-catalyzed peroxidation;
PC-3-15LOS cellular peroxidation; LC/ESR; LC/MS; LC/MS(2); Free radicals
ID CARBON-CENTERED RADICALS; POLYUNSATURATED FATTY-ACIDS;
LIPOXYGENASE-CATALYZED PEROXIDATION; DOCOSAPENTAENOIC ACID;
EICOSAPENTAENOIC ACID; COLORECTAL-CANCER; TANDEM MS; IN-VITRO;
15-LIPOXYGENASE-1; N-3
AB Docosapentaenoic acid (DPA) is a unique fatty acid that exists in two isomeric forms (n-3 and n-6), which differ in their physiological behaviors. DPA can undergo free radical-mediated peroxidation via lipoxygenase (LOX). 15-LOX, one of the LOX isomers, has received much attention in cancer research because of its very different expression level in normal tissues compared to tumors and some bioactive fatty acid metabolites modulating the tumorigenic pathways in cancer. However, the mechanism linking 15-LOX, DPA metabolites, and their bioactivities is still unclear, and the free radicals generated in DPA peroxidation have never been characterized. In this study, we have studied radicals formed from both soybean and human cellular (PC3-15LOS cells) 15-LOX-catalyzed peroxidation of DPAs at various pH's using a combination of LC/ESR/MS with the spin trapping technique. We observed a total of three carbon-centered radicals formed in 15-LOX-DPA (n-3) stemming from its 7-, 17-, and 20-hydroperoxides, whereas only one formed from 17-hydroperoxide in DPA (n-6). A change in the reaction pH from 8.5 (15-LOX enzyme optimum) to 7.4 (physiological) and to 6.5 (tumor, acidic) not only decreased the total radical formation but also altered the preferred site of oxygenation. This pH-dependent alteration of radical formation and oxygenation pattern may have significant implications and provide a basis for our ongoing investigations of LOXs as well as fatty acids in cancer biology. Published by Elsevier Inc.
C1 [Purwaha, Preeti; Gu, Yan; Law, Benedict; Wu, Erxi; Qian, Steven Y.] N Dakota State Univ, Dept Pharmaceut Sci, Coll Pharm Nursing & Allied Sci, Fargo, ND 58105 USA.
[Kelavkar, Uddhav] Mem Hlth Univ Med Ctr, Dept Lab Oncol, Savannah, GA 31404 USA.
[Kelavkar, Uddhav] Mercer Univ, Sch Med, Div Basic Med Sci, Savannah, GA 31404 USA.
[Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA.
[Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Qian, SY (reprint author), N Dakota State Univ, Dept Pharmaceut Sci, Coll Pharm Nursing & Allied Sci, Fargo, ND 58105 USA.
EM steven.qian@ndsu.edu
FU NIH [K22ES-012978, R15CA140833, P20 RR015566, P20 RR020151]
FX This work was supported by NIH Grants K22ES-012978, R15CA140833, and P20
RR015566 (S.Q.) and P20 RR020151 (E.W.).
NR 31
TC 6
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD OCT 1
PY 2011
VL 51
IS 7
BP 1461
EP 1470
DI 10.1016/j.freeradbiomed.2011.07.001
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 818GV
UT WOS:000294740700019
PM 21807091
ER
PT J
AU Halpern, SD
Kohn, R
Dornbrand-Lo, A
Metkus, T
Asch, DA
Volpp, KG
AF Halpern, Scott D.
Kohn, Rachel
Dornbrand-Lo, Aaron
Metkus, Thomas
Asch, David A.
Volpp, Kevin G.
TI Lottery-Based versus Fixed Incentives to Increase Clinicians' Response
to Surveys
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Incentives; response rate; surveys; lottery; behavioral economics
ID RANDOMIZED-TRIAL; MAIL SURVEYS; PHYSICIAN RESPONSE; COST-EFFECTIVENESS;
RATES; CASH; QUESTIONNAIRES; 5-DOLLAR; PAY
AB Objective. To compare the effects of lottery-based and fixed incentives on clinicians' response to surveys.
Data Sources. Three randomized trials with fixed payments and actuarially equivalent lotteries.
Study Design. Trial 1 compared a low-probability/high-payout lottery, a high-probability/low-payout lottery, and no incentive. Trial 2 compared a moderate-probability/moderate-payout lottery with an unconditional fixed payment (payment sent with questionnaire). Trial 3 compared a moderate-probability/moderate-payout lottery with a conditional fixed payment (payment promised following response).
Principal Findings. Neither the low-probability nor high-probability lotteries improved response compared with no incentive. Unconditional fixed payments produced significantly greater response than actuarially equivalent lotteries, but conditional fixed payments did not.
Conclusions. Lottery-based incentives do not improve clinicians' response rates compared with no incentives, and they are inferior to unconditional fixed payments.
C1 [Halpern, Scott D.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Halpern, Scott D.; Asch, David A.; Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Halpern, Scott D.; Dornbrand-Lo, Aaron; Asch, David A.; Volpp, Kevin G.] Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA.
[Halpern, Scott D.; Kohn, Rachel; Asch, David A.] Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA.
[Metkus, Thomas] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Asch, David A.; Volpp, Kevin G.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Halpern, SD (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 723 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM shalpern@exchange.upenn.edu
OI Asch, David/0000-0002-7970-286X
FU Greenwall Foundation; Leonard Davis Institute of Health Economics Center
for Health Incentives; University of Pennsylvania
FX Incentives used in this study came from funds provided by a Greenwall
Foundation Faculty Scholar Award in Bioethics (SDH), the Leonard Davis
Institute of Health Economics Center for Health Incentives (KGV), and
the University of Pennsylvania Medical Education Research Fund (SDH).
None of these sponsors were involved in the preparation of the
manuscript or in the decision to submit the manuscript for publication.
NR 27
TC 13
Z9 13
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0017-9124
J9 HEALTH SERV RES
JI Health Serv. Res.
PD OCT
PY 2011
VL 46
IS 5
BP 1663
EP 1674
DI 10.1111/j.1475-6773.2011.01264.x
PG 12
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 818GN
UT WOS:000294739800018
PM 21492159
ER
PT J
AU Weiner, RB
Hutter, AM
Wang, F
Kim, JH
Wood, MJ
Wang, TJ
Picard, MH
Baggish, AL
AF Weiner, Rory B.
Hutter, Adolph M.
Wang, Francis
Kim, Jonathan H.
Wood, Malissa J.
Wang, Thomas J.
Picard, Michael H.
Baggish, Aaron L.
TI Performance of the 2010 European Society of Cardiology criteria for ECG
interpretation in athletes
SO HEART
LA English
DT Article
ID SUDDEN CARDIAC DEATH; HYPERTROPHIC CARDIOMYOPATHY; LAUSANNE
RECOMMENDATIONS; CARDIOVASCULAR-DISEASE; PERICARDIAL DISEASES; EXERCISE
PHYSIOLOGY; OF-CARDIOLOGY; WORKING GROUP; ELECTROCARDIOGRAPHY;
REHABILITATION
AB Background The European Society of Cardiology (ESC) recently published revised criteria for ECG interpretation in the athlete.
Objective To examine the performance of the 2010 ESC ECG criteria in a population of athletes undergoing preparticipation cardiovascular disease screening.
Methods University athletes (n=508) underwent routine medical history/physical examination and ECG before athletic participation. Transthoracic echocardiography (TTE) was also performed on each participant to detect or exclude cardiac findings with relevance to sport participation. Screening test statistics were calculated to determine the performance of the 2010 ESC criteria, and the performance of the 2010 criteria was compared with the 2005 criteria.
Results Application of the 2010 ESC criteria, compared with the 2005 criteria, reduced the number of participants with abnormal ECG findings from 83/508 (16.3%) to 49/508 (9.6%). The reduction in the number of abnormal ECGs was driven by the reclassification of participants with isolated QRS voltage criteria for left ventricular hypertrophy from abnormal to normal. Of the 49 participants with abnormal ECGs, 14/49 (29%) had a single ECG abnormality and 35/49 (71%) had two or more abnormalities. The use of the 2010 criteria was associated with improved specificity (reduction in the false positive rate) and preserved sensitivity when compared with the 2005 criteria.
Conclusion Application of the 2010 ESC criteria for ECG interpretation in the athlete improves the accuracy of an ECG-inclusive preparticipation screening strategy by reducing the rate of false positive ECGs.
C1 [Weiner, Rory B.; Hutter, Adolph M.; Kim, Jonathan H.; Wood, Malissa J.; Wang, Thomas J.; Picard, Michael H.; Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Wang, Francis] Harvard Univ, Univ Hlth Serv, Cambridge, MA 02138 USA.
RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA.
EM abaggish@partners.org
OI Picard, Michael/0000-0002-9264-3243
NR 25
TC 56
Z9 56
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD OCT
PY 2011
VL 97
IS 19
BP 1573
EP 1577
DI 10.1136/hrt.2011.227330
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 817JH
UT WOS:000294667700008
PM 21602522
ER
PT J
AU Schumacher, FR
Berndt, SI
Siddiq, A
Jacobs, KB
Wang, ZM
Lindstrom, S
Stevens, VL
Chen, C
Mondul, AM
Travis, RC
Stram, DO
Eeles, RA
Easton, DF
Giles, G
Hopper, JL
Neal, DE
Hamdy, FC
Donovan, JL
Muir, K
Al Olama, AA
Kote-Jarai, Z
Guy, M
Severi, G
Gronberg, H
Isaacs, WB
Karlsson, R
Wiklund, F
Xu, JF
Allen, NE
Andriole, GL
Barricarte, A
Boeing, H
Bueno-de-Mesquita, HB
Crawford, ED
Diver, WR
Gonzalez, CA
Gaziano, JM
Giovannucci, EL
Johansson, M
Le Marchand, L
Ma, J
Sieri, S
Stattin, P
Stampfer, MJ
Tjonneland, A
Vineis, P
Virtamo, J
Vogel, U
Weinstein, SJ
Yeager, M
Thun, MJ
Kolonel, LN
Henderson, BE
Albanes, D
Hayes, RB
Feigelson, HS
Riboli, E
Hunter, DJ
Chanock, SJ
Haiman, CA
Kraft, P
AF Schumacher, Fredrick R.
Berndt, Sonja I.
Siddiq, Afshan
Jacobs, Kevin B.
Wang, Zhaoming
Lindstrom, Sara
Stevens, Victoria L.
Chen, Constance
Mondul, Alison M.
Travis, Ruth C.
Stram, Daniel O.
Eeles, Rosalind A.
Easton, Douglas F.
Giles, Graham
Hopper, John L.
Neal, David E.
Hamdy, Freddie C.
Donovan, Jenny L.
Muir, Kenneth
Al Olama, Ali Amin
Kote-Jarai, Zsofia
Guy, Michelle
Severi, Gianluca
Gronberg, Henrik
Isaacs, William B.
Karlsson, Robert
Wiklund, Fredrik
Xu, Jianfeng
Allen, Naomi E.
Andriole, Gerald L.
Barricarte, Aurelio
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Crawford, E. David
Diver, W. Ryan
Gonzalez, Carlos A.
Gaziano, J. Michael
Giovannucci, Edward L.
Johansson, Mattias
Le Marchand, Loic
Ma, Jing
Sieri, Sabina
Stattin, Par
Stampfer, Meir J.
Tjonneland, Anne
Vineis, Paolo
Virtamo, Jarmo
Vogel, Ulla
Weinstein, Stephanie J.
Yeager, Meredith
Thun, Michael J.
Kolonel, Laurence N.
Henderson, Brian E.
Albanes, Demetrius
Hayes, Richard B.
Feigelson, Heather Spencer
Riboli, Elio
Hunter, David J.
Chanock, Stephen J.
Haiman, Christopher A.
Kraft, Peter
TI Genome-wide association study identifies new prostate cancer
susceptibility loci
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID RISK-ASSOCIATED LOCI; AGGRESSIVENESS LOCI; SEQUENCE VARIANTS; COMMON
VARIANT; MULTIPLE LOCI; SCAN; GENE; 8Q24; REPLICATION; SURVIVAL
AB Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade >= 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P = 4.3 x 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 x 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P = 0.72 and P = 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.
C1 [Lindstrom, Sara; Chen, Constance; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Schumacher, Fredrick R.; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Berndt, Sonja I.; Jacobs, Kevin B.; Wang, Zhaoming; Mondul, Alison M.; Weinstein, Stephanie J.; Yeager, Meredith; Albanes, Demetrius; Hayes, Richard B.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, London, England.
[Jacobs, Kevin B.; Wang, Zhaoming] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA.
[Lindstrom, Sara; Chen, Constance; Giovannucci, Edward L.; Stampfer, Meir J.; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Stevens, Victoria L.; Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Travis, Ruth C.; Allen, Naomi E.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Travis, Ruth C.; Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Oxford, England.
[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
[Eeles, Rosalind A.; Kote-Jarai, Zsofia; Guy, Michelle] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England.
[Easton, Douglas F.; Al Olama, Ali Amin] Univ Cambridge, Ctr Canc Genet Epidemiol, Cambridge, England.
[Easton, Douglas F.; Al Olama, Ali Amin] Univ Cambridge, Dept Publ Hlth, Cambridge, England.
[Easton, Douglas F.; Al Olama, Ali Amin] Univ Cambridge, Dept Primary Care, Cambridge, England.
[Easton, Douglas F.; Neal, David E.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Giles, Graham; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Hopper, John L.] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt MEGA Epidemiol, Melbourne, Vic, Australia.
[Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Muir, Kenneth] Univ Warwick, Hlth Sci Res Inst, Coventry CV4 7AL, W Midlands, England.
[Gronberg, Henrik; Karlsson, Robert; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Isaacs, William B.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA.
[Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain.
[Boeing, Heiner] Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Crawford, E. David] Univ Colorado, Aurora, CO USA.
[Gonzalez, Carlos A.] Catalan Inst Oncol ICO IDIBELL RETICC RD06 0020, Unit Nutr Environm & Canc, Barcelona, Spain.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Ma, Jing; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, VA Cooperat Studies Programs, Boston, MA USA.
[Gaziano, J. Michael; Ma, Jing; Stampfer, Meir J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias; Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
[Ma, Jing; Stampfer, Meir J.] Channing Labs, Boston, MA USA.
[Sieri, Sabina] Fdn IRCCS Ist Nazl Tumori, Nutr Epidemiol Unit, Milan, Italy.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Vogel, Ulla] Natl Res Ctr Working Environm, Copenhagen, Denmark.
[Vogel, Ulla] Tech Univ Denmark, Natl Food Inst, Soborg, Denmark.
[Hayes, Richard B.] NYU, Dept Environm Med, Inst Canc, Div Epidemiol,Langone Med Ctr, New York, NY 10016 USA.
[Feigelson, Heather Spencer] Kaiser Permanente, Inst Hlth Res, Denver, CO USA.
RP Kraft, P (reprint author), Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA.
EM pkraft@hsph.harvard.edu
RI Gonzalez, Carlos A/O-4651-2014; Albanes, Demetrius/B-9749-2015; Sieri,
Sabina/K-4667-2016; Vogel, Ulla/I-5048-2012;
OI Karlsson, Robert/0000-0002-8949-2587; Gonzalez, Carlos
A/0000-0003-2822-9715; Sieri, Sabina/0000-0001-5201-172X; Vogel,
Ulla/0000-0001-6807-1524; Eeles, Rosalind/0000-0002-3698-6241; Neal,
David/0000-0002-6033-5086; Hayes, Richard/0000-0002-0918-661X; Mondul,
Alison/0000-0002-8843-1416; Giles, Graham/0000-0003-4946-9099
FU U.S. National Institutes of Health, National Cancer Institute
[U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]; NIH/National
Cancer Institute, Division of Cancer Epidemiology and Genetics); Cancer
Research UK [C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692,
C16913/A6135, C522/A8649]; Institute of Cancer Research and The Everyman
Campaign; Prostate Cancer Research Foundation; Prostate Research
Campaign UK; National Cancer Research Network UK; National Cancer
Research Institute (NCRI) UK; NIHR Biomedical Research Centre at The
Institute of Cancer Research; Royal Marsden NHS Foundation Trust;
National Health and Medical Research Council, Australia [209057, 251533,
450104, 390130]; VicHealth; Cancer Council Victoria; Cancer Council
Queensland; Whitten Foundation; Tattersall's; Health Technology
Assessment Programme [96/20/06, 96/20/99]; Department of Health,
England; Medical Research Council of England [G0500966, ID 75466]; NCRI,
UK; Southwest National Health Service Research and Development; USA Dept
of Defense [W81XWH-04-1-0280]; Yorkshire Cancer Research and Cancer
Research UK; NCRI; NIHR; Swedish Research Council [K2010-70X-20430-04-3,
70867901]; Swedish Cancer Foundation [09-0677]; Hedlund Foundation;
Soderberg Foundation; Enqvist Foundation; Stockholm County Council;
National Cancer Institute [CA112517, CA133009]
FX The BPC3 was supported by the U.S. National Institutes of Health,
National Cancer Institute (cooperative agreements U01-CA98233 to D.J.H.,
U01-CA98710 to M.J.T., U01-CA98216 to E.R., and U01-CA98758 to B.E.H.,
and Intramural Research Program of NIH/National Cancer Institute,
Division of Cancer Epidemiology and Genetics). This work was supported
by Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354,
C5047/A10692, C16913/A6135, and C16913/A6835. We would also like to
thank the following for funding support: The Institute of Cancer
Research and The Everyman Campaign, The Prostate Cancer Research
Foundation, Prostate Research Campaign UK, The National Cancer Research
Network UK, The National Cancer Research Institute (NCRI) UK. We
acknowledge NHS funding to the NIHR Biomedical Research Centre at The
Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.
We also acknowledge grant support from The National Health and Medical
Research Council, Australia (209057, 251533, 450104, 390130), VicHealth,
The Cancer Council Victoria, Cancer Council Queensland, The Whitten
Foundation, and Tattersall's. The ProtecT study is ongoing and is funded
by the Health Technology Assessment Programme (projects 96/20/06,
96/20/99). The ProtecT trial and its linked ProMPT and CAP (Comparison
Arm for ProtecT) studies are supported by Department of Health, England;
Cancer Research UK grant number C522/A8649, Medical Research Council of
England grant number G0500966, ID 75466 and The NCRI, UK. The
epidemiological data for ProtecT were generated though funding from the
Southwest National Health Service Research and Development. DNA
extraction in ProtecT was supported by USA Dept of Defense award
W81XWH-04-1-0280, Yorkshire Cancer Research and Cancer Research UK. The
bio-repository from ProtecT is supported by the NCRI (ProMPT) study and
the Cambridge BMRC grant from NIHR. Financial support for CAPS was
provided through a grant from the Swedish Research Council (grant no
K2010-70X-20430-04-3 and 70867901), the Swedish Cancer Foundation (grant
no 09-0677), the Hedlund Foundation, Soderberg Foundation, Enqvist
Foundation, ALF funds from the Stockholm County Council. W.B.I. was
supported by National Cancer Institute grants CA112517 and CA133009.
NR 41
TC 93
Z9 94
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 1
PY 2011
VL 20
IS 19
BP 3867
EP 3875
DI 10.1093/hmg/ddr295
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 819FE
UT WOS:000294810000014
PM 21743057
ER
PT J
AU Holgerson, PL
Harnevik, L
Hernell, O
Tanner, ACR
Johansson, I
AF Holgerson, P. Lif
Harnevik, L.
Hernell, O.
Tanner, A. C. R.
Johansson, I.
TI Mode of Birth Delivery Affects Oral Microbiota in Infants
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE newborn; Caesarian section; vaginal delivery; bacterial taxa; HOMIM;
Slackia exigua
ID INTESTINAL MICROBIOTA; GUT MICROBIOTA; ROOT CARIES; MICROFLORA;
CHILDREN; IDENTIFICATION; PERIODONTITIS; ACQUISITION; MICROARRAY;
PROFILES
AB Establishment of the microbiota of the gut has been shown to differ between infants delivered by Caesarian section (C-section) and those delivered vaginally. The aim of the present study was to compare the oral microbiota in infants delivered by these different routes. The oral biofilm was assayed by the Human Oral Microbe Identification Microarray (HOMIM) in healthy three-month-old infants, 38 infants born by C-section, and 25 infants delivered vaginally. Among over 300 bacterial taxa targeted by the HOMIM microarray, Slackia exigua was detected only in infants delivered by C-section. Further, significantly more bacterial taxa were detected in the infants delivered vaginally (79 species/species clusters) compared with infants delivered by C-section (54 species/species clusters). Multivariate modeling revealed a strong model that separated the microbiota of C-section and vaginally delivered infants into two distinct colonization patterns. In conclusion, our study indicated differences in the oral microbiota in infants due to mode of delivery, with vaginally delivered infants having a higher number of taxa detected by the HOMIM microarray.
C1 [Holgerson, P. Lif; Harnevik, L.; Johansson, I.] Umea Univ, Dept Odontol, Cariol Sect, S-90187 Umea, Sweden.
[Hernell, O.] Umea Univ, Dept Clin Sci, Pediat Sect, S-90187 Umea, Sweden.
[Tanner, A. C. R.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA.
[Tanner, A. C. R.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
RP Holgerson, PL (reprint author), Umea Univ, Dept Odontol, Cariol Sect, S-90187 Umea, Sweden.
EM pernilla.lif@odont.umu.se
FU Vasterbotten County Council (TUA/FoU); Swedish Patent Revenue
Foundation; Public Health Service [DE-015847]; National Institute of
Dental and Craniofacial Research, USA; Henning and Johan Throne-Holst's
Foundation
FX The present study was supported by grants from Vasterbotten County
Council (TUA/FoU) and The Swedish Patent Revenue Foundation, and by a
Public Health Service Grant DE-015847 (AT) from the National Institute
of Dental and Craniofacial Research, USA, and by Henning and Johan
Throne-Holst's Foundation (PL). Dr. Conny Wikstrom, Umetrics, Sweden, is
acknowledged for expertise support in PLS-DA. The authors declare no
potential conflicts of interest with respect to the authorship and/or
publication of this article.
NR 30
TC 23
Z9 23
U1 1
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD OCT
PY 2011
VL 90
IS 10
BP 1183
EP 1188
DI 10.1177/0022034511418973
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 819PF
UT WOS:000294838200006
ER
PT J
AU Liguori, M
Meier, DS
Hildenbrand, P
Healy, BC
Chitnis, T
Baruch, NF
Khoury, SJ
Weiner, HL
Bakshi, R
Barkhof, F
Guttmann, CRG
AF Liguori, Maria
Meier, Dominik S.
Hildenbrand, Peter
Healy, Brian C.
Chitnis, Tanuja
Baruch, Natalie F.
Khoury, Samia J.
Weiner, Howard L.
Bakshi, Rohit
Barkhof, Frederik
Guttmann, Charles R. G.
TI One year activity on subtraction MRI predicts subsequent 4 year activity
and progression in multiple sclerosis
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID DIAGNOSTIC-CRITERIA; DISEASE-ACTIVITY; LESION BURDEN; DISABILITY;
TRIALS; IMAGES; IMPAIRMENT; PATHOLOGY; PATTERNS; THERAPY
AB Objective To investigate the predictive value of 1 year subtraction MRI (sMRI) on activity and progression over the next 4 years in early phase multiple sclerosis (MS). To compare sensitivity of sMRI and contrast enhanced MRI towards disease activity.
Methods The study was performed on 127 MS patients with brain MRI within 5 years of symptom onset (y0), after 1 year (y1) and after 5 years (y5). Measures of clinical (Expanded Disability Status Scale, relapse rate) and conventional MRI outcomes (brain parenchyma fraction (BPF); T2 lesion volume (T2LV); contrast enhancing lesions (CEL)) were available at all time points. sMRI was obtained from y1-y0, y5-y1 and y5-y0 image pairs and the number of new, enlarged, resolved and regressed lesions was counted.
Results One year lesion change measured by sMRI predicted sMRI lesion change (p<0.0001), BPF and T2LV (p<0.05) changes, as well as clinical relapse rate (p<0.02) in the subsequent 4 years. sMRI measures were retained in stepwise predictive models that included other candidate MRI predictors. Active lesions on sMRI over a 1, 4 or 5 year interval provided a more sensitive assessment of disease activity than number of CEL at y0, y1 and/or y5: 83%, 93% and 90% of patients without CEL showed sMRI activity during the y1-y0, y5-y1, and y5-y0 intervals.
Conclusions sMRI is a feasible and sensitive tool for detecting MS activity and may provide an alternative to contrast enhanced MRI in clinical practice, particularly in cases where CEL are not available or inconclusive. Furthermore, sMRI metrics combined with conventional MRI outcomes (CEL, T2LV, BPF) can increase the prediction of longer term MRI activity and progression.
C1 [Liguori, Maria; Meier, Dominik S.; Hildenbrand, Peter; Guttmann, Charles R. G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Imaging,Dept Radiol, Boston, MA 02115 USA.
[Liguori, Maria; Meier, Dominik S.; Hildenbrand, Peter; Guttmann, Charles R. G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Imaging,Dept Neurol, Boston, MA 02115 USA.
[Liguori, Maria] CNR, Inst Neurol Sci, Mangone, Italy.
[Hildenbrand, Peter] Lahey Clin Fdn, Dept Radiol, Neuroradiol Div, Burlington, MA USA.
[Healy, Brian C.; Chitnis, Tanuja; Baruch, Natalie F.; Khoury, Samia J.; Weiner, Howard L.; Bakshi, Rohit] Harvard Univ, Brigham & Womens Hosp, Sch Med, Partners MS Ctr,Dept Neurol, Boston, MA 02115 USA.
[Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Bakshi, Rohit] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Neuroimaging Res,Dept Neurol, Boston, MA 02115 USA.
[Barkhof, Frederik] Vrije Univ Amsterdam Med Ctr, Dept Radiol, MS Ctr Amsterdam, Amsterdam, Netherlands.
RP Guttmann, CRG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Imaging,Dept Radiol, 221 Longwood Ave,RF 396, Boston, MA 02115 USA.
EM guttmann@bwh.harvard.edu
RI Liguori, Maria/D-4390-2016;
OI Liguori, Maria/0000-0003-4338-0392; khoury, samia/0000-0003-3198-6063
NR 40
TC 8
Z9 8
U1 0
U2 5
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD OCT
PY 2011
VL 82
IS 10
BP 1125
EP 1131
DI 10.1136/jnnp.2011.242115
PG 7
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 818EF
UT WOS:000294733400015
PM 21429902
ER
PT J
AU Kearney, CJ
Lee, JY
Padera, RF
Hsu, HP
Spector, M
AF Kearney, Cathal J.
Lee, Ji Yoo
Padera, Robert F.
Hsu, Hu-Ping
Spector, Myron
TI Extracorporeal Shock Wave-Induced Proliferation of Periosteal Cells
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE shock waves; cambium cell proliferation; tissue engineering; rodent;
immunohistochemistry
ID SMOOTH-MUSCLE ACTIN; BONE-FORMATION; OSTEOGENESIS; EXPRESSION;
CARTILAGE; DIFFERENTIATION; CHONDROGENESIS; FEMUR
AB The cambium cells of the periosteum are an important cell source for select tissue engineering/regenerative medicine applications due to their osteogenic and chondrogenic potential. However, the cambium layer is only 2-5 cells thick, which complicates its harvest, and the low cell number limits its suitability for certain applications. Extracorporeal shock waves (ESWs) have been reported to cause periosteal osteogenesis following cambium layer thickening. This study quantified the proliferation of cambium cells in the femur and tibia of adult rats following ESW treatment at two different energy flux densities. Four days after application of ESWs, there was a significant (3- to 6-fold) increase in cambium layer thickness and cell number. Proliferation was seen with an energy flux density as low as 0.15 mJ/mm(2). The tibial cambium cells were more proliferative than those of the femur, with the cells closest to the ESW source proliferating the most. Within the thickened periosteum, alpha-smooth muscle actin and von Willebrand Factor expression were upregulated, suggesting a vascular role in ESW osteogenesis. Bone formation was seen within the stimulated periosteum at day 4. We propose that non-invasive ESWs can be used to rapidly stimulate cambium cell proliferation, providing a larger cell population for use as a progenitor cell source for tissue engineering applications, than can normally be provided by periosteum. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:1536-1543, 2011
C1 [Kearney, Cathal J.; Padera, Robert F.; Spector, Myron] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Kearney, Cathal J.; Lee, Ji Yoo; Hsu, Hu-Ping; Spector, Myron] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Padera, Robert F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Hsu, Hu-Ping; Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Orthopaed Res Lab, Boston, MA 02115 USA.
RP Spector, M (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
EM mspector@rics.bwh.harvard.edu
OI Kearney, Cathal/0000-0002-9514-6517
FU Department of Veterans Affairs; SANUWAVE Health, Inc.; NICHD
FX The authors would like to acknowledge the Department of Veterans Affairs
and SANUWAVE Health, Inc. for funding and supplies, respectively, for
this project. The collagen II monoclonal antibody developed by Rikard
Holmdahl/Kristofer Rubin was obtained from the Developmental Studies
Hybridoma Bank developed under the auspices of the NICHD and maintained
by The University of Iowa, Department of Biology, Iowa City, IA.
NR 24
TC 6
Z9 6
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD OCT
PY 2011
VL 29
IS 10
BP 1536
EP 1543
DI 10.1002/jor.21346
PG 8
WC Orthopedics
SC Orthopedics
GA 816IV
UT WOS:000294592800013
PM 21448986
ER
PT J
AU Rutgers, KS
van Remoortere, A
van Buchem, MA
Verrips, CT
Greenberg, SM
Bacskai, BJ
Frosch, MP
van Duinen, SG
Maat-Schieman, ML
van der Maarel, SM
AF Rutgers, Kim S.
van Remoortere, Alexandra
van Buchem, Mark A.
Verrips, C. Theo
Greenberg, Steven M.
Bacskai, Brian J.
Frosch, Matthew P.
van Duinen, Sjoerd G.
Maat-Schieman, Marion L.
van der Maarel, Silvere M.
TI Differential recognition of vascular and parenchymal beta amyloid
deposition
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; Amyloid beta; Antibody; Histochemistry; Imaging;
Immunoreactivity
ID HEREDITARY CEREBRAL-HEMORRHAGE; DOMAIN ANTIBODY FRAGMENTS;
ALZHEIMERS-DISEASE; DUTCH TYPE; A-BETA; ANGIOPATHY; SECRETION;
LIBRARIES; DEMENTIA; FIBRILS
AB By phage display, llama-derived heavy chain antibody fragments were selected from non-immune and immune libraries and tested for their affinity and specificity for beta amyloid by phage-ELISA, immunohistochemistry and surface plasmon resonance.
We identified eight distinct heavy chain antibody fragments specific for beta amyloid. While three of them recognized vascular and parenchymal beta amyloid deposits, the remaining five heavy chain antibody fragments recognized vascular beta amyloid specifically, failing to bind to parenchymal beta amyloid.
These heavy chain antibody fragments, selected from different libraries, demonstrated differential affinity for different epitopes when used for immunohistochemistry. These observations indicate that the llama heavy chain antibody fragments are the first immunologic probes with the ability to differentiate between parenchymal and vascular beta amyloid aggregates. This indicates that vascular and parenchymal beta amyloid deposits are heterogeneous in epitope presence/availability. The properties of these heavy chain antibody fragments make them potential candidates for use in in vivo differential diagnosis of Alzheimer disease and cerebral amyloid angiopathy. Continued use and characterization of these reagents will be necessary to fully understand the performance of these immunoreagents. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Rutgers, Kim S.; van der Maarel, Silvere M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2333 ZA Leiden, Netherlands.
[van Remoortere, Alexandra] Leiden Univ, Dept Parasitol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
[van Buchem, Mark A.] Leiden Univ, Dept Radiol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
[Verrips, C. Theo] Univ Utrecht, Dept Mol Cell Biol, NL-3584 CH Utrecht, Netherlands.
[Greenberg, Steven M.; Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Frosch, Matthew P.] Harvard Univ, Sch Med, Charlestown, MA USA.
[van Duinen, Sjoerd G.] Leiden Univ, Dept Pathol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
[van Duinen, Sjoerd G.; Maat-Schieman, Marion L.] Leiden Univ, Dept Neurol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
RP van der Maarel, SM (reprint author), Leiden Univ, Dept Human Genet, Med Ctr, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
EM maarel@lumc.nl
FU IOP Genomics Senter [IGE05005]; National Institutes of Health (NIH)
[AG021084, AG005134]; Centre for Medical Systems Biology within the
Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO)
FX We would like to thank Finnbogi R. Thormodsson, Ph.D., Faculty of
Medicine, University of Iceland, Reykjavik, for providing cryosections
of HCHWA-I patients and Ingrid Hegeman-Kleinn for technical assistance.
We also would like to thank Kim Retera, Ph.D., VU Medical Center,
Amsterdam, for Biacore analysis support. This work was supported by
grants from the IOP Genomics Senter [IGE05005], the National Institutes
of Health (NIH AG021084 and AG005134) and by the Centre for Medical
Systems Biology within the framework of the Netherlands Genomics
Initiative (NGI)/Netherlands Organization for Scientific Research (NWO).
NR 30
TC 10
Z9 11
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD OCT
PY 2011
VL 32
IS 10
BP 1774
EP 1783
DI 10.1016/j.neurobiolaging.2009.11.012
PG 10
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 815SZ
UT WOS:000294551000005
PM 20015576
ER
PT J
AU Costanza, A
Weber, K
Gandy, S
Bouras, C
Hof, PR
Giannakopoulos, P
Canuto, A
AF Costanza, A.
Weber, K.
Gandy, S.
Bouras, C.
Hof, P. R.
Giannakopoulos, P.
Canuto, A.
TI Contact sport-related chronic traumatic encephalopathy in the elderly:
clinical expression and structural substrates
SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
LA English
DT Review
DE Alzheimer's disease; boxing; chronic traumatic encephalopathy; contact
sports; frontotemporal dementia; traumatic brain injuries
ID AMYOTROPHIC-LATERAL-SCLEROSIS; BETA-AMYLOID PROTEIN; NEUROFIBRILLARY
TANGLE DISTRIBUTION; REPETITIVE HEAD-INJURY; BRAIN-INJURY;
ALZHEIMERS-DISEASE; DEMENTIA-PUGILISTICA; PARKINSONISM-DEMENTIA;
PROFESSIONAL BOXERS; COGNITIVE IMPAIRMENT
AB Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.
C1 [Giannakopoulos, P.] Univ Hosp, Dept Psychiat, CH-1225 Geneva, Switzerland.
[Giannakopoulos, P.] Univ Geneva, Fac Med, CH-1225 Geneva, Switzerland.
[Costanza, A.; Weber, K.; Bouras, C.; Canuto, A.] Univ Geneva, Sch Med, Dept Psychiat, CH-1225 Geneva, Switzerland.
[Giannakopoulos, P.] Hosp CHUV, Div Old Age Psychiat, Dept Psychiat, Lausanne, Switzerland.
[Gandy, S.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Gandy, S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Gandy, S.; Hof, P. R.] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY USA.
[Gandy, S.] James J Peters VA Med Ctr, Bronx, NY USA.
[Hof, P. R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA.
RP Giannakopoulos, P (reprint author), Univ Hosp, Dept Psychiat, CH-1225 Geneva, Switzerland.
EM panteleimon.giannakopoulos@unige.ch
FU NIH [AG02219, AG05138]
FX We thank all the technical staff members of the Division of
Neuropsychiatry of the University of Geneva Hospitals for expert
assistance. This work was supported in part by NIH grants AG02219 and
AG05138 (P.R.H., S.G.).
NR 151
TC 44
Z9 44
U1 1
U2 26
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0305-1846
J9 NEUROPATH APPL NEURO
JI Neuropathol. Appl. Neurobiol.
PD OCT
PY 2011
VL 37
IS 6
BP 570
EP 584
DI 10.1111/j.1365-2990.2011.01186.x
PG 15
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 819KZ
UT WOS:000294825300001
PM 21696410
ER
PT J
AU Teich, AF
Hedley-Whyte, ET
Goldman, JE
AF Teich, A. F.
Hedley-Whyte, E. T.
Goldman, J. E.
TI 'Pontinization' of the medulla: two clinical case studies
SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
LA English
DT Letter
ID PONTINE GRAY; NUCLEI; RAT; MIGRATION; BRAIN
C1 [Teich, A. F.; Goldman, J. E.] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10027 USA.
[Teich, A. F.; Goldman, J. E.] New York Presbyterian Hosp, New York, NY USA.
[Hedley-Whyte, E. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol Neuropathol, Boston, MA USA.
RP Teich, AF (reprint author), Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10027 USA.
NR 11
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0305-1846
J9 NEUROPATH APPL NEURO
JI Neuropathol. Appl. Neurobiol.
PD OCT
PY 2011
VL 37
IS 6
BP 689
EP 693
DI 10.1111/j.1365-2990.2011.01171.x
PG 5
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 819KZ
UT WOS:000294825300011
PM 21450049
ER
PT J
AU Hauck, EF
Natarajan, SK
Ohta, H
Ogilvy, CS
Hopkins, LN
Siddiqui, AH
Levy, EI
AF Hauck, Erik F.
Natarajan, Sabareesh K.
Ohta, Hajime
Ogilvy, Christopher S.
Hopkins, L. Nelson
Siddiqui, Adnan H.
Levy, Elad I.
TI Emergent Endovascular Recanalization for Cervical Internal Carotid
Artery Occlusion in Patients Presenting With Acute Stroke
SO NEUROSURGERY
LA English
DT Article
DE Carotid occlusion; Carotid stent; Intracranial stenting; Ischemic stroke
ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; INTRAVENOUS
THROMBOLYSIS
AB BACKGROUND: Acute proximal (cervical) internal carotid artery (ICA) occlusion may cause ischemia of an entire hemisphere or no ischemia at all, depending on the presence of intracranial collaterals.
OBJECTIVE: To retrospectively analyze the clinical results for emergent endovascular carotid recanalization in patients with acute proximal (cervical) ICA occlusion and to assess predictors of recanalization and clinical, neurological, and functional outcome.
METHODS: Emergent endovascular revascularization was attempted in 22 patients presenting with acute stroke secondary to complete cervical ICA occlusion. Patients with pseudo-occlusion were excluded. Recanalization was assessed with the Thrombolysis in Myocardial Ischemia (TIMI) system: grade 0 (no flow) to grade 3 (normal flow).
RESULTS: The median age of the patients was 65 years; mean admission National Institutes of Health Stroke Scale (NIHSS) score was 14. Recanalization (TIMI grade 2/3) occurred in 17 patients (77.3%). Ten patients (45.5%) demonstrated significant clinical improvement during hospitalization (NIHSS improved >= 4 points). Fifty percent of patients had good outcomes (modified Rankin Scale <= 2) after a median follow-up of 3 months. Patient age <70 years and successful recanalization (TIMI grade 2/3) predicted a good outcome (P <= .01). Presence of atrial fibrillation, admission NIHSS score >= 20, and complete ICA occlusion at all levels (cervical, petrocavernous, and intracranial) were associated with poor outcomes (P <= .05). Patients with complete cervical ICA occlusion but partial distal preservation of the vessel were most likely to benefit from the intervention (recanalization in 88.2%; good outcome in 64.7%).
CONCLUSION: Attempts at emergent endovascular carotid recanalization for acute stroke are encouraged, particularly in younger patients with partial distal preservation of the ICA.
C1 [Hauck, Erik F.; Natarajan, Sabareesh K.; Ohta, Hajime; Ogilvy, Christopher S.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Neurosurg, Buffalo, NY 14260 USA.
[Hauck, Erik F.; Natarajan, Sabareesh K.; Ohta, Hajime; Ogilvy, Christopher S.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Sch Med & Biomed Sci, Toshiba Stroke Res Ctr, Buffalo, NY 14260 USA.
[Natarajan, Sabareesh K.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Radiol, Buffalo, NY 14260 USA.
[Hauck, Erik F.; Natarajan, Sabareesh K.; Ohta, Hajime; Ogilvy, Christopher S.; Hopkins, L. Nelson; Siddiqui, Adnan H.; Levy, Elad I.] Millard Fillmore Gates Hosp, Dept Neurosurg, Buffalo, NY USA.
[Ogilvy, Christopher S.] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
RP Levy, EI (reprint author), SUNY Buffalo, Millard Fillmore Gates Hosp, 3 Gates Circle, Buffalo, NY 14209 USA.
EM elevy@ubns.com
FU Toshiba; Boston Scientific; Codman Shurtleff, Inc; ev3/Covidien Vascular
Therapies; Abbott Vascular; National Institutes of Health [NINDS
1R01NS064592-01A1]; University at Buffalo
FX Dr Hopkins receives grant/research support from Toshiba; serves as a
consultant to Abbott, Boston Scientific, Cordis, Micrus, and W. L. Gore;
holds a financial interest in AccessClosure, Augmenix, Boston
Scientific,* Claret Medical Inc., Micrus, and Valor Medical; has a
board/trustee/officer position with AccessClosure, Claret Medical Inc.,
and Micrus (until September, 2010); belongs to the Abbott Vascular
speakers' bureau; and receives honoraria from Bard, Boston Scientific,
Cordis, Memorial Healthcare System, Complete Conference Management,
SCAI, and Cleveland Clinic. Dr Levy receives research grant support
(principal investigator, Stent-Assisted Recanalization in Acute Ischemic
Stroke), other research support (devices), and honoraria from Boston
Scientific and research support from Codman & Shurtleff, Inc and
ev3/Covidien Vascular Therapies; has ownership interests in Intratech
Medical Ltd and Mynx/Access Closure; serves as a consultant on the board
of Scientific Advisors to Codman & Shurtleff, Inc; serves as a
consultant for Codman & Shurtleff, Inc, ev3/Covidien Vascular Therapies,
and TheraSyn Sensors, Inc; and receives fees for carotid stent training
from Abbott Vascular and ev3/Covidien Vascular Therapies. Dr Ogilvy
serves as a consultant to Mizuoho America Inc. Dr Siddiqui has received
research grants from the National Institutes of Health (coinvestigator,
NINDS 1R01NS064592-01A1, Hemodynamic Induction of Pathologic Remodeling
Leading to Intracranial Aneurysms) and the University at Buffalo
(Research Development Award); holds financial interests in Hotspur,
Intratech Medical, StimSox, and Valor Medical; serves as a consultant to
Codman & Shurtleff, Inc, Concentric Medical, ev3/Covidien Vascular
Therapies, GuidePoint Global Consulting, and Penumbra; belongs on the
speakers' bureaus of Codman & Shurtleff, Inc and Genentech; serves on an
advisory board for Codman & Shurtleff; and has received honoraria from
American Association of Neurological Surgeons' courses, an Emergency
Medicine Conference, Genentech, and Neocure Group LLC and from Abbott
Vascular, and Codman & Shurtleff, Inc. for training other
neurointerventionists in carotid stenting and for training physicians in
endovascular stenting for aneurysms.
NR 22
TC 20
Z9 21
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD OCT
PY 2011
VL 69
IS 4
BP 899
EP 907
DI 10.1227/NEU.0b013e31821cfa52
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 817OV
UT WOS:000294684600063
PM 21499144
ER
PT J
AU Lopez-Olivo, MA
Landon, GC
Siff, SJ
Edelstein, D
Pak, C
Kallen, MA
Stanley, M
Zhang, H
Robinson, KC
Suarez-Almazor, ME
AF Lopez-Olivo, Maria A.
Landon, Glenn C.
Siff, Sherwin J.
Edelstein, David
Pak, Chong
Kallen, Michael A.
Stanley, Melinda
Zhang, Hong
Robinson, Kausha C.
Suarez-Almazor, Maria E.
TI Psychosocial determinants of outcomes in knee replacement
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID QUALITY-OF-LIFE; TOTAL JOINT ARTHROPLASTY; SHORT-TERM RECOVERY; TOTAL
HIP; FUNCTIONAL OUTCOMES; SELF-EFFICACY; SURGERY; OSTEOARTHRITIS; PAIN;
POPULATION
AB Objective To identify potential psychosocial and educational barriers to clinical success following knee replacement.
Patients and Methods The authors evaluated 241 patients undergoing total knee replacement, preoperatively and 6 months after surgery. Outcomes included the Western Ontario McMaster (WOMAC) scale and the Knee Society rating system (KSRS). Independent variables included: the medical outcome study-social support scale; depression, anxiety and stress scale; brief COPE inventory; health locus of control; arthritis self-efficacy scale and the life orientation test-revised. Multiple regression models evaluated associations of baseline demographic and psychosocial variables with outcomes at 6 months, controlling for body mass index, comorbidities and baseline outcome scores.
Results Patients' mean age was 65 +/- 9 years; 65% were women. Most patients improved outcomes after surgery. Several psychosocial variables were associated with outcomes. Regression analyses indicated lower education, less tangible support, depression, less problem-solving coping, more dysfunctional coping, lower internal locus of control were associated with worse WOMAC scores (R 2 contribution of psychosocial variables for pain 0.07; for function, 0.14). Older age, lower education, depression and less problem-solving coping were associated with poorer total KSRS scores (R 2 contribution of psychosocial variables to total KSRS model 0.09). Psychosocial variables as a set contributed from 25% to 74% of total explained variance across the models tested.
Conclusion Patients' level of education, tangible support, depression, problem-solving coping, dysfunctional coping and internal locus of control were associated with pain and functional outcomes after knee replacement. The findings suggest that, in addition to medical management, perioperative psychosocial evaluation and intervention are crucial in enhancing knee replacement outcomes.
C1 [Suarez-Almazor, Maria E.] Univ Texas MD Anderson Canc Ctr, Unit 1467, Houston, TX 77030 USA.
[Landon, Glenn C.; Siff, Sherwin J.; Edelstein, David] St Lukes Episcopal Hlth Syst, Houston, TX USA.
[Stanley, Melinda] Dept Vet Affairs Med Ctr, Houston VA HSR&D Ctr Excellence, Hlth Serv Res & Dev Serv, Houston, TX USA.
[Stanley, Melinda] Baylor Coll Med, Houston, TX 77030 USA.
[Stanley, Melinda] VA S Cent Mental Illness Res, Educ & Clin Ctr, N Little Rock, AR USA.
RP Suarez-Almazor, ME (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1467, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM msalmazor@mdanderson.org
FU National Institute for Arthritis, Musculoskeletal and Skin Disorders
(NIAMS) [R01 AR48662]; Agency for Healthcare Research and Quality; VA
HSR&D Houston Center of Excellence [HFP-90-020]
FX This study was supported by a grant from the National Institute for
Arthritis, Musculoskeletal and Skin Disorders (NIAMS; R01 AR48662).
MES-A is the recipient of a K24 career award from the National Institute
for Musculoskeletal and Skin Disorders. She is also the Director of the
Houston Center for Education and Research on Therapeutics, funded by the
Agency for Healthcare Research and Quality. It was also partly supported
by the VA HSR&D Houston Center of Excellence (HFP-90-020). The views
expressed are those of the authors and do not necessarily reflect those
of the Department of Veterans Affairs/Baylor College of Medicine. MES-A
has received honoraria from Zimmer as a speaker at the 2010 Summit on
Musculoskeletal Health Disparities.
NR 47
TC 47
Z9 47
U1 1
U2 16
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 OCT
PY 2011
VL 70
IS 10
BP 1775
EP 1781
DI 10.1136/ard.2010.146423
PG 7
WC Rheumatology
SC Rheumatology
GA 814XX
UT WOS:000294491600013
PM 21791452
ER
PT J
AU Chen, YB
Driscoll, JP
McAfee, SL
Spitzer, TR
Rosenberg, ES
Sanders, R
Moss, RB
Fang, F
Marty, FM
AF Chen, Yi-Bin
Driscoll, Jessica P.
McAfee, Steven L.
Spitzer, Thomas R.
Rosenberg, Eric S.
Sanders, Rebecca
Moss, Ronald B.
Fang, Fang
Marty, Francisco M.
TI Treatment of Parainfluenza 3 Infection With DAS181 in a Patient After
Allogeneic Stem Cell Transplantation
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID RESPIRATORY VIRUS-INFECTIONS; SIALIDASE FUSION PROTEIN; RECIPIENTS;
DIAGNOSIS; THERAPY
AB Parainfluenza virus (PIV) can cause significant morbidity after allogeneic stem cell transplantation (SCT). We report the first use of inhaled DAS181 for PIV in an allogeneic SCT recipient. Symptoms, oxygenation, and pulmonary function tests improved. Nasopharyngeal samples showed a reduction in viral load. DAS181 should be systematically evaluated for severe PIV infection.
C1 [Chen, Yi-Bin; Driscoll, Jessica P.; McAfee, Steven L.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA.
[Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Sanders, Rebecca; Moss, Ronald B.; Fang, Fang] NexBio, San Diego, CA USA.
[Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Chen, YB (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Cox 108,55 Fruit St, Boston, MA 02114 USA.
EM ychen6@partners.org
NR 12
TC 27
Z9 27
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD OCT 1
PY 2011
VL 53
IS 7
BP E77
EP E80
DI 10.1093/cid/cir501
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 815AJ
UT WOS:000294498200005
PM 21880586
ER
PT J
AU Spain, R
Bourdette, D
AF Spain, Rebecca
Bourdette, Dennis
TI The Radiologically Isolated Syndrome: Look (Again) Before You Treat
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE Multiple sclerosis/diagnosis; Multiple sclerosis/therapy; Magnetic
resonance imaging; Incidental findings; Brain/pathology; Disease
progression; Radiologically isolated syndrome
ID UNSUSPECTED MULTIPLE-SCLEROSIS; CLINICALLY ISOLATED SYNDROMES;
DIAGNOSTIC-CRITERIA; FOLLOW-UP; DEMYELINATING LESIONS; INTERNATIONAL
PANEL; PREDICT CONVERSION; MRI CRITERIA; DEFINITE; MS
AB The advent and wide use of magnetic resonance brain imaging has led to in the unexpected detection of lesions that appear typical of multiple sclerosis (MS) in otherwise asymptomatic patients. Several cohorts of patients with the "radiologically isolated syndrome (RIS)" have been studied mainly retrospectively, and a proportion of them do go on to have clinical symptoms of MS. This has led to the not infrequent clinical conundrum of whether or not to treat patients with MRI lesions suggestive of MS, given the knowledge that MS disease-modifying therapies work best when given early in the disease course. However, the decision to proactively treat patients with RIS is countered by the increasing risks associated with MS disease-modifying therapies as well as the uncertain prognostic outcome of RIS. This review will highlight what is and is not known about the long-term outcomes of RIS and present recommendations for clinicians when faced with this challenging situation.
C1 [Spain, Rebecca] Portland VA Med Ctr, Neurol Serv, Portland, OR 97239 USA.
[Spain, Rebecca; Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
RP Spain, R (reprint author), Portland VA Med Ctr, Neurol Serv, Mail Code CR120,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM spainr@ohsu.edu
FU Department of Veterans Affairs Rehabilitation Research & Development
Service
FX We thank Bronwyn Hamilton, MD, for sharing information about the
prevalence of RIS among patients undergoing MRI for headache at Oregon
Health & Science University. Dr. Spain has a Career Development Award
from the Department of Veterans Affairs Rehabilitation Research &
Development Service.
NR 46
TC 10
Z9 12
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
EI 1534-6293
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD OCT
PY 2011
VL 11
IS 5
BP 498
EP 506
DI 10.1007/s11910-011-0213-z
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 814PH
UT WOS:000294468700006
PM 21748263
ER
PT J
AU Cameron, MH
Wagner, JM
AF Cameron, Michelle H.
Wagner, Joanne M.
TI Gait Abnormalities in Multiple Sclerosis: Pathogenesis, Evaluation, and
Advances in Treatment
SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
LA English
DT Review
DE 4-Aminopyridine; Accidental falls; Botulinum toxin; Electric
stimulation; Gait; Multiple sclerosis; Rehabilitation; Gait
abnormalities
ID FUNCTIONAL ELECTRICAL-STIMULATION; LEG CYCLING EXERCISE; WALKING
PERFORMANCE; RANDOMIZED-TRIAL; 6-MINUTE WALK; DOUBLE-BLIND; SPASTICITY;
PEOPLE; COMPOSITE; CAPACITY
AB Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by episodic decline in various neurologic functions. Gait dysfunction in MS is distinguished by decreased gait speed, walking endurance, step length, cadence and joint motion, as well as increased metabolic cost of walking and increased variability of gait. Standardized clinical, timed, and patient-based measures can identify MS patients with gait dysfunction, and observational gait analysis, instrumented walkways, or three-dimensional gait analysis can help determine which problem underlies their gait dysfunction to help direct effective treatment. Exercise may ameliorate all types of gait dysfunction. In addition, gait dysfunction due to weakness may be alleviated by orthoses or functional electrical stimulation; gait dysfunction due to spasticity may be relieved by oral, intrathecal, or intramuscular medications. Assistive devices and balance training may reduce gait dysfunction from imbalance, and dalfampridine may accelerate gait in people with MS who walk slowly.
C1 [Cameron, Michelle H.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Cameron, Michelle H.] Portland VA Med Ctr, Portland, OR USA.
[Wagner, Joanne M.] St Louis Univ, Dept Phys Therapy & Athlet Training, St Louis, MO 63104 USA.
RP Cameron, MH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,CR120, Portland, OR 97239 USA.
EM cameromi@ohsu.edu; jwagne34@slu.edu
FU Acorda; Rehabilitation Research & Development Service, Department of
Veterans Affairs
FX M.H. Cameron: has been a consultant for Innovative Neurotronics; has
received grant support from Acorda; and has received a career
development award from the Rehabilitation Research & Development
Service, Department of Veterans Affairs; J.M. Wagner: none.
NR 50
TC 31
Z9 31
U1 2
U2 17
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1528-4042
J9 CURR NEUROL NEUROSCI
JI Curr. Neurol. Neurosci. Rep.
PD OCT
PY 2011
VL 11
IS 5
BP 507
EP 515
DI 10.1007/s11910-011-0214-y
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 814PH
UT WOS:000294468700007
PM 21779953
ER
PT J
AU Milanesi, A
Brent, GA
AF Milanesi, Anna
Brent, Gregory A.
TI Management of hypothyroidism in pregnancy
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Article
DE hypothyroidism; pregnancy; thyroxine therapy
ID MATERNAL THYROID-FUNCTION; IN-VITRO FERTILIZATION; SUBCLINICAL
HYPOTHYROIDISM; SELENIUM SUPPLEMENTATION; LEVOTHYROXINE TREATMENT;
IODINE DEFICIENCY; AUTOIMMUNE-THYROIDITIS; HORMONE CONCENTRATIONS;
STIMULATING HORMONE; REFERENCE INTERVALS
AB Purpose of review
Examine recent studies on the assessment of thyroid status in pregnancy, approach to thyroid testing, the spectrum of hypothyroidism in pregnancy, and strategies for thyroid replacement in women with known hypothyroidism.
Recent findings
Trimester-specific references range for thyroid-stimulating hormone (TSH) and free thyroxine in pregnancy must take into account iodine and thyroid autoantibody status, race, BMI, as well as other factors. Thyroid testing of only those pregnant women at increased risk for thyroid disease, case finding, will miss 30-80% of women with thyroid disease. Subclinical hypothyroidism is associated with an increasing number of adverse effects including infertility, miscarriage, preterm delivery, and breech presentation at birth. Many pregnant women with known hypothyroidism have an out-of-range TSH at the time of confirmed pregnancy. A variety of strategies are effective at keeping serum TSH normal during pregnancy including preconception increase in thyroxine, increase in thyroxine dose at the time pregnancy is confirmed, or making adjustments based on serum TSH monitoring.
Summary
Evaluation of thyroid status in pregnancy requires an understanding of pregnancy-associated changes in thyroid function tests and how they vary by trimester. The spectrum of hypothyroidism in pregnancy includes isolated thyroid peroxidase antibody positivity, isolated hypothyroxinemia, subclinical and overt hypothyroidism. These patterns, in some situations, may be related to iodine status, selenium status, or underlying thyroid disease. There are a variety of approaches to management of thyroxine replacement in known hypothyroid women at the time of pregnancy that are all effective at maintaining a normal range during pregnancy.
C1 [Milanesi, Anna; Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Dept Med, Los Angeles, CA USA.
[Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
RP Brent, GA (reprint author), 111 VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM gbrent@ucla.edu
FU VA Merit Review funds; Cedars Sinai Clinical Scholars Program
FX G.A. Brent is supported by VA Merit Review funds. A. Milanesi is
supported by the Cedars Sinai Clinical Scholars Program.
NR 54
TC 8
Z9 10
U1 2
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD OCT
PY 2011
VL 18
IS 5
BP 304
EP 309
DI 10.1097/MED.0b013e32834a91d1
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 814KD
UT WOS:000294448700004
PM 21841481
ER
PT J
AU LaRocque, RC
Jentes, ES
AF LaRocque, Regina C.
Jentes, Emily S.
TI Health recommendations for international travel: a review of the
evidence base of travel medicine
SO CURRENT OPINION IN INFECTIOUS DISEASES
LA English
DT Review
DE evidence-based medicine; international travel; travel medicine
ID RABIES POSTEXPOSURE PROPHYLAXIS; 4-DOSE VACCINE SCHEDULE; ILL RETURNED
TRAVELERS; MALARIA CHEMOPROPHYLAXIS; IMMUNIZATION PRACTICES;
ADVISORY-COMMITTEE; DIARRHEA; CHILDREN; TRIAL; SURVEILLANCE
AB Purpose of review
International travel is increasing, including travel to countries with emerging economies. Travel may pose health risks for the individual and contribute to the global spread of infectious diseases. The specialty of travel medicine is aimed at minimizing health risks associated with international travel. The field has emerged in the past 25 years, and the evidence base supporting its clinical practice is growing. This review will describe the evidence base underlying travel medicine, highlight recently updated travel medicine guidelines, and outline future research priorities.
Recent findings
Recommendations for a number of common vaccines for travelers have been updated recently. More sophisticated detection methods are leading to the identification of a wider spectrum of pathogens associated with travelers' diarrhea, and antibiotic resistance is increasingly being identified. New treatment options for malaria are available, and a fifth Plasmodium species causing disease in humans has been identified.
Summary
An evidence base for the practice of travel medicine is emerging. Expert opinion and consensus guidelines continue to play an important role in supporting clinical practice.
C1 [LaRocque, Regina C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[LaRocque, Regina C.] Harvard Univ, Sch Med, Boston, MA USA.
[Jentes, Emily S.] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Atlanta, GA USA.
RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 520,55 Fruit St, Boston, MA 02114 USA.
EM rclarocque@partners.org
FU US Centers for Disease Control and Prevention [U19CI000514]
FX R.C.L.R. is supported by funding from the US Centers for Disease Control
and Prevention (U19CI000514). The authors are grateful to Dr Edward T.
Ryan and Dr Phyllis Kozarsky for critical reading of the manuscript and
to Robert Citorik for assistance with the figures.
NR 48
TC 5
Z9 5
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7375
J9 CURR OPIN INFECT DIS
JI Curr. Opin. Infect. Dis.
PD OCT
PY 2011
VL 24
IS 5
BP 403
EP 409
DI 10.1097/QCO.0b013e32834a1aef
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 814UD
UT WOS:000294481800001
PM 21788892
ER
PT J
AU Charles, RC
Ryan, ET
AF Charles, Richelle C.
Ryan, Edward T.
TI Cholera in the 21st century
SO CURRENT OPINION IN INFECTIOUS DISEASES
LA English
DT Review
DE cholera; diarrhea; outbreak; vaccine; Vibrio cholerae
ID VIBRIO-CHOLERAE; FIELD TRIAL; FOLLOW-UP; EL-TOR; BANGLADESH; INFECTION;
EPIDEMIC; HAITI; TRANSMISSION; VACCINES
AB Purpose of review
This review will focus on recent advances in our understanding of biologic and environmental factors that shape current cholera outbreaks, advances in our understanding of host-pathogen interactions during cholera, and recent evolution of current treatment and cholera prevention strategies.
Recent findings
New research studies have improved our understanding of a number of dynamic factors that shape the ecology of Vibrio cholerae and influence its transmission, including the role of lytic bacteriophage, biofilm formation, a hyperinfectious state of human-passaged V. cholerae, and the impact of severe weather events. Provision of safe water and improved sanitation continue to be the mainstays of preventing cholera transmission; however, the role of cholera vaccination as a control measure in both endemic and epidemic settings is evolving. Recent advances in our understanding of long-lived protective immunity after natural infection may aid in the global efforts to control cholera.
Summary
Improved understanding of factors associated with protective immunity and dynamic factors associated with cholera outbreaks may lead to improved control and prevention strategies for cholera.
C1 [Charles, Richelle C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Charles, Richelle C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA.
EM etryan@partners.org
FU National Institute of Allergy and Infectious Diseases [AI077883,
AI058935, AI089721]; MGH
FX This work was supported by National Institute of Allergy and Infectious
Diseases [AI077883 (ETR), AI058935 (ETR), AI089721 (RCC)] and a MGH
Physician-Scientist Development Award (RCC).
NR 61
TC 34
Z9 35
U1 8
U2 50
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0951-7375
J9 CURR OPIN INFECT DIS
JI Curr. Opin. Infect. Dis.
PD OCT
PY 2011
VL 24
IS 5
BP 472
EP 477
DI 10.1097/QCO.0b013e32834a88af
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 814UD
UT WOS:000294481800011
PM 21799407
ER
PT J
AU Hammerness, PG
Surman, CBH
Chilton, A
AF Hammerness, Paul G.
Surman, Craig B. H.
Chilton, Ashley
TI Adult Attention-Deficit/Hyperactivity Disorder Treatment and
Cardiovascular Implications
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Article
DE ADHD; Treatment; Adult; Medication; Stimulant; Cardiovascular
ID DEFICIT-HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION IMPAIRMENTS;
PLACEBO-CONTROLLED TRIAL; RESTING HEART-RATE; REPORT SCALE ASRS;
LONG-TERM; LISDEXAMFETAMINE DIMESYLATE; OROS METHYLPHENIDATE;
EXTENDED-RELEASE; DOUBLE-BLIND
AB Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder afflicting adults worldwide. This article is an update on the evidence supporting medications for adult ADHD, with particular emphasis on cardiovascular implications. Relevant clinical literature was sought using PubMed searches, with an emphasis on new reports from April 2009 to April 2011. This review describes the efficacy and general tolerability of stimulant and nonstimulant medications for adults with ADHD as seen in contemporary clinical trials. Cardiovascular response to medications for ADHD is primarily seen in heart rate and blood pressure elevations, while less is known about the etiology of rare cardiovascular events or long-term sequelae. Further research is indicated to delineate clinical and functional outcomes for adults with ADHD, as well as long-term safety of medication treatment.
C1 [Hammerness, Paul G.; Surman, Craig B. H.; Chilton, Ashley] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Cambridge, MA 02138 USA.
[Hammerness, Paul G.; Surman, Craig B. H.; Chilton, Ashley] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Hammerness, PG (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA.
EM phammerness@partners.org
FU National Institutes of Health; Hilda and Preston Davis Foundation;
Cephalon; Eli Lilly and Company; ElMindA; GlaxoSmithKline; Johnson
Johnson; McNeil; Merck Co.; New River Pharmaceuticals; Novartis;
Ortho-McNeil-Janssen Pharmaceuticals; Pfizer; Shire; Takeda
Pharmaceuticals North America; McNeil Pharmaceutical
FX Dr. Surman has received research support from the National Institutes of
Health and the Hilda and Preston Davis Foundation.; During the past 2
years, Dr. Hammerness has served on an advisory board for Shire; has
received honoraria from Shire and Ortho-McNeil-Janssen Pharmaceuticals;
and has received grant support from Cephalon, Eli Lilly and Company,
ElMindA, GlaxoSmithKline, Johnson & Johnson, McNeil, Merck & Co., New
River Pharmaceuticals, Novartis, Ortho-McNeil-Janssen Pharmaceuticals,
Pfizer, Shire, and Takeda Pharmaceuticals North America.; Dr. Surman has
served as a consultant for Shire and McNeil Pharmaceutical and received
research support from Shire, Takeda Pharmaceuticals North America, and
McNeil Pharmaceutical.
NR 48
TC 11
Z9 11
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD OCT
PY 2011
VL 13
IS 5
BP 357
EP 363
DI 10.1007/s11920-011-0213-3
PG 7
WC Psychiatry
SC Psychiatry
GA 815CR
UT WOS:000294504200008
PM 21698412
ER
PT J
AU Oliva, EM
Maisel, NC
Gordon, AJ
Harris, AHS
AF Oliva, Elizabeth M.
Maisel, Natalya C.
Gordon, Adam J.
Harris, Alex H. S.
TI Barriers to Use of Pharmacotherapy for Addiction Disorders and How to
Overcome Them
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Article
DE Pharmacotherapy; Pharmacologic interventions; Addiction; Substance
dependence; Medication-assisted treatment; Substance abuse treatment;
Alcohol; Opioids; Barriers; Facilitators
ID SUBSTANCE-ABUSE TREATMENT; RANDOMIZED CONTROLLED-TRIALS; PSYCHIATRY
WFSBP GUIDELINES; OPIOID-DEPENDENT PATIENTS; ALCOHOL-USE DISORDERS;
BUPRENORPHINE TREATMENT; MAINTENANCE THERAPY; PRIMARY-CARE; TREATMENT
ORGANIZATIONS; SUBSTITUTION TREATMENT
AB Substance use disorders are highly prevalent, debilitating conditions for which effective pharmacotherapies exist with a broad evidence base, yet pharmacotherapy for the treatment of addiction disorders is underutilized. The goals of this review are to describe the barriers that may contribute to poor adoption and utilization of pharmacotherapy for alcohol and opioid dependence at the system, provider, and patient level and to discuss ways to overcome those barriers. Multifaceted efforts directed at all three levels may be needed to speed pharmacotherapy adoption. More research is needed to help us better understand barriers from patients' perspectives. Strategies to promote adoption of pharmacotherapy for addiction disorders should be modified to fit the needs of the practice, system, and individual patients. Pharmacotherapy is a valuable tool in the clinical armamentarium of addiction treatment; thus, overcoming barriers to implementation may improve clinical and social outcomes.
C1 [Oliva, Elizabeth M.; Maisel, Natalya C.; Harris, Alex H. S.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA.
[Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Hlth Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA.
[Gordon, Adam J.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA.
RP Oliva, EM (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, 795 Willow Rd,Mailcode 152 MPD, Menlo Pk, CA 94025 USA.
EM elizabeth.oliva@va.gov; natalya.maisel@va.gov; adam.gordon@va.gov;
alexander.harris2@va.gov
FU NIMH NIH HHS [R25 MH080916]
NR 76
TC 26
Z9 26
U1 4
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD OCT
PY 2011
VL 13
IS 5
BP 374
EP 381
DI 10.1007/s11920-011-0222-2
PG 8
WC Psychiatry
SC Psychiatry
GA 815CR
UT WOS:000294504200010
PM 21773951
ER
PT J
AU Moscariello, A
Takx, RAP
Schoepf, UJ
Renker, M
Zwerner, PL
O'Brien, TX
Allmendinger, T
Vogt, S
Schmidt, B
Savino, G
Fink, C
Bonomo, L
Henzler, T
AF Moscariello, Antonio
Takx, Richard A. P.
Schoepf, U. Joseph
Renker, Matthias
Zwerner, Peter L.
O'Brien, Terrence X.
Allmendinger, Thomas
Vogt, Sebastian
Schmidt, Bernhard
Savino, Giancarlo
Fink, Christian
Bonomo, Lorenzo
Henzler, Thomas
TI Coronary CT angiography: image quality, diagnostic accuracy, and
potential for radiation dose reduction using a novel iterative image
reconstruction technique-comparison with traditional filtered back
projection
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Iterative reconstruction; Coronary CT angiography; Image noise;
Radiation dose; Image quality
ID DUAL-SOURCE CT; SPIRAL COMPUTED-TOMOGRAPHY; ARTERY-DISEASE;
TEMPORAL-RESOLUTION; CARDIAC CT; PERFORMANCE; NOISE; CHEST; METAANALYSIS
AB Objectives To compare image noise, image quality and diagnostic accuracy of coronary CT angiography (cCTA) using a novel iterative reconstruction algorithm versus traditional filtered back projection (FBP) and to estimate the potential for radiation dose savings.
Methods Sixty five consecutive patients (48 men; 59.3 +/- 7.7 years) prospectively underwent cCTA and coronary catheter angiography (CCA). Full radiation dose data, using all projections, were reconstructed with FBP. To simulate image acquisition at half the radiation dose, 50% of the projections were discarded from the raw data. The resulting half-dose data were reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE). Full-dose FBP and half-dose iterative reconstructions were compared with regard to image noise and image quality, and their respective accuracy for stenosis detection was compared against CCA.
Results Compared with full-dose FBP, half-dose iterative reconstructions showed significantly (p = 0.001 - p = 0.025) lower image noise and slightly higher image quality. Iterative reconstruction improved the accuracy of stenosis detection compared with FBP (per-patient: accuracy 96.9% vs. 93.8%, sensitivity 100% vs. 100%, specificity 94.6% vs. 89.2%, NPV 100% vs. 100%, PPV 93.3% vs. 87.5%).
Conclusions Iterative reconstruction significantly reduces image noise without loss of diagnostic information and holds the potential for substantial radiation dose reduction from cCTA.
C1 [Moscariello, Antonio; Takx, Richard A. P.; Schoepf, U. Joseph; Renker, Matthias; Zwerner, Peter L.; O'Brien, Terrence X.; Fink, Christian; Henzler, Thomas] Med Univ S Carolina, Heart & Vasc Ctr, Charleston, SC 29425 USA.
[Moscariello, Antonio; Savino, Giancarlo; Bonomo, Lorenzo] Univ Cattolica Sacro Cuore, Dept Bioimaging & Radiol Sci, A Gemelli Hosp, I-00168 Rome, Italy.
[Takx, Richard A. P.] Maastricht Univ Med Ctr, Dept Radiol, Maastricht, Netherlands.
[O'Brien, Terrence X.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Allmendinger, Thomas; Schmidt, Bernhard] Siemens AG, Healthcare Sect, Forchheim, Germany.
[Vogt, Sebastian] Siemens Med Solut USA, Malvern, PA USA.
[Fink, Christian; Henzler, Thomas] Univ Heidelberg, Inst Clin Radiol & Nucl Med, Univ Med Ctr Mannheim, Med Fac Mannheim, Heidelberg, Germany.
RP Schoepf, UJ (reprint author), Med Univ S Carolina, Heart & Vasc Ctr, Ashley River Tower,25 Courtenay Dr, Charleston, SC 29425 USA.
EM schoepf@musc.edu
FU Bayer-Schering; Bracco; General Electric, Medrad; Siemens; Department of
Veterans Affairs
FX UJS is a consultant for and receives research support from
Bayer-Schering, Bracco, General Electric, Medrad, and Siemens. TA, SV,
and BS are employees of Siemens Healthcare. The other authors have no
conflict of interest to disclose.; This study was supported in part by
the Research and Development Program of the Department of Veterans
Affairs. The contents do not represent the views of the Department of
Veterans Affairs or the United States Government.
NR 36
TC 156
Z9 194
U1 1
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
J9 EUR RADIOL
JI Eur. Radiol.
PD OCT
PY 2011
VL 21
IS 10
BP 2130
EP 2138
DI 10.1007/s00330-011-2164-9
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 814QD
UT WOS:000294471100013
PM 21611758
ER
PT J
AU Macco, R
Pelizzoni, I
Arbel-Ornath, M
Codazzi, F
Zacchetti, D
Bacskai, BJ
Grohovaz, F
AF Macco, R.
Pelizzoni, I
Arbel-Ornath, M.
Codazzi, F.
Zacchetti, D.
Bacskai, B. J.
Grohovaz, F.
TI ASTROCYTIC RESPONSE TO OXIDATIVE STRESS: EVIDENCES FROM IN VITRO AND IN
VIVO STUDIES
SO GLIA
LA English
DT Meeting Abstract
DE Astrocyte activation; Oxidative stress; In vivo two-photon microscopy
C1 [Macco, R.; Pelizzoni, I; Codazzi, F.; Zacchetti, D.; Grohovaz, F.] Ist Sci San Raffaele, Div Neurosci, I-20132 Milan, Italy.
[Arbel-Ornath, M.; Bacskai, B. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Arbel-Ornath, M.; Bacskai, B. J.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 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 0894-1491
J9 GLIA
JI Glia
PD OCT
PY 2011
VL 59
SU 1
BP S77
EP S77
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 811CF
UT WOS:000294178900299
ER
PT J
AU Vitte, J
Chareyre, F
Chareyre, B
Bonne, NX
Stemmer-Rachamimov, A
Giovannini, M
AF Vitte, J.
Chareyre, F.
Chareyre, B.
Bonne, N. X.
Stemmer-Rachamimov, A.
Giovannini, M.
TI SNF5 INACTIVATION IN P0 PERMISSIVE CELLS INITIATES FORMATION OF
PERIPHERAL NERVE SHEATH TUMORS (PNST) WITH RHABDOID FEATURES
SO GLIA
LA English
DT Meeting Abstract
DE SMARCB1/Snf5/Ini1; Peripheral Nerve Sheath Tumors; Olfactory Ensheathing
Cells
C1 [Vitte, J.; Chareyre, F.; Chareyre, B.; Bonne, N. X.; Giovannini, M.] Ctr Neural Tumor Res, House Res Inst, Los Angeles, CA USA.
[Stemmer-Rachamimov, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Stemmer-Rachamimov, A.] Harvard Univ, Sch Med, Mol Neurooncol & Pathol Dept, Boston, MA USA.
RI Vitte, Jeremie/B-9874-2017
OI Vitte, Jeremie/0000-0002-2567-7988
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-1491
J9 GLIA
JI Glia
PD OCT
PY 2011
VL 59
SU 1
BP S97
EP S97
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 811CF
UT WOS:000294178900381
ER
PT J
AU Wegener, A
Kerninon, C
Deboux, C
Maire, C
Wegner, M
Oumesmar, BN
AF Wegener, A.
Kerninon, C.
Deboux, C.
Maire, C.
Wegner, M.
Oumesmar, Nait B.
TI FUNCTION OF THE B-HLH TRANSCRIPTION FACTOR OLIG2 IN OLIGODENDROCYTE
DIFFERENTIATION
SO GLIA
LA English
DT Meeting Abstract
DE multiple sclerosis; OLIG2; oligodendrocyte differentiation
C1 [Wegener, A.; Kerninon, C.; Deboux, C.; Oumesmar, Nait B.] Univ Paris 06, INSERM, Cellular & Mol Approaches Myelin Repair U975, F-75013 Paris, France.
[Maire, C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Maire, C.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Wegner, M.] Inst Biochem, Erlangen, Germany.
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 0894-1491
J9 GLIA
JI Glia
PD OCT
PY 2011
VL 59
SU 1
BP S49
EP S49
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 811CF
UT WOS:000294178900188
ER
PT J
AU Carter, EA
Bonab, AA
Goverman, J
Paul, K
Yerxa, J
Tompkins, RG
Fischman, AJ
AF Carter, Edward A.
Bonab, Ali A.
Goverman, Jeremy
Paul, Kasie
Yerxa, John
Tompkins, Ronald G.
Fischman, Alan J.
TI Evaluation of the antioxidant peptide SS31 for treatment of burn-induced
insulin resistance
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Article
DE burn-injury; trauma; insulin-resistance; glucose-tolerance cold-stress;
anti-oxidant oxidative stress; brown adipose tissue; oral glucose
tolerance tests; mu PET; (18)FDG; SS31; SS20; reactive oxygen species
ID OBESE ZUCKER RATS; ALPHA-LIPOIC ACID; OXIDATIVE STRESS; SKELETAL-MUSCLE;
REPERFUSION INJURY; GLUCOSE-TRANSPORT; ADIPOSE-TISSUE; REDOX STATE;
KINASE-B; CELL
AB After severe burn injury and other major traumas, glucose tolerance tests demonstrate delayed glucose disposal. This 'diabetes of injury' could be explained by insulin deficiency, and several studies have shown that soon after trauma (ebb phase) insulin concentrations are reduced in the face of hyperglycemia. After resuscitation of trauma patients (flow phase), p-cell responsiveness normalizes and plasma insulin levels are appropriate or even higher than expected, however, glucose intolerance and hyperglycemia persist. In the acute care setting, several approaches have been used for treating insulin resistance, including insulin infusion, propranolol and glucagon-like-peptide-1 (GLP-1). Recently, it was demonstrated that a tetrapeptide with antioxidant properties D-Arg-Dmt-Lys-Phe-NH2 (SS31), but not its inactive analogue Phe-D-Arg-Phe-Lys-NH2 (SS20) attenuates insulin resistance in mice maintained on a high fat diet. In this report the effects of SS31 and SS20 on burn-induced insulin resistance was studied in mice. Oral glucose tolerance tests (OGTT) were performed in 4 groups of 6 mice with thermal injury with or without pre-treatment with SS31 or SS20 and sham controls. In addition, biodistribution of (18)FDG was measured in burned mice with and without SS31 treatment and shams (subsets of these animals were also studied by mu PET). For comparison purposes, groups of 6 cold-stressed mice with and without SS31 treatment were also studied. The results of these studies demonstrate that SS31 but not SS20 ameliorated burn-induced insulin resistance. In addition, SS31 treatment resulted in marked reduction in the increased (18)FDG uptake by brown adipose tissue (BAT) in burned but not cold-stressed animals; suggesting that the stressors act by different mechanisms. Overall, these studies confirmed that SS31 can be used to reverse burn-induced insulin resistance and provide a firm pre-clinical basis for future clinical trials of SS31 for the treatment of insulin resistance in patients with burn injury.
C1 [Carter, Edward A.; Bonab, Ali A.; Goverman, Jeremy; Paul, Kasie; Yerxa, John; Tompkins, Ronald G.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA 02114 USA.
[Goverman, Jeremy; Paul, Kasie; Yerxa, John; Tompkins, Ronald G.; Fischman, Alan J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Bonab, Ali A.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA.
[Carter, Edward A.; Bonab, Ali A.; Goverman, Jeremy; Tompkins, Ronald G.; Fischman, Alan J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fischman, AJ (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA.
EM aajjff@gmail.com
RI Yerxa, John/E-7252-2017
OI Yerxa, John/0000-0002-5283-3069
FU National Institutes of Health [2P50 GM21700-27A]; Shriners Hospitals for
Children
FX This study was supported in part by grants from the National Institutes
of Health (2P50 GM21700-27A) and the Shriners Hospitals for Children.
NR 50
TC 7
Z9 8
U1 0
U2 7
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD OCT
PY 2011
VL 28
IS 4
BP 589
EP 594
DI 10.3892/ijmm.2011.752
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 815NS
UT WOS:000294532900016
PM 21805045
ER
PT J
AU Hwang, SJ
Suh, MJ
Yoon, JH
Kim, MR
Ryu, KS
Nam, SW
Donahoe, PK
MacLaughlin, DT
Kim, JH
AF Hwang, Seong Jin
Suh, Min Jung
Yoon, Joo Hee
Kim, Mee Ran
Ryu, Ki Sung
Nam, Suk Woo
Donahoe, Patricia K.
MacLaughlin, David T.
Kim, Jang Heub
TI Identification of characteristic molecular signature of Mullerian
inhibiting substance in human HPV-related cervical cancer cells
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE Mullerian inhibiting substance; anti-Mullerian hormone; Mullerian
inhibiting substance type II receptor; CaSki cell line; DNA microarray;
cell cycle
ID HUMAN OVARIAN-CANCER; GENE-EXPRESSION; IN-VIVO;
HEPATOCELLULAR-CARCINOMA; DEPENDENT KINASES; II RECEPTOR; GROWTH;
HORMONE; PATHWAY; FAMILY
AB Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH), is a member of the transforming growth factor-beta (TGF-beta) superfamily that plays an important role in the mesenchymal-epithelial interaction, cell growth and proliferation, extracellular matrix production and tissue remodeling. Previously, we demonstrated that MIS suppressed ovarian cancer cell growth and suggested large-scale genetic elements that could be responsible for anti-neoplastic effects of MIS on ovarian cancer cells. In this study, we demonstrated the expression of MIS type II receptor (MISRII) in the human papillomavirus (HPV)-16-related cervical cancer cell lines CaSki and Si Ha, and a non-HPV-related cervical cancer cell line, C33A. We also showed that MIS inhibited growth of cervical cancer cells, and induced cellular apoptosis of C33A. In addition, we identified a characteristic molecular signature of MIS in CaSki cells by using whole genome expression analysis. Of the 1,690 genes that showed significant expression changes by MIS, 21 genes were related to cell cycle; 13 genes to apoptosis; and 52 genes to the cancer pathway. On performing a search for cell cycle pathways in the KEGG pathway database, several gene expressions at the G(1)/S checkpoint were found. In particular, the expression of p16 and p107 increased and that of E2F2 and E2F3 decreased at an early stage, whereas the expression of E2F4 and E2F5 decreased at a later stage after MIS treatment. These data suggest that MIS produces activity against HPV16-related cervical cancers in vitro, and MIS may also be an effective targeted therapy for HPV16-related cervical cancer. Genetic data obtained here could be useful in determining the treatment strategy of MISR-expressing cervical tumors in the future.
C1 [Hwang, Seong Jin; Suh, Min Jung; Yoon, Joo Hee; Kim, Mee Ran; Ryu, Ki Sung; Kim, Jang Heub] Catholic Univ Korea, Coll Med, Dept Obstet & Gynecol, Seoul 137701, South Korea.
[Nam, Suk Woo] Catholic Univ Korea, Coll Med, Microdissect Genom Res Inst, Dept Pathol, Seoul 137701, South Korea.
[Donahoe, Patricia K.; MacLaughlin, David T.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA.
[Donahoe, Patricia K.; MacLaughlin, David T.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Kim, JH (reprint author), Catholic Univ Korea, Coll Med, Dept Obstet & Gynecol, 505 Banpo Dong, Seoul 137701, South Korea.
EM janghkim@catholic.ac.kr
NR 28
TC 7
Z9 9
U1 0
U2 2
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD OCT
PY 2011
VL 39
IS 4
BP 811
EP 820
DI 10.3892/ijo.2011.1042
PG 10
WC Oncology
SC Oncology
GA 815NU
UT WOS:000294533100007
PM 21573503
ER
PT J
AU Pedrelli, P
Iovieno, N
Vitali, M
Tedeschini, E
Bentley, KH
Papakostas, GI
AF Pedrelli, Paola
Iovieno, Nadia
Vitali, Mario
Tedeschini, Enrico
Bentley, Kate H.
Papakostas, George I.
TI Treatment of Major Depressive Disorder and Dysthymic Disorder With
Antidepressants in Patients With Comorbid Opiate Use Disorders Enrolled
in Methadone Maintenance Therapy A Meta-Analysis
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE antidepressant; placebo; major depressive disorder; opiate-use
disorders; methadone maintenance therapy
ID 2.5-YEAR FOLLOW-UP; EXCLUSION CRITERIA; CLINICAL-TRIALS; SUBSTANCE USE;
DIAGNOSTIC CRITERIA; MAINTAINED PATIENTS; DEPENDENT PATIENTS;
TREATMENT-SEEKING; EXCHANGE PROGRAM; PLACEBO-RESPONSE
AB Depression and opiate-use disorders (abuse, dependence) often co-occur, each condition complicating the course and outcome of the other. It has been recommended that clinicians prescribe antidepressant therapy for mood symptoms in patients with active substance-use disorders, but whether antidepressants are effective in this specific population is not entirely clear. Therefore, the aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder (DD) with comorbid opiate-use disorders currently in methadone maintenance treatment (MMT). Medline/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the treatment of MDD/DD in patients with comorbid opiate-use disorders currently in MMT. The search was limited to articles published between January 1, 1980, and June 30, 2010 (inclusive). Four manuscripts were found eligible for inclusion in our analysis (n = 317 patients). We found no statistically significant difference in response rates between antidepressant and placebo therapy in trials of MDD/DD patients with comorbid opiate-use disorders currently in MMT (risk ratio for response, 1.182; 95% CI: 0.822-1.700; P = 0.366). These results show no difference in the depressive outcome of patients with comorbid opiate-use disorders on MMT whether they are on medication or placebo. Future studies examining the effectiveness of antidepressants while controlling for several variables such as psychosocial treatment and assessing the specific classes of antidepressants are needed.
C1 [Pedrelli, Paola; Iovieno, Nadia; Vitali, Mario; Tedeschini, Enrico; Bentley, Kate H.; Papakostas, George I.] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Iovieno, Nadia] Univ Pisa, Dept Psychiat, Pisa, Italy.
[Vitali, Mario] Univ Roma La Sapienza, Dept Psychiat, Rome, Italy.
[Tedeschini, Enrico] Univ Modena & Reggio Emilia, Dept Psychiat, Modena, Italy.
RP Pedrelli, P (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med, 1 Bowdoin Sq, Boston, MA 02114 USA.
EM ppedrelli@partners.org
RI Papakostas, George/I-6905-2013
OI Papakostas, George/0000-0002-2465-5103
FU Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute
of Mental Health
FX Drs Pedrelli, Iovieno, Vitali, and Tedeschini and Ms Bentley report no
competing interests. Dr Papakostas has served as a consultant for
AstraZeneca PLC, Bristol-Myers Squibb Company, Eli Lilly Company,
GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz
Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc, Pierre
Fabre Laboratories, Shire Pharmaceuticals, and Wyeth, Inc; has received
honoraria from AstraZeneca PLC, Bristol-Myers Squibb Company, Eli Lilly
Company, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz
Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer,
Pierre Fabre Laboratories, Shire Pharmaceuticals, Titan Pharmaceuticals,
and Wyeth Inc; has received research support from Bristol-Myers Squibb
Company, Forest Pharmaceuticals, and the National Institute of Mental
Health; and has served on the speakers' bureau for Bristol-Myers Squibb
Company and Pfizer, Inc.
NR 40
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Z9 9
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD OCT
PY 2011
VL 31
IS 5
BP 582
EP 586
DI 10.1097/JCP.0b013e31822c0adf
PG 5
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 814OU
UT WOS:000294467300007
PM 21869696
ER
PT J
AU Evins, AE
Pachas, G
Mischoulon, D
Urbanoski, K
Carlini, S
Sousa, J
Bentley, K
Rigotti, NA
Nino-Gomez, J
Loebl, T
Janes, AC
Kaufman, MJ
Fava, M
AF Evins, A. Eden
Pachas, Gladys
Mischoulon, David
Urbanoski, Karen
Carlini, Sara
Sousa, Jessica
Bentley, Kate
Rigotti, Nancy A.
Nino-Gomez, Johanna
Loebl, Tsafrir
Janes, Amy C.
Kaufman, Marc J.
Fava, Maurizio
TI A Double-Blind, Placebo-Controlled Trial of the NMDA Glycine Site
Antagonist, GW468816, for Prevention of Relapse to Smoking in Females
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE nicotine; smoking cessation; NMDA; glutamate; relapse prevention;
glycine
ID SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED-TRIAL; INDUCED
DOPAMINE RELEASE; RECEPTOR PARTIAL AGONIST; VENTRAL TEGMENTAL AREA;
PHYSICAL-DEPENDENCE; NUCLEUS-ACCUMBENS; GLUTAMATE RECEPTORS; MK-801
DIZOCILPINE; CHRONIC NICOTINE
AB Relapse to smoking is common after initial abstinence with pharmacotherapy and behavioral support and represents a major clinical challenge. Although mechanisms underlying relapse to smoking have not been elucidated, preclinical studies suggest that glutamate receptors may be involved. We sought to test a selective antagonist of the glycine coagonist site on the glutamate N-methyl-D-aspartate receptor, GW468816, for prevention of relapse in recently abstinent smokers. To do so, we enrolled 264 healthy female smokers in an open 8-week smoking cessation intervention with behavioral therapy and a standard dose of transdermal nicotine replacement therapy with taper and additional gum or lozenge as needed for nicotine withdrawal symptoms. Ninety-eight participants achieved 7-day point prevalence abstinence and were randomized into a 5-week double-blind, placebo-controlled, relapse-prevention trial of GW468816 (200 mg/d) and then followed for 60 days after randomization. There was no effect of treatment on abstinence rates at the end of treatment (chi(2) [1, n = 96] = 0.168, P = 0.838), on the rates of relapse (chi(2) [1, n = 98] = 0.031, P = 1.000) or lapse (chi(2) [1, n = 62] = 0.802, P = 0.423), or on time to relapse (chi(2) [1, n = 98) = 0.001, P = 0.972). No significant relationships were detected between plasma GW468816 concentrations and abstinence, time to relapse, or self-reported craving. In conclusion, despite promising preclinical data that support the use of a selective NMDA glycine site antagonist for prevention of relapse to smoking, we observed no effect of GW468816 on relapse or lapse rates, time to relapse, or craving compared to placebo.
C1 [Evins, A. Eden] Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, Boston, MA 02114 USA.
[Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Janes, Amy C.; Kaufman, Marc J.] McLean Hosp, Belmont, MA 02178 USA.
RP Evins, AE (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, Dept Psychiat, 60 Staniford St, Boston, MA 02114 USA.
EM a_eden_evins@hms.harvard.edu
RI Janes, Amy/A-5322-2013;
OI Janes, Amy/0000-0002-3749-5006; Urbanoski, Karen/0000-0001-7287-7176
FU National Institute of Health [U01DA019378]; GlaxoSmithKline; Abbott
Laboratories; Alkermes, Inc; Aspect Medical Systems; AstraZeneca;
BioResearch; BrainCells Inc; Bristol-Myers Squibb; Cephalon, Inc; CeNeRx
BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli
Lilly and Company; EnVivo Pharmaceuticals, Inc; Euthymics Bioscience,
Inc; Forest Pharmaceuticals, Inc; Ganeden Biotech, Inc; Icon Clinical
Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research
Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM;
NIDA; NIMH; Novartis AG; Organon Pharmaceuticals; PamLab, LLC; Pfizer
Inc; Pharmavite(R) LLC; Photothera; Roche; RCT Logic, LLC;
Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc; Synthelabo;
Wyeth-Ayerst Pharmaceuticals, Inc; Transcept Pharmaceuticals, Inc; Vanda
Pharmaceuticals, Inc.; Pfizer; Janssen; Nordic Naturals; Ganeden; Nabi
Biopharmaceuticals
FX This study was funded by National Institute of Health grant U01DA019378
and by research product and grant support from GlaxoSmithKline (Drs
Evins, Kaufman, and Fava).; Dr Fava has received research support from:
Abbott Laboratories; Alkermes, Inc; Aspect Medical Systems; AstraZeneca;
BioResearch; BrainCells Inc; Bristol-Myers Squibb; Cephalon, Inc; CeNeRx
BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli
Lilly and Company; EnVivo Pharmaceuticals, Inc; Euthymics Bioscience,
Inc; Forest Pharmaceuticals, Inc; Ganeden Biotech, Inc; GlaxoSmithKline;
Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson
Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex
Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis AG; Organon
Pharmaceuticals; PamLab, LLC; Pfizer Inc; Pharmavite (R) LLC;
Photothera; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay
Pharmaceuticals, Inc; Synthelabo; Wyeth-Ayerst Pharmaceuticals, Inc;
Transcept Pharmaceuticals, Inc; and Vanda Pharmaceuticals, Inc.; Dr
Evins has received research support from Pfizer, Janssen, GSK, and
Aspect Medical Systems, and honoraria from Pfizer, Janssen, GSK and
Boehringer Ingelheim. Dr Mischoulon has received research support from
Nordic Naturals, and Ganeden; royalties from Back Bay Scientific and
Lippincott Williams & Wilkins; and honoraria from Pamlab, Nordic
Naturals, and Reed Medical Education. Dr Rigotti has received research
grant support from Pfizer and Nabi Biopharmaceuticals and is an unpaid
consultant for Pfizer and Free and Clear. Drs Pachas, Janes, Urbanoski,
Nino-Gomez, Loebl and Ms Carlini, Sousa, and Bentley have none to
disclose.
NR 49
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Z9 5
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD OCT
PY 2011
VL 31
IS 5
BP 597
EP 602
DI 10.1097/JCP.0b013e31822bb390
PG 6
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 814OU
UT WOS:000294467300010
PM 21869693
ER
PT J
AU Borba, CPC
Fan, X
Copeland, PM
Paiva, A
Freudenreich, O
Henderson, DC
AF Borba, Christina P. C.
Fan, Xiaoduo
Copeland, Paul M.
Paiva, Alexander
Freudenreich, Oliver
Henderson, David C.
TI Placebo-Controlled Pilot Study of Ramelteon for Adiposity and Lipids in
Patients With Schizophrenia
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE ramelteon; schizophrenia; obesity; insulin resistance; glucose
metabolism
ID FATTY-ACID-METABOLISM; GLUCOSE-TOLERANCE; INSULIN SENSITIVITY; VISCERAL
ADIPOSITY; MELATONIN; SCALE; CHOLESTEROL; OLANZAPINE; DENSITY; QUALITY
AB Objective: Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population. In particular, no single agent can correct multiple metabolic abnormalities such as insulin resistance, hyperlipidemia, inflammation, obesity, and fat distribution. We now report a randomized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia.
Methods: A double-blind, placebo-controlled, 8-week pilot trial was conducted, adding ramelteon 8 mg/d to stable outpatients with schizophrenia. Vital signs and anthropometric measurements, including height, weight, waist circumference, and body fat were assessed, and laboratory assays were tracked to monitor changes in metabolic markers.
Results: Twenty-five subjects were randomly assigned to treatment with study drug or placebo, and 20 subjects were included in the final analysis. Ramelteon did not improve anthropometric measurements, glucose metabolism, and inflammatory markers. There was, however, a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group. Although the standard anthropometric measures did not show significant change, the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size.
Conclusions: Although ramelteon decreased cholesterol, treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes. Future studies are needed for patients with schizophrenia with a larger sample size to fully understand ramelteon's effects on abdominal adiposity and lipids.
C1 [Borba, Christina P. C.; Fan, Xiaoduo; Paiva, Alexander; Freudenreich, Oliver; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA.
[Borba, Christina P. C.; Fan, Xiaoduo; Copeland, Paul M.; Freudenreich, Oliver; Henderson, David C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Copeland, Paul M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Borba, CPC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA.
EM cborba@partners.org
FU Takeda Pharmaceuticals North America, Inc; Harvard Clinical and
Translational Science Center, National Center for Research Resources
[M01-RR-01066, 1 UL1 RR025758-01]
FX This study was funded by Takeda Pharmaceuticals North America, Inc, and
supported by grant M01-RR-01066 and grant 1 UL1 RR025758-01, Harvard
Clinical and Translational Science Center, from the National Center for
Research Resources.
NR 30
TC 16
Z9 16
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-0749
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD OCT
PY 2011
VL 31
IS 5
BP 653
EP 658
DI 10.1097/JCP.0b013e31822bb573
PG 6
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 814OU
UT WOS:000294467300018
PM 21869685
ER
PT J
AU Mani, N
Caiola, E
Fortuna, RJ
AF Mani, Nandini
Caiola, Enrico
Fortuna, Robert J.
TI The Influence of Social Networks on Patients' Attitudes Toward Type II
Diabetes
SO JOURNAL OF COMMUNITY HEALTH
LA English
DT Article
DE Primary care; Disease management; Diabetes; Social network; Health
outcomes
ID GLYCEMIC CONTROL; PERCEIVED RISK; FAMILY; MELLITUS; ADULTS; WOMEN
AB Social networks are increasingly recognized as important determinants of many chronic diseases, yet little data exist regarding the influence of social networks on diabetes. We surveyed diabetic patients to determine how social networks affect their overall level of concern regarding diabetes and its complications. We adapted a previously published instrument and surveyed 240 diabetic patients at two primary care practices. Patients recorded the number of family and friends who had diabetes and rated their level of concern about diabetes on a scale of 0% (no concern) to 100% (extremely concerned). Our primary outcome variable was patients' level of concern (< 75% or a parts per thousand yen75%). We developed logistic regression models to determine the effect of disease burden in patients' social networks on expressed level of concern about diabetes. We received 154 surveys (64% response rate). We found that for each additional family member with diabetes, patients expressed a greater level of concern about diabetes (AOR 1.5; 95% CI 1.2-2.0) and its potential complications (AOR 1.4; 95% CI 1.1-1.7). Similarly, patients with an increased number of friends with diabetes expressed greater concern about diabetes (AOR 1.5; 95% CI 1.2-1.9) and its complications (AOR 1.3; 95% CI 1.1-1.7). Patients with a higher prevalence of diabetes within their social networks expressed greater concern about diabetes and diabetic complications. Determining disease burden within patients' social networks may allow physicians to better understand patients' perspectives on their disease and ultimately help them achieve meaningful behavioral change.
C1 [Mani, Nandini] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Revere, MA 02151 USA.
[Mani, Nandini] MGH Revere Hlth Care Ctr, Revere, MA 02151 USA.
[Caiola, Enrico; Fortuna, Robert J.] Univ Rochester, Sch Med & Dent, Ctr Primary Care, Culver Med Grp, Rochester, NY 14609 USA.
RP Mani, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 300 Ocean Ave, Revere, MA 02151 USA.
EM nmani1@partners.org; Enrico_Caiola@urmc.rochester.edu;
Robert_Fortuna@urmc.rochester.edu
NR 12
TC 2
Z9 2
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0094-5145
J9 J COMMUN HEALTH
JI J. Community Health
PD OCT
PY 2011
VL 36
IS 5
BP 728
EP 732
DI 10.1007/s10900-011-9366-6
PG 5
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 812MS
UT WOS:000294298200006
PM 21298473
ER
PT J
AU Prerau, MJ
Eden, UT
AF Prerau, Michael J.
Eden, Uri T.
TI A General Likelihood Framework for Characterizing the Time Course of
Neural Activity
SO NEURAL COMPUTATION
LA English
DT Article
ID SPIKE TRAIN DATA; CROSS-VALIDATION; NONPARAMETRIC REGRESSION; NEURONS;
KERNEL; PATTERNS; INFORMATION; HIPPOCAMPUS; PREDICTION; DISCHARGE
AB We develop a general likelihood-based framework for use in the estimation of neural firing rates, which is designed to choose the temporal smoothing parameters that maximize the likelihood of missing data. This general framework is algorithm-independent and thus can be applied to a multitude of established methods for firing rate or conditional intensity estimation. As a simple example of the use of the general framework, we apply it to the peristimulus time histogram and kernel smoother, the methods most widely used for firing rate estimation in the electrophysiological literature and practice. In doing so, we illustrate how the use of the framework can employ the general point process likelihood as a principled cost function and can provide substantial improvements in estimation accuracy for even the most basic of rate estimation algorithms. In particular, the resultant kernel smoother is simple to implement, efficient to compute, and can accurately determine the bandwidth of a given rate process from individual spike trains. We perform a simulation study to illustrate how the likelihood framework enables the kernel smoother to pick the bandwidth parameter that best predicts missing data, and we show applications to real experimental spike train data. Additionally, we discuss how the general likelihood framework may be used in conjunction with more sophisticated methods for firing rate and conditional intensity estimation and suggest possible applications.
C1 [Prerau, Michael J.; Eden, Uri T.] Boston Univ, Grad Program Neurosci, Boston, MA 02215 USA.
[Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
RP Prerau, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA.
EM prerau@nmr.mgh.harvard.edu; tzvi@bu.edu
FU National Science Foundation [IIS-0643995]
FX This work was supported by the National Science Foundation under grant
number IIS-0643995. We thank Paul Lipton and Howard Eichenbaum for the
use of the experimental data.
NR 44
TC 3
Z9 3
U1 1
U2 2
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0899-7667
J9 NEURAL COMPUT
JI Neural Comput.
PD OCT
PY 2011
VL 23
IS 10
BP 2537
EP 2566
PG 30
WC Computer Science, Artificial Intelligence; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 815SR
UT WOS:000294549600004
PM 21732865
ER
PT J
AU Ghomi, RH
Bredella, MA
Thomas, BJ
Miller, KK
Torriani, M
AF Ghomi, Reza Hosseini
Bredella, Miriam A.
Thomas, Bijoy J.
Miller, Karen K.
Torriani, Martin
TI Modular MR-compatible lower leg exercise device for whole-body scanners
SO SKELETAL RADIOLOGY
LA English
DT Article
DE Exercise; Ergometer; MR-compatible
ID IN-VIVO MRS; CALF MUSCLE; ERGOMETER
AB To develop a modular MR-compatible lower leg exercise device for muscle testing using a clinical 3 T MR scanner.
An exercise device to provide isotonic resistance to plantar- or dorsiflexion was constructed from nonferrous materials and designed for easy setup and use in a clinical environment. Validation tests were performed during dynamic MR acquisitions. For this purpose, the device was tested on the posterior lower leg musculature of five subjects during 3 min of exercise at 30% of maximum voluntary plantarflexion during 31-phosphorus MR spectroscopy (P-31-MRS). Measures of muscle phosphocreatine (PCr), inorganic phosphate (Pi), and pH were obtained before, during, and after the exercise protocol.
At the end of exercise regimen, muscle PCr showed a 28% decrease from resting levels (to 21.8 +/- 3.9 from 30.4 +/- 3.0 mM) and the average PCr recovery rate was 35.3 +/- 8.3 s. Muscle Pi concentrations increased 123% (to 14.6 +/- 4.7 from 6.5 +/- 3.3 mM) and pH decreased 1.5% (to 7.06 +/- 0.14 from 7.17 +/- 0.07) from resting levels.
The described MR-compatible lower leg exercise was an effective tool for data acquisition during dynamic MR acquisitions of the calf muscles. The modular design allows for adaptation to other whole-body MR scanners and incorporation of custom-built mechanical or electronic interfaces and can be used for any MR protocol requiring dynamic evaluation of calf muscles.
C1 [Ghomi, Reza Hosseini; Bredella, Miriam A.; Thomas, Bijoy J.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Ghomi, Reza Hosseini; Bredella, Miriam A.; Thomas, Bijoy J.; Miller, Karen K.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,YAW 6048, Boston, MA 02114 USA.
EM mtorriani@hms.harvard.edu
OI Hosseini Ghomi, Reza/0000-0003-4369-8237
FU National Institutes of Health [RO1 HL-077674, UL1 RR025758, K23
RR-23090]
FX This work was supported in part by National Institutes of Health Grants
RO1 HL-077674, UL1 RR025758, and K23 RR-23090.
NR 17
TC 9
Z9 9
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2348
EI 1432-2161
J9 SKELETAL RADIOL
JI Skeletal Radiol.
PD OCT
PY 2011
VL 40
IS 10
BP 1349
EP 1354
DI 10.1007/s00256-011-1098-2
PG 6
WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
GA 813DH
UT WOS:000294346500013
ER
PT J
AU Antonescu, CR
Zhang, L
Nielsen, GP
Rosenberg, AE
Dal Cin, P
Fletcher, CDM
AF Antonescu, Cristina R.
Zhang, Lei
Nielsen, G. Petur
Rosenberg, Andrew E.
Dal Cin, Paola
Fletcher, Christopher D. M.
TI Consistent t(1;10) with Rearrangements of TGFBR3 and MGEA5 in Both
Myxoinflammatory Fibroblastic Sarcoma and Hemosiderotic Fibrolipomatous
Tumor
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID RING CHROMOSOMES; SOFT-TISSUE; GROWTH; LESION; CELLS; GENE
AB Despite their shared predilection for superficial soft tissue of distal extremities and frequent local recurrences, myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT) have distinct morphologic appearances. Recent studies have identified an identical t(1; 10)(p22; q24) in five cases of MIFS and two of HFLT, as well as common amplifications on 3p11-12. To investigate further their potential relationship and to determine the incidence of t(1; 10) in a larger cohort, we subjected seven MIFS, 14 HFLT, and three cases with mixed morphology, to molecular and cytogenetic analysis. Fluorescence in situ hybridization (FISH) analysis for rearrangements of TGFBR3 on 1p22 and of MGEA5 on 10q24 was performed in all cases, whereas the status of VGLL3 gene amplification on 3p12.1 was investigated in 12 cases. Conventional karyotyping was performed in one HFLT and two cases with mixed MIFS/HFLT histology. Overall 83% of cases showed rearrangements in both TGFBR3 and MGEA5. All three cases with mixed features of MIFS and HFLT were positive. Cytogenetic analysis performed in three cases confirmed an unbalanced der(10) t(1; 10)(p22; q24). VGLL3 gene amplification was noted in 10/12 cases of both histologies. The high incidence of t(1; 10) in MIFS and HFLT reinforces a shared pathogenetic relationship. Furthermore, the co-existence of both components either synchronously or metachronously in a primary or subsequent recurrence, suggest either different morphologic variants or different levels of tumor progression of a single biologic entity. FISH analysis for TGFBR3 and MGEA5 rearrangements can be applied as a reliable diagnostic molecular test when confronted with limited material or a challenging diagnosis. (C) 2011 Wiley-Liss, Inc.
C1 [Antonescu, Cristina R.; Zhang, Lei] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Nielsen, G. Petur; Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Dal Cin, Paola; Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Antonescu, CR (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
EM antonesc@mskcc.org; cfletcher@partners.org
FU [PO1 CA047179-15A2]; [P50 CA140146-01]
FX Supported by: PO1 CA047179-15A2 (CRA), P50 CA140146-01 (CRA).
NR 22
TC 41
Z9 44
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1045-2257
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD OCT
PY 2011
VL 50
IS 10
BP 757
EP 764
DI 10.1002/gcc.20897
PG 8
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 811BQ
UT WOS:000294177300001
PM 21717526
ER
PT J
AU Fang, A
Asnaani, A
Gutner, C
Cook, C
Wilhelm, S
Hofmann, SG
AF Fang, Angela
Asnaani, Anu
Gutner, Cassidy
Cook, Courtney
Wilhelm, Sabine
Hofmann, Stefan G.
TI Rejection sensitivity mediates the relationship between social anxiety
and body dysmorphic concerns
SO JOURNAL OF ANXIETY DISORDERS
LA English
DT Article
DE Dysmorphic concern; Social anxiety; Rejection sensitivity
ID PSYCHOMETRIC PROPERTIES; SELF-REPORT; DSM-V; DISORDER; PREVALENCE; SCALE
AB The goal of this study was to examine the role of rejection sensitivity in the relationship between social anxiety and body dysmorphic concerns. To test our hypothesis that rejection sensitivity mediates the link between social anxiety and body dysmorphic concerns, we administered self-report questionnaires to 209 student volunteers. Consistent with our prediction, rejection sensitivity partially mediated the relationship between social anxiety symptoms and body dysmorphic concerns. The implications of the overlap between these constructs are discussed. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Floor, Boston, MA 02215 USA.
EM shofmann@bu.edu
RI Hofmann, Stefan/B-8769-2014
OI Hofmann, Stefan/0000-0002-3548-9681
FU NIMH NIH HHS [R01 MH078308, R01 MH078308-04]
NR 30
TC 16
Z9 16
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-6185
J9 J ANXIETY DISORD
JI J. Anxiety Disord.
PD OCT
PY 2011
VL 25
IS 7
BP 946
EP 949
DI 10.1016/j.janxdis.2011.06.001
PG 4
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 810CH
UT WOS:000294102500013
PM 21741203
ER
PT J
AU Yoo, JJ
Bichara, DA
Zhao, X
Randolph, MA
Gill, TJ
AF Yoo, Jeong Joon
Bichara, David A.
Zhao, Xing
Randolph, Mark A.
Gill, Thomas J.
TI Implant-assisted meniscal repair in vivo using a chondrocyte-seeded
flexible PLGA scaffold
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
LA English
DT Article
DE meniscal tear; meniscal healing; articular chondrocytes; PLGA mesh
ID VICRYL MESH; LIGAMENT AUGMENTATION; MECHANICAL-PROPERTIES; ENGINEERED
CARTILAGE; FOLLOW-UP; TISSUE; MENISCECTOMY; KNEE; RECONSTRUCTION;
PROLIFERATION
AB A cell-based engineered construct can be used for healing of intractable meniscal lesions. Our aims were to assess the culture conditions (static versus dynamic oscillation) and the healing capacity of the chondrocyte-seeded flexible implants in a heterotopic mouse model. Swine articular chondrocytes were labeled with PKH 26 or DiI dye and seeded onto a flexible PLGA scaffold using dynamic oscillating conditions for 24 h. Half of cell-seeded scaffolds were cultured in the same dynamic conditions, while the remaining scaffolds were cultured statically. After 7 days, scaffolds were placed between swine meniscal discs and were implanted subcutaneously in nude mice for 6 weeks. Additional constructs for assessing in vivo cell tracking were implanted for 12 weeks. Live/dead assays demonstrated labeled chondrocytes attached throughout the scaffold in both culture conditions. DNA measurements showed no significant difference between the culture conditions. A continuous fibro-cartilaginous healing tissue was observed between meniscal discs in all 12 dynamically cultured constructs and 9 of 11 statically cultured ones. There was no evidence of meniscal healing using acellular scaffold as well as in meniscal constructs lacking an implant. Both PKH 26- and DiI-labeled cells were identified along the healing interface. We conclude the chondrocyte-seeded flexible PLGA implants induce healing of meniscal discs in nude mice. Culture conditions after seeding have no apparent effects on healing. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 102-108, 2011.
C1 [Yoo, Jeong Joon; Bichara, David A.; Zhao, Xing; Randolph, Mark A.; Gill, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Lab Musculoskeletal Tissue En, Boston, MA USA.
[Yoo, Jeong Joon] Seoul Natl Univ, Coll Med, Dept Orthopaed Surg, Seoul, South Korea.
[Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab,Div Plast Surg, Boston, MA USA.
RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Lab Musculoskeletal Tissue En, Boston, MA USA.
EM marandolph@partners.org
RI Yoo, Jeong Joon/J-5553-2012
FU Musculoskeletal Transplantation Foundation
FX Contract grant sponsor: The Musculoskeletal Transplantation Foundation
NR 34
TC 11
Z9 11
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1549-3296
J9 J BIOMED MATER RES A
JI J. Biomed. Mater. Res. Part A
PD OCT
PY 2011
VL 99A
IS 1
BP 102
EP 108
DI 10.1002/jbm.a.33168
PG 7
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 811VG
UT WOS:000294243600012
PM 21800420
ER
PT J
AU Mahon, MJ
AF Mahon, Matthew J.
TI Apical membrane segregation of phosphatidylinositol-4,5-bisphosphate
influences parathyroid hormone 1 receptor compartmental signaling and
localization via direct regulation of ezrin in LLC-PK1 cells
SO CELLULAR SIGNALLING
LA English
DT Article
DE Ezrin; Parathyroid hormone; Parathyroid hormone receptor;
Phosphatidylinositol-4.5-bisphosphate; Phospholipase; LLC-PK1
ID EZRIN/RADIXIN/MOESIN ERM PROTEINS; CARBOXYL-TERMINAL REGION;
PHOSPHOLIPASE-C-BETA; ACTIN-BINDING-SITE; PLASMA-MEMBRANE; 4-PHOSPHATE
5-KINASE; PHOSPHATE-TRANSPORT; KIDNEY-CELLS; DOMAIN; ASSOCIATION
AB The parathyroid hormone 1 receptor (PTH1R), a primary regulator of mineral ion homeostasis, is expressed on both the apical and basolateral membranes of kidney proximal tubules and in the LLC-PK1 kidney cell line. In LLC-PK1 cells, apical PTH1R subpopulations are far more effective at signaling via phospholipase (PLC) than basolateral counterparts, revealing the presence of compartmental signaling. Apical PTH1R localization is dependent upon direct interactions with ezrin, an actin-membrane cross-linking scaffold protein. Ezrin undergoes an activation process that is dependent upon phosphorylation and binding to phosphatidylinositol-4,5-bisphosphate (PIP2), a lipid that is selectively concentrated to apical surfaces of polarized epithelia. Consistently, the intracellular probe for PIP2, GFP-PLC delta 1-PH, localizes to the apical membranes of LLC-PK1 cells, directly overlapping ezrin and PTH1R expression. Activation of the apical PTH1R shifts the GFP-PLC delta 1-PH probe from the apical membrane to the cytosol and basolateral membranes, reflecting domain-specific activation of PLC and hydrolysis of PIP2. This compartmental signaling is likely due to the polarized localization of PIP2, the substrate for PLC. PIP2 degradation using a membrane-directed phosphatase shifts ezrin localization to the cytosol and induces ezrin de-phosphorylation, processes consistent with inactivation. PIP2 degradation also shifts PTH1R expression from brush border microvilli to basolateral membranes and markedly blunts PTH-elicited activation of the MAPK pathway. Transient expression of ezrin in HEK293 cells shifts PTH1R expression from the plasma membrane to microvilli-like surface projections that also contain PIP2. As a result, ezrin enhances PTH mediated activation of the PLC pathway in this cell model with increasing total receptor surface expression. Collectively, these findings demonstrate that the apical segregation of PIP2 to the apical domains not only promotes the activation of ezrin and the subsequent formation of the PTH1R containing scaffold, but also ensures the presence of ample substrate for propagating the PLC pathway. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Mahon, Matthew J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Mahon, Matthew J.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
RP Mahon, MJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Their 10, Boston, MA 02114 USA.
EM mahon@helix.mgh.harvard.edu
FU NIH [P01 DK073911]
FX This study was funded by a program project grant from the NIH (P01
DK073911) to Dr. John Potts. Thanks to Dr. Tamas Balla and Monique Arpin
for providing invaluable reagents.
NR 54
TC 1
Z9 1
U1 1
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD OCT
PY 2011
VL 23
IS 10
BP 1659
EP 1668
DI 10.1016/j.cellsig.2011.05.020
PG 10
WC Cell Biology
SC Cell Biology
GA 809FW
UT WOS:000294038200018
PM 21672629
ER
PT J
AU Schapira, L
Schutt, R
AF Schapira, Lidia
Schutt, Russell
TI Training Community Health Workers About Cancer Clinical Trials
SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH
LA English
DT Article
DE Cancer; Clinical trials; Disparities; Community health workers
ID BREAST-CANCER; MEDICAL-RESEARCH; PARTICIPATION; POPULATIONS; CARE;
RECRUITMENT; DISPARITIES; VOLUNTEERS; KNOWLEDGE; AMERICANS
AB Innovative projects to reduce disparities in cancer treatment and research include partnerships between academic and community cancer centers, patient navigation programs and strategies to promote community awareness, education and engagement. A 4 h training program about cancer clinical trials was developed through a needs assessment and in collaboration with community health workers who served as consultants and a larger advisory board comprised of community health workers, educators and clinical trialists. This program was delivered first as a collaboration between a phsycian who is experienced in the conduct of clinical research and two community health workers, and subsequently by the community health workers alone. We report on four workshops attended by a total of 61 community health workers recruited from Boston-area hospitals, community health centers and outreach programs. Support for and knowledge of clinical trials was measured in a pretest and post-test, which also included a satisfaction rating. Participants had a range of prior experience with clinical trials in the context of their personal and professional experience. Mean accuracy of knowledge about clinical trials increased from 72 to 84%, support for clinical trials improved considerably, and satisfaction with the training experience was high. Knowledge gaps and low levels of support for cancer clinical trials among community health workers can be improved with a short training program delivered by other community health workers. Further research is needed to identify the impact of this training on accrual to cancer clinical trials.
C1 [Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02214 USA.
[Schutt, Russell] Univ Massachusetts, Dept Sociol, Boston, MA 02125 USA.
RP Schapira, L (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02214 USA.
EM lschapira@partners.org
FU NCI NIH HHS [1U56CA118641-01]
NR 37
TC 5
Z9 5
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1912
J9 J IMMIGR MINOR HEALT
JI J. Immigr. Minor. Health
PD OCT
PY 2011
VL 13
IS 5
BP 891
EP 898
DI 10.1007/s10903-010-9432-7
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 806ZN
UT WOS:000293857400012
PM 21181445
ER
PT J
AU Kelly, JF
Hoeppner, BB
Urbanoski, KA
Slaymaker, V
AF Kelly, John F.
Hoeppner, Bettina B.
Urbanoski, Karen A.
Slaymaker, Valerie
TI Predicting relapse among young adults: Psychometric validation of the
advanced warning of relapse (AWARE) scale
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Substance use relapse; Young adults; Psychometrics
ID ALCOHOL DEPENDENCE; FIT INDEXES; NUMBER; ABUSE; ADOLESCENTS; COMPONENTS;
RECOVERY; DURATION; SIGNS
AB Objective: Failure to maintain abstinence despite incurring severe harm is perhaps the key defining feature of addiction. Relapse prevention strategies have been developed to attenuate this propensity to relapse, but predicting who will, and who will not, relapse has stymied attempts to more efficiently tailor treatments according to relapse risk profile. Here we examine the psychometric properties of a promising relapse risk measure-the Advance WArning of RElapse (AWARE) scale (Miller & Harris, 2000) in an understudied but clinically important sample of young adults.
Method: Inpatient youth (N = 303: Ages 18-24; 26% female) completed the AWARE scale and the Brief Symptom Inventory-18 (BSI) at the end of residential treatment, and at 1-, 3-, and 6-months following discharge. Internal and convergent validity was tested for each of these four timepoints using confirmatory factor analysis and correlations (with BSI scores). Predictive validity was tested for relapse 1, 3, and 6 months following discharge, as was incremental utility, where AWARE scores were used as predictors of any substance use while controlling for treatment entry substance use severity and having spent time in a controlled environment following treatment.
Results: Confirmatory factor analysis revealed a single, internally consistent, 25-item factor that demonstrated convergent validity and predicted subsequent relapse alone and when controlling for other important relapse risk predictors.
Conclusions: The AWARE scale may be a useful and efficient clinical tool for assessing short-term relapse risk among young people and, thus, could serve to enhance the effectiveness of relapse prevention efforts. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Kelly, John F.; Hoeppner, Bettina B.; Urbanoski, Karen A.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA.
[Slaymaker, Valerie] Hazelden Fdn, Butler Ctr Res, Ctr City, MN 55012 USA.
RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA.
EM jkelly11@partners.org; bhoeppner@partners.org; kurbanoski@partners.org;
VSlaymaker@Hazelden.org
OI Urbanoski, Karen/0000-0001-7287-7176
FU NIAAA [1R21AA018185-01A2]; NIDA [1K01DA027097-01A1]
FX This work was supported by the NIAAA Grant Number # 1R21AA018185-01A2
and NIDA Grant Number #1K01DA027097-01A1. NIH had no role in the study
design, collection, analysis or interpretation of the data, writing the
manuscript, or the decision to submit the paper for publication.
NR 34
TC 4
Z9 4
U1 1
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD OCT
PY 2011
VL 36
IS 10
BP 987
EP 993
DI 10.1016/j.addbeh.2011.05.013
PG 7
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 801ZZ
UT WOS:000293480400006
PM 21700396
ER
PT J
AU Genkinger, JM
Spiegelman, D
Anderson, KE
Bernstein, L
van den Brandt, PA
Calle, EE
English, DR
Folsom, AR
Freudenheim, JL
Fuchs, CS
Giles, GG
Giovannucci, E
Horn-Ross, PL
Larsson, SC
Leitzmann, M
Mannisto, S
Marshall, JR
Miller, AB
Patel, AV
Rohan, TE
Stolzenberg-Solomon, RZ
Verhage, BAJ
Virtamo, J
Willcox, BJ
Wolk, A
Ziegler, RG
Smith-Warner, SA
AF Genkinger, Jeanine M.
Spiegelman, Donna
Anderson, Kristin E.
Bernstein, Leslie
van den Brandt, Piet A.
Calle, Eugenia E.
English, Dallas R.
Folsom, Aaron R.
Freudenheim, Jo L.
Fuchs, Charles S.
Giles, Graham G.
Giovannucci, Edward
Horn-Ross, Pamela L.
Larsson, Susanna C.
Leitzmann, Michael
Mannisto, Satu
Marshall, James R.
Miller, Anthony B.
Patel, Alpa V.
Rohan, Thomas E.
Stolzenberg-Solomon, Rachael Z.
Verhage, Bas A. J.
Virtamo, Jarmo
Willcox, Bradley J.
Wolk, Alicja
Ziegler, Regina G.
Smith-Warner, Stephanie A.
TI A pooled analysis of 14 cohort studies of anthropometric factors and
pancreatic cancer risk
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE pancreatic cancer; anthropometry; pooled analysis; deceased
ID BODY-MASS INDEX; LARGE US COHORT; PHYSICAL-ACTIVITY;
ALCOHOL-CONSUMPTION; UNITED-STATES; GLYCEMIC INDEX; OBESITY; WEIGHT;
HEIGHT; WOMEN
AB Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21-22.9 kg/m(2), pancreatic cancer risk was 47% higher (95% CI:23-75%) among obese (BMI >= 30 kg/m(2)) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09-1.56 comparing BMI >= 25 kg/m(2) to a BMI between 21 and 22.9 kg/m(2)). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m(2)) and not obese at baseline (BMI < 30 kg/m(2)), pancreatic cancer risk was 54% higher (95%CI = 24-93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI >= 10 kg/m(2) between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03-1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.
C1 [Genkinger, Jeanine M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Spiegelman, Donna; Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Anderson, Kristin E.; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Anderson, Kristin E.; Folsom, Aaron R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Div Canc Etiol, Duarte, CA 91010 USA.
[van den Brandt, Piet A.; Verhage, Bas A. J.] Maastricht Univ, Dept Epidemiol, Sch Oncol & Dev Biol GROW, Maastricht, Netherlands.
[Calle, Eugenia E.; Patel, Alpa V.] Amer Canc Soc, Atlanta, GA 30329 USA.
[English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[English, Dallas R.; Giles, Graham G.] Univ Melbourne, Melbourne, Vic, Australia.
[Freudenheim, Jo L.; Marshall, James R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Fuchs, Charles S.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Fuchs, Charles S.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Giovannucci, Edward; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Horn-Ross, Pamela L.] No Calif Canc Ctr, Fremont, CA USA.
[Larsson, Susanna C.; Wolk, Alicja] Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, Stockholm, Sweden.
[Leitzmann, Michael; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Leitzmann, Michael] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany.
[Mannisto, Satu; Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
[Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Willcox, Bradley J.] Univ Hawaii, John A Burns Sch Med, Manoa, HI USA.
[Willcox, Bradley J.] Okinawa Res Ctr Longev Sci, Okinawa, Japan.
[Willcox, Bradley J.] Pacific Hlth Res Inst, Honolulu, HI USA.
[Willcox, Bradley J.] Queens Med Ctr, Honolulu, HI USA.
[Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
RP Genkinger, JM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St, New York, NY 10032 USA.
EM jg3081@columbia.edu
RI Larsson, Susanna/F-6065-2015;
OI Larsson, Susanna/0000-0003-0118-0341; Mannisto,
Satu/0000-0002-8668-3046; Giles, Graham/0000-0003-4946-9099; English,
Dallas/0000-0001-7828-8188
FU National Institutes of Health [CA098566, CA55075]
FX Grant sponsor: National Institutes of Health; Grant numbers: CA098566
and CA55075
NR 44
TC 70
Z9 71
U1 1
U2 4
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 OCT 1
PY 2011
VL 129
IS 7
BP 1708
EP 1717
DI 10.1002/ijc.25794
PG 10
WC Oncology
SC Oncology
GA 798XX
UT WOS:000293246600017
PM 21105029
ER
PT J
AU Evers, K
Noens, I
Steyaert, J
Wagemans, J
AF Evers, Kris
Noens, Ilse
Steyaert, Jean
Wagemans, Johan
TI Combining strengths and weaknesses in visual perception of children with
an autism spectrum disorder: Perceptual matching of facial expressions
SO RESEARCH IN AUTISM SPECTRUM DISORDERS
LA English
DT Article
DE Autism spectrum disorder (ASD); Matching; Facial emotional expressions;
Compensation strategy; Weak central coherence; Enhanced perceptual
functioning
ID PERVASIVE DEVELOPMENTAL DISORDERS; FACE PROCESSING SKILLS; WEAK CENTRAL
COHERENCE; ASPERGER-SYNDROME; EMOTION RECOGNITION; PEOPLE; FIXATION;
DEFICITS; MIND; INDIVIDUALS
AB Background: Children with an autism spectrum disorder (ASD) are known to have an atypical visual perception, with deficits in automatic Gestalt formation and an enhanced processing of visual details. In addition, they are sometimes found to have difficulties in emotion processing.
Methods: In three experiments, we investigated whether 7-to-11-year old children with ASD were showing superiorities or deficits in matching tasks that required focusing on faces with an emotional expression. Throughout these experiments, we increased the complexity of the stimuli and tasks demands.
Results and conclusions: In matching faces with emotional expressions, children with ASD were not able to show superior processing of details in any of the three experiments. They were able to compensate their inferior processing of emotions in some of the experiments (e.g., by using a slower, more sequential processing style). However, when stimulus complexity (e.g., dynamic facial expressions) or task demands (e.g., extracting and remembering the relevant stimulus dimension) increased, they were no longer able to do so, and they did show performance deficits. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Evers, Kris; Wagemans, Johan] Univ Leuven KU Leuven, Expt Psychol Lab, B-3000 Louvain, Belgium.
[Evers, Kris; Steyaert, Jean] Univ Leuven KU Leuven, Dept Neurosci, B-3000 Louvain, Belgium.
[Noens, Ilse] Univ Leuven KU Leuven, Ctr Parenting & Special Educ, B-3000 Louvain, Belgium.
[Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Steyaert, Jean] Univ Hosp Maastricht, Maastricht, Netherlands.
RP Wagemans, J (reprint author), Univ Leuven KU Leuven, Expt Psychol Lab, Tiensestr 102,Bus 3711, B-3000 Louvain, Belgium.
EM johan.wagemans@psy.kuleuven.be
RI Steyaert, Jean/B-5326-2015
OI Steyaert, Jean/0000-0003-2512-4694
NR 67
TC 10
Z9 11
U1 5
U2 32
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1750-9467
J9 RES AUTISM SPECT DIS
JI Res. Autism Spectr. Disord.
PD OCT-DEC
PY 2011
VL 5
IS 4
BP 1327
EP 1342
DI 10.1016/j.rasd.2011.01.004
PG 16
WC Education, Special; Psychology, Developmental; Psychiatry;
Rehabilitation
SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation
GA 785NL
UT WOS:000292235600006
ER
PT J
AU Van Eylen, L
Boets, B
Steyaert, J
Evers, K
Wagemans, J
Noens, I
AF Van Eylen, Lien
Boets, Bart
Steyaert, Jean
Evers, Kris
Wagemans, Johan
Noens, Ilse
TI Cognitive flexibility in autism spectrum disorder: Explaining the
inconsistencies?
SO RESEARCH IN AUTISM SPECTRUM DISORDERS
LA English
DT Article
DE Autism spectrum disorders; Cognitive flexibility; Task-switching;
Wisconsin Card Sorting Task; Disengagement; Task instructions
ID HIGH-FUNCTIONING AUTISM; CARD SORTING TEST;
ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EXECUTIVE FUNCTION; CENTRAL
COHERENCE; YOUNG-CHILDREN; PERFORMANCE; DEFICITS; TASK; SET
AB The Wisconsin Card Sorting Task (WCST) is the only cognitive flexibility task that has consistently shown deficits in individuals with an autism spectrum disorder (ASD). As this is the only task characterized by limited explicit task instructions and a high degree of disengagement required to perform the switch, we hypothesized that cognitive flexibility deficits of individuals with ASD might only become apparent in situations fulfilling these requirements. However, the WCST involves various additional cognitive processes besides switching, making it uncertain whether difficulties are indeed due to cognitive flexibility impairments. The aim of this study was to investigate whether individuals with ASD show cognitive flexibility impairments on a more controlled task-switching variant of the WCST, still fulfilling both requirements. We therefore developed such a task and administered it to 40 high-functioning children with ASD and 40 age- and IQ- matched typically developing controls. As predicted, individuals with ASD made more perseveration errors and had a significantly higher switch cost than typically developing controls, but they performed equally well on the control measures. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Van Eylen, Lien; Noens, Ilse] Katholieke Univ Leuven, Parenting & Special Educ Res Grp, Louvain, Belgium.
[Van Eylen, Lien; Evers, Kris; Wagemans, Johan] Katholieke Univ Leuven, Expt Psychol Lab, Louvain, Belgium.
[Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Steyaert, Jean] Univ Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands.
RP Van Eylen, L (reprint author), Univ Hosp Leuven, Dept Child Psychiat, Herestr 49,Box 7003, B-3000 Louvain, Belgium.
EM Lien.VanEylen@ped.kuleuven.be
RI Steyaert, Jean/B-5326-2015
OI Steyaert, Jean/0000-0003-2512-4694
NR 57
TC 27
Z9 28
U1 9
U2 53
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1750-9467
EI 1878-0237
J9 RES AUTISM SPECT DIS
JI Res. Autism Spectr. Disord.
PD OCT-DEC
PY 2011
VL 5
IS 4
BP 1390
EP 1401
DI 10.1016/j.rasd.2011.01.025
PG 12
WC Education, Special; Psychology, Developmental; Psychiatry;
Rehabilitation
SC Education & Educational Research; Psychology; Psychiatry; Rehabilitation
GA 785NL
UT WOS:000292235600013
ER
PT J
AU Lin, HW
Silver, AL
Cunnane, ME
Sadow, PM
Kieff, DA
AF Lin, Harrison W.
Silver, Amanda L.
Cunnane, Mary E.
Sadow, Peter M.
Kieff, David A.
TI Lateral dermoid cyst of the floor of mouth: Unusual radiologic and
pathologic findings
SO AURIS NASUS LARYNX
LA English
DT Article
DE Dermoid; Neck mass; Neoplasm; Head and neck imaging; Head and neck
pathology
ID MASSES
AB A lateral dermoid cyst is a rare lesion of the floor of mouth, with only 12 cases reported in the literature. We describe the case of a 60-year-old man with a slowly enlarging mass in the submandibular region. Magnetic resonance imaging demonstrated a lesion containing multiple uniformly rounded foci, creating a "sack-of-marbles" appearance. Needle aspirations showed atypical findings, and the mass was excised. Histopathology revealed a cyst containing a keratinizing stratified squamous epithelial lining with apocrine and eccrine glands. These findings were diagnostic of a dermoid cyst, which should be considered in the differential diagnosis of any midline or lateral cervical lesion. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Lin, Harrison W.; Silver, Amanda L.; Kieff, David A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
[Cunnane, Mary E.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA.
[Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Lin, Harrison W.; Silver, Amanda L.; Kieff, David A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Cunnane, Mary E.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM harrison_lin@meei.harvard.edu
NR 8
TC 8
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0385-8146
J9 AURIS NASUS LARYNX
JI Auris Nasus Larynx
PD OCT
PY 2011
VL 38
IS 5
BP 650
EP 653
DI 10.1016/j.anl.2011.01.002
PG 4
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 762HG
UT WOS:000290465200017
PM 21334151
ER
PT J
AU Kang, JH
Wiggs, JL
Haines, J
Abdrabou, W
Pasquale, LR
AF Kang, Jae Hee
Wiggs, Janey L.
Haines, Jonathan
Abdrabou, Wael
Pasquale, Louis R.
TI Reproductive factors and NOS3 variant interactions in primary open-angle
glaucoma
SO MOLECULAR VISION
LA English
DT Article
ID HORMONE REPLACEMENT THERAPY; OXIDE SYNTHASE GENE; HUMOR OUTFLOW
FACILITY; MESHWORK CELL-VOLUME; NITRIC-OXIDE; INTRAOCULAR-PRESSURE;
TRABECULAR MESHWORK; RELAXING FACTOR; BLOOD-FLOW; VITREOUS CONCENTRATION
AB Purpose: To investigate whether associations with the nitric oxide synthase gene (NOS3) variants and risk of primary open-angle glaucoma (POAG) depend on female reproductive factors.
Methods: Two functional and two tagging single nucleotide polymorphisms (SNPs; T-786C: rs2070744, Glu298Asp: rs1799983, rs7830, and rs3918188) were evaluated in a nested case-control study from the Nurses' Health Study (women followed 1980 - 2002). Participants were aged >= 40 years and Caucasian, who were followed biennially with update information on reproductive factors. We included 374 Nurses' Health Study (NHS) cases and 1,085 controls, matched on age and eye exam at the matched cases' diagnosis dates. Relative risks (RRs) were estimated using multivariable conditional logistic regression.
Results: Among women with age at menarche <13 years, compared with the CC homozygotes of the rs3918188 tagging SNP, the wild-type AA homozygotes were at significantly reduced risk of POAG (RR=0.31, 95% CI=0.16, 0.59); however, for women with age at menarche >= 13 years, the SNP was not associated with POAG (p-interaction=0.0007). Among parous women with 3+ children, carriers of the minor variant (T) allele of the functional Glu298Asp SNP were at increased risk, while among parous women with 1-2 children, they were not (p-interaction=0.003). No significant interactions between NOS3 SNPs and oral contraceptive use in POAG were detected.
Conclusions: These data provide further support for the notion that NOS3 genotype - female reproductive health interactions are important in POAG pathogenesis.
C1 [Wiggs, Janey L.; Abdrabou, Wael; Pasquale, Louis R.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Kang, Jae Hee; Pasquale, Louis R.] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02114 USA.
[Kang, Jae Hee; Pasquale, Louis R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Haines, Jonathan] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA.
RP Pasquale, LR (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM Louis_Pasquale@meei.harvard.edu
RI Haines, Jonathan/C-3374-2012
FU National Institutes of Health [CA87969, CA49449, CA055075, EY09611,
HL35464, EY015473]; Wyeth Pharmaceuticals; Research to Prevent
Blindness; Harvard Glaucoma Center of Excellence; Margolis Foundation
FX This work was supported by grants CA87969, CA49449, CA055075, EY09611,
HL35464, and EY015473 from the National Institutes of Health. Jae Hee
Kang has received research funding (2008-2009) from Wyeth
Pharmaceuticals. Louis R. Pasquale is also supported by a Research to
Prevent Blindness Physician Scientist award in New York City. This work
is also supported by the Harvard Glaucoma Center of Excellence (L. R.
P., J.L.W.) and by the Margolis Foundation (L. R. P.). The authors have
no proprietary or commercial interest in any materials discussed in this
paper. We are indebted to the participants and staff of the Nurses'
Health Study.
NR 46
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Z9 9
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD SEP 30
PY 2011
VL 17
IS 275
BP 2544
EP 2551
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 833MT
UT WOS:000295890300001
PM 22025889
ER
PT J
AU Lochner, C
Stein, DJ
Woods, D
Pauls, DL
Franklin, ME
Loerke, EH
Keuthen, NJ
AF Lochner, Christine
Stein, Dan J.
Woods, Douglas
Pauls, David L.
Franklin, Martin E.
Loerke, Elizabeth H.
Keuthen, Nancy J.
TI The validity of DSM-IV-TR criteria B and C of hair-pulling disorder
(trichotillomania): Evidence from a clinical study
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Trichotillomania; Diagnostic criteria; DSM; Hair-pulling
ID MGH HAIRPULLING SCALE; PHENOMENOLOGY; IMPAIRMENT; DISABILITY
AB In both DSM-IV-TR and the ICD-10, hair-pulling disorder (trichotillomania, or TTM) is described as hair-pulling, with a rising urge or tension prior to pulling or when attempting to resist, and pleasure, relief or gratification during or after pulling. However, it has been questioned whether all patients with hair-pulling experience these other phenomena, and whether they occur with all pulling episodes. The objective of this study was to examine the DSM-IV-TR requirement of criteria B and C for a diagnosis of TTM in a sample of people with hair-pulling. A multi-site sample of adults with hair-pulling who met both DSM-IV-TR diagnostic criteria B and C (n=82.89.13%) were compared to those who failed to satisfy both B and C (n=10, 10.87%) on a number of clinical variables. There were no differences in hair-pulling severity, levels of comorbid depressive and anxiety symptoms, number of comorbid body-focused repetitive behaviors, or impairment between those patients who did and did not meet criteria B and C. Our study does not provide convincing support for the inclusion of the current diagnostic criteria B and C for TTM in DSM-5. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Lochner, Christine; Stein, Dan J.] Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7505 Tygerberg, South Africa.
[Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Health, ZA-7925 Cape Town, South Africa.
[Woods, Douglas] Univ Wisconsin, Dept Psychol, Milwaukee, WI 53201 USA.
[Pauls, David L.; Loerke, Elizabeth H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA USA.
[Pauls, David L.; Loerke, Elizabeth H.; Keuthen, Nancy J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.
[Franklin, Martin E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Lochner, C (reprint author), POB 19063, ZA-7505 Tygerberg, South Africa.
EM cl2@sun.ac.za
RI Citations, TLC SAB/C-4006-2011; Stein, Dan/A-1752-2008
OI Stein, Dan/0000-0001-7218-7810
NR 22
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Z9 8
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD SEP 30
PY 2011
VL 189
IS 2
BP 276
EP 280
DI 10.1016/j.psychres.2011.07.022
PG 5
WC Psychiatry
SC Psychiatry
GA 831RG
UT WOS:000295748200020
PM 21813182
ER
PT J
AU Zhu, H
Shyh-Chang, N
Segre, AV
Shinoda, G
Shah, SP
Einhorn, WS
Takeuchi, A
Engreitz, JM
Hagan, JP
Kharas, MG
Urbach, A
Thornton, JE
Triboulet, R
Gregory, RI
Altshuler, D
Daley, GQ
AF Zhu, Hao
Shyh-Chang, Ng
Segre, Ayellet V.
Shinoda, Gen
Shah, Samar P.
Einhorn, William S.
Takeuchi, Ayumu
Engreitz, Jesse M.
Hagan, John P.
Kharas, Michael G.
Urbach, Achia
Thornton, James E.
Triboulet, Robinson
Gregory, Richard I.
Altshuler, David
Daley, George Q.
CA DIAGRAM Consortium
MAGIC Investigators
TI The Lin28/let-7 Axis Regulates Glucose Metabolism
SO CELL
LA English
DT Article
ID LET-7 MICRORNA FAMILY; HUMAN HEPATOCELLULAR-CARCINOMA;
CAENORHABDITIS-ELEGANS; PROMOTES TRANSFORMATION; INSULIN-RESISTANCE;
TRANSGENIC MICE; MESSENGER-RNA; STEM-CELLS; LIN-28; LIN28
AB The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating-metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, them TOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism.
C1 [Zhu, Hao; Shyh-Chang, Ng; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Hagan, John P.; Kharas, Michael G.; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Daley, George Q.] Childrens Hosp, Stem Cell Transplantat Program, Stem Cell Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Zhu, Hao; Shyh-Chang, Ng; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Hagan, John P.; Kharas, Michael G.; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA.
[Zhu, Hao] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Zhu, Hao; Einhorn, William S.; Kharas, Michael G.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Segre, Ayellet V.; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Dept Med, Boston, MA 02114 USA.
[Segre, Ayellet V.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Segre, Ayellet V.; Altshuler, David] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Engreitz, Jesse M.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Shyh-Chang, Ng; Hagan, John P.; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Hagan, John P.] Ohio State Univ, Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Daley, George Q.] Howard Hughes Med Inst, Boston, MA USA.
[Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA USA.
RP Daley, GQ (reprint author), Childrens Hosp, Stem Cell Transplantat Program, Stem Cell Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
RI Segre, Ayellet/E-9800-2010; Rudan, Igor/I-1467-2012; Singleton,
Andrew/C-3010-2009; Colaus, PsyColaus/K-6607-2013; Altshuler,
David/A-4476-2009; Palmer, Lyle/K-3196-2014; Boehm,
Bernhard/F-8750-2015; Naitza, Silvia/D-5620-2017; Ripatti,
Samuli/H-9446-2014; Polasek, Ozren/B-6002-2011; Meitinger,
Thomas/O-1318-2015; Kyvik, Kirsten /K-5680-2016; Visvikis-Siest,
Sophie/H-2324-2014;
OI Rudan, Igor/0000-0001-6993-6884; Altshuler, David/0000-0002-7250-4107;
Palmer, Lyle/0000-0002-1628-3055; Ripatti, Samuli/0000-0002-0504-1202;
Polasek, Ozren/0000-0002-5765-1862; Kyvik, Kirsten /0000-0003-2981-0245;
Visvikis-Siest, Sophie/0000-0001-8104-8425; Jorgensen,
Torben/0000-0001-9453-2830; Hagan, John/0000-0003-0295-4898; Kaprio,
Jaakko/0000-0002-3716-2455; de Geus, Eco/0000-0001-6022-2666; Pichler,
Irene/0000-0001-8251-0757; Magi, Reedik/0000-0002-2964-6011; Willems van
Dijk, Ko/0000-0002-2172-7394; Zhu, Hao/0000-0002-8417-9698; van
Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Kivimaki,
Mika/0000-0002-4699-5627; Shyh-Chang, Ng/0000-0003-3138-9525; Zeggini,
Eleftheria/0000-0003-4238-659X; Seedorf, Udo/0000-0003-4652-5358; Hide,
Winston/0000-0002-8621-3271; Kumari, Meena/0000-0001-9716-1035; Melzer,
David/0000-0002-0170-3838
FU US NIH; Graduate Training in Cancer Research Grant; American Cancer
Society; Agency for Science, Technology and Research, Singapore; NIH
NIDDK; American Diabetes Association; National Human Genome Research
Institute (NHGRI); US National Institute of General Medical Sciences
(NIGMS); Burroughs Wellcome Fund; Leukemia and Lymphoma Society
FX We thank John Powers, Harith Rajagopalan, Jason Locasale, Abdel Saci,
Akash Patnaik, Charles Kaufman, Christian Mosimann and Lewis Cantley for
invaluable discussions and advice, Roderick Bronson and the Harvard
Medical School Rodent Histopathology Core for mouse tissue pathology,
and the Harvard Neurobehavior Laboratory for CLAMS experiments. This
work was supported by grants from the US NIH to G. Q. D., a Graduate
Training in Cancer Research Grant and a American Cancer Society
Postdoctoral Fellowship to H.Z., the NSS Scholarship from the Agency for
Science, Technology and Research, Singapore for N.S.C, an NIH NIDDK
Diseases Career Development Award to M. G. K, and an American Diabetes
Association Postdoctoral Fellowship for A. V. S. J.M.E. was supported by
the National Human Genome Research Institute (NHGRI). R. I. G. was
supported by US National Institute of General Medical Sciences (NIGMS)
and is a Pew Research Scholar. D. A. is a Distinguished Clinical Scholar
of the Doris Duke Charitable Foundation. G. Q. D. is a recipient of
Clinical Scientist Awards in Translational Research from the Burroughs
Wellcome Fund and the Leukemia and Lymphoma Society, and an investigator
of the Howard Hughes Medical Institute and the Manton Center for Orphan
Disease Research. H.Z. and N.S.C designed and performed the experiments,
and wrote the manuscript. A. V. S. and D. A. performed bioinformatic
analysis on let-7 targets in GWAS. G. S. and S. P. S. performed
expression analysis, metabolic assays and mouse husbandry. G. S., W. S.
E. and A. T. generated the mouse strains. J.E.T, R. T. and R. I. G.
assisted with the luciferase assays. J.P.H., R. I. G., G. S., and A. T
generated the conditional knockout mice. M. G. K. helped to design the
experiments. G. Q. D. designed and supervised experiments, and wrote the
manuscript. The authors declare no competing financial interests.
NR 55
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U1 4
U2 85
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD SEP 30
PY 2011
VL 147
IS 1
BP 81
EP 94
DI 10.1016/j.cell.2011.08.033
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 827AJ
UT WOS:000295396700017
PM 21962509
ER
PT J
AU Chiarle, R
Zhang, Y
Frock, RL
Lewis, SM
Molinie, B
Ho, YJ
Myers, DR
Choi, VW
Compagno, M
Malkin, DJ
Neuberg, D
Monti, S
Giallourakis, CC
Gostissa, M
Alt, FW
AF Chiarle, Roberto
Zhang, Yu
Frock, Richard L.
Lewis, Susanna M.
Molinie, Benoit
Ho, Yu-Jui
Myers, Darienne R.
Choi, Vivian W.
Compagno, Mara
Malkin, Daniel J.
Neuberg, Donna
Monti, Stefano
Giallourakis, Cosmas C.
Gostissa, Monica
Alt, Frederick W.
TI Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome
Breaks and Rearrangements in B Cells
SO CELL
LA English
DT Article
ID END-JOINING PATHWAY; CLASS SWITCH RECOMBINATION; CYTIDINE DEAMINASE AID;
DNA BREAKS; C-MYC; HYPERMUTATION; LYMPHOCYTES; CANCER; IDENTIFICATION;
TRANSCRIPTION
AB Whereas chromosomal translocations are common pathogenetic events in cancer, mechanisms that promote them are poorly understood. To elucidate translocation mechanisms in mammalian cells, we developed high-throughput, genome-wide translocation sequencing (HTGTS). We employed HTGTS to identify tens of thousands of independent translocation junctions involving fixed I-SceI meganuclease-generated DNA double-strand breaks (DSBs) within the c-myc oncogene or IgH locus of B lymphocytes induced for activation-induced cytidine deaminase (AID)-dependent IgH class switching. DSBs translocated widely across the genome but were preferentially targeted to transcribed chromosomal regions. Additionally, numerous AID-dependent and AID-independent hot spots were targeted, with the latter comprising mainly cryptic I-SceI targets. Comparison of translocation junctions with genome-wide nuclear run-ons revealed a marked association between transcription start sites and translocation targeting. The majority of translocation junctions were formed via end-joining with short microhomologies. Our findings have implications for diverse fields, including gene therapy and cancer genomics.
C1 [Chiarle, Roberto; Zhang, Yu; Frock, Richard L.; Lewis, Susanna M.; Ho, Yu-Jui; Myers, Darienne R.; Choi, Vivian W.; Compagno, Mara; Malkin, Daniel J.; Gostissa, Monica; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Chiarle, Roberto; Zhang, Yu; Frock, Richard L.; Lewis, Susanna M.; Ho, Yu-Jui; Myers, Darienne R.; Choi, Vivian W.; Compagno, Mara; Malkin, Daniel J.; Gostissa, Monica; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Chiarle, Roberto; Zhang, Yu; Frock, Richard L.; Lewis, Susanna M.; Ho, Yu-Jui; Myers, Darienne R.; Choi, Vivian W.; Compagno, Mara; Malkin, Daniel J.; Gostissa, Monica; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Chiarle, Roberto; Compagno, Mara] Univ Turin, Dept Biomed Sci & Human Oncol, I-10126 Turin, Italy.
[Chiarle, Roberto; Compagno, Mara] Univ Turin, CERMS, I-10126 Turin, Italy.
[Molinie, Benoit; Giallourakis, Cosmas C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Neuberg, Donna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Monti, Stefano] 5 Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA.
[Monti, Stefano] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA.
RP Zhang, Y (reprint author), Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA.
EM zhang@idi.harvard.edu; cgiallourakis@partners.org;
gostissa@idi.harvard.edu; alt@enders.tch.harvard.edu
OI Monti, Stefano/0000-0002-9376-0660; CHIARLE,
Roberto/0000-0003-1564-8531; Frock, Richard/0000-0001-6963-4931
FU NIH [5P01CA92625, AI070837, 5T32CA070083-13]; Leukemia and Lymphoma
Society of America (LLS); AIRC [ERC-2009-StG, 242965]; V Foundation; CRI
postdoctoral fellowship
FX We thank Barry Sleckman for providing unpublished information about
circular PCR translocation cloning of RAG-generated DSBs. This work was
supported by NIH grant 5P01CA92625 and a Leukemia and Lymphoma Society
of America (LLS) SCOR grant to F. W. A., grants from AIRC and grant FP7
ERC-2009-StG (Proposal No. 242965-"Lunely'') to R. C., an NIH KO8 grant
AI070837 to C. C. G., and a V Foundation Scholar award to M. G. Y.Z. was
supported by CRI postdoctoral fellowship and R. L. F. by NIH training
grant 5T32CA070083-13. F. W. A. is an Investigator of the Howard Hughes
Medical Institute. F. W. A. is a member of the scientific advisory board
of Cellectis Pharmaceuticals.
NR 46
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U1 4
U2 22
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD SEP 30
PY 2011
VL 147
IS 1
BP 107
EP 119
DI 10.1016/j.cell.2011.07.049
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 827AJ
UT WOS:000295396700019
PM 21962511
ER
PT J
AU Archuleta, TL
Du, YQ
English, CA
Lory, S
Lesser, C
Ohi, MD
Ohi, R
Spiller, BW
AF Archuleta, Tara L.
Du, Yaqing
English, Chauca A.
Lory, Stephen
Lesser, Cammie
Ohi, Melanie D.
Ohi, Ryoma
Spiller, Benjamin W.
TI The Chlamydia Effector Chlamydial Outer Protein N (CopN) Sequesters
Tubulin and Prevents Microtubule Assembly
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID III SECRETION TRANSLOCATOR; STATHMIN-LIKE DOMAIN; HOST-CELLS; IN-VITRO;
DYNAMIC INSTABILITY; BACTERIAL INVASION; TRACHOMATIS; POLYMERIZATION;
CHAPERONES; SHIGELLA
AB Chlamydia species are obligate intracellular pathogens that utilize a type three secretion system to manipulate host cell processes. Genetic manipulations are currently not possible in Chlamydia, necessitating study of effector proteins in heterologous expression systems and severely complicating efforts to relate molecular strategies used by Chlamydia to the biochemical activities of effector proteins. CopN is a chlamydial type three secretion effector that is essential for virulence. Heterologous expression of CopN in cells results in loss of microtubule spindles and metaphase plate formation and causes mitotic arrest. CopN is a multidomain protein with similarity to type three secretion system "plug" proteins from other organisms but has functionally diverged such that it also functions as an effector protein. Weshow that CopN binds directly to alpha beta-tubulin but not to microtubules (MTs). Furthermore, CopN inhibits tubulin polymerization by sequestering free alpha beta-tubulin, similar to one of the mechanisms utilized by stathmin. Although CopN and stathmin share no detectable sequence identity, both influence MT formation by sequestration of alpha beta-tubulin. CopN displaces stathmin from preformed stathmin-tubulin complexes, indicating that the proteins bind overlapping sites on tubulin. CopN is the first bacterial effector shown to disrupt MT formation directly. This recognition affords a mechanistic understanding of a strategy Chlamydia species use to manipulate the host cell cycle.
C1 [Archuleta, Tara L.; Spiller, Benjamin W.] Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37232 USA.
[Archuleta, Tara L.] Vanderbilt Univ, Div Chem & Phys Biol, Sch Med, Nashville, TN 37232 USA.
[Du, Yaqing; English, Chauca A.; Ohi, Melanie D.; Ohi, Ryoma] Vanderbilt Univ, Dept Cell & Dev Biol, Sch Med, Nashville, TN 37232 USA.
[Spiller, Benjamin W.] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Sch Med, Nashville, TN 37232 USA.
[Lory, Stephen; Lesser, Cammie] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Lesser, Cammie] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Spiller, BW (reprint author), Vanderbilt Univ, Dept Pharmacol, Sch Med, Nashville, TN 37232 USA.
EM benjamin.spiller@vanderbilt.edu
FU National Institutes of Health [5T90 DA022873]; National Center for
Research Resources [UL1RR024975-01, DK058404]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant UL1RR024975-01 from the National Center for Research
Resources and Grant DK058404 (to B. W. S.) and Grant NIH 5T90 DA022873
(to T. L. A.).
NR 64
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U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 30
PY 2011
VL 286
IS 39
BP 33992
EP 33998
DI 10.1074/jbc.M111.258426
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 823WW
UT WOS:000295159200031
PM 21841198
ER
PT J
AU Avsar, KB
Stoeckel, LE
Bolding, MS
White, DM
Tagamets, MA
Holcomb, HH
Lahti, AC
AF Avsar, Kathy Burton
Stoeckel, Luke Edward
Bolding, Mark Steven
White, David Matthew
Tagamets, Malle Anne
Holcomb, Henry Hilliard
Lahti, Adrienne Carol
TI Aberrant visual circuitry associated with normal spatial match-to-sample
accuracy in schizophrenia
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE fMRI; Anterior cingulate cortex; Visual perception; Working memory;
Dorsolateral prefrontal cortex
ID DORSOLATERAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX;
WORKING-MEMORY TASK; EVENT-RELATED FMRI; 1ST-EPISODE SCHIZOPHRENIA;
PHYSIOLOGICAL DYSFUNCTION; TALAIRACH ATLAS; STROOP TASK; BRAIN;
PERFORMANCE
AB A goal of this study was to evaluate the function of the anterior cingulate cortex (ACC) and of the dorsolateral prefrontal cortex (DLPFC) in medicated patients with schizophrenia (SZ), a small group of first-degree relatives, and healthy controls using a visual delayed match-to-sample task in conjunction with functional magnetic resonance imaging ( fMRI). To mitigate performance differences between SZ and healthy controls, we used a novel task that allows for individualized adjustment of task difficulty to match ability level. We also trained participants on the task prior to scanning. Using an event-related design, we modeled three components of the match-to-sample trial: visual encoding, delay, and discrimination. We did not find significant differences in ACC/medial frontal cortex activation between the groups. However, compared to healthy controls, SZ showed decreased activation in visual processing areas during the encoding and discrimination phases of the task and in the ventrolateral prefrontal cortex during the delay. These findings emphasize the tendency of schizophrenia subjects to solve perceptual memory problems by engaging diverse regions. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Avsar, Kathy Burton; Bolding, Mark Steven; White, David Matthew; Lahti, Adrienne Carol] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA.
[Avsar, Kathy Burton] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA.
[Stoeckel, Luke Edward] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Bolding, Mark Steven] Univ Alabama Birmingham, Dept Vis Sci, Birmingham, AL 35294 USA.
[Tagamets, Malle Anne; Holcomb, Henry Hilliard] Univ Maryland, Maryland Psychiat Res Ctr, Sch Med, Baltimore, MD 21247 USA.
RP Lahti, AC (reprint author), Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, SC 501,1530 3rd Ave S, Birmingham, AL 35294 USA.
EM alahti@uab.edu
OI White, David/0000-0002-6372-5311
FU National Alliance for Research on Schizophrenia and Depression (NARSAD)
FX This work was supported by a National Alliance for Research on
Schizophrenia and Depression (NARSAD), Independent Investigator Award to
A. C. Lahti. We want to thank all the volunteers with schizophrenia and
their families who so gracefully took part in this project and the staff
of the Maryland Psychiatric Research Center at the University of
Maryland. We also want to thank Alan Francis for his assistance on data
preprocessing.
NR 65
TC 1
Z9 1
U1 2
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
EI 1872-7506
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD SEP 30
PY 2011
VL 193
IS 3
BP 138
EP 143
DI 10.1016/j.pscychresns.2011.03.008
PG 6
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 822TV
UT WOS:000295073400002
PM 21782395
ER
PT J
AU Epstein, J
Perez, DL
Ervin, K
Pan, H
Kocsis, JH
Butler, T
Stern, E
Silbersweig, DA
AF Epstein, Jane
Perez, David Lewis
Ervin, Kate
Pan, Hong
Kocsis, James Howard
Butler, Tracy
Stern, Emily
Silbersweig, David Alan
TI Failure to segregate emotional processing from cognitive sensorimotor
processing in major depression
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE fMRI; Ventral striatum; Functional connectivity; Principal component
analysis; Default mode network; Neuroimaging
ID DEFAULT-MODE NETWORK; FUNCTIONAL CONNECTIVITY; MOOD DISORDERS;
PREFRONTAL CORTEX; CINGULATE CORTEX; BRAIN-FUNCTION; FMRI; MEMORY; SELF;
ABNORMALITIES
AB Most functional neuroimaging studies of major depressive disorder (MDD) employ univariate methods of statistical analysis to localize abnormalities of neural activity. Less has been done to investigate functional relations between these regions, or with regions not usually implicated in depression. Examination of intraneuronal and interneural network relations is important for the advancement of emerging network models for MDD. Principal component analysis (PCA), a multivariate statistical method, was used to examine differences in functional connectivity between 10 unmedicated patients with MDD and 12 healthy subjects engaged in a positive word viewing task. In healthy subjects, principal component (PC) 1 (33% variance) revealed functional connectivity of task-specific sensory, linguistic, and motor regions, along with functional anticorrelations in the default mode network; PC2 (10% variance) displayed functional connectivity of areas involved in emotional processing. This segregation of functions did not occur in the depressed group, where regions involved in emotional functions appeared in PC1 (34% variance) co-varying with those involved in linguistic, motor, and default mode network processing. The lack of segregation of emotional processing from cognitive and sensorimotor functions may represent a systems level neural substrate for a core phenomenon of depression: the interconnection of affective disturbance with experience, cognition, and behavior. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Epstein, Jane; Ervin, Kate; Silbersweig, David Alan] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Pan, Hong; Stern, Emily] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Perez, David Lewis] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kocsis, James Howard; Butler, Tracy] Weill Cornell Med Coll, Dept Psychiat, New York Presbyterian Hosp, New York, NY 10065 USA.
[Perez, David Lewis] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Epstein, J (reprint author), Brigham & Womens Hosp, Funct Neuroimaging Lab, Dept Psychiat, 824 Boylston St, Chestnut Hill, MA 02467 USA.
EM janeepsteinmd@gmail.com
RI Stern, Emily/E-6035-2011
FU National Alliance for Research on Schizophrenia and Depression; Pritzker
Network for the Study of Depression; New York Community Trust
FX The authors thank the following individuals for their assistance: Jude
Allen (subject recruitment and characterization, study coordination, and
data management), Susie de Rubertis and Elizabeth Levitan (subject
recruitment and characterization), Hong Gu (development of imaging
sequence), Josefino Borja (MRI technologist) and Eva Catenaccio (figure
design). This work was supported by the National Alliance for Research
on Schizophrenia and Depression, the Pritzker Network for the Study of
Depression, and the DeWitt Wallace Fund of the New York Community Trust.
All co-authors report no conflicts of interest.
NR 50
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Z9 11
U1 3
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD SEP 30
PY 2011
VL 193
IS 3
BP 144
EP 150
DI 10.1016/j.pscychresns.2011.01.012
PG 7
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 822TV
UT WOS:000295073400003
PM 21764265
ER
PT J
AU Letai, A
AF Letai, Anthony
TI Targeting Bcl-2 in CLL: cui bono?
SO BLOOD
LA English
DT Editorial Material
ID INHIBITOR; FAMILY
AB Antagonizing function of Bcl-2 is an attractive goal in chronic lymphocytic leukemia (CLL) and other lymphoid malignancies. In this issue of Blood, Al-harbi et al describe a way to combine mRNA expression data from several Bcl-2 family members into a tool that predicts in vitro sensitivity of CLL cells to ABT-737, a small molecule Bcl-2 antagonist.(1)
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Letai, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 6
TC 0
Z9 0
U1 1
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 29
PY 2011
VL 118
IS 13
BP 3453
EP 3454
DI 10.1182/blood-2011-08-370346
PG 4
WC Hematology
SC Hematology
GA 826MW
UT WOS:000295359300007
PM 21960677
ER
PT J
AU Smith, MR
Neuberg, D
Flinn, IW
Grever, MR
Lazarus, HM
Rowe, JM
Dewald, G
Bennett, JM
Paietta, EM
Byrd, JC
Hussein, MA
Appelbaum, FR
Larson, RA
Litzow, MR
Tallman, MS
AF Smith, Mitchell R.
Neuberg, Donna
Flinn, Ian W.
Grever, Michael R.
Lazarus, Hillard M.
Rowe, Jacob M.
Dewald, Gordon
Bennett, John M.
Paietta, Elisabeth M.
Byrd, John C.
Hussein, Mohamad A.
Appelbaum, Frederick R.
Larson, Richard A.
Litzow, Mark R.
Tallman, Martin S.
TI Incidence of therapy-related myeloid neoplasia after initial therapy for
chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus
fludarabine: long-term follow-up of US Intergroup Study E2997
SO BLOOD
LA English
DT Article
ID PHASE-III TRIAL; RITUXIMAB; REGIMEN
AB Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P = .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone. (Blood. 2011;118(13):3525-3527)
C1 [Smith, Mitchell R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN USA.
[Grever, Michael R.; Byrd, John C.] Ohio State Univ, Columbus, OH 43210 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Rowe, Jacob M.] Rambam Med Ctr, Haifa, Israel.
[Dewald, Gordon; Litzow, Mark R.] Mayo Clin, Rochester, MN USA.
[Bennett, John M.] Univ Rochester, Ctr Canc, Rochester, NY USA.
[Paietta, Elisabeth M.] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA.
[Hussein, Mohamad A.] Univ S Florida, Tampa, FL USA.
[Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA.
[Tallman, Martin S.] Northwestern Univ, Sch Med, Chicago, IL USA.
RP Smith, MR (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM m_smith@fccc.edu
OI Larson, Richard/0000-0001-9168-3203; Smith, Mitchell/0000-0003-1428-8765
FU Public Health Service [CA23318, CA66636, CA21115, CA27525, CA14548,
CA16116, CA77658, CA04919, CA38926, CA13650, CA17145, CA11083, CA14958,
CA032291, CA031946]; National Cancer Institute; National Institutes of
Health; Department of Health and Human Services
FX This study was coordinated by the Eastern Cooperative Oncology Group
(Robert L. Comis, MD, Chair) and supported in part by Public Health
Service grants CA23318, CA66636, CA21115, CA27525, CA14548, CA16116,
CA77658, CA04919, CA38926, CA13650, CA17145, CA11083, CA14958, CA032291,
and CA031946; and by grants from the National Cancer Institute, the
National Institutes of Health, and the Department of Health and Human
Services. Its contents are solely the responsibility of the authors and
do not necessarily represent the official views of the National Cancer
Institute.
NR 12
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U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 29
PY 2011
VL 118
IS 13
BP 3525
EP 3527
DI 10.1182/blood-2011-03-342485
PG 3
WC Hematology
SC Hematology
GA 826MW
UT WOS:000295359300018
PM 21803850
ER
PT J
AU Shaknovich, R
Cerchietti, L
Tsikitas, L
Kormaksson, M
De, S
Figueroa, ME
Ballon, G
Yang, SN
Weinhold, N
Reimers, M
Clozel, T
Luttrop, K
Ekstrom, TJ
Frank, J
Vasanthakumar, A
Godley, LA
Michor, F
Elemento, O
Melnick, A
AF Shaknovich, Rita
Cerchietti, Leandro
Tsikitas, Lucas
Kormaksson, Matthias
De, Subhajyoti
Figueroa, Maria E.
Ballon, Gianna
Yang, Shao Ning
Weinhold, Nils
Reimers, Mark
Clozel, Thomas
Luttrop, Karin
Ekstrom, Tomas J.
Frank, Jared
Vasanthakumar, Aparna
Godley, Lucy A.
Michor, Franziska
Elemento, Olivier
Melnick, Ari
TI DNA methyltransferase 1 and DNA methylation patterning contribute to
germinal center B-cell differentiation
SO BLOOD
LA English
DT Article
ID SOMATIC HYPERMUTATION; CYTOSINE METHYLATION; DEAMINASE AID; DNMT1;
ASSAY; TARGETS; CANCER; GENE; HYPERMETHYLATION; LYMPHOMAGENESIS
AB The phenotype of germinal center (GC) B cells includes the unique ability to tolerate rapid proliferation and the mutagenic actions of activation induced cytosine deaminase (AICDA). Given the importance of epigenetic patterning in determining cellular phenotypes, we examined DNA methylation and the role of DNA methyltransferases in the formation of GCs. DNA methylation profiling revealed a marked shift in DNA methylation patterning in GC B cells versus resting/naive B cells. This shift included significant differential methylation of 235 genes, with concordant inverse changes in gene expression affecting most notably genes of the NFkB and MAP kinase signaling pathways. GC B cells were predominantly hypomethylated compared with naive B cells and AICDA binding sites were highly overrepresented among hypomethylated loci. GC B cells also exhibited greater DNA methylation heterogeneity than naive B cells. Among DNA methyltransferases (DNMTs), only DNMT1 was significantly up-regulated in GC B cells. Dnmt1 hypomorphic mice displayed deficient GC formation and treatment of mice with the DNA methyltransferase inhibitor decitabine resulted in failure to form GCs after immune stimulation. Notably, the GC B cells of Dnmt1 hypomorphic animals showed evidence of increased DNA damage, suggesting dual roles for DNMT1 in DNA methylation and double strand DNA break repair. (Blood. 2011;118(13):3559-3569)
C1 [Shaknovich, Rita; Cerchietti, Leandro; Tsikitas, Lucas; Figueroa, Maria E.; Yang, Shao Ning; Clozel, Thomas; Frank, Jared; Melnick, Ari] Weill Cornell Med Coll, Div Hematol Oncol, Dept Med, New York, NY 10065 USA.
[Shaknovich, Rita; Ballon, Gianna] Weill Cornell Med Coll, Dept Pathol, Div Immunopathol, New York, NY 10065 USA.
[Kormaksson, Matthias] Weill Cornell Med Coll, Div Biostat & Epidemiol, Dept Publ Hlth, New York, NY 10065 USA.
[De, Subhajyoti; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[De, Subhajyoti] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Weinhold, Nils] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
[Reimers, Mark] Virginia Commonwealth Univ, Dept Biostat, Sch Med, Richmond, VA USA.
[Luttrop, Karin; Ekstrom, Tomas J.] Karolinska Inst, Lab Med Epigenet, Dept Clin Neurosci, Stockholm, Sweden.
[Vasanthakumar, Aparna; Godley, Lucy A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA.
RP Melnick, A (reprint author), Weill Cornell Med Coll, Div Hematol Oncol, Dept Med, 1300 York Ave, New York, NY 10065 USA.
EM amm2014@med.cornell.edu
OI Cerchietti, Leandro/0000-0003-0608-1350
FU Leukemia & Lymphoma Society [LLS 6304-11]; Leukemia & Lymphoma Society
SCOR [LLS 7017-09]; Chemotherapy Foundation; Burroughs Wellcome Clinical
Translational Scientist Award; HFSP; Swedish Cancer Society.; [K08
CA127353]; [CA129831]; [CA129831-03S1]; [R01CA138234]; [U54CA143798]
FX This research was supported by K08 CA127353 (R.S.), Leukemia & Lymphoma
Society Translational Research Program Award LLS 6304-11 (R.S.), and
Leukemia & Lymphoma Society SCOR LLS 7017-09 (A.M.). A.M. is also
supported by the Chemotherapy Foundation, a Leukemia & Lymphoma Society
Scholar Award, and a Burroughs Wellcome Clinical Translational Scientist
Award. L.A.G. is supported by CA129831 and CA129831-03S1. F.M. is
supported by R01CA138234 and U54CA143798. S. D. is a recipient of an
HFSP fellowship. T.J.E. and K.L. were supported by the Swedish Cancer
Society.
NR 45
TC 49
Z9 50
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 29
PY 2011
VL 118
IS 13
BP 3559
EP 3569
DI 10.1182/blood-2011-06-357996
PG 11
WC Hematology
SC Hematology
GA 826MW
UT WOS:000295359300022
PM 21828137
ER
PT J
AU Nilsson, RJA
Balaj, L
Hulleman, E
van Rijn, S
Pegtel, DM
Walraven, M
Widmark, A
Gerritsen, WR
Verheul, HM
Vandertop, WP
Noske, DP
Skog, J
Wurdinger, T
AF Nilsson, R. Jonas A.
Balaj, Leonora
Hulleman, Esther
van Rijn, Sjoerd
Pegtel, D. Michiel
Walraven, Maudy
Widmark, Anders
Gerritsen, Winald R.
Verheul, Henk M.
Vandertop, W. Peter
Noske, David P.
Skog, Johan
Wurdinger, Thomas
TI Blood platelets contain tumor-derived RNA biomarkers
SO BLOOD
LA English
DT Article
ID LUNG-CANCER; GENE-EXPRESSION; PROSTATE-CANCER; GROWTH-FACTOR;
ANGIOGENESIS; MICROVESICLES; EXOSOMES; PLASMA; THROMBOSPONDIN-1;
DIAGNOSTICS
AB Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer. (Blood. 2011; 118(13):3680-3683)
C1 [Nilsson, R. Jonas A.; Balaj, Leonora; Hulleman, Esther; van Rijn, Sjoerd; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands.
[Nilsson, R. Jonas A.; Balaj, Leonora; Hulleman, Esther; van Rijn, Sjoerd; Vandertop, W. Peter; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands.
[Nilsson, R. Jonas A.; Widmark, Anders] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Balaj, Leonora; Skog, Johan; Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA.
[Balaj, Leonora; Skog, Johan; Wurdinger, Thomas] Harvard Univ, Sch Med, Boston, MA USA.
[Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Pediat Oncol, NL-1081 HV Amsterdam, Netherlands.
[Pegtel, D. Michiel] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Pathol, NL-1081 HV Amsterdam, Netherlands.
[Walraven, Maudy; Gerritsen, Winald R.; Verheul, Henk M.] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands.
RP Wurdinger, T (reprint author), Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
EM t.wurdinger@vumc.nl
RI Gerritsen, W.R./H-8031-2014; Pegtel, Dirk/M-8393-2015
OI Pegtel, Dirk/0000-0002-7357-4406
FU Lion's Cancer Research Foundation; Umea University (Sweden); Stichting
Translational Research CCA/VU University Medical Center; Swedish
Research Council; NWO-VIDI
FX This work was supported by Lion's Cancer Research Foundation, Umea
University (Sweden); Stichting Translational Research CCA/VU University
Medical Center, Swedish Research Council (R.J.A.N.); and NWO-VIDI
(T.W.).
NR 33
TC 42
Z9 42
U1 3
U2 13
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 29
PY 2011
VL 118
IS 13
BP 3680
EP 3683
DI 10.1182/blood-2011-03-344408
PG 4
WC Hematology
SC Hematology
GA 826MW
UT WOS:000295359300034
PM 21832279
ER
PT J
AU Woo, AJ
Kim, J
Xu, J
Huang, H
Cantor, AB
AF Woo, Andrew J.
Kim, Jonghwan
Xu, Jian
Huang, Hui
Cantor, Alan B.
TI Role of ZBP-89 in human globin gene regulation and erythroid
differentiation
SO BLOOD
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA-1; LOCUS-CONTROL REGION; MODEL-BASED ANALYSIS;
KRUPPEL-LIKE FACTOR; BINDING-PROTEIN; FETAL-HEMOGLOBIN; GAMMA-GLOBIN;
FACTOR EKLF; FACTOR SP1; EXPRESSION
AB The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf, and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34(+) cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral short hair-pin RNAs knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the histone deacetylase inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation. (Blood. 2011; 118(13):3684-3693)
C1 [Woo, Andrew J.; Kim, Jonghwan; Xu, Jian; Huang, Hui; Cantor, Alan B.] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Woo, Andrew J.; Kim, Jonghwan; Xu, Jian; Huang, Hui; Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Cantor, AB (reprint author), Childrens Hosp Boston, Div Pediat Hematol Oncol, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA.
EM alan.cantor@childrens.harvard.edu
FU National Institutes of Health [P01 HL32262-25]
FX A.B.C. is supported by the National Institutes of Health (grant P01
HL32262-25).
NR 50
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U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 29
PY 2011
VL 118
IS 13
BP 3684
EP 3693
DI 10.1182/blood-2011-03-341446
PG 10
WC Hematology
SC Hematology
GA 826MW
UT WOS:000295359300035
PM 21828133
ER
PT J
AU Fuchs, TA
Bhandari, AA
Wagner, DD
AF Fuchs, Tobias A.
Bhandari, Ashish A.
Wagner, Denisa D.
TI Histones induce rapid and profound thrombocytopenia in mice
SO BLOOD
LA English
DT Article
ID PLATELET-AGGREGATION; HEPARIN; BLOOD; COAGULATION; THROMBOSIS; BINDING;
SEPSIS; TRAPS
AB Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen crosslinked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with alpha IIb beta 3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or alpha IIb beta 3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage. (Blood. 2011; 118(13):3708-3714)
C1 [Fuchs, Tobias A.; Bhandari, Ashish A.; Wagner, Denisa D.] Immune Dis Inst, Boston, MA 02115 USA.
[Fuchs, Tobias A.; Bhandari, Ashish A.; Wagner, Denisa D.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA.
[Fuchs, Tobias A.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Fuchs, TA (reprint author), Immune Dis Inst, 3 Blackfan Cir,3rd Fl, Boston, MA 02115 USA.
EM fuchs@idi.harvard.edu; wagner@idi.harvard.edu
RI Fuchs, Tobias/F-1189-2013
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [P01 HL056949]; Deutsche Forschungsgemeinschaft, Germany [FU
742/1-1]
FX This work was supported by the National Heart, Lung, and Blood Institute
of the National Institutes of Health (grant P01 HL056949, D. D. W.) and
a fellowship from the Deutsche Forschungsgemeinschaft, Germany (FU
742/1-1, T.A. F.).
NR 26
TC 116
Z9 117
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 29
PY 2011
VL 118
IS 13
BP 3708
EP 3714
DI 10.1182/blood-2011-01-332676
PG 7
WC Hematology
SC Hematology
GA 826MW
UT WOS:000295359300038
PM 21700775
ER
PT J
AU Yang, YP
Wang, H
Yu, H
Yeap, BY
Liang, TT
Wang, GJ
Cheng, T
Yang, YG
AF Yang, Yanping
Wang, Hui
Yu, Hui
Yeap, Beow Yong
Liang, Tingting
Wang, Guanjun
Cheng, Tao
Yang, Yong-Guang
TI IFN-gamma promotes graft-versus-leukemia effects without directly
interacting with leukemia cells in mice after allogeneic hematopoietic
cell transplantation
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; CD8(+) T-CELLS; HOST-DISEASE;
INTERFERON-GAMMA; NOTCH; INHIBITION; CHIMERAS; GVHD
AB The ability of IFN-gamma to enhance graft-versus-leukemia (GVL) activity without direct interaction with leukemia cells was examined by comparing GVL effects against IFN-gamma receptor-deficient (GRKO) leukemia between wild-type (WT) and IFN-gamma-deficient (GKO) allogeneic hematopoietic cell transplantation (allo-HCT). We established a primary IFN-gamma-unresponsive T-cell leukemia model using virally-transduced GRKO B6 mouse bone marrow cells overexpressing Notch1. We first assessed GVL effects in lethally-irradiated B6 mice receiving CD4-depleted allo-HCT from WT or GKO BALB/c donors. Administration of CD4(+) cell-depleted allo-HCT from WT, but not GKO, BALB/c donors mediated significant GVL effects against GRKO leukemia. Similar results were obtained in preestablished allogeneic chimeras receiving delayed donor lymphocyte infusion (DLI). Although both WT and GKO DLI achieved significant anti-tumor responses, the former was markedly stronger than the latter. These data indicate that IFN-gamma is capable of promoting GVL effects via mechanisms independent of its interaction with leukemia cells. (Blood. 2011; 118(13):3721-3724)
C1 [Wang, Hui; Liang, Tingting; Yang, Yong-Guang] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA.
[Yang, Yanping; Liang, Tingting; Wang, Guanjun] Jilin Univ, Bethune Hosp 1, Changchun 130023, Jilin, Peoples R China.
[Yang, Yanping; Wang, Hui; Liang, Tingting; Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA.
[Yu, Hui; Cheng, Tao] Univ Pittsburgh, Sch Med, Inst Canc, Canc Stem Cell Program,Dept Radiat Oncol, Pittsburgh, PA USA.
[Yeap, Beow Yong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Cheng, Tao] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China.
[Cheng, Tao] Chinese Acad Med Sci, Ctr Stem Cell Med, Tianjin, Peoples R China.
RP Yang, YG (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 630 W 168th St,Mail Box 127, New York, NY 10032 USA.
EM guanjunwang2006@163.com; yy2324@columbia.edu
FU National Institutes of Health [5P01CA111519-020002, RC1 HL100117]; NSFC
[81090410, 30825017, 2011CB964800]; Ministry of Health of China; China
Scholarship Council; Leukemia & Lymphoma Society
FX This work was supported by grants from the National Institutes of Health
(5P01CA111519-020002 and RC1 HL100117 to Y.G.Y.), NSFC (81090410,
30825017 and 2011CB964800 to T. C.), and the Ministry of Health of China
(a Key Clinical Program 2010 to GW). Y.Y. and T. L. are partially
supported by awards from the China Scholarship Council. T. C. is a
recipient of the scholar award from the Leukemia & Lymphoma Society.
NR 22
TC 4
Z9 5
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 29
PY 2011
VL 118
IS 13
BP 3721
EP 3724
DI 10.1182/blood-2010-05-283887
PG 4
WC Hematology
SC Hematology
GA 826MW
UT WOS:000295359300040
PM 21835954
ER
PT J
AU Seton, M
AF Seton, Margaret
TI Providing for Those Who Have Too Little
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Seton, M (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 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 SEP 29
PY 2011
VL 365
IS 13
BP 1169
EP 1171
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825YO
UT WOS:000295318400003
PM 21991890
ER
PT J
AU Cunningham, J
Harisinghani, MG
Taheri, D
AF Cunningham, John
Harisinghani, Mukesh G.
Taheri, Diana
TI Case 30-2011: A 62-Year-Old Woman with Renal Failure
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SYSTEMIC-SCLEROSIS; SCLERODERMA; CRISIS; CLASSIFICATION; SUBSETS; DRUGS
C1 [Cunningham, John] Royal Free & Univ Coll London, Sch Med, Ctr Nephrol, London, England.
[Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Taheri, Diana] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Harisinghani, Mukesh G.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Taheri, Diana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Cunningham, J (reprint author), Royal Free & Univ Coll London, Sch Med, Ctr Nephrol, London, England.
FU Harvard Medical School Department of Continuing Education, Boston;
Abbott; Amgen; Ineos; Shire; Leo; Genzyme; Fresenius
FX Presented at the Internal Medicine Comprehensive Review and Update 2010;
course director, Ravi Thadhani, M. D., Massachusetts General Hospital;
sponsored by the Harvard Medical School Department of Continuing
Education, Boston.; Dr. Cunningham reports receiving consulting fees
from Abbott, Amgen, Ineos, Shire, Leo, Genzyme, and Fresenius; grant
support from Amgen and Abbott; and payment for the development of
educational presentations, including service on speakers' bureaus, from
Amgen, Fresenius, Shire, and Abbott. No other potential conflict of
interest relevant to this article was reported.
NR 16
TC 0
Z9 0
U1 1
U2 2
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 SEP 29
PY 2011
VL 365
IS 13
BP 1234
EP 1244
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825YO
UT WOS:000295318400013
ER
PT J
AU Overmoyer, BA
Lee, JM
Younger, J
AF Overmoyer, Beth A.
Lee, Janie M.
Younger, Jerry
TI Case 17-2011: A Woman with a Mass in the Breast and Overlying Skin
Changes REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID CANCER; MRI
C1 [Overmoyer, Beth A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lee, Janie M.; Younger, Jerry] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Overmoyer, BA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 4
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 SEP 29
PY 2011
VL 365
IS 13
BP 1260
EP 1260
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825YO
UT WOS:000295318400028
ER
PT J
AU Geng, EH
Hunt, PW
Diero, LO
Kimaiyo, S
Somi, GR
Okong, P
Bangsberg, DR
Bwana, MB
Cohen, CR
Otieno, JA
Wabwire, D
Elul, B
Nash, D
Easterbrook, PJ
Braitstein, P
Musick, BS
Martin, JN
Yiannoutsos, CT
Wools-Kaloustian, K
AF Geng, Elvin H.
Hunt, Peter W.
Diero, Lameck O.
Kimaiyo, Sylvester
Somi, Geofrey R.
Okong, Pius
Bangsberg, David R.
Bwana, Mwebesa B.
Cohen, Craig R.
Otieno, Juliana A.
Wabwire, Deo
Elul, Batya
Nash, Denis
Easterbrook, Philippa J.
Braitstein, Paula
Musick, Beverly S.
Martin, Jeffrey N.
Yiannoutsos, Constantin T.
Wools-Kaloustian, Kara
TI Trends in the clinical characteristics of HIV-infected patients
initiating antiretroviral therapy in Kenya, Uganda and Tanzania between
2002 and 2009
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Article
ID SUB-SAHARAN AFRICA; MULTILEVEL ANALYSIS; EARLY MORTALITY; PROGRAM;
ADULTS; TUBERCULOSIS; RIFAMPICIN; SURVIVAL; DISEASE
AB Background: East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described.
Methods: We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm(3) or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors.
Results: Among 48, 658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pretherapy CD4 counts rose from 87 cells/mm(3) (IQR: 26-161) in 2002-03 to 154 cells/mm(3) (IQR: 71-233) in 2008-09 (p < 0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis.
Conclusions: Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed.
C1 [Geng, Elvin H.; Hunt, Peter W.; Cohen, Craig R.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA.
[Braitstein, Paula; Musick, Beverly S.; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara] Indiana Univ, Dept Med, Indianapolis, IN USA.
[Bangsberg, David R.; Bwana, Mwebesa B.] Mbarara Univ Sci & Technol, Dept Med, Mbarara, Uganda.
[Somi, Geofrey R.] Natl AIDS Control Program, Dar Es Salaam, Tanzania.
[Easterbrook, Philippa J.] Infect Dis Inst, Kampala, Uganda.
[Diero, Lameck O.; Kimaiyo, Sylvester] Moi Univ, Dept Med, Eldoret, Kenya.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA.
[Okong, Pius] St Francis Hosp, Kampala, Uganda.
[Wabwire, Deo] Makerere Univ Johns Hopkins Univ Res Collaborat, Kampala, Uganda.
[Otieno, Juliana A.] Kisumu MTCT Plus Initiat, Kisumu, Kenya.
[Elul, Batya; Nash, Denis] Int Ctr AIDS Care & Treatment Programs, New York, NY USA.
RP Geng, EH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, 995 Potrero Ave, San Francisco, CA 94143 USA.
EM genge@php.ucsf.edu
FU National Institutes of Health [K23 AI084544, U01 AI069911, P30
AI027763]; United States President's Emergency Plan for AIDS Relief
(PEPFAR)
FX This study received financial support from the National Institutes of
Health (K23 AI084544, U01 AI069911, P30 AI027763) and the United States
President's Emergency Plan for AIDS Relief (PEPFAR). All authors are
members of the East Africa International Epidemiologic Databases to
Evaluate AIDS (IeDEA) Consortium.
NR 25
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U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD SEP 28
PY 2011
VL 14
AR 46
DI 10.1186/1758-2652-14-46
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 839GU
UT WOS:000296354300001
PM 21955541
ER
PT J
AU Majumder, S
Richardson, A
Strong, R
Oddo, S
AF Majumder, Smita
Richardson, Arlan
Strong, Randy
Oddo, Salvatore
TI Inducing Autophagy by Rapamycin Before, but Not After, the Formation of
Plaques and Tangles Ameliorates Cognitive Deficits
SO PLOS ONE
LA English
DT Article
ID EXACERBATES TAU PATHOLOGY; P70 S6 KINASE; ALZHEIMERS-DISEASE; A-BETA;
LIFE-SPAN; AMYLOID-BETA; MOUSE MODEL; IN-VIVO; SIGNALING PATHWAY;
TRANSGENIC MODEL
AB Previous studies have shown that inducing autophagy ameliorates early cognitive deficits associated with the build-up of soluble amyloid-beta (A beta). However, the effects of inducing autophagy on plaques and tangles are yet to be determined. While soluble A beta and tau represent toxic species in Alzheimer's disease (AD) pathogenesis, there is well documented evidence that plaques and tangles also are detrimental to normal brain function. Thus, it is critical to assess the effects of inducing autophagy in an animal model with established plaques and tangles. Here we show that rapamycin, when given prophylactically to 2-month-old 3xTg-AD mice throughout their life, induces autophagy and significantly reduces plaques, tangles and cognitive deficits. In contrast, inducing autophagy in 15-month-old 3xTg-AD mice, which have established plaques and tangles, has no effects on AD-like pathology and cognitive deficits. In conclusion, we show that autophagy induction via rapamycin may represent a valid therapeutic strategy in AD when administered early in the disease progression.
C1 [Majumder, Smita; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Majumder, Smita; Richardson, Arlan; Strong, Randy; Oddo, Salvatore] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA.
[Richardson, Arlan; Strong, Randy] S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA.
RP Majumder, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
EM oddo@uthscsa.edu
FU National Institute on Aging (NIA) [K99/R00AG29729-4, R01AG037637];
William and Ella Owens Medical Research Foundation; [RC2AG036613]
FX This work was supported by National Institute on Aging (NIA) grant
awards K99/R00AG29729-4 and R01AG037637 (Oddo, Principal Investigator),
RC2AG036613 (Richardson, Principal Investigator, Strong and Oddo,
Project Co-leaders), and by an award from the William and Ella Owens
Medical Research Foundation to S.O. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 95
TC 127
Z9 133
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 28
PY 2011
VL 6
IS 9
AR e25416
DI 10.1371/journal.pone.0025416
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834CT
UT WOS:000295936900063
PM 21980451
ER
PT J
AU Roffman, JL
Nitenson, AZ
Agam, Y
Isom, M
Friedman, JS
Dyckman, KA
Brohawn, DG
Smoller, JW
Goff, DC
Manoach, DS
AF Roffman, Joshua L.
Nitenson, Adam Z.
Agam, Yigal
Isom, Marlisa
Friedman, Jesse S.
Dyckman, Kara A.
Brohawn, David G.
Smoller, Jordan W.
Goff, Donald C.
Manoach, Dara S.
TI A Hypomethylating Variant of MTHFR, 677C > T, Blunts the Neural Response
to Errors in Patients with Schizophrenia and Healthy Individuals
SO PLOS ONE
LA English
DT Article
ID HUMAN CEREBRAL-CORTEX; METHYLENETETRAHYDROFOLATE REDUCTASE; ANTERIOR
CINGULATE; EXECUTIVE FUNCTION; DNA-METHYLATION; COMMON MUTATION;
POLYMORPHISMS; PERFORMANCE; DISORDERS; NEURONS
AB Background: Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.
Methodology/Principal Findings: Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele.
Conclusions/Significance: These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene.
C1 [Roffman, Joshua L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
Harvard Univ, Sch Med, Charlestown, MA USA.
RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
EM jroffman@partners.org
FU National Institute of Mental Health [5R01MH067720]; Howard Hughes
Medical Institute
FX This paper was funded by the National Institute of Mental Health
(5R01MH067720) to DSM. and a Howard Hughes Medical Institute
Physician-Scientist Early Career Award to JLR. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
TC 15
Z9 16
U1 1
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 SEP 28
PY 2011
VL 6
IS 9
AR e25253
DI 10.1371/journal.pone.0025253
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834CT
UT WOS:000295936900040
PM 21980405
ER
PT J
AU Soulieres, I
Dawson, M
Gernsbacher, MA
Mottron, L
AF Soulieres, Isabelle
Dawson, Michelle
Gernsbacher, Morton Ann
Mottron, Laurent
TI The Level and Nature of Autistic Intelligence II: What about Asperger
Syndrome?
SO PLOS ONE
LA English
DT Article
ID PERVASIVE DEVELOPMENTAL DISORDERS; SPECTRUM DISORDERS; FLUID
INTELLIGENCE; CHILDREN; PERSPECTIVE; ABILITY; IQ; INDIVIDUALS;
PERFORMANCE; PERCEPTION
AB A distinctively uneven profile of intelligence is a feature of the autistic spectrum. Within the spectrum, Asperger individuals differ from autistics in their early speech development and in being less likely to be characterized by visuospatial peaks. While different specific strengths characterize different autistic spectrum subgroups, all such peaks of ability have been interpreted as deficits: isolated, aberrant, and irreconcilable with real human intelligence. This view has recently been challenged by findings of autistic strengths in performance on Raven's Progressive Matrices (RPM), an important marker of general and fluid intelligence. We investigated whether these findings extend to Asperger syndrome, an autistic spectrum subgroup characterized by verbal peaks of ability, and whether the cognitive mechanisms underlying autistic and Asperger RPM performance differ. Thirty-two Asperger adults displayed a significant advantage on RPM over Wechsler Full-Scale and Performance scores relative to their typical controls, while in 25 Asperger children an RPM advantage was found over Wechsler Performance scores only. As previously found with autistics, Asperger children and adults achieved RPM scores at a level reflecting their Wechsler peaks of ability. Therefore, strengths in RPM performance span the autistic spectrum and imply a common mechanism advantageously applied to different facets of cognition. Autistic spectrum intelligence is atypical, but also genuine, general, and underestimated.
C1 [Soulieres, Isabelle; Dawson, Michelle; Mottron, Laurent] Univ Montreal, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ, Canada.
[Soulieres, Isabelle] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.
[Gernsbacher, Morton Ann] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA.
RP Soulieres, I (reprint author), Univ Montreal, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ, Canada.
EM isabelle@nmr.mgh.harvard.edu
FU Canadian Institutes for Health Research (CIHR) [MOP-84243]
FX This work was supported by a grant from Canadian Institutes for Health
Research (CIHR; grant MOP-84243) to LM and a postdoctoral award from
CIHR to IS. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 37
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Z9 23
U1 12
U2 23
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 SEP 28
PY 2011
VL 6
IS 9
AR e25372
DI 10.1371/journal.pone.0025372
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834CT
UT WOS:000295936900056
PM 21991394
ER
PT J
AU Weisberg, E
Ray, A
Nelson, E
Adamia, S
Barrett, R
Sattler, M
Zhang, CS
Daley, JF
Frank, D
Fox, E
Griffin, JD
AF Weisberg, Ellen
Ray, Arghya
Nelson, Erik
Adamia, Sophia
Barrett, Rosemary
Sattler, Martin
Zhang, Chengsheng
Daley, John F.
Frank, David
Fox, Edward
Griffin, James D.
TI Reversible Resistance Induced by FLT3 Inhibition: A Novel Resistance
Mechanism in Mutant FLT3-Expressing Cells
SO PLOS ONE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; INTERNAL TANDEM
DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; ACTIVATING MUTATION; POINT
MUTATIONS; IN-VITRO; CONSTITUTIVE ACTIVATION; CLINICAL RESISTANCE;
THERAPEUTIC TARGET
AB Objectives: Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML) are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors.
Methods: MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression.
Results and Conclusions: We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance.
C1 [Weisberg, Ellen; Ray, Arghya; Nelson, Erik; Adamia, Sophia; Barrett, Rosemary; Sattler, Martin; Frank, David; Griffin, James D.] Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, Boston, MA 02115 USA.
[Zhang, Chengsheng] Dana Farber Canc Inst, Cytogenet Core Facil, Boston, MA 02115 USA.
[Daley, John F.] Dana Farber Canc Inst, Hematol Neoplasia Flow Cytometry Facil, Boston, MA 02115 USA.
[Fox, Edward] Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA.
RP Weisberg, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, Boston, MA 02115 USA.
EM ellen_weisberg@dfci.harvard.edu
FU National Institutes of Health (NIH) [CA66996, CA134660-03]
FX JDG is supported by National Institutes of Health (NIH) grant CA66996
and MS is supported by NIH grant CA134660-03. JDG has a financial
interest with Novartis Pharma AG. 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 13
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 SEP 28
PY 2011
VL 6
IS 9
AR e25351
DI 10.1371/journal.pone.0025351
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834CT
UT WOS:000295936900054
PM 21980431
ER
PT J
AU Nasr, S
Liu, N
Devaney, KJ
Yue, XM
Rajimehr, R
Ungerleider, LG
Tootell, RBH
AF Nasr, Shahin
Liu, Ning
Devaney, Kathryn J.
Yue, Xiaomin
Rajimehr, Reza
Ungerleider, Leslie G.
Tootell, Roger B. H.
TI Scene-Selective Cortical Regions in Human and Nonhuman Primates
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID HUMAN VISUAL-CORTEX; FUSIFORM FACE AREA; PARAHIPPOCAMPAL PLACE AREA;
HUMAN EXTRASTRIATE CORTEX; INFERIOR TEMPORAL CORTEX; FUNCTIONAL MRI;
CEREBRAL-CORTEX; VISUOTOPIC ORGANIZATION; RETROSPLENIAL CORTEX; OBJECT
PERCEPTION
AB fMRI studies have revealed three scene-selective regions in human visual cortex [the parahippocampal place area (PPA), transverse occipital sulcus (TOS), and retrosplenial cortex (RSC)], which have been linked to higher-order functions such as navigation, scene perception/recognition, and contextual association. Here, we document corresponding (presumptively homologous) scene-selective regions in the awake macaque monkey, based on direct comparison to human maps, using identical stimuli and largely overlapping fMRI procedures. In humans, our results showed that the three scene-selective regions are centered near-but distinct from-the gyri/sulci for which they were originally named. In addition, all these regions are located within or adjacent to known retinotopic areas. Human RSC and PPA are located adjacent to the peripheral representation of primary and secondary visual cortex, respectively. Human TOS is located immediately anterior/ventral to retinotopic area V3A, within retinotopic regions LO-1, V3B, and/or V7. Mirroring the arrangement of human regions fusiform face area (FFA) and PPA (which are adjacent to each other in cortex), the presumptive monkey homolog of human PPA is located adjacent to the monkey homolog of human FFA, near the posterior superior temporal sulcus. Monkey TOS includes the region predicted from the human maps (macaque V4d), extending into retinotopically defined V3A. A possible monkey homolog of human RSC lies in the medial bank, near peripheral V1. Overall, our findings suggest a homologous neural architecture for scene-selective regions in visual cortex of humans and nonhuman primates, analogous to the face-selective regions demonstrated earlier in these two species.
C1 [Nasr, Shahin; Devaney, Kathryn J.; Yue, Xiaomin; Rajimehr, Reza; Tootell, Roger B. H.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Liu, Ning; Ungerleider, Leslie G.; Tootell, Roger B. H.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Nasr, S (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA.
EM shahin@nmr.mgh.harvard.edu
FU NIH [R01 MH67529, R01 EY017081]; Martinos Center for Biomedical Imaging;
NCRR; MIND Institute [1S10RR023401, 1S10RR019, 1S10RR023043]; NIMH
FX This work was supported by NIH Grants R01 MH67529 and R01 EY017081 ( R.
B. H. T.), the Martinos Center for Biomedical Imaging, the NCRR, the
MIND Institute, Shared Instrumentation Grants 1S10RR023401, 1S10RR019,
and 1S10RR023043, and the NIMH Intramural Research Program.
NR 89
TC 81
Z9 82
U1 0
U2 11
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 28
PY 2011
VL 31
IS 39
BP 13771
EP 13785
DI 10.1523/JNEUROSCI.2792-11.2011
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 826OP
UT WOS:000295363800010
PM 21957240
ER
PT J
AU Syed, Z
Stultz, CM
Scirica, BM
Guttag, JV
AF Syed, Zeeshan
Stultz, Collin M.
Scirica, Benjamin M.
Guttag, John V.
TI Computationally Generated Cardiac Biomarkers for Risk Stratification
After Acute Coronary Syndrome
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID AMERICAN-HEART-ASSOCIATION; ACUTE MYOCARDIAL-INFARCTION; SCIENTIFIC
STATEMENT; CLINICAL CARDIOLOGY; RANDOMIZED-TRIALS; TIME-SERIES; DEATH;
STRATEGIES; THERAPY; DISEASE
AB The existing tools for estimating the risk of death in patients after they experience acute coronary syndrome are commonly based on echocardiography and clinical risk scores (for example, the TIMI risk score). These identify a small group of high-risk patients who account for only a minority of the deaths that occur in patients after acute coronary syndrome. Here, we investigated the use of three computationally generated cardiac biomarkers for risk stratification in this population: morphologic variability (MV), symbolic mismatch (SM), and heart rate motifs (HRM). We derived these biomarkers from time-series analyses of continuous electrocardiographic data collected from patients in the TIMI-DISPERSE2 clinical trial through machine learning and data mining methods designed to extract information that is difficult to visualize directly in these data. We evaluated these biomarkers in a blinded, prespecified, and fully automated study on more than 4500 patients in the MERLIN-TIMI36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36) clinical trial. Our results showed a strong association between all three computationally generated cardiac biomarkers and cardiovascular death in the MERLIN-TIMI36 trial over a 2-year period after acute coronary syndrome. Moreover, the information in each of these biomarkers was independent of the information in the others and independent of the information provided by existing clinical risk scores, electrocardiographic metrics, and echocardiography. The addition of MV, SM, and HRM to existing metrics significantly improved model discrimination, as well as the precision and recall of prediction rules based on left ventricular ejection fraction. These biomarkers can be extracted from data that are routinely captured from patients with acute coronary syndrome and will allow for more accurate risk stratification and potentially for better patient treatment.
C1 [Syed, Zeeshan] Univ Michigan, Ann Arbor, MI 48109 USA.
[Stultz, Collin M.; Scirica, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Stultz, Collin M.; Guttag, John V.] MIT, Cambridge, MA 02139 USA.
[Scirica, Benjamin M.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
RP Syed, Z (reprint author), Univ Michigan, Ann Arbor, MI 48109 USA.
EM zhs@umich.edu
FU National Science Foundation; American Heart Association; Center for
Integration of Medicine and Innovative Technology; Quanta Computer;
Harvard-MIT Division of Health Sciences and Technology; AstraZeneca LLC;
CV Therapeutics (now Gilead Sciences); Brigham and Women's Hospital
FX Supported by the National Science Foundation, the American Heart
Association, the Center for Integration of Medicine and Innovative
Technology, Quanta Computer, and the Harvard-MIT Division of Health
Sciences and Technology. The TIMI-DISPERSE2 trial was supported by
AstraZeneca LLC. The MERLIN-TIMI36 trial was supported by CV
Therapeutics (now Gilead Sciences).; B.M.S. has received research
support via Brigham and Women's Hospital from Gilead Sciences and served
as a paid consultant. The other authors declare that they have no
competing interests. The Massachusetts Institute of Technology has
submitted a patent application for the use of the MV analysis with Z.S.,
C. M. S., and J.V.G. listed as inventors.
NR 38
TC 4
Z9 4
U1 0
U2 5
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 SEP 28
PY 2011
VL 3
IS 102
AR 102ra95
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 826AH
UT WOS:000295323200006
PM 21957173
ER
PT J
AU Soremekun, OA
Brown, DFM
Pines, JM
AF Soremekun, Olan A.
Brown, David F. M.
Pines, Jesse M.
TI Ambulance Diversion and Survival Among Patients With Acute Myocardial
Infarction
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID ASSOCIATION
C1 [Soremekun, Olan A.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA.
[Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Pines, Jesse M.] George Washington Univ, Dept Emergency Med, Washington, DC USA.
RP Soremekun, OA (reprint author), Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA.
EM olanrewaju.soremekun@uphs.upenn.edu
NR 3
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD SEP 28
PY 2011
VL 306
IS 12
BP 1324
EP 1325
DI 10.1001/jama.2011.1352
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825FQ
UT WOS:000295257000014
PM 21954474
ER
PT J
AU Barry, MJ
Meleth, S
Lee, JY
Kreder, KJ
Avins, AL
Nickel, JC
Roehrborn, CG
Crawford, ED
Foster, HE
Kaplan, SA
McCullough, A
Andriole, GL
Naslund, MJ
Williams, OD
Kusek, JW
Meyers, CM
Betz, JM
Cantor, A
McVary, KT
AF Barry, Michael J.
Meleth, Sreelatha
Lee, Jeannette Y.
Kreder, Karl J.
Avins, Andrew L.
Nickel, J. Curtis
Roehrborn, Claus G.
Crawford, E. David
Foster, Harris E., Jr.
Kaplan, Steven A.
McCullough, Andrew
Andriole, Gerald L.
Naslund, Michael J.
Williams, O. Dale
Kusek, John W.
Meyers, Catherine M.
Betz, Joseph M.
Cantor, Alan
McVary, Kevin T.
CA Complementary Alternative Med Urol
TI Effect of Increasing Doses of Saw Palmetto Extract on Lower Urinary
Tract Symptoms A Randomized Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID BENIGN PROSTATIC HYPERPLASIA; CLINICAL-RESEARCH; HEALTH-STATUS; IMPACT
INDEX; SCALE; MEN; QUESTIONNAIRE; PHYTOTHERAPY; DYSFUNCTION; VALIDATION
AB Context Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d).
Objective To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH.
Design, Setting, and Participants A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions.
Interventions One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks.
Main Outcome Measures Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, post-void residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms.
Results Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -0.36) with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P=.91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified.
Conclusion Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo.
C1 [Barry, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Meleth, Sreelatha; Williams, O. Dale; Cantor, Alan] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA.
[Lee, Jeannette Y.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA.
[Kreder, Karl J.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA.
[Avins, Andrew L.] No Calif Kaiser Permanente, Div Res, Oakland, CA USA.
[Nickel, J. Curtis] Queens Univ, Dept Urol, Kingston, ON, Canada.
[Roehrborn, Claus G.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
[Crawford, E. David] Univ Colorado, Sect Urol Oncol, Denver, CO 80202 USA.
[Foster, Harris E., Jr.] Yale Univ, Sch Med, Urol Sect, New Haven, CT USA.
[Kaplan, Steven A.] Weill Cornell Med Coll, Dept Urol, New York, NY USA.
[McCullough, Andrew] NYU, Urol Associates, New York, NY USA.
[Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Naslund, Michael J.] Univ Maryland, Maryland Prostate Ctr, Baltimore, MD 21201 USA.
[Kusek, John W.] NIDDK, Bethesda, MD USA.
[Meyers, Catherine M.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
[Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[McVary, Kevin T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM mbarry@partners.org
FU GlaxoSmithKline; Pfizer; Watson; Astellas; Ferring; Taris; Triton; Farr
Labs; Trillium; Cernelle; Johnson Johnson; Amgen; Bayer; Caris; France
Foundation; GenProbe; Steba Biotech; Ortho-Clinical Diagnostics; Ferring
Pharmaceuticals; Lilly/ICOS; Allergan; National Institute of Diabetes
and Digestive and Kidney Diseases; Watson Pharm; Neotract; National
Institutes of Health (NIH), National Institute of Diabetes and Digestive
and Kidney Diseases [U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835,
U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01
DK63831, U01 DK63778, U01 DK63788]; National Center for Complementary
and Alternative Medicine; Office of Dietary Supplements, NIH
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Barry reported serving on the
board of and receiving salary support as president of the not-for-profit
(501[3]c) Foundation for Informed Medical Decision Making
(http://www.fimdm.org), which develops content for patient education
programs. The foundation has an arrangement with a for-profit company,
Health Dialog, to coproduce and market these programs to health care
organizations. Dr Lee reported that funds were paid to her institution
for consultancy to Merck. Dr Nickel reported receiving consultation
funds from GlaxoSmithKline, Pfizer, Watson, Astellas, Ferring, Taris,
Triton, Farr Labs, Trillium, Cernelle, and Johnson & Johnson; having
provided expert testimony for GlaxoSmithKline; and having received
payment for development of educational presentations from the Canadian
Urological Association. Dr Crawford reported receiving payment for
lectures from Ferring Pharmaceuticals and GlaxoSmithKline. Dr Andriole
reported receiving consultation funds from Amgen, Bayer, Caris, France
Foundation, GenProbe, GlaxoSmithKline, Steba Biotech, Ortho-Clinical
Diagnostics, and Ferring Pharmaceuticals; having received royalties from
Up to Date; receiving payment for development of educational
presentations from Amgen; having stock and/or stock options in
Envisioneering Medical, Viking Medical, Augmenix, and Cambridge Endo;
and receiving travel, accommodations, and meeting expenses from Amgen,
Augmenix, Bayer, Cambridge Endo, Caris, France Foundation, GenProbe,
Myriad Genetics, Steba Biotech, and Ortho Clinical Diagnostics. Dr
Naslund reported receiving payment for lectures from GlaxoSmithKline and
sanofi-aventis, as well as payment for development of educational
presentations for France Foundation. Dr McVary reported receiving
consultancy funds from Lilly/ICOS, Allergan, National Institute of
Diabetes and Digestive and Kidney Diseases, Watson Pharm, and Neotract,
as well as payment for lectures from GlaxoSmithKline. No other
disclosures were reported.; This study was funded by cooperative
agreements U01 DK63795, U01 DK63797, U01 DK63825, U01 DK63835, U01
DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63883, U01
DK63831, U01 DK63778, and U01 DK63788 from the National Institutes of
Health (NIH), National Institute of Diabetes and Digestive and Kidney
Diseases. Support was also provided by the National Center for
Complementary and Alternative Medicine and the Office of Dietary
Supplements, NIH. Saw palmetto fruit extract and matching placebo were
donated by Rottapharm/Madaus, Cologne, Germany. This study was conducted
under an Investigational New Drug Application from the US Food and Drug
Administration.
NR 28
TC 55
Z9 55
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 SEP 28
PY 2011
VL 306
IS 12
BP 1344
EP 1351
DI 10.1001/jama.2011.1364
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825FQ
UT WOS:000295257000023
PM 21954478
ER
PT J
AU Maher, AR
Maglione, M
Bagley, S
Suttorp, M
Hu, JH
Ewing, B
Wang, Z
Timmer, M
Sultzer, D
Shekelle, PG
AF Maher, Alicia Ruelaz
Maglione, Margaret
Bagley, Steven
Suttorp, Marika
Hu, Jian-Hui
Ewing, Brett
Wang, Zhen
Timmer, Martha
Sultzer, David
Shekelle, Paul G.
TI Efficacy and Comparative Effectiveness of Atypical Antipsychotic
Medications for Off-Label Uses in Adults A Systematic Review and
Meta-analysis
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED-TRIAL; SEROTONIN
REUPTAKE INHIBITORS; GENERALIZED ANXIETY DISORDER; CONTROLLED
CLINICAL-TRIAL; NURSING-HOME RESIDENTS; FUMARATE QUETIAPINE XR;
DOUBLE-BLIND TRIAL; A-DOUBLE-BLIND; ALZHEIMERS-DISEASE
AB Context Atypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder.
Objective To perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration.
Data Sources and Study Selection Relevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events.
Data Extraction Independent article review and study quality assessment by 2 investigators.
Data Synthesis Of 12 228 citations identified, 162 contributed data to the efficacy review. Among 14 placebo-controlled trials of elderly patients with dementia reporting a total global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH]=87), stroke (NNH=53 for risperidone), extrapyramidal symptoms (NNH=10 for olanzapine; NNH=20 for risperidone), and urinary tract symptoms (NNH range=16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal symptoms.
Conclusions Benefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common. JAMA. 2011;306(12):1359-1369
C1 [Maher, Alicia Ruelaz; Maglione, Margaret; Suttorp, Marika; Hu, Jian-Hui; Ewing, Brett; Wang, Zhen; Timmer, Martha; Shekelle, Paul G.] So Calif Evidence Based Practice Ctr, RAND Hlth, Santa Monica, CA 90401 USA.
[Bagley, Steven] VA Palo Alto Healthcare Syst, Palo Alto, CA USA.
[Sultzer, David; Shekelle, Paul G.] W Los Angeles VA Med Ctr, Los Angeles, CA USA.
[Sultzer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Maher, AR (reprint author), So Calif Evidence Based Practice Ctr, RAND Hlth, 1776 Main St, Santa Monica, CA 90401 USA.
EM Alicia.Ruelaz@cshs.org
RI Wang, Zhen/D-5991-2013
OI Wang, Zhen/0000-0002-9368-6149
FU Eli Lilly; RAND Corporation; Agency for Healthcare Research and Quality
[HHSA2902007100621]; Department of Veterans Affairs
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Sultzer reported that he received
research support for an Alzheimer disease study from Eli Lilly (no
direct or indirect salary was paid to him) and consulting fees from RAND
Corporation for his work as member of a technical expert panel for the
Agency for Healthcare Research and Quality that performed the initial
analysis. No other disclosures were reported.; This article is based on
research conducted by the Southern California Evidence-Based Practice
Center under contract HHSA2902007100621 with the Agency for Healthcare
Research and Quality. This work was commissioned by the Agency for
Healthcare Research and Quality as an update to an earlier report. Drs
Sultzer and Shekelle are also supported by the Department of Veterans
Affairs.
NR 99
TC 191
Z9 199
U1 9
U2 37
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 SEP 28
PY 2011
VL 306
IS 12
BP 1359
EP 1369
DI 10.1001/jama.2011.1360
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825FQ
UT WOS:000295257000025
PM 21954480
ER
PT J
AU Murphy, RM
Shah, RV
Malhotra, R
Pappagianopoulos, PP
Hough, SS
Systrom, DM
Semigran, MJ
Lewis, GD
AF Murphy, Ryan M.
Shah, Ravi V.
Malhotra, Rajeev
Pappagianopoulos, Paul P.
Hough, Stacyann S.
Systrom, David M.
Semigran, Marc J.
Lewis, Gregory D.
TI Exercise Oscillatory Ventilation in Systolic Heart Failure An Indicator
of Impaired Hemodynamic Response to Exercise
SO CIRCULATION
LA English
DT Article
DE congestive heart failure; exercise testing; heart failure; ventilation
ID CHEYNE-STOKES RESPIRATION; IDIOPATHIC DILATED CARDIOMYOPATHY; CARDIAC
TRANSPLANTATION; WEDGE PRESSURE; SLEEP; MORTALITY; MECHANISM; SECONDARY;
HYPERVENTILATION; CHEMOSENSITIVITY
AB Background-Exercise oscillatory ventilation (EOV) is a noninvasive parameter that potently predicts outcomes in systolic heart failure (HF). However, mechanistic insights into EOV have been limited by the absence of studies relating EOV to invasive hemodynamic measurements and blood gases performed during exercise.
Methods and Results-Fifty-six patients with systolic HF (mean +/- SEM age, 59 +/- 2 years; left ventricular ejection fraction, 30 +/- 1%) and 19 age-matched control subjects were studied with incremental cardiopulmonary exercise testing. Fick cardiac outputs, filling pressures, and arterial blood gases were measured at 1-minute intervals during exercise. We detected EOV in 45% of HF (HF + EOV) patients and in none of the control subjects. The HF + EOV group did not differ from the HF patients without EOV (HF - EOV) in age, sex, body mass index, left ventricular ejection fraction, or origin of HF. Univariate predictors of the presence of EOV in HF, among measurements performed during exercise, included higher right atrial pressure and pulmonary capillary wedge pressure and lower cardiac index (CI) but not PaCO(2) or PaO(2). Multivariate logistic regression identified that low exercise CI is the strongest predictor of EOV (odds ratio, 1.39 for each 1.0-L.min(-1).m(-2) decrement in CI; 95% confidence interval, 1.14-1.70; P=0.001). Among HF patients with EOV, exercise CI was inversely related to EOV cycle length (R=-0.71) and amplitude (R=-0.60; both P<0.001). In 11 HF + EOV subjects treated with 12 weeks of sildenafil, EOV cycle length and amplitude decreased proportionately to increases in CI.
Conclusion-Exercise oscillatory ventilation is closely related to reduced CI and elevated filling pressures during exercise and may be an important surrogate for exercise-induced hemodynamic impairment in HF patients.
C1 [Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Heart Failure & Cardiac Transplantat Unit,Cardiol, Boston, MA 02114 USA.
[Pappagianopoulos, Paul P.; Hough, Stacyann S.; Systrom, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA.
RP Lewis, GD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Heart Failure & Cardiac Transplantat Unit,Cardiol, Bigelow 800,Fruit St, Boston, MA 02114 USA.
EM glewis@partners.org
OI Systrom, David/0000-0002-9610-6330; Malhotra, Rajeev/0000-0003-0120-4630
FU National Heart, Lung, and Blood Institute [NIH-K23HL091106]; National
Heart, Lung, and Blood Institute Heart Failure Network [U01-HL084877];
American Heart Association [11POST000002]; Heart Failure Research
Innovation Fund
FX We gratefully acknowledge support from the National Heart, Lung, and
Blood Institute (NIH-K23HL091106, Dr Lewis); the National Heart, Lung,
and Blood Institute Heart Failure Network training grant (U01-HL084877,
to Drs Shah and Lewis); the American Heart Association Post-Doctoral
Fellowship Award (11POST000002, to Dr Shah); and the Heart Failure
Research Innovation Fund (to R. M. Murphy and Dr Lewis).
NR 45
TC 38
Z9 39
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 27
PY 2011
VL 124
IS 13
BP 1442
EP U196
DI 10.1161/CIRCULATIONAHA.111.024141
PG 14
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 824QV
UT WOS:000295218000017
PM 21875912
ER
PT J
AU Goldstein, JA
Chinnaiyan, KM
Abidov, A
Achenbach, S
Berman, DS
Hayes, SW
Hoffmann, U
Lesser, JR
Mikati, IA
O'Neil, BJ
Shaw, LJ
Shen, MYH
Valeti, US
Raff, GL
AF Goldstein, James A.
Chinnaiyan, Kavitha M.
Abidov, Aiden
Achenbach, Stephan
Berman, Daniel S.
Hayes, Sean W.
Hoffmann, Udo
Lesser, John R.
Mikati, Issam A.
O'Neil, Brian J.
Shaw, Leslee J.
Shen, Michael Y. H.
Valeti, Uma S.
Raff, Gilbert L.
CA CT-STAT Investigators
TI The CT-STAT (Coronary Computed Tomographic Angiography for Systematic
Triage of Acute Chest Pain Patients to Treatment) Trial
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE acute chest pain; coronary computed tomography; cost of care; diagnostic
effectiveness; emergency department
ID CARDIOVASCULAR-MAGNETIC-RESONANCE; AMERICAN-HEART-ASSOCIATION;
RANDOMIZED CONTROLLED-TRIAL; APPROPRIATE USE CRITERIA;
EMERGENCY-DEPARTMENT; NUCLEAR-CARDIOLOGY; TASK-FORCE; UNSTABLE ANGINA;
ARTERY-DISEASE; COMPREHENSIVE STRATEGY
AB Objectives The purpose of this study was to compare the efficiency, cost, and safety of a diagnostic strategy employing early coronary computed tomographic angiography (CCTA) to a strategy employing rest-stress myocardial perfusion imaging (MPI) in the evaluation of acute low-risk chest pain.
Background In the United States, >8 million patients require emergency department evaluation for acute chest pain annually at an estimated diagnostic cost of >$10 billion.
Methods This multicenter, randomized clinical trial in 16 emergency departments ran between June 2007 and November 2008. Patients were randomly allocated to CCTA (n = 361) or MPI (n = 338) as the index noninvasive test. The primary outcome was time to diagnosis; the secondary outcomes were emergency department costs of care and safety, defined as freedom from major adverse cardiac events in patients with normal index tests, including 6-month follow-up.
Results The CCTA resulted in a 54% reduction in time to diagnosis compared with MPI (median 2.9 h [25th to 75th percentile: 2.1 to 4.0 h] vs. 6.3 h [25th to 75th percentile: 4.2 to 19.0 h], p < 0.0001). Costs of care were 38% lower compared with standard (median $2,137 [25th to 75th percentile: $1,660 to $3,077] vs. $3,458 [25th to 75th percentile: $2,900 to $4,297], p < 0.0001). The diagnostic strategies had no difference in major adverse cardiac events after normal index testing (0.8% in the CCTA arm vs. 0.4% in the MPI arm, p = 0.29).
Conclusions In emergency department acute, low-risk chest pain patients, the use of CCTA results in more rapid and cost-efficient safe diagnosis than rest-stress MPI. Further studies comparing CCTA to other diagnostic strategies are needed to optimize evaluation of specific patient subsets. (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment [CT-STAT]; NCT00468325) (J Am Coll Cardiol 2011; 58: 1414-22) (C) 2011 by the American College of Cardiology Foundation
C1 [Goldstein, James A.; Chinnaiyan, Kavitha M.; Raff, Gilbert L.] William Beaumont Hosp, Div Cardiol, Royal Oak, MI 48073 USA.
[Abidov, Aiden] Univ Arizona, Div Cardiol, Tucson, AZ USA.
[Achenbach, Stephan] Univ Giessen, Dept Cardiol, Giessen, Germany.
[Berman, Daniel S.; Hayes, Sean W.] Cedars Sinai Med Ctr, Dept Imaging, Los Angeles, CA 90048 USA.
[Berman, Daniel S.; Hayes, Sean W.] Cedars Sinai Med Ctr, Dept Cardiol, Los Angeles, CA 90048 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Lesser, John R.] Minneapolis Heart Inst, Minneapolis, MN USA.
[Mikati, Issam A.] Northwestern Univ, Div Cardiol, Sch Med, Chicago, IL USA.
[O'Neil, Brian J.] Wayne State Univ, Sch Med, Dept Emergency Med, Detroit, MI USA.
[Shaw, Leslee J.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA.
[Shen, Michael Y. H.] Cleveland Clin Florida, Div Cardiol, Ft Lauderdale, FL USA.
[Valeti, Uma S.] Univ Minnesota, Minneapolis, MN USA.
RP Raff, GL (reprint author), William Beaumont Hosp, Div Cardiol, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA.
EM graff@beaumont.edu
FU Bayer Pharmaceuticals; Sarver Heart Center; Siemens
FX From the *Division of Cardiology, William Beaumont Hospital, Royal Oak,
Michigan; dagger Division of Cardiology, University of Arizona, Tucson,
Arizona; double dagger Department of Cardiology, University of Giessen,
Giessen, Germany; Departments of Imaging and Cardiology, Cedars-Sinai
Medical Center, Los Angeles, California; parallel to Department of
Radiology, Massachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts; Minneapolis Heart Institute, Minneapolis,
Minnesota; #Division of Cardiology, Northwestern University Medical
School, Chicago, Illinois; **Department of Emergency Medicine, Wayne
State University Medical School, Detroit, Michigan; dagger dagger
Division of Cardiology, Emory University School of Medicine, Atlanta,
Georgia; double dagger double dagger Division of Cardiology, Cleveland
Clinic Florida, Fort Lauderdale, Florida; and the University of
Minnesota, Minneapolis, Minnesota. This study was funded by a research
grant from Bayer Pharmaceuticals. Bayer Pharmaceuticals did not design,
conduct, analyze, or interpret this study, nor did it prepare or review
this manuscript. Dr. Abidov has served on the Speakers' Bureau of
Astellas Pharma and has received grant support from Sarver Heart Center.
Drs. Achenbach and Lesser have received research grants and speaker
honoraria from Siemens. Dr. O'Neil is on the Speakers' Bureau of Bristol
Myers-Squibb and Sanofi-Aventis; and is an unpaid consultant for
Heartscape and ZOLL Circulation. All other authors have reported that
they have no relationships relevant to the contents of this paper to
disclose.
NR 45
TC 209
Z9 214
U1 1
U2 2
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 SEP 27
PY 2011
VL 58
IS 14
BP 1414
EP 1422
DI 10.1016/j.jacc.2011.03.068
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 824PH
UT WOS:000295213900003
PM 21939822
ER
PT J
AU Camargo, CA
AF Camargo, Carlos A., Jr.
TI Vitamin D and Cardiovascular Disease Time for Large Randomized Trials
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE heart failure; mineral metabolism; myocardial infarction; parathyroid
hormone; vitamin D
ID SERUM 25-HYDROXYVITAMIN D; HEART-FAILURE; D DEFICIENCY; MORTALITY;
METAANALYSIS; SUPPLEMENTS; PREVENTION
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA.
EM ccamargo@partners.org
NR 18
TC 7
Z9 8
U1 0
U2 2
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 SEP 27
PY 2011
VL 58
IS 14
BP 1442
EP 1444
DI 10.1016/j.jacc.2011.06.037
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 824PH
UT WOS:000295213900007
PM 21939826
ER
PT J
AU Kapoor, JR
Kapoor, R
Hellkamp, AS
Hernandez, AF
Heidenreich, PA
Fonarow, GC
AF Kapoor, John R.
Kapoor, Roger
Hellkamp, Anne S.
Hernandez, Adrian F.
Heidenreich, Paul A.
Fonarow, Gregg C.
TI Payment Source, Quality of Care, and Outcomes in Patients Hospitalized
With Heart Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE outcomes; payment source; quality
ID INITIATE LIFESAVING TREATMENT; ORGANIZED PROGRAM; OPTIMIZE-HF;
SOCIOECONOMIC-STATUS; RACIAL-DIFFERENCES; CLINICAL-OUTCOMES
AB Objectives The aim of this study was to analyze the relationship between payment source and quality of care and outcomes in heart failure (HF).
Background HF is a major cause of morbidity and mortality. There is a lack of studies assessing the association of payment source with HF quality of care and outcomes.
Methods A total of 99,508 HF admissions from 244 sites between January 2005 and September 2009 were analyzed. Patients were grouped on the basis of payer status (private/health maintenance organization, no insurance, Medicare, or Medicaid) with private/health maintenance organization as the reference group.
Results The no-insurance group was less likely to receive evidence-based beta-blockers (adjusted odds ratio [OR]: 0.73; 95% confidence interval [CI]: 0.62 to 0.86), implantable cardioverter-defibrillator (OR: 0.59; 95% CI: 0.50 to 0.70), or anticoagulation for atrial fibrillation (OR: 0.73; 95% CI: 0.61 to 0.87). Similarly, the Medicaid group was less likely to receive evidence-based beta-blockers (OR: 0.86; 95% CI: 0.78 to 0.95) or implantable cardioverter-defibrillators (OR: 0.86; 95% CI: 0.78 to 0.96). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers were prescribed less frequently in the Medicare group (OR: 0.89; 95% CI: 0.81 to 0.98). The Medicare, Medicaid, and no-insurance groups had longer hospital stays. Higher adjusted rates of in-hospital mortality were seen in patients with Medicaid (OR: 1.22; 95% CI: 1.06 to 1.41) and in patients with reduced systolic function with no insurance.
Conclusions Decreased quality of care and outcomes for patients with HF were observed in the no-insurance, Medicaid, and Medicare groups compared with the private/health maintenance organization group. (J Am Coll Cardiol 2011; 58:1465-71) (C) 2011 by the American College of Cardiology Foundation
C1 [Kapoor, John R.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60031 USA.
[Kapoor, Roger] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Hellkamp, Anne S.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA.
[Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
RP Kapoor, JR (reprint author), Univ Chicago, Pritzker Sch Med, 5841 S Maryland Ave, Chicago, IL 60031 USA.
EM doctorjrk@gmail.com
RI Hernandez, Adrian F./A-7818-2016
OI Heidenreich, Paul/0000-0001-7730-8490; Hernandez, Adrian
F./0000-0003-3387-9616
FU Medtronic; Ortho-McNeil; AHA Pharmaceutical Roundtable; GlaxoSmithKline;
Johnson Johnson; Proventys; Amylin Pharmaceuticals; National Heart,
Lung, and Blood Institute
FX From the *University of Chicago Pritzker School of Medicine, Chicago,
Illinois; dagger Harvard Medical School, Massachusetts General Hospital,
Boston, Massachusetts; double dagger Duke Clinical Research Institute,
Durham, North Carolina; Veterans Affairs Palo Alto Health Care System,
Palo Alto, California; and the parallel to Ahmanson-UCLA Cardiomyopathy
Center, Los Angeles, California. The Get With the Guidelines Heart
Failure (GWTG-HF) program is provided by the American Heart Association
(AHA). The GWTG-HF program 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
has received research support from Johnson & Johnson, Proventys, and
Amylin Pharmaceuticals. Dr. Heidenreich has received grant support from
Medtronic. Dr. Fonarow has received research support from the National
Heart, Lung, and Blood Institute (significant), is a consultant for
Novartis (significant) and Scios (modest), and has received an
honorarium from Medtronic (modest). All other authors have reported that
they have no relationships relevant to the contents of this paper to
disclose.
NR 14
TC 20
Z9 20
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 SEP 27
PY 2011
VL 58
IS 14
BP 1465
EP 1471
DI 10.1016/j.jacc.2011.06.034
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 824PH
UT WOS:000295213900011
PM 21939830
ER
PT J
AU Van den Stock, J
Tamietto, M
Sorger, B
Pichon, S
Grezes, J
de Gelder, B
AF Van den Stock, Jan
Tamietto, Marco
Sorger, Bettina
Pichon, Swann
Grezes, Julie
de Gelder, Beatrice
TI Cortico-subcortical visual, somatosensory, and motor activations for
perceiving dynamic whole-body emotional expressions with and without
striate cortex (V1)
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE blindsight; body expressions; consciousness
ID NON-CONSCIOUS RECOGNITION; FACIAL EXPRESSIONS; AFFECTIVE BLINDSIGHT;
AMYGDALA RESPONSES; BODILY EXPRESSIONS; MACAQUE MONKEY; AREA-MT; BRAIN;
THREAT; FEAR
AB Patients with striate cortex damage and clinical blindness retain the ability to process certain visual properties of stimuli that they are not aware of seeing. Here we investigated the neural correlates of residual visual perception for dynamic whole-body emotional actions. Angry and neutral emotional whole-body actions were presented in the intact and blind visual hemifield of a cortically blind patient with unilateral destruction of striate cortex. Comparisons of angry vs. neutral actions performed separately in the blind and intact visual hemifield showed in both cases increased activation in primary somatosensory, motor, and premotor cortices. Activations selective for intact hemifield presentation of angry compared with neutral actions were located subcortically in the right lateral geniculate nucleus and cortically in the superior temporal sulcus, prefrontal cortex, precuneus, and intraparietal sulcus. Activations specific for blind hemifield presentation of angry compared with neutral actions were found in the bilateral superior colliculus, pulvinar nucleus of the thalamus, amygdala, and right fusiform gyrus. Direct comparison of emotional modulation in the blind vs. intact visual hemifield revealed selective activity in the right superior colliculus and bilateral pulvinar for angry expressions, thereby showing a selective involvement of these subcortical structures in nonconscious visual emotion perception.
C1 [Van den Stock, Jan; Tamietto, Marco; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
[Van den Stock, Jan; de Gelder, Beatrice] Katholieke Univ Leuven, Brain & Emot Lab Leuven, Dept Neurosci, B-3000 Louvain, Belgium.
[Tamietto, Marco] Univ Turin, Dept Psychol, I-10123 Turin, Italy.
[Sorger, Bettina] Maastricht Univ, Dept Neuropsychol, NL-6200 MD Maastricht, Netherlands.
[Pichon, Swann] Univ Geneva, Lab Behav Neurol & Imaging Cognit, Dept Neurosci, Sch Med, CH-1211 Geneva, Switzerland.
[Grezes, Julie] Ecole Normale Super, Cognit Neurosci Lab, Inst Natl Sante & Rech Med, Dept Cognit Studies,U960, F-75005 Paris, France.
[de Gelder, Beatrice] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA.
RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands.
EM degelder@nmr.mgh.harvard.edu
RI Van den Stock, Jan/F-1906-2014; pichon, swann/M-2966-2014; Grezes,
Julie/E-5060-2016;
OI Van den Stock, Jan/0000-0001-5756-3195; pichon,
swann/0000-0001-5697-702X; Tamietto, Marco/0000-0002-8815-8499
FU European Commission [FP6-2005-NEST-Path, Imp 043403-COBOL]; Fonds voor
Wetenschappelijk Onderzoek-Vlaanderen; Netherlands Organization for
Scientific Research Postdoctoral Veni [451-07-032]; Fondazione Carlo
Molo, Turin, Italy
FX B.d.G., S.P., and J.G. were supported by European Commission
Communication with Emotional Body Language (COBOL) Grant
FP6-2005-NEST-Path Imp 043403-COBOL. J.V.d.S. is a postdoctoral
researcher supported by Fonds voor Wetenschappelijk
Onderzoek-Vlaanderen. M. T. was supported by Netherlands Organization
for Scientific Research Postdoctoral Veni Grant 451-07-032 and partly by
the Fondazione Carlo Molo, Turin, Italy.
NR 61
TC 48
Z9 48
U1 3
U2 26
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 27
PY 2011
VL 108
IS 39
BP 16188
EP 16193
DI 10.1073/pnas.1107214108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825FB
UT WOS:000295255300019
PM 21911384
ER
PT J
AU Baliram, R
Latif, R
Berkowitz, J
Frid, S
Colaianni, G
Sun, L
Zaidi, M
Davies, TF
AF Baliram, Ramkumarie
Latif, Rauf
Berkowitz, Joshua
Frid, Simon
Colaianni, Graziana
Sun, Li
Zaidi, Mone
Davies, Terry F.
TI Thyroid-stimulating hormone induces a Wnt-dependent, feed-forward loop
for osteoblastogenesis in embryonic stem cell cultures
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID BONE-MARROW-CELLS; RECOMBINANT TSH; PKC-DELTA; IN-VITRO; RECEPTOR;
PATHWAY; OSTEOPROTEGERIN; DIFFERENTIATION; EXPRESSION; WOMEN
AB We have shown that the anterior pituitary hormone, thyroid-stimulating hormone (TSH), can bypass the thyroid to exert a direct protective effect on the skeleton. Thus, we have suggested that a low TSH level may contribute to the bone loss of hyperthyroidism that has been attributed traditionally to high thyroid hormone levels. Earlier mouse genetic, cell-based, and clinical studies together have established that TSH inhibits osteoclastic bone resorption. However, the direct influence of TSH on the osteoblast has remained unclear. Here, we have used a model system developed from murine ES cells, induced to form mature mineralizing osteoblasts, and show that TSH stimulates osteoblast differentiation primarily through the activation of protein kinase C delta and the up-regulation of the noncanonical Wnt components frizzled and Wnt5a. We predict that a TSH-induced, fast-forward short loop in bone marrow permits Wnt5a production, which, in addition to enhancing osteoblast differentiation, also stimulates osteoprotegerin secretion to attenuate bone resorption by neighboring osteoclasts. We surmise that this loop should uncouple bone formation from bone resorption with a net increase in bone mass, which is what has been observed upon injecting TSH.
C1 [Baliram, Ramkumarie; Latif, Rauf; Berkowitz, Joshua; Frid, Simon; Davies, Terry F.] Mt Sinai Sch Med, Thyroid Res Lab, New York, NY 10029 USA.
[Colaianni, Graziana; Sun, Li; Zaidi, Mone; Davies, Terry F.] Mt Sinai Sch Med, Mt Sinai Bone Program, New York, NY 10029 USA.
[Colaianni, Graziana; Sun, Li; Zaidi, Mone; Davies, Terry F.] James J Peters VA Med Ctr, New York, NY 10029 USA.
RP Davies, TF (reprint author), Mt Sinai Sch Med, Thyroid Res Lab, New York, NY 10029 USA.
EM terry.davies@mssm.edu
OI Colaianni, Graziana/0000-0001-8501-5399
FU National Institutes of Health [DK080459, DK069713, DK052464, AG40132,
DK70526]; David Owen Segal Endowment; VA Merit Review Program
FX This work was supported in part by National Institutes of Health Grants
DK080459 (M.Z., L. S., and T. F. D.), DK069713 and DK052464 (T. F. D.),
AG40132 and DK70526 (M.Z.), the David Owen Segal Endowment, and the VA
Merit Review Program (T. F. D.).
NR 29
TC 18
Z9 19
U1 0
U2 1
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 SEP 27
PY 2011
VL 108
IS 39
BP 16277
EP 16282
DI 10.1073/pnas.1110286108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825FB
UT WOS:000295255300034
PM 21911383
ER
PT J
AU Huang, YT
Lin, XH
Liu, Y
Chirieac, LR
McGovern, R
Wain, J
Heist, R
Skaug, V
Zienolddiny, S
Haugen, A
Su, L
Fox, EA
Wong, KK
Christiani, DC
AF Huang, Yen-Tsung
Lin, Xihong
Liu, Yan
Chirieac, Lucian R.
McGovern, Ray
Wain, John
Heist, Rebecca
Skaug, Vidar
Zienolddiny, Shanbeh
Haugen, Aage
Su, Li
Fox, Edward A.
Wong, Kwok-Kin
Christiani, David C.
TI Cigarette smoking increases copy number alterations in nonsmall-cell
lung cancer
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE tumor genome; multimarker analyses
ID GROWTH-FACTOR-I; BINDING PROTEIN-3; PLASMA-LEVELS; RISK; GENOME; IGF;
ADENOCARCINOMA; POLYMORPHISM; EXPOSURE
AB Cigarette smoking has been a well-established risk factor of lung cancer for decades. How smoking contributes to tumorigenesis in the lung remains not fully understood. Here we report the results of a genome-wide study of DNA copy number and smoking pack-years in a large collection of nonsmall-cell lung cancer (NSCLC) tumors. Genome-wide analyses of DNA copy number and pack-years of cigarette smoking were performed on 264 NSCLC tumors, which were divided into discovery and validation sets. The copy number-smoking associations were investigated in three scales: whole-genome, chromosome/arm, and focal regions. We found that heavy cigarette smokers (>60 pack-years) have significantly more copy number gains than non-or light smokers (<= 60 pack-years) (P = 2.46 x 10(-4)), especially in 8q and 12q. Copy number losses tend to occur away from genes in non/light smokers (P = 5.15 x 10(-5)) but not in heavy smokers (P = 0.52). Focal copy number analyses showed that there are strong associations of copy number and cigarette smoking pack-years in 12q23 (P = 9.69 x 10(-10)) where IGF1 (insulin-like growth factor 1) is located. All of the above analyses were tested in the discovery set and confirmed in the validation set. DNA double-strand break assays using human bronchial epithelial cell lines treated with cigarette smoke condensate were also performed, and indicated that cigarette smoke condensate leads to genome instability in human bronchial epithelial cells. We conclude that cigarette smoking leads to more copy number alterations, which may be mediated by the genome instability.
C1 [Huang, Yen-Tsung; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Huang, Yen-Tsung; Lin, Xihong; McGovern, Ray] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Heist, Rebecca; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Liu, Yan; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Fox, Edward A.] Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA.
[Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Wain, John; Heist, Rebecca] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Wain, John] Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA.
[Christiani, David C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Skaug, Vidar; Zienolddiny, Shanbeh; Haugen, Aage] Natl Inst Occupat Hlth, Dept Biol & Chem Working Environm, N-0033 Oslo, Norway.
RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM dchris@hsph.harvard.edu
RI Huang, Yen-Tsung/I-1003-2014; Zienolddiny, Shanbeh/O-7392-2015;
OI wong, kwok kin/0000-0001-6323-235X
FU National Institutes of Health [CA076404, CA134294, CA092824, CA074386,
CA090578, CA122794, CA140594, CA141576]; Raymond P. Lavietes Foundation;
Norwegian Cancer Society
FX We thank the participants of the Molecular and Genetic Analysis of Lung
Cancer Study; Dr. Cheng Li for his advice on data preprocessing; the
Harvard School of Public Health Lung Cancer Study Group: Dr. Kofi
Asomaning, Dr. Eugene Mark, Dr. Matthew Kulke, Dr. Wei Zhou, Dr.
Geoffrey Liu, Marcia Chertok, Andrea Shafer, Lauren Cassidy, Maureen
Convery, and Salvatore Mucci; Drs. Panos Fidias and Bruce A. Chabner and
the physicians and surgeons of the Massachusetts General Hospital Cancer
Center; and Dr. Lodve Stangeland for recruiting patients. This study is
supported by National Institutes of Health Grants CA076404 and CA134294
(to Y.-T. H. and X. L.); National Institutes of Health Grants CA092824,
CA074386, and CA090578 (to D. C. C.) and CA122794, CA140594, and
CA141576 (to K. K. W.); the Raymond P. Lavietes Foundation (D. C. C.);
and the Norwegian Cancer Society (A. H.).
NR 29
TC 25
Z9 25
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 SEP 27
PY 2011
VL 108
IS 39
BP 16345
EP 16350
DI 10.1073/pnas.1102769108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825FB
UT WOS:000295255300046
PM 21911369
ER
PT J
AU Gutierrez, A
Snyder, EL
Marino-Enriquez, A
Zhang, YX
Sioletic, S
Kozakewich, E
Grebliunaite, R
Ou, WB
Sicinska, E
Raut, CP
Demetri, GD
Perez-Atayde, AR
Wagner, AJ
Fletcher, JA
Fletcher, CDM
Look, AT
AF Gutierrez, Alejandro
Snyder, Eric L.
Marino-Enriquez, Adrian
Zhang, Yi-Xiang
Sioletic, Stefano
Kozakewich, Elena
Grebliunaite, Ruta
Ou, Wen-bin
Sicinska, Ewa
Raut, Chandrajit P.
Demetri, George D.
Perez-Atayde, Antonio R.
Wagner, Andrew J.
Fletcher, Jonathan A.
Fletcher, Christopher D. M.
Look, A. Thomas
TI Aberrant AKT activation drives well-differentiated liposarcoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID MDM2 AMPLIFICATION; TISSUE TUMORS; EXPRESSION; MUTATION; PATHWAY; PLAYS;
MTOR
AB Well-differentiated liposarcoma (WDLPS), one of the most common human sarcomas, is poorly responsive to radiation and chemotherapy, and the lack of animal models suitable for experimental analysis has seriously impeded functional investigation of its pathobiology and development of effective targeted therapies. Here, we show that zebrafish expressing constitutively active Akt2 in mesenchymal progenitors develop WDLPS that closely resembles the human disease. Tumor incidence rates were 8% in p53 wild-type zebrafish, 6% in p53 heterozygotes, and 29% in p53-homozygous mutant zebrafish (P = 0.013), indicating that aberrant Akt activation collaborates with p53 mutation in WDLPS pathogenesis. Analysis of primary clinical specimens of WDLPS, and of the closely related dedifferentiated liposarcoma (DDLPS) subtype, revealed immunohistochemical evidence of AKT activation in 27% of cases. Western blot analysis of a panel of cell lines derived from patients with WDLPS or DDLPS revealed robust AKT phosphorylation in all cell lines examined, even when these cells were cultured in serum-free media. Moreover, BEZ235, a small molecule inhibitor of PI3K and mammalian target of rapamycin that effectively inhibits AKT activation in these cells, impaired viability at nanomolar concentrations. Our findings are unique in providing an animal model to decipher the molecular pathogenesis of WDLPS, and implicate AKT as a previously unexplored therapeutic target in this chemoresistant sarcoma.
C1 [Gutierrez, Alejandro; Kozakewich, Elena; Grebliunaite, Ruta; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Snyder, Eric L.; Sicinska, Ewa] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Snyder, Eric L.; Sicinska, Ewa] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA.
[Snyder, Eric L.; Zhang, Yi-Xiang; Sioletic, Stefano; Sicinska, Ewa; Demetri, George D.; Wagner, Andrew J.] Dana Farber Canc Inst, Ludwig Ctr Dana Farber, Harvard Canc Ctr, Boston, MA 02215 USA.
[Zhang, Yi-Xiang; Sioletic, Stefano; Raut, Chandrajit P.; Demetri, George D.; Wagner, Andrew J.; Fletcher, Jonathan A.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA.
[Gutierrez, Alejandro; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Perez-Atayde, Antonio R.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Snyder, Eric L.; Marino-Enriquez, Adrian; Ou, Wen-bin; Fletcher, Jonathan A.; Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Snyder, Eric L.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
RP Gutierrez, A (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
EM Alejandro_Gutierrez@dfci.harvard.edu; thomas_look@dfci.harvard.edu
OI Gutierrez, Alejandro/0000-0002-0249-9007
FU Novartis; Roche/Genentech; Pfizer; Exelixis; Harvard Catalyst \ The
Harvard Clinical and Translational Science Center (National Institutes
of Health), Harvard University [UL1 RR 025758]; Ludwig Center at
Dana-Farber/Harvard Cancer Center; Harvard Medical School; National
Institutes of Health [1K08CA133103]; Fundacion Alfonso Martin Escudero
FX C.P.R. is a consultant for Novartis and participates in clinical trials
of Novartis. G.D.D. is a consultant for Novartis, Pfizer, Ariad, Johnson
& Johnson, PharmaMar, Genentech, Infinity Pharmaceuticals, EMD-Serono,
Glaxo Smith Kline, Amgen, Daiichi-Sankyo, ArQule, Enzon,
Millenium/Takeda; is a member of the scientific advisory board of
Plexxikon, ZioPharm, Nereus, N-of-One, and Kolltan Pharmaceuticals; and
participates in clinical trials of Novartis, Pfizer, Ariad, Johnson &
Johnson, PharmaMar, and Infinity Pharmaceuticals. A.J.W. is a consultant
for Novartis, Roche/Genentech, Sanofi, Pfizer, EMD-Serono, and
participates in clinical trials supported by Novartis, Roche/Genentech,
Pfizer, and Exelixis.; We thank G. Molind and L. Zhang for zebrafish
husbandry, J. Testa for the myristoylated mouse Akt2 transgene used in
these studies, and D. E. Fisher for the SU-CCS-1 cell line. This work
was conducted with support from Harvard Catalyst vertical bar The
Harvard Clinical and Translational Science Center (National Institutes
of Health Award UL1 RR 025758 and financial contributions from Harvard
University and its affiliated academic health care centers), as well as
the Ludwig Center at Dana-Farber/Harvard Cancer Center and Harvard
Medical School; A. G. is supported by National Institutes of Health
Grant 1K08CA133103 and is a scholar of the American Society of
Hematology-Amos Medical Faculty Development program; and A. M.-E. is
supported by Fundacion Alfonso Martin Escudero.
NR 26
TC 26
Z9 26
U1 0
U2 3
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 SEP 27
PY 2011
VL 108
IS 39
BP 16386
EP 16391
DI 10.1073/pnas.1106127108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825FB
UT WOS:000295255300053
PM 21930930
ER
PT J
AU Vallabhajosyula, P
Tena, A
Yamada, K
Sachs, DH
AF Vallabhajosyula, Prashanth
Tena, Aseda
Yamada, Kazuhiko
Sachs, David H.
TI Signal Joint T-Cell Receptor Excision Circle Assay in Miniature Swine
SO TRANSPLANTATION
LA English
DT Article
DE T-cell receptor excision circle; Signal joint TREC; Pig; T cell
ID MISMATCHED RENAL-ALLOGRAFTS; RECENT THYMIC EMIGRANTS; HIV-INFECTION;
TRANSPLANTATION TOLERANCE; PERIPHERAL-BLOOD; ANTIRETROVIRAL THERAPY;
IMMUNE RECONSTITUTION; STABLE INDUCTION; OUTPUT; AGE
AB Objective: Assays for T cell receptor excision circles (TREC) have been utilized in human, primate, and mouse models as a measure of thymic activity, but no comparable assay has been described in artiodactyls. We describe the development of the porcine signal joint (sj) TREC assay, and provide a likely reason for previous difficulties in its identification in artiodactyls.
Design and Methods: Utilizing the homology between the known genomic sequences in sjTREC in human and mouse, polymerase chain reaction (PCR) primers were derived for the putative porcine sjTREC. Primers from the psi J alpha side of the sjTREC were derived from the known porcine sequence.
Results: The sjTREC in two artiodactyls, swine and sheep, was identified using forward primers from the psi J alpha region, and reverse primers from the putative delta-rec region. Unlike in the detection of primate TRECs, initially the use of similar primers close to the delta-rec failed to yield the sjTREC product. Marching about 800 basepairs into delta-rec, primers derived from a homology region between human and mouse led to the detection of sjTREC. Comparing sjTREC amongst the species revealed highest homology between the two artiodactyls. A quantitative PCR (QPCR) assay of porcine sjTREC was also developed.
Conclusion: Identification and analysis of the sjTREC sequences in two artiodactyls suggested why previous attempts at cloning the pig TREC using known sjTREC sequences were unsuccessful. The development of the porcine signal joint TREC assay should enable a more direct quantification of thymic activity in porcine models of transplant biology.
C1 [Sachs, David H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02129 USA.
[Vallabhajosyula, Prashanth] Hosp Univ Penn, Dept Surg, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Dept Surg, Bldg 149,13th St, Boston, MA 02129 USA.
EM david.sachs@tbrc.mgh.harvard.edu
FU American College of Surgeons; American Society of Transplant Surgeons;
Roche Scientific Research Fellowship; Ruth L. Kirschstein National
Research Scholarship [F32 AI066699-02]
FX This work was supported by the American College of Surgeons Fellowship,
American Society of Transplant Surgeons, Roche Scientific Research
Fellowship, Ruth L. Kirschstein National Research Scholarship Award (5
F32 AI066699-02) (P.V.).
NR 41
TC 4
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD SEP 27
PY 2011
VL 92
IS 6
BP 634
EP 640
DI 10.1097/TP.0b013e31822b9287
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 818NE
UT WOS:000294757900007
PM 21822172
ER
PT J
AU Nishimura, H
Scalea, J
Wang, ZR
Shimizu, A
Moran, S
Gillon, B
Sachs, DH
Yamada, K
AF Nishimura, Hiroaki
Scalea, Joseph
Wang, Zhirui
Shimizu, Akira
Moran, Shannon
Gillon, Bradford
Sachs, David H.
Yamada, Kazuhiko
TI First Experience With the Use of a Recombinant CD3 Immunotoxin as
Induction Therapy in Pig-to-Primate Xenotransplantation: The Effect of
T-Cell Depletion on Outcome
SO TRANSPLANTATION
LA English
DT Article
DE GalT-KO; Renal graft; Thymokidney; T-cell depletion;
Xenotransplantation; Large animal model
ID THYMIC TRANSPLANTATION; XENOGRAFT REJECTION; NUCLEAR TRANSFER; MINIATURE
SWINE; BABOON MODEL; TOLERANCE; MACROPHAGE; BARRIER
AB Background. We have previously reported life-supporting kidney xenograft-survival greater than 80 days using a steroid-free antithymocyte globulin (ATG)-based induction regimen (ATG regimen) in a GalT-KO pig-to-baboon thymokidney (TK) model. We evaluated two induction regimens, a newly developed anti-monkey CD3 recombinant immunotoxin (anti-CD3 rIT) and an anti-human CD2 antibody (LoCD2), by assessing T-cell depletion (TCD) and graft survival.
Methods. Four baboons received anti-CD3 rIT; the time course of TCD was studied in two animals and the other two received GalT-KO TK transplants. Two additional baboons underwent GalT-KO TK transplantation after treatment with LoCD2. All other treatments were identical to previous TCD studies with ATG. TCD was assessed by flow-cytometry; renal function was evaluated by serum creatinine and histology.
Results. Baboons that received the anti-CD3 rIT died from pneumonia or cardiac failure on days 15 and 23. Both animals in the rIT group died with functioning grafts. Thymokidney grafts from baboons treated with the LoCD2 regimen were rejected by day 14. TCD levels in baboons receiving the anti-CD3 rIT regimen were 150 to 250 cells/mu L for at least 14 days, whereas baboons receiving the LoCD2 recovered to more than 300 cells/mu L by day 7.
Conclusions. The newly developed anti-CD3 rIT could be a useful TCD agent in baboons. However, optimal dosage, treatment duration, and bioactivity must be studied to avoid side effects. A LoCD2-based regimen was not effective for preventing xenogeneic rejection. Optimal TCD levels less than 250/mu L during the induction period seem to be important for success of xeno-thymokidney transplantation.
C1 [Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH East, Transplantat Biol Res Ctr,Organ Transplantat Tole, Boston, MA 02129 USA.
RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH East, Transplantat Biol Res Ctr,Organ Transplantat Tole, Bldg 149-9014,13th St, Boston, MA 02129 USA.
EM kaz.yamada@tbrc.mgh.harvard.edu
FU NIH [5PO1-A145897, 19209043 A]
FX This work was supported by NIH Program Project 5PO1-A145897 (Project 1),
RPrEP Core, and DF/HCC, and Grant-in-aid for 19209043 A.
NR 22
TC 12
Z9 12
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD SEP 27
PY 2011
VL 92
IS 6
BP 641
EP 647
DI 10.1097/TP.0b013e31822b92a5
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 818NE
UT WOS:000294757900008
PM 21822171
ER
PT J
AU Yeh, H
Kitchens, WH
Elias, N
Kelsey, PB
Markmann, JF
Hertl, M
AF Yeh, Heidi
Kitchens, William H.
Elias, Nahel
Kelsey, Peter B.
Markmann, James F.
Hertl, Martin
TI Hyperlipidemia due to Biliary Stricture After Living-Donor Liver
Transplantation
SO TRANSPLANTATION
LA English
DT Letter
ID CIRRHOSIS
C1 [Yeh, Heidi; Kitchens, William H.; Elias, Nahel; Markmann, James F.; Hertl, Martin] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA.
[Kelsey, Peter B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Yeh, H (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Transplantat, White Bldg 516,55 Fruit St, Boston, MA 02114 USA.
EM hyeh@partners.org
NR 8
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD SEP 27
PY 2011
VL 92
IS 6
BP E29
EP E30
DI 10.1097/TP.0b013e31822d095d
PG 3
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 818NE
UT WOS:000294757900002
PM 21909017
ER
PT J
AU Roper, J
Richardson, MP
Wang, WV
Richard, LG
Chen, W
Coffee, EM
Sinnamon, MJ
Lee, L
Chen, PC
Bronson, RT
Martin, ES
Hung, KE
AF Roper, Jatin
Richardson, Michael P.
Wang, Wei Vivian
Richard, Larissa Georgeon
Chen, Wei
Coffee, Erin M.
Sinnamon, Mark J.
Lee, Lydia
Chen, Peng-Chieh
Bronson, Roderick T.
Martin, Eric S.
Hung, Kenneth E.
TI The Dual PI3K/mTOR Inhibitor NVP-BEZ235 Induces Tumor Regression in a
Genetically Engineered Mouse Model of PIK3CA Wild-Type Colorectal Cancer
SO PLOS ONE
LA English
DT Article
ID PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; RENAL-CELL CARCINOMA;
RAPAMYCIN INHIBITOR; MAMMALIAN TARGET; SIGNALING PATHWAYS;
ANTITUMOR-ACTIVITY; MTORC1 PATHWAY; COLON-CANCER; PI3K; GROWTH
AB Purpose: To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC).
Experimental Design: PIK3CA mutant and wild-type human CRC cell lines were treated in vitro with NVP-BEZ235, and the resulting effects on proliferation, apoptosis, and signaling were assessed. Colonic tumors from a genetically engineered mouse (GEM) model for sporadic wild-type PIK3CA CRC were treated in vivo with NVP-BEZ235. The resulting effects on macroscopic tumor growth/regression, proliferation, apoptosis, angiogenesis, and signaling were examined.
Results: In vitro treatment of CRC cell lines with NVP-BEZ235 resulted in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a corresponding decrease in cell viability (median IC50 = 9.0-14.3 nM). Similar effects were seen in paired isogenic CRC cell lines that differed only in the presence or absence of an activating PIK3CA mutant allele. In vivo treatment of colonic tumor-bearing mice with NVP-BEZ235 resulted in transient PI3K inhibition and sustained blockade of mTORC1/mTORC2 signaling. Longitudinal tumor surveillance by optical colonoscopy demonstrated a 97% increase in tumor size in control mice (p = 0.01) vs. a 43% decrease (p = 0.008) in treated mice. Ex vivo analysis of the NVP-BEZ235-treated tumors demonstrated a 56% decrease in proliferation (p = 0.003), no effects on apoptosis, and a 75% reduction in angiogenesis (p = 0.013).
Conclusions: These studies provide the preclinical rationale for studies examining the efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type CRC.
C1 [Roper, Jatin; Richardson, Michael P.; Wang, Wei Vivian; Chen, Wei; Coffee, Erin M.; Sinnamon, Mark J.; Lee, Lydia; Hung, Kenneth E.] Tufts Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA.
[Richard, Larissa Georgeon; Chen, Peng-Chieh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Bronson, Roderick T.; Martin, Eric S.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA.
RP Roper, J (reprint author), Tufts Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA.
EM khung@tuftsmedicalcenter.org
OI Roper, Jatin/0000-0002-8851-1352
FU National Cancer Institute [2U01CA084301]; National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) [5K08DK7803325, R03DK088014,
T32-DK07542]
FX This study was supported by grants from the National Cancer Institute
(2U01CA084301) and the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK)(5K08DK7803325, R03DK088014, and T32-DK07542).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 69
TC 50
Z9 55
U1 2
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 26
PY 2011
VL 6
IS 9
AR e25132
DI 10.1371/journal.pone.0025132
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 834BK
UT WOS:000295932100020
PM 21966435
ER
PT J
AU Yeung, A
Hails, K
Chang, T
Trinh, NH
Fava, M
AF Yeung, Albert
Hails, Kate
Chang, Trina
Trinh, Nhi-Ha
Fava, Maurizio
TI A study of the effectiveness of telepsychiatry-based culturally
sensitive collaborative treatment of depressed Chinese Americans
SO BMC PSYCHIATRY
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; PRIMARY-CARE; DSM-IV;
INTERVENTION; VALIDATION; OUTCOMES; MINI
AB Background: Chinese American patients with Major Depressive Disorder (MDD) tend to underutilize mental health services and are more likely to seek help in primary care settings than from mental health specialists. Our team has reported that Culturally Sensitive Collaborative Treatment (CSCT) is effective in improving recognition and treatment engagement of depressed Chinese Americans in primary care. The current study builds on this prior research by incorporating telemedicine technology into the CSCT model.
Methods/Design: We propose a randomized controlled trial to evaluate the acceptability and effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention targeted toward Chinese Americans. Patients meeting the study's eligibility criteria will receive either treatment as usual or the intervention under investigation. The six-month intervention involves: 1) an initial psychiatric interview using a culturally sensitive protocol via videoconference; 2) eight scheduled phone visits with a care manager assigned to the patient, who will monitor the patient's progress, as well as medication side effects and dosage if applicable; and 3) collaboration between the patient's PCP, psychiatrist, and care manager. Outcome measures include depressive symptom severity as well as patient and PCP satisfaction with the telepsychiatry-based care management service.
Discussion: The study investigates the T-CSCT model, which we believe will increase the feasibility and practicality of the CSCT model by adopting telemedicine technology. We anticipate that this model will expand access to culturally competent psychiatrists fluent in patients' native languages to improve treatment of depressed minority patients in primary care settings.
C1 [Yeung, Albert; Hails, Kate; Chang, Trina; Trinh, Nhi-Ha; Fava, Maurizio] Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA.
RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA.
EM ayeung@partners.org
FU National Institute of Mental Health [R01 MH079831]; AstraZeneca; CeNeRx;
Euthymics; Forest; GlaxoSmithKline; Johnson Johnson; Pfizer; Abbott
Laboratories; Alkermes, Inc.; Aspect Medical Systems; BioResearch;
BrainCells Inc.; Bristol-Myers Squibb; Cephalon, Inc.; CeNeRx BioPharma;
Clinical Trials Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and
Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.;
Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; Icon Clinical
Research; i3 Innovus; Johnson & Johnson Pharmaceutical Research
Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM;
NIDA; NIMH; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.; Pfizer
Inc.; Pharmavite(Register trademark) LLC; Photothera; Roche; RCT Logic,
LLC; SanofiAventis US LLC; Shire; Solvay Pharmaceuticals, Inc;
Synthelabo; Wyeth-Ayerst Laboratories
FX This project is supported by a grant (R01 MH079831) from the National
Institute of Mental Health.; Dr. Chang has received research funding
from AstraZeneca, CeNeRx, Euthymics, Forest, GlaxoSmithKline, Johnson &
Johnson, and Pfizer.; Abbott Laboratories; Alkermes, Inc.; Aspect
Medical Systems; AstraZeneca; BioResearch; BrainCells Inc.;
Bristol-Myers Squibb; Cephalon, Inc.; CeNeRx BioPharma; Clinical Trials
Solutions, LLC; Clintara, LLC; Covidien; Eli Lilly and Company; EnVivo
Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest
Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon
Clinical Research; i3 Innovus; Johnson & Johnson Pharmaceutical Research
& Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD;
NCCAM; NIDA; NIMH; Novartis AG; Organon Pharmaceuticals; PamLab, LLC.;
Pfizer Inc.; Pharmavite (R) LLC; Photothera; Roche; RCT Logic, LLC;
SanofiAventis US LLC; Shire; Solvay Pharmaceuticals, Inc.; Synthelabo;
Wyeth-Ayerst Laboratories
NR 24
TC 15
Z9 15
U1 5
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-244X
J9 BMC PSYCHIATRY
JI BMC Psychiatry
PD SEP 26
PY 2011
VL 11
AR 154
DI 10.1186/1471-244X-11-154
PG 8
WC Psychiatry
SC Psychiatry
GA 832GA
UT WOS:000295790000001
PM 21943315
ER
PT J
AU Goroll, AH
AF Goroll, Allan H.
TI When It Comes to Primary Care, More May Be More
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID HYPERTENSION; FUTURE
C1 [Goroll, Allan H.] Harvard Univ, Sch Med, Boston, MA 02493 USA.
[Goroll, Allan H.] Massachusetts Gen Hosp, Med Serv, Boston, MA 02493 USA.
RP Goroll, AH (reprint author), Harvard Univ, Sch Med, 15 Parkman St,Ste 645, Boston, MA 02493 USA.
EM ahgoroll@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 SEP 26
PY 2011
VL 171
IS 17
BP 1550
EP 1551
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 824RY
UT WOS:000295221000006
PM 21949162
ER
PT J
AU Zhang, YT
Zhou, L
Gellad, W
AF Zhang, Yuting
Zhou, Lei
Gellad, Walid
TI The True Cost of Discounted Medication Programs reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Zhang, Yuting; Zhou, Lei] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Gellad, Walid] Univ Pittsburgh, Sch Med, Div Gen Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.
[Gellad, Walid] RAND Corp, Pittsburgh, PA USA.
RP Zhang, YT (reprint author), Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, 130 De Soto St,Crabtree Hall A664, Pittsburgh, PA 15261 USA.
EM ytzhang@pitt.edu
OI Zhang, Yuting/0000-0002-6460-6779
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD SEP 26
PY 2011
VL 171
IS 17
BP 1595
EP 1596
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 824RY
UT WOS:000295221000025
ER
PT J
AU Mendelson, T
Meltzer, M
Campbell, EG
Caplan, AL
Kirkpatrick, JN
AF Mendelson, Todd
Meltzer, Michele
Campbell, Eric G.
Caplan, Arthur L.
Kirkpatrick, James N.
TI The Proactive Management of "Relationship With Industry" by ACC/AHA in
the Creation of Our Cardiovascular Clinical Practice Guidelines reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Kirkpatrick, James N.] Univ Penn, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Mendelson, Todd] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Mendelson, Todd; Caplan, Arthur L.; Kirkpatrick, James N.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA.
[Meltzer, Michele] Thomas Jefferson Univ, Dept Med, Div Rheumatol, Philadelphia, PA 19107 USA.
[Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA.
RP Kirkpatrick, JN (reprint author), Univ Penn, Dept Med, Div Cardiovasc Med, 3400 Spruce St,9014 Gates, Philadelphia, PA 19104 USA.
EM james.kirkpatrick@uphs.upenn.edu
NR 2
TC 0
Z9 0
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 SEP 26
PY 2011
VL 171
IS 17
BP 1599
EP 1600
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 824RY
UT WOS:000295221000031
ER
PT J
AU Casarett, D
Richardson, D
Smith, D
Johnson, M
AF Casarett, David
Richardson, Diane
Smith, Dawn
Johnson, Megan
TI Palliative Care Units: The Best Option for the Most Distressed reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Casarett, David] Univ Penn, Perelman Sch Med, Div Geriatr Med, Philadelphia, PA 19104 USA.
[Richardson, Diane; Smith, Dawn; Johnson, Megan] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
RP Casarett, D (reprint author), Univ Penn, Perelman Sch Med, Div Geriatr Med, 3615 Chestnut St, Philadelphia, PA 19104 USA.
EM casarett@mail.med.upenn.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD SEP 26
PY 2011
VL 171
IS 17
BP 1601
EP 1602
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 824RY
UT WOS:000295221000036
ER
PT J
AU Xiao, JJ
Jing, ZC
Ellinor, PT
Liang, DD
Zhang, H
Liu, Y
Chen, XL
Pan, L
Lyon, R
Liu, Y
Peng, LY
Liang, XQ
Sun, YF
Popescu, LM
Condorelli, G
Chen, YH
AF Xiao, Junjie
Jing, Zhi-Cheng
Ellinor, Patrick T.
Liang, Dandan
Zhang, Hong
Liu, Ying
Chen, Xiaoli
Pan, Lei
Lyon, Robert
Liu, Yi
Peng, Lu-Ying
Liang, Xingqun
Sun, Yunfu
Popescu, Laurentiu M.
Condorelli, Gianluigi
Chen, Yi-Han
TI MicroRNA-134 as a potential plasma biomarker for the diagnosis of acute
pulmonary embolism
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; CIRCULATING
MICRORNAS; COMPUTED-TOMOGRAPHY; HEART-FAILURE; CARDIOVASCULAR-DISEASES;
CANCER; MORTALITY; CARCINOMA; MARKER
AB Background: Acute pulmonary embolism (APE) remains a diagnostic challenge due to a variable clinical presentation and the lack of a reliable screening tool. MicroRNAs (miRNAs) regulate gene expression in a wide range of pathophysiologic processes. Circulating miRNAs are emerging biomarkers in heart failure, type 2 diabetes and other disease states; however, using plasma miRNAs as biomarkers for the diagnosis of APE is still unknown.
Methods: Thirty-two APE patients, 32 healthy controls, and 22 non-APE patients (reported dyspnea, chest pain, or cough) were enrolled in this study. The TaqMan miRNA microarray was used to identify dysregulated miRNAs in the plasma of APE patients. The TaqMan-based miRNA quantitative real-time reverse transcription polymerase chain reactions were used to validate the dysregulated miRNAs. The receiver-operator characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of the miRNA identified as the candidate biomarker.
Results: Plasma miRNA-134 (miR-134) level was significantly higher in the APE patients than in the healthy controls or non-APE patients. The ROC curve showed that plasma miR-134 was a specific diagnostic predictor of APE with an area under the curve of 0.833 (95% confidence interval, 0.737 to 0.929; P < 0.001).
Conclusions: Our findings indicated that plasma miR-134 could be an important biomarker for the diagnosis of APE. Because of this finding, large-scale investigations are urgently needed to pave the way from basic research to clinical utilization.
C1 [Xiao, Junjie; Liang, Dandan; Zhang, Hong; Liu, Ying; Chen, Xiaoli; Pan, Lei; Liu, Yi; Peng, Lu-Ying; Liang, Xingqun; Sun, Yunfu; Chen, Yi-Han] Tongji Univ, Minist Educ, China E Hosp, Key Lab Arrhythmias,Sch Med, Shanghai 200092, Peoples R China.
[Xiao, Junjie; Liang, Dandan; Zhang, Hong; Liu, Ying; Liu, Yi; Peng, Lu-Ying; Chen, Yi-Han] Tongji Univ, Inst Med Genet, Shanghai 200092, Peoples R China.
[Jing, Zhi-Cheng] Tongji Univ, Shanghai Pulm Hosp, Dept Pulm Circulat, Shanghai 200092, Peoples R China.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Lyon, Robert; Condorelli, Gianluigi] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Popescu, Laurentiu M.] Carol Davila Univ Med & Pharm, Dept Cellular & Mol Med, Bucharest, Romania.
RP Chen, YH (reprint author), Tongji Univ, Minist Educ, China E Hosp, Key Lab Arrhythmias,Sch Med, Shanghai 200092, Peoples R China.
EM yihanchen@tongji.edu.cn
OI Condorelli, Gianluigi/0000-0003-0481-6843
FU "973" Program Fund of China [2007CB512100, 2011CB504006]; Ministry of
Education, China; Science and Techonology Commission of Shanghai
Municipality [10JC1414700]; Key Laboratory of Arrhythmias, Ministry of
Education, China (East Hospital, Tongji University School of Medicine);
National Institutes of Health [R01HL104156, R21DA027021, R01HL092577]
FX This work was supported by the "973" Program Fund of China (2007CB512100
and 2011CB504006); the Yangtze Scholars Program Fund by the Ministry of
Education, China; the Program Fund for Innovative Research Teams by the
Ministry of Education, China; the Major Project Fund of Science and
Techonology Commission of Shanghai Municipality (10JC1414700) (all to
Y.-H.C.); the Youth Fund of the Key Laboratory of Arrhythmias, Ministry
of Education, China (East Hospital, Tongji University School of
Medicine) (to DDL and HZ); and National Institutes of Health grants
(R01HL104156, R21DA027021, R01HL092577, to P.T.E).
NR 34
TC 40
Z9 43
U1 1
U2 18
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD SEP 24
PY 2011
VL 9
AR 159
DI 10.1186/1479-5876-9-159
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 832RR
UT WOS:000295825000001
PM 21943159
ER
PT J
AU Jost, S
Quillay, H
Reardon, J
Peterson, E
Simmons, RP
Parry, BA
Bryant, NNP
Binder, WD
Altfeld, M
AF Jost, Stephanie
Quillay, Heloise
Reardon, Jeff
Peterson, Eric
Simmons, Rachel P.
Parry, Blair A.
Bryant, Nancy N. P.
Binder, William D.
Altfeld, Marcus
TI Changes in Cytokine Levels and NK Cell Activation Associated with
Influenza
SO PLOS ONE
LA English
DT Article
ID NATURAL-KILLER-CELLS; ACUTE RESPIRATORY SYNDROME; ACUTE HIV-1 INFECTION;
VIRUS-INFECTION; T-CELLS; HUMORAL IMMUNITY; DENDRITIC CELLS;
UNITED-STATES; A VIRUS; RESPONSES
AB Several studies have highlighted the important role played by murine natural killer (NK) cells in the control of influenza infection. However, human NK cell responses in acute influenza infection, including infection with the 2009 pandemic H1N1 influenza virus, are poorly documented. Here, we examined changes in NK cell phenotype and function and plasma cytokine levels associated with influenza infection and vaccination. We show that absolute numbers of peripheral blood NK cells, and particularly those of CD56(bright) NK cells, decreased upon acute influenza infection while this NK cell subset expanded following intramuscular influenza vaccination. NK cells exposed to influenza antigens were activated, with higher proportions of NK cells expressing CD69 in study subjects infected with seasonal influenza strains. Vaccination led to increased levels of CD25+ NK cells, and notably CD56(bright) CD25+ NK cells, whereas decreased amounts of this subset were present in the peripheral blood of influenza infected individuals, and predominantly in study subjects infected with the 2009 pandemic H1N1 influenza virus. Finally, acute influenza infection was associated with low plasma concentrations of inflammatory cytokines, including IFN-gamma, MIP-1 beta, IL-2 and IL-15, and high levels of the anti-inflammatory cytokines IL-10 and IL-1ra. Altogether, these data suggest a role for the CD56(bright) NK cell subset in the response to influenza, potentially involving their recruitment to infected tissues and a local production and/or uptake of inflammatory cytokines.
C1 [Jost, Stephanie; Quillay, Heloise; Reardon, Jeff; Peterson, Eric; Simmons, Rachel P.; Altfeld, Marcus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst Massachusetts Gen Hosp,Massachusetts I, Boston, MA 02215 USA.
[Parry, Blair A.; Binder, William D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Bryant, Nancy N. P.] Massachusetts Gen Hosp, Massachusetts Gen Hosp Med Walk Clin, Boston, MA 02114 USA.
RP Jost, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst Massachusetts Gen Hosp,Massachusetts I, Boston, MA 02215 USA.
EM maltfeld@partners.org
OI Simmons, Rachel/0000-0003-2498-7965
FU Doris Duke Charitable Foundation; Philip T. and Susan M. Ragon
Foundation; Swiss National Science Foundation [PBELP3-122872];
Massachusetts General Hospital Executive Committee
FX This work was supported by the Doris Duke Charitable Foundation (MA;
http://www.ddcf.org/) and the Philip T. and Susan M. Ragon Foundation
(MA; http://www.ragoninstitute.org). SJ was supported by the Swiss
National Science Foundation (PBELP3-122872; http://www.snf.ch) and the
Massachusetts General Hospital Executive Committee on Research Fund for
Medical Discovery. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 61
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U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 23
PY 2011
VL 6
IS 9
AR e25060
DI 10.1371/journal.pone.0025060
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825IZ
UT WOS:000295267100019
PM 21966414
ER
PT J
AU Ladeira, A
Fregni, F
Campanha, C
Valasek, CA
De Ridder, D
Brunoni, AR
Boggio, PS
AF Ladeira, Andrea
Fregni, Felipe
Campanha, Camila
Valasek, Claudia Aparecida
De Ridder, Dirk
Brunoni, Andre Russwsky
Boggio, Paulo Sergio
TI Polarity-Dependent Transcranial Direct Current Stimulation Effects on
Central Auditory Processing
SO PLOS ONE
LA English
DT Article
ID MOTOR CORTEX; PHOSPHENE THRESHOLDS; PREFRONTAL CORTEX; DC STIMULATION;
PURE-TONES; MODULATION; LOUDNESS; HUMANS; MEMORY; FACILITATION
AB Given the polarity dependent effects of transcranial direct current stimulation (tDCS) in facilitating or inhibiting neuronal processing, and tDCS effects on pitch perception, we tested the effects of tDCS on temporal aspects of auditory processing. We aimed to change baseline activity of the auditory cortex using tDCS as to modulate temporal aspects of auditory processing in healthy subjects without hearing impairment. Eleven subjects received 2mA bilateral anodal, cathodal and sham tDCS over auditory cortex in a randomized and counterbalanced order. Subjects were evaluated by the Random Gap Detection Test (RGDT), a test measuring temporal processing abilities in the auditory domain, before and during the stimulation. Statistical analysis revealed a significant interaction effect of time vs. tDCS condition for 4000 Hz and for clicks. Post-hoc tests showed significant differences according to stimulation polarity on RGDT performance: anodal improved 22.5% and cathodal decreased 54.5% subjects' performance, as compared to baseline. For clicks, anodal also increased performance in 29.4% when compared to baseline. tDCS presented polarity-dependent effects on the activity of the auditory cortex, which results in a positive or negative impact in a temporal resolution task performance. These results encourage further studies exploring tDCS in central auditory processing disorders.
C1 [Ladeira, Andrea; Campanha, Camila; Valasek, Claudia Aparecida; Boggio, Paulo Sergio] Univ Prebiteriana Mackenzie, Social & Cognit Neurosci Lab, Sao Paulo, Brazil.
[Ladeira, Andrea; Campanha, Camila; Valasek, Claudia Aparecida; Boggio, Paulo Sergio] Univ Prebiteriana Mackenzie, Dev Disorders Program, Ctr Hlth & Biol Sci, Sao Paulo, Brazil.
[Fregni, Felipe] Spaulding Rehabil Hosp, Lab Neuromodulat, Boston, MA USA.
[Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA.
[De Ridder, Dirk] Univ Antwerp Hosp, BRAI2N TRI, Antwerp, Belgium.
[De Ridder, Dirk] Univ Antwerp Hosp, Dept Neurosurg, Antwerp, Belgium.
[Brunoni, Andre Russwsky] Univ Sao Paulo, Inst Psicol, Nucleo Neurociencias & Comportamento, Sao Paulo, Brazil.
RP Ladeira, A (reprint author), Univ Prebiteriana Mackenzie, Social & Cognit Neurosci Lab, Sao Paulo, Brazil.
EM boggio@mackenzie.br
RI Boggio, Paulo/K-6272-2012; Brunoni, Andre/H-8394-2012
OI Boggio, Paulo/0000-0002-6109-0447; Brunoni, Andre/0000-0002-6310-3571
FU MackPesquisa; CNPq [305718/2009-6]; FAPESP
FX This work was supported by MackPesquisa. PSB is supported by a CNPq
researcher grant (305718/2009-6). AL was supported by a Master grant
(MackPesquisa). CC is supported by a PhD grant (FAPESP). CAV is
supported by a Master grant (FAPESP). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 33
Z9 33
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 23
PY 2011
VL 6
IS 9
AR e25399
DI 10.1371/journal.pone.0025399
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825IZ
UT WOS:000295267100055
PM 21966519
ER
PT J
AU Tzatsos, A
Paskaleva, P
Lymperi, S
Contino, G
Stoykova, S
Chen, Z
Wong, KK
Bardeesy, N
AF Tzatsos, Alexandros
Paskaleva, Polina
Lymperi, Stephania
Contino, Gianmarco
Stoykova, Svetlana
Chen, Zhao
Wong, Kwok-Kin
Bardeesy, Nabeel
TI Lysine-specific Demethylase 2B (KDM2B)-let-7-Enhancer of Zester Homolog
2 (EZH2) Pathway Regulates Cell Cycle Progression and Senescence in
Primary Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID POLYCOMB GROUP; TUMOR-SUPPRESSOR; SKELETAL-MUSCLE; NASOPHARYNGEAL
CARCINOMA; EMBRYONIC FIBROBLASTS; MICRORNA EXPRESSION; PROTEIN EZH2;
SELF-RENEWAL; STEM-CELLS; P16(INK4A)
AB Sustained expression of the histone demethylase, KDM2B (Ndy1/FBXL10/JHDM1B), bypasses cellular senescence in primary mouse embryonic fibroblasts (MEFs). Here, we show that KDM2B is a conserved regulator of lifespan in multiple primary cell types and defines a program in which this chromatin-modifying enzyme counteracts the senescence-associated down-regulation of the EZH2 histone methyltransferase. Senescence in MEFs epigenetically silences KDM2B and induces the tumor suppressor miRNAs let-7b and miR-101, which target EZH2. Forced expression of KDM2B promotes immortalization by silencing these miRNAs through locus-specific histone H3 K36me2 demethylation, leading to EZH2 up-regulation. Overexpression of let-7b down-regulates EZH2, induces premature senescence, and counteracts immortalization of MEFs driven by KDM2B. The KDM2B-let-7-EZH2 pathway also contributes to the proliferation of immortal Ink4a/Arf null fibroblasts suggesting that, beyond its anti-senescence role in primary cells, this histone-modifying enzyme functions more broadly in the regulation of cellular proliferation.
C1 [Tzatsos, Alexandros; Paskaleva, Polina; Contino, Gianmarco; Stoykova, Svetlana; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lymperi, Stephania] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Chen, Zhao; Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chen, Zhao; Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Tzatsos, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, CPZN4216,185 Cambridge St, Boston, MA 02114 USA.
EM atzatsos@partners.org; nelbardeesy@partners.org
OI Contino, Gianmarco/0000-0001-5874-0405; wong, kwok
kin/0000-0001-6323-235X
FU National Institutes of Health, NCI/Harvard GI SPORE [P50 CA127003, R01
CA133557-01]; Waxman Foundation; Andrew Warshaw Institute; Nestora fund
FX This work was supported by a National Institutes of Health, NCI/Harvard
GI SPORE Grant (P50 CA127003 and R01 CA133557-01). This work was also
supported by grants from the Waxman Foundation, the Andrew Warshaw
Institute (to N. B.), and from the Nestora fund (to A. T.).
NR 38
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U1 1
U2 5
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 SEP 23
PY 2011
VL 286
IS 38
BP 33061
EP 33069
DI 10.1074/jbc.M111.257667
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 821IR
UT WOS:000294968800025
PM 21757686
ER
PT J
AU Xiang, XJ
Huang, W
Haile, CN
Kosten, TA
AF Xiang, Xiaojun
Huang, Wen
Haile, Colin N.
Kosten, Therese A.
TI Hippocampal GluR1 associates with behavior in the elevated plus maze and
shows sex differences
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE CREB; AMPA; Anxiety; Female; Rat
ID ELEMENT-BINDING PROTEIN; ANXIETY-RELATED BEHAVIOR; ESTROUS-CYCLE; FEMALE
RATS; AMPA RECEPTORS; DEFICIENT MICE; CA1 REGION; IN-VIVO; CREB; MEMORY
AB The hippocampus is involved in anxiety as well as spatial memory formation and is sexually dimorphic. Female rats typically show less anxiety in elevated plus maze procedure (EPM), a standard animal model of anxiety. Many intracellular proteins, including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 and the cyclic AMP response element-binding protein (CREB), in hippocampus contribute to memory formation. However, less is known about the roles for hippocampal GluR1 and CREB in anxiety. We examined behavior in EPM in male and female rats and obtained hippocampal tissue samples to determine levels of GluR1 and CREB with western blots. EPM results showed that female rats exhibited less anxiety-like behaviors than male rats. Further, behaviors in EPM were significantly correlated with hippocampal GluR1 levels, but not with CREB. Yet, both proteins showed sex differences with lower levels in female rats. These data not only suggest some potential bases for sex differences in behaviors to which the hippocampus contributes but demonstrate that there is a strong association between hippocampal GluR1 levels and anxiety as assessed with EPM. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Xiang, Xiaojun; Huang, Wen; Haile, Colin N.; Kosten, Therese A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Xiang, Xiaojun; Huang, Wen; Haile, Colin N.; Kosten, Therese A.] Michael E Debakey Vet Adm Med Ctr, Houston, TX 77030 USA.
[Xiang, Xiaojun] Cent S Univ, Mental Hlth Inst, Xiangya Hosp 2, Changsha, Hunan, Peoples R China.
RP Kosten, TA (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM tkosten@bcm.edu
OI Haile, Colin/0000-0001-8293-7291
FU National Institute on Drug Abuse [DA 020117]; Chinese government
FX This research was supported by a National Institute on Drug Abuse grant
to TAK (DA 020117). XX was supported by a fellowship from the Chinese
government. We thank Dr. Alicia Walf for her expert guidance in the
elevated plus maze procedure and its analysis.
NR 44
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Z9 15
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD SEP 23
PY 2011
VL 222
IS 2
BP 326
EP 331
DI 10.1016/j.bbr.2011.03.068
PG 6
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 780ED
UT WOS:000291836400008
PM 21497621
ER
PT J
AU Chakraborty, N
Menze, MA
Malsam, J
Aksan, A
Hand, SC
Toner, M
AF Chakraborty, Nilay
Menze, Michael A.
Malsam, Jason
Aksan, Alptekin
Hand, Steven C.
Toner, Mehmet
TI Cryopreservation of Spin-Dried Mammalian Cells
SO PLOS ONE
LA English
DT Article
ID VITRIFICATION SOLUTIONS; DESICCATION TOLERANCE; TREHALOSE SOLUTIONS;
STEM-CELLS; LIPOSOMES; PRESERVATION; TEMPERATURES; KINETICS; DROPLETS;
EMBRYOS
AB This study reports an alternative approach to achieve vitrification where cells are pre-desiccated prior to cooling to cryogenic temperatures for storage. Chinese Hamster Ovary (CHO) cells suspended in a trehalose solution were rapidly and uniformly desiccated to a low moisture content (<0.12 g of water per g of dry weight) using a spin-drying technique. Trehalose was also introduced into the cells using a high-capacity trehalose transporter (TRET1). Fourier Transform Infrared Spectroscopy (FTIR) was used to examine the uniformity of water concentration distribution in the spin-dried samples. 62% of the cells were shown to survive spin-drying in the presence of trehalose following immediate rehydration. The spin-dried samples were stored in liquid nitrogen (LN(2)) at a vitrified state. It was shown that following re-warming to room temperature and re-hydration with a fully complemented cell culture medium, 51% of the spin-dried and vitrified cells survived and demonstrated normal growth characteristics. Spin-drying is a novel strategy that can be used to improve cryopreservation outcome by promoting rapid vitrification.
C1 [Chakraborty, Nilay; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
[Chakraborty, Nilay; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Boston, MA USA.
[Chakraborty, Nilay; Toner, Mehmet] Shriners Hosp Children, Boston, MA USA.
[Menze, Michael A.] Eastern Illinois Univ, Dept Biol Sci, Charleston, IL 61920 USA.
[Malsam, Jason; Aksan, Alptekin] Univ Minnesota, Dept Mech Engn, Biostabilizat Lab, Minneapolis, MN 55455 USA.
[Hand, Steven C.] Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA.
RP Chakraborty, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA.
EM chakraborty.nilay@mgh.harvard.edu
RI Chakraborty, Nilay/C-3118-2009; Aksan, Alptekin/C-1579-2014;
OI Aksan, Alptekin/0000-0001-9891-1715; Menze, Michael/0000-0003-1072-5462
FU National Institutes of Health [2 RO1 DK046270-14A1, 5 R01 GM086886];
Biopreservation Core Resource, University of Minnesota, Minneapolis,
Minnesota
FX This work was supported by National Institutes of Health (www.NIH.gov)
grants 2 RO1 DK046270-14A1 and 5 R01 GM086886. The authors would like to
thank the Biopreservation Core Resource, University of Minnesota,
Minneapolis, Minnesota 55455 for providing necessary funding for the
Fourier Transform Infrared Spectroscopy Studies. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 31
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U1 0
U2 16
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 SEP 22
PY 2011
VL 6
IS 9
AR e24916
DI 10.1371/journal.pone.0024916
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825IJ
UT WOS:000295265100030
PM 21966385
ER
PT J
AU Coleman, JJ
Ghosh, S
Okoli, I
Mylonakis, E
AF Coleman, Jeffrey J.
Ghosh, Suman
Okoli, Ikechukwu
Mylonakis, Eleftherios
TI Antifungal Activity of Microbial Secondary Metabolites
SO PLOS ONE
LA English
DT Article
ID BIOSYNTHETIC GENE-CLUSTER; CYTOCHROME BC(1) COMPLEX;
ASPERGILLUS-FUMIGATUS; CANDIDA-ALBICANS; CAENORHABDITIS-ELEGANS;
GLIOTOXIN PRODUCTION; FUSARIUM-OXYSPORUM; ILICICOLIN-H; IN-VITRO;
IDENTIFICATION
AB Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen of natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary metabolites capable of conferring an increase in survival to infected nematodes. In this screen, the two compound treatments conferring the highest survival rates were members of the epipolythiodioxopiperazine (ETP) family of fungal secondary metabolites, acetylgliotoxin and a derivative of hyalodendrin. The abundance of fungal secondary metabolites indentified in this screen prompted further studies investigating the interaction between opportunistic pathogenic fungi and Aspergillus fumigatus, because of the ability of the fungus to produce a plethora of secondary metabolites, including the well studied ETP gliotoxin. We found that cell-free supernatant of A. fumigatus was able to inhibit the growth of Candida albicans through the production of a secreted product. Comparative studies between a wild-type and an A. fumigatus Delta gliP strain unable to synthesize gliotoxin demonstrate that this secondary metabolite is the major factor responsible for the inhibition. Although toxic to organisms, gliotoxin conferred an increase in survival to C. albicans-infected C. elegans in a dose dependent manner. As A. fumigatus produces gliotoxin in vivo, we propose that in addition to being a virulence factor, gliotoxin may also provide an advantage to A. fumigatus when infecting a host that harbors other opportunistic fungi.
C1 [Coleman, Jeffrey J.; Ghosh, Suman; Okoli, Ikechukwu; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Harvard Med Sch, Div Infect Dis, Boston, MA 02114 USA.
RP Coleman, JJ (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Div Infect Dis, Boston, MA 02114 USA.
EM emylonakis@partners.org
RI Ghosh, Suman/F-3453-2013; Coleman, Jeffrey/E-2981-2015;
OI Coleman, Jeffrey/0000-0001-8579-1996
FU National Institutes of Health [AI075286, AI070569, AI07061]
FX This work was supported by the National Institutes of Health trough, an
R01 award (AI075286), and an R21 award (AI070569) to EM, and a T32
(AI07061) to JJC. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
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U2 26
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 SEP 22
PY 2011
VL 6
IS 9
AR e25321
DI 10.1371/journal.pone.0025321
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825IJ
UT WOS:000295265100087
PM 21966496
ER
PT J
AU Izar, B
Rai, A
Raghuram, K
Rotruck, J
Carpenter, J
AF Izar, Benjamin
Rai, Ansaar
Raghuram, Karthikram
Rotruck, Jill
Carpenter, Jeffrey
TI Comparison of Devices Used for Stent-Assisted Coiling of Intracranial
Aneurysms
SO PLOS ONE
LA English
DT Article
ID SINGLE-CENTER EXPERIENCE; WIDE-NECKED ANEURYSMS; SELF-EXPANDING STENT;
CEREBRAL ANEURYSMS; NEUROFORM STENT; ENTERPRISE STENT; FOLLOW-UP;
ENDOVASCULAR OCCLUSION; MIDTERM; EMBOLIZATION
AB Introduction: Two self-expandable stents, the Neuroform and the Enterprise stent, are widely used for stent-assisted coiling (SAC) of complex shaped intracranial aneurysms. However, comparative knowledge about technical feasibility, peri-and post-procedural morbidity and mortality, packing densities as well as follow-up data is limited.
Material and Methods: We conducted a retrospective study to investigate differences in aneurysms stented with the Enterprise or Neuroform stents. Angiographic follow-up (mean 19.42 months) was available in 72.6% (61/84) of aneurysms treated with stent-assisted coiling. We further sought to compare stent-assisted coiling to a matched patient population with aneurysms treated by conventional coil embolization.
Results: The stenting success rate of the Enterprise was higher compared to the Neuroform stent (46/48 and 42/51, respectively). In 5 of 9 cases in which the Neuroform stent was not navigable to the landing zone, we successfully deployed an Enterprise stent instead. Eventually, 42 aneurysms were coiled after stenting in each group. We observed no significant differences in peri-procedural complication rate, post-procedural hospital stay, packing density, recurrence rate or number of in-stent stenosis. Strikingly, 36.1% of followed aneurysms in the SAC group showed progressive occlusion on angiographic follow-up imaging. The packing density was significantly higher in aneurysms treated by SAC as compared to conventionally coiled aneurysms, while recanalization rate was significantly lower in the SAC group.
Conclusion: The procedural success rate is higher using the Enterprise, but otherwise both stents exhibited similar characteristics. Lower recurrence frequency and complication rates comparable to conventional coil embolization emphasize the importance of stent-assisted coiling in the treatment of complex aneurysms. Progressive occlusion on angiographic follow-up was a distinct and frequent observation in the SAC group and may in part be due to flow diversion.
C1 [Izar, Benjamin] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Rai, Ansaar; Raghuram, Karthikram; Carpenter, Jeffrey] W Virginia Univ, Dept Radiol, Morgantown, WV 26506 USA.
[Rotruck, Jill] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA.
RP Izar, B (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
EM jcarpenter@hsc.wvu.edu
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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 SEP 22
PY 2011
VL 6
IS 9
AR e24875
DI 10.1371/journal.pone.0024875
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825IJ
UT WOS:000295265100023
PM 21966374
ER
PT J
AU Mantopoulos, D
Murakami, Y
Comander, J
Thanos, A
Roh, M
Miller, JW
Vavvas, DG
AF Mantopoulos, Dimosthenis
Murakami, Yusuke
Comander, Jason
Thanos, Aristomenis
Roh, Miin
Miller, Joan W.
Vavvas, Demetrios G.
TI Tauroursodeoxycholic Acid (TUDCA) Protects Photoreceptors from Cell
Death after Experimental Retinal Detachment
SO PLOS ONE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; BILE-ACID; INDUCED APOPTOSIS; RAT
HEPATOCYTES; HUNTINGTONS-DISEASE; EXPERIMENTAL-MODEL; DEGENERATION;
ACTIVATION; NECROSIS; CYTOLYSIS
AB Background: Detachment of photoreceptors from the underlying retinal pigment epithelium is seen in various retinal disorders such as retinal detachment and age-related macular degeneration and leads to loss of photoreceptors and vision. Pharmacologic inhibition of photoreceptor cell death may prevent this outcome. This study tests whether systemic administration of tauroursodeoxycholic acid (TUDCA) can protect photoreceptors from cell death after experimental retinal detachment in rodents.
Methodology/Principal Findings: Retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with vehicle or TUDCA (500 mg/kg). TUNEL staining was used to evaluate cell death. Photoreceptor loss was evaluated by measuring the relative thickness of the outer nuclear layer (ONL). Macrophage recruitment, oxidative stress, cytokine levels, and caspase levels were also quantified. Three days after detachment, TUDCA decreased the number of TUNEL-positive cells compared to vehicle (651 +/- 68/mm(2) vs. 1314 +/- 68/mm(2), P = 0.001) and prevented the reduction of ONL thickness ratio (0.84 +/- 0.03 vs. 0.65 +/- 0.03, P = 0.002). Similar results were obtained after 5 days of retinal detachment. Macrophage recruitment and expression levels of TNF-a and MCP-1 after retinal detachment were not affected by TUDCA treatment, whereas increases in activity of caspases 3 and 9 as well as carbonyl-protein adducts were almost completely inhibited by TUDCA treatment.
Conclusions/Significance: Systemic administration of TUDCA preserved photoreceptors after retinal detachment, and was associated with decreased oxidative stress and caspase activity. TUDCA may be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment.
C1 [Mantopoulos, Dimosthenis; Murakami, Yusuke; Comander, Jason; Thanos, Aristomenis; Roh, Miin; Miller, Joan W.; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, Boston, MA USA.
RP Mantopoulos, D (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, Boston, MA USA.
EM vavvas@meei.harvard.edu
OI Comander, Jason/0000-0002-4257-7145; Vavvas,
Demetrios/0000-0002-8622-6478
FU Research to Prevent Blindness Foundation; Lions Eye Research Fund;
Onassis Foundation; National Eye Institute [EY014104]; Yeatts Family
Fund
FX The Research to Prevent Blindness Foundation, the Lions Eye Research
Fund (D. G. V.), the Onassis Foundation (D. G. V.), National Eye
Institute Grant EY014104 (Massachusetts Eye and Ear Infirmary core
grant), and Yeatts Family Fund (D. G. V. and J.W.M). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 42
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U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 22
PY 2011
VL 6
IS 9
AR e24245
DI 10.1371/journal.pone.0024245
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825IJ
UT WOS:000295265100006
PM 21961034
ER
PT J
AU Wan, Q
Kerr, C
Pritchett, D
Hamalainen, M
Moore, C
Jones, S
AF Wan, Qian
Kerr, Catherine
Pritchett, Dominique
Haemaelaeinen, Matti
Moore, Christopher
Jones, Stephanie
TI Dynamics of Dynamics within a Single Data Acquisition Session: Variation
in Neocortical Alpha Oscillations in Human MEG
SO PLOS ONE
LA English
DT Article
ID PRIMARY SOMATOSENSORY CORTEX; VISUOSPATIAL ATTENTION; OCCIPITAL CORTEX;
EVOKED-RESPONSES; MU RHYTHM; MODULATION; EEG; SYNCHRONIZATION;
FLUCTUATIONS; PERFORMANCE
AB Background: Behavioral paradigms applied during human recordings in electro- and magneto-encephalography (EEG and MEG) typically require 1-2 hours of data collection. Over this time scale, the natural fluctuations in brain state or rapid learning effects could impact measured signals, but are seldom analyzed.
Methods and Findings: We investigated within-session dynamics of neocortical alpha (7-14 Hz) rhythms and their allocation with cued-attention using MEG recorded from primary somatosensory neocortex (SI) in humans. We found that there were significant and systematic changes across a single similar to 1 hour recording session in several dimensions, including increased alpha power, increased differentiation in attention-induced alpha allocation, increased distinction in immediate time-locked post-cue evoked responses in SI to different visual cues, and enhanced power in the immediate cue-locked alpha band frequency response. Further, comparison of two commonly used baseline methods showed that conclusions on the evolution of alpha dynamics across a session were dependent on the normalization method used.
Conclusions: These findings are important not only as they relate to studies of oscillations in SI, they also provide a robust example of the type of dynamic changes in brain measures within a single session that are overlooked in most human brain imaging/recording studies.
C1 [Wan, Qian; Pritchett, Dominique; Moore, Christopher] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[Wan, Qian; Kerr, Catherine] Harvard Univ, Harvard Osher Res Ctr, Sch Med, Boston, MA 02115 USA.
[Haemaelaeinen, Matti; Jones, Stephanie] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Wan, Q (reprint author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM srjones@nmr.mgh.harvard.edu
RI Hamalainen, Matti/C-8507-2013;
OI Pritchett, Dominique/0000-0003-1187-1162
FU National Institutes of Health (NIH) [P41RR14075, K25MH072941,
K01AT003459, 1RO1-NS045130-01, T32GM007484]; National Science Foundation
(NSF) [0316933]; Osher Institute; Athinoula A. Martinos Center for
Biomedical Imaging; McGovern Institute for Brain Research
FX This work was supported by the National Institutes of Health (NIH):
P41RR14075, K25MH072941, K01AT003459, 1RO1-NS045130-01, T32GM007484, the
National Science Foundation (NSF): 0316933, and the Osher Institute. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; The authors wish
to thank Athinoula A. Martinos Center for Biomedical Imaging, the
McGovern Institute for Brain Research, the Osher Institute, National
Institute of Health, and the National Science Foundation for their
support of this research.
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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 SEP 22
PY 2011
VL 6
IS 9
AR e24941
DI 10.1371/journal.pone.0024941
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825IJ
UT WOS:000295265100033
PM 21966388
ER
PT J
AU Liong, M
Tassa, C
Shaw, SY
Lee, H
Weissleder, R
AF Liong, Monty
Tassa, Carlos
Shaw, Stanley Y.
Lee, Hakho
Weissleder, Ralph
TI Multiplexed Magnetic Labeling Amplification Using Oligonucleotide
Hybridization
SO ADVANCED MATERIALS
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; PROTEIN; NANOPARTICLES; CANCER
AB Multiplexed Magnetic Labeling Amplification Using Oligonucleotide Hybridization Oligonucleotide hybridization was used as a cell-labeling method to significantly amplify the loading of magnetic probes onto target cells. The method utilized short oligonucleotides as the binding agents between antibodies and superparamagnetic iron oxide. This method not only enabled multiplexed analysis, but also allowed detection of multiple markers on a single sample containing only scant cell numbers.
C1 [Liong, Monty; Tassa, Carlos; Shaw, Stanley Y.; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Ctr Syst Biol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA.
RP Lee, H (reprint author), Harvard Univ, Ctr Syst Biol, Massachusetts Gen Hosp, Sch Med, 185 Cambridge St, Boston, MA 02114 USA.
EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu
FU National Institute of Health [R01-EB004626, U54-CA119349]; TPEN
[HHSN268201000044C]
FX We thank S. S. Agasti, M. Fernandez-Suarez, R. Mazitschek, T. Reiner,
and H. Shao for helpful discussions; I. Bagayev, A. Chudnovskiy, V.
Cortez-Retamozo, and A. Newton for assistance in cell experiments; N.
Sergeyev for providing the cross-linked iron oxide particles; and Y.
Fisher-Jeffes for reviewing the manuscript. This work was supported in
part by National Institute of Health Grants R01-EB004626, U54-CA119349,
and TPEN contract (HHSN268201000044C).
NR 20
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Z9 15
U1 2
U2 31
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0935-9648
J9 ADV MATER
JI Adv. Mater.
PD SEP 22
PY 2011
VL 23
IS 36
BP H254
EP +
DI 10.1002/adma.201101401
PG 5
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 824VC
UT WOS:000295229300004
PM 21780311
ER
PT J
AU Reeves, RK
Rajakumar, PA
Evans, TI
Connole, M
Gillis, J
Wong, FE
Kuzmichev, YV
Carville, A
Johnson, RP
AF Reeves, R. Keith
Rajakumar, Premeela A.
Evans, Tristan I.
Connole, Michelle
Gillis, Jacqueline
Wong, Fay E.
Kuzmichev, Yury V.
Carville, Angela
Johnson, R. Paul
TI Gut inflammation and indoleamine deoxygenase inhibit IL-17 production
and promote cytotoxic potential in NKp44(+) mucosal NK cells during SIV
infection
SO BLOOD
LA English
DT Article
ID NATURAL-KILLER-CELLS; SIMIAN IMMUNODEFICIENCY VIRUS; SECONDARY
LYMPHOID-TISSUE; ROR-GAMMA-T; RHESUS MACAQUES; HIV-1 INFECTION; NKP46(+)
CELLS; I INTERFERON; HLA-B; DIFFERENTIATION
AB Natural killer (NK) cells are classically viewed as effector cells that kill virus-infected and neoplastic cells, but recent studies have identified a rare mucosal NK-cell subpopulation secreting the TH17 cytokine IL-22. Here, we report identification of 2 distinct lineages of mucosal NK cells characterized as NKG2A(+)NFIL3(+)RORC(-) and NKp44(+)NFIL3(+)RORC(+). NKG2A(+) NK cells were systemically distributed, cytotoxic, and secreted IFN-gamma, whereas NKp44(+) NK cells were mucosae-restricted, noncytotoxic, and produced IL-22 and IL-17. During SIV infection, NKp44(+) NK cells became apoptotic, were depleted, and had an altered functional profile characterized by decreased IL-17 secretion; increased IFN-gamma secretion; and, surprisingly, increased potential for cytotoxicity. NKp44(+) NK cells showed no evidence of direct SIV infection; rather, depletion and altered function were associated with SIV-induced up-regulation of inflammatory mediators in the gut, including indoleamine 2,3-dioxygenase 1. Furthermore, treatment of NKp44(+) NK cells with indoleamine 2,3-dioxygenase 1 catabolites in vitro ablated IL-17 production in a dose-dependent manner, whereas other NK-cell functions were unaffected. Thus lentiviral infection both depletes and modifies the functional repertoire of mucosal NK cells involved in the maintenance of gut integrity, a finding that highlights the plasticity of this rare mucosal NK-cell population. (Blood. 2011;118(12):3321-3330)
C1 [Reeves, R. Keith; Rajakumar, Premeela A.; Evans, Tristan I.; Connole, Michelle; Gillis, Jacqueline; Wong, Fay E.; Kuzmichev, Yury V.; Johnson, R. Paul] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA.
[Carville, Angela] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Primate Med, Southborough, MA 01772 USA.
[Johnson, R. Paul] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Johnson, R. Paul] Harvard Univ, Boston, MA 02115 USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA.
EM paul_johnson@hms.harvard.edu
FU National Institutes of Health [AI071306, AI090735, RR00168]; Center for
HIV/AIDS Vaccine Immunology/HIV Vaccine Trials Network [U19 AI
067854-04]
FX This work was supported through National Institutes of Health grants
AI071306, AI090735, and RR00168, and Center for HIV/AIDS Vaccine
Immunology/HIV Vaccine Trials Network Early Career Investigator award
U19 AI 067854-04 to R.K.R.
NR 50
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U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 22
PY 2011
VL 118
IS 12
BP 3321
EP 3330
DI 10.1182/blood-2011-04-347260
PG 10
WC Hematology
SC Hematology
GA 823KK
UT WOS:000295120900019
PM 21791421
ER
PT J
AU Faraday, N
Yanek, LR
Yang, XP
Mathias, R
Herrera-Galeano, JE
Suktitipat, B
Qayyum, R
Johnson, AD
Chen, MH
Tofler, GH
Ruczinski, I
Friedman, AD
Gylfason, A
Thorsteinsdottir, U
Bray, PF
O'Donnell, CJ
Becker, DM
Becker, LC
AF Faraday, Nauder
Yanek, Lisa R.
Yang, Xiao Ping
Mathias, Rasika
Herrera-Galeano, J. Enrique
Suktitipat, Bhoom
Qayyum, Rehan
Johnson, Andrew D.
Chen, Ming-Huei
Tofler, Geoffrey H.
Ruczinski, Ingo
Friedman, Alan D.
Gylfason, Arnaldur
Thorsteinsdottir, Unnur
Bray, Paul F.
O'Donnell, Christopher J.
Becker, Diane M.
Becker, Lewis C.
TI Identification of a specific intronic PEAR1 gene variant associated with
greater platelet aggregability and protein expression
SO BLOOD
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ASPIRIN RESISTANCE; CARDIOVASCULAR EVENTS;
AGGREGATION; HERITABILITY; METAANALYSIS; ACTIVATION; PATHWAYS; HISTORY;
DISEASE
AB Genetic variation is thought to contribute to variability in platelet function; however, the specific variants and mechanisms that contribute to altered platelet function are poorly defined. With the use of a combination of fine mapping and sequencing of the platelet endothelial aggregation receptor 1 (PEAR1) gene we identified a common variant (rs12041331) in intron 1 that accounts for <= 15% of total phenotypic variation in platelet function. Association findings were robust in 1241 persons of European ancestry (P = 2.22 x 10(-8)) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 x 10(-27)) and in an independent sample of 2755 persons of European descent (P = 1.64 x 10(-5)). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 x 10(-6)) for the relation between the PEAR1 gene and platelet function phenotype. A dose-response relation between the number of G alleles at rs12041331 and expression of PEAR1 protein in human platelets was confirmed by Western blotting and ELISA. Similarly, the Gallele was associated with greater protein expression in a luciferase reporter assay. These experiments identify the precise genetic variant in PEAR1 associated with altered platelet function and provide a plausible biologic mechanism to explain the association between variation in the PEAR1 gene and platelet function phenotype. (Blood. 2011;118(12):3367-3375)
C1 [Faraday, Nauder] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Yanek, Lisa R.; Yang, Xiao Ping; Mathias, Rasika; Herrera-Galeano, J. Enrique; Suktitipat, Bhoom; Qayyum, Rehan; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, GeneSTAR Res Program, Dept Med, Baltimore, MD 21205 USA.
[Johnson, Andrew D.; Chen, Ming-Huei; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Chen, Ming-Huei] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tofler, Geoffrey H.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia.
[Ruczinski, Ingo] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Friedman, Alan D.] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Baltimore, MD USA.
[Gylfason, Arnaldur; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland.
[Bray, Paul F.] Thomas Jefferson Sch Med, Dept Med, Div Hematol, Philadelphia, PA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA.
RP Faraday, N (reprint author), Johns Hopkins Univ Hosp, 298 Meyer Bldg,600 N Wolfe St, Baltimore, MD 21287 USA.
EM nfaraday@jhmi.edu
RI Johnson, Andrew/G-6520-2013;
OI Qayyum, Rehan/0000-0003-3086-8014; Suktitipat, Bhoom/0000-0001-8034-7757
FU National Heart, Lung, and Blood Institute (NHLBI) through the PROGENI
[U01 HL72518]; STAMPEED consortia [R01 HL087698-01]; Johns Hopkins
General Clinical Research Center; National Center for Research Resources
[M01-RR000052]; NHLBI [N01-HC-25195]; Affymetrix Inc [N02-HL-6-4278];
Department of Medicine at Boston University School of Medicine; Boston
Medical Center; [R01-HL-48157]
FX This work was supported by the National Heart, Lung, and Blood Institute
(NHLBI) through the PROGENI (U01 HL72518) and STAMPEED (R01 HL087698-01)
consortia and by grant R01-HL-48157. A portion of this work was
supported by resources of the Johns Hopkins General Clinical Research
Center, funded through the National Center for Research Resources (grant
M01-RR000052). This work was also supported by the NHLBI's Framingham
Heart Study (contract no. N01-HC-25195) and its contract with Affymetrix
Inc for genotyping services (contract no. N02-HL-6-4278). A portion of
this research used the Linux Cluster for Genetic Analysis (LinGA-II)
funded by the Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center.
NR 20
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Z9 34
U1 1
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 22
PY 2011
VL 118
IS 12
BP 3367
EP 3375
DI 10.1182/blood-2010-11-320788
PG 9
WC Hematology
SC Hematology
GA 823KK
UT WOS:000295120900025
PM 21791418
ER
PT J
AU Guo, CG
Yoon, HS
Franklin, A
Jain, S
Ebert, A
Cheng, HL
Hansen, E
Despo, O
Bossen, C
Vettermann, C
Bates, JG
Richards, N
Myers, D
Patel, H
Gallagher, M
Schlissel, MS
Murre, C
Busslinger, M
Giallourakis, CC
Alt, FW
AF Guo, Chunguang
Yoon, Hye Suk
Franklin, Andrew
Jain, Suvi
Ebert, Anja
Cheng, Hwei-Ling
Hansen, Erica
Despo, Orion
Bossen, Claudia
Vettermann, Christian
Bates, Jamie G.
Richards, Nicholas
Myers, Darienne
Patel, Harin
Gallagher, Michael
Schlissel, Mark S.
Murre, Cornelis
Busslinger, Meinrad
Giallourakis, Cosmas C.
Alt, Frederick W.
TI CTCF-binding elements mediate control of V(D)J recombination
SO NATURE
LA English
DT Article
ID B-CELL DEVELOPMENT; HEAVY-CHAIN LOCUS; VH GENE SEGMENTS; IGH LOCUS;
REGULATORY ELEMENTS; INTRONIC ENHANCER; ANTISENSE TRANSCRIPTION;
LYMPHOCYTE DEVELOPMENT; NUCLEAR-ORGANIZATION; REGION
AB Immunoglobulin heavy chain (IgH) variable region exons are assembled from V-H, D and J(H) gene segments in developing B lymphocytes. Within the 2.7-megabase mouse Igh locus, V(D)J recombination is regulated to ensure specific and diverse antibody repertoires. Here we report in mice a key Igh V(D)J recombination regulatory region, termed intergenic control region 1 (IGCR1), which lies between the V-H and D clusters. Functionally, IGCR1 uses CTCF looping/insulator factor-binding elements and, correspondingly, mediates Igh loops containing distant enhancers. IGCR1 promotes normal B-cell development and balances antibody repertoires by inhibiting transcription and rearrangement of D-H-proximal V-H gene segments and promoting rearrangement of distal V-H segments. IGCR1 maintains ordered and lineage-specific V-H(D)J(H) recombination by suppressing V-H joining to D segments not joined to J(H) segments, and V-H to DJ(H) joins in thymocytes, respectively. IGCR1 is also required for feedback regulation and allelic exclusion of proximal V-H-to-DJ(H) recombination. Our studies elucidate a long-sought Igh V(D) J recombination control region and indicate a new role for the generally expressed CTCF protein.
C1 [Guo, Chunguang; Yoon, Hye Suk; Franklin, Andrew; Jain, Suvi; Cheng, Hwei-Ling; Hansen, Erica; Despo, Orion; Richards, Nicholas; Myers, Darienne; Patel, Harin; Gallagher, Michael; Giallourakis, Cosmas C.; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA.
[Guo, Chunguang; Yoon, Hye Suk; Franklin, Andrew; Jain, Suvi; Cheng, Hwei-Ling; Hansen, Erica; Despo, Orion; Richards, Nicholas; Myers, Darienne; Patel, Harin; Gallagher, Michael; Giallourakis, Cosmas C.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Ebert, Anja; Busslinger, Meinrad] Res Inst Mol Pathol, A-1030 Vienna, Austria.
[Bossen, Claudia; Murre, Cornelis] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Vettermann, Christian; Bates, Jamie G.; Schlissel, Mark S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Giallourakis, Cosmas C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, 300 Longwood Ave, Boston, MA 02115 USA.
EM cgiallourakis@partners.org; alt@enders.tch.harvard.edu
RI Busslinger, Meinrad/J-1249-2016
OI Busslinger, Meinrad/0000-0002-9111-9351
FU NIH [RO1 AI20047, RO1 HL48702, RO1 AI40227, CA054198-20, K08 AI070839];
Austrian GEN-AU initiative; Boehringer Ingelheim; Cancer Research
Institute; Marie Curie Fellowship; EMBO
FX We thank Y. Fujiwara and P.-Y. Huang for generating chimaeric mice. This
work was supported by NIH grants RO1 AI20047 (to F. W. A.), RO1 HL48702
and AI40227 (to M. S. S.), CA054198-20 (to C. M.) and K08 AI070839 (to
C. C. G.). M. B. was supported by the Austrian GEN-AU initiative and
Boehringer Ingelheim. C. G. is supported by an Irvington Institute
Postdoctoral Fellowship from the Cancer Research Institute. C. V. is
supported by a Marie Curie Fellowship. C. B. is supported by an EMBO
fellowship. F. W. A. is an Investigator of the Howard Hughes Medical
Institute.
NR 53
TC 113
Z9 117
U1 1
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 424
EP U182
DI 10.1038/nature10495
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500032
PM 21909113
ER
PT J
AU Choi, JH
Banks, AS
Kamenecka, TM
Busby, SA
Chalmers, MJ
Kumar, N
Kuruvilla, DS
Shin, YS
He, YJ
Bruning, JB
Marciano, DP
Cameron, MD
Laznik, D
Jurczak, MJ
Schurer, SC
Vidovic, D
Shulman, GI
Spiegelman, BM
Griffin, PR
AF Choi, Jang Hyun
Banks, Alexander S.
Kamenecka, Theodore M.
Busby, Scott A.
Chalmers, Michael J.
Kumar, Naresh
Kuruvilla, Dana S.
Shin, Youseung
He, Yuanjun
Bruning, John B.
Marciano, David P.
Cameron, Michael D.
Laznik, Dina
Jurczak, Michael J.
Schuerer, Stephan C.
Vidovic, Dusica
Shulman, Gerald I.
Spiegelman, Bruce M.
Griffin, Patrick R.
TI Antidiabetic actions of a non-agonist PPAR gamma ligand blocking
Cdk5-mediated phosphorylation
SO NATURE
LA English
DT Article
ID ACTIVATED-RECEPTOR-GAMMA; ADIPOCYTE DIFFERENTIATION; SKELETAL-MUSCLE;
ROSIGLITAZONE; EXPRESSION; OBESITY; POTENT; THIAZOLIDINEDIONE;
PPAR-GAMMA-2; MODULATORS
AB PPAR gamma is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone(1). These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPAR gamma-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPAR gamma by Cdk5 (ref. 2). Here we describe novel synthetic compounds that have a unique mode of binding to PPAR gamma, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover, one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPAR gamma drugs. Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPAR gamma.
C1 [Choi, Jang Hyun; Banks, Alexander S.; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Choi, Jang Hyun; Banks, Alexander S.; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Metab & Chron Dis, Boston, MA 02115 USA.
[Choi, Jang Hyun; Banks, Alexander S.; Laznik, Dina; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kamenecka, Theodore M.; Shin, Youseung; He, Yuanjun; Cameron, Michael D.; Griffin, Patrick R.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA.
[Busby, Scott A.; Chalmers, Michael J.; Kumar, Naresh; Kuruvilla, Dana S.; Marciano, David P.; Cameron, Michael D.; Griffin, Patrick R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
[Kamenecka, Theodore M.; Cameron, Michael D.; Griffin, Patrick R.] Scripps Res Inst, SRMSC, Jupiter, FL 33458 USA.
[Bruning, John B.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA.
[Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Internal Med, New Haven, CT 06510 USA.
[Jurczak, Michael J.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA.
[Schuerer, Stephan C.; Vidovic, Dusica] Univ Miami, Ctr Computat Sci, Miami, FL 33136 USA.
RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu; pgriffin@scripps.edu
RI Choi, Jang Hyun/B-3055-2012; Banks, Alexander/B-4832-2012
OI Banks, Alexander/0000-0003-1787-6925
FU National Institutes of Health (NIH), National Institute of Mental Health
[U54-MH074404]; National Institute of General Medical Sciences
[R01-GM084041]; National Institute of Diabetes and Digestive and Kidney
Diseases [1RC4DK090861]; NIH [DK31405]
FX We are grateful for support from S. Novick for assistance in the HDX
studies and from R. D. Garcia-Ordonez in protein production and
mutagenesis. We are grateful for support from B. Pascal and S. Willis
for software analysing the HDX data. We are grateful to R. Gupta and P.
Cohen for their critical comments on the manuscript. This work was
supported in part by the Intramural Research Program of the National
Institutes of Health (NIH), National Institute of Mental Health (grant
U54-MH074404, H. Rosen principal investigator), the National Institute
of General Medical Sciences (grant R01-GM084041, P. R. G.) and the
National Institute of Diabetes and Digestive and Kidney Diseases (grant
1RC4DK090861, B. M. S.). This work also supported by NIH DK31405 to
B.M.S.
NR 28
TC 200
Z9 208
U1 4
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 22
PY 2011
VL 477
IS 7365
BP 477
EP U131
DI 10.1038/nature10383
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822WH
UT WOS:000295080500043
PM 21892191
ER
PT J
AU Raje, NS
Steele, DJR
Lawrimore, TM
Johri, AM
Sohani, AR
AF Raje, Noopur S.
Steele, David J. R.
Lawrimore, Tara M.
Johri, Amer M.
Sohani, Aliyah R.
TI Case 29-2011: A 66-Year-Old Woman with Cardiac and Renal Failure
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID DIAGNOSED MULTIPLE-MYELOMA; PLASMA-EXCHANGE; AL AMYLOIDOSIS;
DEXAMETHASONE; BORTEZOMIB; THERAPY; CHEMOTHERAPY; NEPHROPATHY;
IMPROVEMENT; CRITERIA
C1 [Raje, Noopur S.] Dept Med, Div Hematol Oncol, Boston, MA 02101 USA.
[Steele, David J. R.] Dept Med, Div Nephrol, Boston, MA USA.
[Johri, Amer M.] Dept Med, Div Cardiol, Boston, MA USA.
[Lawrimore, Tara M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Raje, Noopur S.; Steele, David J. R.; Johri, Amer M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lawrimore, Tara M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA.
[Sohani, Aliyah R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA.
RP Raje, NS (reprint author), Dept Med, Div Hematol Oncol, Boston, MA 02101 USA.
NR 30
TC 3
Z9 3
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
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD SEP 22
PY 2011
VL 365
IS 12
BP 1129
EP 1138
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 822WR
UT WOS:000295081600013
PM 21992126
ER
PT J
AU Lencer, WI
von Andrian, UH
AF Lencer, Wayne I.
von Andrian, Ulrich H.
TI Eliciting Mucosal Immunity
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID DENDRITIC CELLS
C1 [Lencer, Wayne I.] Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[von Andrian, Ulrich H.] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
RP Lencer, WI (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA 02115 USA.
RI von Andrian, Ulrich/A-5775-2008
FU NIDDK NIH HHS [P30 DK034854, R01 DK048106, R37 DK048106]
NR 7
TC 4
Z9 5
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 SEP 22
PY 2011
VL 365
IS 12
BP 1151
EP 1153
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 822WR
UT WOS:000295081600017
PM 21992128
ER
PT J
AU Calabro, FJ
Soto-Faraco, S
Vaina, LM
AF Calabro, F. J.
Soto-Faraco, S.
Vaina, L. M.
TI Acoustic facilitation of object movement detection during self-motion
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE flow parsing; visual search; multisensory perception; visual motion;
auditory motion
ID VISUAL-SEARCH; SENSORY MODALITIES; RETINAL MOTION; AUDIOVISUAL
INTEGRATION; AUDITORY MOTION; PERCEPTION; VISION; INFORMATION; PARALLEL;
CAPTURE
AB In humans, as well as most animal species, perception of object motion is critical to successful interaction with the surrounding environment. Yet, as the observer also moves, the retinal projections of the various motion components add to each other and extracting accurate object motion becomes computationally challenging. Recent psychophysical studies have demonstrated that observers use a flow-parsing mechanism to estimate and subtract self-motion from the optic flow field. We investigated whether concurrent acoustic cues for motion can facilitate visual flow parsing, thereby enhancing the detection of moving objects during simulated self-motion. Participants identified an object (the target) that moved either forward or backward within a visual scene containing nine identical textured objects simulating forward observer translation. We found that spatially co-localized, directionally congruent, moving auditory stimuli enhanced object motion detection. Interestingly, subjects who performed poorly on the visual-only task benefited more from the addition of moving auditory stimuli. When auditory stimuli were not co-localized to the visual target, improvements in detection rates were weak. Taken together, these results suggest that parsing object motion from self-motion-induced optic flow can operate on multisensory object representations.
C1 [Calabro, F. J.; Vaina, L. M.] Boston Univ, Dept Biomed Engn, Brain & Vis Res Lab, Boston, MA 02215 USA.
[Soto-Faraco, S.] Univ Pompeu Fabra, ICREA, Barcelona, Spain.
[Soto-Faraco, S.] Univ Pompeu Fabra, Dept Tecnol Informacio & Comunicac, Barcelona, Spain.
[Vaina, L. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02215 USA.
[Vaina, L. M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA.
RP Vaina, LM (reprint author), Boston Univ, Dept Biomed Engn, Brain & Vis Res Lab, Boston, MA 02215 USA.
EM vaina@bu.edu
RI Brain and Cognition, Center/H-5448-2011; Consolider Ingenio 2010,
BRAINGLOT/D-1235-2009; SOTO-FARACO, SALVADOR/B-8400-2011;
OI SOTO-FARACO, SALVADOR/0000-0002-4799-3762; Calabro,
Finnegan/0000-0002-8092-3942
FU NIH [RO1NS064100]; Ministerio de Ciencia e Innovacion [PSI2010-15426,
CSD2007-00012]; Comissionat per a Universitats i Recerca del DIUE
[SRG2009-092]; European Research Council [StG-2010 263145]; Sound Field
Laboratory at Sargent College, Boston University [P30 DC04663]
FX L.M.V. and F.J.C. were supported by NIH grant RO1NS064100 to L.M.V.
S.S.F. was supported by grants from the Ministerio de Ciencia e
Innovacion (PSI2010-15426 and CSD2007-00012), by the Comissionat per a
Universitats i Recerca del DIUE (SRG2009-092) and by the European
Research Council (StG-2010 263145).; We thank Gerald Kidd and Chris
Mason for their helpful suggestions and for generously making available
to us the resources of the Sound Field Laboratory at Sargent College,
Boston University, supported by grant P30 DC04663. We also thank Franco
Rupcich, Benvy Caldwell and Megan Menard for helping with psychophysical
data collection and subject recruitment, and Leonardo Sassi for
developing and implementing a preliminary version of the object motion
task.
NR 52
TC 15
Z9 15
U1 4
U2 9
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD SEP 22
PY 2011
VL 278
IS 1719
BP 2840
EP 2847
DI 10.1098/rspb.2010.2757
PG 8
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA 805NG
UT WOS:000293733600019
PM 21307050
ER
PT J
AU Zamakhchari, M
Wei, GX
Dewhirst, F
Lee, J
Schuppan, D
Oppenheim, FG
Helmerhorst, EJ
AF Zamakhchari, Maram
Wei, Guoxian
Dewhirst, Floyd
Lee, Jaeseop
Schuppan, Detlef
Oppenheim, Frank G.
Helmerhorst, Eva J.
TI Identification of Rothia Bacteria as Gluten-Degrading Natural Colonizers
of the Upper Gastro-Intestinal Tract
SO PLOS ONE
LA English
DT Article
ID COMBINATION ENZYME THERAPY; CELIAC-DISEASE; TISSUE TRANSGLUTAMINASE;
GLIADIN PEPTIDES; PROLYL-ENDOPEPTIDASE; T-CELLS; SP-NOV; SPRUE;
ENDOPROTEASE; MICROBIOME
AB Background: Gluten proteins, prominent constituents of barley, wheat and rye, cause celiac disease in genetically predisposed subjects. Gluten is notoriously difficult to digest by mammalian proteolytic enzymes and the protease-resistant domains contain multiple immunogenic epitopes. The aim of this study was to identify novel sources of gluten-digesting microbial enzymes from the upper gastro-intestinal tract with the potential to neutralize gluten epitopes.
Methodology/Principal Findings: Oral microorganisms with gluten-degrading capacity were obtained by a selective plating strategy using gluten agar. Microbial speciations were carried out by 16S rDNA gene sequencing. Enzyme activities were assessed using gliadin-derived enzymatic substrates, gliadins in solution, gliadin zymography, and 33-mer alpha-gliadin and 26-mer gamma-gliadin immunogenic peptides. Fragments of the gliadin peptides were separated by RP-HPLC and structurally characterized by mass spectrometry. Strains with high activity towards gluten were typed as Rothia mucilaginosa and Rothia aeria. Gliadins (250 mu g/ml) added to Rothia cell suspensions (OD(620) 1.2) were degraded by 50% after similar to 30 min of incubation. Importantly, the 33-mer and 26-mer immunogenic peptides were also cleaved, primarily C-terminal to Xaa-Pro-Gln (XPQ) and Xaa-Pro-Tyr (XPY). The major gliadin-degrading enzymes produced by the Rothia strains were similar to 70-75 kDa in size, and the enzyme expressed by Rothia aeria was active over a wide pH range (pH 3-10).
Conclusion/Significance: While the human digestive enzyme system lacks the capacity to cleave immunogenic gluten, such activities are naturally present in the oral microbial enzyme repertoire. The identified bacteria may be exploited for physiologic degradation of harmful gluten peptides.
C1 [Zamakhchari, Maram; Wei, Guoxian; Lee, Jaeseop; Oppenheim, Frank G.; Helmerhorst, Eva J.] Boston Univ, Dept Periodontol & Oral Biol, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA.
[Dewhirst, Floyd] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA.
[Schuppan, Detlef] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Sch Med, Boston, MA 02215 USA.
[Schuppan, Detlef] Johannes Gutenberg Univ Mainz, Div Mol & Translat Med, Mainz, Germany.
RP Zamakhchari, M (reprint author), Boston Univ, Dept Periodontol & Oral Biol, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA.
EM helmer@bu.edu
OI Wei, Guoxian/0000-0001-5115-3697; Helmerhorst, Eva/0000-0002-4803-3018
FU National Institutes of Health [DE016937, DK073254, AI078385, DE05672,
DE7652, AI087803, DE18132]
FX This study was supported by grants from the National Institutes of
Health: DE016937 (FD), DK073254 (DS), AI078385 (DS) DE05672 (FO) and
DE7652 (FO) AI087803 (EJH), DE18132 (EJH). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 41
TC 26
Z9 26
U1 1
U2 21
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 SEP 21
PY 2011
VL 6
IS 9
AR e24455
DI 10.1371/journal.pone.0024455
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825HM
UT WOS:000295262100010
PM 21957450
ER
PT J
AU Maleki, N
Becerra, L
Nutile, L
Pendse, G
Brawn, J
Bigal, M
Burstein, R
Borsook, D
AF Maleki, Nasim
Becerra, Lino
Nutile, Lauren
Pendse, Gautam
Brawn, Jennifer
Bigal, Marcelo
Burstein, Rami
Borsook, David
TI Migraine attacks the Basal Ganglia
SO MOLECULAR PAIN
LA English
DT Article
DE Headache; Pain; Migraine; fMRI; Functional Connectivity; Morphometry;
Gray Matter Volume; Basal Ganglia
ID HUMAN BRAIN; CENTRAL SENSITIZATION; PREFRONTAL CORTEX; THERMAL STIMULI;
CEREBRAL-CORTEX; CNS ACTIVATION; SPINY NEURONS; PAIN; HEADACHE; THALAMUS
AB Background: With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF).
Results: In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain.
Conclusions: Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.
C1 [Becerra, Lino; Nutile, Lauren; Pendse, Gautam; Borsook, David] Harvard Univ, Sch Med, Dept Psychiat, PAIN Grp,Brain Imaging Ctr,McLean Hosp, Belmont, MA 02478 USA.
[Maleki, Nasim; Brawn, Jennifer] Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, Boston, MA 02115 USA.
[Becerra, Lino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA.
[Becerra, Lino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
[Bigal, Marcelo] Merck & Co Inc, Merck Investigator Studies Program, N Wales, PA 19454 USA.
[Bigal, Marcelo] Merck & Co Inc, Sci Educ Grp, Merck Res Labs, N Wales, PA 19454 USA.
[Bigal, Marcelo; Borsook, David] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10461 USA.
[Burstein, Rami] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Borsook, D (reprint author), Harvard Univ, Sch Med, Dept Psychiat, PAIN Grp,Brain Imaging Ctr,McLean Hosp, Belmont, MA 02478 USA.
EM dborsook@partners.org
FU NIH [K24 NS064050, R01 NS056195]; Merck and Co.
FX The work was supported in by grants from NIH (K24 NS064050 (NINDS) and
R01 NS056195 (NINDS) to DB) (data collection) and an Investigator
Initiated Grant from Merck and Co. (Data Analysis).
NR 89
TC 57
Z9 60
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-8069
J9 MOL PAIN
JI Mol. Pain
PD SEP 21
PY 2011
VL 7
AR 71
DI 10.1186/1744-8069-7-71
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 832UD
UT WOS:000295833000001
PM 21936901
ER
PT J
AU Ramos, OV
Torterolo, P
Lim, V
Chase, MH
Sampogna, S
Yamuy, J
AF Ramos, Oscar V.
Torterolo, Pablo
Lim, Vincent
Chase, Michael H.
Sampogna, Sharon
Yamuy, Jack
TI The role of mesopontine NGF in sleep and wakefulness
SO BRAIN RESEARCH
LA English
DT Article
DE Neurotrophin; Brainstem; Reticular formation; LDT; PPT;
Immunohistochemistry
ID NERVE GROWTH-FACTOR; PEDUNCULOPONTINE TEGMENTAL NUCLEI; INDUCED ACTIVE
SLEEP; EYE-MOVEMENT SLEEP; NEUROTROPHIN-LIKE IMMUNOREACTIVITY; PONTINE
RETICULAR-FORMATION; RAT SYMPATHETIC NEURONS; REM-SLEEP;
CHOLINE-ACETYLTRANSFERASE; BRAIN-STEM
AB The microinjection of nerve growth factor (NGF) into the cat pontine tegmentum rapidly induces rapid eye movement (REM) sleep. To determine if NGF is involved in naturally-occurring REM sleep, we examined whether it is present in mesopontine cholinergic structures that promote the initiation of REM sleep, and whether the blockade of NGF production in these structures suppresses REM sleep. We found that cholinergic neurons in the cat dorso-lateral mesopontine tegmentum exhibited NGF-like immunoreactivity. In addition, the microinjection of an oligodeoxyribonucleotide (OD) directed against cat NGF mRNA into this region resulted in a reduction in the time spent in REM sleep in conjunction with an increase in the time spent in wakefulness. Sleep and wakefulness returned to baseline conditions 2 to 5 days after antisense OD administration. The preceding antisense OD-induced effects occurred in conjunction with the suppression of NGF-like immunoreactivity within the site of antisense OD injection. These data support the hypothesis that NGF is involved in the modulation of naturally-occurring sleep and wakefulness. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Yamuy, Jack] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Ramos, Oscar V.; Lim, Vincent; Chase, Michael H.; Sampogna, Sharon] Websci Int, Los Angeles, CA 90024 USA.
[Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA.
[Torterolo, Pablo] Univ Republica, Fac Med, Dept Fisiol, Montevideo, Uruguay.
RP Yamuy, J (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
EM jyamuy@ucla.edu
FU USPHS [MH59284]
FX Supported by USPHS grant MH59284. The authors thank Trent Wenzel for his
excellent technical assistance.
NR 64
TC 1
Z9 2
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD SEP 21
PY 2011
VL 1413
BP 9
EP 23
DI 10.1016/j.brainres.2011.06.066
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 825QM
UT WOS:000295297200002
PM 21840513
ER
PT J
AU Scarcelli, G
Kim, P
Yun, SH
AF Scarcelli, Giuliano
Kim, Pilhan
Yun, Seok Hyun
TI In Vivo Measurement of Age-Related Stiffening in the Crystalline Lens by
Brillouin Optical Microscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID EYE LENS; ELASTIC PROPERTIES; REFRACTIVE-INDEX; LIGHT-SCATTERING;
NUCLEAR CATARACT; BOVINE LENS; PRESBYOPIA; STIFFNESS; TRANSPARENCY;
BIOMECHANICS
AB The biophysical and biomechanical properties of the crystalline lens (e.g., viscoelasticity) have long been implicated in accommodation and vision problems, such as presbyopia and cataracts. However, it has been difficult to measure such parameters noninvasively. Here, we used in vivo Brillouin optical microscopy to characterize material acoustic properties at GHz frequency and measure the longitudinal elastic moduli of lenses. We obtained three-dimensional elasticity maps of the lenses in live mice, which showed biomechanical heterogeneity in the cortex and nucleus of the lens with high spatial resolution. An in vivo longitudinal study of mice over a period of 2 months revealed a marked age-related stiffening of the lens nucleus. We found remarkably good correlation (log-log linear) between the Brillouin elastic modulus and the Young's modulus measured by conventional mechanical techniques at low frequencies (similar to 1 Hz). Our results suggest that Brillouin microscopy is potentially useful for basic and animal research and clinical ophthalmology.
C1 [Scarcelli, Giuliano; Kim, Pilhan; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Scarcelli, Giuliano; Kim, Pilhan; Yun, Seok Hyun] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Yun, Seok Hyun] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA.
RP Yun, SH (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM syun@hms.harvard.edu
RI Kim, Pilhan/C-1836-2011;
OI Kim, Pilhan/0000-0001-8388-1840; scarcelli, giuliano/0000-0002-1736-077X
FU National Institutes of Health [R2 1EB008472]; National Science of
Foundation [CBET-0853773]; Department of Defense [FA9550-04-1-0079];
Center for Integration of Medical Innovation and Technology; Milton
Foundation; Tosteson Fellowship
FX This work was supported by grants from the National Institutes of Health
(R2 1EB008472), National Science of Foundation (CBET-0853773),
Department of Defense (FA9550-04-1-0079), Center for Integration of
Medical Innovation and Technology, and Milton Foundation. G.S received
financial support from the Tosteson Fellowship.
NR 42
TC 41
Z9 42
U1 2
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD SEP 21
PY 2011
VL 101
IS 6
BP 1539
EP 1545
DI 10.1016/j.bpj.2011.08.008
PG 7
WC Biophysics
SC Biophysics
GA 824JD
UT WOS:000295197300029
PM 21943436
ER
PT J
AU McCarthy, DM
Zhang, X
Darnell, SB
Sangrey, GR
Yanagawa, Y
Sadri-Vakili, G
Bhide, PG
AF McCarthy, Deirdre M.
Zhang, Xuan
Darnell, Shayna B.
Sangrey, Gavin R.
Yanagawa, Yuchio
Sadri-Vakili, Ghazaleh
Bhide, Pradeep G.
TI Cocaine Alters BDNF Expression and Neuronal Migration in the Embryonic
Mouse Forebrain
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; CELL-CYCLE EXIT; PRENATAL COCAINE;
CEREBRAL-CORTEX; CORTICAL-NEURONS; INTERNEURON MIGRATION; DEVELOPING
NEOCORTEX; PROTEIN EXPRESSION; BASAL FOREBRAIN; D-3 RECEPTOR
AB Prenatal cocaine exposure impairs brain development and produces lasting alterations in cognitive function. In a prenatal cocaine exposure mouse model, we found that tangential migration of GABA neurons from the basal to the dorsal forebrain and radial neuron migration within the dorsal forebrain were significantly decreased during the embryonic period. The decrease in the tangential migration occurred early in gestation and normalized by late gestation, despite ongoing cocaine exposure. The decrease in radial migration was associated with altered laminar positioning of neurons in the medial prefrontal cortex. The cocaine exposure led to transient decreases in the expression of Tbr2 and Tbr1, transcription factors associated with intermediate progenitor cells and newborn neurons of the dorsal forebrain, respectively, although neurogenesis was not significantly altered. Since cocaine can modulate brain derived neurotrophic factor (BDNF) expression in the mature brain, we examined whether cocaine can alter BDNF expression in the embryonic brain. We found a transient decrease in BDNF protein expression in the cocaine-exposed embryonic forebrain early in gestation. By late gestation, the BDNF expression recovered to control levels, despite ongoing cocaine exposure. In basal forebrain explants from cocaine-exposed embryos, cell migration was significantly decreased, corroborating the in vivo data on tangential GABA neuron migration. Since BDNF can influence tangential neuronal migration, we added BDNF to the culture medium and observed increased cell migration. Our data suggest that cocaine can alter tangential and radial neuronal migration as well as BDNF expression in the embryonic brain and that decreased BDNF may mediate cocaine's effects on neuronal migration.
C1 [McCarthy, Deirdre M.; Zhang, Xuan; Bhide, Pradeep G.] Harvard Univ, Dept Neurol, MassGen Inst Neurodegenerat Dis, Sch Med, Charlestown, MA 02129 USA.
[Darnell, Shayna B.; Sangrey, Gavin R.; Sadri-Vakili, Ghazaleh] Harvard Univ, NeuroEpigenetcis Lab, MassGen Inst Neurodegenerat Dis, Sch Med, Charlestown, MA 02129 USA.
[Darnell, Shayna B.; Sangrey, Gavin R.; Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Yanagawa, Yuchio] Gunma Univ, Grad Sch Med, Gunma 3718511, Japan.
RP Bhide, PG (reprint author), Florida State Univ, Coll Med, 1115 W Call St, Tallahassee, FL 32306 USA.
EM Pradeep.Bhide@med.fsu.edu
OI Bhide, Pradeep/0000-0003-4236-9415
FU U.S. Public Health Service [RO1DA020796, P30NS045776, R01DA022339]
FX This work was supported by U.S. Public Health Service Grants
RO1DA020796, P30NS045776, and R01DA022339. We are grateful to Igor
Bagayev for expert assistance with confocal microscopy and to the staff
of the Massachusetts General Hospital's Center for Comparative Medicine
for expert assistance with mouse colony management and drug
administration.
NR 65
TC 19
Z9 21
U1 0
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 21
PY 2011
VL 31
IS 38
BP 13400
EP 13411
DI 10.1523/JNEUROSCI.2944-11.2011
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 822XG
UT WOS:000295083300006
PM 21940433
ER
PT J
AU Schierberl, K
Hao, J
Tropea, TF
Ra, S
Giordano, TP
Xu, QH
Garraway, SM
Hofmann, F
Moosmang, S
Striessnig, J
Inturrisi, CE
Rajadhyaksha, AM
AF Schierberl, Kathryn
Hao, Jin
Tropea, Thomas F.
Ra, Stephen
Giordano, Thomas P.
Xu, Qinghao
Garraway, Sandra M.
Hofmann, Franz
Moosmang, Sven
Striessnig, Joerg
Inturrisi, Charles E.
Rajadhyaksha, Anjali M.
TI Ca(v)1.2 L-Type Ca2+ Channels Mediate Cocaine-Induced GluA1 Trafficking
in the Nucleus Accumbens, a Long-Term Adaptation Dependent on Ventral
Tegmental Area Ca(v)1.3 Channels
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PROTEIN-KINASE-II; INDUCED BEHAVIORAL SENSITIZATION; EVOKED SYNAPTIC
PLASTICITY; AMPA RECEPTOR PLASTICITY; CORD DORSAL-HORN;
CALCIUM-CHANNELS; CREB PHOSPHORYLATION; GLUR1 PHOSPHORYLATION; SURFACE
EXPRESSION; GLUTAMATE-RECEPTOR
AB AMPA receptor (AMPAR) plasticity at glutamatergic synapses in the mesoaccumbal dopaminergic pathway has been implicated in persistent cocaine-induced behavioral responses; however, the precise mechanism underlying these changes remains unknown. Utilizing cocaine psychomotor sensitization, we have examined phosphorylation of GluA1 at key residues serine 845 (S845) and S831, as well as GluA1 cell surface levels in the nucleus accumbens (NAc) of cocaine-preexposed mice and the role of brain-specific Ca(v)1.2 and Ca(v)1.3 L-type Ca2+ channels (LTCCs), therein. We found higher basal levels of S845 phospho-GluA1 (P-GluA1) and cell surface GluA1 in the NAc following protracted withdrawal from cocaine exposure, changes that occur independently of LTCCs. In contrast, we found that a cocaine challenge that elicits expression of the cocaine-sensitized response increases S831 P-GluA1 that further increases surface GluA1 beyond the higher basal levels. Intra-NAc pharmacological manipulations indicate that the Ca(v)1.2-activated CaM kinase II (CaMKII) mediates cocaine-induced increase in S831 P-GluA1 and that both Ca(v)1.2-activated CaMKII and extracellular signal-regulated kinase 2 (ERK2) mediate the increase in GluA1 cell surface levels specific to the sensitized response. Experiments using adenoassociated viral vectors expressing Ca(v)1.3 and ERK2 siRNA further indicate that recruitment of the Cav1.2 pathway in the NAc is dependent on ventral tegmental area Ca(v)1.3 LTCCs and ERK2. Together, these results identify candidate pathways that mediate cocaine-induced AMPAR plasticity in the NAc and provide a mechanism linking LTCCs and GluA1 plasticity to cocaine-induced persistent behavioral changes.
C1 [Schierberl, Kathryn; Xu, Qinghao; Inturrisi, Charles E.; Rajadhyaksha, Anjali M.] Weill Cornell Med Coll, Grad Program Neurosci, New York, NY 10065 USA.
[Hao, Jin; Tropea, Thomas F.; Ra, Stephen; Giordano, Thomas P.; Rajadhyaksha, Anjali M.] Weill Cornell Med Coll, Dept Pediat, Div Pediat Neurol, New York, NY 10065 USA.
[Garraway, Sandra M.; Inturrisi, Charles E.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA.
[Giordano, Thomas P.; Rajadhyaksha, Anjali M.] Harvard Univ, Martinos Ctr Biomed Engn, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA.
[Hofmann, Franz] Tech Univ Munich, Res Grp 923, D-80802 Munich, Germany.
[Moosmang, Sven] Tech Univ Munich, Inst Pharmacol, D-80802 Munich, Germany.
[Striessnig, Joerg] Inst Pharm Pharmacol & Toxicol, A-6020 Innsbruck, Austria.
RP Rajadhyaksha, AM (reprint author), Weill Cornell Med Coll, Grad Program Neurosci, 1300 York Ave,Box 91, New York, NY 10065 USA.
EM amr2011@med.cornell.edu
RI Inturrisi, Charles/E-7365-2013
FU NIDA [K01 DA14057, R21 DA023686, DA007274-19, DA001457, DA000198,
DA005130]; Austrian Science Fund [P20670]; Deutsche
Forschungsgemeinschaft
FX This work was supported by NIDA Grants K01 DA14057 (A.M.R.), R21
DA023686 (A.M.R.), and DA007274-19 (K.S.), Austrian Science Fund P20670
(J.S.), Deutsche Forschungsgemeinschaft (F.H., S.M.), and NIDA Grants
DA001457, DA000198, and DA005130 (C.E.I.). We thank Michael J. Glass,
Andrew A. Pieper, and Anni S. Lee for their helpful suggestions in
manuscript preparation and Barry A. Kosofsky for useful discussions.
NR 82
TC 36
Z9 37
U1 2
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 21
PY 2011
VL 31
IS 38
BP 13562
EP 13575
DI 10.1523/JNEUROSCI.2315-11.2011
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 822XG
UT WOS:000295083300020
PM 21940447
ER
PT J
AU Devor, A
Sakadzic, S
Saisan, PA
Yaseen, MA
Roussakis, E
Srinivasan, VJ
Vinogradov, SA
Rosen, BR
Buxton, RB
Dale, AM
Boas, DA
AF Devor, Anna
Sakadzic, Sava
Saisan, Payam A.
Yaseen, Mohammad A.
Roussakis, Emmanuel
Srinivasan, Vivek J.
Vinogradov, Sergei A.
Rosen, Bruce R.
Buxton, Richard B.
Dale, Anders M.
Boas, David A.
TI "Overshoot" of O-2 Is Required to Maintain Baseline Tissue Oxygenation
at Locations Distal to Blood Vessels
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SOMATOSENSORY CORTEX; OXIDATIVE-METABOLISM; 2-PHOTON MICROSCOPY;
PARTIAL-PRESSURE; CEREBRAL-CORTEX; FLOW; TENSION; STIMULATION;
ACTIVATION; PHOSPHORESCENCE
AB In vivo imaging of cerebral tissue oxygenation is important in defining healthy physiology and pathological departures associated with cerebral disease. We used a recently developed two-photon microscopy method, based on a novel phosphorescent nanoprobe, to image tissue oxygenation in the rat primary sensory cortex in response to sensory stimulation. Our measurements showed that a stimulus-evoked increase in tissue pO(2) depended on the baseline pO(2) level. In particular, during sustained stimulation, the steady-state pO(2) at low-baseline locations remained at the baseline, despite large pO(2) increases elsewhere. In contrast to the steady state, where pO(2) never decreased below the baseline, transient decreases occurred during the "initial dip" and "poststimulus undershoot." These results suggest that the increase in blood oxygenation during the hemodynamic response, which has been perceived as a paradox, may serve to prevent a sustained oxygenation drop at tissue locations that are remote from the vascular feeding sources.
C1 [Devor, Anna; Saisan, Payam A.; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Devor, Anna; Buxton, Richard B.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA.
[Devor, Anna; Sakadzic, Sava; Yaseen, Mohammad A.; Srinivasan, Vivek J.; Rosen, Bruce R.; Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02114 USA.
[Roussakis, Emmanuel; Vinogradov, Sergei A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
RP Devor, A (reprint author), Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
EM adevor@ucsd.edu
FU NINDS [NS051188, NS057198, NS057476, NS055104]; NIBIB [EB00790,
EB009118, EB2066, EB007279]
FX We gratefully acknowledge support from NINDS (Grants NS051188 and
NS057198 to A. D., NS057476 and NS055104 to D. A. B.) and NIBIB (Grants
EB00790 to A. M. D., EB009118 to A. D., EB2066 to B. R. R., and EB007279
to S. A. V.).
NR 32
TC 60
Z9 61
U1 2
U2 8
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 21
PY 2011
VL 31
IS 38
BP 13676
EP 13681
DI 10.1523/JNEUROSCI.1968-11.2011
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 822XG
UT WOS:000295083300031
PM 21940458
ER
PT J
AU Alemozaffar, M
Regan, MM
Cooperberg, MR
Wei, JT
Michalski, JM
Sandler, HM
Hembroff, L
Sadetsky, N
Saigal, CS
Litwin, MS
Klein, E
Kibel, AS
Hamstra, DA
Pisters, LL
Kuban, DA
Kaplan, ID
Wood, DP
Ciezki, J
Dunn, RL
Carroll, PR
Sanda, MG
AF Alemozaffar, Mehrdad
Regan, Meredith M.
Cooperberg, Matthew R.
Wei, John T.
Michalski, Jeff M.
Sandler, Howard M.
Hembroff, Larry
Sadetsky, Natalia
Saigal, Christopher S.
Litwin, Mark S.
Klein, Eric
Kibel, Adam S.
Hamstra, Daniel A.
Pisters, Louis L.
Kuban, Deborah A.
Kaplan, Irving D.
Wood, David P.
Ciezki, Jay
Dunn, Rodney L.
Carroll, Peter R.
Sanda, Martin G.
TI Prediction of Erectile Function Following Treatment for Prostate Cancer
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID QUALITY-OF-LIFE; RADICAL RETROPUBIC PROSTATECTOMY; EXTERNAL-BEAM
RADIOTHERAPY; SEXUAL FUNCTION; INDEX COMPOSITE; UNITED-STATES; OUTCOMES;
SURVIVORS; THERAPY; URINARY
AB Context Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking.
Objective To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics.
Design Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N=1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years' follow-up (n=1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort.
Main Outcome Measures Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment.
Results Two years after prostate cancer treatment, 368 (37% [95% CI, 34%-40%]) of all patients and 335 (48% [95% CI, 45%-52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%-56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual's pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74-0.80] for prostatectomy; 0.87 [95% CI, 0.80-0.94] for external radiotherapy; and 0.90 [95% CI, 0.85-0.95] for brachytherapy).
Conclusion Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. JAMA. 2011;306(11):1205-1214 www.jama.com
C1 [Alemozaffar, Mehrdad; Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02215 USA.
[Kaplan, Irving D.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA USA.
[Regan, Meredith M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Cooperberg, Matthew R.; Sadetsky, Natalia; Carroll, Peter R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
[Wei, John T.; Wood, David P.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA.
[Hamstra, Daniel A.] Univ Michigan, Dept Radiat Oncol, Sch Med, Ann Arbor, MI 48109 USA.
[Dunn, Rodney L.] Univ Michigan, Sch Med, Dept Biostat Core, Ann Arbor, MI USA.
[Michalski, Jeff M.] Washington Univ, Dept Radiat Oncol, St Louis, MO USA.
[Kibel, Adam S.] Washington Univ, Dept Surg, St Louis, MO USA.
[Sandler, Howard M.] Cedars Sinai Med Ctr, Dept Radiat Oncol, Los Angeles, CA 90048 USA.
[Hembroff, Larry] Michigan State Univ, Off Survey Res, Inst Publ Policy & Social Res, E Lansing, MI 48824 USA.
[Saigal, Christopher S.; Litwin, Mark S.] UCLA Ctr Hlth Sci, Dept Urol, Los Angeles, CA USA.
[Litwin, Mark S.] UCLA Ctr Hlth Sci, Dept Hlth Serv, Los Angeles, CA USA.
[Klein, Eric] Cleveland Clin Hosp, Glickman Urol & Kidney Inst, Cleveland, OH USA.
[Ciezki, Jay] Cleveland Clin Hosp, Dept Radiat Oncol, Cleveland, OH USA.
[Pisters, Louis L.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Kuban, Deborah A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
RP Sanda, MG (reprint author), Beth Israel Deaconess Med Ctr, Div Urol, 330 Brookline Ave,Rabb 440, Boston, MA 02215 USA.
EM msanda@bidmc.harvard.edu
RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Wei,
John/E-8967-2012
FU National Institutes of Health (NIH) [R01 CA 95662, 1RC1CA146596];
Takeda; Abbott; Amgen; sanofi-aventis; Dendreon; Radiation Oncology
Institute
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. None of the coauthors have been
compensated specifically for work related to this manuscript other than
having received research support from the National Institutes of Health
(NIH) to cover costs of conducting the study. Dr Cooperberg reported
serving as a consultant for Denreon and Ortho-Centocor and receiving
payment for lectures from Takeda, Abbott, and Amgen. Dr Wei reported
serving as a consultant for Envisioneering Inc and sanofi-aventis;
serving as an expert witness for Genprobe; serving as a proctor for
American Medical Systems; and receiving research funding from
sanofi-aventis. Dr Michaliski reported making donations to charity in
lieu of honoraria for his role as a board member for Elekta Inc,
Augmenix Inc, and Viewray. Dr Sandler reported serving as a consultant
for Varian, Calypso Medical, Millennium-Takeda, and Centocor-Ortho
Biotech. Dr Kibel reported serving as a consultant for Myraid, Caris,
Dendreon, sanofi-aventis, Cougar, and Ferring; receiving payment for
lectures from Dendreon; and holding stock in Myriad. Dr Kuban serving as
a consultant for Ferring Pharmaceuticals and bioTheranostics and as a
lecturer supported by the Radiation Oncology Institute. Dr Wood reported
serving as a consultant for Intuitive Surgical and holding stock in that
company. Dr Carroll reported receiving an institutional research grant
from Abbott. Dr Sanda reported receiving a lecture honnorarium from Eli
Lily. No other authors reported financial disclosures.; The study was
supported by NIH grants R01 CA 95662 and 1RC1CA146596
NR 40
TC 126
Z9 131
U1 2
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 SEP 21
PY 2011
VL 306
IS 11
BP 1205
EP 1214
DI 10.1001/jama.2011.1333
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 822HB
UT WOS:000295033500021
PM 21934053
ER
PT J
AU Barry, MJ
AF Barry, Michael J.
TI Helping Patients Make Better Personal Health Decisions The Promise of
Patient-Centered Outcomes Research
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Barry, Michael J.] Massachusetts Gen Hosp, Div Gen Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA.
[Barry, Michael J.] Harvard Univ, Sch Med, Boston, MA USA.
[Barry, Michael J.] Fdn Informed Med Decis Making, Boston, MA USA.
RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, Med Practices Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM mbarry@partners.org
NR 10
TC 11
Z9 11
U1 0
U2 4
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 SEP 21
PY 2011
VL 306
IS 11
BP 1258
EP 1259
DI 10.1001/jama.2011.1363
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 822HB
UT WOS:000295033500030
PM 21934062
ER
PT J
AU Li, XH
Zhang, D
Liu, B
AF Li, Xinhua
Zhang, Da
Liu, Bob
TI A practical approach to estimate the weighted CT dose index over an
infinite integration length
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; DOSIMETRY; PROFILES; CTDI100
AB The CT scanner-displayed radiation dose information is based on CT dose index (CTDI) over an integration length of 100 mm (CTDI(100)), which is lower than the CTDI over an infinite integration length (CTDI(infinity)). In an adult or a pediatric body CT scan, the limiting equilibrium dose can be established near the central scan plane, and CTDI(infinity) more closely indicates the accumulated dose than CTDI(100). The aim of this study was to (a) evaluate CTDI efficiencies, epsilon (CTDI(100)) = CTDI(100)/CTDI(infinity), for a multi-detector CT (MDCT) scanner, (b) examine the dependences of epsilon (CTDI(100)) on kV, beam width, phantom diameter, phantom length and position in phantom and (c) investigate how to estimate CTDI(infinity) based on the CT scanner-displayed information. We performed a comprehensive Geant4-based simulation study of a clinical CT scanner, and calculated epsilon (CTDI(100)) for a range of parameters. The results were compared with the epsilon (CTDI(100)) data of previous studies. Differences in the epsilon (CTDI(100)) values of these studies were assessed. A broad analysis of the epsilon (CTDI(100)) variations with the above-mentioned parameters was presented. Based on the results, we proposed a practical approach to obtain the weighted CTDI(infinity) using the CT scanner-displayed information. A reference combination of 120 kV and a beam width close to 20 mm can be selected to determine the efficiencies of the weighted CTDI by using either phantom measurements or computer simulations. The results can be applied to estimate the weighted CTDI(infinity) for 80-140 kV and the beam widths within 40 mm. Errors in the weighted CTDI(infinity) due to the variations of kV and beam width can be 5% or less for the MDCT scanners.
C1 [Li, Xinhua; Zhang, Da; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA.
RP Liu, B (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA.
EM bliu7@bics.bwh.harvard.edu
NR 26
TC 15
Z9 15
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 SEP 21
PY 2011
VL 56
IS 18
BP 5789
EP 5803
DI 10.1088/0031-9155/56/18/002
PG 15
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 818WT
UT WOS:000294787300004
PM 21846935
ER
PT J
AU Gu, SX
Gupta, R
Kyprianou, I
AF Gu, Songxiang
Gupta, Rajiv
Kyprianou, Iacovos
TI Computational high-resolution heart phantoms for medical imaging and
dosimetry simulations
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID CARDIAC MR; LEFT-VENTRICLE; SEGMENTATION; MODELS; IMAGES; DISEASE
AB Cardiovascular disease in general and coronary artery disease (CAD) in particular, are the leading cause of death worldwide. They are principally diagnosed using either invasive percutaneous transluminal coronary angiograms or non-invasive computed tomography angiograms (CTA). Minimally invasive therapies for CAD such as angioplasty and stenting are rendered under fluoroscopic guidance. Both invasive and non-invasive imaging modalities employ ionizing radiation and there is concern for deterministic and stochastic effects of radiation. Accurate simulation to optimize image quality with minimal radiation dose requires detailed, gender-specific anthropomorphic phantoms with anatomically correct heart and associated vasculature. Such phantoms are currently unavailable. This paper describes an open source heart phantom development platform based on a graphical user interface. Using this platform, we have developed seven high-resolution cardiac/coronary artery phantoms for imaging and dosimetry from seven high-quality CTA datasets. To extract a phantom from a coronary CTA, the relationship between the intensity distribution of the myocardium, the ventricles and the coronary arteries is identified via histogram analysis of the CTA images. By further refining the segmentation using anatomy-specific criteria such as vesselness, connectivity criteria required by the coronary tree and image operations such as active contours, we are able to capture excellent detail within our phantoms. For example, in one of the female heart phantoms, as many as 100 coronary artery branches could be identified. Triangular meshes are fitted to segmented high-resolution CTA data. We have also developed a visualization tool for adding stenotic lesions to the coronaries. The male and female heart phantoms generated so far have been cross-registered and entered in the mesh-based Virtual Family of phantoms with matched age/gender information. Any phantom in this family, along with user-defined stenoses, can be used to obtain clinically realistic projection images with the Monte Carlo code penMesh for optimizing imaging and dosimetry.
C1 [Gu, Songxiang; Kyprianou, Iacovos] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Gupta, Rajiv] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Gu, SX (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM songxiang.gu@fda.hhs.gov; rgupta1@partners.org;
iacovos.kyprianou@fda.hhs.gov
FU FDA; National Institute of Biomedical Imaging and Bioengineering of the
National Institute of Health; Food and Drug Administration Office of
Women's Health
FX Dr Songxiang Gu was supported in part by a grant from the FDA Critical
Path. Dr Kyprianou's research was supported in part by the National
Institute of Biomedical Imaging and Bioengineering of the National
Institute of Health and by the Food and Drug Administration Office of
Women's Health. Special gratitude is expressed for the help and
recommendations of Dr Rongping Zeng, Dr Aldo Badano, Dr Kyle Myers, Dr
Andreu Badal-Soler, Dr Camille Vidal and Mr Samir Abboud.
NR 46
TC 8
Z9 8
U1 1
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 SEP 21
PY 2011
VL 56
IS 18
BP 5845
EP 5864
DI 10.1088/0031-9155/56/18/005
PG 20
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 818WT
UT WOS:000294787300007
PM 21852725
ER
PT J
AU Shima, K
Morikawa, T
Yamauchi, M
Kuchiba, A
Imamura, Y
Liao, XY
Meyerhardt, JA
Fuchs, CS
Ogino, S
AF Shima, Kaori
Morikawa, Teppei
Yamauchi, Mai
Kuchiba, Aya
Imamura, Yu
Liao, Xiaoyun
Meyerhardt, Jeffrey A.
Fuchs, Charles S.
Ogino, Shuji
TI TGFBR2 and BAX Mononucleotide Tract Mutations, Microsatellite
Instability, and Prognosis in 1072 Colorectal Cancers
SO PLOS ONE
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; POPULATION-BASED SAMPLE; MOLECULAR
PATHOLOGICAL EPIDEMIOLOGY; III COLON-CANCER; DNA METHYLATION; LINE-1
HYPOMETHYLATION; ADJUVANT CHEMOTHERAPY; KRAS MUTATION; BRAF MUTATION;
BETA RECEPTOR
AB Background: Mononucleotide tracts in the coding regions of the TGFBR2 and BAX genes are commonly mutated in microsatellite instability-high (MSI-high) colon cancers. The receptor TGFBR2 plays an important role in the TGFB1 (transforming growth factor-beta, TGF-beta) signaling pathway, and BAX plays a key role in apoptosis. However, a role of TGFBR2 or BAX mononucleotide mutation in colorectal cancer as a prognostic biomarker remains uncertain.
Methodology/Principal Findings: We utilized a database of 1072 rectal and colon cancers in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study). Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusted for clinical, pathological and molecular features including the CpG island methylator phenotype (CIMP), LINE-1 methylation, and KRAS, BRAF and PIK3CA mutations. MSI-high was observed in 15% (162/1072) of all colorectal cancers. TGFBR2 and BAX mononucleotide mutations were detected in 74% (117/159) and 30% (48/158) of MSI-high tumors, respectively. In Kaplan-Meier analysis as well as univariate and multivariate Cox regression analyses, compared to microsatellite stable (MSS)/MSI-low cases, MSI-high cases were associated with superior colorectal cancer-specific survival [adjusted HR, 0.34; 95% confidence interval (CI), 0.20-0.57] regardless of TGFBR2 or BAX mutation status. Among MSI-high tumors, TGFBR2 mononucleotide mutation was associated with CIMP-high independent of other variables [multivariate odds ratio, 3.57; 95% CI, 1.66-7.66; p = 0.0011].
Conclusions: TGFBR2 or BAX mononucleotide mutations are not associated with the patient survival outcome in MSI-high colorectal cancer. Our data do not support those mutations as prognostic biomarkers (beyond MSI) in colorectal carcinoma.
C1 [Shima, Kaori; Morikawa, Teppei; Yamauchi, Mai; Kuchiba, Aya; Imamura, Yu; Liao, Xiaoyun; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Shima, Kaori; Morikawa, Teppei; Yamauchi, Mai; Kuchiba, Aya; Imamura, Yu; Liao, Xiaoyun; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA.
[Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Shima, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
FU United States National Institutes of Health (NIH) [P01CA87969,
P01CA55075, P50CA127003, K07CA122826, R01CA151993]; Bennett Family Fund;
Entertainment Industry Foundation through National Colorectal Cancer
Research Alliance
FX This work was supported by United States National Institutes of Health
(NIH) grants P01CA87969 (to SE Hankinson), P01CA55075 (to WC Willett),
P50CA127003 (to CSF), K07CA122826 (to SO) and R01CA151993 (to SO), and
in part by grants from the Bennett Family Fund and from the
Entertainment Industry Foundation through National Colorectal Cancer
Research Alliance. The content is solely the responsibility of the
authors and does not necessarily represent the official views of NCI or
NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 72
TC 15
Z9 15
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 20
PY 2011
VL 6
IS 9
AR e25062
DI 10.1371/journal.pone.0025062
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825GY
UT WOS:000295260400043
PM 21949851
ER
PT J
AU Lo Re, V
Teal, V
Localio, AR
Amorosa, VK
Kaplan, DE
Gross, R
AF Lo Re, Vincent, III
Teal, Valerie
Localio, A. Russell
Amorosa, Valerianna K.
Kaplan, David E.
Gross, Robert
TI Relationship Between Adherence to Hepatitis C Virus Therapy and
Virologic Outcomes
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; INITIATED ANTIRETROVIRAL THERAPY;
HUMAN-IMMUNODEFICIENCY-VIRUS; PEGINTERFERON ALPHA-2A; COMBINATION
THERAPY; SUSTAINED RESPONSE; PHARMACY RECORDS; VIRAL LOAD; INFECTION;
COMPLICATIONS
AB Background: Adherence to therapy with pegylated interferon and ribavirin for hepatitis C virus (HCV) infection has been incompletely examined.
Objective: To evaluate the relationship between adherence to HCV therapy and early and sustained virologic response, assess changes in adherence over time, and examine risk factors for nonadherence.
Design: Retrospective cohort study.
Setting: National Veterans Affairs Hepatitis C Clinical Case Registry.
Patients: 5706 HCV-infected patients (genotypes 1, 2, 3, or 4) with at least 1 prescription for both pegylated interferon and ribavirin between 2003 and 2006 and HCV RNA results before and after treatment initiation.
Measurements: Adherence was calculated over 12-week intervals by using pharmacy refill data. End points included early virologic response (decrease of >= 2 log(10) HCV RNA at 12 weeks) and sustained virologic response (undetectable HCV RNA 24 weeks after the end of treatment).
Results: Early virologic response increased with higher levels of adherence to ribavirin therapy over the initial 12 weeks (patients with HCV genotype 1 or 4, 25 of 68 [37%] with <= 40% adherence vs. 1367 of 2187 [63%] with 91% to 100% adherence [P < 0.001]; patients with HCV genotype 2 or 3, 12 of 18 [67%] with <= 40% adherence vs. 651 of 713 [91%] with 91% to 100% adherence [P < 0.001]). Among patients with HCV genotype 1 or 4, sustained response increased with higher adherence to ribavirin therapy over the second, third, and fourth 12-week intervals. Results were similar for adherence to interferon therapy. Mean adherence to therapy with interferon and ribavirin decreased by 3.4 and 6.6 percentage points per 12-week interval, respectively (P for trend < 0.001 for each drug). Patients who received growth factors or thyroid medications during treatment had higher mean adherence to antiviral therapy.
Limitation: This was an observational study without standardized timing for outcome measurements.
Conclusion: Early and sustained virologic responses increased with higher levels of adherence to interferon and ribavirin therapy. Adherence to therapy with both antivirals decreased over time, but more so for ribavirin.
C1 [Lo Re, Vincent, III] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Lo Re, V (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM vincentl@mail.med.upenn.edu
RI Lo Re, Vincent/N-7817-2015;
OI Teal, Valerie/0000-0001-7116-5353
FU Department of Veterans Affairs; National Institutes of Health [K01
AI070001]; Agency for Healthcare Research and Quality Centers for
Education and Research on Therapeutics [HS10399]
FX This material is based on work supported in part by the Department of
Veterans Affairs. The contents do not represent the views of the
Department of Veterans Affairs or the U.S. Government.; By grant K01
AI070001 from the National Institutes of Health (Dr. Lo Re), grant
HS10399 from the Agency for Healthcare Research and Quality Centers for
Education and Research on Therapeutics cooperative agreement (Drs. Lo
Re, Localio, and Gross), and a Department of Veterans Affairs
Competitive Pilot Project Fund grant (Drs. Lo Re and Amorosa).
NR 37
TC 27
Z9 27
U1 0
U2 6
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 SEP 20
PY 2011
VL 155
IS 6
BP 353
EP U46
DI 10.7326/0003-4819-155-6-201109200-00003
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 822HA
UT WOS:000295033400014
PM 21930852
ER
PT J
AU Chou, R
Arora, B
Dana, T
Fu, RW
Walker, M
Humphrey, L
AF Chou, Roger
Arora, Bhaskar
Dana, Tracy
Fu, Rongwei
Walker, Miranda
Humphrey, Linda
TI Screening Asymptomatic Adults With Resting or Exercise
Electrocardiography: A Review of the Evidence for the US Preventive
Services Task Force
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Review
ID CORONARY-HEART-DISEASE; MIDDLE-AGED MEN; LEFT-VENTRICULAR HYPERTROPHY;
FACTOR INTERVENTION TRIAL; ST-SEGMENT DEPRESSION; ALL-CAUSE MORTALITY;
APPARENTLY HEALTHY-MEN; CARDIOVASCULAR RISK-FACTORS;
SILENT-MYOCARDIAL-ISCHEMIA; T-WAVE ABNORMALITIES
AB Background: Coronary heart disease is the leading cause of death in adults. Screening for abnormalities by using resting or exercise electrocardiography (ECG) might help identify persons who would benefit from interventions to reduce cardiovascular risk.
Purpose: To update the 2004 U. S. Preventive Services Task Force evidence review on screening for resting or exercise ECG abnormalities in asymptomatic adults.
Data Sources: MEDLINE (2002 through January 2011), the Cochrane Library database (through the fourth quarter of 2010), and reference lists.
Study Selection: Randomized, controlled trials and prospective cohort studies.
Data Extraction: Investigators abstracted details about the study population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria.
Data Synthesis: No study evaluated clinical outcomes or use of risk-reducing therapies after screening versus no screening. No study estimated how accurately resting or exercise electrocardiography classified participants into high-, intermediate-, or low-risk groups, compared with traditional risk factor assessment alone. Sixty-three prospective cohort studies evaluated abnormalities on resting or exercise ECG as predictors of cardiovascular events after adjustment for traditional risk factors. Abnormalities on resting ECG (ST-segment or T-wave abnormalities, left ventricular hypertrophy, bundle branch block, or left-axis deviation) or exercise ECG (ST-segment depression with exercise, chronotropic incompetence, abnormal heart rate recovery, or decreased exercise capacity) were associated with increased risk (pooled hazard ratio estimates, 1.4 to 2.1). Evidence on harms was limited, but direct harms seemed minimal (for resting ECG) or small (for exercise ECG). No study estimated harms from subsequent testing or interventions, although rates of angiography after exercise ECG ranged from 0.6% to 2.9%.
Limitations: Only English-language studies were included. Statistical heterogeneity was present in several of the pooled analyses.
Conclusion: Abnormalities on resting or exercise ECG are associated with an increased risk for subsequent cardiovascular events after adjustment for traditional risk factors, but the clinical implications of these findings are unclear.
C1 [Chou, Roger] Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Mailcode BICC, Portland, OR 97239 USA.
Portland VA Med Ctr, Portland, OR USA.
RP Chou, R (reprint author), Oregon Hlth & Sci Univ, Oregon Evidence Based Practice Ctr, Mailcode BICC, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM chour@ohsu.edu
FU Agency for Healthcare Research and Quality [HHSA-290-2007-10057-I-EPC3]
FX By contract number HHSA-290-2007-10057-I-EPC3, Task Order No. 3, from
the Agency for Healthcare Research and Quality.
NR 100
TC 63
Z9 63
U1 1
U2 8
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 SEP 20
PY 2011
VL 155
IS 6
BP 375
EP U74
DI 10.7326/0003-4819-155-6-201109200-00006
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 822HA
UT WOS:000295033400017
PM 21930855
ER
PT J
AU Jewell, CM
Lopez, SCB
Irvine, DJ
AF Jewell, Christopher M.
Lopez, Sandra C. Bustamante
Irvine, Darrell J.
TI In situ engineering of the lymph node microenvironment via intranodal
injection of adjuvant-releasing polymer particles
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID ANTITUMORAL IMMUNITY; TLR LIGANDS; T-CELLS; ANTIGEN; RESPONSES;
MICROSPHERES; SIZE; IMMUNOTHERAPY; PHAGOCYTOSIS; IMMUNIZATION
AB Recent studies have demonstrated a simple, potentially universal strategy to enhance vaccine potency, via intralymph node (i.LN) injection. To date, intranodal immunization studies have focused on the delivery of unadjuvanted vaccines (e. g., naked DNA, peptide, or protein). We hypothesized that combining i.LN vaccination with controlled release biomaterials permitting sustained dosing of molecular adjuvants to the local tissue microenvironment would further enhance this promising vaccination strategy. To test this idea, we encapsulated the Toll-like receptor-3 ligand poly(inosiniccytidylic acid) (polyIC) in biodegradable poly(lactide-co-glycolide) microparticles (MPs) designed to remain extracellular and release polyIC in the LN over several days. Intranodal injection of MPs increased persistence of polyIC in LNs compared to the same dose of soluble polyIC or polyIC formulated in nanoparticles, leading to increased accumulation of Toll-like receptor agonist in LN-resident antigen presenting cells and more enduring dendritic cell activation. Intralymph node injection of ovalbumin mixed with polyIC-releasing MPs enhanced the humoral response and expanded ovalbumin-specific T cells to frequencies as high as 18% among all CD8(+) cells following a single injection (8.2-fold greater than the same vaccine given i.m.), a response that could not be matched by antigen mixed with polyIC-loaded nanoparticles or a 10-fold greater dose of soluble polyIC. Thus, i.LN immunization with slow release-formulated adjuvants may be a broadly applicable strategy to enhance therapeutic or prophylactic vaccines.
C1 [Jewell, Christopher M.; Lopez, Sandra C. Bustamante; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
[Jewell, Christopher M.; Lopez, Sandra C. Bustamante; Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Jewell, Christopher M.; Irvine, Darrell J.] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA.
[Jewell, Christopher M.; Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Jewell, Christopher M.; Irvine, Darrell J.] Harvard, Charlestown, MA 02129 USA.
RP Irvine, DJ (reprint author), MIT, Dept Mat Sci & Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM djirvine@mit.edu
FU Ragon Institute of Massachusetts General Hospital; Massachusetts
Institute of Technology; Harvard and The Gates Foundation; National
Cancer Institute [P30-CA14051]
FX This work was supported in part by the Ragon Institute of Massachusetts
General Hospital, Massachusetts Institute of Technology, and Harvard and
The Gates Foundation. C.M.J. is a Ragon Institute Postdoctoral Fellow.
D.J.I. is an investigator of the Howard Hughes Medical Institute. Core
facilities were supported by Koch Institute Cancer Center Support Grant
P30-CA14051 (National Cancer Institute).
NR 32
TC 81
Z9 83
U1 6
U2 51
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 SEP 20
PY 2011
VL 108
IS 38
BP 15745
EP 15750
DI 10.1073/pnas.1105200108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822FS
UT WOS:000295030000023
PM 21896725
ER
PT J
AU Saylor, PJ
Lee, RJ
Smith, MR
AF Saylor, Philip J.
Lee, Richard J.
Smith, Matthew R.
TI Emerging Therapies to Prevent Skeletal Morbidity in Men With Prostate
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; ORAL SODIUM
CLODRONATE; PLACEBO-CONTROLLED TRIAL; BONE-MINERAL DENSITY;
DOUBLE-BLIND; ZOLEDRONIC ACID; FRACTURE RISK; SEX STEROIDS; OLDER MEN
AB Skeletal morbidity is a prominent burden to men with advanced prostate cancer throughout the natural history of the disease. Bone metastases can cause pain and greatly elevate the risk for fractures and other structural complications. Distinct from the problem of metastases, treatment-related osteoporosis and associated fragility fractures are potential complications of androgen-deprivation therapy. Bone-targeted therapies for prostate cancer have therefore been the focus of considerable research and drug development efforts. The osteoclast is a validated therapeutic target in the management of prostate cancer. Osteoclast inhibition with zoledronic acid (a bisphosphonate) or with denosumab (a monoclonal antibody to RANK ligand) reduces risk for skeletal events in men with castration-resistant prostate cancer metastatic to bone. Osteoclast inhibition with any of several bisphosphonates improves bone mineral density, a surrogate for osteoporotic fracture risk. Denosumab and toremifene (a selective estrogen receptor modulator) have each been shown to reduce osteoporotic fracture risk among men receiving androgen-deprivation therapy. Beta-emitting radiopharmaceuticals reduce pain due to metastatic disease. Investigations involving alpha-emitting radium-223, endothelin-A receptor antagonists atrasentan and zibotentan, proto-oncogene tyrosine-protein kinase (SRC) inhibitor dasatinib, and tyrosine kinase inhibitor cabozantinib (XL184) are ongoing in clinical trials and are also discussed.
C1 [Saylor, Philip J.] Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA.
RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA.
EM psaylor@partners.org
FU Prostate Cancer Foundation; American Society of Clinical Oncology (ASCO)
Cancer Foundation; Physician Research Training Award (Prostate Cancer
Research Program, Department of Defense); National Institutes of Health
[5K24CA121990-02]
FX Supported by Young Investigator Awards from the Prostate Cancer
Foundation and American Society of Clinical Oncology (ASCO) Cancer
Foundation (P. J. S.), by a Physician Research Training Award (Prostate
Cancer Research Program, Department of Defense) and a Career Development
Award from the ASCO Cancer Foundation (R. J. L.), and by National
Institutes of Health K24 Midcareer Investigator Award No.
5K24CA121990-02 and awards from the Prostate Cancer Foundation (M.R.S.).
NR 73
TC 38
Z9 38
U1 0
U2 4
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 SEP 20
PY 2011
VL 29
IS 27
BP 3705
EP 3714
DI 10.1200/JCO.2010.34.4994
PG 10
WC Oncology
SC Oncology
GA 821CL
UT WOS:000294952300016
PM 21860001
ER
PT J
AU Arnaout, A
Leblebjian, H
Bartel, S
Hassett, MJ
AF Arnaout, A.
Leblebjian, H.
Bartel, S.
Hassett, M. J.
TI Relative dose intensity (RDI) assessment in an academic center.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 [Arnaout, A.; Leblebjian, H.; Bartel, S.; Hassett, M. J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 139
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600134
PM 27958144
ER
PT J
AU Arun, B
Biswas, S
Tankhiwale, N
Blackford, AL
Gutierrez-Barrera, AM
Litton, JK
Hortobagy, GN
Amos, CI
Parmigiani, G
AF Arun, B.
Biswas, S.
Tankhiwale, N.
Blackford, A. L.
Gutierrez-Barrera, A. M.
Litton, J. K.
Hortobagy, G. N.
Amos, C. I.
Parmigiani, G.
TI Assessing the added value of breast tumor markers in breast cancer
genetic risk prediction model BRCAPRO
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ N Texas, Hlth Sci Ctr, Ft Worth, TX USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 164
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600158
PM 27957957
ER
PT J
AU Buckley, JM
Coopey, S
Samphao, S
Specht, MC
Hughes, KS
Gadd, M
Taghian, AG
Smith, BL
AF Buckley, J. M.
Coopey, S.
Samphao, S.
Specht, M. C.
Hughes, K. S.
Gadd, M.
Taghian, A. G.
Smith, B. L.
TI Recurrence rates and long-term survival in women diagnosed with breast
cancer at age 40 and younger
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 [Buckley, J. M.; Coopey, S.; Samphao, S.; Specht, M. C.; Hughes, K. S.; Gadd, M.; Taghian, A. G.; Smith, B. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 70
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600068
PM 27958096
ER
PT J
AU Carp, SA
Wanyo, C
Specht, MC
Schapira, L
Moy, B
Finkelstein, DM
Boas, D
Isakoff, SJ
AF Carp, S. A.
Wanyo, C.
Specht, M. C.
Schapira, L.
Moy, B.
Finkelstein, D. M.
Boas, D.
Isakoff, S. J.
TI Functional metabolic tomographic optical breast imaging (TOBI) to
monitor response to neoadjuvant therapy in breast cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Charlestown, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 60
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600058
PM 27958134
ER
PT J
AU Childs, SK
Chen, Y
Pochebit, S
Golshan, M
Duggan, MM
Wong, JS
Harris, JR
Bellon, JR
AF Childs, S. K.
Chen, Y.
Pochebit, S.
Golshan, M.
Duggan, M. M.
Wong, J. S.
Harris, J. R.
Bellon, J. R.
TI Surgical margins and the risk of local-regional recurrence (LRR)
following mastectomy for early-stage breast cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Radiat Oncol Program, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Faulkner Hosp, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 95
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600092
PM 27957926
ER
PT J
AU Hattangadi, JA
Taback, N
Neville, BA
Harris, JR
Punglia, RS
AF Hattangadi, J. A.
Taback, N.
Neville, B. A.
Harris, J. R.
Punglia, R. S.
TI Accelerated partial breast irradiation using brachytherapy (APBIb) for
breast cancer (bca): Predictors of use and guideline concordance
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Harvard Radiat Oncol Program, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 84
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600082
PM 27958075
ER
PT J
AU Schneider, BP
Wang, M
Stearns, V
Martino, S
Jones, VE
Perez, EA
Saphner, TJ
Wolff, AC
Sledge, GW
Wood, W
Davidson, NE
Sparano, JA
AF Schneider, B. P.
Wang, M.
Stearns, V.
Martino, S.
Jones, V. E.
Perez, E. A.
Saphner, T. J.
Wolff, A. C.
Sledge, G. W.
Wood, W.
Davidson, N. E.
Sparano, J. A.
TI Relationship between taxane-induced neuropathy and clinical outcomes
after adjuvant chemotherapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Angeles Clin & Res Inst, Santa Monica, CA USA.
North Star Lodge Canc Ctr, Yakima, WA USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Green Bay Oncol, Green Bay, WI USA.
Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
Emory Univ Hosp, Atlanta, GA 30322 USA.
Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Albert Einstein Coll Med, Bronx, NY 10467 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 270
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600256
PM 27957989
ER
PT J
AU Sgroi, D
Carney, E
Richardson, E
Steffel, L
Binns, SN
Finkelstein, DM
Shepherd, LE
Kesty, NC
Schnabel, C
Erlander, MG
Ingle, JN
Porter, P
Paik, S
Muss, HB
Pritchard, KI
Tu, D
Goss, PE
AF Sgroi, D.
Carney, E.
Richardson, E.
Steffel, L.
Binns, S. N.
Finkelstein, D. M.
Shepherd, L. E.
Kesty, N. C.
Schnabel, C.
Erlander, M. G.
Ingle, J. N.
Porter, P.
Paik, S.
Muss, H. B.
Pritchard, K. I.
Tu, D.
Goss, P. E.
TI Prediction of late recurrences by breast cancer index in the NCIC CTG
MA.17 cohort
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
BioTheranostics Inc, San Diego, CA USA.
Mayo Clin, Rochester, MN USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
NCIC Clin Trials Grp, Kingston, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 2
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600003
PM 27958176
ER
PT J
AU Sperduto, PW
Kased, N
Roberge, D
Shanley, R
Chao, ST
Bhatt, AK
Brown, PD
Shih, HA
Kirkpatrick, J
Gaspar, LE
AF Sperduto, P. W.
Kased, N.
Roberge, D.
Shanley, R.
Chao, S. T.
Bhatt, A. K.
Brown, P. D.
Shih, H. A.
Kirkpatrick, J.
Gaspar, L. E.
CA Graded Prognostic Assessment
TI The effect of tumor subtype on survival and the graded prognostic
assessment (GPA) for patients with breast cancer and brain metastases.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Minnesota, Gamma Knife Ctr, Waconia, MN USA.
Minneapolis Radiat Oncol, Waconia, MN USA.
Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA.
McGill Univ, Dept Radiat Oncol, Ctr Hlth, Montreal, PQ H3A 2T5, Canada.
Univ Minnesota, Minneapolis, MN USA.
Cleveland Clin Fdn, Cleveland, OH 44195 USA.
Univ Wisconsin Hosp, Dept Radiat Oncol, Madison, WI USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
Duke Univ, Med Ctr, Durham, NC USA.
Univ Colorado Denver, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 238
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600227
PM 27958084
ER
PT J
AU Valero, M
Dominici, LS
Golshan, M
AF Valero, M.
Dominici, L. S.
Golshan, M.
TI Use of intraoperative digital specimen mammography to improve operative
efficiency.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2011
VL 29
IS 27
SU S
MA 138
PG 1
WC Oncology
SC Oncology
GA V31JT
UT WOS:000208880600133
PM 27958142
ER
PT J
AU Lucero, CA
Oda, G
Cox, K
Maldonado, F
Lombardo, J
Wojcik, R
Holodniy, M
AF Lucero, Cynthia A.
Oda, Gina
Cox, Kenneth
Maldonado, Frank
Lombardo, Joseph
Wojcik, Richard
Holodniy, Mark
TI Enhanced health event detection and influenza surveillance using a joint
Veterans Affairs and Department of Defense biosurveillance application
SO BMC MEDICAL INFORMATICS AND DECISION MAKING
LA English
DT Article
ID COMMUNITY-BASED EPIDEMICS; SYNDROMIC SURVEILLANCE; OUTBREAK DETECTION;
EARLY NOTIFICATION; SYSTEM
AB Background: The establishment of robust biosurveillance capabilities is an important component of the U.S. strategy for identifying disease outbreaks, environmental exposures and bioterrorism events. Currently, U.S. Departments of Defense (DoD) and Veterans Affairs (VA) perform biosurveillance independently. This article describes a joint VA/DoD biosurveillance project at North Chicago-VA Medical Center (NC-VAMC). The Naval Health Clinics-Great Lakes facility physically merged with NC-VAMC beginning in 2006 with the full merger completed in October 2010 at which time all DoD care and medical personnel had relocated to the expanded and remodeled NC-VAMC campus and the combined facility was renamed the Lovell Federal Health Care Center (FHCC). The goal of this study was to evaluate disease surveillance using a biosurveillance application which combined data from both populations.
Methods: A retrospective analysis of NC-VAMC/Lovell FHCC and other Chicago-area VAMC data was performed using the ESSENCE biosurveillance system, including one infectious disease outbreak (Salmonella/Taste of Chicago-July 2007) and one weather event (Heat Wave-July 2006). Influenza-like-illness (ILI) data from these same facilities was compared with CDC/Illinois Sentinel Provider and Cook County ESSENCE data for 2007-2008.
Results: Following consolidation of VA and DoD facilities in North Chicago, median number of visits more than doubled, median patient age dropped and proportion of females rose significantly in comparison with the pre-merger NC-VAMC facility. A high-level gastrointestinal alert was detected in July 2007, but only low-level alerts at other Chicago-area VAMCs. Heat-injury alerts were triggered for the merged facility in June 2006, but not at the other facilities. There was also limited evidence in these events that surveillance of the combined population provided utility above and beyond the VA-only and DoD-only components. Recorded ILI activity for NC-VAMC/Lovell FHCC was more pronounced in the DoD component, likely due to pediatric data in this population. NCVAMC/Lovell FHCC had two weeks of ILI activity exceeding both the Illinois State and East North Central Regional baselines, whereas Hines VAMC had one and Jesse Brown VAMC had zero.
Conclusions: Biosurveillance in a joint VA/DoD facility showed potential utility as a tool to improve surveillance and situational awareness in an area with Veteran, active duty and beneficiary populations. Based in part on the results of this pilot demonstration, both agencies have agreed to support the creation of a combined VA/DoD ESSENCE biosurveillance system which is now under development.
C1 [Lucero, Cynthia A.; Oda, Gina; Holodniy, Mark] US Dept Vet Affairs, Off Publ Hlth, Off Publ Hlth Surveillance & Res, Palo Alto, CA 94304 USA.
[Cox, Kenneth] Armed Forces Hlth Surveillance Ctr, Med Informat Project, Silver Spring, MD 20910 USA.
[Cox, Kenneth] Armed Forces Hlth Surveillance Ctr, Special Project, Silver Spring, MD 20910 USA.
[Maldonado, Frank] US Dept Vet Affairs, Captain James A Lovell Fed Hlth Care Ctr, N Chicago, IL 60064 USA.
[Lombardo, Joseph; Wojcik, Richard] Johns Hopkins Univ, Appl Phys Lab, ESSENCE Grp, Laurel, MD 20723 USA.
RP Lucero, CA (reprint author), US Dept Vet Affairs, Off Publ Hlth, Off Publ Hlth Surveillance & Res, 3801 Miranda Ave 132, Palo Alto, CA 94304 USA.
EM cynthia.lucero@va.gov
NR 37
TC 6
Z9 7
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6947
J9 BMC MED INFORM DECIS
JI BMC Med. Inform. Decis. Mak.
PD SEP 19
PY 2011
VL 11
AR 56
DI 10.1186/1472-6947-11-56
PG 12
WC Medical Informatics
SC Medical Informatics
GA 832DE
UT WOS:000295781100001
PM 21929813
ER
PT J
AU Merquiol, E
Uzi, D
Mueller, T
Goldenberg, D
Nahmias, Y
Xavier, RJ
Tirosh, B
Shibolet, O
AF Merquiol, Emmanuelle
Uzi, Dotan
Mueller, Tobias
Goldenberg, Daniel
Nahmias, Yaakov
Xavier, Ramnik J.
Tirosh, Boaz
Shibolet, Oren
TI HCV Causes Chronic Endoplasmic Reticulum Stress Leading to Adaptation
and Interference with the Unfolded Protein Response
SO PLOS ONE
LA English
DT Article
ID HEPATITIS-C VIRUS; ER STRESS; SUBGENOMIC REPLICONS; VIRAL REPLICATION;
OXIDATIVE STRESS; PHOSPHATASE 2A; CORE PROTEIN; CELL-CULTURE; IN-VITRO;
TRANSCRIPTION
AB Background: The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded. This stress induces a cyto-protective signaling cascades termed the unfolded protein response (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic sub-lethal ER stress causes cells to adapt by attenuation of UPR activation. Hepatitis C virus (HCV), a major human pathogen, was shown to cause ER stress, however it is unclear whether HCV induces chronic ER stress, and if so whether adaptation mechanisms are initiated. We wanted to characterize the kinetics of HCV-induced ER stress during infection and assess adaptation mechanisms and their significance.
Methods and Findings: The HuH7.5.1 cellular system and HCV-transgenic (HCV-Tg) mice were used to characterize HCV-induced ER stress/UPR pathway activation and adaptation. HCV induced a wave of acute ER stress peaking 2-5 days post-infection, which rapidly subsided thereafter. UPR pathways were activated including IRE1 and EIF2 alpha phosphorylation, ATF6 cleavage and XBP-1 splicing. Downstream target genes including GADD34, ERdj4, p58ipk, ATF3 and ATF4 were upregulated. CHOP, a UPR regulated protein was activated and translocated to the nucleus. Remarkably, UPR activity did not return to baseline but remained elevated for up to 14 days post infection suggesting that chronic ER stress is induced. At this time, cells adapted to ER stress and were less responsive to further drug-induced ER stress. Similar results were obtained in HCV-Tg mice. Suppression of HCV by Interferon-alpha 2 alpha treatment, restored UPR responsiveness to ER stress tolerant cells.
Conclusions: Our study shows, for the first time, that HCV induces adaptation to chronic ER stress which was reversed upon viral suppression. These finding represent a novel viral mechanism to manipulate cellular response pathways.
C1 [Merquiol, Emmanuelle; Uzi, Dotan] Hadassah Hebrew Univ, Med Ctr, Div Med, Liver Unit, Jerusalem, Israel.
[Tirosh, Boaz] Fac Med, Sch Pharmacol, Inst Drug Res, Jerusalem, Israel.
[Mueller, Tobias] Charite, CVK, Med Klin MS Hepatol & Gastroenterol, D-13353 Berlin, Germany.
[Goldenberg, Daniel] Hadassah Hebrew Univ, Med Ctr, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel.
[Nahmias, Yaakov] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Rachel & Selim Benin Sch Comp Sci & Engn, Ctr Bioengn, Jerusalem, Israel.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastroenterol Unit, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA.
[Shibolet, Oren] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Gastroenterol & Liver Dis, Liver Unit, IL-69978 Tel Aviv, Israel.
RP Merquiol, E (reprint author), Hadassah Hebrew Univ, Med Ctr, Div Med, Liver Unit, Jerusalem, Israel.
EM orensh@tasmc.health.gov.il
RI Nahmias, Yaakov/H-4725-2013;
OI Nahmias, Yaakov/0000-0002-6051-616X
FU Israel Science Foundation [1668/08, 78/09]; Bi-National Science
Foundation [2007083]; Kamea Scientific Foundation of the Israeli
Government
FX This research was supported by the Morasha Program of Israel Science
Foundation (grant No. 1668/08) and the Bi-National Science Foundation
(grant No. 2007083) to OS and by the Israel Science Foundation (grant
78/09) to BT. DG is supported by the Kamea Scientific Foundation of the
Israeli Government. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 49
TC 53
Z9 55
U1 1
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 SEP 19
PY 2011
VL 6
IS 9
AR e24660
DI 10.1371/journal.pone.0024660
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825FZ
UT WOS:000295257900027
PM 21949742
ER
PT J
AU Shi, DL
Bedford, NM
Cho, HS
AF Shi, Donglu
Bedford, Nicholas M.
Cho, Hoon-Sung
TI Engineered Multifunctional Nanocarriers for Cancer Diagnosis and
Therapeutics
SO SMALL
LA English
DT Review
ID WALLED CARBON NANOTUBES; DIFFUSE OPTICAL TOMOGRAPHY; SEMICONDUCTOR
QUANTUM DOTS; CONTROLLED DRUG-RELEASE; IN-VIVO; MAGNETIC NANOPARTICLES;
BREAST-CANCER; IRON-OXIDE; PROSTATE-CANCER; MACROMOLECULAR THERAPEUTICS
AB This article reviews advances in the design and development of multifunctional carbon-based and/or magnetic nanoparticle systems (or simply 'nanocarriers') for early cancer diagnosis and spatially and temporally controlled therapy. The critical issues in cancer diagnosis and treatment are addressed based on novel nanotechnologies such as real-time in-vivo imaging, drug storage and release, and specific cancer-cell targeting. The implementation of nanocarriers into animal models and the subsequent effectiveness in treating tumors is also reviewed. Recommendations for future research are given.
C1 [Shi, Donglu] Tongji Univ, Inst Adv Mat & Nano Biomed, Shanghai 200092, Peoples R China.
[Shi, Donglu; Bedford, Nicholas M.] Univ Cincinnati, Dept Chem & Mat Engn, Cincinnati, OH 45221 USA.
[Cho, Hoon-Sung] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Cho, Hoon-Sung] Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA.
RP Shi, DL (reprint author), Tongji Univ, Inst Adv Mat & Nano Biomed, Shanghai 200092, Peoples R China.
EM shid@ucmail.uc.edu
FU Dayton Area Graduate Studies Institute
FX The authors would collectively like to thank Dr. Giovanni Pauletti and
Chris Huth (University of Cincinnati) for their critical review and
editing of this manuscript. The authors are grateful to Dr. Haiqing Dong
for developing the schematic drawing of Figure 1. We would also like to
thank Drs. San-Yuan Chen (National Chiao Tung University), Hongjie Dai
(Stanford University), Qinghua Lu (Shanghai Jiao Tong University), James
F. Rusling (University of Connecticut), Z. John Zhang (Georgia Institute
of Technology), and Zhuang Liu (Soochow University) for kindly provides
figures for this review. N.M. Bedford would like to acknowledge the
financial support from the Dayton Area Graduate Studies Institute.
NR 156
TC 55
Z9 58
U1 5
U2 107
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1613-6810
J9 SMALL
JI Small
PD SEP 19
PY 2011
VL 7
IS 18
BP 2549
EP 2567
DI 10.1002/smll.201100436
PG 19
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 826VB
UT WOS:000295382500001
PM 21648074
ER
PT J
AU Barnitz, RA
Chaigne-Delalande, B
Bolton, DL
Lenardo, MJ
AF Barnitz, R. Anthony
Chaigne-Delalande, Benjamin
Bolton, Diane L.
Lenardo, Michael J.
TI Exposed Hydrophobic Residues in Human Immunodeficiency Virus Type 1 Vpr
Helix-1 Are Important for Cell Cycle Arrest and Cell Death
SO PLOS ONE
LA English
DT Article
ID INDUCED G(2) ARREST; HIV-1 VPR; NUCLEAR-LOCALIZATION; VIRION
INCORPORATION; PROTEIN VPR; T-CELLS; UBIQUITIN LIGASE; MUTATIONAL
ANALYSIS; REGULATORY PROTEIN; ACCESSORY PROTEIN
AB The human immunodeficiency virus type 1 (HIV-1) accessory protein viral protein R (Vpr) is a major determinant for virus-induced G2/M cell cycle arrest and cytopathicity. Vpr is thought to perform these functions through the interaction with partner proteins. The NMR structure of Vpr revealed solvent exposed hydrophobic amino acids along helices 1 and 3 of Vpr, which could be putative protein binding domains. We previously showed that the hydrophobic patch along helix-3 was important for G2/M blockade and cytopathicity. Mutations of the exposed hydrophobic residues along helix-1 were found to reduce Vpr-induced cell cycle arrest and cell death as well. The levels of toxicity during virion delivery of Vpr correlated with G2/M arrest. Thus, the exposed hydrophobic amino acids in the amino-terminal helix-1 are important for the cell cycle arrest and cytopathicity functions of Vpr.
C1 [Barnitz, R. Anthony; Chaigne-Delalande, Benjamin; Bolton, Diane L.; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Barnitz, R. Anthony; Lenardo, Michael J.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA.
RP Barnitz, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM lenardo@nih.gov
OI Barnitz, Tony/0000-0002-9634-4558; Tripp, Ralph/0000-0002-2924-9956
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 56
TC 6
Z9 6
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 SEP 16
PY 2011
VL 6
IS 9
AR e24924
DI 10.1371/journal.pone.0024924
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 824BI
UT WOS:000295173800049
PM 21949789
ER
PT J
AU Krajewska, M
You, ZR
Rong, J
Kress, C
Huang, XS
Yang, JS
Kyoda, T
Leyva, R
Banares, S
Hu, Y
Sze, CH
Whalen, MJ
Salmena, L
Hakem, R
Head, BP
Reed, JC
Krajewski, S
AF Krajewska, Maryla
You, Zerong
Rong, Juan
Kress, Christina
Huang, Xianshu
Yang, Jinsheng
Kyoda, Tiffany
Leyva, Ricardo
Banares, Steven
Hu, Yue
Sze, Chia-Hung
Whalen, Michael J.
Salmena, Leonardo
Hakem, Razqallah
Head, Brian P.
Reed, John C.
Krajewski, Stan
TI Neuronal Deletion of Caspase 8 Protects against Brain Injury in Mouse
Models of Controlled Cortical Impact and Kainic Acid-Induced
Excitotoxicity
SO PLOS ONE
LA English
DT Article
ID PROGRAMMED CELL-DEATH; FOCAL CEREBRAL-ISCHEMIA; C-JUN; HEAD-INJURY;
IN-VITRO; ORGANOTYPIC CULTURES; NERVOUS-SYSTEM; JNK ACTIVATION;
APOPTOSIS; MICE
AB Background: Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8(-/-)), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system.
Methodology/Principal Findings: Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNF alpha (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8(-/-) mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging.
Conclusions: Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma.
C1 [Krajewska, Maryla; Rong, Juan; Kress, Christina; Huang, Xianshu; Kyoda, Tiffany; Leyva, Ricardo; Banares, Steven; Sze, Chia-Hung; Reed, John C.; Krajewski, Stan] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
[You, Zerong; Yang, Jinsheng; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA.
[Hu, Yue; Head, Brian P.] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA.
[Hu, Yue] VA San Diego Healthcare Syst, San Diego, CA USA.
[Salmena, Leonardo; Hakem, Razqallah] Ontario Canc Inst, Dept Med Biophys, Toronto, ON M4X 1K9, Canada.
RP Krajewska, M (reprint author), Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
EM jreed@sanfordburnham.org; stan@sanfordburnham.org
FU NIH [NS36821, CA69381]; DoD [W81XWH-08-2-0067, W81XWH-07-1-0569]; VA
CDA-2
FX Supported by the NIH grants (NS36821 [SK]; CA69381 [JCR]) and DoD grants
(W81XWH-08-2-0067 [SK]; W81XWH-07-1-0569 [JCR]); VA CDA-2 [BPH]. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 89
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U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 16
PY 2011
VL 6
IS 9
AR e24341
DI 10.1371/journal.pone.0024341
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 824BI
UT WOS:000295173800020
PM 21957448
ER
PT J
AU Qin, W
Bajaj, V
Malinowska, I
Lu, X
MacConaill, L
Wu, CL
Kwiatkowski, DJ
AF Qin, Wei
Bajaj, Vineeta
Malinowska, Izabela
Lu, Xin
MacConaill, Laura
Wu, Chin-Lee
Kwiatkowski, David J.
TI Angiomyolipoma Have Common Mutations in TSC2 but No Other Common Genetic
Events
SO PLOS ONE
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; LYMPHANGIOLEIOMYOMATOSIS; HETEROZYGOSITY;
ACTIVATION; NEOPLASMS; FREQUENT; PATHWAY; FUTURE; GROWTH; MTOR
AB Renal angiomyolipoma are part of the PEComa family of neoplasms, and occur both in association with Tuberous Sclerosis Complex (TSC) and independent of that disorder. Previous studies on the molecular genetic alterations that occur in angiomyolipoma are very limited. We evaluated 9 angiomyolipoma for which frozen tissue was available from a consecutive surgical series. Seven of 8 samples subjected to RT-PCR-cDNA sequencing showed mutations in TSC2; none showed mutations in TSC1 or RHEB. Six of the seven mutations were deletions. We searched for 983 activating and inactivating mutations in 115 genes, and found none in these tumors. Similarly analysis for genomic regions of loss or gain, assessed by Affymetrix SNP6.0 analysis, showed no abnormalities. Loss of heterozygosity in the TSC2 region was commonly seen, except in patients with low frequency TSC2 mutations. We conclude that sporadic renal angiomyolipoma usually have mutations in TSC2, but not TSC1 or RHEB, and have no other common genomic events, among those we searched for. However, chromosomal translocations and gene fusion events were not assessed here. TSC2 inactivation by mutation is a consistent and likely necessary genetic event in the pathogenesis of most angiomyolipoma.
C1 [Qin, Wei; Bajaj, Vineeta; Malinowska, Izabela; Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, Translat Med Div, Boston, MA 02115 USA.
[Lu, Xin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Lu, Xin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[MacConaill, Laura] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
RP Qin, W (reprint author), Brigham & Womens Hosp, Dept Med, Translat Med Div, 75 Francis St, Boston, MA 02115 USA.
EM dk@rics.bwh.harvard.edu
RI Malinowska, Izabela/A-4816-2013
FU National Institutes of Health [NIH NCI 1P01CA120964-01A1]; NIH NINDS
[4R37NS031535-18]
FX This work was funded by National Institutes of Health grants NIH NCI
1P01CA120964-01A1 and NIH NINDS 4R37NS031535-18. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 25
TC 16
Z9 16
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 SEP 16
PY 2011
VL 6
IS 9
AR e24919
DI 10.1371/journal.pone.0024919
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 824BI
UT WOS:000295173800048
PM 21949787
ER
PT J
AU Williams, BL
Hornig, M
Buie, T
Bauman, ML
Paik, MC
Wick, I
Bennett, A
Jabado, O
Hirschberg, DL
Lipkin, WI
AF Williams, Brent L.
Hornig, Mady
Buie, Timothy
Bauman, Margaret L.
Paik, Myunghee Cho
Wick, Ivan
Bennett, Ashlee
Jabado, Omar
Hirschberg, David L.
Lipkin, W. Ian
TI Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in
the Intestines of Children with Autism and Gastrointestinal Disturbances
SO PLOS ONE
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; ISOMALTASE GENE-EXPRESSION; SPECTRUM
DISORDERS; SUCRASE-ISOMALTASE; DIETARY INTERVENTION; MICROBIAL
COMMUNITY; COLONIC MICROBIOTA; REGRESSIVE AUTISM; VIRAL-INFECTION; GUT
MICROBIOTA
AB Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism.
C1 [Williams, Brent L.; Hornig, Mady; Wick, Ivan; Bennett, Ashlee; Jabado, Omar; Hirschberg, David L.; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
[Buie, Timothy] Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA.
[Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Bauman, Margaret L.] Massachusetts Gen Hosp, LADDERS, Boston, MA 02114 USA.
[Bauman, Margaret L.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Paik, Myunghee Cho] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA.
RP Williams, BL (reprint author), Columbia Univ, Ctr Infect & Immun, New York, NY 10027 USA.
EM wil2001@columbia.edu
FU National Institutes of Health [NS047537]; Google.org; Department of
Defense; Cure Autism Now (CAN)
FX This work was supported by National Institutes of Health (NS047537),
Google.org, Department of Defense, and Cure Autism Now (CAN). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 93
TC 97
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U1 8
U2 39
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 SEP 16
PY 2011
VL 6
IS 9
AR e24585
DI 10.1371/journal.pone.0024585
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 824BI
UT WOS:000295173800029
PM 21949732
ER
PT J
AU Delmore, JE
Issa, GC
Lemieux, ME
Rahl, PB
Shi, JW
Jacobs, HM
Kastritis, E
Gilpatrick, T
Paranal, RM
Qi, J
Chesi, M
Schinzel, AC
McKeown, MR
Heffernan, TP
Vakoc, CR
Bergsagel, PL
Ghobrial, IM
Richardson, PG
Young, RA
Hahn, WC
Anderson, KC
Kung, AL
Bradner, JE
Mitsiades, CS
AF Delmore, Jake E.
Issa, Ghayas C.
Lemieux, Madeleine E.
Rahl, Peter B.
Shi, Junwei
Jacobs, Hannah M.
Kastritis, Efstathios
Gilpatrick, Timothy
Paranal, Ronald M.
Qi, Jun
Chesi, Marta
Schinzel, Anna C.
McKeown, Michael R.
Heffernan, Timothy P.
Vakoc, Christopher R.
Bergsagel, P. Leif
Ghobrial, Irene M.
Richardson, Paul G.
Young, Richard A.
Hahn, William C.
Anderson, Kenneth C.
Kung, Andrew L.
Bradner, James E.
Mitsiades, Constantine S.
TI BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
SO CELL
LA English
DT Article
ID B-CELL LINE; MULTIPLE-MYELOMA; BCL-2 FAMILY; TRANSCRIPTION FACTORS;
TRANSGENIC MICE; SOLID TUMORS; BONE-MARROW; EXPRESSION; CANCER;
ACTIVATION
AB MYC contributes to the pathogenesis of a majority of human cancers, yet strategies to modulate the function of the c-Myc oncoprotein do not exist. Toward this objective, we have targeted MYC transcription by interfering with chromatin-dependent signal transduction to RNA polymerase, specifically by inhibiting the acetyl-lysine recognition domains (bromodomains) of putative coactivator proteins implicated in transcriptional initiation and elongation. Using a selective small-molecule bromodomain inhibitor, JQ1, we identify BET bromodomain proteins as regulatory factors for c-Myc. BET inhibition by JQ1 downregulates MYC transcription, followed by genome-wide downregulation of Myc-dependent target genes. In experimental models of multiple myeloma, a Myc-dependent hematologic malignancy, JQ1 produces a potent antiproliferative effect associated with cell-cycle arrest and cellular senescence. Efficacy of JQ1 in three murine models of multiple myeloma establishes the therapeutic rationale for BET bromodomain inhibition in this disease and other malignancies characterized by pathologic activation of c-Myc.
C1 [Delmore, Jake E.; Issa, Ghayas C.; Jacobs, Hannah M.; Kastritis, Efstathios; Gilpatrick, Timothy; Paranal, Ronald M.; Qi, Jun; Schinzel, Anna C.; McKeown, Michael R.; Heffernan, Timothy P.; Ghobrial, Irene M.; Richardson, Paul G.; Hahn, William C.; Anderson, Kenneth C.; Bradner, James E.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Lemieux, Madeleine E.; Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Lemieux, Madeleine E.; Kung, Andrew L.] Childrens Hosp Boston, Boston, MA 02215 USA.
[Rahl, Peter B.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA.
[Shi, Junwei; Vakoc, Christopher R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Chesi, Marta; Bergsagel, P. Leif] Mayo Clin Arizona, Ctr Comprehens Canc, Scottsdale, AZ 85259 USA.
[Ghobrial, Irene M.; Richardson, Paul G.; Anderson, Kenneth C.; Bradner, James E.; Mitsiades, Constantine S.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA.
[Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Hahn, William C.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA.
RP Bradner, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM james_bradner@dfci.harvard.edu; constantine_mitsiades@dfci.harvard.edu
RI Bergsagel, Peter/A-7842-2011; Young, Richard/F-6495-2012;
OI Bergsagel, Peter/0000-0003-1523-7388; Young,
Richard/0000-0001-8855-8647; Lemieux, Madeleine/0000-0001-6355-8691;
Vakoc, Christopher/0000-0002-1158-7180; Kung, Andrew/0000-0002-9091-488X
FU Chambers Medical Foundation; Stepanian Fund for Myeloma Research;
Richard J. Corman Foundation; American Cancer Society
[120272-PF-11-042-01-DMC]; Burroughs-Wellcome Fund; Smith Family Award;
Damon-Runyon Cancer Research Foundation; MMRF; [NIH-K08CA128972];
[NIH-R01CA050947]; [NIH-R01HG002668]; [NIH-R01CA46455]
FX We are grateful to S. Lowe for sharing unpublished information; A. Azab,
D. McMillin, C. Ott, and A. Roccaro for technical support; E. Fox for
microarray data; J. Daley and S. Lazo-Kallanian for flow cytometry; the
MMRF, MMRC, and Broad Institute for establishing the MM Genomics Portal
(http://www.broadinstitute.org/mmgp/). This research was supported by
NIH-K08CA128972 (J.E.B.), NIH-R01CA050947 (C.S.M.), NIH-R01HG002668
(R.A.Y.), and NIH-R01CA46455 (R.A.Y.); the Chambers Medical Foundation
(P.G.R., C.S.M.); the Stepanian Fund for Myeloma Research (P.G.R.,
C.S.M.); and the Richard J. Corman Foundation (P.G.R., C.S.M.); an
American Cancer Society Postdoctoral Fellowship, 120272-PF-11-042-01-DMC
(P.B.R.); the Burroughs-Wellcome Fund, the Smith Family Award, the
Damon-Runyon Cancer Research Foundation, and the MMRF (to J.E.B.).
NR 63
TC 859
Z9 866
U1 20
U2 144
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD SEP 16
PY 2011
VL 146
IS 6
BP 903
EP 916
DI 10.1016/j.cell.2011.08.017
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 825GB
UT WOS:000295258100013
PM 21889194
ER
PT J
AU Wu, XL
Zhou, TQ
Zhu, J
Zhang, BS
Georgiev, I
Wang, C
Chen, XJ
Longo, NS
Louder, M
McKee, K
O'Dell, S
Perfetto, S
Schmidt, SD
Shi, W
Wu, L
Yang, YP
Yang, ZY
Yang, ZJ
Zhang, ZH
Bonsignori, M
Crump, JA
Kapiga, SH
Sam, NE
Haynes, BF
Simek, M
Burton, DR
Koff, WC
Doria-Rose, NA
Connors, M
Mullikin, JC
Nabel, GJ
Roederer, M
Shapiro, L
Kwong, PD
Mascola, JR
AF Wu, Xueling
Zhou, Tongqing
Zhu, Jiang
Zhang, Baoshan
Georgiev, Ivelin
Wang, Charlene
Chen, Xuejun
Longo, Nancy S.
Louder, Mark
McKee, Krisha
O'Dell, Sijy
Perfetto, Stephen
Schmidt, Stephen D.
Shi, Wei
Wu, Lan
Yang, Yongping
Yang, Zhi-Yong
Yang, Zhongjia
Zhang, Zhenhai
Bonsignori, Mattia
Crump, John A.
Kapiga, Saidi H.
Sam, Noel E.
Haynes, Barton F.
Simek, Melissa
Burton, Dennis R.
Koff, Wayne C.
Doria-Rose, Nicole A.
Connors, Mark
Mullikin, James C.
Nabel, Gary J.
Roederer, Mario
Shapiro, Lawrence
Kwong, Peter D.
Mascola, John R.
CA NISC Comparative Sequencing Progra
TI Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by
Structures and Deep Sequencing
SO SCIENCE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; GP120; BROAD;
INDIVIDUALS; SELECTION; BREADTH; EPITOPE; GLYCOPROTEIN; DIVERSITY
AB Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.
C1 [Wu, Xueling; Zhou, Tongqing; Zhu, Jiang; Zhang, Baoshan; Georgiev, Ivelin; Wang, Charlene; Chen, Xuejun; Longo, Nancy S.; Louder, Mark; McKee, Krisha; O'Dell, Sijy; Perfetto, Stephen; Schmidt, Stephen D.; Shi, Wei; Wu, Lan; Yang, Yongping; Yang, Zhi-Yong; Yang, Zhongjia; Zhang, Zhenhai; Nabel, Gary J.; Roederer, Mario; Shapiro, Lawrence; Kwong, Peter D.; Mascola, John R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Zhang, Zhenhai; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Bonsignori, Mattia; Haynes, Barton F.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Crump, John A.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Crump, John A.] Duke Univ, Med Ctr, Div Infect Dis & Int Hlth, Dept Med, Durham, NC 27710 USA.
[Crump, John A.; Sam, Noel E.] Tumaini Univ, Kilimanjaro Christian Med Ctr, Moshi, Tanzania.
[Crump, John A.; Sam, Noel E.] Tumaini Univ, Kilimanjaro Christian Med Coll, Moshi, Tanzania.
[Kapiga, Saidi H.; Sam, Noel E.] Kilimanjaro Reprod Hlth Programme, Moshi, Tanzania.
[Simek, Melissa; Koff, Wayne C.] Int AIDS Vaccine Initiat IAVI, New York, NY 10038 USA.
[Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbiol Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Massachusetts Gen Hosp, Massachusetts Inst Technol & Harvard, Ragon Inst, Cambridge, MA 02129 USA.
[Doria-Rose, Nicole A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA.
RP Kwong, PD (reprint author), NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov; jmascola@nih.gov
RI Schmidt, Stephen/B-5398-2012; Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU Vaccine Research Center, National Institute of Allergy and Infectious
Diseases; National Human Genome Research Institute, NIH; International
AIDS Vaccine Initiative's Neutralizing Antibody Consortium; NIH [AI 5U19
AI 067854-06]; U.S. Department of Energy, Basic Energy Sciences, Office
of Science [W-31-109-Eng-38]
FX X.W., T.Z., J.Z., G.J.N., M. R., L. S., P. D. K., and J.R.M. designed
research; B.Z., C. W., X. C., M. L., K. M., S.O.D., S. P., S. D. S., W.
S., L. W., Y.Y., Z.Y.Y., Z.Y., NISC, and J.M. performed experiments; X.
W. isolated and characterized VRC01-like antibodies by RSC3 probe,
devised and prepared samples for 454 pyrosequencing, and assisted with
functional characterization; T.Z. determined and analyzed structures of
VRC-PG04 and VRC03 with gp120 and assisted with functional
characterization; J.Z. devised and carried out computational
bioinformatics on the antibodyome; M. B., J.A.C, S. H. K, N.E.S., and B.
F. H. contributed donor 0219 materials; M. S., D. R. B., and W. C. K
contributed Protocol G materials, including donor 74; N.D.R. and M. C.
contributed donor 45 materials; X. W., T.Z., J.Z, I. G., N.S.L., Z.Z.,
L. S., P. D. K., and J. R. M. analyzed the data; and L. S., G.J.N., P.
D. K., and J. R. M. wrote the paper, on which all authors commented. We
thank J. Almeida and D. Douek for protocols of PBMC cDNA preparation and
for helpful discussions; J. Stuckey for assistance with figures; T. Wrin
for sequence information on the donor 74 virus; J. Binley, D.
Montefiori, L. Morris, and G. Tomaras for donor 0219 serum
characterization; and all of the IAVI Protocol G team members and the
Protocol G clinical investigators, specifically, G. Miiro, A. Pozniak,
D. McPhee, O. Manigart, E. Karita, A. Inwoley, W. Jaoko, J. DeHovitz,
L.-G. Bekker, P. Pitisuttithum, R. Paris, J. Serwanga, and S. Allen. We
also thank H. Sato, I. Wilson, and members of the Structural Biology
Section and Structural Bioinformatics Core, Vaccine Research Center, for
discussions or comments on the manuscript. Support for this work was
provided by the Intramural Research Program of the Vaccine Research
Center, National Institute of Allergy and Infectious Diseases, and the
National Human Genome Research Institute, NIH; by grants from the
International AIDS Vaccine Initiative's Neutralizing Antibody
Consortium; and by the Center for HIV AIDS Vaccine Immunology grant AI
5U19 AI 067854-06 from NIH. Use of sector 22 (Southeast Region
Collaborative Access Team) at the Advanced Photon Source was supported
by the U.S. Department of Energy, Basic Energy Sciences, Office of
Science, under contract W-31-109-Eng-38. Structure factors and
coordinates for antibodies VRC03 and VRC-PG04 in complex with HIV-1
gp120 have been deposited with the Protein Data Bank under accession
codes 3SE8 and 3SE9, respectively. We have also deposited deep
sequencing data for donors 45 and 74 (Appendices 1 to 4) used in this
study to National Center for Biotechnology Information Short Reads
Archives (SRA) under accession no. SRP006992. Information deposited with
GenBank includes the heavy-and light-chain variable region sequences of
probe-identified antibodies VRC-PG04 and VRC-PG04b (accession nos.
JN159464 to JN159467), VRC-CH30, VRC-CH31, and VRC-CH32 (JN159434 to
JN159439), and VRC-CH33 and VRC-CH34 (JN159470 to 159473), as well as
the sequences of genomically identified neutralizers: 24 heavy chains
from donor 74, 2008 (JN159440 to JN159463), two heavy chains from donor
45, 2008 (JN159474 and JN159475), two light chains from donor 45, 2001
(JN159468 and JN159469), and 1561 unique sequences associated with
neutralizing CDR H3 distributions with at least one low divergent member
shown in Fig. 6B and fig. S16 (JN157873 to JN159433).
NR 37
TC 431
Z9 436
U1 5
U2 79
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD SEP 16
PY 2011
VL 333
IS 6049
BP 1593
EP 1602
DI 10.1126/science.1207532
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 820JE
UT WOS:000294900900034
PM 21835983
ER
PT J
AU Scheid, JF
Mouquet, H
Ueberheide, B
Diskin, R
Klein, F
Oliveira, TYK
Pietzsch, J
Fenyo, D
Abadir, A
Velinzon, K
Hurley, A
Myung, S
Boulad, F
Poignard, P
Burton, DR
Pereyra, F
Ho, DD
Walker, BD
Seaman, MS
Bjorkman, PJ
Chait, BT
Nussenzweig, MC
AF Scheid, Johannes F.
Mouquet, Hugo
Ueberheide, Beatrix
Diskin, Ron
Klein, Florian
Oliveira, Thiago Y. K.
Pietzsch, John
Fenyo, David
Abadir, Alexander
Velinzon, Klara
Hurley, Arlene
Myung, Sunnie
Boulad, Farid
Poignard, Pascal
Burton, Dennis R.
Pereyra, Florencia
Ho, David D.
Walker, Bruce D.
Seaman, Michael S.
Bjorkman, Pamela J.
Chait, Brian T.
Nussenzweig, Michel C.
TI Sequence and Structural Convergence of Broad and Potent HIV Antibodies
That Mimic CD4 Binding
SO SCIENCE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; MEMORY
B-CELLS; NEUTRALIZING ANTIBODIES; TYPE-1 GP120; ENVELOPE GLYCOPROTEIN;
EPITOPE; RECEPTOR; GP41; INDIVIDUALS
AB Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.
C1 [Scheid, Johannes F.; Mouquet, Hugo; Klein, Florian; Oliveira, Thiago Y. K.; Pietzsch, John; Abadir, Alexander; Velinzon, Klara; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Scheid, Johannes F.] Charite, D-10117 Berlin, Germany.
[Ueberheide, Beatrix; Fenyo, David; Myung, Sunnie; Chait, Brian T.] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10065 USA.
[Diskin, Ron; Bjorkman, Pamela J.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Pietzsch, John] Free Univ Berlin, Dept Biol Chem & Pharm, D-14195 Berlin, Germany.
[Hurley, Arlene] Rockefeller Univ, Rockefeller Univ Hosp, New York, NY 10065 USA.
[Boulad, Farid] Mem Sloan Kettering Canc Ctr, Bone Marrow Transplant Serv, New York, NY 10065 USA.
[Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Poignard, Pascal] Int AIDS Vaccine Initiat, New York, NY 10028 USA.
[Burton, Dennis R.; Pereyra, Florencia; Walker, Bruce D.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA.
[Pereyra, Florencia; Walker, Bruce D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA.
[Pereyra, Florencia; Walker, Bruce D.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Ho, David D.; Walker, Bruce D.; Bjorkman, Pamela J.; Nussenzweig, Michel C.] Howard Hughes Med Inst, New York, NY 10065 USA.
Aaron Diamond AIDS Res Ctr, New York, NY 10065 USA.
[Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@mail.rockefeller.edu
RI poignard, pascal/N-6678-2013; Mouquet, Hugo/M-2750-2014;
OI Oliveira, Thiago/0000-0002-2654-0879; Ueberheide,
Beatrix/0000-0003-2512-0204; Fenyo, David/0000-0001-5049-3825
FU NIH [P01 AI081677, RR00862, RR022220]; Bill & Melinda Gates Foundation's
Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine
Immune Monitoring Consortium [38619s, 38660]; Gordon and Betty Moore
Foundation; Stanford Synchrotron Radiation Lightsource; German Research
Foundation (Deutsche Forschungsgemeinschaft) [KL 2389/1-1]
FX The data reported in this paper are tabulated in the supporting online
material, and the coordinates for the 3BNC60 Fab as well as the antibody
sequences have been deposited in the Protein Data Bank and the European
Molecular Biology Laboratory-European Bioinformatics Institute database
[accession codes: 3RPI (3BNC60 coordinates), HE584535 to HE584554
(antibody sequences)]. We thank the HIV-positive donors for their
support. We thank M. Jankovic for discussions and help with cloning of
HIV envelope constructs; R. Wyatt for the plasmid of YU2-gp140; J.
Mascola for the plasmid of 2CC-core and YU2-gp120 mutants; and M.
Connors for access to patient NIH45; C. Gaebler, M. Warncke, P. M.
Marcovecchio, and H. Gao for help with protein expression; K. Moss for
patient coordination. We thank F. McCutchan, G. Shaw, B. Hahn, J.
Baalwa, D. Montefiori, F. Gao, M. Thomson, J. Overbaugh, R. Swanstrom,
L. Morris, J. Kim, L. Zhang, D. Ellenberger, and C. Williamson for
contributing the HIV-1 Envelope plasmids used in our neutralization
panel. We thank M. Simek, F. Priddy, and all the study participants and
research staff at each of the International AIDS Vaccine Initiative
(IAVI) Protocol G project; clinical and site team members; and all of
the Protocol G clinical investigators, specifically, G. Miiro, A.
Pozniak, D. McPhee, O. Manigart, E. Karita, A. Inwoley, W. Jaoko, J.
DeHovitz, L.-G. Bekker, P. Pitisuttithum, R. Paris, J. Serwanga, and S.
Allen for samples from one broadly neutralizing serum donor from
Protocol G. We thank L. Walker for providing data on the neutralizing
specificity of the Protocol G donor. In connection with this work,
M.C.N. and J. F. S. have a pending patent application with the U. S.
Patent and Trademark Office, patent number U. S. 61/486,960, entitled
"Human Immunodeficiency Virus Neutralizing Antibodies and Methods of Use
Thereof." The reagents are available with a Materials Transfer
Agreement. The work was supported by NIH grants P01 AI081677, RR00862,
and RR022220, and by the Bill & Melinda Gates Foundation's Collaboration
for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine Immune
Monitoring Consortium, grant numbers 38619s and 38660. We thank the
Molecular Observatory at Caltech (supported by the Gordon and Betty
Moore Foundation) and the Stanford Synchrotron Radiation Lightsource. F.
K. was supported by the German Research Foundation (Deutsche
Forschungsgemeinschaft, KL 2389/1-1). M.C.N., P. J. B, and B. D. W. are
Howard Hughes Medical Institute Investigators.
NR 36
TC 470
Z9 476
U1 6
U2 53
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD SEP 16
PY 2011
VL 333
IS 6049
BP 1633
EP 1637
DI 10.1126/science.1207227
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 820JE
UT WOS:000294900900044
PM 21764753
ER
PT J
AU Thangasamy, A
Rogge, J
Krishnegowda, NK
Freeman, JW
Ammanamanchi, S
AF Thangasamy, Amalraj
Rogge, Jessica
Krishnegowda, Naveen K.
Freeman, James W.
Ammanamanchi, Sudhakar
TI Novel Function of Transcription Factor Nrf2 as an Inhibitor of RON
Tyrosine Kinase Receptor-mediated Cancer Cell Invasion
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OXIDATIVE STRESS; BREAST-CANCER; ACTIVATION; MICE; SULFORAPHANE;
SENSITIVITY; PREVENTION; MUTATIONS
AB Recepteur d' origine nantais (RON), a tyrosine kinase receptor, is aberrantly expressed in human tumors and promotes cancer cell invasion. RON receptor activation is also associated with resistance to tamoxifen treatment in breast cancer cells. Nrf2 is a positive regulator of cytoprotective genes. Using chromatin immunoprecipitation (ChIP) and site-directed mutagenesis studies of the RON promoter, we identified Nrf2 as a negative regulator of RON gene expression. High Nrf2 and low RON expression was observed in normal mammary tissue whereas high RON and low or undetectable expression of Nrf2 was observed in breast tumors. The Nrf2 inducer sulforaphane (SFN) as well as ectopic Nrf2 expression or knock-down of the Nrf2 negative regulator keap1, which stabilizes Nrf2, inhibited RON expression and invasion of carcinoma cells. Consequently, our studies identified a novel functional role for Nrf2 as a "repressor" and RON kinase as a molecular target of SFN, which mediates the anti-tumor effects of SFN. These results are not limited to breast cancer cells since the Nrf2 inducer SFN stabilized Nrf2 and inhibited RON expression in carcinoma cells from various tumor types.
C1 [Thangasamy, Amalraj; Rogge, Jessica; Krishnegowda, Naveen K.; Freeman, James W.; Ammanamanchi, Sudhakar] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Med Oncol, San Antonio, TX 78229 USA.
[Freeman, James W.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA.
RP Ammanamanchi, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Med Oncol, San Antonio, TX 78229 USA.
EM sammanamanchi@hotmail.com
FU Veterans Administration
FX This work was supported by the Veterans Administration Merit Award (to
J. W. F.).
NR 20
TC 13
Z9 14
U1 2
U2 5
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 SEP 16
PY 2011
VL 286
IS 37
BP 32115
EP 32122
DI 10.1074/jbc.M111.245746
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 818CK
UT WOS:000294726800021
PM 21799005
ER
PT J
AU Delgado, GA
Truesdell, AG
Kirchner, RM
Zuzek, RW
Pomerantsev, EV
Gordon, PC
Regnante, RA
AF Delgado, Gabriel A.
Truesdell, Alexander G.
Kirchner, Robert M.
Zuzek, Ryan W.
Pomerantsev, Eugene V.
Gordon, Paul C.
Regnante, Richard A.
TI An Angiographic and Intravascular Ultrasound Study of the Left Anterior
Descending Coronary Artery in Takotsubo Cardiomyopathy
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID APICAL BALLOONING SYNDROME; TAKO-TSUBO CARDIOMYOPATHY; LEFT-VENTRICULAR
DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; PLAQUE
RUPTURE; FEATURES; DISEASE
AB The precise cause of takotsubo cardiomyopathy (TC) remains controversial. Plaque rupture with transient thrombotic occlusion of a transapical left anterior descending coronary artery (LAD) has been advanced as a potential mechanism. To explore this hypothesis, the investigators analyzed data from 11 patients prospectively enrolled in the Rhode Island Takotsubo Cardiomyopathy Registry who underwent coronary angiography and intravascular ultrasound evaluation of the LAD during their initial presentation. Despite the presence of nonobstructive coronary artery disease, no culprit lesion was identified in any patient. Similarly, the course of the LAD failed to account for the characteristic left ventricular apical ballooning seen in TC. In conclusion, an atherosclerotic coronary lesion in the LAD causing an aborted myocardial infarction may not be the primary underlying cause of TC, and nonobstructive coronary artery disease and TC may coexist without a direct causal association. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:888-891)
C1 [Delgado, Gabriel A.; Truesdell, Alexander G.; Kirchner, Robert M.; Zuzek, Ryan W.; Gordon, Paul C.; Regnante, Richard A.] Brown Univ, Div Cardiol, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Pomerantsev, Eugene V.] Harvard Univ, Cardiac Invas Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Truesdell, AG (reprint author), Brown Univ, Div Cardiol, Warren Alpert Med Sch, Providence, RI 02912 USA.
EM atruesdell@lifespan.org
FU Abbott Cardiovascular Systems Inc., Santa Clara, California;
Accumetrics, Inc., San Diego, California; AstraZeneca, Wilmington,
Delaware; Boston Scientific Corporation, Natick, Massachusetts;
Bristol-Myers Squibb, New York, New York; Cordis Corporation, a Johnson
& Johnson Company, Bridge-water, New Jersey; Hoffman-La Roche, Inc.,
Nutley, New Jersey; Eli Lilly & Company, Indianapolis, Indiana; MEDRAD,
Inc., Warrendale, Pennsylvania; MD Scientific, LLC, Charlotte, North
Carolina; Medtronic Vascular, Inc., Santa Rosa, California;
Sanofi-Aventis, Malvern, Pennsylvania; Schering Plough Research
Institute, a Division of Schering Corporation, Kenilworth, New Jersey;
Spectranetics Corporation, Colorado Springs, Colorado
FX Dr. Gordon receives grant and research support from Abbott
Cardiovascular Systems, Inc., Santa Clara, California; Accumetrics,
Inc., San Diego, California; AstraZeneca, Wilmington, Delaware; Boston
Scientific Corporation, Natick, Massachusetts; Bristol-Myers Squibb, New
York, New York; Cordis Corporation, a Johnson & Johnson Company,
Bridge-water, New Jersey; Hoffman-La Roche, Inc., Nutley, New Jersey;
Eli Lilly & Company, Indianapolis, Indiana; MEDRAD, Inc., Warrendale,
Pennsylvania; MD Scientific, LLC, Charlotte, North Carolina; Medtronic
Vascular, Inc., Santa Rosa, California; Sanofi-Aventis, Malvern,
Pennsylvania; Schering Plough Research Institute, a Division of Schering
Corporation, Kenilworth, New Jersey; and the Spectranetics Corporation,
Colorado Springs, Colorado.
NR 22
TC 14
Z9 16
U1 0
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 15
PY 2011
VL 108
IS 6
BP 888
EP 891
DI 10.1016/j.amjcard.2011.05.012
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 826KJ
UT WOS:000295352700022
PM 21741604
ER
PT J
AU Ueland, T
Aukrust, P
Omdal, TR
Damas, JK
Endresen, K
Ren, F
Hysing, J
Giugliano, RP
AF Ueland, Thor
Aukrust, Pal
Omdal, Tom Roar
Damas, Jan Kristian
Endresen, Knut
Ren, Fang
Hysing, Jan
Giugliano, Robert P.
TI Effect of eptifibatide on platelet-mediated inflammation in acute
coronary syndromes
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Letter
DE Acute coronary syndrome; Platelets; Inflammation; GP IIb/IIIa antagonism
ID ANTIPLATELET THERAPY; ATHEROSCLEROSIS; DISEASE
C1 [Ueland, Thor; Aukrust, Pal] Univ Oslo, Rikshosp, Oslo Univ Hosp, Internal Med Res Inst, N-0027 Oslo, Norway.
[Ueland, Thor; Aukrust, Pal] Univ Oslo, Fac Med, N-0027 Oslo, Norway.
[Aukrust, Pal] Univ Oslo, Rikshosp, Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, N-0027 Oslo, Norway.
[Endresen, Knut] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Cardiol, N-0027 Oslo, Norway.
[Omdal, Tom Roar] Sorlandet Sykehus Arendal, Arendal, Norway.
[Damas, Jan Kristian] St Olavs Hosp, Dept Infect Dis, Trondheim, Norway.
[Ren, Fang; Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
[Hysing, Jan] Sykehuset Telemark HF, Skien, Norway.
RP Ueland, T (reprint author), Univ Oslo, Rikshosp, Oslo Univ Hosp, Internal Med Res Inst, N-0027 Oslo, Norway.
EM thor.ueland@medisin.uio.no
NR 9
TC 3
Z9 4
U1 0
U2 2
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 SEP 15
PY 2011
VL 151
IS 3
BP 385
EP 387
DI 10.1016/j.ijcard.2011.06.117
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 824PP
UT WOS:000295214700046
PM 21782261
ER
PT J
AU Harzstark, AL
Small, EJ
Weinberg, VK
Sun, J
Ryan, CJ
Lin, AM
Fong, L
Brocks, DR
Rosenberg, JE
AF Harzstark, Andrea L.
Small, Eric J.
Weinberg, Vivian K.
Sun, Janine
Ryan, Charles J.
Lin, Amy M.
Fong, Lawrence
Brocks, Dion R.
Rosenberg, Jonathan E.
TI A Phase 1 Study of Everolimus and Sorafenib for Metastatic Clear Cell
Renal Cell Carcinoma
SO CANCER
LA English
DT Article
DE renal cell carcinoma; clear cell; everolimus; sorafenib; mammalian
target of rapamycin (mTOR) inhibitor; tyrosine kinase inhibitor;
combination therapy
ID INTERFERON-ALPHA; III TRIAL; RAPAMYCIN; EFFICACY
AB BACKGROUND: The current study was conducted to assess the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor effect of everolimus, a mammalian target of rapamycin inhibitor, in combination with sorafenib, a tyrosine kinase inhibitor, in patients with metastatic clear cell renal cell carcinoma. METHODS: Sequential cohorts of patients received escalating doses of everolimus and sorafenib in 28-day cycles in the absence of a dose-limiting toxicity (DLT) or disease progression were examined. RESULTS: Twenty patients with a median age of 65 years received therapy in 3 cohorts. Dose level 1 was comprised of everolimus at a dose of 2.5 mg daily and sorafenib at a dose of 400 mg twice daily (6 patients), dose level 2 was comprised of everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily (8 patients), and dose level 3 was comprised of everolimus at a dose of 10 mg daily and sorafenib at a dose of 200 mg twice daily (6 patients). DLTs included grade 4 (according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) hyperuricemia with grade 2 gout and grade 3 lipase associated with grade 2 pancreatitis at dose level 2, and grade 3 rash in 2 patients at dose level 3. Dose level 2 (everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily) was established as the maximum tolerated dose. Treatment-related adverse events occurring in >20% of patients included diarrhea, hand-foot syndrome, hypertension, hypophosphatemia, hypothyroidism, and rash. Five of 20 patients achieved Response Evaluation Criteria In Solid Tumors (RECIST)-defined partial responses, all of which occurred in patients without a history of prior systemic therapy. Seven of 8 patients treated at dose level 2 experienced a partial response or stable disease. Pharmacokinetic analysis revealed no interaction between everolimus and sorafenib. CONCLUSIONS: The combination of everolimus and sorafenib was associated with acceptable toxicity and evidence of antitumor activity in previously untreated patients with metastatic renal cell carcinoma. Cancer 2011;117:4194-200. (C) 2011 American Cancer Society.
C1 [Harzstark, Andrea L.; Small, Eric J.; Sun, Janine; Ryan, Charles J.; Lin, Amy M.; Fong, Lawrence] Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Brocks, Dion R.] Univ Alberta, Edmonton, AB, Canada.
[Rosenberg, Jonathan E.] Dana Farber Canc Inst, Dept Med, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
RP Harzstark, AL (reprint author), Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, 1600 Divisadero St,POB 1711, San Francisco, CA 94143 USA.
EM andrea.harzstark@ucsf.edu
FU Novartis Oncology; Novartis
FX Supported in part by Novartis Oncology. Dr. Ryan has received honoraria
from Novartis. Dr. Rosenberg has received research support, consulting
fees, and honoraria from Novartis.
NR 12
TC 34
Z9 34
U1 0
U2 2
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 SEP 15
PY 2011
VL 117
IS 18
BP 4194
EP 4200
DI 10.1002/cncr.25931
PG 7
WC Oncology
SC Oncology
GA 824EU
UT WOS:000295186000015
PM 21387258
ER
PT J
AU Haas, JS
Brawarsky, P
Iyer, A
Fitzmaurice, GM
Neville, BA
Earle, C
AF Haas, Jennifer S.
Brawarsky, Phyllis
Iyer, Aarthi
Fitzmaurice, Garrett M.
Neville, Bridget A.
Earle, Craig
TI Association of Area Sociodemographic Characteristics and Capacity for
Treatment With Disparities in Colorectal Cancer Care and Mortality
SO CANCER
LA English
DT Article
DE colorectal cancer; disparities; regional variation; treatment
ID ADJUVANT CHEMOTHERAPY USE; COLON-CANCER; UNITED-STATES; MEDICARE
BENEFICIARIES; REGIONAL-VARIATIONS; RADIATION-THERAPY; SURGEON VOLUME;
LUNG-CANCER; POPULATION; BREAST
AB BACKGROUND: Disparities in treatment and mortality for colorectal cancer (CRC) may reflect differences in access to specialized care or other characteristics of the area where an individual lives. METHODS: Surveillance, Epidemiology and End Results Program-Medicare data for seniors diagnosed with CRC were linked to area measures of the sociodemographic characteristics and the capacity of surgeons, medical oncologists, and radiation oncologists. Outcomes included receipt of stage-appropriate CRC care and mortality. RESULTS: After adjustment, blacks and Hispanics were less likely than whites to undergo surgery (odds ratio [OR] 0.57, 95% confidence interval (CI) 0.52-0.63 and OR 0.82, 95% CI 0.70-0.95, respectively). Individuals who lived in areas with the highest tertile of surgeon capacity were more likely to undergo resection than those in the lowest, and use of surgery declined as the percentage of blacks in the area increased. Adjustment for the area measures resulted in a modest decline in disparities in care relative to whites (5.3% for black). Blacks also experienced greater all-cause and cancer-specific mortality than whites. Further adjustment for area sociodemographics and surgeon capacity reduced the disparity in mortality between blacks and whites. Although there was a similar black/white disparity in the use of adjuvant chemotherapy, the disparity remained after adjustment for area characteristics, although use of chemotherapy was greater in areas with the greatest capacity of medical oncologists. CONCLUSIONS: Sociodemographic characteristics and measures of the availability of specialized cancer providers in the area in which an individual resides modestly mediated disparities in the receipt of CRC care and mortality, suggesting that other factors may also be important. Cancer 2011;117:4267-76. (C) 2011 American Cancer Society.
C1 [Haas, Jennifer S.; Brawarsky, Phyllis; Iyer, Aarthi] Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02120 USA.
[Haas, Jennifer S.; Brawarsky, Phyllis; Iyer, Aarthi; Fitzmaurice, Garrett M.] Harvard Univ, Sch Med, Boston, MA USA.
[Fitzmaurice, Garrett M.] McLean Hosp, Lab Psychiat Biostat, Boston, MA USA.
[Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Earle, Craig] Canc Care Ontario, Toronto, ON, Canada.
[Earle, Craig] Ontario Inst Canc Res, Toronto, ON, Canada.
RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, 1620 Tremont St, Boston, MA 02120 USA.
EM jhaas@partners.org
FU American Cancer Society [RSGT CPHPS-114979]
FX Supported by grants from the American Cancer Society (RSGT
CPHPS-114979).
NR 31
TC 29
Z9 29
U1 1
U2 5
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 SEP 15
PY 2011
VL 117
IS 18
BP 4267
EP 4276
DI 10.1002/cncr.26034
PG 10
WC Oncology
SC Oncology
GA 824EU
UT WOS:000295186000023
PM 21413000
ER
PT J
AU Buss, MK
Lessen, DS
Sullivan, AM
Von Roenn, J
Arnold, RM
Block, SD
AF Buss, Mary K.
Lessen, David S.
Sullivan, Amy M.
Von Roenn, Jamie
Arnold, Robert M.
Block, Susan D.
TI Hematology/Oncology Fellows' Training in Palliative Care
SO CANCER
LA English
DT Article
DE palliative care; oncology education and training; pain and symptom
management; psychosocial care; communication skills
ID OF-LIFE CARE; GLOBAL CORE CURRICULUM; CANCER PAIN MANAGEMENT; MEDICAL
ONCOLOGY; NATIONAL-SURVEY; CLINICAL ONCOLOGY; AMERICAN SOCIETY;
COMMUNICATION; RECOGNITION; RECOMMENDATIONS
AB BACKGROUND: Palliative care is recognized as integral to the practice of oncology, yet many oncologists report inadequate training in critical palliative care domains, such as symptom management, psychosocial care, and communication skills. The authors of this report sought to assess the quantity and quality of palliative care education within oncology fellowships. METHODS: Second-year oncology fellows completed a 104-item survey that was modified and adapted from a national survey of medical students and residents. Items allowed comparison between palliative care and nonpalliative care topics. RESULTS: Of 402 eligible fellows, 63.2% responded (n = 254). Respondents were: 52% men, 62% Caucasian, and 64% US medical school graduates. Twenty-six percent had completed a palliative care rotation. Fellows rated the overall quality of fellowship teaching more highly than teaching on palliative care (3.7 v 3.0 on a 1-5 scale; t=10.2; P < .001). Rates of being observed (81%) and receiving feedback (80%) on an end-of-life communication skill were high. Psychosocial needs of patients received some attention: Fifty-seven percent of fellows reported that they were conveyed as a core competency, but only 32% of fellows received explicit education on assessing and managing depression at the end of life. Fellows rarely reported receiving explicit education on opioid rotation (33%). Fellows scored a median of 2 of 4 items that tested basic palliative care knowledge, and only 23% correctly performed an opioid conversion. CONCLUSIONS: Fellows rated the quality of palliative care education as inferior to overall oncology training and may benefit from more teaching on pain management, psychosocial care, and communication skills. Cancer 2011;117:4304-11. (C) 2077 American Cancer Society
C1 [Buss, Mary K.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Palliat Care Consultat Serv, Div Gen Internal Med,Gynecol Med Oncol Prog, Boston, MA 02215 USA.
[Buss, Mary K.] Harvard Univ, Sch Med, Boston, MA USA.
[Lessen, David S.] SE Florida Hematol Oncol Grp, Ft Lauderdale, FL USA.
[Sullivan, Amy M.] Virginia Commonwealth Univ, Sch Med, Dept Social & Behav Sci, Richmond, VA USA.
[Von Roenn, Jamie] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Von Roenn, Jamie] Feinberg Sch Med, Chicago, IL USA.
[Arnold, Robert M.] Univ Pittsburgh Hosp, Inst Doctor Patient Commun, Sect Palliat Care & Med Eth, Pittsburgh, PA USA.
[Arnold, Robert M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Block, Susan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Block, Susan D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Buss, MK (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Palliat Care Consultat Serv, Div Gen Internal Med,Gynecol Med Oncol Prog, 330 Brookline Ave,Rose 144, Boston, MA 02215 USA.
EM mbuss@bidmc.harvard.edu
NR 30
TC 36
Z9 36
U1 0
U2 9
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 SEP 15
PY 2011
VL 117
IS 18
BP 4304
EP 4311
DI 10.1002/cncr.25952
PG 8
WC Oncology
SC Oncology
GA 824EU
UT WOS:000295186000027
PM 21365618
ER
PT J
AU Villar, J
Cabrera, NE
Valladares, F
Casula, M
Flores, C
Blanch, L
Quilez, ME
Santana-Rodriguez, N
Kacmarek, RM
Slutsky, AS
AF Villar, Jesus
Cabrera, Nuria E.
Valladares, Francisco
Casula, Milena
Flores, Carlos
Blanch, Lluis
Elisa Quilez, Maria
Santana-Rodriguez, Norberto
Kacmarek, Robert M.
Slutsky, Arthur S.
TI Activation of the Wnt/beta-Catenin Signaling Pathway by Mechanical
Ventilation Is Associated with Ventilator-Induced Pulmonary Fibrosis in
Healthy Lungs
SO PLOS ONE
LA English
DT Article
ID END-EXPIRATORY PRESSURE; RESPIRATORY-DISTRESS-SYNDROME; GENE-EXPRESSION;
PHOSPHOINOSITIDE 3-KINASE; INFLAMMATORY RESPONSES; TIDAL VOLUME;
BETA-CATENIN; INJURY MODEL; CELL FACTOR; MICE
AB Background: Mechanical ventilation (MV) with high tidal volumes (V(T)) can cause or aggravate lung damage, so-called ventilator induced lung injury (VILI). The relationship between specific mechanical events in the lung and the cellular responses that result in VILI remains incomplete. Since activation of Wnt/beta-catenin signaling has been suggested to be central to mechanisms of lung healing and fibrosis, we hypothesized that the Wnt/beta-catenin signaling plays a role during VILI.
Methodology/Principal Findings: Prospective, randomized, controlled animal study using adult, healthy, male Sprague-Dawley rats. Animals (n = 6/group) were randomized to spontaneous breathing or two strategies of MV for 4 hours: low tidal volume (V(T)) (6 mL/kg) or high V(T) (20 mL/kg). Histological evaluation of lung tissue, measurements of WNT5A, total beta-catenin, non-phospho (Ser33/37/Thr41) beta-catenin, matrix metalloproteinase-7 (MMP-7), cyclin D1, vascular endothelial growth factor (VEGF), and axis inhibition protein 2 (AXIN2) protein levels by Western blot, and WNT5A, non-phospho (Ser33/37/Thr41) beta-catenin, MMP-7, and AXIN2 immunohistochemical localization in the lungs were analyzed. High-V(T) MV caused lung inflammation and perivascular edema with cellular infiltrates and collagen deposition. Protein levels of WNT5A, non-phospho (Ser33/37/Thr41) beta-catenin, MMP-7, cyclin D1, VEGF, and AXIN2 in the lungs were increased in all ventilated animals although high-V(T) MV was associated with significantly higher levels of WNT5A, non-phospho (Ser33/37/Thr41) beta-catenin, MMP-7, cyclin D1, VEGF, and AXIN2 levels.
Conclusions/Significance: Our findings demonstrate that the Wnt/beta-catenin signaling pathway is modulated very early by MV in lungs without preexistent lung disease, suggesting that activation of this pathway could play an important role in both VILI and lung repair. Modulation of this pathway might represent a therapeutic option for prevention and/or management of VILI.
C1 [Villar, Jesus; Cabrera, Nuria E.; Valladares, Francisco; Casula, Milena; Flores, Carlos; Blanch, Lluis; Elisa Quilez, Maria] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
[Villar, Jesus; Cabrera, Nuria E.; Casula, Milena; Santana-Rodriguez, Norberto] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain.
[Villar, Jesus; Slutsky, Arthur S.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada.
[Valladares, Francisco] Univ La Laguna, Dept Anat Pathol & Histol, Tenerife, Spain.
[Flores, Carlos] Hosp Univ NS Candelaria, Res Unit, Santa Cruz De Tenerife, Spain.
[Blanch, Lluis; Elisa Quilez, Maria] Corp Sanitaria Parc Tauli, Crit Care Ctr, Barcelona, Spain.
[Santana-Rodriguez, Norberto] Hosp Univ Dr Negrin, Dept Thorac Surg, Las Palmas Gran Canaria, Spain.
[Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA.
[Slutsky, Arthur S.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada.
[Slutsky, Arthur S.] King Saud Univ, Riyadh, Saudi Arabia.
RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
EM jesus.villar54@gmail.com
FU Ministry of Science, Spain [SAF 2004-06833, PI10/0393]
FX This work was supported by grants from the Ministry of Science, Spain
(SAF 2004-06833 and PI10/0393). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 42
TC 33
Z9 36
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 SEP 15
PY 2011
VL 6
IS 9
AR e23914
DI 10.1371/journal.pone.0023914
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822JR
UT WOS:000295041700002
PM 21935365
ER
PT J
AU Patterson, HC
Kraus, M
Wang, DH
Shahsafaei, A
Henderson, JM
Seagal, J
Otipoby, KL
Thai, TH
Rajewsky, K
AF Patterson, Heide Christine
Kraus, Manfred
Wang, Donghai
Shahsafaei, Aliakbar
Henderson, Joel M.
Seagal, Jane
Otipoby, Kevin L.
Thai, To-Ha
Rajewsky, Klaus
TI Cytoplasmic Iga Serine/Threonines Fine-Tune Ig alpha Tyrosine
Phosphorylation and Limit Bone Marrow Plasma Cell Formation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ANTIGEN RECEPTOR COMPLEX; HIGH-AFFINITY RECEPTOR; ACTIVATION MOTIF ITAM;
B-LYMPHOCYTE; MICE; PROLIFERATION; RESPONSES; KINASE; BETA;
DIFFERENTIATION
AB Ig alpha serine 191 and 197 and threonine 203, which are located in proximity of the Ig alpha ITAM, dampen Ig alpha ITAM tyrosine phosphorylation. In this study, we show that mice with targeted mutations of Ig alpha S191, 197, and T203 displayed elevated serum IgG2c and IgG2b concentrations and had elevated numbers of IgG2c- and IgG2b-secreting cells in the bone marrow. BCR-induced Ig alpha tyrosine phosphorylation was slightly increased in splenic B cells. Our results suggest that Ig alpha serine/threonines limit formation of IgG2c- and IgG2b-secreting bone marrow plasma cells, possibly by fine-tuning Ig alpha tyrosine-mediated BCR signaling. The Journal of Immunology, 2011, 187: 2853-2858.
C1 [Patterson, Heide Christine; Kraus, Manfred; Wang, Donghai; Seagal, Jane; Otipoby, Kevin L.; Thai, To-Ha; Rajewsky, Klaus] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Patterson, Heide Christine; Kraus, Manfred; Wang, Donghai; Seagal, Jane; Otipoby, Kevin L.; Thai, To-Ha; Rajewsky, Klaus] Immune Dis Inst, Boston, MA 02115 USA.
[Patterson, Heide Christine; Shahsafaei, Aliakbar; Henderson, Joel M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kraus, Manfred] Merck Res Labs, Boston, MA 02115 USA.
[Wang, Donghai] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
[Henderson, Joel M.] Boston Univ, Med Ctr, Boston, MA 02118 USA.
[Seagal, Jane] Abbott Biores Ctr, Worcester, MA 01605 USA.
[Otipoby, Kevin L.] Biogen Idec Inc, Cambridge, MA 02142 USA.
[Thai, To-Ha] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Rajewsky, K (reprint author), Childrens Hosp, Program Cellular & Mol Med, 200 Longwood Ave, Boston, MA 02115 USA.
EM rajewsky@idi.harvard.edu
FU National Institutes of Health [R37 AI054636]; Deutsche
Forschungsgemeinschaft; T32 training grant
FX This work was supported by the National Institutes of Health (Grant R37
AI054636) and a research fellowship from the Deutsche
Forschungsgemeinschaft and T32 training grant (transfusion medicine) (to
H. C. P.).
NR 35
TC 5
Z9 5
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 15
PY 2011
VL 187
IS 6
BP 2853
EP 2858
DI 10.4049/jimmunol.1101143
PG 6
WC Immunology
SC Immunology
GA 822HI
UT WOS:000295034200003
PM 21841126
ER
PT J
AU Lu, TX
Hartner, J
Lim, EJ
Fabry, V
Mingler, MK
Cole, ET
Orkin, SH
Aronow, BJ
Rothenberg, ME
AF Lu, Thomas X.
Hartner, Jochen
Lim, Eun-Jin
Fabry, Victoria
Mingler, Melissa K.
Cole, Eric T.
Orkin, Stuart H.
Aronow, Bruce J.
Rothenberg, Marc E.
TI MicroRNA-21 Limits In Vivo Immune Response-Mediated Activation of the
IL-12/IFN-gamma Pathway, Th1 Polarization, and the Severity of
Delayed-Type Hypersensitivity
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EXPERIMENTAL ASTHMA; DENDRITIC CELLS; EXPRESSION; GENE; PATHOGENESIS;
INFLAMMATION; CYTOKINES; GAMMA; DISSECTION; INNATE
AB An altered balance between Th1 and Th2 cytokines is responsible for a variety of immunoinflammatory disorders such as asthma, yet the role of posttranscriptional mechanisms, such as those mediated by microRNAs (miRs), in adjusting the relative magnitude and balance of Th cytokine expression have been largely unexplored. In this study, we show that miR-21 has a central role in setting a balance between Th1 and Th2 responses to Ags. Targeted ablation of miR-21 in mice led to reduced lung eosinophilia after allergen challenge, with a broadly reprogrammed immunoactivation transcriptome and significantly increased levels of the Th1 cytokine IFN-gamma. Biological network-based transcriptome analysis of OVA-challenged miR-21(-/-) mice identified an unexpected prominent dysregulation of IL-12/IFN-gamma pathways as the most significantly affected in the lungs, with a key role for miR-21 in IFN-g signaling and T cell polarization, consistent with a functional miR-21 binding site in IL-12p35. In support of these hypotheses, miR-21 deficiency led dendritic cells to produce more IL-12 after LPS stimulation and OVA-challenged CD4(+) T lymphocytes to produce increased IFN-gamma and decreased IL-4. Further, loss of miR-21 significantly enhanced the Th1-associated delayed-type hypersensitivity cutaneous responses. Thus, our results define miR-21 as a major regulator of Th1 versus Th2 responses, defining a new mechanism for regulating polarized immunoinflammatory responses. The Journal of Immunology, 2011, 187: 3362-3373.
C1 [Lu, Thomas X.; Lim, Eun-Jin; Fabry, Victoria; Mingler, Melissa K.; Cole, Eric T.; Rothenberg, Marc E.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Div Allergy & Immunol,Med Ctr, Cincinnati, OH 45229 USA.
[Lu, Thomas X.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Grad Program Mol & Dev Biol,Med Ctr, Cincinnati, OH 45229 USA.
[Lu, Thomas X.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Phys Scientist Training Program,Med Ctr, Cincinnati, OH 45229 USA.
[Hartner, Jochen; Orkin, Stuart H.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Hartner, Jochen; Orkin, Stuart H.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Hartner, Jochen; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Aronow, Bruce J.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Div Biomed Informat,Med Ctr, Cincinnati, OH 45229 USA.
RP Rothenberg, ME (reprint author), Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Div Allergy & Immunol,Med Ctr, 3333 Burnet Ave,ML7028, Cincinnati, OH 45229 USA.
EM Rothenberg@cchmc.org
FU National Heart, Lung, and Blood Institute [F30HL104892]; Albert J. Ryan
Foundation; National Institutes of Health [T32HD046387, R01AI083450];
National Institute of Diabetes and Digestive and Kidney Diseases
[P30DK049216]; Campaign Urging Research for Eosinophilic Disease;
Buckeye Foundation; Food Allergy Project/Food Allergy Initiative
FX This work was supported by the Ruth L. Kirschstein National Research
Service Award for individual predoctoral M.D./Ph.D. fellows
(F30HL104892) from the National Heart, Lung, and Blood Institute (to
T.X.L.), the Ryan Fellowship from the Albert J. Ryan Foundation (to
T.X.L.), and the Organogenesis Training grant (National Institutes of
Health Grant T32HD046387 to T.X.L.). Targeted mice were generated in the
Center for Excellence in Molecular Hematology at Children's Hospital
Boston, which is supported in part by a grant from the National
Institute of Diabetes and Digestive and Kidney Diseases (P30DK049216).
Additionally, this work was supported by National Institutes of Health
Grant R01AI083450 (to M.E.R.), the Campaign Urging Research for
Eosinophilic Disease, the Buckeye Foundation, and the Food Allergy
Project/Food Allergy Initiative.
NR 40
TC 130
Z9 152
U1 0
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 15
PY 2011
VL 187
IS 6
BP 3362
EP 3373
DI 10.4049/jimmunol.1101235
PG 12
WC Immunology
SC Immunology
GA 822HI
UT WOS:000295034200056
PM 21849676
ER
PT J
AU Zhou, F
Sikorski, TW
Ficarro, SB
Webber, JT
Marto, JA
AF Zhou, Feng
Sikorski, Timothy W.
Ficarro, Scott B.
Webber, James T.
Marto, Jarrod A.
TI Online Nanoflow Reversed Phase-Strong Anion Exchange-Reversed Phase
Liquid Chromatography-Tandem Mass Spectrometry Platform for Efficient
and In-Depth Proteome Sequence Analysis of Complex Organisms
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID STRONG CATION-EXCHANGE; LINEAR ION-TRAP; SHOTGUN PROTEOMICS;
SACCHAROMYCES-CEREVISIAE; AFFINITY PURIFICATION; POLYACRYLAMIDE-GELS;
SIGNALING NETWORKS; YEAST PROTEOME; DYNAMIC-RANGE; STEM-CELLS
AB The dynamic range of protein expression in complex organisms coupled with the stochastic nature of discovery-driven tandem mass spectrometry (MS/MS) analysis continues to impede comprehensive sequence analysis and often provides only limited information for low-abundance proteins. High-performance fractionation of proteins or peptides prior to mass spectrometry analysis can mitigate these effects, though achieving an optimal combination of automation, reproducibility, separation peak capacity, and sample yield remains a significant challenge. Here we demonstrate an automated nanoflow 3-D liquid chromatography (LC)-MS/MS platform based on high-pH reversed phase (RP), strong anion exchange (SAX), and low-pH reversed phase (RP) separation stages for analysis of complex proteomes. We observed that RP-SAX-RP outperformed RP-RP for analysis of tryptic peptides derived from Escherichia coli and enabled identification of proteins present at a level of SO copies per cell in Saccharomyces cerevisiae, corresponding to an estimated detection limit of 500 amol, from 40 mu g of total lysate on a low-resolution 3-D ion trap mass spectrometer. A similar study performed on a LTQ:Orbitrap yielded over 4000 unique proteins from 5 mu g of total yeast lysate analyzed in a single, 101 fraction RP-SAX-RP LC-MS/MS acquisition, providing an estimated detection limit of 65 amol for proteins expressed at 50 copies per cell.
C1 [Zhou, Feng; Sikorski, Timothy W.; Ficarro, Scott B.; Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Ficarro, Scott B.; Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA.
[Zhou, Feng; Sikorski, Timothy W.; Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,Smith 1158A, Boston, MA 02215 USA.
EM jarrod_marto@dfci.harvard.edu
OI Webber, James/0000-0001-8594-9888
FU National Institutes of Health, NHGRI [P50HG004233]; NINDS [P01NS047572]
FX The authors thank Eric Smith for assistance with the figures. In
addition the authors thank Keith Fadgen, Jim Murphy, and Geoff Gerhardt
of Waters Corp. for valuable discussions and technical assistance.
Generous support for this work was provided by the Dana-Farber Cancer
Institute and the National Institutes of Health, NHGRI (Grant
P50HG004233) and NINDS (Grant P01NS047572).
NR 71
TC 30
Z9 34
U1 1
U2 31
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD SEP 15
PY 2011
VL 83
IS 18
BP 6996
EP 7005
DI 10.1021/ac200639v
PG 10
WC Chemistry, Analytical
SC Chemistry
GA 818XM
UT WOS:000294790000013
PM 21851055
ER
PT J
AU Ouillette, P
Collins, R
Shakhan, S
Li, JH
Peres, E
Kujawski, L
Talpaz, M
Kaminski, M
Li, C
Shedden, K
Malek, SN
AF Ouillette, Peter
Collins, Roxane
Shakhan, Sajid
Li, Jinghui
Peres, Edward
Kujawski, Lisa
Talpaz, Moshe
Kaminski, Mark
Li, Cheng
Shedden, Kerby
Malek, Sami N.
TI Acquired genomic copy number aberrations and survival in chronic
lymphocytic leukemia
SO BLOOD
LA English
DT Article
ID SIGNIFICANT CLINICAL ACTIVITY; ACUTE MYELOGENOUS LEUKEMIA; ACUTE
MYELOID-LEUKEMIA; MUTATION STATUS; CLL PATIENTS; CHROMOSOMAL
TRANSLOCATIONS; GENETIC-CHARACTERIZATION; TELOMERE DYSFUNCTION;
UNIPARENTAL DISOMY; CD38 EXPRESSION
AB Genomic aberrations are of predominant importance to the biology and clinical outcome of patients with chronic lymphocytic leukemia (CLL), and FISH-based genomic risk classifications are routinely used in clinical decision making in CLL. One of the known limitations of CLL FISH is the inability to comprehensively interrogate the CLL genome for genomic changes. In an effort at overcoming the existing limitations in CLL genome analysis, we have analyzed high-purity DNA isolated from FACS-sorted CD19(+) cells and paired CD3(+) or buccal cells from 255 patients with CLL for acquired genomic copy number aberrations (aCNAs) with the use of ultra-high-density Affymetrix SNP 6.0 arrays. Overall, >= 2 subchromosomal aCNAs were found in 39% (100 of 255) of all cases analyzed, whereas >= 3 subchromosomal aCNAs were detected in 20% (50 of 255) of cases. Subsequently, we have correlated genomic lesion loads (genomic complexity) with the clinical outcome measures time to first therapy and overall survival. With the use of multivariate analyses incorporating the most important prognostic factors in CLL together with SNP 6.0 array-based genomic lesion loads at various thresholds, we identify elevated CLL genomic complexity as an independent and powerful marker for the identification of patients with aggressive CLL and short survival. (Blood. 2011;118(11):3051-3061)
C1 [Ouillette, Peter; Collins, Roxane; Shakhan, Sajid; Li, Jinghui; Peres, Edward; Kujawski, Lisa; Talpaz, Moshe; Kaminski, Mark; Malek, Sami N.] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA.
[Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Li, Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Shedden, Kerby] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
RP Malek, SN (reprint author), Univ Michigan, Dept Internal Med, Div Hematol & Oncol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM smalek@med.umich.edu
FU National Institutes of Health [1R01 CA136537-01]; Leukemia & Lymphoma
Society of America; National Institutes of Health through the University
of Michigan's Cancer Center [5 P30 CA46592]
FX This work was supported by the National Institutes of Health through
grant 1R01 CA136537-01 (S.N.M.), by the Translational Research Program
of the Leukemia & Lymphoma Society of America (S.N.M.), and in part by
the National Institutes of Health through the University of Michigan's
Cancer Center Support Grant (5 P30 CA46592).
NR 50
TC 59
Z9 59
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 15
PY 2011
VL 118
IS 11
BP 3051
EP 3061
DI 10.1182/blood-2010-12-327858
PG 11
WC Hematology
SC Hematology
GA 821DU
UT WOS:000294955900022
PM 21795749
ER
PT J
AU Wilson, AJ
Holson, E
Wagner, F
Zhang, YL
Fass, DM
Haggarty, SJ
Bhaskara, S
Hiebert, SW
Schreiber, SL
Khabele, D
AF Wilson, Andrew J.
Holson, Edward
Wagner, Florence
Zhang, Yan-Ling
Fass, Daniel M.
Haggarty, Stephen J.
Bhaskara, Srividya
Hiebert, Scott W.
Schreiber, Stuart L.
Khabele, Dineo
TI The DNA damage mark pH2AX differentiates the cytotoxic effects of small
molecule HDAC inhibitors in ovarian cancer cells
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE histone deacetylase inhibitors (HDACi); pH2AX; ovarian cancer
ID HISTONE DEACETYLASE INHIBITORS; COLON-CANCER; EPITHELIAL OVARIAN;
ANTITUMOR-ACTIVITY; TUMOR-CELLS; GROWTH; BENZAMIDE; APOPTOSIS; POTENT;
FK228
AB High grade epithelial ovarian cancers are relatively sensitive to DNA damaging platinum-based chemotherapy, suggesting that the dependencies of ovarian tumors on DNA damage response pathways can be harnessed for therapeutic purposes. Our goal was to determine if the DNA damage mark gamma- H2AX phosphorylation (pH2AX) could be used to identify suitable cytotoxic histone deacetylase inhibitors (HDACi) for ovarian cancer treatment. Nineteen chemically diverse HDACi compounds were tested in 7 ovarian cancer cell lines. Fluorescent, biochemical and cell-based assays were performed to assess DNA damage by induction of pH2AX and to measure cell viability and apoptosis. The relationships between pH2AX and the cellular effects of cell viability and apoptosis were calculated. Selected HDACi were tested in combination with cisplatin and other DNA damaging agents to determine if the HDACi improved upon the effects of the DNA damaging agents. The HDACi compounds induced differing levels of pH2AX expression. High levels of pH2AX in HDACi-treated ovarian cancer cells were tightly associated with decreased cell viability and increased apoptosis. Consequently, a ketone-based HDACi was chosen and found to enhance the effects of cisplatin, even in ovarian cancer cells with extreme resistance to DNA damaging drugs. In conclusion, a fluorescent-based assay for pH2AX can be used to determine cellular responses to HDACi in vitro and may be a useful tool to identify potentially more effective HDACi for the treatment of ovarian cancer. In addition, these results lend support to the inclusion of ketone-derived HDACi compounds for future development.
C1 [Wilson, Andrew J.; Khabele, Dineo] Vanderbilt Univ Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, Nashville, TN 37203 USA.
[Bhaskara, Srividya] Vanderbilt Univ Sch Med, Dept Biochem, Nashville, TN USA.
[Hiebert, Scott W.; Khabele, Dineo] Vanderbilt Univ Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Holson, Edward; Wagner, Florence; Zhang, Yan-Ling; Fass, Daniel M.; Haggarty, Stephen J.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Chem Biol Program, Broad Inst, Cambridge, MA 02138 USA.
RP Khabele, D (reprint author), Vanderbilt Univ Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, Nashville, TN 37203 USA.
EM dineo.khabele@vanderbilt.edu
OI Bhaskara, Srividya/0000-0002-2182-9585; Haggarty, Stephen
J./0000-0002-7872-168X
FU NIH [1K08CA148887-01, 5P30 CA068485, CA091408 5 U54, 1UL1 RR024975,
5R01DA028301-02]
FX NIH grants: 1K08CA148887-01 (D.K.); 5P30 CA068485; CA091408 5 U54; 1UL1
RR024975; and 5R01DA028301-02 (S.J.H.), Stanley Medical Research
Institute. The Gynecologic Cancer Foundation and Gloucester
Pharmaceuticals (Celgene Corp.) (D.K.). The Vanderbilt
immunohistochemistry, Translational Pathology Shared Resource and
High-Throughput Screening Cores. The Broad Institute Visiting Faculty
Program.
NR 48
TC 19
Z9 20
U1 0
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD SEP 15
PY 2011
VL 12
IS 6
BP 484
EP 493
DI 10.4161/cbt.12.6.15956
PG 10
WC Oncology
SC Oncology
GA 821DJ
UT WOS:000294954700003
PM 21738006
ER
PT J
AU Mostaghel, EA
Marck, BT
Plymate, SR
Vessella, RL
Balk, S
Matsumoto, AM
Nelson, PS
Montgomery, RB
AF Mostaghel, Elahe A.
Marck, Brett T.
Plymate, Stephen R.
Vessella, Robert L.
Balk, Stephen
Matsumoto, Alvin M.
Nelson, Peter S.
Montgomery, R. Bruce
TI Resistance to CYP17A1 Inhibition with Abiraterone in
Castration-Resistant Prostate Cancer: Induction of Steroidogenesis and
Androgen Receptor Splice Variants
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENE-EXPRESSION; CYTOCHROME P450(17-ALPHA); THERAPEUTIC IMPLICATIONS;
STEROIDAL INHIBITORS; ANTITUMOR-ACTIVITY; PROGRESSION; ACETATE;
DEHYDROGENASE; GROWTH; ANTIANDROGEN
AB Purpose: Abiraterone is a potent inhibitor of the steroidogenic enzyme CYP17A1 and suppresses tumor growth in patients with castration-resistant prostate cancer (CRPC). The effectiveness of abiraterone in reducing tumor androgens is not known, nor have mechanisms contributing to abiraterone resistance been established.
Experimental Design: We treated human CRPC xenografts with abiraterone and measured tumor growth, tissue androgens, androgen receptor (AR) levels, and steroidogenic gene expression versus controls.
Results: Abiraterone suppressed serum PSA levels and improved survival in two distinct CRPC xenografts: median survival of LuCaP35CR improved from 17 to 39 days (HR = 3.6, P = 0.0014) and LuCaP23CR from 14 to 24 days (HR = 2.5, P = 0.0048). Abiraterone strongly suppressed tumor androgens, with testosterone (T) decreasing from 0.49 +/- 0.22 to 0.03 +/- 0.01 pg/mg (P < 0.0001), and from 0.69 +/- 0.36 to 0.03 +/- 0.01 pg/mg (P = 0.002) in abiraterone-treated 23CR and 35CR, respectively, with comparable decreases in tissue DHT. Treatment was associated with increased expression of full-length AR (AR(FL)) and truncated AR variants (AR(FL) 2.3-fold, P = 0.008 and AR(del567es) 2.7-fold, P = 0.036 in 23 CR; AR(FL) 3.4-fold, P = 0.001 and AR(V7) 3.1-fold, P = 0.0003 in 35CR), and increased expression of the abiraterone target CYP17A1 (similar to 2.1- fold, P = 0.0001 and P = 0.028 in 23CR and 35CR, respectively) and transcript changes in other enzymes modulating steroid metabolism.
Conclusions: These studies indicate that abiraterone reduces CRPC growth via suppression of intratumoral androgens and that resistance to abiraterone may occur through mechanisms that include upregulation of CYP17A1, and/or induction of AR and AR splice variants that confer ligand-independent AR transactivation. Clin Cancer Res; 17(18); 5913-25. (C) 2011 AACR.
C1 [Mostaghel, Elahe A.; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
[Mostaghel, Elahe A.; Plymate, Stephen R.; Matsumoto, Alvin M.; Nelson, Peter S.; Montgomery, R. Bruce] Univ Washington, Dept Med, Seattle, WA USA.
[Marck, Brett T.; Plymate, Stephen R.; Matsumoto, Alvin M.; Montgomery, R. Bruce] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Vessella, Robert L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Balk, Stephen] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Mostaghel, EA (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA.
EM emostagh@fhcrc.org
FU Cougar Biotechnology; Prostate Cancer Foundation; Damon Runyon Cancer
Research Foundation [CI-40-08]; NIH [K23 CA122820, P50 CA97186]; Cancer
Center [P30 CA015704]; Veterans Affairs Research Service
FX R.B. Montomery received commercial research grant from Cougar
Biotechnology. The other authors disclosed no potential conflicts of
interest.; Prostate Cancer Foundation (Career Development Award to E.A.
Mostaghel and Synergy Award to S. Balk, R.B. Montgomery, and P. S.
Nelson); Damon Runyon Cancer Research Foundation (Damon Runyon-Genentech
Clinical Investigator Award CI-40-08 to E.A. Mostaghel); NIH [Career
Development Award K23 CA122820 to E.A. Mostaghel; Pacific Northwest
Prostate Cancer SPORE P50 CA97186 (R.L. Vessella, P. S. Nelson); the
Cancer Center Support Grant to Fred Hutchinson Cancer Research Center
(P30 CA015704 pilot to R.B. Montgomery)]; and the Veterans Affairs
Research Service (S.R. Plymate).
NR 42
TC 278
Z9 282
U1 3
U2 21
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 SEP 15
PY 2011
VL 17
IS 18
BP 5913
EP 5925
DI 10.1158/1078-0432.CCR-11-0728
PG 13
WC Oncology
SC Oncology
GA 821CM
UT WOS:000294952400009
PM 21807635
ER
PT J
AU Kim, SG
Veena, MS
Basak, SK
Han, E
Tajima, T
Gjertson, DW
Starr, J
Eidelman, O
Pollard, HB
Srivastava, M
Srivatsan, ES
Wang, MB
AF Kim, Suejung G.
Veena, Mysore S.
Basak, Saroj K.
Han, Eugene
Tajima, Tracey
Gjertson, David W.
Starr, Joshua
Eidelman, Ofer
Pollard, Harvey B.
Srivastava, Meera
Srivatsan, Eri S.
Wang, Marilene B.
TI Curcumin Treatment Suppresses IKK beta Kinase Activity of Salivary Cells
of Patients with Head and Neck Cancer: A Pilot Study
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID FACTOR-KAPPA-B; INDEPENDENT PATHWAY; CARCINOMA; INHIBITION; GROWTH;
INTERLEUKIN-6; PROLIFERATION
AB Purpose: To determine whether curcumin would inhibit I kappa B kinase beta (IKK beta) kinase activity and suppress expression of proinflammatory cytokines in head and neck squamous cell carcinoma cancer (HNSCC) patients.
Experimental Design: Saliva was collected before and after subjects chewed curcumin tablets. Protein was extracted and IKK beta kinase activity measured. Interleukin (IL)-6 and IL-8 levels in the salivary supernatants were measured by ELISA. IL-6, IL-8, and other interleukin were also measured independently with ELISA to confirm the inhibitory effect of curcumin on expression and secretion of salivary cytokines.
Results: Curcumin treatment led to a reduction in IKK beta kinase activity in the salivary cells of HNSCC patients ( P < 0.05). Treatment of UM-SCC1 cells with curcumin as well as with post-curcumin salivary supernatant showed a reduction of IKK beta kinase activity. Significant reduction of IL-8 levels ( P < 0.05) was seen in post-curcumin samples from patients with dental caries. Although there was reduced IL-8 expression in 8 of 21 post-curcumin samples of HNSCC patients, the data did not reach statistical significance. Saliva samples from HNSCC patients were also analyzed in a blinded fashion for expression of cytokines. IL-10, IFN-gamma, IL-12p70, and IL-2 clustered together, and granulocyte macrophage colony stimulating factor and TNF-alpha clustered together. Log(10) ratio analysis showed decrease in expression of all nine cytokines in both the salivary supernatant and salivary cells of curcumin-treated samples.
Conclusions: Curcumin inhibited IKK beta kinase activity in the saliva of HNSCC patients, and this inhibition correlated with reduced expression of a number of cytokines. IKK beta kinase could be a useful biomarker for detecting the effect of curcumin in head and neck cancer. Clin Cancer Res; 17( 18); 5953-61. (C) 2011 AACR.
C1 [Wang, Marilene B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, Los Angeles, CA 90095 USA.
[Gjertson, David W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Kim, Suejung G.; Veena, Mysore S.; Basak, Saroj K.; Han, Eugene; Srivatsan, Eri S.; Wang, Marilene B.] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA.
[Tajima, Tracey] VA Greater Los Angeles Healthcare Syst, Dept Dent, Los Angeles, CA USA.
[Starr, Joshua; Eidelman, Ofer; Pollard, Harvey B.; Srivastava, Meera] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Starr, Joshua; Eidelman, Ofer; Pollard, Harvey B.; Srivastava, Meera] Uniformed Serv Univ Hlth Sci, Sch Med, Inst Mol Med, Bethesda, MD 20814 USA.
RP Wang, MB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Head & Neck Surg, 200 UCLA Med Plaza,Suite 550, Los Angeles, CA 90095 USA.
EM mbwang@ucla.edu
FU VAGLAHS; West Los Angeles Surgical Education Research Center; UCLA; NIH
[R21 CA116826-01]; Veterans Administration, Washington, DC
FX The study was supported by funds from VAGLAHS, West Los Angeles Surgical
Education Research Center, UCLA Academic Senate grant (M.B. Wang), NIH
(R21 CA116826-01 to M. Wang), and Merit grant from the Veterans
Administration, Washington, DC (E.S. Srivatsan).
NR 20
TC 26
Z9 26
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 15
PY 2011
VL 17
IS 18
BP 5953
EP 5961
DI 10.1158/1078-0432.CCR-11-1272
PG 9
WC Oncology
SC Oncology
GA 821CM
UT WOS:000294952400013
PM 21821700
ER
PT J
AU Yang, XM
Turke, AB
Qi, J
Song, Y
Rexer, BN
Miller, TW
Janne, PA
Arteaga, CL
Cantley, LC
Engelman, JA
Asara, JM
AF Yang, Xuemei
Turke, Alexa B.
Qi, Jie
Song, Youngchul
Rexer, Brent N.
Miller, Todd W.
Jaenne, Pasi A.
Arteaga, Carlos L.
Cantley, Lewis C.
Engelman, Jeffrey A.
Asara, John M.
TI Using Tandem Mass Spectrometry in Targeted Mode to Identify Activators
of Class IA PI3K in Cancer
SO CANCER RESEARCH
LA English
DT Article
ID TYROSINE KINASE INHIBITORS; CELL LUNG-CANCER; QUANTITATIVE PROTEOMICS;
BREAST-CANCER; ACQUIRED-RESISTANCE; MET AMPLIFICATION; PIK3CA MUTATIONS;
PATHWAY; PROTEINS; GROWTH
AB Phosphatiditylinositide-3-kinase (PI3K) is activated in some cancers by direct mutation, but it is activated more commonly in cancer by mutation of upstream acting receptor tyrosine kinases (TK). At present, there is no systematic method to determine which TK signaling cascades activate PI3K in certain cancers, despite the likely utility of such information to help guide selection of tyrosine kinase inhibitor (TKI) drug strategies for personalized therapy. Here, we present a quantitative liquid chromatography tandem mass spectrometry approach that identifies upstream activators of PI3K both in vitro and in vivo. Using non-small cell lung carcinoma to illustrate this approach, we show a correct identification of the mechanism of PI3K activation in several models, thereby identifying the most appropriate TKI to downregulate PI3K signaling. This approach also determined the molecular mechanisms and adaptors required for PI3K activation following inhibition of the mTOR kinase TORC1. We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation. Overall, our findings establish a mass spectrometric approach to identify functional interactions that govern PI3K regulation in cancer cells. Using this technique to define the pathways that activate PI3K signaling in a given tumor could help inform clinical decision making by helping guide personalized therapeutic strategies for different patients. Cancer Res; 71(18); 5965-75. (C) 2011 AACR.
C1 [Yang, Xuemei; Cantley, Lewis C.; Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
[Turke, Alexa B.; Qi, Jie; Song, Youngchul; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Thorac Canc, Boston, MA 02114 USA.
[Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Rexer, Brent N.; Miller, Todd W.; Arteaga, Carlos L.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
RP Asara, JM (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
EM jengelman@partners.org; jasara@bidmc.harvard.edu
RI Cantley, Lewis/D-1800-2014
OI Cantley, Lewis/0000-0002-1298-7653
FU NIH [5P01CA120964-04, K08 CA120060, R01CA137008, R01CA140594,
R01-GM41890, P01CA089021, R01CA135257-01, R01CA136851, P50CA98131]; NIH
DF/HCC Cancer Center [5P30CA006516-46]; NIH DF/HCC [P50 CA127003]; NCI
[P50CA090578]; NIH Vanderbilt-Ingram Cancer Center [P30CA68485]; ACS
[CRP-07-234]; Stand Up to Cancer/AACR Dream Team Translational Cancer
Research Grant [SU2C-AACR-DT0209]
FX The work was supported in part by NIH 5P01CA120964-04 and NIH DF/HCC
Cancer Center Support Grant 5P30CA006516-46 (J.M. Asara), NIH K08
CA120060 (J.A. Engelman), R01CA137008 (J.A. Engelman, P. A. Janne),
R01CA140594 (J.A. Engelman), NIH DF/HCC Gastrointestinal Cancers SPORE
P50 CA127003 (J.A. Engelman and L. C. Cantley), NCI Lung SPORE
P50CA090578 (J.A. Engelman, P. A. Janne), NIH R01-GM41890 and
P01CA089021 (L. C. Cantley), NIH R01CA135257-01 (P. A. Janne and J.A.
Engelman), and NIH R01CA136851 (P. A. Janne). NIH Breast Cancer SPORE
P50CA98131, NIH Vanderbilt-Ingram Cancer Center Support Grant
P30CA68485, ACS Clinical Research Professorship Grant CRP-07-234 (C. L.
Arteaga), and Stand Up to Cancer/AACR Dream Team Translational Cancer
Research Grant, grant no. SU2C-AACR-DT0209 (C. L. Arteaga and L. C.
Cantley).
NR 50
TC 10
Z9 11
U1 1
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 SEP 15
PY 2011
VL 71
IS 18
BP 5965
EP 5975
DI 10.1158/0008-5472.CAN-11-0445
PG 11
WC Oncology
SC Oncology
GA 819QJ
UT WOS:000294843600003
PM 21775521
ER
PT J
AU Anand, S
Wilson, C
Hasan, T
Maytin, EV
AF Anand, Sanjay
Wilson, Clara
Hasan, Tayyaba
Maytin, Edward V.
TI Vitamin D3 Enhances the Apoptotic Response of Epithelial Tumors to
Aminolevulinate-Based Photodynamic Therapy
SO CANCER RESEARCH
LA English
DT Article
ID INDUCED PROTOPORPHYRIN-IX; PROSTATE-CANCER CELLS; NECROSIS-FACTOR-ALPHA;
METHYL-AMINOLEVULINATE; IN-VITRO; 1-ALPHA,25-DIHYDROXYVITAMIN D-3;
PORPHOBILINOGEN DEAMINASE; ACTINIC KERATOSES; ACID; DIFFERENTIATION
AB Photodynamic therapy, mediated by exogenously administered aminolevulinic acid (ALA-PDT), followed by exposure to a laser or broadband light source, is a promising modality for treatment of many types of cancers; however, it remains inadequate to treat large, deep, solid tumors. In this article, we report that calcitriol, the active form of vitamin D3, can be administered before ALA as a nontoxic preconditioning regimen to markedly increase the efficacy of ALA-PDT. Using mouse models of squamous cell skin cancer for preclinical proof of concept, we showed that calcitriol, delivered topically or intraperitoneally, increased tumoral accumulation of the PDT-activated ALA product protoporphyrin-IX (PpIX) up to 10-fold, mainly by altering expression of the porphyrin-synthesis enzymes coproporphyrinogen oxidase (increased) and ferrochelatase (decreased). Calcitriol-pretreated tumors underwent enhanced apoptotic cell death after ALA-based PDT. Mechanistic studies have documented activation of the extrinsic apoptotic pathway, with specific cleavage of caspase-8 and increased production of TNF-alpha in tumors preconditioned by calcitriol treatment before receiving ALA-PDT. Very low doses of calcitriol (0.1-1 mu g/kg body weight) were sufficient to elicit tumor-selective enhancement to ALA-PDT efficacy, rendering toxicity concerns negligible. Our findings define a simple, nontoxic, and highly effective preconditioning regimen to enhance the response of epithelial tumors to ALA-PDT, possibly broadening its clinical applications by selectively enhancing accumulation of photosensitizer PpIX together with TNF-a in tumors. Cancer Res; 71(18); 6040-50. (C) 2011 AACR.
C1 [Anand, Sanjay; Maytin, Edward V.] Cleveland Clin, Dept Dermatol, Lerner Res Inst, Cleveland, OH 44195 USA.
[Anand, Sanjay; Wilson, Clara; Maytin, Edward V.] Cleveland Clin, Dept Biomed Engn, Lerner Res Inst, Cleveland, OH 44195 USA.
[Hasan, Tayyaba; Maytin, Edward V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.
RP Maytin, EV (reprint author), Cleveland Clin, Dept Dermatol, Lerner Res Inst, Mailstop ND 20,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM maytine@ccf.org
FU National Cancer Institute/NIH [P01-CA84203]
FX This work was supported by the National Cancer Institute/NIH grant
P01-CA84203 (T. Hasan and E.V. Maytin).
NR 50
TC 39
Z9 39
U1 0
U2 9
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 SEP 15
PY 2011
VL 71
IS 18
BP 6040
EP 6050
DI 10.1158/0008-5472.CAN-11-0805
PG 11
WC Oncology
SC Oncology
GA 819QJ
UT WOS:000294843600010
PM 21807844
ER
PT J
AU Sasaki, T
Koivunen, J
Ogino, A
Yanagita, M
Nikiforow, S
Zheng, W
Lathan, C
Marcoux, JP
Du, JY
Okuda, K
Capelletti, M
Shimamura, T
Ercan, D
Stumpfova, M
Xiao, Y
Weremowicz, S
Butaney, M
Heon, S
Wilner, K
Christensen, JG
Eck, MJ
Wong, KK
Lindeman, N
Gray, NS
Rodig, SJ
Janne, PA
AF Sasaki, Takaaki
Koivunen, Jussi
Ogino, Atsuko
Yanagita, Masahiko
Nikiforow, Sarah
Zheng, Wei
Lathan, Christopher
Marcoux, J. Paul
Du, Jinyan
Okuda, Katsuhiro
Capelletti, Marzia
Shimamura, Takeshi
Ercan, Dalia
Stumpfova, Magda
Xiao, Yun
Weremowicz, Stanislawa
Butaney, Mohit
Heon, Stephanie
Wilner, Keith
Christensen, James G.
Eck, Michel J.
Wong, Kwok-Kin
Lindeman, Neal
Gray, Nathanael S.
Rodig, Scott J.
Jaenne, Pasi A.
TI A Novel ALK Secondary Mutation and EGFR Signaling Cause Resistance to
ALK Kinase Inhibitors
SO CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; ANAPLASTIC LYMPHOMA KINASE; CHRONIC MYELOID-LEUKEMIA;
EML4-ALK FUSION GENE; GEFITINIB; AMPLIFICATION; IMATINIB; THERAPY;
TUMORS; IDENTIFICATION
AB Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers. However, their efficacy will ultimately be limited by the development of acquired drug resistance. Here we report two mechanisms of ALK TKI resistance identified from a crizotinib-treated non-small cell lung cancer (NSCLC) patient and in a cell line generated from the resistant tumor (DFCI076) as well as from studying a resistant version of the ALK TKI (TAE684)-sensitive H3122 cell line. The crizotinib-resistant DFCI076 cell line harbored a unique L1152R ALK secondary mutation and was also resistant to the structurally unrelated ALK TKI TAE684. Although the DFCI076 cell line was still partially dependent on ALK for survival, it also contained concurrent coactivation of epidermal growth factor receptor (EGFR) signaling. In contrast, the TAE684-resistant (TR3) H3122 cell line did not contain an ALK secondary mutation but instead harbored coactivation of EGFR signaling. Dual inhibition of both ALK and EGFR was the most effective therapeutic strategy for the DFCI076 and H3122 TR3 cell lines. We further identified a subset (3/50; 6%) of treatment naive NSCLC patients with ALK rearrangements that also had concurrent EGFR activating mutations. Our studies identify resistance mechanisms to ALK TKIs mediated by both ALK and by a bypass signaling pathway mediated by EGFR. These mechanisms can occur independently, or in the same cancer, suggesting that the combination of both ALK and EGFR inhibitors may represent an effective therapy for these subsets of NSCLC patients. Cancer Res; 71(18); 6051-60. (C) 2011 AACR.
C1 [Sasaki, Takaaki; Koivunen, Jussi; Ogino, Atsuko; Yanagita, Masahiko; Nikiforow, Sarah; Lathan, Christopher; Marcoux, J. Paul; Okuda, Katsuhiro; Capelletti, Marzia; Shimamura, Takeshi; Ercan, Dalia; Stumpfova, Magda; Butaney, Mohit; Heon, Stephanie; Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA.
[Sasaki, Takaaki; Koivunen, Jussi; Ogino, Atsuko; Yanagita, Masahiko; Nikiforow, Sarah; Lathan, Christopher; Marcoux, J. Paul; Okuda, Katsuhiro; Capelletti, Marzia; Shimamura, Takeshi; Ercan, Dalia; Stumpfova, Magda; Butaney, Mohit; Heon, Stephanie; Wong, Kwok-Kin; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Zheng, Wei; Eck, Michel J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Zheng, Wei; Eck, Michel J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA.
[Xiao, Yun; Weremowicz, Stanislawa; Lindeman, Neal; Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Nikiforow, Sarah; Lathan, Christopher; Marcoux, J. Paul; Shimamura, Takeshi; Heon, Stephanie; Wong, Kwok-Kin; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Du, Jinyan] Broad Inst, Cambridge, MA USA.
[Wilner, Keith; Christensen, James G.] Pfizer Global Res & Dev, Dept Res Pharmacol, La Jolla, CA USA.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820,450 Brookline Ave, Boston, MA 02215 USA.
EM pjanne@partners.org
OI Sasaki, Takaaki/0000-0002-6505-8786; wong, kwok kin/0000-0001-6323-235X
FU NIH [R01CA136851, R01CA135257]; Cammarata Family Foundation; NCI
[P50CA090578]
FX This study was supported by NIH R01CA136851 (N.S. Gray and P. A. Janne),
R01CA135257 (P. A. Janne), The Cammarata Family Foundation Research Fund
(P. A. Janne), and by the NCI Lung SPORE P50CA090578 (P.A. Janne).
NR 31
TC 270
Z9 278
U1 1
U2 25
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 SEP 15
PY 2011
VL 71
IS 18
BP 6051
EP 6060
DI 10.1158/0008-5472.CAN-11-1340
PG 10
WC Oncology
SC Oncology
GA 819QJ
UT WOS:000294843600011
PM 21791641
ER
PT J
AU Mylonakis, E
Muse, VV
Mino-Kenudson, M
AF Mylonakis, Eleftherios
Muse, Victorine V.
Mino-Kenudson, Mari
TI A Man with Pemphigus Vulgaris and Lung Nodules Cryptococcal infection of
the lung and central nervous system
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MENINGITIS; NEOFORMANS; THERAPY; ERA; MANAGEMENT; DIAGNOSIS
C1 [Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mylonakis, Eleftherios] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Muse, Victorine V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
FU Harvard Medical School Department of Continuing Education; Astellas; T2
Biosystems; Pfizer; Biomedical Systems
FX This case was discussed at the postgraduate course Infectious Diseases
of Adults, sponsored by the Harvard Medical School Department of
Continuing Education, Course Directors Stephen B. Calderwood, Nesli
Basgoz, and Jay A. Fishman.; Dr. Mylonakis reports receiving grant
support from Astellas and T2 Biosystems, fees for board membership from
Astellas, and lecture fees from Pfizer. Dr. Muse reports receiving
consulting fees and lecture fees from Biomedical Systems. No other
potential conflict of interest relevant to this article was reported.
NR 15
TC 0
Z9 1
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 SEP 15
PY 2011
VL 365
IS 11
BP 1043
EP 1050
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819UR
UT WOS:000294857300014
PM 21916643
ER
PT J
AU Goss, PE
Richardson, H
AF Goss, Paul E.
Richardson, Harriet
TI Exemestane for Breast-Cancer Prevention REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID WOMEN
C1 [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Richardson, Harriet] NCIC Clin Trials Grp, Kingston, ON, Canada.
RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM pgoss@partners.org
NR 5
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 SEP 15
PY 2011
VL 365
IS 11
BP 1057
EP 1058
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819UR
UT WOS:000294857300020
ER
PT J
AU Haspel, RL
Cserti-Gazdewich, C
Dzik, WH
AF Haspel, Richard L.
Cserti-Gazdewich, Christine
Dzik, Walter H.
TI Renal Improvement in Myeloma with Plasma Exchange
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID REMOVAL
C1 [Haspel, Richard L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Cserti-Gazdewich, Christine] Univ Hlth Network, Toronto, ON, Canada.
[Dzik, Walter H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Haspel, RL (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
EM rhaspel@bidmc.harvard.edu
NR 5
TC 2
Z9 2
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 SEP 15
PY 2011
VL 365
IS 11
BP 1061
EP 1062
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819UR
UT WOS:000294857300027
PM 21916653
ER
PT J
AU Branda, JA
Linskey, K
Kim, YA
Steere, AC
Ferraro, MJ
AF Branda, John A.
Linskey, Katy
Kim, Yeowon A.
Steere, Allen C.
Ferraro, Mary Jane
TI Two-Tiered Antibody Testing for Lyme Disease With Use of 2 Enzyme
Immunoassays, a Whole-Cell Sonicate Enzyme Immunoassay Followed by a
VlsE C6 Peptide Enzyme Immunoassay
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID LINKED-IMMUNOSORBENT-ASSAY; BORRELIA-BURGDORFERI; ANTIGENIC VARIATION;
IGG ELISA; DIAGNOSIS; SERODIAGNOSIS
AB Background. Lyme disease (LD) antibody testing currently involves a 2-tiered algorithm with a whole-cell sonicate (WCS) enzyme immunoassay (EIA), followed by IgM/IgG Western immunoblots. A single EIA using the C6 peptide of the Borrelia burgdorferi variable-major protein-like sequence expressed lipoprotein provides similar or better sensitivity but less specificity, compared with standard 2-tiered testing. Here, we investigated an alternative 2-tiered strategy, in which the first step remained a WCS EIA, but immunoblotting was replaced by a C6 EIA.
Methods. We determined the sensitivity of the 3 testing strategies with use of 91 serum samples from research study patients with LD and 78 serum samples from patients with LD whose samples were submitted to our hospital's clinical laboratory. Specificity was measured using 54 patients with other illnesses and 1246 healthy subjects from areas where the infection is endemic and nonendemic.
Results. The 2-EIA algorithm in early LD had similar sensitivity as C6 testing alone, and both strategies had better sensitivity than did standard 2-tiered testing (61% and 64%, respectively, vs 48%; P = .03 and P = .008). For late disease, all 3 strategies had 100% sensitivity. The specificity of the 2-EIA algorithm was equal to that of standard 2-tiered testing, and both 2-tiered strategies were more specific than C6 testing alone (for both, 99.5% vs 98.4%; P = .01). The positive predictive value of the 2-EIA algorithm was 70%, compared with 66% for standard 2-tiered testing and 43% for the C6 EIA alone.
Conclusions. The 2-EIA strategy matched the individual strengths of the C6 EIA and Western blotting, without the drawbacks. The 2 EIAs provided sensitivity comparable to that of the C6 EIA but maintained the specificity of standard 2-tiered testing.
C1 [Branda, John A.] Massachusetts Gen Hosp, Clin Microbiol Lab, Dept Pathol, Boston, MA 02114 USA.
[Branda, John A.; Linskey, Katy; Kim, Yeowon A.; Steere, Allen C.; Ferraro, Mary Jane] Harvard Univ, Sch Med, Boston, MA USA.
[Steere, Allen C.; Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Branda, JA (reprint author), Massachusetts Gen Hosp, Clin Microbiol Lab, Dept Pathol, GRB 526, Boston, MA 02114 USA.
EM branda.john@mgh.harvard.edu
FU CDC [CCU110291]; English, Bonter, Mitchell Foundation; Eshe Fund;
Massachusetts General Hospital; Viramed Biotech AG; Diasorin
FX This work was supported by the CDC (cooperative agreement CCU110291 to
A. C. S.), the English, Bonter, Mitchell Foundation, the Eshe Fund, and
the Lyme Disease and Arthritis Research Fund at Massachusetts General
Hospital (to A. C. S.).; A. C. S. has received a research grant from
Viramed Biotech AG in the past, to support an earlier study. J. A. B.
has received a research grant from Diasorin, to support a separate
study. M. J. F. has been a member of the scientific advisory board at
bioMerieux. All other authors report no potential conflicts.
NR 21
TC 40
Z9 40
U1 0
U2 4
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 SEP 15
PY 2011
VL 53
IS 6
BP 541
EP 547
DI 10.1093/cid/cir464
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 813JQ
UT WOS:000294363100013
PM 21865190
ER
PT J
AU Ruel, TD
Zanoni, BC
Ssewanyana, I
Cao, HY
Havlir, DV
Kamya, M
Achan, J
Charlebois, ED
Feeney, ME
AF Ruel, Theodore D.
Zanoni, Brian C.
Ssewanyana, Isaac
Cao, Huyen
Havlir, Diane V.
Kamya, Moses
Achan, Jane
Charlebois, Edwin D.
Feeney, Margaret E.
TI Sex Differences in HIV RNA Level and CD4 Cell Percentage During
Childhood
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID VIRUS TYPE-1 INFECTION; VIRAL LOAD; GENE-EXPRESSION; CHRONIC HEPATITIS;
IMMUNE-RESPONSE; PLASMA HIV; PROGRESSION; ACTIVATION; AIDS; CHILDREN
AB Background. HIV-infected women have lower HIV RNA levels and higher CD4-cell counts than do men. This observation has been attributed to the immunomodulatory effects of sex steroid hormones, such as estrogen and progesterone. Limited data exist regarding potential sex differences in HIV RNA level and CD4 parameters among prepubertal children with untreated HIV infection.
Methods. We examined the relationship of sex to HIV RNA level and CD4 parameters among 670 perinatally HIV-infected, antiretroviral therapy-naive African children aged < 18 years (median age, 4.8 years) using multivariate linear regression. In a subset of 188 children, we used longitudinal data to compare changes in HIV RNA levels and CD4 percentage over time. Levels of CD4 and CD8 T-cell activation (CD38+HLA-DR+) were also compared between boys and girls.
Results. Female children had lower HIV RNA levels (P = .0004) and higher CD4 percentages (P < .0001), compared to male children. Multivariate linear regression demonstrated an independent association of sex with both HIV RNA level and CD4 percentage after controlling for other covariates. Multilevel mixed-effects linear regression analysis of longitudinal HIV RNA level and CD4 parameter data showed that sex differences persisted across all observed ages. Levels of T-cell activation did not differ between the sexes.
Conclusions. Significant sex differences in HIV RNA levels and CD4 parameters are present in HIV-infected children before the onset of puberty. These data suggest that intrinsic genetic differences between male and female individuals, unrelated to sex steroid hormone levels, influence HIV RNA level and CD4 parameters in HIV-infected individuals.
C1 [Feeney, Margaret E.] Univ Calif San Francisco, Div Expt Med, Dept Med, San Francisco, CA 94110 USA.
[Ruel, Theodore D.; Feeney, Margaret E.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94110 USA.
[Zanoni, Brian C.; Feeney, Margaret E.] MGH MIT & Harvard, Ragon Inst, Boston, MA USA.
[Zanoni, Brian C.; Feeney, Margaret E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Zanoni, Brian C.; Feeney, Margaret E.] McCord Hosp, Sinikithemba Clin, Durban, South Africa.
[Zanoni, Brian C.; Feeney, Margaret E.] McCord Hosp, Philani Program, Durban, South Africa.
[Ssewanyana, Isaac] Joint Clin Res Ctr, Kampala, Uganda.
[Kamya, Moses] Makerere Univ, Coll Hlth Sci, Dept Med, Kampala, Uganda.
[Achan, Jane] Makerere Univ, Coll Hlth Sci, Dept Paediat, Kampala, Uganda.
RP Feeney, ME (reprint author), Univ Calif San Francisco, Div Expt Med, Dept Med, 1001 Potrero Ave,Bldg 3,Rm 525A, San Francisco, CA 94110 USA.
EM margaret.feeney@ucsf.edu
FU Sullivan Family Foundation; Elizabeth Glaser Pediatric AIDS Foundation;
National Institute of Health [A151982, K236045901A2, R01AI068497];
Jewelers for Children Elizabeth Glaser Scientist Award
FX This work was supported by the Sullivan Family Foundation (Philani
Program), the Elizabeth Glaser Pediatric AIDS Foundation (to M. E. F.),
and the National Institute of Health (grants A151982 to D. H.,
K236045901A2 to T. D. R, and R01AI068497 to M. E. F.). M. E. F. is the
recipient of the Jewelers for Children Elizabeth Glaser Scientist Award.
NR 36
TC 7
Z9 7
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 15
PY 2011
VL 53
IS 6
BP 592
EP 599
DI 10.1093/cid/cir484
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 813JQ
UT WOS:000294363100022
PM 21840929
ER
PT J
AU Kollef, MH
Golan, Y
Micek, ST
Shorr, AF
Restrepo, MI
AF Kollef, Marin H.
Golan, Yoav
Micek, Scott T.
Shorr, Andrew F.
Restrepo, Marcos I.
TI Appraising Contemporary Strategies to Combat Multidrug Resistant
Gram-Negative Bacterial Infections-Proceedings and Data From the
Gram-Negative Resistance Summit
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE-UNIT; COMBINATION
ANTIBIOTIC-THERAPY; CRITICALLY-ILL PATIENTS; INADEQUATE ANTIMICROBIAL
TREATMENT; BLOOD-STREAM INFECTION; PSEUDOMONAS-AERUGINOSA;
DISEASES-SOCIETY; SEPTIC SHOCK; STAPHYLOCOCCUS-AUREUS
AB The emerging problem of antibiotic resistance, especially among Gram-negative bacteria (GNB), has become a serious threat to global public health. Very few new antibacterial classes with activity against antibiotic-resistant GNB have been brought to market. Renewed and growing attention to the development of novel compounds targeting antibiotic-resistant GNB, as well as a better understanding of strategies aimed at preventing the spread of resistant bacterial strains and preserving the efficacy of existing antibiotic agents, has occurred. The Gram-Negative Resistance Summit convened national opinion leaders for the purpose of analyzing current literature, epidemiologic trends, clinical trial data, therapeutic options, and treatment guidelines related to the management of antibiotic-resistant GNB infections. After an in-depth analysis, the Summit investigators were surveyed with regard to 4 clinical practice statements. The results then were compared with the same survey completed by 138 infectious disease and critical care physicians and are the basis of this article.
C1 [Kollef, Marin H.] Washington Univ, Sch Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA.
[Golan, Yoav] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Micek, Scott T.] Barnes Jewish Hosp, St Louis, MO 63110 USA.
[Shorr, Andrew F.] Georgetown Univ, Washington, DC USA.
[Shorr, Andrew F.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.] Audie L Murphy Vet Hosp, Div Pulm & Crit Care Med, Dept Med, San Antonio, TX USA.
RP Kollef, MH (reprint author), Washington Univ, Sch Med, Div Pulm & Crit Care Med, 660 S Euclid Ave,Campus Box 8052, St Louis, MO 63110 USA.
EM mkollef@dom.wustl.edu
RI Restrepo, Marcos/H-4442-2014
FU Consensus Medical Communication; Astellas; Sanofi Pasteur; Astrazeneca;
Therafan; Forest Laboratories and Novartis; TRIUS; Covidien; BARD;
National Heart, Lung, and Blood Institute [K23HL096054]; University of
Colorado School of Medicine; Consensus Medical Communications;
Ortho-McNeil Janssen Scientific Affairs, LLC.; Merck; Cubist; Pfizer;
Johnson Johnson; National Heart, Lung, and Blood Institute;
GlaxoSmithKline
FX This work was supported by Consensus Medical Communication (consulting
fees and travel support to M. H. K., Y. G., S. T. M., M. I. R.; payment
for the development of educational presentations to S. T. M.; payment
for writing manuscript to all authors); Merck (payment for lectures to
M. H. K. and Y. G., manuscript preparation to M. H. K., and consultancy
to Y. G.; grant support to Y. G.); Pfizer (Wyeth) (payment for lectures
to M. H. K., Y. G., and M. I. R.; payment for manuscript preparation to
M. H. K.; payment for consultancies to Y. G. and M. I. R.; grant support
to Y. G. and S. T. M.); Astellas (payment for lectures and manuscript
preparation to M. H. K., grant support to Y. G.); Sanofi Pasteur and
Astrazeneca (payment for lectures and manuscript preparation to M. H.
K.); Cubist (grant support to Y. G. and S. T. M.; payment for lectures
to Y. G.); Vernco MedEd (payment for the development of educational
presentations to S. T. M.); Ortho-McNeil-Janssen (Johnson & Johnson)
(payment for board membership and consultancy to M. I. R.; grants to Y.
G. and S. T. M.); Therafan (payment for board membership and consultancy
to M. I. R.); Forest Laboratories and Novartis (payment for board
membership to M. I. R.); TRIUS (payment for consultancy to M. I. R.);
Covidien and BARD (payment for lectures to M. I. R.). M. I. R. is
supported and his time partially protected by a grant from the National
Heart, Lung, and Blood Institute (award no. K23HL096054).; Supplement
sponsorship. This article was published as part of a supplement entitled
"Appraising Contemporary Strategies to Combat Multidrug Resistant
Gram-Negative Bacterial Infections-Proceedings and Data From the
Gram-Negative Resistance Summit," jointly sponsored by the University of
Colorado School of Medicine and Consensus Medical Communications and is
supported by an educational grant from Ortho-McNeil Janssen Scientific
Affairs, LLC.; Potential conflicts of interest. Yoav Golan, MD: is on
the speakers' bureau for Merck, Pfizer, and Cubist; received grants
and/or research support from Merck, Cubist, Pfizer, Astellas, and
Johnson & Johnson; is a consultant for Merck, Pfizer, and Cubist. Marin
Kollef, MD: is on the speakers' bureau for Merck, Pfizer, Astellas,
Sanofi Pasteur, and AstraZeneca. Scott Micek, PharmD: no reported
conflicts or financial disclosures. Marcos Restrepo, MD: is on the
speakers' bureau for Covidien; received grant and/or research support
from the National Heart, Lung, and Blood Institute; is also a consultant
for Ortho-McNeil-Janssen (Johnson & Johnson), Forest Laboratories,
Novartis, Theravance, and Pfizer (Wyeth). Andrew Shorr, MD: is on the
speakers' bureau for Astellas, AstraZeneca, Boehringer Ingleheim,
Covidien, and Pfizer; received grants and/or research support from
Astellas, GlaxoSmithKline, and Pfizer; is a consultant for Astellas,
Bayer, Bard, Cadence Pharmaceuticals, Canyon Pharmaceuticals, Johnson &
Johnson, Eli Lilly and Company, Eisai Pharmaceuticals, Forest
Laboratories, MedCo, and Theravance.
NR 95
TC 34
Z9 35
U1 2
U2 9
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 SEP 15
PY 2011
VL 53
SU 2
BP S33
EP S55
DI 10.1093/cid/cir475
PG 23
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 813LE
UT WOS:000294367300001
PM 21868447
ER
PT J
AU Kachadourian, R
Pugazhenthi, S
Velmurugan, K
Backos, DS
Franklin, CC
McCord, JM
Day, BJ
AF Kachadourian, Remy
Pugazhenthi, Subbiah
Velmurugan, Kalpana
Backos, Donald S.
Franklin, Christopher C.
McCord, Joe M.
Day, Brian J.
TI 2 ',5 '-Dihydroxychalcone-induced glutathione is mediated by oxidative
stress and kinase signaling pathways
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE ROS; Nrf2; AP-1; MCF-7/AREc32; Metalloporphyrin; Free radicals
ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; CANCER RESISTANCE PROTEIN; GLUTAMATE
CYSTEINE LIGASE; HAMSTER V79 CELLS; HEME OXYGENASE-1; ANTIOXIDANT
RESPONSE; MOLECULAR-MECHANISMS; INDUCED EXPRESSION; ENDOTHELIAL-CELLS;
IN-VITRO
AB Hydroxychalcones are naturally:occurring compounds that continue to attract considerable interest because of their anti-inflammatory and antiangiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide synthase and to induce the expression of heme oxygenase-1. This study examines the mechanisms by which 2',5'-dihydroxychalcone (2',5'-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant-response elements (MCF-7/AREc32). The 2',5'-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP(5+), suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2',5'-DHC treatment induced phosphorylation of the c-Jun N-terminal kinase (JNK) pathway, which was also inhibited by MnTDE-1,3-IP(5+). These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, whereas 2',5'-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, cotreatment with MnTDE-1,3-IP(5+) did not decrease 2',5'-DHC-induced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein kinase (MAPK) pathways showed a role for JNK and p38MAPK in mediating the 2',5'-DHC-induced Nrf2 response. These findings suggest that the 2',5'-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Kachadourian, Remy; Day, Brian J.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
[Kachadourian, Remy; Pugazhenthi, Subbiah; McCord, Joe M.; Day, Brian J.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
[Pugazhenthi, Subbiah; Velmurugan, Kalpana] Denver VA Med Ctr, Denver, CO 80220 USA.
[Backos, Donald S.; Franklin, Christopher C.; Day, Brian J.] Univ Colorado Denver, Dept Pharmaceut Sci, Aurora, CO 80045 USA.
RP Day, BJ (reprint author), Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
EM dayb@njhealth.org
OI Backos, Donald/0000-0001-6735-6210
FU NIH [HL755223, HL84469, ES015678, ES017582]; VA Merit Review
[NEUD-004-07F]
FX This work was supported by NIH Grants HL755223, HL84469, ES015678, and
ES017582 to B.J. Day and VA Merit Review NEUD-004-07F to S. Pugazhenthi.
The authors thank Gregory Mahaffey for his help with immunoblotting. Dr.
Day is a consultant for and holds equity in Aeolus Pharmaceuticals,
which is commercially developing metalloporphyrins as human therapeutic
agents.
NR 56
TC 10
Z9 11
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP 15
PY 2011
VL 51
IS 6
BP 1146
EP 1154
DI 10.1016/j.freeradbiomed.2011.05.041
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 813WB
UT WOS:000294399800006
PM 21712085
ER
PT J
AU Yu, Y
Bhangale, TR
Fagerness, J
Ripke, S
Thorleifsson, G
Tan, PL
Souied, EH
Richardson, AJ
Merriam, JE
Buitendijk, GHS
Reynolds, R
Raychaudhuri, S
Chin, KA
Sobrin, L
Evangelou, E
Lee, PH
Lee, AY
Leveziel, N
Zack, DJ
Campochiaro, B
Campochiaro, P
Smith, RT
Barile, GR
Guymer, RH
Hogg, R
Chakravarthy, U
Robman, LD
Gustafsson, O
Sigurdsson, H
Ortmann, W
Behrens, TW
Stefansson, K
Uitterlinden, AG
van Duijn, CM
Vingerling, JR
Klaver, CCW
Allikmets, R
Brantley, MA
Baird, PN
Katsanis, N
Thorsteinsdottir, U
Ioannidis, JPA
Daly, MJ
Graham, RR
Seddon, JM
AF Yu, Yi
Bhangale, Tushar R.
Fagerness, Jesen
Ripke, Stephan
Thorleifsson, Gudmar
Tan, Perciliz L.
Souied, Eric H.
Richardson, Andrea J.
Merriam, Joanna E.
Buitendijk, Gabrielle H. S.
Reynolds, Robyn
Raychaudhuri, Soumya
Chin, Kimberly A.
Sobrin, Lucia
Evangelou, Evangelos
Lee, Phil H.
Lee, Aaron Y.
Leveziel, Nicolas
Zack, Donald J.
Campochiaro, Betsy
Campochiaro, Peter
Smith, R. Theodore
Barile, Gaetano R.
Guymer, Robyn H.
Hogg, Ruth
Chakravarthy, Usha
Robman, Luba D.
Gustafsson, Omar
Sigurdsson, Haraldur
Ortmann, Ward
Behrens, Timothy W.
Stefansson, Kari
Uitterlinden, Andre G.
van Duijn, Cornelia M.
Vingerling, Johannes R.
Klaver, Caroline C. W.
Allikmets, Rando
Brantley, Milam A., Jr.
Baird, Paul N.
Katsanis, Nicholas
Thorsteinsdottir, Unnur
Ioannidis, John P. A.
Daly, Mark J.
Graham, Robert R.
Seddon, Johanna M.
TI Common variants near FRK/COL10A1 and VEGFA are associated with advanced
age-related macular degeneration
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H; GENETIC-ASSOCIATION; RISK;
SUSCEPTIBILITY; METAANALYSIS; HAPLOTYPE; DISEASE; LOCI; ANGIOGENESIS
AB Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 x 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 x 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD.
C1 [Yu, Yi; Reynolds, Robyn; Chin, Kimberly A.; Seddon, Johanna M.] Tufts Univ, Sch Med, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Inst Clin Res & Hlth Policy Studies, 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.; Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Tufts Med Ctr, Boston, MA 02111 USA.
[Bhangale, Tushar R.] Genentech Inc, Human Genet Grp, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
[Ortmann, Ward; Behrens, Timothy W.; Graham, Robert R.] Genentech Inc, Human Genet Grp, Immunol & Tissue Growth & Repair Dept, San Francisco, CA 94080 USA.
[Fagerness, Jesen; Ripke, Stephan; Raychaudhuri, Soumya; Lee, Phil H.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Fagerness, Jesen; Ripke, Stephan; Raychaudhuri, Soumya; Lee, Phil H.; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Thorleifsson, Gudmar; Gustafsson, Omar; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, IS-101 Reykjavik, Iceland.
[Tan, Perciliz L.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA.
[Tan, Perciliz L.; Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA.
[Tan, Perciliz L.; Katsanis, Nicholas] Duke Univ, Dept Pediat, Durham, NC 27710 USA.
[Souied, Eric H.; Leveziel, Nicolas] Univ Paris Est Creteil, Hop Intercommunal Creteil, Dept Ophthalmol, F-94000 Creteil, France.
[Souied, Eric H.; Leveziel, Nicolas] UPEC, Dept Ophthalmol, Fac Med Henri Mondor, Creteil, France.
[Richardson, Andrea J.; Guymer, Robyn H.; Robman, Luba D.; Baird, Paul N.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Merriam, Joanna E.; Smith, R. Theodore; Barile, Gaetano R.; Allikmets, Rando] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA.
[Buitendijk, Gabrielle H. S.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
[Buitendijk, Gabrielle H. S.; van Duijn, Cornelia M.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
[Sobrin, Lucia] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
[Evangelou, Evangelos; Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Lee, Aaron Y.; Brantley, Milam A., Jr.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
[Lee, Aaron Y.; Brantley, Milam A., Jr.] Barnes Retina Inst, St Louis, MO 63144 USA.
[Zack, Donald J.; Campochiaro, Betsy; Campochiaro, Peter] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
[Zack, Donald J.; Campochiaro, Betsy; Campochiaro, Peter] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
[Zack, Donald J.; Campochiaro, Betsy] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Mol Biol & Genet, Baltimore, MD 21287 USA.
[Zack, Donald J.; Campochiaro, Betsy] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA.
[Hogg, Ruth; Chakravarthy, Usha] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland.
[Sigurdsson, Haraldur] Natl Univ Hosp Reykjavik, Dept Ophthalmol, IS-101 Reykjavik, Iceland.
[Sigurdsson, Haraldur; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Allikmets, Rando] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Zack, Donald J.] UPMC, Inst Vis, Paris, France.
RP Seddon, JM (reprint author), Tufts Univ, Sch Med, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, 800 Washington St,450, Boston, MA 02111 USA.
EM jseddon@tuftsmedicalcenter.org
RI du, zhao jiang/F-6229-2011; Ioannidis, John/G-9836-2011; Katsanis,
Nicholas/E-1837-2012; Evangelou, Evangelos/C-3033-2013; Klaver,
Caroline/A-2013-2016;
OI smith, theodore/0000-0002-1693-943X; Katsanis,
Nicholas/0000-0002-2480-0171; Hogg, Ruth/0000-0001-9413-2669; Baird,
Paul/0000-0002-1305-3502; Zack, Don/0000-0002-7966-1973; Lee,
Aaron/0000-0002-7452-1648; Evangelou, Evangelos/0000-0002-5488-2999
FU National Eye Institute; National Institute of Mental Health [R01
MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01
MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01
MH81800, U01 MH46276, U01 MH46289, U01 MH46318, U01 MH79469, U01
MH79470]; National Institutes of Health, Bethesda, MD, USA [RO1-EY11309,
RO1-EY13435, R24-EY017404, P30-EY 001765, K12-EY16335]; Massachusetts
Lions Eye Research Fund, Inc.; Research to Prevent Blindness, Inc., New
York, NY, USA; Foundation Fighting Blindness, Owing Mills, MD, USA;
Macula Vision Research Foundation; Kaplen Foundation; Widgeon Point
Charitable Foundation; Alcon Research Institute; Fight for Sight;
National Health and Medical Research Council of Australia Centre for
Clinical Research Excellence [529923]; Victorian Government; American
Macular Degeneration Foundation; 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, USA
FX We thank the participants, their families and numerous ophthalmologists
throughout the country who participated in this study, the MIGen study
group and the Brigham and Women's Hospital PhenoGenetic Project for
providing DNA samples that were used in this study, the AREDS Research
Group, and Dr J. Barre, Dr. J. C. Danan and P. Ledudal from the Clinical
Researches Functional Unit, CHI Creteil, France. The MMAP dataset used
for the analyses described in this manuscript was obtained from the NEI
Study of Age-Related Macular Degeneration (NEI-AMD) Database found at
http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number
phs000182.v2.p1. Funding support for NEI-AMD was provided by the
National Eye Institute. We would like to thank NEI-AMD participants and
the NEI-AMD Research Group for their valuable contribution to this
research. Funding support for the Genome-Wide Association of
Schizophrenia Study was provided by the National Institute of Mental
Health (R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587,
R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01
MH81800, U01 MH46276, U01 MH46289 U01 MH46318, U01 MH79469, and U01
MH79470) and the genotyping of samples was provided through the Genetic
Association Information Network (GAIN). The datasets used for the
analyses described in this manuscript were obtained from the database of
Genotypes and Phenotypes (dbGaP) found at
http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number
phs000021.v3.p2. Samples and associated phenotype data for the
Genome-Wide Association of Schizophrenia Study were provided by the
Molecular Genetics of Schizophrenia Collaboration (PI: Pablo V. Gejman,
Evanston Northwestern Healthcare (ENH) and Northwestern University,
Evanston, IL, USA).; We deeply appreciate the support of a generous
anonymous donor to the research of J.M.S., without whom the Tufts/MGH
genome-wide association study would not have been possible. This
research was also supported in part by grants RO1-EY11309, RO1-EY13435,
R24-EY017404, P30-EY 001765 and K12-EY16335 from the National Institutes
of Health, Bethesda, MD, USA; Massachusetts Lions Eye Research Fund,
Inc.; Unrestricted grants and Career Development Award from Research to
Prevent Blindness, Inc., New York, NY, USA; Foundation Fighting
Blindness, Owing Mills, MD, USA; The Macula Vision Research Foundation;
Kaplen Foundation; Widgeon Point Charitable Foundation; the Alcon
Research Institute; a Fight for Sight postdoctoral award; the National
Health and Medical Research Council of Australia Centre for Clinical
Research Excellence No. 529923-Translational Clinical Research in Major
Eye Diseases and a Practitioner Fellowship to R. H. G. and Operational
Infrastructure Support from the Victorian Government; American Macular
Degeneration Foundation; 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, USA. Funding to pay the Open Access publication charges for
this article was provided by the Macular Degeneration Research Fund,
Tufts Medical Center.
NR 51
TC 129
Z9 130
U1 1
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD SEP 15
PY 2011
VL 20
IS 18
BP 3699
EP 3709
DI 10.1093/hmg/ddr270
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 814IP
UT WOS:000294442200016
PM 21665990
ER
PT J
AU Xie, PX
Kranzler, HR
Krauthammer, M
Cosgrove, KP
Oslin, D
Anton, RF
Farrer, LA
Picciotto, MR
Krystal, JH
Zhao, HY
Gelernter, J
AF Xie, Pingxing
Kranzler, Henry R.
Krauthammer, Michael
Cosgrove, Kelly P.
Oslin, David
Anton, Raymond F.
Farrer, Lindsay A.
Picciotto, Marina R.
Krystal, John H.
Zhao, Hongyu
Gelernter, Joel
TI Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor
Gene Protect Against Nicotine Dependence
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE CHRNA4; deep sequencing; imaging genetics; nicotine dependence;
nonsynonymous; rare variants
ID VENTRAL TEGMENTAL AREA; MULTILOCUS GENOTYPE DATA; GENOMEWIDE LINKAGE
SCAN; SMOKING-BEHAVIOR; SEMISTRUCTURED ASSESSMENT; ALCOHOLISM SSADDA;
DRUG-DEPENDENCE; SUBUNIT GENE; IN-VIVO; ASSOCIATION
AB Background: Several studies report association of alpha-4 nicotinic acetylcholine receptors (encoded by CHRNA4) with nicotine dependence (ND). A meta-analysis of genomewide linkage studies for ND implicated a single chromosomal region, which includes CHRNA4, as genome-wide significant.
Methods: After establishing that common variants are unlikely to completely account for this linkage, we investigated the distribution of CHRNA4 rare variants by sequencing the coding exons and flanking intronic regions of CHRNA4 in 209 European American (EA) ND cases and 183 EA control subjects. Because most of the rare variants that we detected (and all nonsynonymous changes) were in Exon 5, we sequenced Exon 5 in an additional 1000 ND cases and 1000 non-ND comparison subjects, both of which included equal numbers of EAs and African Americans.
Results: Comparison subjects had a higher frequency of rare nonsynonymous variants in the Exon 5 region (encoding the large intercellular loop of the alpha 4 subunit; Fisher's Exact Test p = .009; association test p = .009, odds ratio = .43; weighted-sum method p = .014), indicating a protective effect against ND. Considering data from the two stages combined and only nonsynonymous variants predicted to alter protein function, the association was stronger (Fisher's Exact Test p = .005; association test p = .008, odds ratio = .29; weighted-sum method p = .005). Single-photon emission computed tomography imaging results were consistent with functionality.
Conclusions: CHRNA4 functional rare variants may reduce ND risk. This is the first demonstration that rare functional variants at a candidate locus protect against substance dependence to our knowledge, suggesting a novel mechanism of substance dependence heritability that is potentially of general importance.
C1 [Xie, Pingxing; Zhao, Hongyu; Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Cosgrove, Kelly P.; Picciotto, Marina R.; Krystal, John H.; Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Krauthammer, Michael] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Xie, Pingxing; Cosgrove, Kelly P.; Krystal, John H.; Gelernter, Joel] VA Connecticut Healthcare Ctr, West Haven, CT USA.
[Kranzler, Henry R.; Oslin, David] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Anton, Raymond F.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Anton, Raymond F.] Med Univ S Carolina, Dept Psychiat, Ctr Alcohol & Drug Programs, Charleston, SC 29425 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol & Biostat, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Genet & Genom, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA.
RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Human Genet Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA.
EM joel.gelernter@yale.edu
RI Picciotto, Marina/F-8747-2012; Cosgrove, Kelly/J-7004-2013;
OI Picciotto, Marina/0000-0002-4404-1280; Farrer,
Lindsay/0000-0001-5533-4225
FU National Institute of Health [R01 DA12690, R01 DA12849, R01 AA11330, R01
AA017535, K01 DA020651, R01 DA015577, 2P50-AA012870, K05 AA017435, R01
DA030976]; Vetrans Affairs (VA) VISN1 MIRECC; VA Alcohol Research
Center; Clinical Neuroscience Division of the VA National Center for
Posttraumatic Stress Disorder; Alkermes; GlaxoSmithKline; Gilead; Merck;
ACNP Alcohol Clinical Trials Initiative (ACTIVE); Janssen Research
Foundation
FX This study was supported by National Institute of Health Grant Nos. R01
DA12690, R01 DA12849, R01 AA11330, R01 AA017535, K01 DA020651, R01
DA015577, 2P50-AA012870, K05 AA017435, R01 DA030976 and the Vetrans
Affairs (VA) VISN1 MIRECC, VA Alcohol Research Center, and the Clinical
Neuroscience Division of the VA National Center for Posttraumatic Stress
Disorder. Ann Marie Lacobelle provided technical assistance. We thank
the individuals and families participating in this work and the
interviewers at all the participating sites for collecting the data.;
Dr. Kranzler has received consulting fees from Alkermes,
GlaxoSmithKline, and Gilead and research support from Merck. Dr. Anton
reports being a consultant for Eli Lilly, GlaxoSmithKline, and Alkermes
for the past 2 years. Drs. Kranzler and Anton also report associations
with Eli Lilly, Merck, Janssen, Schering Plough, Lundbeck, Alkermes,
GlaxoSmithKline, Abbott, and Johnson & Johnson; these companies provide
support to the ACNP Alcohol Clinical Trials Initiative (ACTIVE) and they
receive support from ACTIVE. Dr. Picciotto has received an honorarium
from Targacept. Dr. Krystal reports serving as a scientific consultant
and/or on the scientific advisory board to the following companies:
Aisling Capital, AstraZeneca Pharmaceuticals, Brintnall & Nicolini,
Easton Associates, Gilead Sciences, GlaxoSmithKline, Janssen
Pharmaceuticals, Lundbeck Research USA, Medivation, Merz
Pharmaceuticals, MK Medical Communications, F. Hoffmann-La Roche, SK
Holdings Co., Takeda Industries, Teva Pharmaceutical Industries, Abbott
Laboratories, Bristol-Myers Squibb, Eisai, Eli Lilly and Co, Lohocla
Research Corporation, Naurex and Pfizer Pharmaceuticals. Dr. Krystal
holds less than US$ 150 in exercisable warrant options with Tetragenex
Pharmaceuticals, is the principal investigator of a multicenter study in
which Janssen Research Foundation has provided drug and some financial
support to the Department of Veterans Affairs, and is a cosponsor for
two patents under review for glutamatergic agents targeting the
treatment of depression, including one that involves the antide-pressant
effects of ketamine. The other authors report no biomedical financial
interests or potential conflicts of interest.
NR 49
TC 33
Z9 33
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD SEP 15
PY 2011
VL 70
IS 6
BP 528
EP 536
DI 10.1016/j.biopsych.2011.04.017
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 810UX
UT WOS:000294154100007
PM 21683344
ER
PT J
AU Cardenas, VA
Durazzo, TC
Gazdzinski, S
Mon, A
Studholme, C
Meyerhoff, DJ
AF Cardenas, Valerie A.
Durazzo, Timothy C.
Gazdzinski, Stefan
Mon, Anderson
Studholme, Colin
Meyerhoff, Dieter J.
TI Brain Morphology at Entry into Treatment for Alcohol Dependence Is
Related to Relapse Propensity
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Abstinence; deformation morphometry; longitudinal; relapse
ID CHRONIC CIGARETTE-SMOKING; CONSUMPTION FOLLOWING TREATMENT; SUBSTANCE
USE DISORDERS; ORBITOFRONTAL CORTEX; PROBLEM DRINKING; ADDICTION; DRUG;
INDIVIDUALS; MORPHOMETRY; PREDICTORS
AB Background: We examined whether any differences in brain volumes at entry into alcohol dependence treatment differentiate subsequent Abstainers from Relapsers.
Methods: Individuals in alcohol dependence treatment (n = 75) underwent magnetic resonance imaging approximately 6 +/- 4 days after their last alcoholic drink, and 40 age-matched nonsmoking light drinkers (LD) were studied as control subjects. At follow-up 7.8 +/- 2.6 months later, 23 alcoholics (31%) had abstained from drinking and 52 (69%) had relapsed. Deformation morphometry compared Relapsers, Abstainers, and LD.
Results: Compared with LD, future Abstainers had smaller brain tissue volumes in the left amygdala, hippocampal head, and entorhinal cortex and bilaterally in the thalamus and adjacent subcortical white matter (WM) and had larger volume in the left lateral orbitofrontal region. Compared with LD, future Relapsers had smaller brain tissue volumes in the right middle temporal, occipital, and superior frontal WM. Compared with future Abstainers, future Relapsers had smaller tissue volumes primarily in bilateral orbitofrontal cortex and surrounding WM. Results were virtually unaffected after controlling for common comorbidities.
Conclusions: At entry into alcohol dependence treatment, the brain tructure of future Relapsers differs from that of future Abstainers. Future Relapsers have smaller brain volumes in regions of the mesocorticolimbic reward system that are critically involved in impulse control, emotional regulation, craving, and evaluation and anticipation of stimulus salience and hedonics. Structural abnormalities of this circuitry might confer greater risk for resumption of hazardous drinking after treatment and might contribute to the definition of a neurobiological relapse risk profile in alcohol dependence.
C1 [Cardenas, Valerie A.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94121 USA.
[Cardenas, Valerie A.; Durazzo, Timothy C.; Gazdzinski, Stefan; Mon, Anderson; Studholme, Colin; Meyerhoff, Dieter J.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
RP Cardenas, VA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,114M, San Francisco, CA 94121 USA.
EM valerie.cardenas-nicolson@ucsf.edu
FU National Institutes of Health [R01AA10788, K08DA24136, R03EB008136,
P01AA11493, P41RR023953]
FX This material is the result of work supported by National Institutes of
Health [R01AA10788, K08DA24136, R03EB008136, P01AA11493, P41RR023953],
which were administered by the Northern California Institute for
Research and Education, and with resources and the use of facilities of
the Veterans Affairs Medical Center, San Francisco, California. We thank
Mary Rebecca Young, Bill Clift, Jeanne Eichenbaum, and Drs. Peter Banys
and Ellen Herbst of the Veterans Administration Substance Abuse Day
Hospital and Dr. David Pating, Karen Moise, and their colleagues at the
Kaiser Permanente Chemical Dependency Recovery Program in San Francisco
for their valuable assistance in recruiting participants. We also wish
to extend our gratitude to the study participants, who made this
research possible.
NR 43
TC 33
Z9 33
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD SEP 15
PY 2011
VL 70
IS 6
BP 561
EP 567
DI 10.1016/j.biopsych.2011.04.003
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 810UX
UT WOS:000294154100011
PM 21601177
ER
PT J
AU Kuralay, F
Campuzano, S
Haake, DA
Wang, J
AF Kuralay, Filiz
Campuzano, Susana
Haake, David A.
Wang, Joseph
TI Highly sensitive disposable nucleic acid biosensors for direct
bioelectronic detection in raw biological samples
SO TALANTA
LA English
DT Article
DE Screen-printed gold electrodes; Dithiols; Self-assembled monolayer; DNA
hybridization; Raw samples
ID SELF-ASSEMBLED MONOLAYERS; PRINTED GOLD ELECTRODES; ELECTROCHEMICAL
IMPEDANCE SPECTROSCOPY; CARBON ELECTRODES; DNA MONOLAYERS;
HYBRIDIZATION; MERCAPTOHEXANOL; AMPLIFICATION; GENOSENSOR; SURFACES
AB The development of rapid, low-cost and reliable diagnostic methods is crucial for the identification and treatment of many diseases. Screen-printed gold electrodes (Au/SPEs), coated with a ternary monolayer interface, involving hexanedithiol (HDT), a specific thiolated capture probe (SHCP), and 6-mercapto-1 hexanol (MCH) (SHCP/HDT/MCH) are shown here to offer direct and sensitive detection of nucleic acid hybridization events in untreated raw biological samples (serum, urine and crude bacterial lysate solutions). The composition of the ternary monolayer was modified and tailored to the surface of the Au/SPE. The resulting SHCP/HDT/MCH monolayer has demonstrated to be extremely useful for enhancing the performance of disposable nucleic acid sensors based on screen-printed electrodes. Compared to common SHCP/MCH binary interfaces, the new ternary self-assembled monolayer (SAM) resulted in a 10-fold improvement in the signal (S)-to-noise (N) ratio (S/N) for 1 nM target DNA. The SHCP/HDT/MCH-modified Au/SPEs allowed the direct quantification of the target DNA down to 25 pM (0.25 fmol) and 100 pM (1 fmol) in undiluted/untreated serum and urine samples, respectively, and of 16S rRNA Escherichia coli (E. con) corresponding to 3000 CFU mu L-1 in raw cell lysate samples. The new SAM-coated screen-printed electrodes also displayed favorable non-fouling properties after a 24 h exposure to raw human serum and urine samples, offering great promise as cost-effective nucleic acid sensors for a wide range of decentralized genetic tests. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Kuralay, Filiz; Campuzano, Susana; Wang, Joseph] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA.
[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, Los Angeles, CA 90073 USA.
RP Wang, J (reprint author), Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA.
EM josephwang@ucsd.edu
RI Campuzano Ruiz, Susana/C-6448-2011; Wang, Joseph/C-6175-2011
FU National Institutes of Health [U01 AI075565]; Scientific and Technical
Council of Turkey (TUBITAK); Programa Becas Complutense del Amo
FX Financial support from the National Institutes of Health (Award U01
AI075565) is gratefully acknowledged. FK and SC acknowledge fellowships
from The Scientific and Technical Council of Turkey (TUBITAK) and
Programa Becas Complutense del Amo (2010-2011), respectively. The
authors would like to acknowledge S. Marx and C. Halford for their
assistance.
NR 42
TC 25
Z9 26
U1 5
U2 47
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0039-9140
EI 1873-3573
J9 TALANTA
JI Talanta
PD SEP 15
PY 2011
VL 85
IS 3
BP 1330
EP 1337
DI 10.1016/j.talanta.2011.06.012
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 809YO
UT WOS:000294092800018
PM 21807191
ER
PT J
AU Ontoria, JM
Bufi, LL
Torrisi, C
Bresciani, A
Giomini, C
Rowley, M
Serafini, S
Bin, H
Hao, W
Steinkuhler, C
Jones, P
AF Ontoria, Jesus M.
Bufi, Laura Llauger
Torrisi, Caterina
Bresciani, Alberto
Giomini, Claudia
Rowley, Michael
Serafini, Sergio
Bin, Hu
Hao, Wu
Steinkuehler, Christian
Jones, Philip
TI Identification of a series of
4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent
smoothened antagonist hedgehog pathway inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Hedgehog pathway; Smoothened antagonist; Hedgehog inhibitor
ID SMALL-MOLECULE INHIBITORS; SIGNALING PATHWAY; CANCER; CYCLOPAMINE
AB The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable of inhibiting the pathway have been identified through uHTS screening. Extensive exploration of the scaffold identified the key functionalities necessary for potency, enabling potent nanomolar Smo antagonists like 91 and 94 to be developed. Optimization resulted in the most advanced compounds displaying low serum shift, clean off-targets profile, and moderate clearance in both rats and dogs. These compounds are valuable tools with which to probe the biology of the Hh-pathway. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Ontoria, Jesus M.; Bufi, Laura Llauger; Torrisi, Caterina; Bresciani, Alberto; Giomini, Claudia; Rowley, Michael; Serafini, Sergio; Steinkuehler, Christian; Jones, Philip] IRBM, Merck Res Labs Rome, I-00040 Rome, Italy.
[Bin, Hu; Hao, Wu] WuXi AppTec Co Ltd, Shanghai 200131, Peoples R China.
RP Jones, P (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, 450 Brookline Ave, Boston, MA 02115 USA.
EM philip_jones@dfci.harvard.edu
NR 20
TC 17
Z9 18
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD SEP 15
PY 2011
VL 21
IS 18
BP 5274
EP 5282
DI 10.1016/j.bmcl.2011.07.031
PG 9
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 809KB
UT WOS:000294051800031
PM 21803580
ER
PT J
AU Muraglia, E
Ontoria, JM
Branca, D
Dessole, G
Bresciani, A
Fonsi, M
Giuliano, C
Bufi, LL
Monteagudo, E
Palumbi, MC
Torrisi, C
Rowley, M
Steinkuhler, C
Jones, P
AF Muraglia, Ester
Ontoria, Jesus M.
Branca, Danila
Dessole, Gabriella
Bresciani, Alberto
Fonsi, Massimiliano
Giuliano, Claudio
Bufi, Laura Llauger
Monteagudo, Edith
Palumbi, Maria Cecilia
Torrisi, Caterina
Rowley, Michael
Steinkuehler, Christian
Jones, Philip
TI N-(2-alkylaminoethyl)-4-(1,2,4-oxadiazol-5-yl)piperazine-1-carboxamides
as highly potent smoothened antagonists
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Hedgehog pathway; Smoothened antagonist; Hedgehog inhibitor
ID HEDGEHOG SIGNALING PATHWAY; INHIBITION; METABOLISM; CANCER; CYCLOPAMINE;
DISCOVERY; DOGS
AB Smoothened (Smo) antagonists are emerging as new therapies for the treatment of neoplasias with aberrantly reactivated hedgehog (Hh) signaling pathway. A novel series of 4-[ 3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl] piperazinyl ureas as smoothened antagonists was recently described, herein the series has been further optimized through the incorporation of a basic amine into the urea. This development resulted in identification of some exceptionally potent smoothened antagonists with low serum shifts, however, reductive ring opening on the 1,2,4-oxadiazole in rats limits the applicability of these compounds in in vivo studies. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Muraglia, Ester; Ontoria, Jesus M.; Branca, Danila; Dessole, Gabriella; Bresciani, Alberto; Fonsi, Massimiliano; Giuliano, Claudio; Bufi, Laura Llauger; Monteagudo, Edith; Palumbi, Maria Cecilia; Torrisi, Caterina; Rowley, Michael; Steinkuehler, Christian; Jones, Philip] IRBM, Merck Res Labs Rome, I-00040 Rome, Italy.
RP Jones, P (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, 450 Brookline Ave, Boston, MA 02115 USA.
EM philip_jones@dfci.harvard.edu
NR 22
TC 14
Z9 15
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD SEP 15
PY 2011
VL 21
IS 18
BP 5283
EP 5288
DI 10.1016/j.bmcl.2011.07.030
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 809KB
UT WOS:000294051800032
PM 21802943
ER
PT J
AU Carpenter, D
Joffe, S
AF Carpenter, Daniel
Joffe, Steven
TI Information Disclosure and the Physician Payments Sunshine Act Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Carpenter, Daniel] Harvard Univ, Dept Govt, Cambridge, MA 02138 USA.
[Joffe, Steven] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Carpenter, D (reprint author), Harvard Univ, Dept Govt, Cambridge, MA 02138 USA.
EM dcarpenter@gov.harvard.edu
OI Joffe, Steven/0000-0002-0667-7384
NR 0
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 SEP 14
PY 2011
VL 306
IS 10
BP 1087
EP 1088
DI 10.1001/jama.2011.1299
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819DS
UT WOS:000294806200020
ER
PT J
AU Michelena, HI
Khanna, AD
Mahoney, D
Margaryan, E
Topilsky, Y
Suri, RM
Eidem, B
Edwards, WD
Sundt, TM
Enriquez-Sarano, M
AF Michelena, Hector I.
Khanna, Amber D.
Mahoney, Douglas
Margaryan, Edit
Topilsky, Yan
Suri, Rakesh M.
Eidem, Ben
Edwards, William D.
Sundt, Thoralf M., III
Enriquez-Sarano, Maurice
TI Incidence of Aortic Complications in Patients With Bicuspid Aortic
Valves
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ASCENDING AORTA; INTERNATIONAL REGISTRY; EJECTION FRACTION; DISSECTION
IRAD; MARFAN-SYNDROME; HEART-DISEASE; RISK-FACTORS; ECHOCARDIOGRAPHY;
ANEURYSMS; DILATATION
AB Context Bicuspid aortic valve (BAV), the most common congenital heart defect, has been thought to cause frequent and severe aortic complications; however, long-term, population-based data are lacking.
Objective To determine the incidence of aortic complications in patients with BAV in a community cohort and in the general population.
Design, Setting, and Participants In this retrospective cohort study, we conducted comprehensive assessment of aortic complications of patients with BAV living in a population-based setting in Olmsted County, Minnesota. We analyzed long-term follow-up of a cohort of all Olmsted County residents diagnosed with definite BAV by echocardiography from 1980 to 1999 and searched for aortic complications of patients whose bicuspid valves had gone undiagnosed. The last year of follow-up was 2008-2009.
Main Outcome Measure Thoracic aortic dissection, ascending aortic aneurysm, and aortic surgery.
Results The cohort included 416 consecutive patients with definite BAV diagnosed by echocardiography, mean (SD) follow-up of 16 (7) years (6530 patient-years). Aortic dissection occurred in 2 of 416 patients; incidence of 3.1 (95% CI, 0.5-9.5) cases per 10 000 patient-years, age-adjusted relative-risk 8.4 (95% CI, 2.1-33.5; P=.003) compared with the county's general population. Aortic dissection incidences for patients 50 years or older at baseline and bearers of aortic aneurysms at baseline were 17.4 (95% CI, 2.9-53.6) and 44.9(95% CI, 7.5-138.5) cases per 10 000 patient-years, respectively. Comprehensive search for aortic dissections in undiagnosed bicuspid valves revealed 2 additional patients, allowing estimation of aortic dissection incidence in bicuspid valve patients irrespective of diagnosis status (1.5; 95% CI, 0.4-3.8 cases per 10 000 patient-years), which was similar to the diagnosed cohort. Of 384 patients without baseline aneurysms, 49 developed aneurysms at follow-up, incidence of 84.9 (95% CI, 63.3-110.9) cases per 10 000 patient-years and an age-adjusted relative risk 86.2 (95% CI, 65.1-114; P<.001 compared with the general population). The 25-year rate of aortic surgery was 25% (95% CI, 17.2%-32.8%).
Conclusions In the population of patients with BAV, the incidence of aortic dissection over a mean of 16 years of follow-up was low but significantly higher than in the general population. JAMA. 2011;306(10):1104-1113 www.jama.com
C1 [Michelena, Hector I.; Khanna, Amber D.; Margaryan, Edit; Topilsky, Yan; Eidem, Ben; Enriquez-Sarano, Maurice] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA.
[Mahoney, Douglas] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Suri, Rakesh M.] Mayo Clin, Div Cardiovasc Surg, Rochester, MN 55905 USA.
[Edwards, William D.] Mayo Clin, Div Anat Pathol, Rochester, MN 55905 USA.
[Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA.
RP Michelena, HI (reprint author), Mayo Clin, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA.
EM michelena.hector@mayo.edu
FU Department of Internal Medicine of the Mayo Clinic, Rochester, Minnesot;
Division of Cardiovascular Diseases of the Mayo Clinic
FX Partially funded by a faculty development grant awarded to Dr Michelena
by the Department of Internal Medicine of the Mayo Clinic, Rochester,
Minnesot. The Division of Cardiovascular Diseases of the Mayo Clinic
supported the costs of survey creation and mailings, as well as
statistical analysis costs.
NR 40
TC 166
Z9 169
U1 1
U2 5
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 SEP 14
PY 2011
VL 306
IS 10
BP 1104
EP 1112
DI 10.1001/jama.2011.1286
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819DS
UT WOS:000294806200024
PM 21917581
ER
PT J
AU Fredman, G
Oh, SF
Ayilavarapu, S
Hasturk, H
Serhan, CN
Van Dyke, TE
AF Fredman, Gabrielle
Oh, Sungwhan F.
Ayilavarapu, Srinivas
Hasturk, Hatice
Serhan, Charles N.
Van Dyke, Thomas E.
TI Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by
Resolvin E1
SO PLOS ONE
LA English
DT Article
ID ATHEROSCLEROTIC CARDIOVASCULAR-DISEASE; EDITORS CONSENSUS PERIODONTITIS;
JOURNAL-OF-CARDIOLOGY; LIPID MEDIATORS; PORPHYROMONAS-GINGIVALIS;
JUVENILE PERIODONTITIS; INFLAMMATORY RESPONSE; SUPEROXIDE PRODUCTION;
ARACHIDONIC-ACID; TISSUE-DAMAGE
AB Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 mu M) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A(4). Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1-100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression.
C1 [Fredman, Gabrielle; Ayilavarapu, Srinivas; Hasturk, Hatice; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Cambridge, MA USA.
[Fredman, Gabrielle; Oh, Sungwhan F.; Serhan, Charles N.] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Med, Ctr Expt Therapeut & Reperfus Injury,Sch Med, Boston, MA 02115 USA.
RP Fredman, G (reprint author), Forsyth Inst, Dept Periodontol, Cambridge, MA USA.
EM tvandyke@forsyth.org
FU National Institutes of Health [DE-019938, DE-015566, GM38765]
FX This study was supported in part by National Institutes of Health Grants
DE-019938 (C.N. Serhan and T.E. Van Dyke), DE-015566 (T.E. Van Dyke) and
GM38765 (C.N. Serhan). No additional external funding was received for
this study. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 57
TC 47
Z9 46
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 14
PY 2011
VL 6
IS 9
AR e24422
DI 10.1371/journal.pone.0024422
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822JC
UT WOS:000295039700021
PM 21935407
ER
PT J
AU Thurber, GM
Weissleder, R
AF Thurber, Greg Michael
Weissleder, Ralph
TI A Systems Approach for Tumor Pharmacokinetics
SO PLOS ONE
LA English
DT Article
ID METASTATIC COLORECTAL-CANCER; SOLID TUMORS; MODELING ANALYSIS;
BLOOD-FLOW; MONOCLONAL-ANTIBODIES; OXYGEN-TRANSPORT; DRUG DISCOVERY;
NORMAL-TISSUES; IN-VIVO; DELIVERY
AB Recent advances in genome inspired target discovery, small molecule screens, development of biological and nanotechnology have led to the introduction of a myriad of new differently sized agents into the clinic. The differences in small and large molecule delivery are becoming increasingly important in combination therapies as well as the use of drugs that modify the physiology of tumors such as anti-angiogenic treatment. The complexity of targeting has led to the development of mathematical models to facilitate understanding, but unfortunately, these studies are often only applicable to a particular molecule, making pharmacokinetic comparisons difficult. Here we develop and describe a framework for categorizing primary pharmacokinetics of drugs in tumors. For modeling purposes, we define drugs not by their mechanism of action but rather their rate-limiting step of delivery. Our simulations account for variations in perfusion, vascularization, interstitial transport, and non-linear local binding and metabolism. Based on a comparison of the fundamental rates determining uptake, drugs were classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism. Simulations comparing small molecule versus macromolecular drugs show a sharp difference in distribution, which has implications for multi-drug therapies. The tissue-level distribution differs widely in tumors for small molecules versus macromolecular biologic drugs, and this should be considered in the design of agents and treatments. An example using antibodies in mouse xenografts illustrates the different in vivo behavior. This type of transport analysis can be used to aid in model development, experimental data analysis, and imaging and therapeutic agent design.
C1 [Thurber, Greg Michael; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02115 USA.
RP Thurber, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02115 USA.
EM gthurber@alum.mit.edu; rweissleder@mgh.harvard.edu
OI Thurber, Greg/0000-0001-7570-2080
FU National Institutes of Health (NIH) [T32 CA079443]
FX Funding was provided by National Institutes of Health (NIH) grant T32
CA079443. The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 67
TC 40
Z9 40
U1 5
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 14
PY 2011
VL 6
IS 9
AR e24696
DI 10.1371/journal.pone.0024696
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822JC
UT WOS:000295039700036
PM 21935441
ER
PT J
AU Venkatesh, AK
Geisler, BP
Chambers, JJG
Baugh, CW
Bohan, JS
Schuur, JD
AF Venkatesh, Arjun K.
Geisler, Benjamin P.
Chambers, Jennifer J. Gibson
Baugh, Christopher W.
Bohan, J. Stephen
Schuur, Jeremiah D.
TI Use of Observation Care in US Emergency Departments, 2001 to 2008
SO PLOS ONE
LA English
DT Article
ID OBSERVATION UNITS; STATES
AB Background: Observation care is a core component of emergency care delivery, yet, the prevalence of emergency department (ED) observation units (OUs) and use of observation care after ED visits is unknown. Our objective was to describe the 1) prevalence of OUs in United States (US) hospitals, 2) clinical conditions most frequently evaluated with observation, and 3) patient and hospital characteristics associated with use of observation.
Methods: Retrospective analysis of the proportion of hospitals with dedicated OUs and patient disposition after ED visit (discharge, inpatient admission or observation evaluation) using the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2001 to 2008. NHAMCS is an annual, national probability sample of ED visits to US hospitals conducted by the Center for Disease Control and Prevention. Logistic regression was used to assess hospital-level predictors of OU presence and polytomous logistic regression was used for patient-level predictors of visit disposition, each adjusted for multi-level sampling data. OU analysis was limited to 2007-2008.
Results: In 2007-2008, 34.1% of all EDs had a dedicated OU, of which 56.1% were under ED administrative control (EDOU). Between 2001 and 2008, ED visits resulting in a disposition to observation increased from 642,000 (0.60% of ED visits) to 2,318,000 (1.87%, p < .05). Chest pain was the most common reason for ED visit resulting in observation and the most common observation discharge diagnosis (19.1% and 17.1% of observation evaluations, respectively). In hospital-level adjusted analysis, hospital ownership status (non-profit or government), non-teaching status, and longer ED length of visit (>3.6 h) were predictive of OU presence. After patient-level adjustment, EDOU presence was associated with increased disposition to observation (OR 2.19).
Conclusions: One-third of US hospitals have dedicated OUs and observation care is increasingly used for a range of clinical conditions. Further research is warranted to understand the quality, cost and efficiency of observation care.
C1 [Venkatesh, Arjun K.] Brigham & Womens Hosp Massachusetts Gen Hosp Harv, Boston, MA USA.
[Geisler, Benjamin P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA.
[Chambers, Jennifer J. Gibson] Univ New England, Coll Osteopath Med, Biddeford, ME USA.
[Baugh, Christopher W.; Bohan, J. Stephen; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Baugh, Christopher W.; Bohan, J. Stephen; Schuur, Jeremiah D.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA.
RP Venkatesh, AK (reprint author), Brigham & Womens Hosp Massachusetts Gen Hosp Harv, Boston, MA USA.
EM akvenkatesh@partners.org
RI Geisler, Benjamin/A-9244-2010
OI Geisler, Benjamin/0000-0003-1704-6067
FU NCRR NIH HHS [UL1 RR 025758, UL1 RR025758]
NR 26
TC 35
Z9 35
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 SEP 14
PY 2011
VL 6
IS 9
AR e24326
DI 10.1371/journal.pone.0024326
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 822JC
UT WOS:000295039700017
PM 21935398
ER
PT J
AU Williams, KW
Sohn, JW
Donato, J
Lee, CE
Zhao, JJ
Elmquist, JK
Elias, CF
AF Williams, Kevin W.
Sohn, Jong-Woo
Donato, Jose, Jr.
Lee, Charlotte E.
Zhao, Jean J.
Elmquist, Joel K.
Elias, Carol F.
TI The Acute Effects of Leptin Require PI3K Signaling in the Hypothalamic
Ventral Premammillary Nucleus
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PROOPIOMELANOCORTIN NEURONS; ARCUATE NUCLEUS; ENERGY-BALANCE;
LUTEINIZING-HORMONE; RECOMBINANT LEPTIN; RAPID INHIBITION; POMC NEURONS;
FEMALE MICE; RAT-BRAIN; RECEPTOR
AB Evidence suggests that the role played by the adipocyte-derived hormone leptin in female reproductive physiology is mediated in part by neurons located within the ventral premammillary nucleus (PMV). Leptin activates PMV neurons; however, the intracellular signaling pathway and channel(s) involved remain undefined. Notably, leptin's excitatory and inhibitory effects within hypothalamic and brainstem nuclei share the intracellular signaling cascade phosphoinositide 3 kinase (PI3K). Therefore, we assessed whether PI3K signaling is required for the acute effect of leptin to alter cellular activity of PMV neurons that express leptin receptors (LepR PMV neurons). Leptin caused a rapid depolarization in the majority of LepR PMV neurons in patch-clamp recordings of hypothalamic slices, while a subset of LepR PMV neurons were hyperpolarized in response to leptin. Data were obtained from both male and female mice and results demonstrate that the acute effect of leptin on LepR PMV neurons was identical for both sexes. Pharmacological inhibition of PI3K prevented the acute leptin-induced change in neuronal activity of LepR PMV neurons, indicating a PI3K-dependent mechanism of leptin action. Similarly, mice with genetically disrupted PI3K signaling in LepR PMV neurons failed to alter cellular activity in response to leptin. Moreover, the leptin-induced depolarization was dependent on a putative TRPC channel. In contrast, the leptin-induced-hyperpolarization required the activation of a putative Katp channel. Collectively, these results suggest that PI3K signaling in LepR PMV neurons is essential for leptin-induced alteration in cellular activity, and these data may suggest a cellular correlate in which leptin contributes to the initiation of reproductive development.
C1 [Williams, Kevin W.; Sohn, Jong-Woo; Donato, Jose, Jr.; Lee, Charlotte E.; Elmquist, Joel K.; Elias, Carol F.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, Dallas, TX 75390 USA.
[Zhao, Jean J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Elmquist, Joel K.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
RP Williams, KW (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Kevin.Williams@UTSouthwestern.edu
RI Sohn, Jong Woo/D-6700-2014; Donato, Jose Jr./A-9662-2010;
OI Donato, Jose Jr./0000-0002-6183-3861; Elias, Carol
F/0000-0001-9878-9203
FU NIH [HD061539, K01DK087780, R01DK53301, R01MH61583, R01DK088423,
RL1DK081185, PL1 DK081182, UL1RR024923]; University of Texas
Southwestern Medical Center at Dallas; American Diabetes Association
[7-07-MN-17]
FX This work was supported by NIH Grant HD061539 and Regent's Scholar
Research Award (University of Texas Southwestern Medical Center at
Dallas) grants (to C. F. E.), American Diabetes Association Grant
7-07-MN-17 (to J.-W.S.), NIH Grant K01DK087780 (to K. W. W.), and NIH
Grants R01DK53301, R01MH61583, R01DK088423, and RL1DK081185 (to J.K.E.).
This work was also supported by NIH Grants PL1 DK081182 and UL1RR024923.
NR 61
TC 29
Z9 30
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 14
PY 2011
VL 31
IS 37
BP 13147
EP 13156
DI 10.1523/JNEUROSCI.2602-11.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 819QA
UT WOS:000294841900014
PM 21917798
ER
PT J
AU Bogdan, R
Santesso, DL
Fagerness, J
Perlis, RH
Pizzagalli, DA
AF Bogdan, Ryan
Santesso, Diane L.
Fagerness, Jesen
Perlis, Roy H.
Pizzagalli, Diego A.
TI Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1) Genetic
Variation and Stress Interact to Influence Reward Learning
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID EVENT-RELATED POTENTIALS; HEDONIC CAPACITY; PERCEIVED STRESS; EXTERNAL
INFORMATION; ANTERIOR CINGULATE; SIGNAL-DETECTION; DOPAMINE; DEPRESSION;
REINFORCEMENT; ANXIETY
AB Stress is a general risk factor for psychopathology, but the mechanisms underlying this relationship remain largely unknown. Animal studies and limited human research suggest that stress can induce anhedonic behavior. Moreover, emerging data indicate that genetic variation within the corticotropin-releasing hormone type 1 receptor gene (CRHR1) at rs12938031 may promote psychopathology, particularly in the context of stress. Using an intermediate phenotypic neurogenetics approach, we assessed how stress and CRHR1 genetic variation (rs12938031) influence reward learning, an important component of anhedonia. Psychiatrically healthy female participants (n = 75) completed a probabilistic reward learning task during stress and no-stress conditions while 128-channel event-related potentials were recorded. Fifty-six participants were also genotyped across CRHR1. Response bias, an individual's ability to modulate behavior as a function of reward, was the primary behavioral variable of interest. The feedback-related positivity (FRP) in response to reward feedback was used as a neural index of reward learning. Relative to the no-stress condition, acute stress was associated with blunted response bias as well as a smaller and delayed FRP (indicative of disrupted reward learning) and reduced anterior cingulate and orbitofrontal cortex activation to reward. Critically, rs12938031 interacted with stress to influence reward learning: both behaviorally and neurally, A homozygotes showed stress-induced reward learning abnormalities. These findings indicate that acute, uncontrollable stressors reduce participants' ability to modulate behavior as a function of reward, and that such effects are modulated by CRHR1 genotype. Homozygosity for the A allele at rs12938031 may increase risk for psychopathology via stress-induced reward learning deficits.
C1 [Pizzagalli, Diego A.] McLean Hosp, Ctr Depress Anxiety & Stress Res, Belmont, MA 02478 USA.
[Pizzagalli, Diego A.] McLean Hosp, Neuroimaging Ctr, Belmont, MA 02478 USA.
[Pizzagalli, Diego A.] Harvard Univ, Sch Med, Belmont, MA 02478 USA.
[Bogdan, Ryan; Santesso, Diane L.; Pizzagalli, Diego A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Perlis, Roy H.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA.
[Fagerness, Jesen; Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Perlis, Roy H.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Pizzagalli, DA (reprint author), McLean Hosp, Ctr Depress Anxiety & Stress Res, 115 Mill St, Belmont, MA 02478 USA.
EM dap@mclean.harvard.edu
OI Bogdan, Ryan/0000-0002-1430-1045
FU Harvard University; NIMH [R01 MH68376, R21 MH078979]; National Alliance
for Research on Schizophrenia and Depression Independent Investigator
Award; ANT North America Inc.; AstraZeneca; Bristol-Myers Squibb; Eli
Lilly and Company; GlaxoSmithKline; Pfizer; Proteus
FX This work was supported by Sackler Scholar in Psychobiology (Harvard
University) and Mind, Brain, and Behavior (Harvard University) grants
awarded to R. B., and by NIMH Grants R01 MH68376 and R21 MH078979, Merck
Awards for Genome-Related Research (Harvard University), Talley Fund
(Harvard University) grants, and a 2008 National Alliance for Research
on Schizophrenia and Depression Independent Investigator Award (D. A.
P.). We thank Brian Galloway, Miles Nugent, Avram Holmes, Yuliya
Nikolova, Sara Rubenstein, Courtney Bagge, Scott Coffey, and Yan Emily
Yuan for their assistance. Parts of this paper have been presented
previously at the 22nd Annual Meeting of the Society for Research in
Psychopathology (September 2008; Pittsburgh, PA), the 23rd Annual
Meeting of the Society for Research in Psychopathology (September 2009;
Minneapolis, MN), and the 49th Annual Meeting of the Society for
Psychophysiological Research (October 2009; Berlin, Germany).; D.A.P.
has received consulting fees from ANT North America Inc. (Advanced Neuro
Technology) and AstraZeneca, and honoraria from AstraZeneca. R. H. P.
has received honoraria and speaker's or consulting fees from
AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company,
GlaxoSmithKline, Pfizer, and Proteus. R. H. P. is a major stockholder in
Concordant Rater Systems, LLC. R. B., D. L. S., and J.F. declare no
competing financial interests.
NR 60
TC 32
Z9 33
U1 3
U2 11
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 14
PY 2011
VL 31
IS 37
BP 13246
EP 13254
DI 10.1523/JNEUROSCI.2661-11.2011
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 819QA
UT WOS:000294841900023
PM 21917807
ER
PT J
AU Suri, P
Miyakoshi, A
Hunter, DJ
Jarvik, JG
Rainville, J
Guermazi, A
Li, L
Katz, JN
AF Suri, Pradeep
Miyakoshi, Asako
Hunter, David J.
Jarvik, Jeffrey G.
Rainville, James
Guermazi, Ali
Li, Ling
Katz, Jeffrey N.
TI Does lumbar spinal degeneration begin with the anterior structures? A
study of the observed epidemiology in a community-based population
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
DE degenerative cascade; degeneration; disk; facet joint; arthritis;
lumbar; spine
ID FACET JOINT OSTEOARTHRITIS; LOW-BACK-PAIN; DISC DEGENERATION;
CORONARY-ARTERY; VARIABILITY; PROGRESSION; DISEASE; DESIGN; COHORT
AB Background-: Prior studies that have concluded that disk degeneration uniformly precedes facet degeneration have been based on convenience samples of individuals with low back pain. We conducted a study to examine whether the view that spinal degeneration begins with the anterior spinal structures is supported by epidemiologic observations of degeneration in a community-based population.
Methods-: 361 participants from the Framingham Heart Study were included in this study. The prevalences of anterior vertebral structure degeneration (disk height loss) and posterior vertebral structure degeneration (facet joint osteoarthritis) were characterized by CT imaging. The cohort was divided into the structural subgroups of participants with 1) no degeneration, 2) isolated anterior degeneration (without posterior degeneration), 3) combined anterior and posterior degeneration, and 4) isolated posterior degeneration (without anterior structure degeneration). We determined the prevalence of each degeneration pattern by age group < 45, 45-54, 55-64, >= 65. In multivariate analyses we examined the association between disk height loss and the response variable of facet joint osteoarthritis, while adjusting for age, sex, BMI, and smoking.
Results-: As the prevalence of the no degeneration and isolated anterior degeneration patterns decreased with increasing age group, the prevalence of the combined anterior/posterior degeneration pattern increased. 22% of individuals demonstrated isolated posterior degeneration, without an increase in prevalence by age group. Isolated posterior degeneration was most common at the L5-S1 and L4-L5 spinal levels. In multivariate analyses, disk height loss was independently associated with facet joint osteoarthritis, as were increased age (years), female sex, and increased BMI (kg/m(2)), but not smoking.
Conclusions-: The observed epidemiology of lumbar spinal degeneration in the community-based population is consistent with an ordered progression beginning in the anterior structures, for the majority of individuals. However, some individuals demonstrate atypical patterns of degeneration, beginning in the posterior joints. Increased age and BMI, and female sex may be related to the occurrence of isolated posterior degeneration in these individuals.
C1 [Suri, Pradeep] VA Boston Healthcare Syst, Div PM&R, Boston, MA USA.
[Suri, Pradeep; Rainville, James] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA.
[Suri, Pradeep] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Suri, Pradeep; Hunter, David J.; Rainville, James; Li, Ling] New England Baptist Hosp, Div Res, Boston, MA USA.
[Miyakoshi, Asako; Jarvik, Jeffrey G.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA.
[Miyakoshi, Asako; Jarvik, Jeffrey G.] Univ Washington, Med Ctr, Dept Neurol Surg, Seattle, WA 98195 USA.
[Miyakoshi, Asako; Jarvik, Jeffrey G.] Univ Washington, Med Ctr, Dept Hlth Serv, Seattle, WA 98195 USA.
[Hunter, David J.] Univ Sydney, No Clin Sch, Sydney, NSW 2006, Australia.
[Guermazi, Ali] Boston Univ, Sch Med, Dept Radiol, Boston, MA 02118 USA.
[Katz, Jeffrey N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA USA.
[Katz, Jeffrey N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA USA.
RP Suri, P (reprint author), VA Boston Healthcare Syst, Div PM&R, Boston, MA USA.
EM pradeepsuri1@gmail.com
RI Hunter, David/A-4622-2010
OI Hunter, David/0000-0003-3197-752X
FU Rehabilitation Medicine Scientist Training Program (RMSTP); National
Institutes of Health [K12 HD001097]; NIH/NIAMS [K24 AR 02123, P60 AR
47782, R01 1AR 054912-01A2]; Australian Research Council; AHRQ [R01
HS19222-01]
FX PS is funded by the Rehabilitation Medicine Scientist Training Program
(RMSTP) and the National Institutes of Health (K12 HD001097). JNK is
funded in part by NIH/NIAMS K24 AR 02123 and NIH/NIAMS P60 AR 47782. DJH
is funded by an Australian Research Council Future Fellowship. JGJ is
funded in part by AHRQ R01 HS19222-01 and NIH/NIAMS R01 1AR 054912-01A2
NR 32
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Z9 23
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD SEP 13
PY 2011
VL 12
AR 202
DI 10.1186/1471-2474-12-202
PG 7
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 827TC
UT WOS:000295450100002
PM 21914197
ER
PT J
AU Wedick, NM
Brennan, AM
Sun, Q
Hu, FB
Mantzoros, CS
van Dam, RM
AF Wedick, Nicole M.
Brennan, Aoife M.
Sun, Qi
Hu, Frank B.
Mantzoros, Christos S.
van Dam, Rob M.
TI Effects of caffeinated and decaffeinated coffee on biological risk
factors for type 2 diabetes: a randomized controlled trial
SO NUTRITION JOURNAL
LA English
DT Article
ID INSULIN-RESISTANCE; CHLOROGENIC ACID; GLUCOSE-TOLERANCE; FETUIN-A;
CONSUMPTION; METAANALYSIS; SENSITIVITY; MELLITUS; HEALTHY; PLASMA
AB Background: Coffee consumption has been associated with a lower risk of type 2 diabetes in prospective cohort studies, but the underlying mechanisms remain unclear. The aim of this study was to evaluate the effects of regular and decaffeinated coffee on biological risk factors for type 2 diabetes.
Methods: Randomized parallel-arm intervention conducted in 45 healthy overweight volunteers who were nonsmokers and regular coffee consumers. Participants were assigned to consumption of 5 cups (177 mL each) per day of instant caffeinated coffee, decaffeinated coffee, or no coffee (i.e., water) for 8 weeks.
Results: Average age was 40 years and body mass index was 29.5 kg/m(2). Compared with consuming no coffee, consumption of caffeinated coffee increased adiponectin (difference in change from baseline 1.4 mu g/mL; 95% CI: 0.2, 2.7) and interleukin-6 (difference: 60%; 95% CI: 8, 138) concentrations and consumption of decaffeinated coffee decreased fetuin-A concentrations (difference: -20%; 95% CI: -35, -1). For measures of glucose tolerance, insulin sensitivity, and insulin secretion, no significant differences were found between treatment groups.
Conclusions: Although no changes in glycemia and/or insulin sensitivity were observed after 8 weeks of coffee consumption, improvements in adipocyte and liver function as indicated by changes in adiponectin and fetuin-A concentrations may contribute to beneficial metabolic effects of long-term coffee consumption.
C1 [Wedick, Nicole M.; Sun, Qi; Hu, Frank B.; van Dam, Rob M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Brennan, Aoife M.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Hu, Frank B.; van Dam, Rob M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Sun, Qi; Hu, Frank B.; van Dam, Rob M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA 02115 USA.
[Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
RP Wedick, NM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
EM nwedick@hsph.harvard.edu
RI van Dam, Rob/F-9674-2010
OI van Dam, Rob/0000-0002-7354-8734
FU Boston Obesity Nutrition Research Center [2005-P-000377/2]; National
Center for Research Resources [UL1RR025758]
FX We gratefully thank the participants of the Coffee Trial for their
participation and the General Clinical Research Center nurses and
nutritionists at Beth Israel Deaconess Medical Center for their
invaluable contribution to the conduct of the trial. We are grateful to
David J. Greenblatt (Tufts University School of Medicine and Tufts
Medical Center, Boston, MA) for measurement of caffeine concentrations,
Peter C. Hollman and Dini Venema (RIKILT Institute of Food Safety,
Wageningen, The Netherlands) for the measurement of chlorogenic acid,
and Sandy Slow (Canterbury Health Laboratories, Christchurch, New
Zealand) for the measurement of trigonelline. The research for this
study was financially supported by a Boston Obesity Nutrition Research
Center pilot and feasibility grant (grant#: 2005-P-000377/2) and by
Clinical Translational Science Award UL1RR025758 to Harvard University
and Beth Israel Deaconess Medical Center from the National Center for
Research Resources. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Center for Research Resources or the National Institutes of
Health. The clinical trial registration number is NCT00305097. The
coffee was supplied by Nestle.
NR 29
TC 50
Z9 50
U1 5
U2 41
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2891
J9 NUTR J
JI Nutr. J.
PD SEP 13
PY 2011
VL 10
AR 93
DI 10.1186/1475-2891-10-93
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 826TJ
UT WOS:000295377300002
PM 21914162
ER
PT J
AU Tucker, JD
Peng, H
Wang, KD
Chang, H
Zhang, SM
Yang, LG
Yang, B
AF Tucker, Joseph D.
Peng, Hua
Wang, Kaidi
Chang, Helena
Zhang, Sen-Miao
Yang, Li-Gang
Yang, Bin
TI Female Sex Worker Social Networks and STI/HIV Prevention in South China
SO PLOS ONE
LA English
DT Article
ID HIV PREVENTION; ENTERTAINMENT WORKERS; MIGRANT WORKERS; RISK-FACTORS;
YUNNAN PROVINCE; KAIYUAN CITY; INFECTION; BEHAVIOR; INTERVENTION; HEALTH
AB Background: Reducing harm associated with selling and purchasing sex is an important public health priority in China, yet there are few examples of sustainable, successful programs to promote sexual health among female sex workers. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female sex workers to collectively organize, advocate for their rights, and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female sex workers in South China to determine their potential for sexual health promotion.
Methods/Principal Findings: Semi-structured interviews with 34 low-income female sex workers and 28 health outreach members were used to examine how social relationships affected condom use and negotiation, STI/HIV testing and health-seeking behaviors, and dealing with violent clients. These data suggested that sex worker's laoxiang (hometown social connections) were more powerful than relationships between women selling sex at the same venue in establishing the terms and risk of commercial sex. Female sex workers from the same hometown often migrated to the city with their laoxiang and these social connections fulfilled many of the functions of nongovernmental organizations, including collective mobilization, condom promotion, violence mitigation, and promotion of health-seeking behaviors. Outreach members observed that sex workers accompanied by their laoxiang were often more willing to accept STI/HIV testing and trust local sexual health services.
Conclusions/Significance: Organizing STI/HIV prevention services around an explicitly defined laoxiang social network may provide a strong foundation for sex worker health programs. Further research on dyadic interpersonal relationships between female sex workers, group dynamics and norm establishment, and the social network characteristics are needed.
C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Tucker, Joseph D.; Peng, Hua; Zhang, Sen-Miao; Yang, Li-Gang; Yang, Bin] Guangdong Prov STD Control Ctr, Guangzhou, Guangdong, Peoples R China.
[Wang, Kaidi] Harvard Univ, Sch Med, Boston, MA USA.
[Chang, Helena] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
EM jtucker4@partners.org
FU National Institutes of Health [US NIH 1K01TW008200-01A1]; Harvard
Institute for Global Health
FX Support for this research came from an National Institutes of Health
Fogarty K01 Award (US NIH 1K01TW008200-01A1) and the Harvard Institute
for Global Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 63
TC 15
Z9 16
U1 0
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 13
PY 2011
VL 6
IS 9
AR e24816
DI 10.1371/journal.pone.0024816
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 825ZV
UT WOS:000295321800067
PM 21931856
ER
PT J
AU Taguchi, A
Politi, K
Pitteri, SJ
Lockwood, WW
Faca, VM
Kelly-Spratt, K
Wong, CH
Zhang, Q
Chin, A
Park, KS
Goodman, G
Gazdar, AF
Sage, J
Dinulescu, DM
Kucherlapati, R
DePinho, RA
Kemp, CJ
Varmus, HE
Hanash, SM
AF Taguchi, Ayumu
Politi, Katerina
Pitteri, Sharon J.
Lockwood, William W.
Faca, Vitor M.
Kelly-Spratt, Karen
Wong, Chee-Hong
Zhang, Qing
Chin, Alice
Park, Kwon-Sik
Goodman, Gary
Gazdar, Adi F.
Sage, Julien
Dinulescu, Daniela M.
Kucherlapati, Raju
DePinho, Ronald A.
Kemp, Christopher J.
Varmus, Harold E.
Hanash, Samir M.
TI Lung Cancer Signatures in Plasma Based on Proteome Profiling of Mouse
Tumor Models
SO CANCER CELL
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; OVARIAN-CANCER; CELL-ADHESION;
CLINICOPATHOLOGICAL FEATURES; IMPROVE DETECTION; FACTOR RECEPTOR;
SERUM-PROTEINS; K-RAS; MICE; ADENOCARCINOMAS
AB We investigated the potential of in-depth quantitative proteomics to reveal plasma protein signatures that reflect lung tumor biology. We compared plasma protein profiles of four mouse models of lung cancer with profiles of models of pancreatic, ovarian, colon, prostate, and breast cancer and two models of inflammation. A protein signature for Titf1/Nkx2-1, a known lineage-survival oncogene in lung cancer, was found in plasmas of mouse models of lung adenocarcinoma. An EGFR signature was found in plasma of an EGFR mutant model, and a distinct plasma signature related to neuroendocrine development was uncovered in the small-cell lung cancer model. We demonstrate relevance to human lung cancer of the protein signatures identified on the basis of mouse models.
C1 [Taguchi, Ayumu; Pitteri, Sharon J.; Faca, Vitor M.; Kelly-Spratt, Karen; Wong, Chee-Hong; Zhang, Qing; Chin, Alice; Goodman, Gary; Kemp, Christopher J.; Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Politi, Katerina; Lockwood, William W.; Varmus, Harold E.] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10021 USA.
[Park, Kwon-Sik; Sage, Julien] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
[Gazdar, Adi F.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
[Gazdar, Adi F.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Dinulescu, Daniela M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Eugene Braunwald Res Ctr,Dept Pathol, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Belfer Inst Appl Canc Sci,Dept Med Oncol, Boston, MA 02115 USA.
RP Hanash, SM (reprint author), Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
EM shanash@fhcrc.org
RI Xiao, Yang/B-5668-2012; Faca, Vitor/A-3989-2013;
OI FACA, VITOR MARCEL/0000-0003-3205-7944; Pitteri,
Sharon/0000-0002-3119-873X
FU National Cancer Institute; Canary Foundation; Labrecque Foundation;
Uniting Against Lung Cancer Foundation; Department of Defense (DOD)
[W81XWH-10-1-0263]; Burroughs Wellcome; V Foundation; Mary Kay Ash
Foundation; Rivkin Foundation
FX Funding support was provided by the National Cancer Institute's Mouse
Models of Human Cancer program; the Canary, Labrecque, and Uniting
Against Lung Cancer Foundations; and the Department of Defense (DOD)
Congressionally Mandated Lung Cancer Research program. K.S.P. is a
Parker B. Francis Fellow. D.M.D. is supported by the DOD (grant no.
W81XWH-10-1-0263) and by the Burroughs Wellcome, V Foundation, Mary Kay
Ash, and Rivkin Foundations. The authors declare no competing financial
interests.
NR 55
TC 94
Z9 95
U1 1
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD SEP 13
PY 2011
VL 20
IS 3
BP 289
EP 299
DI 10.1016/j.ccr.2011.08.007
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 824MJ
UT WOS:000295205700006
PM 21907921
ER
PT J
AU De Raedt, T
Walton, Z
Yecies, JL
Li, DA
Chen, YM
Malone, CF
Maertens, O
Jeong, SM
Bronson, RT
Lebleu, V
Kalluri, R
Normant, E
Haigis, MC
Manning, BD
Wong, KK
Macleod, KF
Cichowski, K
AF De Raedt, Thomas
Walton, Zandra
Yecies, Jessica L.
Li, Danan
Chen, Yimei
Malone, Clare F.
Maertens, Ophelia
Jeong, Seung Min
Bronson, Roderick T.
Lebleu, Valerie
Kalluri, Raghu
Normant, Emmanuel
Haigis, Marcia C.
Manning, Brendan D.
Wong, Kwok-Kin
Macleod, Kay F.
Cichowski, Karen
TI Exploiting Cancer Cell Vulnerabilities to Develop a Combination Therapy
for Ras-Driven Tumors
SO CANCER CELL
LA English
DT Article
ID ENDOPLASMIC-RETICULUM-STRESS; UNFOLDED PROTEIN RESPONSE;
NEUROFIBROMATOSIS TYPE-1 GENE; OXIDATIVE STRESS; LUNG-CANCER; MUTATIONS;
AUTOPHAGY; HSP90; SUPPRESSOR; REVEALS
AB Ras-driven tumors are often refractory to conventional therapies. Here we identify a promising targeted therapeutic strategy for two Ras-driven cancers: Nf1-deficient malignancies and Kras/p53 mutant lung cancer. We show that agents that enhance proteotoxic stress, including the HSP90 inhibitor IPI-504, induce tumor regression in aggressive mouse models, but only when combined with rapamycin. These agents synergize by promoting irresolvable ER stress, resulting in catastrophic ER and mitochondrial damage. This process is fueled by oxidative stress, which is caused by IPI-504-dependent production of reactive oxygen species, and the rapamycin-dependent suppression of glutathione, an important endogenous antioxidant. Notably, the mechanism by which these agents cooperate reveals a therapeutic paradigm that can be expanded to develop additional combinations.
C1 [De Raedt, Thomas; Malone, Clare F.; Maertens, Ophelia; Wong, Kwok-Kin; Cichowski, Karen] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[De Raedt, Thomas; Walton, Zandra; Yecies, Jessica L.; Li, Danan; Malone, Clare F.; Maertens, Ophelia; Bronson, Roderick T.; Lebleu, Valerie; Kalluri, Raghu; Manning, Brendan D.; Wong, Kwok-Kin; Cichowski, Karen] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[De Raedt, Thomas; Wong, Kwok-Kin; Cichowski, Karen] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA.
[Walton, Zandra; Li, Danan] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Yecies, Jessica L.; Manning, Brendan D.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
[Chen, Yimei; Macleod, Kay F.] Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA.
[Jeong, Seung Min; Haigis, Marcia C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Lebleu, Valerie; Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Div Matrix Biol, Boston, MA 02115 USA.
[Normant, Emmanuel] Infin Pharmaceut, Cambridge, MA 02139 USA.
RP Cichowski, K (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM kcichowski@rics.bwh.harvard.edu
RI Kalluri, Raghu/E-2677-2015;
OI Kalluri, Raghu/0000-0002-2190-547X; wong, kwok kin/0000-0001-6323-235X
FU NCI [CA129814]; Ludwig Center at DF/HCC [CA122794, CA140594]; Children's
Tumor Foundation; Research Foundation Flanders (FWO)
FX We thank Wade Harper, Steve Elledge, Nathanael Gray, Heather Harding,
and Hugues de The for helpful discussions. This work was supported by
the NCI KC: (CA129814) and the Ludwig Center at DF/HCC; KWW: (CA122794,
CA140594). TD is a recipient of the Young Investigator Award of the
Children's Tumor Foundation. OM is a Postdoctoral Fellow of the Research
Foundation Flanders (FWO).
NR 52
TC 96
Z9 97
U1 2
U2 24
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD SEP 13
PY 2011
VL 20
IS 3
BP 400
EP 413
DI 10.1016/j.ccr.2011.08.014
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 824MJ
UT WOS:000295205700014
PM 21907929
ER
PT J
AU Pyati, UJ
Gjini, E
Carbonneau, S
Lee, JS
Guo, F
Jette, CA
Kelsell, DP
Look, AT
AF Pyati, Ujwal J.
Gjini, Evisa
Carbonneau, Seth
Lee, Jeong-Soo
Guo, Feng
Jette, Cicely A.
Kelsell, David P.
Look, A. Thomas
TI p63 Mediates an Apoptotic Response to Pharmacological and
Disease-Related ER Stress in the Developing Epidermis
SO DEVELOPMENTAL CELL
LA English
DT Article
ID UNFOLDED-PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; PROGRAMMED
CELL-DEATH; TRANSCRIPTION FACTOR; TRANSMEMBRANE PROTEIN; MESSENGER-RNA;
MAMMALIAN-CELLS; GENE-EXPRESSION; P53 FAMILY; ZEBRAFISH
AB Endoplasmic reticulum (ER) stress triggers tissue-specific responses that culminate in either cellular adaptation or apoptosis, but the genetic networks distinguishing these responses are not well understood. Here we demonstrate that ER stress induced in the developing zebrafish causes rapid apoptosis in the brain, spinal cord, tail epidermis, lens, and epiphysis. Focusing on the tail epidermis, we uncover an apoptotic response that depends on Puma, but not on p53 or Chop. puma is transcriptionally activated during this ER stress response in a p53-independent manner, and is an essential mediator of epidermal apoptosis. We demonstrate that the p63 transcription factor is upregulated to initiate this apoptotic pathway and directly activates puma transcription in response to ER stress. We also show that a mutation of human Connexin 31, which causes erythrokeratoderma variabilis, induces ER stress and p63-dependent epidermal apoptosis in the zebrafish embryo, thus implicating this pathway in the pathogenesis of inherited disease.
C1 [Pyati, Ujwal J.; Gjini, Evisa; Carbonneau, Seth; Lee, Jeong-Soo; Guo, Feng; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Pyati, Ujwal J.; Gjini, Evisa; Carbonneau, Seth; Lee, Jeong-Soo; Guo, Feng; Look, A. Thomas] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Jette, Cicely A.] Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA.
[Kelsell, David P.] Queen Mary Univ London, Ctr Cutaneous Res, Inst Cell & Mol Sci, Barts & London Sch Med & Dent, London E1 2AT, England.
RP Gjini, E (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM evisa_gjini@dfci.harvard.edu; thomas_look@dfci.harvard.edu
FU Alex's Lemonade Stand Foundation; NIH [3R01CA119066-04S1, R01CA119066]
FX We thank John Gilbert, Elspeth Payne, and Samuel Sidi for critical
readings of the manuscript. Confocal microscopy images for this study
were acquired in the Confocal and Light Microscopy Core Facility at the
Dana-Farber Cancer Institute with the assistance of Lisa Cameron. U.J.P.
was supported by the Alex's Lemonade Stand Foundation Young Investigator
Award, U.J.P. and S.C. by NIH 3R01CA119066-04S1, and A.T.L. by NIH
R01CA119066.
NR 51
TC 23
Z9 23
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD SEP 13
PY 2011
VL 21
IS 3
BP 492
EP 505
DI 10.1016/j.devcel.2011.07.012
PG 14
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 822PA
UT WOS:000295060900014
PM 21920315
ER
PT J
AU O'Brien, TX
AF O'Brien, Terrence X.
TI Iron Metabolism, Anemia, and Heart Failure
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE anemia; heart failure; iron
ID MORTALITY
C1 [O'Brien, Terrence X.] Med Univ S Carolina, Charleston, SC 29425 USA.
[O'Brien, Terrence X.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP O'Brien, TX (reprint author), Med Univ S Carolina, 25 Courtenay Dr,ART 7063, Charleston, SC 29425 USA.
EM obriente@musc.edu
NR 11
TC 1
Z9 1
U1 0
U2 0
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 SEP 13
PY 2011
VL 58
IS 12
BP 1252
EP 1253
DI 10.1016/j.jacc.2011.03.060
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 816NP
UT WOS:000294609400011
PM 21903059
ER
PT J
AU DeSantis, SM
Toole, JM
Kratz, JM
Uber, WE
Wheat, MJ
Stroud, MR
Ikonomidis, JS
Spinale, FG
AF DeSantis, Stacia M.
Toole, J. Matthew
Kratz, John M.
Uber, Walter E.
Wheat, Margaret J.
Stroud, Martha R.
Ikonomidis, John S.
Spinale, Francis G.
TI Early Postoperative Outcomes and Blood Product Utilization in Adult
Cardiac Surgery The Post-Aprotinin Era
SO CIRCULATION
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the American-Heart-Association
CY NOV 12-16, 2010
CL Chicago, IL
SP Amer Heart Assoc
DE aprotinin; cardiac surgery; blood products; bleeding; postoperative
outcomes
ID CORONARY-ARTERY-BYPASS; RANDOMIZED CLINICAL-TRIALS; GRAFT-SURGERY; RISK;
METAANALYSIS; MORTALITY; SAFETY; COHORT; PUMP
AB Background-Aprotinin was a commonly used pharmacological agent for homeostasis in cardiac surgery but was discontinued, resulting in the extensive use of lysine analogues. This study tested the hypothesis that early postoperative adverse events and blood product utilization would affected in this post-aprotinin era.
Methods and Results-Adult patients (n = 781) undergoing coronary artery bypass, valve replacement, or both from November 1, 2005, to October 31, 2008, at a single institution were included. Multiple logistic regression modeling and propensity scoring were performed on 29 preoperative and intraoperative variables in patients receiving aprotinin (n = 325) or lysine analogues (n = 456). The propensity-adjusted relative risk (RR) for the intraoperative use of packed red blood cells (RR, 0.75; 95% confidence interval [CI], 0.57 to 0.99), fresh frozen plasma (RR, 0.37; 95% CI, 0.21 to 0.64), and cryoprecipitate (RR: 0.06; 95% CI, 0.02 to 0.22) were lower in the aprotinin versus lysine analog group (all P < 0.05). The risk for mortality (RR, 0.53; 95% CI, 0.16 to 1.79) and neurological events (RR, 0.87; 95% CI, 0.35 to 2.18) remained similar between groups, whereas a trend for reduced risk for renal dysfunction was observed in the aprotinin group.
Conclusions-In the post-aprotinin era, with the exclusive use of lysine analogues, the relative risk of early postoperative outcomes such as mortality and renal dysfunction have not improved, but the risk for the intraoperative use of blood products has increased. Thus, improvements in early postoperative outcomes have not been realized with the discontinued use of aprotinin, but rather increased blood product use has occurred with the attendant costs and risks inherent with this strategy. (Circulation. 2011; 124[suppl 1]: S62-S69.)
C1 [Toole, J. Matthew; Kratz, John M.; Stroud, Martha R.; Ikonomidis, John S.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29403 USA.
[DeSantis, Stacia M.] Med Univ S Carolina, Dept Biostat & Epidemiol, Charleston, SC 29403 USA.
[Uber, Walter E.; Wheat, Margaret J.] Med Univ S Carolina, Dept Pharm Serv, Charleston, SC 29403 USA.
Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA.
RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, 114 Doughty St, Charleston, SC 29403 USA.
EM wilburnm@musc.edu
FU NHLBI NIH HHS [HL59165, R01 HL059165, R42 HL099258]
NR 30
TC 13
Z9 13
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 13
PY 2011
VL 124
IS 11
SU 1
BP S62
EP S69
DI 10.1161/CIRCULATIONAHA.110.002543
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 818VB
UT WOS:000294782800008
PM 21911820
ER
PT J
AU Dixon, JA
Gorman, RC
Stroud, RE
Mukherjee, R
Meyer, EC
Baker, NL
Morita, M
Hamamoto, H
Ryan, LP
Gorman, JH
Spinale, FG
AF Dixon, Jennifer A.
Gorman, Robert C.
Stroud, Robert E.
Mukherjee, Rupak
Meyer, Evan C.
Baker, Nathaniel L.
Morita, Masato
Hamamoto, Hirotsugu
Ryan, Liam P.
Gorman, Joseph H., III
Spinale, Francis G.
TI Targeted Regional Injection of Biocomposite Microspheres Alters
Post-Myocardial Infarction Remodeling and Matrix Proteolytic Pathways
SO CIRCULATION
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the American-Heart-Association
CY NOV 12-16, 2010
CL Chicago, IL
SP Amer Heart Assoc
DE infarct expansion; matrix metalloproteinase; tissue inhibitor of matrix
metalloproteinases
ID LEFT-VENTRICULAR FUNCTION; MYOCARDIAL-INFARCTION; HEART-FAILURE; CARDIAC
FIBROSIS; TGF-BETA; MICRORNAS; EXPANSION; METALLOPROTEINASES; WALL;
CARDIOMYOPATHY
AB Background-Although localized delivery of biocomposite materials, such as calcium hydroxyapatite (CHAM), have been demonstrated to potentially attenuate adverse left ventricular (LV) remodeling after myocardial infarction (MI), the underlying biological mechanisms for this effect remain unclear. This study tested the hypothesis that targeted CHAM injections would alter proteolytic pathways (matrix metalloproteinases [MMPs] and tissue inhibitors of MMPs [TIMPs]) and would be associated with parameters of post-MI LV remodeling.
Methods and Results-MI was induced in adult sheep followed by 20 targeted injections of a total volume of 1.3 mL (n = 6) or 2.6 mL of CHAM (n = 5) or saline (n = 13) and LV end-diastolic volume (EDV) and MMP/TIMP profiles in the MI region were measured at 8 weeks after MI. LV EDV decreased with 2.6 mL CHAM versus MI only (105.4 +/- 7.5 versus 80.6 +/- 4.2 respectively, P < 0.05) but not with 1.3 mL CHAM (94.5 +/- 5.0, P = 0.32). However, MI thickness increased by 2-fold in both CHAM groups compared with MI only (P < 0.05). MMP-13 increased 40-fold in the MI only group (P < 0.05) but fell by >6-fold in both CHAM groups (P < 0.05). MMP-7 increased approximately 1.5-fold in the MI only group (P < 0.05) but decreased to referent control values in both CHAM groups in the MI region (P < 0.05). Collagen content was reduced by approximately 30% in the CHAM groups compared with MI only (P < 0.05).
Conclusions-Differential effects on LV remodeling and MMP/TIMP profiles occurred with CHAM. Thus, targeted injection of a biocomposite material can favorably affect the post-MI remodeling process and therefore holds promise as a treatment strategy in and of itself, or as a matrix with potentially synergistic effects with localized pharmacological or cellular therapies. (Circulation. 2011; 124[suppl 1]:S35-S45.)
C1 [Dixon, Jennifer A.; Stroud, Robert E.; Mukherjee, Rupak; Meyer, Evan C.; Baker, Nathaniel L.; Spinale, Francis G.] Med Univ S Carolina, Charleston, SC 29425 USA.
Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Gorman, Robert C.; Morita, Masato; Hamamoto, Hirotsugu; Ryan, Liam P.; Gorman, Joseph H., III] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
[Gorman, Robert C.; Morita, Masato; Hamamoto, Hirotsugu; Ryan, Liam P.; Gorman, Joseph H., III] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
RP Spinale, FG (reprint author), Strom Thurmond Res Ctr, 114 Doughty St,Suite 625, Charleston, SC 29425 USA.
EM wilburnm@musc.edu
FU NHLBI NIH HHS [HL63954, R01 HL063954, HL73021, R01 HL059165-12, HL59165,
HL57952, HL95608, R01 HL057952-12, P01 HL078825, R01 HL073021, R01
HL059165, R01 HL063954-12, R01 HL095608, R01 HL095608-03, R01 HL057952,
HL78825, R01 HL073021-08]
NR 41
TC 6
Z9 6
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 13
PY 2011
VL 124
IS 11
SU 1
BP S35
EP S45
DI 10.1161/CIRCULATIONAHA.111.035774
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 818VB
UT WOS:000294782800005
PM 21911817
ER
PT J
AU Aung, T
Chapuy, B
Vogel, D
Wenzel, D
Oppermann, M
Lahmann, M
Weinhage, T
Menck, K
Hupfeld, T
Koch, R
Trumper, L
Wulf, GG
AF Aung, Thiha
Chapuy, Bjoern
Vogel, Daniel
Wenzel, Dirk
Oppermann, Martin
Lahmann, Marlen
Weinhage, Toni
Menck, Kerstin
Hupfeld, Timo
Koch, Raphael
Truemper, Lorenz
Wulf, Gerald G.
TI Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma
modulated by ATP-binding cassette transporter A3
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; TUMOR-DERIVED EXOSOMES; MULTIVESICULAR BODIES;
MULTIDRUG-RESISTANCE; TRANSFERRIN RECEPTOR; MEMBRANE-VESICLES;
DRUG-RESISTANCE; II CELLS; RITUXIMAB; ABCA3
AB Targeting the surface of malignant cells has evolved into a cornerstone in cancer therapy, paradigmatically introduced by the success of humoral immunotherapy against CD20 in malignant lymphoma. However, tumor cell susceptibility to immunochemotherapy varies, with mostly a fatal outcome in cases of resistant disease. Here, we show that lymphoma exosomes shield target cells from antibody attack and that exosome biogenesis is modulated by the lysosome-related organelle-associated ATP-binding cassette (ABC) transporter A3 (ABCA3). B-cell lymphoma cells released exosomes that carried CD20, bound therapeutic anti-CD20 antibodies, consumed complement, and protected target cells from antibody attack. ABCA3, previously shown to mediate resistance to chemotherapy, was critical for the amounts of exosomes released, and both pharmacological blockade and the silencing of ABCA3 enhanced susceptibility of target cells to antibody-mediated lysis. Mechanisms of cancer cell resistance to drugs and antibodies are linked in an ABCA3-dependent pathway of exosome secretion.
C1 [Aung, Thiha; Chapuy, Bjoern; Vogel, Daniel; Lahmann, Marlen; Weinhage, Toni; Menck, Kerstin; Hupfeld, Timo; Koch, Raphael; Truemper, Lorenz; Wulf, Gerald G.] Univ Gottingen, Dept Hematol & Oncol, D-37075 Gottingen, Germany.
[Chapuy, Bjoern] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Wenzel, Dirk] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany.
[Oppermann, Martin] Univ Gottingen, Dept Cellular & Mol Immunol, D-37073 Gottingen, Germany.
RP Wulf, GG (reprint author), Univ Gottingen, Dept Hematol & Oncol, D-37075 Gottingen, Germany.
EM gwulf@med.uni-goettingen.de
OI Menck, Kerstin/0000-0002-8188-0163; Weinhage, Toni/0000-0003-4337-9260
FU Deutsche Forschungsgemeinschaft [DFG Wu 310/3-1]; University Medicine
Goettingen
FX We thank Sabrina Becker of the Flow Cytometry Core Facility at the
University of Goettingen. This work was supported by the Deutsche
Forschungsgemeinschaft Grant DFG Wu 310/3-1 (to G.G.W.) and by a
University Medicine Goettingen Jacob-Henle program grant (to T.A.).
NR 55
TC 58
Z9 61
U1 4
U2 16
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 SEP 13
PY 2011
VL 108
IS 37
BP 15336
EP 15341
DI 10.1073/pnas.1102855108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819DF
UT WOS:000294804900069
PM 21873242
ER
PT J
AU Song, JW
Munn, LL
AF Song, Jonathan W.
Munn, Lance L.
TI Fluid forces control endothelial sprouting
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE 3D angiogenesis on a chip; collagen gel; structural remodeling;
alternative to animal model; vessel analog
ID LAMINAR SHEAR-STRESS; NITRIC-OXIDE; CAPILLARY MORPHOGENESIS; CELL
PROLIFERATION; INTERSTITIAL FLOW; TUMOR VASCULATURE; TIP CELLS;
IN-VITRO; ANGIOGENESIS; GROWTH
AB During angiogenesis, endothelial cells (ECs) from intact blood vessels quickly infiltrate avascular regions via vascular sprouting. This process is fundamental to many normal and pathological processes such as wound healing and tumor growth, but its initiation and control are poorly understood. Vascular endothelial cell growth factor (VEGF) can promote vessel dilation and angiogenic sprouting, but given the complex nature of vascular morphogenesis, additional signals are likely necessary to determine, for example, which vessel segments sprout, which dilate, and which remain quiescent. Fluid forces exerted by blood and plasma are prime candidates that might codirect these processes, but it is not known whether VEGF cooperates with mechanical fluid forces to mediate angiogenesis. Using a microfluidic tissue analog of angiogenic sprouting, we found that fluid shear stress, such as exerted by flowing blood, attenuates EC sprouting in a nitric oxide-dependent manner and that interstitial flow, such as produced by extravasating plasma, directs endothelial morphogenesis and sprout formation. Furthermore, positive VEGF gradients initiated sprouting but negative gradients inhibited sprouting, promoting instead sheet-like migration analogous to vessel dilation. These results suggest that ECs integrate signals from fluid forces and local VEGF gradients to achieve such varied goals as vessel dilation and sprouting.
C1 [Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Charlestown, MA 02129 USA.
EM munn@steele.mgh.harvard.edu
RI Munn, Lance/L-3950-2016; Song, Jonathan/C-1922-2013
OI Munn, Lance/0000-0003-0698-7232; Song, Jonathan/0000-0002-6991-5298
FU National Cancer Institute
FX We are grateful to P. Au, G. Cheng, and J. Tse for performing the
retroviral transfections of the HUVECs provided to us by the Center for
Vascular Excellence at Brigham and Women's Hospital. We thank R. Samuel
for her assistance with counting filopodia, A. Jain for helpful
discussions, and R. Jain for his invaluable insight and suggestions.
Funding was provided by the National Cancer Institute (L.L.M).
NR 50
TC 142
Z9 144
U1 5
U2 76
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 SEP 13
PY 2011
VL 108
IS 37
BP 15342
EP 15347
DI 10.1073/pnas.1105316108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819DF
UT WOS:000294804900070
PM 21876168
ER
PT J
AU Ilic, N
Utermark, T
Widlund, HR
Roberts, TM
AF Ilic, Nina
Utermark, Tamara
Widlund, Hans R.
Roberts, Thomas M.
TI PI3K-targeted therapy can be evaded by gene amplification along the
MYC-eukaryotic translation initiation factor 4E (eIF4E) axis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOID-LEUKEMIA; CAP-BINDING
PROTEIN; CELL LUNG-CANCER; C-MYC; BCR-ABL; PHOSPHATIDYLINOSITOL
3-KINASES; TRASTUZUMAB RESISTANCE; INCREASED EXPRESSION; MET
AMPLIFICATION
AB The PI3K pathway is frequently activated in cancer; therefore, considerable effort is focused on identifying compounds that can inhibit specific pathway components, particularly the hallmark oncogene PIK3CA. Although targeted inhibition of a cancer survival gene holds significant promise, there are concerns that drug resistance may emerge within the cancerous cells, thus limiting clinical efficacy. Using genetically defined human mammary epithelial cells, we evolved resistance to the PI3K/mammalian target of rapamycin (mTOR) inhibitor BEZ235, and by genome-wide copy number analyses, we identified MYC and eIF4E amplification within the resistant cells. Importantly, either MYC or eukaryotic translation initiation factor 4E (eIF4E) was required to bypass pharmacological PI3K/mTOR inhibition in resistant cells. Furthermore, these cells displayed elevated 5' cap-dependent protein translation. Collectively, these findings suggest that analysis of drivers of protein translation could facilitate the identification of cancer lesions that confer resistance to PI3K pathway-targeted drugs.
C1 [Ilic, Nina; Utermark, Tamara; Roberts, Thomas M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA.
[Widlund, Hans R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA.
EM thomas_roberts@dfci.harvard.edu
FU Department of Defense Breast [W81XWH-08-1-0747]; National Institutes of
Health [CA089393, CA030002, CA89021]; Stand Up to Cancer
FX The authors thank Dr. Edward Fox and the Dana-Farber Cancer Institute
Microarray Core for excellent assistance with microarray studies and
SOLiD sequencing, Dr. Julien Senechal for FACS operation, and Dr.
Malcolm Whitman for helpful advice regarding lipid kinase assays. We are
grateful to Drs. Daniel Silver and Linda Clayton for critical comments
on the manuscript. We thank the Cytogenetics Core of Dana-Farber Harvard
Cancer Center (P30 CA006516) for performing FISH analysis. This work was
supported by Department of Defense Breast Cancer Research Program
Pre-doctoral Fellowship W81XWH-08-1-0747 (to N.I.); National Institutes
of Health Grants CA089393 (to T. M. R.), CA030002 (to T. M. R.), and
CA89021 (to T. M. R.); and Stand Up to Cancer (to T.M.R.).
NR 52
TC 104
Z9 105
U1 2
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 13
PY 2011
VL 108
IS 37
BP E699
EP U607
DI 10.1073/pnas.1108237108
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819DF
UT WOS:000294804900008
PM 21876152
ER
PT J
AU Sedaghat, AR
Wilke, CO
AF Sedaghat, Ahmad R.
Wilke, Claus O.
TI Kinetics of the viral cycle influence pharmacodynamics of antiretroviral
therapy
SO BIOLOGY DIRECT
LA English
DT Article
DE HIV; viral dynamics; HAART; antiretroviral therapy; viral life cycle;
pharmacodynamics; IC50
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; REVERSE-TRANSCRIPTASE; PROTEASE
INHIBITORS; DRUG SUSCEPTIBILITY; CLEARANCE RATE; HIV; TYPE-1; DYNAMICS;
REPLICATION
AB Background: More and more antiretroviral therapies are being developed for treatment of HIV infection. The in-vivo efficacy of these drugs is commonly predicted based on in-vitro measures of antiviral effect. One primary invitro measure is the IC50, the amount of drug required for 50% inhibition of viral replication. We have previously shown that HIV life-cycle kinetics impact clinically observed HIV viral dynamics. Here we present a mathematical model of how they affect the pharmacodynamics of antiretroviral drugs.
Results: We find that experimentally measured antiretroviral IC50s are determined by three factors: (i) intrinsic drug properties (e. g. drug-target binding), (ii) kinetics of the HIV life cycle, and (iii) kinetics of drug-inhibited infected cells. Our model predicts that the IC50 is a declining function of the duration of the drug-susceptible stage in the host cell. We combine our model with known viral life-cycle kinetics to derive a measure of intrinsic properties, reflecting drug action, for known antiretroviral drugs from previously measured IC50s. We show that this measure of intrinsic drug property correlates very well with in vitro-measured antiviral activity, whereas experimentally measured IC50 does not.
Conclusions: Our results have implications for understanding pharmacodynamics of and improving activity of antiretroviral drugs. Our findings predict that drug activity can be improved through co-administration of synergistic drugs that delay the viral life cycle but are not inhibitory by themselves. Moreover, our results may easily extend to treatment of other pathogens.
C1 [Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
[Wilke, Claus O.] Univ Texas Austin, Sect Integrat Biol, Ctr Computat Biol & Bioinformat, Austin, TX 78712 USA.
[Wilke, Claus O.] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA.
RP Sedaghat, AR (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
EM ahmad_sedaghat@meei.harvard.edu
RI Wilke, Claus/B-4643-2008
OI Wilke, Claus/0000-0002-7470-9261
FU NIH [R01 GM088344]
FX The authors would like to thank Robert F. Siliciano for critical reading
of and feedback regarding this manuscript. This work was supported in
part by NIH grant R01 GM088344 to C.O.W.
NR 33
TC 3
Z9 3
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD SEP 12
PY 2011
VL 6
AR 42
DI 10.1186/1745-6150-6-42
PG 10
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 832XX
UT WOS:000295845200001
PM 21910865
ER
PT J
AU Grady, D
Berkowitz, SA
Katz, MH
AF Grady, Deborah
Berkowitz, Seth A.
Katz, Mitchell H.
TI Opioids for Chronic Pain
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID CHRONIC NONCANCER PAIN; THERAPY; PRESCRIPTIONS; MANAGEMENT; OVERDOSE
C1 [Grady, Deborah; Berkowitz, Seth A.] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco VA Med Ctr, San Francisco, CA 94115 USA.
[Grady, Deborah; Berkowitz, Seth A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA.
[Katz, Mitchell H.] Dept Hlth Serv, Los Angeles, CA USA.
RP Grady, D (reprint author), Univ Calif San Francisco, Gen Internal Med Sect, San Francisco VA Med Ctr, 1635 Divisadero St,Ste 600, San Francisco, CA 94115 USA.
OI Berkowitz, Seth/0000-0003-1030-4297
NR 14
TC 20
Z9 20
U1 0
U2 2
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 SEP 12
PY 2011
VL 171
IS 16
BP 1426
EP 1427
DI 10.1001/archinternmed.2011.213
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819KY
UT WOS:000294825100001
PM 21670333
ER
PT J
AU Steinman, MA
AF Steinman, Michael A.
TI Using Patients to Promote Evidence-Based Prescribing
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Steinman, MA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,POB 181G, San Francisco, CA 94121 USA.
EM mike.steinman@ucsf.edu
FU NIA NIH HHS [K23 AG030999]
NR 7
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD SEP 12
PY 2011
VL 171
IS 16
BP 1468
EP 1469
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819KY
UT WOS:000294825100009
PM 21911630
ER
PT J
AU Fihn, SD
Bucher, JB
McDonell, M
Diehr, P
Rumsfeld, JS
Doak, M
Dougherty, C
Gerrity, M
Heidenreich, P
Larsen, G
Lee, PI
Lucas, L
McBryde, C
Nelson, K
Plomondon, ME
Stadius, M
Bryson, C
AF Fihn, Stephan D.
Bucher, Joy B.
McDonell, Mary
Diehr, Paula
Rumsfeld, John S.
Doak, Melanie
Dougherty, Cynthia
Gerrity, Martha
Heidenreich, Paul
Larsen, Greg
Lee, Peter I.
Lucas, Linda
McBryde, Connor
Nelson, Karin
Plomondon, Mary E.
Stadius, Michael
Bryson, Christopher
TI Collaborative Care Intervention for Stable Ischemic Heart Disease
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; AMERICAN-COLLEGE; STATIN THERAPY; MANAGEMENT;
HEALTH; ANGINA; POPULATION; DEPRESSION; GUIDELINES; MORTALITY
AB Background: Accumulating evidence suggests that collaborative models of care enhance communication among primary care providers, improving quality of care and outcomes for patients with chronic conditions. We sought to determine whether a multifaceted intervention that used a collaborative care model and was directed through primary care providers would improve symptoms of angina, self-perceived health, and concordance with practice guidelines for managing chronic stable angina.
Methods: We conducted a prospective trial, cluster randomized by provider, involving patients with symptomatic ischemic heart disease recruited from primary care clinics at 4 academically affiliated Department of Veterans Affairs health care systems. Primary end points were changes over 12 months in symptoms on the Seattle Angina Questionnaire, self-perceived health, and concordance with practice guidelines.
Results: In total, 183 primary care providers and 703 patients participated in the study. Providers accepted and implemented 91.6% of 701 recommendations made by collaborative care teams. Almost half were related to medications, including adjustments to beta-blockers, long-acting nitrates, and statins. The intervention did not significantly improve symptoms of angina or selfperceived health, although end points favored collaborative care for 10 of 13 prespecified measures. While concordance with practice guidelines improved 4.5% more among patients receiving collaborative care than among those receiving usual care (P<.01), this was mainly because of increased use of diagnostic testing rather than increased use of recommended medications.
Conclusion: A collaborative care intervention was well accepted by primary care providers and modestly improved receipt of guideline-concordant care but not symptoms or self-perceived health in patients with stable angina.
C1 [Fihn, Stephan D.; Bucher, Joy B.; McDonell, Mary; Diehr, Paula; Dougherty, Cynthia; Nelson, Karin; Stadius, Michael; Bryson, Christopher] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98101 USA.
[Fihn, Stephan D.; Nelson, Karin; Bryson, Christopher] Univ Washington, Dept Med, Seattle, WA USA.
[Diehr, Paula] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Dougherty, Cynthia] Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA.
[Bucher, Joy B.] Virginia Mason Med Ctr, Dept Primary Care, Seattle, WA 98101 USA.
[Rumsfeld, John S.; McBryde, Connor; Plomondon, Mary E.] Univ Colorado, VA Eastern Colorado Hlth Care Syst, Denver, CO 80202 USA.
[Doak, Melanie; Gerrity, Martha; Larsen, Greg; Lucas, Linda] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA.
[Doak, Melanie; Gerrity, Martha; Larsen, Greg; Lucas, Linda] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Heidenreich, Paul; Lee, Peter I.] Stanford Univ, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
[Heidenreich, Paul; Lee, Peter I.] Stanford Univ, Dept Med, Palo Alto, CA 94304 USA.
RP Fihn, SD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1100 Olive Way,Ste 1400, Seattle, WA 98101 USA.
EM stephan.fihn@va.gov
FU Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development Service [IHI 02-062, RCD 03-177]
FX This work was supported by grant IHI 02-062 from the Department of
Veterans Affairs, Veterans Health Administration, Health Services
Research and Development Service (Drs Fihn, Rumsfeld, Heidenreich, and
Gerrity). Dr Bryson was supported by Career Development Award RCD 03-177
from the same funding source.
NR 27
TC 17
Z9 17
U1 1
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 SEP 12
PY 2011
VL 171
IS 16
BP 1471
EP 1479
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819KY
UT WOS:000294825100011
PM 21911632
ER
PT J
AU Cho, E
Curhan, G
Hankinson, SE
Kantoff, P
Atkins, MB
Stampfer, M
Choueiri, TK
AF Cho, Eunyoung
Curhan, Gary
Hankinson, Susan E.
Kantoff, Philip
Atkins, Michael B.
Stampfer, Meir
Choueiri, Toni K.
TI Prospective Evaluation of Analgesic Use and Risk of Renal Cell Cancer
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PRIMARY PREVENTION; UNITED-STATES;
CARDIOVASCULAR EVENTS; ASPIRIN; WOMEN; METAANALYSIS; DISEASE;
ACETAMINOPHEN; PARACETAMOL
AB Background: Epidemiologic data suggest that analgesic use increases the risk of renal cell cancer (RCC), but few prospective studies have been published. We investigated the association between analgesic use and RCC in 2 large prospective studies.
Methods: We examined the relationship between analgesic use and RCC risk in the Nurses' Health Study and the Health Professionals Follow-up Study. Use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen was ascertained in 1990 in the Nurses' Health Study and in 1986 in the Health Professionals Follow-up Study, and every 2 years thereafter. We evaluated baseline and duration of use of analgesics.
Results: During follow-up of 16 years among 77 525 women and 20 years among 49 403 men, we documented 333 RCC cases. Aspirin and acetaminophen use were not associated with RCC risk. However, regular use of nonaspirin NSAIDs was associated with an increased RCC risk; the pooled multivariate relative risk was 1.51 (95% confidence interval, 1.12-2.04) at baseline. The absolute risk differences for users vs nonusers of nonaspirin NSAIDs were 9.15 per 100 000 person-years in women and 10.92 per 100 000 person-years in men. There was a dose-response relationship between duration of nonaspirin NSAID use and RCC risk; compared with non-regular use, the pooled multivariate relative risks were 0.81 (95% confidence interval, 0.59-1.11) for use less than 4 years, 1.36 (0.98-1.89) for 4 to less than 10 years, and 2.92 (1.71-5.01) for use for 10 or more years (P<.001 for trend).
Conclusion: Our prospective data suggest that longer duration of use of nonaspirin NSAIDs may increase the risk of RCC.
C1 [Cho, Eunyoung; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Cho, Eunyoung; Curhan, Gary; Hankinson, Susan E.; Stampfer, Meir] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Kantoff, Philip; Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Curhan, Gary; Hankinson, Susan E.; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Dept Epidemiol, Boston, MA 02115 USA.
[Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Cho, E (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM eunyoung.cho@channing.harvard.edu
FU National Institutes of Health [CA137764, CA87969, CA55075]; Kidney
Cancer Association; Dana-Farber/Harvard Cancer Center [NIH P50CA101942]
FX This study was supported by research grants CA137764, CA87969, and
CA55075 from the National Institutes of Health; the Kidney Cancer
Association; and grant NIH P50CA101942 from the Dana-Farber/Harvard
Cancer Center Kidney Cancer Specialized Programs of Research Excellence.
NR 40
TC 20
Z9 20
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD SEP 12
PY 2011
VL 171
IS 16
BP 1487
EP 1493
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819KY
UT WOS:000294825100013
PM 21911634
ER
PT J
AU Munshi, MN
AF Munshi, Medha N.
TI Hypoglycemia Associated With Impaired Renal Function Reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Munshi, MN (reprint author), Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, 110 Francis St,Lowry Med Off Bldg,Ste 1B, Boston, MA 02215 USA.
EM mmunshi@bidmc.harvard.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD SEP 12
PY 2011
VL 171
IS 16
BP 1512
EP 1512
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 819KY
UT WOS:000294825100032
ER
PT J
AU Zerbini, LF
Tamura, RE
Correa, RG
Czibere, A
Cordeiro, J
Bhasin, M
Simabuco, FM
Wang, YH
Gu, XS
Li, LL
Sarkar, D
Zhou, JR
Fisher, PB
Libermann, TA
AF Zerbini, Luiz F.
Tamura, Rodrigo E.
Correa, Ricardo G.
Czibere, Akos
Cordeiro, Jason
Bhasin, Manoj
Simabuco, Fernando M.
Wang, Yihong
Gu, Xuesong
Li, Linglin
Sarkar, Devanand
Zhou, Jin-Rong
Fisher, Paul B.
Libermann, Towia A.
TI Combinatorial Effect of Non-Steroidal Anti-inflammatory Drugs and
NF-kappa B Inhibitors in Ovarian Cancer Therapy
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; EXPRESSING MDA-7/IL-24-MEDIATED APOPTOSIS;
SELECTIVELY INDUCES APOPTOSIS; VASCULAR-PERMEABILITY FACTOR; CARCINOMA
CELL-LINES; MELANOMA DIFFERENTIATION; BREAST-CANCER; CLINICAL
PHARMACOKINETICS; TUMOR-GROWTH; HUMAN-PLASMA
AB Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD) 45 alpha and gamma and JNK activation. The NF-kappa B family of transcription factors has been implicated in ovarian cancer development. We previously established NF-kappa B/I kappa B signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-kB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NFkB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-kB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.
C1 [Zerbini, Luiz F.; Tamura, Rodrigo E.] Univ Cape Town, Med Biochem Div, Fac Hlth Sci, ICGEB, ZA-7925 Cape Town, South Africa.
[Correa, Ricardo G.] Sanford Burnham Inst Med Res, La Jolla, CA USA.
[Czibere, Akos] Univ Dusseldorf, Dept Haematol Oncol & Clin Immunol, Dusseldorf, Germany.
[Zerbini, Luiz F.; Cordeiro, Jason; Bhasin, Manoj; Simabuco, Fernando M.; Wang, Yihong; Gu, Xuesong; Libermann, Towia A.] Beth Israel Deaconess Med Ctr, BIDMC Genom & Prote Ctr, Boston, MA 02215 USA.
[Zerbini, Luiz F.; Cordeiro, Jason; Bhasin, Manoj; Simabuco, Fernando M.; Wang, Yihong; Gu, Xuesong; Li, Linglin; Zhou, Jin-Rong; Libermann, Towia A.] Harvard Univ, Sch Med, Boston, MA USA.
[Li, Linglin; Zhou, Jin-Rong] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
[Sarkar, Devanand; Fisher, Paul B.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Sch Med, VCU Inst Mol Med,VCU Massey Canc Ctr, Richmond, VA USA.
RP Zerbini, LF (reprint author), Univ Cape Town, Med Biochem Div, Fac Hlth Sci, ICGEB, ZA-7925 Cape Town, South Africa.
EM luiz.zerbini@uct.ac.za
RI tamura, rodrigo/C-3085-2012; Correa, Ricardo/G-7613-2012; tamura,
rodrigo/O-9846-2014; Zerbini, Luiz /B-7720-2015;
OI Correa, Ricardo/0000-0001-6940-7034; tamura,
rodrigo/0000-0001-7767-0887; Libermann, Towia/0000-0002-4006-8179
FU ICGEB; National Institutes of Health [1R01 CA85467, P50 CA090381, P50
CA105009, 1R01 CA097318, 1R01 CA127641, P01 CA104177]; Hershey
Foundation; Samuel Waxman Cancer Research Foundation; Department of
Defense [PC051217, OC0060439]
FX RET is a recipient of the ICGEB post-doctoral fellowship. This research
was supported by National Institutes of Health grants 1R01 CA85467, P50
CA090381, P50 CA105009 and the Hershey Foundation (TAL), NIH grants 1R01
CA097318, 1R01 CA127641, P01 CA104177, the Samuel Waxman Cancer Research
Foundation (PBF) and Department of Defense grants PC051217 and OC0060439
(LFZ). DS is a Harrison Scholar in Cancer Research and a Blick Scholar
in the VCU Massey Cancer Center and the VCU School of Medicine. PBF
holds the Thelma Newmeyer Corman Chair in Cancer Research in the VCU
Massey Cancer Center and is a SWCRF Investigator. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 67
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Z9 27
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 SEP 12
PY 2011
VL 6
IS 9
AR e24285
DI 10.1371/journal.pone.0024285
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819CO
UT WOS:000294803200010
PM 21931671
ER
PT J
AU Manola, JB
Gray, RJ
AF Manola, Judith B.
Gray, Robert J.
TI When Bad Things Happen to Good Studies
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID CISPLATIN PLUS FLUOROURACIL; STAGE OROPHARYNX CARCINOMA;
COOPERATIVE-ONCOLOGY-GROUP; NECK-CANCER; RANDOMIZED-TRIAL; PHASE-III;
RADIATION-THERAPY; COMPETING RISK; ADVANCED HEAD; CHEMOTHERAPY
C1 [Manola, Judith B.; Gray, Robert J.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Manola, JB (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 22
TC 6
Z9 6
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 SEP 10
PY 2011
VL 29
IS 26
BP 3497
EP 3499
DI 10.1200/JCO.2011.37.1393
PG 3
WC Oncology
SC Oncology
GA 818CG
UT WOS:000294726400003
PM 21844501
ER
PT J
AU Chen, AB
Schrag, D
AF Chen, Aileen B.
Schrag, Deborah
TI Is Computed Tomography Simulation Associated With Improved Survival, or
Is This Finding a Result of Confounding Variables? Reply to M. Koshy
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID CELL LUNG-CANCER; RADIATION-THERAPY; RADIOTHERAPY
C1 [Chen, Aileen B.; Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Chen, Aileen B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Chen, AB (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
NR 7
TC 1
Z9 1
U1 1
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 SEP 10
PY 2011
VL 29
IS 26
BP 3587
EP 3588
DI 10.1200/JCO.2011.37.2334
PG 3
WC Oncology
SC Oncology
GA 818CG
UT WOS:000294726400019
ER
PT J
AU Bloch, DB
Nobre, RA
Bernstein, GA
Yang, WH
AF Bloch, Donald B.
Nobre, Rita A.
Bernstein, Gillian A.
Yang, Wei-Hong
TI Identification and characterization of protein interactions in the
mammalian mRNA processing body using a novel two-hybrid assay
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE mRNA degradation; mRNA processing body; Two-hybrid assay
ID P-BODIES; SACCHAROMYCES-CEREVISIAE; DECAPPING COMPLEX; STRESS GRANULES;
DCP1; LOCALIZATION; BINDING; EDC3; METAZOA; REGION
AB Components of the mRNA processing body (P-body) regulate critical steps in mRNA storage, transport, translation and degradation. At the core of the P-body is the decapping complex, which removes the 5' cap from de-adenylated mRNAs and mediates an irreversible step in mRNA degradation. The assembly of P-bodies in Saccharomyces cerevisiae, Arabidopsis thaliana and Drosophila melanogaster has been previously described. Less is known about the assembly of mammalian P-bodies. To investigate the interactions that occur between components of mammalian P-bodies, we developed a fluorescence-based, two-hybrid assay system. The assay depends on the ability of one P-body component, fused to an exogenous nuclear localization sequence (NLS), to recruit other P-body components to the nucleus. The assay was used to investigate interactions between P-body components Ge-1, DCP2, DCP1, EDC3, RAP55, and RCK. The results of this study show that the modified two-hybrid assay can be used to identify protein interactions that occur in a macromolecular complex. The assay can also be used to efficiently detect protein interaction domains. The results provide important insights into mammalian P-body assembly and demonstrate similarities, and critical differences, between P-body assembly in mammalian cells compared with that of other species. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Bloch, Donald B.] Harvard Univ, Sch Med,Dept Med, Massachusetts Gen Hosp, Rheumatol Unit,Ctr Immunol & Inflammatory Dis Gen, Boston, MA 02114 USA.
RP Bloch, DB (reprint author), Harvard Univ, Sch Med,Dept Med, Massachusetts Gen Hosp, Rheumatol Unit,Ctr Immunol & Inflammatory Dis Gen, Bulfinch 1,55 Fruit St, Boston, MA 02114 USA.
EM bloch@helix.mgh.harvard.edu
FU Massachusetts General Hospital
FX Funding for this study was provided by the Massachusetts General
Hospital, which did not have a role in any aspect of the conduct of the
research.
NR 31
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U1 1
U2 8
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD SEP 10
PY 2011
VL 317
IS 15
BP 2183
EP 2199
DI 10.1016/j.yexcr.2011.05.027
PG 17
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 804VP
UT WOS:000293682400010
PM 21672539
ER
PT J
AU Yin, JM
Dai, AL
LeCureux, J
Arango, T
Kutzler, MA
Yan, J
Lewis, MG
Khan, A
Sardesai, NY
Montefiore, D
Ruprecht, R
Weiner, DB
Boyer, JD
AF Yin, Jiangmei
Dai, Anlan
LeCureux, Jonathan
Arango, Tatiana
Kutzler, Michele A.
Yan, Jian
Lewis, Mark G.
Khan, Amir
Sardesai, Niranjan Y.
Montefiore, David
Ruprecht, Ruth
Weiner, David B.
Boyer, Jean D.
TI High antibody and cellular responses induced to HIV-1 clade C envelope
following DNA vaccines delivered by electroporation
SO VACCINE
LA English
DT Article
DE SHIV; DNA vaccine; RANTES; Clade C
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VIVO ELECTROPORATION; IMMUNE-RESPONSES;
RHESUS MACAQUES; RANTES; VACCINATION; EXPRESSION; PLASMID; ENV;
IMMUNOGENICITY
AB Background: Clade C is the predominant HIV-1 strain infecting people in sub-Saharan Africa, India, and China and there is a critical need for a vaccine targeted to these areas. In this study we tested a DNA based vaccine that encodes the SIVgag, SIVpol and HIV-1 envelope clade C.
Methods: Rhesus macaques were immunized by electroporation with the DNA plasmid encoding optimized SIVgag, SIVpol and an HIV-1 env clade C with or without the adjuvant RANTES. Animals were monitored for immune responses and challenged following the final immunization with 25 animal infectious doses (AID) of SHIV-1157ipd3N4.
Results: We found that the vaccine induced high levels of antigen specific IFN-gamma producing effector cells and the capacity for CD4+ and CD8+ to proliferate upon antigen stimulation. Importantly, we found that the vaccine induced antibody titers as high as 1/4000. These antibodies were capable of neutralizing tier 1 HIV-1 viruses. Finally, when macaques were challenged with SHIV, viral loads were controlled in vaccinated groups.
Conclusion: We conclude that immunization with a simian/human immunodeficiency virus DNA-based vaccine delivered by electroporation can induce cellular and humoral immune responses that are able to control viral replication. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Yin, Jiangmei; Dai, Anlan; LeCureux, Jonathan; Arango, Tatiana; Yan, Jian; Weiner, David B.; Boyer, Jean D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Kutzler, Michele A.] Drexel Univ, Coll Med, Philadelphia, PA 19102 USA.
[Lewis, Mark G.] Bioqual, Res Sect, Rockville, MD 20850 USA.
[Khan, Amir; Sardesai, Niranjan Y.] Inovio Pharmaceut, Blue Bell, PA 19422 USA.
[Montefiore, David] Duke Univ, Durham, NC 27710 USA.
[Ruprecht, Ruth] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ruprecht, Ruth] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Boyer, JD (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, 422 Curie Blvd,505 SCL, Philadelphia, PA 19104 USA.
EM boyerj@maiLmed.upenn.edu
RI Yin, Jiangmei/G-1952-2011; Weiner, David/H-8579-2014;
OI LeCureux, Jonathan/0000-0003-4444-8790
FU National Institutes of Health (NIH) [N01-AI-50010, P01-A1-071739,
R01-A1-071186]; NIH/NIAID/DAIDS [HHSN272200800063C]
FX This research was supported in part by National Institutes of Health
(NIH) Grants N01-AI-50010, P01-A1-071739, R01-A1-071186, A.K., N.Y.S.
acknowledge funding in part from an NIH/NIAID/DAIDS - HVDDT award to
Inovio HHSN272200800063C" - and the National Institutes of Health
Intramural Research Program. J.Y. performed research, generated the data
presented and wrote the paper. A.D., J.L., T.A., and M.G.L., all
performed research and generated the data presented. M.A.K., J.Y., A.K.,
N.Y.S, and D.B.W. provided reagents and guidance. J.D.B. designed
experiments and oversaw the project.
NR 24
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD SEP 9
PY 2011
VL 29
IS 39
SI SI
BP 6763
EP 6770
DI 10.1016/j.vaccine.2010.12.055
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 828JL
UT WOS:000295497200007
PM 21195801
ER
PT J
AU Funkhouser, E
Levine, DA
Gerald, JK
Houston, TK
Johnson, NK
Allison, JJ
Kiefe, CI
AF Funkhouser, Ellen
Levine, Deborah A.
Gerald, Joe K.
Houston, Thomas K.
Johnson, Nancy K.
Allison, Jeroan J.
Kiefe, Catarina I.
TI Recruitment activities for a nationwide, population-based,
group-randomized trial: the VA MI-Plus study
SO IMPLEMENTATION SCIENCE
LA English
DT Article
ID HEALTH-SERVICES RESEARCH; CARE; PARTICIPATION; INTERVENTIONS; DESIGN;
IMPACT
AB Background: The Veterans Health Administration (VHA) oversees the largest integrated healthcare system in the United States. The feasibility of a large-scale, nationwide, group-randomized implementation trial of VHA outpatient practices has not been reported. We describe the recruitment and enrollment of such a trial testing a clinician-directed, Internet-delivered intervention for improving the care of postmyocardial infarction patients with multiple comorbidities.
Methods: With a recruitment goal of 200 eligible community-based outpatient clinics, parent VHA facilities (medical centers) were recruited because they oversee their affiliated clinics and the research conducted there. Eligible facilities had at least four VHA-owned and -operated primary care clinics, an affiliated Institutional Review Board (IRB), and no ongoing, potentially overlapping, quality-improvement study. Between December 2003 and December 2005, in two consecutive phases, we used initial and then intensified recruitment strategies.
Results: Overall, 48 of 66 (73%) eligible facilities were recruited. Of the 219 clinics and 957 clinicians associated with the 48 facilities, 168 (78%) clinics and 401 (42%) clinicians participated. The median time from initial facility contact to clinic enrollment was 222 days, which decreased by over one-third from the first to the second recruitment phase (medians: 323 and 195 days, respectively; p < .001), when more structured recruitment with physician recruiters was implemented and a dedicated IRB manager was added to the coordinating center staff.
Conclusions: Large group-randomized trials benefit from having dedicated physician investigators and IRB personnel involved in recruitment. A large-scale, nationally representative, group-randomized trial of community-based clinics is feasible within the VHA or a similar national healthcare system.
C1 [Funkhouser, Ellen; Johnson, Nancy K.] Birmingham VA Med Ctr, VA Res Enhancement Award Program REAP, Birmingham, AL USA.
[Funkhouser, Ellen; Levine, Deborah A.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA.
[Levine, Deborah A.] Univ Michigan, Ann Arbor VA Healthcare Syst, Ann Arbor, MI 48109 USA.
[Levine, Deborah A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Levine, Deborah A.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA.
[Levine, Deborah A.] Vet Affairs Hlth Serv Res & Dev Ctr Excelle, Ann Arbor, MI USA.
[Gerald, Joe K.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA.
[Houston, Thomas K.; Allison, Jeroan J.; Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
RP Funkhouser, E (reprint author), Birmingham VA Med Ctr, VA Res Enhancement Award Program REAP, Birmingham, AL USA.
EM emfunk@uab.edu
RI Houston, Thomas/F-2469-2013;
OI Allison, Jeroan/0000-0003-4472-2112
FU VA Health Services Research and Development (HSRD) [SDR 03-090-1];
National Heart, Lung, and Blood Institute [R01 HL70786]
FX This project was funded in part by grant SDR 03-090-1 from the VA Health
Services Research and Development (HSR&D) and by grant number R01
HL70786 from the National Heart, Lung, and Blood Institute.
NR 30
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U1 0
U2 1
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 SEP 9
PY 2011
VL 6
AR 105
DI 10.1186/1748-5908-6-105
PG 11
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 828AO
UT WOS:000295472800001
PM 21906278
ER
PT J
AU Hambardzumyan, D
Cheng, YK
Haeno, H
Holland, EC
Michor, F
AF Hambardzumyan, Dolores
Cheng, Yu-Kang
Haeno, Hiroshi
Holland, Eric C.
Michor, Franziska
TI The Probable Cell of Origin of NF1-and PDGF-Driven Glioblastomas
SO PLOS ONE
LA English
DT Article
ID NEURAL STEM-CELLS; SELF-RENEWAL; NEUROEPITHELIAL CELLS; GLIAL
PROGENITORS; MOUSE MODELS; ADULT BRAIN; GLIOMA; PATHWAYS; CANCER; NF1
AB Primary glioblastomas are subdivided into several molecular subtypes. There is an ongoing debate over the cell of origin for these tumor types where some suggest a progenitor while others argue for a stem cell origin. Even within the same molecular subgroup, and using lineage tracing in mouse models, different groups have reached different conclusions. We addressed this problem from a combined mathematical modeling and experimental standpoint. We designed a novel mathematical framework to identify the most likely cells of origin of two glioma subtypes. Our mathematical model of the unperturbed in vivo system predicts that if a genetic event contributing to tumor initiation imparts symmetric self-renewing cell division (such as PDGF overexpression), then the cell of origin is a transit amplifier. Otherwise, the initiating mutations arise in stem cells. The mathematical framework was validated with the RCAS/tv-a system of somatic gene transfer in mice. We demonstrated that PDGF-induced gliomas can be derived from GFAP-expressing cells of the subventricular zone or the cortex (reactive astrocytes), thus validating the predictions of our mathematical model. This interdisciplinary approach allowed us to determine the likelihood that individual cell types serve as the cells of origin of gliomas in an unperturbed system.
C1 [Hambardzumyan, Dolores] Cleveland Clin, Dept Regenerat Med, Cleveland, OH 44106 USA.
[Cheng, Yu-Kang; Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Cheng, Yu-Kang; Haeno, Hiroshi; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Cheng, Yu-Kang] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA.
[Cheng, Yu-Kang] Weill Cornell Med Coll, Triinst Training Program Computat Biol & Med, New York, NY USA.
[Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, Brain Tumor Ctr, New York, NY 10021 USA.
[Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA.
[Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[Holland, Eric C.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
RP Hambardzumyan, D (reprint author), Cleveland Clin, Dept Regenerat Med, Cleveland, OH 44106 USA.
EM michor@jimmy.harvard.edu
FU National Institutes of Health [U54CA143798]
FX This work was supported by National Institutes of Health U54CA143798.
The funder had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 47
TC 12
Z9 12
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 9
PY 2011
VL 6
IS 9
AR e24454
DI 10.1371/journal.pone.0024454
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819CN
UT WOS:000294803100035
PM 21931722
ER
PT J
AU Stefan, M
Jacobson, EM
Huber, AK
Greenberg, DA
Li, CW
Skrabanek, L
Conception, E
Fadlalla, M
Ho, K
Tomer, Y
AF Stefan, Mihaela
Jacobson, Eric M.
Huber, Amanda K.
Greenberg, David A.
Li, Cheuk Wun
Skrabanek, Luce
Conception, Erlinda
Fadlalla, Mohammed
Ho, Kenneth
Tomer, Yaron
TI Novel Variant of Thyroglobulin Promoter Triggers Thyroid Autoimmunity
through an Epigenetic Interferon alpha-modulated Mechanism
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN GENOME; HASHIMOTOS-THYROIDITIS; SUSCEPTIBILITY GENE; LINKAGE
ANALYSIS; DISEASE; TRANSCRIPTION; ASSOCIATION; GRAVES; IDENTIFICATION;
METHYLATIONS
AB Autoimmune thyroid diseases (AITD) arise from complex interactions between genetic, epigenetic, and environmental factors. Whole genome linkage scans and association studies have established thyroglobulin (TG) as a major AITD susceptibility gene. However, the causative TG variants and the pathogenic mechanisms are unknown. Here, we describe a genetic/epigenetic mechanism by which a newly identified TG promoter single-nucleotide polymorphism (SNP) variant predisposes to AITD. Sequencing analyses followed by case control and family-based association studies identified an SNP (-1623A -> G) that was associated with AITD in the Caucasian population (p = 0.006). We show that the nucleotide substitution introduced by SNP (-1623A/G) modified a binding site for interferon regulatory factor-1 (IRF-1), a major interferon-induced transcription factor. Using chromatin immunoprecipitation, we demonstrated that IRF-1 binds to the 5' TG promoter motif, and the transcription factor binding correlates with active chromatin structure and is marked by enrichment of mono-methylated Lys-4 residue of histone H3, a signature of active transcriptional enhancers. Using reporter mutations and siRNA approaches, we demonstrate that the disease-associated allele (G) conferred increased TG promoter activity through IRF-1 binding. Finally, treatment of thyroid cells with interferon alpha, a known trigger of AITD, increased TG promoter activity only when it interacted with the disease-associated variant through IRF-1 binding. These results reveal a new mechanism of interaction between environmental (IFN alpha) and genetic (TG) factors to trigger AITD.
C1 [Stefan, Mihaela; Huber, Amanda K.; Conception, Erlinda; Ho, Kenneth; Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA.
[Jacobson, Eric M.; Li, Cheuk Wun; Fadlalla, Mohammed] Univ Cincinnati, Div Endocrinol, Cincinnati, OH 45267 USA.
[Greenberg, David A.] Columbia Univ, Div Stat Genet, New York, NY 10032 USA.
[Skrabanek, Luce] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA.
[Skrabanek, Luce] Cornell Univ, Weill Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA.
[Stefan, Mihaela; Tomer, Yaron] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
RP Stefan, M (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA.
EM mihaela.stefan@mssm.edu; yaron.tomer@mssm.edu
FU National Institutes of Health [DK61659, DK067555, DK073681, MH48858,
NS27941]; Veterans Affairs merit award; American Thyroid Association
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK61659, DK067555, and DK073681 (to Y. T.) and Grants
MH48858 and NS27941 (to D. A. G.). This work was also supported by a
Veterans Affairs merit award (to Y. T.).; Supported by a grant from the
American Thyroid Association.
NR 50
TC 22
Z9 23
U1 0
U2 5
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 SEP 9
PY 2011
VL 286
IS 36
BP 31168
EP 31179
DI 10.1074/jbc.M111.247510
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 814WI
UT WOS:000294487500012
PM 21757724
ER
PT J
AU Li, Y
Si, R
Feng, Y
Chen, HH
Zou, L
Wang, E
Zhang, M
Warren, HS
Sosnovik, DE
Chao, W
AF Li, Yan
Si, Rui
Feng, Yan
Chen, Howard H.
Zou, Lin
Wang, E.
Zhang, Ming
Warren, H. Shaw
Sosnovik, David E.
Chao, Wei
TI Myocardial Ischemia Activates an Injurious Innate Immune Signaling via
Cardiac Heat Shock Protein 60 and Toll-like Receptor 4
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEAT-SHOCK-PROTEIN; NF-KAPPA-B; REPERFUSION INJURY; CARDIOMYOCYTE
APOPTOSIS; SERUM DEPRIVATION; DEATH-DOMAIN; INFLAMMATION; TLR4;
MACROPHAGES; PATHWAY
AB Innate immune response after transient ischemia is the most common cause of myocardial inflammation and may contribute to injury, yet the detailed signaling mechanisms leading to such a response are not well understood. Herein we tested the hypothesis that myocardial ischemia activates interleukin receptor-associated kinase-1 (IRAK-1), a kinase critical for the innate immune signaling such as that of Toll-like receptors (TLRs), via a mechanism that involves heat shock proteins (HSPs) and TLRs. Coronary artery occlusion induced a rapid myocardial IRAK-1 activation within 30 min in wild-type (WT), TLR2(-/-), or Trif(-/-) mice, but not in TLR4(def) or MyD88(-/-) mice. HSP60 protein was markedly increased in serum or in perfusate of isolated heart following ischemia/reperfusion (I/R). In vitro, recombinant HSP60 induced IRAK-1 activation in cells derived from WT, TLR2(-/-), or Trif(-/-) mice, but not from TLR4(def) or MyD88(-/-) mice. Both myocardial ischemia-and HSP60-induced IRAK-1 activation was abolished by anti-HSP60 antibody. Moreover, HSP60 treatment of cardiomyocytes (CMs) led to marked activation of caspase-8 and -3, but not -9. Expression of dominant-negative mutant of Fas-associated death domain protein or a caspase-8 inhibitor completely blocked HSP60-induced caspase-8 activation, suggesting that HSP60 likely activates an apoptotic program via the death-receptor pathway. In vivo, I/R-induced myocardial apoptosis and cytokine expression were significantly attenuated in TLR4def mice or in WT mice treated with anti-HSP60 antibody compared with WT controls. Taken together, the current study demonstrates that myocardial ischemia activates an innate immune signaling via HSP60 and TLR4, which plays an important role in mediating apoptosis and inflammation during I/R.
C1 [Li, Yan; Si, Rui; Feng, Yan; Zou, Lin; Wang, E.; Zhang, Ming; Chao, Wei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA.
[Chen, Howard H.; Sosnovik, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA.
[Warren, H. Shaw] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA USA.
[Li, Yan] Huazhong Univ Sci & Technol, Union Hosp, Dept Pathol, Tongji Med Coll, Wuhan 430030, Peoples R China.
RP Chao, W (reprint author), Massachusetts Gen Hosp, Room 4-212,149 13th St, Charlestown, MA 02129 USA.
EM wchao@partners.org
RI Feng, Yan/H-5808-2012
FU National Institutes of Health [R01GM080906, R01HL093038]; American Heart
Association [0755890T]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01GM080906 and R01HL093038. This work was also supported
by American Heart Association Grant-in-Aid 0755890T.
NR 65
TC 59
Z9 65
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 9
PY 2011
VL 286
IS 36
BP 31308
EP 31319
DI 10.1074/jbc.M111.246124
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 814WI
UT WOS:000294487500026
PM 21775438
ER
PT J
AU Yang, R
Fredman, G
Krishnamoorthy, S
Agrawal, N
Irimia, D
Piomelli, D
Serhan, CN
AF Yang, Rong
Fredman, Gabrielle
Krishnamoorthy, Sriram
Agrawal, Nitin
Irimia, Daniel
Piomelli, Daniele
Serhan, Charles N.
TI Decoding Functional Metabolomics with Docosahexaenoyl Ethanolamide
(DHEA) Identifies Novel Bioactive Signals
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CANNABINOID RECEPTOR; WHOLE-BLOOD; FATTY-ACIDS; ANANDAMIDE;
ENDOCANNABINOIDS; PLATELETS; INJURY; BINDS; D1; INFLAMMATION
AB Neuroinflammation and traumatic brain injury involve activation of inflammatory cells and production of local pro-inflammatory mediators that can amplify tissue damage. Using LC-UV-MS-MS-based lipidomics in tandem with functional screening at the single-cell level in microfluidic chambers, we identified a series of novel bioactive oxygenated docosahexaenoyl ethanolamide( DHEA) derived products that regulated leukocyte motility. These included 10,17-dihydroxydocosahexaenoyl ethanolamide (10,17-diHDHEA) and 15-hydroxy-16(17)-epoxy-docosapentaenoyl ethanolamide (15-HEDPEA), each of which was an agonist of recombinant CB2 receptors with EC50 3.9 X 10(-10) and 1.0 X 10(-10)M. In human whole blood, 10,17-diHDHEA and 15-HEDPEA at concentrations as low as 10 pM each prevented formation of platelet-leukocyte aggregates involving either platelet-monocyte or platelet-polymorphonuclear leukocyte. In vivo, 15-HEDPEA was organ-protective in mouse reperfusion second organ injury. Together these results indicate that DHEA oxidative metabolism produces potent novel molecules with anti-inflammatory and organ-protective properties.
C1 [Yang, Rong; Fredman, Gabrielle; Krishnamoorthy, Sriram; Serhan, Charles N.] Brigham & Womens Hosp, Harvard Inst Med, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Yang, Rong; Fredman, Gabrielle; Krishnamoorthy, Sriram; Serhan, Charles N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Agrawal, Nitin; Irimia, Daniel] Shriners Hosp Children, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, BioMEMS Resource Ctr, Boston, MA 02129 USA.
[Agrawal, Nitin; Irimia, Daniel] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92617 USA.
[Piomelli, Daniele] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92617 USA.
[Piomelli, Daniele] Italian Inst Technol, I-16163 Genoa, Italy.
RP Serhan, CN (reprint author), Brigham & Womens Hosp, Harvard Inst Med, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, 829,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM cnserhan@zeus.bwh.harvard.edu
OI Irimia, Daniel/0000-0001-7347-2082
FU National Institutes of Health [R01NS067686, RC2AT005909, R01DE019938]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01NS067686 (to C. N. S.), RC2AT005909 (to C. N. S.), and
R01DE019938 (to C. N. S. and D. I.).
NR 42
TC 29
Z9 30
U1 0
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 9
PY 2011
VL 286
IS 36
BP 31532
EP 31541
DI 10.1074/jbc.M111.237990
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 814WI
UT WOS:000294487500048
PM 21757729
ER
PT J
AU Lane, SW
Wang, YZJ
Lo Celso, C
Ragu, C
Bullinger, L
Sykes, SM
Ferraro, F
Shterental, S
Lin, CP
Gilliland, DG
Scadden, DT
Armstrong, SA
Williams, DA
AF Lane, Steven W.
Wang, Yingzi J.
Lo Celso, Cristina
Ragu, Christine
Bullinger, Lars
Sykes, Stephen M.
Ferraro, Francesca
Shterental, Sebastian
Lin, Charles P.
Gilliland, D. Gary
Scadden, David T.
Armstrong, Scott A.
Williams, David A.
TI Differential niche and Wnt requirements during acute myeloid leukemia
progression
SO BLOOD
LA English
DT Article
ID STEM-CELL NICHE; HEMATOPOIETIC STEM; PROGENITOR CELLS; BETA-CATENIN;
IN-VIVO; AML; MICROENVIRONMENT; TRANSFORMATION; CHEMOTHERAPY; RESISTANCE
AB Hematopoietic stem cells (HSCs) engage in complex bidirectional signals with the hematopoietic microenvironment (HM), and there is emerging evidence that leukemia stem cells (LSCs) may use similar interactions. Using a syngeneic retroviral model of MLL-AF9 induced acute myeloid leukemia (AML), we have identified 2 different stages of leukemia progression, propagated by "pre-LSCs" and established leukemia (LSCs) and compared the homing properties of these distinctive entities to that of normal HSCs. The homing and microlocalization of pre-LSCs was most similar to long-term HSCs and was dependent on cell-intrinsic Wnt signaling. In contrast, the homing of established LSCs was most similar to that of committed myeloid progenitors and distinct from HSCs. Although osteoblast-derived Dickkopf-1,a potent Wnt inhibitor known to impair HSC function, dramatically impaired normal HSC localization within the bone marrow, it did not affect pre-LSCs, LSC homing, or AML development. Mechanistically, cell-intrinsic Wnt activation was observed in human and murine AML samples, explaining the independence of MLL-AF9 LSCs from niche-derived Wnt signals. These data identify differential engagement of HM associated with leukemic progression and identify an LSC niche that is physically distinct and independent of the constraints of Wnt signaling that apply to normal HSCs. (Blood. 2011; 118(10): 2849-2856)
C1 [Lane, Steven W.; Wang, Yingzi J.; Bullinger, Lars; Armstrong, Scott A.; Williams, David A.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston, Boston, MA 02115 USA.
[Lane, Steven W.; Wang, Yingzi J.; Bullinger, Lars; Armstrong, Scott A.; Williams, David A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lane, Steven W.; Wang, Yingzi J.; Lo Celso, Cristina; Ragu, Christine; Bullinger, Lars; Sykes, Stephen M.; Ferraro, Francesca; Scadden, David T.; Armstrong, Scott A.; Williams, David A.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Lane, Steven W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Wang, Yingzi J.] Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia.
[Lo Celso, Cristina] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London, England.
[Lo Celso, Cristina; Ragu, Christine; Sykes, Stephen M.; Ferraro, Francesca; Scadden, David T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Stem Cell & Regenerat Biol,Ctr Regenerat Med, Boston, MA 02115 USA.
[Bullinger, Lars] Univ Hosp, Dept Internal Med 3, Ulm, Germany.
[Sykes, Stephen M.; Shterental, Sebastian; Gilliland, D. Gary] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Gilliland, D. Gary] Merck Res Labs, N Wales, PA USA.
RP Williams, DA (reprint author), Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston, 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA.
EM dscadden@mgh.harvard.edu; scott.armstrong@childrens.harvard.edu;
dawilliams@childrens.harvard.edu
RI Lane, Steven/C-3215-2012;
OI Lane, Steven/0000-0002-8050-6209; Lo Celso,
Cristina/0000-0002-1163-4207; Ragu, Christine/0000-0002-1150-1105
FU National Health and Medical Research Council of Australia;
Australia/United States Fulbright Commission; Hematology Society of
Australia and New Zealand; National Institutes of Health [DK62757,
HL44851, CA66996]; Leukemia & Lymphoma Society; American Cancer Society;
Deutsche Forschungsgemeinschaft [Heisenberg-Stipendium BU 1339/3-1]
FX S.W.L. was supported by the National Health and Medical Research Council
of Australia, Australia/United States Fulbright Commission and
Hematology Society of Australia and New Zealand. D. A. W. was supported
by the National Institutes of Health (DK62757). D. T. S. was supported
by the National Institutes of Health (HL44851). S. A. A. was supported
by the National Institutes of Health (CA66996). Work performed in the
laboratory of S. A. A. was also supported by the Leukemia & Lymphoma
Society and the American Cancer Society. L. B. was supported in part by
the Deutsche Forschungsgemeinschaft (Heisenberg-Stipendium BU 1339/3-1).
NR 29
TC 61
Z9 62
U1 0
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 8
PY 2011
VL 118
IS 10
BP 2849
EP 2856
DI 10.1182/blood-2011-03-345165
PG 8
WC Hematology
SC Hematology
GA 819BX
UT WOS:000294801500032
PM 21765021
ER
PT J
AU Li, WH
Ahn, AC
AF Li, Weihui
Ahn, Andrew C.
TI Subcutaneous Fascial Bands-A Qualitative and Morphometric Analysis
SO PLOS ONE
LA English
DT Article
ID CONNECTIVE-TISSUE; NETWORK; BODY
AB Background: Although fascial bands within the subcutaneous (SQ) layer are commonly seen in ultrasound images, little is known about their functional role, much less their structural characteristics. This study's objective is to describe the morphological features of SQ fascial bands and to systematically evaluate the bands using image analyses tools and morphometric measures.
Methods: In 28 healthy volunteers, ultrasound images were obtained at three body locations: the lateral aspect of the upper arm, medial aspect of the thigh and posterior aspect of lower leg. Using image analytical techniques, the total SQ band area, fascial band number, fascial band thickness, and SQ zone (layer) thickness were determined. In addition, the SQ spatial coherence was calculated based on the eigenvalues associated with the largest and smallest eigenvectors of the images.
Results: Fascial bands at these sites were contiguous with the dermis and the epimysium forming an interconnected network within the subcutaneous tissue. Subcutaneous blood vessels were also frequently encased by these fascial bands. The total SQ fascial band area was greater at the thigh and calf compared to the arm and was unrelated to SQ layer (zone) thickness. The thigh was associated with highest average number of fascial bands while calf was associated with the greatest average fascial band thickness. Across body regions, greater SQ zone thickness was associated with thinner fascial bands. SQ coherence was significantly associated with SQ zone thickness and body location (calf with statistically greater coherence compared to arm).
Conclusion: Fascial bands are structural bridges that mechanically link the skin, subcutaneous layer, and deeper muscle layers. This cohesive network also encases subcutaneous vessels and may indirectly mediate blood flow. The quantity and morphological characteristics of the SQ fascial band may reflect the composite mechanical forces experienced by the body part.
C1 [Li, Weihui; Ahn, Andrew C.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Ahn, Andrew C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
RP Li, WH (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM weihuil@gmail.com
FU National Center for Complementary Alternative Medicine (NCCAM)
[K23-AT003238, P30AT005895, K24-AT004095]; Bernard Osher Foundation;
National Center for Research Resources [UL1RR025758]
FX This research was supported by grant number K23-AT003238, P30AT005895,
and K24-AT004095 of the National Center for Complementary Alternative
Medicine (NCCAM) and supported in part by a gift from The Bernard Osher
Foundation. The project described was supported by Clinical
Translational Science Award UL1RR025758 to Harvard University and Beth
Israel Deaconess Medical Center from the National Center for Research
Resources. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National Center
for Complementary Alternative Medicine or the National Center for
Research Resources or the National Institutes of Health. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 13
TC 2
Z9 3
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 8
PY 2011
VL 6
IS 9
AR e23987
DI 10.1371/journal.pone.0023987
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819CK
UT WOS:000294802800017
PM 21931632
ER
PT J
AU Matulonis, UA
Hirsch, M
Palescandolo, E
Kim, E
Liu, J
van Hummelen, P
MacConaill, L
Drapkin, R
Hahn, WC
AF Matulonis, Ursula A.
Hirsch, Michelle
Palescandolo, Emanuele
Kim, Eejung
Liu, Joyce
van Hummelen, Paul
MacConaill, Laura
Drapkin, Ronny
Hahn, William C.
TI High Throughput Interrogation of Somatic Mutations in High Grade Serous
Cancer of the Ovary
SO PLOS ONE
LA English
DT Article
ID PHASE-II; LUNG-CANCER; GEFITINIB; CARCINOMA; ONCOGENE; GENE
AB Background: Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology.
Methodology/Principal Findings: The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had >= 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRF alpha, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%).
Conclusions/Significance: Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population.
C1 [Matulonis, Ursula A.; Palescandolo, Emanuele; Kim, Eejung; Liu, Joyce; van Hummelen, Paul; MacConaill, Laura; Drapkin, Ronny; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hirsch, Michelle; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Womens & Perinatal Pathol Div, Boston, MA 02115 USA.
RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM Ursula_matulonis@dfci.harvard.edu
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
FU Ovarian Cancer Specialized Program of Research Excellence [P50CA105009];
Madeline Franchi Ovarian Cancer Fund; Women's Executive Council of the
Dana-Farber Cancer Institute; Novartis Pharmaceuticals
FX Funding was provided by the following sources: Ovarian Cancer
Specialized Program of Research Excellence (P50CA105009), the Madeline
Franchi Ovarian Cancer Fund, and the Women's Executive Council of the
Dana-Farber Cancer Institute. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.; Drs. Hahn and Drapkin both serve as consultants for and
have received research grants from Novartis Pharmaceuticals. This did
not alter the authors' adherence to all the PLoS ONE policies on sharing
data and materials. The other authors have no conflicts of interest to
report.
NR 21
TC 26
Z9 27
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 SEP 8
PY 2011
VL 6
IS 9
AR e24433
DI 10.1371/journal.pone.0024433
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819CK
UT WOS:000294802800050
PM 21931712
ER
PT J
AU Milane, L
Duan, ZF
Amiji, M
AF Milane, Lara
Duan, Zhenfeng
Amiji, Mansoor
TI Therapeutic Efficacy and Safety of Paclitaxel/Lonidamine Loaded
EGFR-Targeted Nanoparticles for the Treatment of Multi-Drug Resistant
Cancer
SO PLOS ONE
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR-1; PEPTIDE LIGAND; CELLS; GLYCOLYSIS;
APOPTOSIS; GROWTH; DELIVERY; WARBURG; OXYGEN
AB The treatment of multi-drug resistant (MDR) cancer is a clinical challenge. Many MDR cells over-express epidermal growth factor receptor (EGFR). We exploit this expression through the development of EGFR-targeted, polymer blend nanocarriers for the treatment of MDR cancer using paclitaxel (a common chemotherapeutic agent) and lonidamine (an experimental drug; mitochondrial hexokinase 2 inhibitor). An orthotopic model of MDR human breast cancer was developed in nude mice and used to evaluate the safety and efficacy of nanoparticle treatment. The efficacy parameters included tumor volume measurements from day 0 through 28 days post-treatment, terminal tumor weight measurements, tumor density and morphology assessment through hematoxylin and eosin staining of excised tumors, and immunohistochemistry of tumor sections for MDR protein markers (P-glycoprotein, Hypoxia Inducible Factor, EGFR, Hexokinase 2, and Stem Cell Factor). Toxicity was assessed by tracking changes in animal body weight from day 0 through 28 days post-treatment, by measuring plasma levels of the liver enzymes ALT (Alanine Aminotransferase) and LDH (lactate dehydrogenase), and by white blood cell and platelet counts. In these studies, this nanocarrier system demonstrated superior efficacy relative to combination (paclitaxel/lonidamine) drug solution and single agent treatments in nanoparticle and solution form. The combination nanoparticles were the only treatment group that decreased tumor volume, sustaining this decrease until the 28 day time point. In addition, treatment with the EGFR-targeted lonidamine/paclitaxel nanoparticles decreased tumor density and altered the MDR phenotype of the tumor xenografts. These EGFR-targeted combination nanoparticles were considerably less toxic than solution treatments. Due to the flexible design and simple conjugation chemistry, this nanocarrier system could be used as a platform for the development of other MDR cancer therapies; the use of this system for EGFR-targeted, combination paclitaxel/lonidamine therapy is an advance in personalized medicine.
C1 [Milane, Lara; Amiji, Mansoor] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA.
[Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA.
RP Milane, L (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA.
EM m.amiji@neu.edu
RI Amiji, Mansoor/A-4365-2014
OI Amiji, Mansoor/0000-0001-6170-881X
FU National Cancer Institute, National Institutes of Health [R01 CA-119617,
R01 CA-119617S1, R21 CA-135594]
FX This study was supported by the National Cancer Institute, National
Institutes of Health through grants R01 CA-119617 and R01 CA-119617S1
(ARRA Supplement), and R21 CA-135594. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 23
TC 37
Z9 37
U1 3
U2 40
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 8
PY 2011
VL 6
IS 9
AR e24075
DI 10.1371/journal.pone.0024075
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819CK
UT WOS:000294802800020
PM 21931642
ER
PT J
AU Scheer, FAJL
Michelson, AD
Frelinger, AL
Evoniuk, H
Kelly, EE
McCarthy, M
Doamekpor, LA
Barnard, MR
Shea, SA
AF Scheer, Frank A. J. L.
Michelson, Alan D.
Frelinger, Andrew L., III
Evoniuk, Heather
Kelly, Erin E.
McCarthy, Mary
Doamekpor, Lauren A.
Barnard, Marc R.
Shea, Steven A.
TI The Human Endogenous Circadian System Causes Greatest Platelet
Activation during the Biological Morning Independent of Behaviors
SO PLOS ONE
LA English
DT Article
ID SUDDEN CARDIAC DEATH; NIGHT-SHIFT WORKERS; FLOW-CYTOMETRY;
MYOCARDIAL-INFARCTION; MELATONIN; AGGREGATION; RHYTHM; THROMBOSIS;
DISORDERS; FREQUENCY
AB Background: Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (similar to 9AM), potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1) platelet function and (2) platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.
Methodology/Principal Findings: We studied 12 healthy adults (6 female) who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP) IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p <= 0.01). These circadian peaks occurred at a circadian phase corresponding to 8-9AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8PM). The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.
Conclusions/Significance: These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans-independent of the sleep/wake cycle, other behavioral influences and the environment. The similar to 9AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous circadian influences on platelet function could contribute to the morning peak in adverse cardiovascular events as seen in many epidemiological studies.
C1 [Scheer, Frank A. J. L.; Evoniuk, Heather; Kelly, Erin E.; McCarthy, Mary; Doamekpor, Lauren A.; Shea, Steven A.] Brigham & Womens Hosp, Med Chronobiol Program, Div Sleep Med, Boston, MA 02115 USA.
[Scheer, Frank A. J. L.; Shea, Steven A.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA.
[Michelson, Alan D.; Frelinger, Andrew L., III; Barnard, Marc R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Platelet Res Studies,Div Hematol Oncol,Childr, Boston, MA 02115 USA.
RP Scheer, FAJL (reprint author), Brigham & Womens Hosp, Med Chronobiol Program, Div Sleep Med, 75 Francis St, Boston, MA 02115 USA.
EM fscheer@rics.bwh.harvard.edu; sshea@hms.harvard.edu
RI Scheer, Frank/C-2795-2012;
OI Shea, Steven/0000-0003-1949-0954
FU National Institutes of Health [NIH-R01-HL76409, NIH-K24-HL076446,
NIH-P30-HL101299]; [NCRR-GCRC-M01-RR02635]
FX National Institutes of Health: NIH-R01-HL76409; NIH-K24-HL076446 in
support of SAS; NIH-P30-HL101299 in support of FAJLS;
NCRR-GCRC-M01-RR02635. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
TC 36
Z9 36
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 8
PY 2011
VL 6
IS 9
AR e24549
DI 10.1371/journal.pone.0024549
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819CK
UT WOS:000294802800064
PM 21931750
ER
PT J
AU Patel, MR
Mahaffey, KW
Garg, J
Pan, GH
Singer, DE
Hacke, W
Breithardt, G
Halperin, JL
Hankey, GJ
Piccini, JP
Becker, RC
Nessel, CC
Paolini, JF
Berkowitz, SD
Fox, KAA
Califf, RM
AF Patel, Manesh R.
Mahaffey, Kenneth W.
Garg, Jyotsna
Pan, Guohua
Singer, Daniel E.
Hacke, Werner
Breithardt, Guenter
Halperin, Jonathan L.
Hankey, Graeme J.
Piccini, Jonathan P.
Becker, Richard C.
Nessel, Christopher C.
Paolini, John F.
Berkowitz, Scott D.
Fox, Keith A. A.
Califf, Robert M.
CA ROCKET AF Investigators
TI Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID INTENT-TO-TREAT; ANTITHROMBOTIC THERAPY; STROKE PREVENTION;
NON-INFERIORITY; TRIALS; THROMBOPROPHYLAXIS; PHARMACODYNAMICS;
PHARMACOKINETICS; ANTICOAGULATION; ARTHROPLASTY
AB Background
The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin.
Methods
In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism.
Results
In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P < 0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P < 0.001 for noninferiority; P = 0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P = 0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P = 0.02) and fatal bleeding (0.2% vs. 0.5%, P = 0.003) in the rivaroxaban group.
Conclusions
In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials. gov number, NCT00403767.)
C1 [Patel, Manesh R.; Mahaffey, Kenneth W.; Garg, Jyotsna; Piccini, Jonathan P.; Becker, Richard C.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA.
[Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27705 USA.
[Pan, Guohua; Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA.
[Paolini, John F.; Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA.
[Hacke, Werner] Univ Heidelberg, Heidelberg, Germany.
[Breithardt, Guenter] Hosp Univ Munster, Munster, Germany.
[Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA.
[Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia.
[Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
RP Patel, MR (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Rm 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA.
EM manesh.patel@duke.edu
RI Arkhipov, Mikhail/Q-2316-2015; Urina, Miguel/H-2605-2016; Zadionchenko,
Vladimir/A-7445-2016; De Caterina, Raffaele/K-3857-2016; bladin,
chris/B-9136-2013; Mazurov, Vadim/J-9643-2014; Walters,
Darren/A-7069-2011; Sinkiewicz, Wladyslaw/G-5169-2014; Parsons,
Mark/G-3750-2014; Hankey, Graeme /H-4968-2014; Libis, Roman/O-9193-2015;
OI Urina, Miguel/0000-0001-6003-4622; Zadionchenko,
Vladimir/0000-0003-2377-5266; De Caterina, Raffaele/0000-0003-1637-574X;
Mazurov, Vadim/0000-0002-0797-2051; Hankey, Graeme /0000-0002-6044-7328;
Libis, Roman/0000-0003-0130-990X; Pardo-Oviedo, Juan
Mauricio/0000-0003-0084-3449; Prabhakaran, Dorairaj/0000-0002-3172-834X;
Michel, GALINIER/0000-0003-1735-3390; Kaste, Markku/0000-0001-6557-6412;
Macleod, Malcolm Robert/0000-0001-9187-9839
FU Johnson Johnson; Bayer
FX Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials. gov
number, NCT00403767.
NR 27
TC 2616
Z9 2743
U1 40
U2 232
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 SEP 8
PY 2011
VL 365
IS 10
BP 883
EP 891
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 816JX
UT WOS:000294595600004
PM 21830957
ER
PT J
AU Winter, HS
Gervais, DA
Branda, JA
AF Winter, Harland S.
Gervais, Debra A.
Branda, John A.
TI Case 27-2011: A 17-Year-Old Boy with Abdominal Pain and Weight Loss
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CROHNS-DISEASE; TUBERCULOSIS; DIAGNOSIS; CHILDREN; HISTOPLASMOSIS;
INFECTION; SYMPTOMS
C1 [Winter, Harland S.] Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA.
[Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Winter, Harland S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Gervais, Debra A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Winter, HS (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA.
NR 14
TC 3
Z9 3
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 SEP 8
PY 2011
VL 365
IS 10
BP 940
EP 950
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 816JX
UT WOS:000294595600012
PM 21899455
ER
PT J
AU Shen, SY
Zhang, ZB
Tucker, JD
Chang, HL
Zhang, GR
Lin, AH
AF Shen, Song-Ying
Zhang, Zhou-Bin
Tucker, Joseph D.
Chang, Helena
Zhang, Guan-Rong
Lin, Ai-Hua
TI Peer-based behavioral health program for drug users in China: a pilot
study
SO BMC PUBLIC HEALTH
LA English
DT Article
ID SEXUALLY-TRANSMITTED INFECTIONS; HIV-INFECTION; HIV/AIDS PREVENTION;
GUANGDONG PROVINCE; RISK BEHAVIORS; HARM REDUCTION; HEPATITIS-C;
PREVALENCE; TRANSMISSION; EDUCATION
AB Background: Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.
Methods: A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).
Results: Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.
Conclusions: This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.
C1 [Shen, Song-Ying; Zhang, Guan-Rong; Lin, Ai-Hua] Sun Yat Sen Univ, Dept Med Stat & Epidemiol, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China.
[Zhang, Zhou-Bin] Guangzhou Ctr Dis Control & Prevent, Guangzhou, Guangdong, Peoples R China.
[Tucker, Joseph D.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Chang, Helena] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
RP Lin, AH (reprint author), Sun Yat Sen Univ, Dept Med Stat & Epidemiol, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China.
EM linaihua@mail.sysu.edu.cn
FU AIDS Prevention Foundation [WA2005-6]; Ministry of Health of People's
Republic of China
FX We thank the managers, doctors and nurses at the Guangzhou Municipal
Drug User Detention Center and the Guangzhou Baiyun District Drug User
Detention Center for their support and participation in the project and
all those who distributed and collected questionnaires. This study was
supported by applied research program of AIDS Prevention Foundation
grant number WA2005-6 funded by Ministry of Health of People's Republic
of China.
NR 48
TC 4
Z9 4
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD SEP 7
PY 2011
VL 11
AR 693
DI 10.1186/1471-2458-11-693
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 832HN
UT WOS:000295795000001
PM 21899764
ER
PT J
AU Esterhazy, D
Stutzer, I
Wang, HY
Rechsteiner, MP
Beauchamp, J
Dobeli, H
Hilpert, H
Matile, H
Prummer, M
Schmidt, A
Lieske, N
Boehm, B
Marselli, L
Bosco, D
Kerr-Conte, J
Aebersold, R
Spinas, GA
Moch, H
Migliorini, C
Stoffel, M
AF Esterhazy, Daria
Stuetzer, Ina
Wang, Haiyan
Rechsteiner, Markus P.
Beauchamp, Jeremy
Doebeli, Heinz
Hilpert, Hans
Matile, Hugues
Prummer, Michael
Schmidt, Alexander
Lieske, Nora
Boehm, Bernhard
Marselli, Lorella
Bosco, Domenico
Kerr-Conte, Julie
Aebersold, Ruedi
Spinas, Giatgen Andreia
Moch, Holger
Migliorini, Cristiano
Stoffel, Markus
TI Bace2 Is a beta Cell-Enriched Protease that Regulates Pancreatic beta
Cell Function and Mass
SO CELL METABOLISM
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE; ALZHEIMERS-DISEASE;
INSULIN-SECRETION; MICE LACKING; ASP1 BACE2; COLLECTRIN; IDENTIFICATION;
EXPRESSION; MOUSE
AB Decreased beta cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human beta cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented beta cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of beta cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic beta cell mass.
C1 [Esterhazy, Daria; Stuetzer, Ina; Schmidt, Alexander; Lieske, Nora; Aebersold, Ruedi; Stoffel, Markus] ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
[Esterhazy, Daria; Stuetzer, Ina; Rechsteiner, Markus P.; Schmidt, Alexander; Aebersold, Ruedi; Spinas, Giatgen Andreia; Moch, Holger; Stoffel, Markus] ETH, Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland.
[Wang, Haiyan; Beauchamp, Jeremy; Doebeli, Heinz; Hilpert, Hans; Matile, Hugues; Prummer, Michael; Migliorini, Cristiano] F Hoffmann La Roche, CH-4070 Basel, Switzerland.
[Rechsteiner, Markus P.; Moch, Holger] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland.
[Spinas, Giatgen Andreia] Univ Zurich Hosp, Div Endocrinol Diabet & Clin Nutr, CH-8091 Zurich, Switzerland.
[Boehm, Bernhard] Univ Ulm, Div Endocrinol & Diabet, D-89070 Ulm, Germany.
[Marselli, Lorella] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA.
[Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8091 Zurich, Switzerland.
[Stoffel, Markus] Univ Zurich, Fac Med, CH-8091 Zurich, Switzerland.
[Bosco, Domenico] Univ Hosp Geneva, Cell Isolat & Transplantat Ctr, CH-1121 Geneva, Switzerland.
[Kerr-Conte, Julie] Univ Lille 2, INSERM, U859, Dept Surg, F-59045 Lille, France.
RP Stoffel, M (reprint author), ETH, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
EM stoffel@imsb.biol.ethz.ch
RI Prummer, Michael/G-6464-2011; Boehm, Bernhard/F-8750-2015
OI Prummer, Michael/0000-0001-9896-3929;
FU JDRF International; F. Hoffmann-La Roche
FX This work was in part sponsored by the JDRF International and by F.
Hoffmann-La Roche. We thank P. Salvioni, A. Benardeau, W. Riboulet, S.
Uhles, M. Brecheisen, S. Sewing, and T. Lave for helpful discussions and
technical expertise. We thank P. Halban for generously providing the
804G conditioned medium for the islet proliferation assays.
NR 40
TC 54
Z9 56
U1 0
U2 6
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 SEP 7
PY 2011
VL 14
IS 3
BP 365
EP 377
DI 10.1016/j.cmet.2011.06.018
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 830MD
UT WOS:000295660200011
PM 21907142
ER
PT J
AU Tucker, EJ
Hershman, SG
Kohrer, C
Belcher-Timme, CA
Patel, J
Goldberger, OA
Christodoulou, J
Silberstein, JM
McKenzie, M
Ryan, MT
Compton, AG
Jaffe, JD
Carr, SA
Calvo, SE
RajBhandary, UL
Thorburn, DR
Mootha, VK
AF Tucker, Elena J.
Hershman, Steven G.
Koehrer, Caroline
Belcher-Timme, Casey A.
Patel, Jinal
Goldberger, Olga A.
Christodoulou, John
Silberstein, Jonathon M.
McKenzie, Matthew
Ryan, Michael T.
Compton, Alison G.
Jaffe, Jacob D.
Carr, Steven A.
Calvo, Sarah E.
RajBhandary, Uttam L.
Thorburn, David R.
Mootha, Vamsi K.
TI Mutations in MTFMT Underlie a Human Disorder of Formylation Causing
Impaired Mitochondrial Translation
SO CELL METABOLISM
LA English
DT Article
ID INITIATOR TRANSFER-RNA; COMPLEX I DEFICIENCY; PROTEIN-SYNTHESIS;
SACCHAROMYCES-CEREVISIAE; GENOME; INITIATION-FACTOR-2; IDENTIFICATION;
COMPENDIUM; SUBUNITS; NUCLEAR
AB The metazoan mitochondrial translation machinery is unusual in having a single tRNA(Met) that fulfills the dual role of the initiator and elongator tRNA(Met). A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(Met)), which is used for translation initiation; however, the requirement of formylation for initiation in human mitochondria is still under debate. Using targeted sequencing of the mtDNA and nuclear exons encoding the mitochondrial proteome (MitoExome), we identified compound heterozygous mutations in MTFMT in two unrelated children presenting with Leigh syndrome and combined OXPHOS deficiency. Patient fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of MTFMT. Furthermore, patient fibroblasts have dramatically reduced fMet-tRNA(Met) levels and an abnormal formylation profile of mitochondrially translated COX1. Our findings demonstrate that MTFMT is critical for efficient human mitochondrial translation and reveal a human disorder of Met-tRNA(Met) formylation.
C1 [Tucker, Elena J.; Compton, Alison G.; Thorburn, David R.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia.
[Thorburn, David R.] Royal Childrens Hosp, Genet Hlth Serv Victoria, Melbourne, Vic 3052, Australia.
[Tucker, Elena J.; Thorburn, David R.] Univ Melbourne, Dept Paediat, Melbourne, Vic 3052, Australia.
[Hershman, Steven G.; Belcher-Timme, Casey A.; Goldberger, Olga A.; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Hershman, Steven G.; Belcher-Timme, Casey A.; Goldberger, Olga A.; Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Hershman, Steven G.; Belcher-Timme, Casey A.; Patel, Jinal; Goldberger, Olga A.; Jaffe, Jacob D.; Carr, Steven A.; Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA.
[Koehrer, Caroline; RajBhandary, Uttam L.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Christodoulou, John] Childrens Hosp Westmead, Genet Metab Disorders Res Unit, Sydney, NSW 2006, Australia.
[Christodoulou, John] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia.
[Christodoulou, John] Univ Sydney, Discipline Genet Med, Sydney, NSW 2006, Australia.
[Silberstein, Jonathon M.] Princess Margaret Hosp Children, Dept Neurol, Perth, WA 6008, Australia.
[McKenzie, Matthew] Monash Univ, Monash Inst Med Res, Ctr Reprod & Dev, Melbourne, Vic 3168, Australia.
[Ryan, Michael T.] La Trobe Univ, Dept Biochem, Melbourne, Vic 3086, Australia.
[Ryan, Michael T.] La Trobe Univ, ARC Ctr Excellence Coherent Xray Sci, Melbourne, Vic 3086, Australia.
RP Thorburn, DR (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Melbourne, Vic 3052, Australia.
EM david.thorburn@mcri.edu.au; vamsi@hms.harvard.edu
RI Ryan, Michael/C-6673-2011; Tucker, Elena/B-3487-2012; Thorburn,
David/G-6266-2013; Christodoulou, John/E-5866-2015;
OI Ryan, Michael/0000-0003-2586-8829; Hershman, Steven/0000-0001-9167-7380;
thorburn, david/0000-0002-7725-9470; McKenzie,
Matthew/0000-0001-7508-1800; Compton, Alison/0000-0002-2725-7055;
Christodoulou, John/0000-0002-8431-0641
FU Australian Postgraduate Award; National Defense Science and Engineering
Graduate Fellowship; Australian National Health and Medical Research
Council (NHMRC); Victorian Government; Ramaciotti Foundation; James and
Vera Lawson Trust; NHMRC; National Institutes of Health [GM17151,
GM077465, GM097136]
FX We thank J. Silke and P. Ekert for providing the
pF_5x_UAS_MCS_SV40_puroGEV16-W vector, C. Guiducci, C. Sougnez, L.
Ambrogia, and J. Wilkinson, for assistance with sample preparation and
sequencing, T. Fennel, M. DePristo, E. Banks, and K. Garimella for
assistance with bioinformatic analysis, S. Flynn for assistance with
IRBs, and the subjects and referring physicians who participated in the
study. This work was supported by an Australian Postgraduate Award to
E.J.T., a National Defense Science and Engineering Graduate Fellowship
to S.G.H., an Australian National Health and Medical Research Council
(NHMRC) Career Development Award to M.M., an NHMRC Principal Research
fellowship to D.R.T., the Victorian Government's Operational
Infrastructure Support Program, and grants from the Ramaciotti
Foundation and the James and Vera Lawson Trust to M.M., the NHMRC to
MM., M.T.R. and D.R.T., and the National Institutes of Health to U.L.R.
(GM17151) and to V.K.M. (GM077465 and GM097136).
NR 29
TC 52
Z9 54
U1 0
U2 5
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 SEP 7
PY 2011
VL 14
IS 3
BP 428
EP 434
DI 10.1016/j.cmet.2011.07.010
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 830MD
UT WOS:000295660200016
PM 21907147
ER
PT J
AU Lewis, JH
Li, RJ
Jia, X
Watkins, WT
Lou, YF
Song, WY
Jiang, SB
AF Lewis, John H.
Li, Ruijiang
Jia, Xun
Watkins, W. Tyler
Lou, Yifei
Song, William Y.
Jiang, Steve B.
TI Mitigation of motion artifacts in CBCT of lung tumors based on tracked
tumor motion during CBCT acquisition
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID CONE-BEAM CT; 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; RESPIRATORY MOTION;
RADIOTHERAPY; SHRINKAGE; CANCER; RECONSTRUCTION; LOCALIZATION; MODEL;
PROJECTIONS
AB An algorithm capable of mitigating respiratory motion blurring artifacts in cone-beam computed tomography (CBCT) lung tumor images based on the motion of the tumor during the CBCT scan is developed. The tumor motion trajectory and probability density function (PDF) are reconstructed from the acquired CBCT projection images using a recently developed algorithm Lewis et al (2010 Phys. Med. Biol. 55 2505-22). Assuming that the effects of motion blurring can be represented by convolution of the static lung (or tumor) anatomy with the motion PDF, a cost function is defined, consisting of a data fidelity term and a total variation regularization term. Deconvolution is performed through iterative minimization of this cost function. The algorithm was tested on digital respiratory phantom, physical respiratory phantom and patient data. A clear qualitative improvement is evident in the deblurred images as compared to the motion-blurred images for all cases. Line profiles show that the tumor boundaries are more accurately and clearly represented in the deblurred images. The normalized root-mean-squared error between the images used as ground truth and the motion-blurred images are 0.29, 0.12 and 0.30 in the digital phantom, physical phantom and patient data, respectively. Deblurring reduces the corresponding values to 0.13, 0.07 and 0.19. Application of a -700 HU threshold to the digital phantom results in tumor dimension measurements along the superior-inferior axis of 2.8, 1.8 and 1.9 cm in the motion-blurred, ground truth and deblurred images, respectively. Corresponding values for the physical phantom are 3.4, 2.7 and 2.7 cm. A threshold of -500 HU applied to the patient case gives measurements of 3.1, 1.6 and 1.7 cm along the SI axis in the CBCT, 4DCT and deblurred images, respectively. This technique could provide more accurate information about a lung tumor's size and shape on the day of treatment.
C1 [Lewis, John H.; Li, Ruijiang; Jia, Xun; Watkins, W. Tyler; Song, William Y.; Jiang, Steve B.] Univ Calif San Diego, Ctr Adv Radiotherapy Technol, La Jolla, CA 92093 USA.
[Lewis, John H.; Li, Ruijiang; Jia, Xun; Watkins, W. Tyler; Song, William Y.; Jiang, Steve B.] Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA.
[Lewis, John H.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Lewis, John H.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Lou, Yifei] Univ Calif Los Angeles, Dept Math, Los Angeles, CA 90095 USA.
RP Lewis, JH (reprint author), Univ Calif San Diego, Ctr Adv Radiotherapy Technol, La Jolla, CA 92093 USA.
EM sbjiang@ucsd.edu
FU Varian Medical Systems, Inc.
FX This work was partially supported by Varian Medical Systems, Inc.
NR 43
TC 6
Z9 6
U1 1
U2 2
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 SEP 7
PY 2011
VL 56
IS 17
BP 5485
EP 5502
DI 10.1088/0031-9155/56/17/003
PG 18
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 818WK
UT WOS:000294786400006
PM 21813959
ER
PT J
AU Liu, EB
Ferreyra, L
Fischer, SL
Pavan, JV
Nates, SV
Hudson, NR
Tirado, D
Dyer, DW
Chodosh, J
Seto, D
Jones, MS
AF Liu, Elizabeth B.
Ferreyra, Leonardo
Fischer, Stephen L.
Pavan, Jorge V.
Nates, Silvia V.
Hudson, Nolan Ryan
Tirado, Damaris
Dyer, David W.
Chodosh, James
Seto, Donald
Jones, Morris S.
TI Genetic Analysis of a Novel Human Adenovirus with a Serologically Unique
Hexon and a Recombinant Fiber Gene
SO PLOS ONE
LA English
DT Article
ID EPIDEMIC KERATOCONJUNCTIVITIS; GASTROENTERITIS; INTERNALIZATION;
PROTEINS; EVASION
AB In February of 1996 a human adenovirus (formerly known as Ad-Cor-96-487) was isolated from the stool of an AIDS patient who presented with severe chronic diarrhea. To characterize this apparently novel pathogen of potential public health significance, the complete genome of this adenovirus was sequenced to elucidate its origin. Bioinformatic and phylogenetic analyses of this genome demonstrate that this virus, heretofore referred to as HAdV-D58, contains a novel hexon gene as well as a recombinant fiber gene. In addition, serological analysis demonstrated that HAdV-D58 has a different neutralization profile than all previously characterized HAdVs. Bootscan analysis of the HAdV-D58 fiber gene strongly suggests one recombination event.
C1 [Liu, Elizabeth B.; Seto, Donald] George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA USA.
[Liu, Elizabeth B.; Seto, Donald] George Mason Univ, Dept Syst Biol, Manassas, VA USA.
[Ferreyra, Leonardo; Pavan, Jorge V.; Nates, Silvia V.] Natl Univ Cordoba, Inst Virol, Sch Med Sci, Cordoba, Argentina.
[Fischer, Stephen L.] USN, Hosp Camp Pendleton, Camp Pendleton, CA USA.
[Hudson, Nolan Ryan; Tirado, Damaris] David Grant USAF Med Ctr, Clin Invest Facil, 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,Dept Ophthalmol, Boston, MA USA.
[Jones, Morris S.] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA USA.
RP Liu, EB (reprint author), George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA USA.
EM morris.jones@cdph.ca.gov
FU United States Air Force Surgeon General [FDG20040024E]; Research to
Prevent Blindness, Inc.; [R01EY013124]; [P30EY014104]
FX This research was supported by R01EY013124 (DS, MSJ and JC) and
P30EY014104 (JC). MSJ was also funded by the United States Air Force
Surgeon General-approved Clinical Investigation No. FDG20040024E. JC was
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 24
TC 27
Z9 35
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 7
PY 2011
VL 6
IS 9
AR e24491
DI 10.1371/journal.pone.0024491
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819CH
UT WOS:000294802500054
PM 21915339
ER
PT J
AU Yonesaka, K
Zejnullahu, K
Okamoto, I
Satoh, T
Cappuzzo, F
Souglakos, J
Ercan, D
Rogers, A
Roncalli, M
Takeda, M
Fujisaka, Y
Philips, J
Shimizu, T
Maenishi, O
Cho, YG
Sun, JS
Destro, A
Taira, K
Takeda, K
Okabe, T
Swanson, J
Itoh, H
Takada, M
Lifshits, E
Okuno, K
Engelman, JA
Shivdasani, RA
Nishio, K
Fukuoka, M
Varella-Garcia, M
Nakagawa, K
Janne, PA
AF Yonesaka, Kimio
Zejnullahu, Kreshnik
Okamoto, Isamu
Satoh, Taroh
Cappuzzo, Federico
Souglakos, John
Ercan, Dalia
Rogers, Andrew
Roncalli, Massimo
Takeda, Masayuki
Fujisaka, Yasuhito
Philips, Juliet
Shimizu, Toshio
Maenishi, Osamu
Cho, Yonggon
Sun, Jason
Destro, Annarita
Taira, Koichi
Takeda, Koji
Okabe, Takafumi
Swanson, Jeffrey
Itoh, Hiroyuki
Takada, Minoru
Lifshits, Eugene
Okuno, Kiyotaka
Engelman, Jeffrey A.
Shivdasani, Ramesh A.
Nishio, Kazuto
Fukuoka, Masahiro
Varella-Garcia, Marileila
Nakagawa, Kazuhiko
Jaenne, Pasi A.
TI Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed
Therapeutic Antibody Cetuximab
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER;
CHRONIC MYELOID-LEUKEMIA; WILD-TYPE; MET AMPLIFICATION; IN-VIVO;
GEFITINIB; MUTATIONS; CHEMOTHERAPY
AB Cetuximab, an antibody directed against the epidermal growth factor receptor, is an effective clinical therapy for patients with colorectal, head and neck, and non-small cell lung cancer, particularly for those with KRAS and BRAF wild-type cancers. Treatment in all patients is limited eventually by the development of acquired resistance, but little is known about the underlying mechanism. Here, we show that activation of ERBB2 signaling in cell lines, either through ERBB2 amplification or through heregulin up-regulation, leads to persistent extracellular signal-regulated kinase 1/2 signaling and consequently to cetuximab resistance. Inhibition of ERBB2 or disruption of ERBB2/ERBB3 heterodimerization restores cetuximab sensitivity in vitro and in vivo. A subset of colorectal cancer patients who exhibit either de novo or acquired resistance to cetuximab-based therapy has ERBB2 amplification or high levels of circulating heregulin. Collectively, these findings identify two distinct resistance mechanisms, both of which promote aberrant ERBB2 signaling, that mediate cetuximab resistance. Moreover, these results suggest that ERBB2 inhibitors, in combination with cetuximab, represent a rational therapeutic strategy that should be assessed in patients with cetuximab-resistant cancers.
C1 [Yonesaka, Kimio; Okamoto, Isamu; Satoh, Taroh; Takeda, Masayuki; Fujisaka, Yasuhito; Shimizu, Toshio; Nakagawa, Kazuhiko] Kinki Univ, Sch Med, Dept Med Oncol, Osaka 5898511, Japan.
[Yonesaka, Kimio; Zejnullahu, Kreshnik; Ercan, Dalia; Rogers, Andrew; Sun, Jason; Okabe, Takafumi; Swanson, Jeffrey; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA.
[Yonesaka, Kimio; Zejnullahu, Kreshnik; Ercan, Dalia; Rogers, Andrew; Philips, Juliet; Sun, Jason; Okabe, Takafumi; Swanson, Jeffrey; Shivdasani, Ramesh A.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Yonesaka, Kimio; Fukuoka, Masahiro] Izumi Municipal Hosp, Dept Med Oncol, Osaka 5940071, Japan.
[Cappuzzo, Federico; Roncalli, Massimo; Destro, Annarita] Ist Clin Humanitas, I-20089 Rozzano, Italy.
[Souglakos, John] Univ Crete, Lab Tumor Biol, Sch Med, Iraklion 71110, Greece.
[Souglakos, John] Univ Hosp Heraklion, Iraklion 71110, Greece.
[Maenishi, Osamu; Itoh, Hiroyuki] Kinki Univ, Sch Med, Dept Pathol, Osaka 5898511, Japan.
[Cho, Yonggon; Varella-Garcia, Marileila] Univ Colorado, Ctr Canc, Aurora, CO 80045 USA.
[Taira, Koichi; Takeda, Koji] Osaka City Gen Hosp, Dept Clin Oncol, Osaka 5340021, Japan.
[Takada, Minoru; Fukuoka, Masahiro] Kinki Univ, Sch Med, Sakai Hosp, Dept Med Oncol, Osaka 5900132, Japan.
[Lifshits, Eugene; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
[Okuno, Kiyotaka] Kinki Univ, Sch Med, Dept Surg, Osaka 5898511, Japan.
[Shivdasani, Ramesh A.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Shivdasani, Ramesh A.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Nishio, Kazuto] Kinki Univ, Sch Med, Dept Genome Biol, Osaka 5898511, Japan.
RP Nakagawa, K (reprint author), Kinki Univ, Sch Med, Dept Med Oncol, Osaka 5898511, Japan.
EM nakagawa@med.kindai.ac.jp; pjanne@partners.org
RI Cho, Yong Gon/Q-9924-2016;
OI Cho, Yong Gon/0000-0003-3011-6875; Cappuzzo,
Federico/0000-0002-6295-6767; Roncalli, Massimo/0000-0002-7901-8910
FU NIH [RO1CA114465, R01CA135257, P50 CA58187]; American Cancer Society
[RSG0610201CCE]; Lung Cancer [SPORE P50 CA090578]; Gastrointestinal
Cancer [SPORE P50 CA127003]; William Randolph Hearst Foundation; Hazel
and Samuel Bellin research fund; Cammarata Family Foundation; Roche
FX Supported by NIH grants RO1CA114465 (P.A.J.), R01CA135257 (P.A.J. and
J.A.E.), and P50 CA58187 (M. V.-G.); American Cancer Society
RSG0610201CCE (P.A.J. and J.A.E.); the Lung Cancer SPORE P50 CA090578
(P.A.J. and J.A.E.); the Gastrointestinal Cancer SPORE P50 CA127003
(P.A.J. and J.A.E.); the William Randolph Hearst Foundation (R. A. S.);
the Hazel and Samuel Bellin research fund (P.A.J.); and Cammarata Family
Foundation Research Fund (P.A.J.).; P.A.J. has consulted for Genentech
and Roche. J.A.E. has consulted for Roche and Bristol-Myers Squibb. T.
Satoh has consulted for Merck-Serono, Bristol-Myers Squib,
Chugai-Pharmaceuticals, Takeda, Sanofi-Aventis, Taiho Pharmaceutical,
Pfizer, and Daiichi-Sankyo P.A.J. and J.A.E. have received royalties
from Roche on intellectual property not related to this work. A patent
has been filed by Dana-Farber Cancer Institute involving the use of MET
and EGFR inhibitors to overcome resistance to EGFR inhibitors.
NR 38
TC 186
Z9 187
U1 6
U2 21
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 SEP 7
PY 2011
VL 3
IS 99
AR 99ra86
DI 10.1126/scitranslmed.3002442
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 817HY
UT WOS:000294663900005
PM 21900593
ER
PT J
AU Dhaliwal, G
AF Dhaliwal, Gurpreet
TI The Mechanics of Reasoning
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Dhaliwal, G (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM gurpreet.dhaliwal@ucsf.edu
NR 3
TC 0
Z9 0
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD SEP 7
PY 2011
VL 306
IS 9
BP 918
EP 919
DI 10.1001/jama.2011.1027
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 815QT
UT WOS:000294542600001
PM 21900128
ER
PT J
AU van Ryn, M
Saha, S
AF van Ryn, Michelle
Saha, Somnath
TI Exploring Unconscious Bias in Disparities Research and Medical Education
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID HEALTH-CARE; PROVIDERS; CONTRIBUTE
C1 [van Ryn, Michelle] Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55414 USA.
[Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA.
[Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA.
RP van Ryn, M (reprint author), Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, 925 SE Delaware St,Ste 221, Minneapolis, MN 55414 USA.
EM vanry001@umn.edu
FU NHLBI NIH HHS [R01 HL085631]
NR 14
TC 19
Z9 19
U1 2
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 SEP 7
PY 2011
VL 306
IS 9
BP 995
EP 996
DI 10.1001/jama.2011.1275
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 815QT
UT WOS:000294542600020
PM 21900142
ER
PT J
AU Gao, G
Xie, A
Huang, SC
Zhou, AY
Zhang, JH
Herman, AM
Ghassemzadeh, S
Jeong, EM
Kasturirangan, S
Raicu, M
Sobieski, MA
Bhat, G
Tatooles, A
Benz, EJ
Kamp, TJ
Dudley, SC
AF Gao, Ge
Xie, An
Huang, Shu-Ching
Zhou, Anyu
Zhang, Jianhua
Herman, Amanda M.
Ghassemzadeh, Sassan
Jeong, Euy-Myoung
Kasturirangan, Srinivasan
Raicu, Mihai
Sobieski, Michael A., II
Bhat, Geetha
Tatooles, Antone
Benz, Edward J., Jr.
Kamp, Timothy J.
Dudley, Samuel C., Jr.
TI Role of RBM25/LUC7L3 in Abnormal Cardiac Sodium Channel Splicing
Regulation in Human Heart Failure
SO CIRCULATION
LA English
DT Article
DE angiotensin II; arrhythmia; cardiomyopathy; gene expression; sodium
ID GENE-EXPRESSION; ATRIAL-FIBRILLATION; SELECTION; NETWORKS; PROTEIN;
CANCER
AB Background-Human heart failure is associated with decreased cardiac voltage-gated Na(+) channel current (encoded by SCN5A), and the changes have been implicated in the increased risk of sudden death in heart failure. Nevertheless, the mechanism of SCN5A downregulation is unclear. A number of human diseases are associated with alternative mRNA splicing, which has received comparatively little attention in the study of cardiac disease. Splicing factor expression profiles during human heart failure and a specific splicing pathway for SCN5A regulation were explored in this study.
Methods and Results-Gene array comparisons between normal human and heart failure tissues demonstrated that 17 splicing factors, associated with all major spliceosome components, were upregulated. Two of these splicing factors, RBM25 and LUC7L3, were elevated in human heart failure tissue and mediated truncation of SCN5A mRNA in both Jurkat cells and human embryonic stem cell-derived cardiomyocytes. RBM25/LUC7L3-mediated abnormal SCN5A mRNA splicing reduced Na(+) channel current 91.1 +/- 9.3% to a range known to cause sudden death. Overexpression of either splicing factor resulted in an increase in truncated mRNA and a concomitant decrease in the full-length SCN5A transcript.
Conclusions-Of the 17 mRNA splicing factors upregulated in heart failure, RBM25 and LUC7L3 were sufficient to explain the increase in truncated forms and the reduction in full-length Na(+) channel transcript. Because the reduction in channels was in the range known to be associated with sudden death, interruption of this abnormal mRNA processing may reduce arrhythmic risk in heart failure. (Circulation. 2011; 124: 1124-1131.)
C1 [Gao, Ge; Xie, An; Jeong, Euy-Myoung; Raicu, Mihai; Dudley, Samuel C., Jr.] Univ Illinois, Cardiol Sect, Div Cardiol, Chicago, IL 60612 USA.
[Gao, Ge; Xie, An; Jeong, Euy-Myoung; Raicu, Mihai; Dudley, Samuel C., Jr.] Jesse Brown VAMC, Chicago, IL USA.
[Huang, Shu-Ching; Zhou, Anyu; Benz, Edward J., Jr.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Zhang, Jianhua; Herman, Amanda M.; Kamp, Timothy J.] Univ Wisconsin, Div Cardiovasc Med, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Ghassemzadeh, Sassan] Univ Illinois, Coll Med, Chicago, IL USA.
[Kasturirangan, Srinivasan] Univ Illinois, Div Neonatol, Dept Pediat, Chicago, IL 60612 USA.
[Sobieski, Michael A., II; Bhat, Geetha; Tatooles, Antone] Advocate Christ Med Ctr, Oak Lawn, IL USA.
RP Dudley, SC (reprint author), Univ Illinois, Cardiol Sect, Div Cardiol, 840 S Wood St,MC 715, Chicago, IL 60612 USA.
EM scdudley@uic.edu
OI Kamp, Timothy/0000-0003-2103-7876
FU National Heart, Lung, and Blood Institute [R01 HL085558, R01 HL073753,
P01 HL058000]; Veterans Affairs MERIT
FX This work was supported by grants from the National Heart, Lung, and
Blood Institute (R01 HL085558, R01 HL073753, P01 HL058000) and a
Veterans Affairs MERIT grant.
NR 33
TC 24
Z9 28
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 6
PY 2011
VL 124
IS 10
BP 1124
EP U112
DI 10.1161/CIRCULATIONAHA.111.044495
PG 13
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 815VF
UT WOS:000294557400016
PM 21859973
ER
PT J
AU Roberts, LD
AF Roberts, Lee D.
TI Funding: Fondation Leducq Transatlantic Career Development Award
SO CIRCULATION
LA English
DT Editorial Material
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
RP Roberts, LD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
NR 2
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 6
PY 2011
VL 124
IS 10
BP F58
EP F58
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 815VF
UT WOS:000294557400002
ER
PT J
AU Dabora, SL
Franz, DN
Ashwal, S
Sagalowsky, A
DiMario, FJ
Miles, D
Cutler, D
Krueger, D
Uppot, RN
Rabenou, R
Camposano, S
Paolini, J
Fennessy, F
Lee, N
Woodrum, C
Manola, J
Garber, J
Thiele, EA
AF Dabora, Sandra L.
Franz, David Neal
Ashwal, Stephen
Sagalowsky, Arthur
DiMario, Francis J., Jr.
Miles, Daniel
Cutler, Drew
Krueger, Darcy
Uppot, Raul N.
Rabenou, Rahmin
Camposano, Susana
Paolini, Jan
Fennessy, Fiona
Lee, Nancy
Woodrum, Chelsey
Manola, Judith
Garber, Judy
Thiele, Elizabeth A.
TI Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney
Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease
SO PLOS ONE
LA English
DT Article
ID RENAL-CELL CARCINOMA; GROWTH FACTOR-D; RAPAMYCIN ANALOG CCI-779;
PULMONARY LYMPHANGIOLEIOMYOMATOSIS; MUTATIONAL ANALYSIS; IMPROVED
SURVIVAL; MAMMALIAN TARGET; LUNG-FUNCTION; MOUSE MODEL; COMPLEX
AB Background: Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.
Methods: We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.
Results: 36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).
Conclusions: Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.
C1 [Dabora, Sandra L.] Biogen Idec Hemophilia, Weston, MA USA.
[Uppot, Raul N.; Camposano, Susana; Paolini, Jan; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fennessy, Fiona; Manola, Judith; Garber, Judy] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Franz, David Neal; Krueger, Darcy] Univ Cincinnati, Cincinnati, OH USA.
[Ashwal, Stephen; Cutler, Drew] Loma Linda Univ, Loma Linda, CA 92350 USA.
[Sagalowsky, Arthur] Univ Texas SW, Dallas, TX USA.
[DiMario, Francis J., Jr.] Univ Connecticut, Hartford, CT 06112 USA.
[Miles, Daniel; Rabenou, Rahmin] NYU, New York, NY USA.
[Lee, Nancy; Woodrum, Chelsey] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Dabora, SL (reprint author), Biogen Idec Hemophilia, Weston, MA USA.
EM sandy.dabora@gmail.com
FU National Institute of Health/National Cancer Institute [R01CA107164];
Tuberous Sclerosis Alliance planning and supplement grants; Brigham and
Women's Hospital Research Institute
FX This trial was funded by the following grants to SD: National Institute
of Health/National Cancer Institute (R01CA107164), Tuberous Sclerosis
Alliance planning and supplement grants, and the Brigham and Women's
Hospital Research Institute Bridge Funding Award. Wyeth/Pfizer supplied
study drug at no charge per an investigator originated proposal written
by SD. The funders played no role in the design of the trial, data
collection and analysis, decision to publish, or preparation of the
manuscript. SD designed the experiments, directed the analysis of the
data, wrote the first draft of the manuscript, and directed the final
editing of the manuscript. SD is currently an employee of Biogen Idec
Hemophilia, however the reported trial was completed when SD was on
staff at Brigham and Women's Hospital.
NR 56
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U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 6
PY 2011
VL 6
IS 9
AR e23379
DI 10.1371/journal.pone.0023379
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 817QP
UT WOS:000294689200005
PM 21915260
ER
PT J
AU Lindquist, S
Karitkina, D
Langnaese, K
Posevitz-Fejfar, A
Schraven, B
Xavier, R
Seed, B
Lindquist, JA
AF Lindquist, Sabine
Karitkina, Diana
Langnaese, Kristina
Posevitz-Fejfar, Anita
Schraven, Burkhart
Xavier, Ramnik
Seed, Brian
Lindquist, Jonathan A.
TI Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains
Differentially Modulates Src Kinase Activity in Brain Maturation
SO PLOS ONE
LA English
DT Article
ID FAMILY TYROSINE KINASES; T-CELL-ACTIVATION; TRANSMEMBRANE ADAPTER
PROTEIN; DOWN-REGULATION; MUTANT MICE; SIGNAL-TRANSDUCTION; NEGATIVE
REGULATION; LIPID RAFTS; PC12 CELLS; C-SRC
AB Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG. We demonstrate in newborn (P1) mice that PAG negatively regulates Src family kinases (SFK). P1 Pag1(-/-)mouse brains show decreased recruitment of Csk into lipid rafts, reduced phosphorylation of the inhibitory tyrosines within SFKs, and an increase in SFK activity of >/= 50%. While in brain of P1 mice, PAG and Csk are highly and ubiquitously expressed, little Csk is found in adult brain suggesting altered modes of SFK regulation. In adult brain Pag1-deficiency has no effect upon Csk-distribution or inhibitory tyrosine phosphorylation, but kinase activity is now reduced (-20-30%), pointing to the development of a compensatory mechanism that may involve PSD93. The distribution of the Csk-homologous kinase CHK is not altered. Importantly, since the activities of Fyn and Src are decreased in adult Pag1(-/-)mice, thus presenting the reversed phenotype of P1, this provides the first in vivo evidence for a Csk-independent positive regulatory function for PAG in the brain.
C1 [Lindquist, Sabine] Hannover Med Sch, Dept Neurol, D-3000 Hannover, Germany.
[Lindquist, Sabine; Karitkina, Diana] Leibniz Inst Neurobiol, Magdeburg, Germany.
[Langnaese, Kristina] Otto Von Guericke Univ, Inst Biochem & Cell Biol, Magdeburg, Germany.
[Posevitz-Fejfar, Anita; Schraven, Burkhart; Lindquist, Jonathan A.] Otto Von Guericke Univ, Inst Mol & Clin Immunol, Magdeburg, Germany.
[Schraven, Burkhart] Helmholtz Ctr Infect Res, Dept Immune Control, Braunschweig, Germany.
[Xavier, Ramnik; Seed, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA.
RP Lindquist, S (reprint author), Hannover Med Sch, Dept Neurol, D-3000 Hannover, Germany.
EM lindquist.sabine@mh-hannover.de
FU German Ministry for Education and Research (Bundesministerium fur
Bildung und Forschung (BMBF)) [FKZ 01ZZ0407]; German Research Society
(DFG) [1031/1-3]
FX B.S. and J.L. are members of the Magdeburg Center for Systems Biology
(MACS) and the SYBILLA consortium [European Union 7th Frame Program].
This work was supported by the German Ministry for Education and
Research (Bundesministerium fur Bildung und Forschung (BMBF)) NBL3
program- FKZ 01ZZ0407, Startup grant to S. L. and in part by the German
Research Society (DFG)[JL 1031/1-3] to J.L. 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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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 6
PY 2011
VL 6
IS 9
AR e23978
DI 10.1371/journal.pone.0023978
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 817QP
UT WOS:000294689200014
PM 21915273
ER
PT J
AU Triantafyllou, C
Wald, LL
Hoge, RD
AF Triantafyllou, Christina
Wald, Lawrence L.
Hoge, Richard D.
TI Echo-Time and Field Strength Dependence of BOLD Reactivity in Veins and
Parenchyma Using Flow-Normalized Hypercapnic Manipulation
SO PLOS ONE
LA English
DT Article
ID CEREBRAL-BLOOD-FLOW; HUMAN MOTOR CORTEX; FUNCTIONAL MRI; 7 T;
OXYGEN-CONSUMPTION; FMRI; ACTIVATION; HUMANS; SIGNAL; EPI
AB While the BOLD (Blood Oxygenation Level Dependent) contrast mechanism has demonstrated excellent sensitivity to neuronal activation, its specificity with regards to differentiating vascular and parenchymal responses has been an area of ongoing concern. By inducing a global increase in Cerebral Blood Flow (CBF), we examined the effect of magnetic field strength and echo-time (TE) on the gradient-echo BOLD response in areas of cortical gray matter and in resolvable veins. In order to define a quantitative index of BOLD reactivity, we measured the percent BOLD response per unit fractional change in global gray matter CBF induced by inhaling carbon dioxide (CO(2)). By normalizing the BOLD response to the underlying CBF change and determining the BOLD response as a function of TE, we calculated the change in R(2)* (Delta R(2)*) per unit fractional flow change; the Flow Relaxation Coefficient, (FRC) for 3T and 1.5T in parenchymal and large vein compartments. The FRC in parenchymal voxels was 1.76 +/- 0.54 fold higher at 3T than at 1.5T and was 2.96 +/- 0.66 and 3.12 +/- 0.76 fold higher for veins than parenchyma at 1.5T and 3T respectively, showing a quantitative measure of the increase in specificity to parenchymal sources at 3T compared to 1.5T. Additionally, the results allow optimization of the TE to prioritize either maximum parenchymal BOLD response or maximum parenchymal specificity. Parenchymal signals peaked at TE values of 62.0 +/- 11.5 ms and 41.5 +/- 7.5 ms for 1.5T and 3T, respectively, while the response in the major veins peaked at shorter TE values; 41.0 +/- 6.9 ms and 21.5 +/- 1.0 ms for 1.5T and 3T. These experiments showed that at 3T, the BOLD CNR in parenchymal voxels exceeded that of 1.5T by a factor of 1.9 +/- 0.4 at the optimal TE for each field.
C1 [Triantafyllou, Christina] MIT, McGovern Inst Brain Res, AA Martinos Imaging Ctr, Cambridge, MA 02139 USA.
[Triantafyllou, Christina; Wald, Lawrence L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA USA.
[Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Hoge, Richard D.] Inst Univ Geriatrie Montreal, Ctr Rech, Unite Neuroimagerie Fonct, Montreal, PQ, Canada.
[Hoge, Richard D.] Univ Montreal, Montreal, PQ, Canada.
RP Triantafyllou, C (reprint author), MIT, McGovern Inst Brain Res, AA Martinos Imaging Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM ctrianta@mit.edu
RI Wald, Lawrence/D-4151-2009
FU National Institutes of Health; National Center for Research Resources
(NCRR); P41 Regional Resource Grant [P41RR14075, RO1RR1453A01]; Mental
Illness and Neuroscience Discovery (MIND) Institute; Canadian National
Science and Engineering Council [355583-2010]; Canadian Institutes of
Health Research [MOP 84378]
FX This research was supported by grants from the National Institutes of
Health, the National Center for Research Resources (NCRR), the P41
Regional Resource Grant P41RR14075, RO1RR1453A01, the Mental Illness and
Neuroscience Discovery (MIND) Institute, the Canadian National Science
and Engineering Council (355583-2010) and the Canadian Institutes of
Health Research (MOP 84378). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 24
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 6
PY 2011
VL 6
IS 9
AR e24519
DI 10.1371/journal.pone.0024519
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 817QP
UT WOS:000294689200052
PM 21915346
ER
PT J
AU Zhao, B
Zou, J
Wang, HF
Johannsen, E
Peng, CW
Quackenbush, J
Mar, JC
Morton, CC
Freedman, ML
Blacklow, SC
Aster, JC
Bernstein, BE
Kieff, E
AF Zhao, Bo
Zou, James
Wang, Hongfang
Johannsen, Eric
Peng, Chih-wen
Quackenbush, John
Mar, Jessica C.
Morton, Cynthia Casson
Freedman, Matthew L.
Blacklow, Stephen C.
Aster, Jon C.
Bernstein, Bradley E.
Kieff, Elliott
TI Epstein-Barr virus exploits intrinsic B-lymphocyte transcription
programs to achieve immortal cell growth
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE leukemia; lymphoma; Notch; development
ID SIGNAL-BINDING-PROTEIN; LONG-RANGE INTERACTION; NUCLEAR ANTIGEN-2;
C-MYC; J-KAPPA; CIS-ELEMENT; PROMOTER; GENOME; FATE; GENE
AB Epstein-Barr virus nuclear antigen 2 (EBNA2) regulation of transcription through the cell transcription factor RBPJ is essential for resting B-lymphocyte (RBL) conversion to immortal lymphoblast cell lines (LCLs). ChIP-seq of EBNA2 and RBPJ sites in LCL DNA found EBNA2 at 5,151 and RBPJ at 10,529 sites. EBNA2 sites were enriched for RBPJ (78%), early B-cell factor (EBF, 39%), RUNX (43%), ETS (39%), NF.B (22%), and PU.1 (22%) motifs. These motif associations were confirmed by LCL RBPJ ChIP-seq finding 72% RBPJ occupancy and Encyclopedia Of DNA Elements LCL ChIP-seq finding EBF, NF.B RELA, and PU. 1 at 54%, 31%, and 17% of EBNA2 sites. EBNA2 and RBPJ were predominantly at intergene and intron sites and only 14% at promoter sites. K-means clustering of EBNA2 site transcription factors identified RELA-ETS, EBF-RUNX, EBF, ETS, RBPJ, and repressive RUNX clusters, which ranked from highest to lowest in H3K4me1 signals and nucleosome depletion, indicative of active chromatin. Surprisingly, although quantitatively less, the same genome sites in RBLs exhibited similar high-level H3K4me1 signals and nucleosome depletion. The EBV genome also had an LMP1 promoter EBF site, which proved critical for EBNA2 activation. LCL HiC data mapped intergenic EBNA2 sites to EBNA2 upregulated genes. FISH and chromatin conformation capture linked EBNA2/RBPJ enhancers 428 kb 5' of MYC to MYC. These data indicate that EBNA2 evolved to target RBL H3K4me1 modified, nucleosome-depleted, nonpromoter sites to drive B-lymphocyte proliferation in primary human infection. The primed RBL program likely supports antigen-induced proliferation.
C1 [Zhao, Bo; Johannsen, Eric; Peng, Chih-wen; Kieff, Elliott] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Zhao, Bo; Johannsen, Eric; Peng, Chih-wen; Kieff, Elliott] Brigham & Womens Hosp, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Wang, Hongfang; Morton, Cynthia Casson; Blacklow, Stephen C.; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Zou, James] Massachusetts Gen Hosp, Sch Engn & Appl Sci, Boston, MA 02114 USA.
[Zou, James; Bernstein, Bradley E.] Massachusetts Gen Hosp, Broad Inst, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Zou, James; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Quackenbush, John; Mar, Jessica C.] Harvard Univ, Dana Farber Canc Inst, Dept Canc Biol, Cambridge, MA 02138 USA.
[Freedman, Matthew L.] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA.
RP Kieff, E (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM ekieff@rics.bwh.harvard.edu
FU National Institutes of Health [R01CA047006, R01CA131354, R01CA085180,
1P50 HG004233, U54 HG004570]; Roadmap Epigenomics Mapping Center [U01
ES017155]
FX We thank Dr. Richard Myers and Encyclopedia of DNA Elements (ENCODE) for
EBF, PU.1, P300, RELA, PolII LCL ChIP-seq data; Drs. Ben Gewurz,
Federica DePalma, Mark Fogg, Ellen Cahir-McFarland, Daniel Portal, and
Micheal Calderwood for discussion; and Andrew Gagne and Pedro Teixeira
for data conversion. This work was supported in part by National
Institutes of Health Grants R01CA047006, R01CA131354, R01CA085180, and
1P50 HG004233, ENCODE Grant U54 HG004570, and Roadmap Epigenomics
Mapping Center U01 ES017155 (to B.E.B.).
NR 49
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Z9 64
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 6
PY 2011
VL 108
IS 36
BP 14902
EP 14907
DI 10.1073/pnas.1108892108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 815QZ
UT WOS:000294543400041
PM 21746931
ER
PT J
AU Wang, HF
Zou, J
Zhao, B
Johannsen, E
Ashworth, T
Wong, HF
Pear, WS
Schug, J
Blacklow, SC
Arnett, KL
Bernstein, BE
Kieff, E
Aster, JC
AF Wang, Hongfang
Zou, James
Zhao, Bo
Johannsen, Eric
Ashworth, Todd
Wong, Hoifung
Pear, Warren S.
Schug, Jonathan
Blacklow, Stephen C.
Arnett, Kelly L.
Bernstein, Bradley E.
Kieff, Elliott
Aster, Jon C.
TI Genome-wide analysis reveals conserved and divergent features of
Notch1/RBPJ binding in human and murine T-lymphoblastic leukemia cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE CSL; lymphoma; transformation
ID TRANSCRIPTION FACTOR-BINDING; BARR-VIRUS EBNA2; BIDIRECTIONAL PROMOTERS;
HUMAN STAF/ZNF143; C-MYC; ACTIVATION; LINEAGE; GROWTH; SPECIFICATION;
CHROMATIN
AB Notch1 regulates gene expression by associating with the DNA-binding factor RBPJ and is oncogenic in murine and human T-cell progenitors. Using ChIP-Seq, we find that in human and murine T-lymphoblastic leukemia (TLL) genomes Notch1 binds preferentially to promoters, to RBPJ binding sites, and near imputed ZNF143, ETS, and RUNX sites. ChIP-Seq confirmed that ZNF143 binds to similar to 40% of Notch1 sites. Notch1/ZNF143 sites are characterized by high Notch1 and ZNF143 signals, frequent cobinding of RBPJ (generally through sites embedded within ZNF143 motifs), strong promoter bias, and relatively low mean levels of activating chromatin marks. RBPJ and ZNF143 binding to DNA is mutually exclusive in vitro, suggesting RBPJ/Notch1 and ZNF143 complexes exchange on these sites in cells. K-means clustering of Notch1 binding sites and associated motifs identified conserved Notch1-RUNX, Notch1-ETS, Notch1-RBPJ, Notch1-ZNF143, and Notch1-ZNF143-ETS clusters with different genomic distributions and levels of chromatin marks. Although Notch1 binds mainly to gene promoters, similar to 75% of direct target genes lack promoter binding and are presumably regulated by enhancers, which were identified near MYC, DTX1, IGF1R, IL7R, and the GIMAP cluster. Human and murine TLL genomes also have many sites that bind only RBPJ. Murine RBPJ-only sites are highly enriched for imputed REST (a DNA-binding transcriptional repressor) sites, whereas human RPBJ-only sites lack REST motifs and are more highly enriched for imputed CREB sites. Thus, there is a conserved network of cis-regulatory factors that interacts with Notch1 to regulate gene expression in TLL cells, as well as unique classes of divergent RBPJ-only sites that also likely regulate transcription.
C1 [Zou, James] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Wang, Hongfang; Ashworth, Todd; Wong, Hoifung; Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Zhao, Bo; Johannsen, Eric; Kieff, Elliott] Brigham & Womens Hosp, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Zhao, Bo; Johannsen, Eric; Kieff, Elliott] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Pear, Warren S.] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA.
[Schug, Jonathan] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Blacklow, Stephen C.; Arnett, Kelly L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Bernstein, Bradley E.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Pathol, Boston, MA 02114 USA.
RP Zou, J (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM jzou@fas.harvard.edu; ekieff@rics.bwh.harvard.edu;
jaster@rics.bwh.harvard.edu
RI Arnett, Kelly/C-4816-2012;
OI Arnett, Kelly/0000-0001-5117-3647
FU National Institutes of Health [P01CA119070, R01CA047006, R01CA131354,
R01 CA085180]; Leukemia and Lymphoma Society; The Howard Hughes Medical
Institute; National Human Genome Research Institute; National Institutes
of Health Epigenome Mapping Centers Consortium [U54 HG004570, U01
ES017155]; National Science Foundation
FX We thank Jeremiah Huang for technical assistance and the University of
Pennsylvania Diabetes and Endocrinology Center for the use of the
Functional Genomics Core (P30-DK19525). This work was supported in part
by National Institutes of Health Grant P01CA119070 and a Specialized
Center of Research grant from the Leukemia and Lymphoma Society (to
J.C.A., S.C.B., and W.S.P.); The Howard Hughes Medical Institute, the
National Human Genome Research Institute, and the National Institutes of
Health Epigenome Mapping Centers Consortium, Encyclopedia Of DNA
Elements Grant U54 HG004570, and Roadmap Epigenomics Grant U01 ES017155
(to B.E.B.); National Institutes of Health Grants R01CA047006,
R01CA131354, and R01 CA085180 (to E.K.); and a National Science
Foundation Graduate Student Fellowship (to J.Z.).
NR 43
TC 102
Z9 103
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 SEP 6
PY 2011
VL 108
IS 36
BP 14908
EP 14913
DI 10.1073/pnas.1109023108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 815QZ
UT WOS:000294543400042
PM 21737748
ER
PT J
AU Jaff, MR
AF Jaff, Michael R.
TI The Breakthrough Balloon for Critical Limb Ischemia?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE drug-coated balloons; peripheral artery disease
ID ARTERIAL-DISEASE; ANGIOPLASTY; BYPASS; METAANALYSIS; THERAPY; TRIAL;
VEIN
C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jaff, Michael R.] Abbott Vasc, Abbott Pk, IL USA.
[Jaff, Michael R.] Boston Sci, Natick, MA USA.
[Jaff, Michael R.] Covidien Corp, Dublin, Ireland.
[Jaff, Michael R.] Cordis Endovasc, Bridgewater, NJ USA.
[Jaff, Michael R.] Medtron Vasc, Santa Rosa, CA USA.
RP Jaff, MR (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM mjaff@partners.org
NR 19
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 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD SEP 6
PY 2011
VL 58
IS 11
BP 1110
EP 1111
DI 10.1016/j.jacc.2011.06.009
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 814KG
UT WOS:000294449200004
PM 21884946
ER
PT J
AU McNamara, DM
Starling, RC
Cooper, LT
Boehmer, JP
Mather, PJ
Janosko, KM
Gorcsan, J
Kip, KE
Dec, GW
AF McNamara, Dennis M.
Starling, Randall C.
Cooper, Leslie T.
Boehmer, John P.
Mather, Paul J.
Janosko, Karen M.
Gorcsan, John, III
Kip, Kevin E.
Dec, G. William
CA IMAC Investigators
TI Clinical and Demographic Predictors of Outcomes in Recent Onset Dilated
Cardiomyopathy Results of the IMAC (Intervention in Myocarditis and
Acute Cardiomyopathy)-2 Study
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiomyopathy; echocardiography; myocardial function; outcomes;
recovery
ID LEFT-VENTRICULAR FUNCTION; CHRONIC HEART-FAILURE; CONTROLLED TRIAL;
TRANSPLANTATION; CARVEDILOL; SOCIETY
AB Objectives We sought to determine clinical and demographic predictors of recovery of left ventricular function for subjects with recent onset cardiomyopathy (ROCM).
Background Although ROCM is a frequent reason for consultation and transplantation referral, its prognosis and natural history on contemporary therapy are unknown.
Methods In the multicenter IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 study, subjects with a left ventricular ejection fraction (LVEF) of <= 0.40, fewer than 6 months of symptom duration, and an evaluation consistent with idiopathic dilated cardiomyopathy or myocarditis were enrolled. LVEF was reassessed at 6 months, and subjects were followed up for 4 years. LVEF and event-free survival were compared by race, sex, and clinical phenotype.
Results The cohort of 373 persons was 38% female and 21% black, with a mean age of 45 +/- 14 years. At entry, 91% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and 82% were receiving beta-blockers, which increased to 92% and 94% at 6 months. LVEF was 0.24 +/- 0.08 at entry and 0.40 +/- 0.12 at 6 months (mean increase: 17 +/- 13 ejection fraction units). Transplant-free survival at 1, 2, and 4 years was 94%, 92%, and 88%, respectively; survival free of heart failure hospitalization was 88%, 82%, and 78%, respectively. In analyses adjusted for sex, baseline LVEF, and blood pressure, LVEF at 6 months was significantly lower in blacks than in nonblacks (p = 0.02). Left ventricular end-diastolic diameter at presentation was the strongest predictor of LVEF at 6 months (p < 0.0001).
Conclusions Outcomes in ROCM are favorable but differ by race. Left ventricular end-diastolic diameter by transthoracic echo at presentation was most predictive of subsequent myocardial recovery. (Genetic Modulation of Left Ventricular Recovery in Recent Onset Cardiomyopathy; NCT00575211) (J Am Coll Cardiol 2011; 58: 1112-8) (C) 2011 by the American College of Cardiology Foundation
C1 [McNamara, Dennis M.; Janosko, Karen M.; Gorcsan, John, III] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA.
[Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA.
[Cooper, Leslie T.] Mayo Clin, Rochester, MN USA.
[Boehmer, John P.] Penn State Hershey Med Ctr, Hershey, PA USA.
[Mather, Paul J.] Thomas Jefferson Univ, Jefferson Med Coll, Jefferson Heart Inst, Philadelphia, PA 19107 USA.
[Kip, Kevin E.] Univ S Florida, Tampa, FL USA.
[Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Starling, Randall C.] Medtronic, Minneapolis, MN USA.
[Starling, Randall C.] Novartis, Basel, Switzerland.
RP McNamara, DM (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, 200 Lothrop St,566 Scaife Hall, Pittsburgh, PA 15213 USA.
EM mcnamaradm@upmc.edu
FU National Heart, Lung, and Blood Institute [HL075038, HL086918, HL69912];
National Institutes of Health, Bethesda, Maryland; Novartis
FX From the Cardiovascular Institute, University of Pittsburgh Medical
Center, Pittsburgh, Pennsylvania; dagger Cleveland Clinic, Cleveland,
Ohio; double dagger Mayo Clinic, Rochester, Minnesota; Penn State
Hershey Medical Center, Hershey, Pennsylvania; vertical bar vertical bar
Jefferson Heart Institute, Jefferson College of Medicine, Philadelphia,
Pennsylvania; University of South Florida, Tampa, Florida; and the #
Massachusetts General Hospital, Boston, Massachusetts. This study was
supported by National Heart, Lung, and Blood Institute contracts
HL075038, HL086918, and HL69912, National Institutes of Health,
Bethesda, Maryland. Dr. Starling is on the advisory board of Medtronic
and Novartis; has received research support from Novartis; and has stock
options in Cardiomens. All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose.
NR 17
TC 68
Z9 75
U1 0
U2 4
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 SEP 6
PY 2011
VL 58
IS 11
BP 1112
EP 1118
DI 10.1016/j.jacc.2011.05.033
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 814KG
UT WOS:000294449200005
PM 21884947
ER
PT J
AU Ng, K
Chen, CC
AF Ng, Kimberly
Chen, Clark C.
TI Oncogene addiction and non-oncogene addiction in glioblastoma therapy
SO CHINESE MEDICAL JOURNAL
LA English
DT Editorial Material
ID ADJUVANT TEMOZOLOMIDE; CANCER-THERAPY; RADIOTHERAPY; KINASE; CELLS; MYC;
TUMORIGENESIS; CONCOMITANT; GLIOMAS; GENOME
C1 [Chen, Clark C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02115 USA.
[Chen, Clark C.] Beth Israel Deaconess Med Ctr, Div Neurosurg, Boston, MA 02215 USA.
RP Chen, CC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Jimmy Fund 620A,44 Binney St, Boston, MA 02115 USA.
EM clarkchen@ucsd.edu
NR 29
TC 1
Z9 1
U1 1
U2 2
PU CHINESE MEDICAL ASSOC
PI BEIJING
PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD SEP 5
PY 2011
VL 124
IS 17
BP 2565
EP 2568
DI 10.3760/cma.j.issn.0366-6999.2011.17.001
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825QO
UT WOS:000295297400001
PM 22040404
ER
PT J
AU Zhu, ZL
Li, GA
AF Zhu, Zhonglin
Li, Guoan
TI Construction of 3D human distal femoral surface models using a 3D
statistical deformable model
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Statistical shape model; Knee; 3D knee model; Fluoroscopic images
ID PROXIMAL FEMUR; SHAPE MODELS; RECONSTRUCTION; VALIDATION; REGISTRATION;
RADIOGRAPHS; KINEMATICS; SYSTEM
AB Construction of 3D geometric surface models of human knee joint is always a challenge in biomedical engineering. This study introduced an improved statistical shape model (SSM) method that only uses 2D images of a joint to predict the 3D joint surface model. The SSM was constructed using 40 distal femur models of human knees. In this paper, a series validation and parametric analysis suggested that more than 25 distal femur models are needed to construct the SSM; each distal femur should be described using at least 3000 nodes in space; and two 2D fluoroscopic images taken in 45 directions should be used for the 3D surface shape prediction. Using this SSM method, ten independent distal femurs from 10 independent living subjects were predicted using their 2D plane fluoroscopic images. The predicted models were compared to their native 3D distal femur models constructed using their 3D MR images. The results demonstrated that using two fluoroscopic images of the knee, the overall difference between the predicted distal femur surface and the MR image-based surface was 0.16 +/- 1.16 mm. These data indicated that the SSM method could be a powerful method for construction of 3D surface geometries of the distal femur. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Zhu, Zhonglin; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA.
[Zhu, Zhonglin] Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, GRJ 1215,55 Fruit St, Boston, MA 02114 USA.
EM gli1@partners.org
FU National Institutes of Health [R01 AR055612]; China Scholarship Council
[2010621146]
FX This study was partially supported by a grant from National Institutes
of Health (R01 AR055612) and a grant from the China Scholarship Council
(2010621146)
NR 32
TC 18
Z9 20
U1 2
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
J9 J BIOMECH
JI J. Biomech.
PD SEP 2
PY 2011
VL 44
IS 13
BP 2362
EP 2368
DI 10.1016/j.jbiomech.2011.07.006
PG 7
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 820VM
UT WOS:000294934200004
PM 21783195
ER
PT J
AU Son, EY
Ichida, JK
Wainger, BJ
Toma, JS
Rafuse, VF
Woolf, CJ
Eggan, K
AF Son, Esther Y.
Ichida, Justin K.
Wainger, Brian J.
Toma, Jeremy S.
Rafuse, Victor F.
Woolf, Clifford J.
Eggan, Kevin
TI Conversion of Mouse and Human Fibroblasts into Functional Spinal Motor
Neurons
SO CELL STEM CELL
LA English
DT Article
ID EMBRYONIC STEM-CELLS; PROGENITOR CELLS; GENE-EXPRESSION; DEFINED
FACTORS; MOTONEURONS; DIFFERENTIATION; NESTIN
AB The mammalian nervous system comprises many distinct neuronal subtypes, each with its own phenotype and differential sensitivity to degenerative disease. Although specific neuronal types can be isolated from rodent embryos or engineered from stem cells for translational studies, transcription factor-mediated reprogramming might provide a more direct route to their generation. Here we report that the forced expression of select transcription factors is sufficient to convert mouse and human fibroblasts into induced motor neurons (iMNs). iMNs displayed a morphology, gene expression signature, electrophysiology, synaptic functionality, in vivo engraftment capacity, and sensitivity to degenerative stimuli similar to those of embryo-derived motor neurons. We show that the converting fibroblasts do not transit through a proliferative neural progenitor state, and thus form bona fide motor neurons via a route distinct from embryonic development. Our findings demonstrate that fibroblasts can be converted directly into a specific differentiated and functional neural subtype, the spinal motor neuron.
C1 [Son, Esther Y.; Ichida, Justin K.; Eggan, Kevin] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Son, Esther Y.; Ichida, Justin K.; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Son, Esther Y.; Eggan, Kevin] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Wainger, Brian J.; Woolf, Clifford J.] Childrens Hosp, Program Neurobiol, Boston, MA 02115 USA.
[Wainger, Brian J.; Woolf, Clifford J.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
[Wainger, Brian J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Toma, Jeremy S.; Rafuse, Victor F.] Dalhousie Univ, Dept Anat & Neurobiol, Halifax, NS B3H 1X5, Canada.
RP Eggan, K (reprint author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM keggan@scrb.harvard.edu
FU Howard Hughes Medical Institute; Harvard Stem Cell Institute;
P2ALS; New York Stem Cell Foundation; NIH [1RC2 NS069395-01,
R01 HD045732-03, 5T32GM007592]; Novartis Institutes for BioMedical
Research; Stan and Fiona Druckenmiller/New York Stem Cell Foundation;
Natural Sciences and Engineering Research Council of Canada
FX We are grateful to A.C. Carter for help with lineage tracing experiments
and E. Kiskinis, S. de Boer, G. Boulting, and J. Rivera-Feliciano for
providing reagents and helpful discussions. We would also like to thank
B. Tilton for assistance with FAGS, K. Harrison for providing the mouse
Hb9 cDNA, N. Atwater for assistance with glia preparation, J. Sandoe and
K. Sandor for help with molecular cloning, K. Koszka for help with mouse
husbandry, and M.Y. Son for help with the diagram in Figure 1. This work
was made possible by support provided by the Howard Hughes Medical
Institute, the Harvard Stem Cell Institute, P2ALS, the New
York Stem Cell Foundation, NIH GO grant 1RC2 NS069395-01, and NIH grant
R01 HD045732-03 to K.E. J.K.I. is supported by the Novartis Institutes
for BioMedical Research and a Stan and Fiona Druckenmiller/New York Stem
Cell Foundation postdoctoral fellowship. B.J.W. is supported by NIH
Training Grant 5T32GM007592. C.J.W. used facilities provided by the
Children's Hospital Boston Intellectual and Developmental Disabilities
Research Center and the NIH. J.S.T. was funded by a Natural Sciences and
Engineering Research Council of Canada graduate student scholarship
award. V.F.R is supported by the Natural Sciences and Engineering
Research Council of Canada. The authors are filing a patent based on the
results reported in this paper. K.E. is a member of the iPierian
scientific advisory board.
NR 29
TC 270
Z9 287
U1 4
U2 32
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 SEP 2
PY 2011
VL 9
IS 3
BP 205
EP 218
DI 10.1016/j.stem.2011.07.014
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 822DN
UT WOS:000295024200008
PM 21852222
ER
PT J
AU Zacharek, SJ
Fillmore, CM
Lau, AN
Gludish, DW
Chou, A
Ho, JWK
Zamponi, R
Gazit, R
Bock, C
Jager, N
Smith, ZD
Kim, TM
Saunders, AH
Wong, J
Lee, JH
Roach, RR
Rossi, DJ
Meissner, A
Gimelbrant, AA
Park, PJ
Kim, CF
AF Zacharek, Sima J.
Fillmore, Christine M.
Lau, Allison N.
Gludish, David W.
Chou, Alan
Ho, Joshua W. K.
Zamponi, Raffaella
Gazit, Roi
Bock, Christoph
Jaeger, Natalie
Smith, Zachary D.
Kim, Tae-min
Saunders, Arven H.
Wong, Janice
Lee, Joo-Hyeon
Roach, Rebecca R.
Rossi, Derrick J.
Meissner, Alex
Gimelbrant, Alexander A.
Park, Peter J.
Kim, Carla F.
TI Lung Stem Cell Self-Renewal Relies on BMI1-Dependent Control of
Expression at Imprinted Loci
SO CELL STEM CELL
LA English
DT Article
ID P57(KIP2)
AB BMI1 is required for the self-renewal of stem cells in many tissues including the lung epithelial stem cells, Bronchioalveolar Stem Cells (BASCs). Imprinted genes, which exhibit expression from only the maternally or paternally inherited allele, are known to regulate developmental processes, but what their role is in adult cells remains a fundamental question. Many imprinted genes were derepressed in Bmi1 knockout mice, and knockdown of Cdkn1c (p57) and other imprinted genes partially rescued the self-renewal defect of Bmi1 mutant lung cells. Expression of p57 and other imprinted genes was required for lung cell self-renewal in culture and correlated with repair of lung epithelial cell injury in vivo. Our data suggest that BM11-dependent regulation of expressed alleles at imprinted loci, distinct from imprinting per se, is required for control of lung stem cells. We anticipate that the regulation and function of imprinted genes is crucial for self-renewal in diverse adult tissue-specific stem cells.
C1 [Zacharek, Sima J.; Fillmore, Christine M.; Lau, Allison N.; Gludish, David W.; Chou, Alan; Zamponi, Raffaella; Saunders, Arven H.; Wong, Janice; Lee, Joo-Hyeon; Roach, Rebecca R.; Kim, Carla F.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
[Gazit, Roi; Rossi, Derrick J.] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Zacharek, Sima J.; Fillmore, Christine M.; Lau, Allison N.; Gludish, David W.; Chou, Alan; Zamponi, Raffaella; Saunders, Arven H.; Wong, Janice; Lee, Joo-Hyeon; Roach, Rebecca R.; Gimelbrant, Alexander A.; Kim, Carla F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Ho, Joshua W. K.; Kim, Tae-min; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Zacharek, Sima J.; Fillmore, Christine M.; Lau, Allison N.; Gludish, David W.; Chou, Alan; Zamponi, Raffaella; Gazit, Roi; Bock, Christoph; Jaeger, Natalie; Smith, Zachary D.; Saunders, Arven H.; Wong, Janice; Lee, Joo-Hyeon; Roach, Rebecca R.; Rossi, Derrick J.; Meissner, Alex; Kim, Carla F.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Ho, Joshua W. K.; Park, Peter J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Bock, Christoph; Jaeger, Natalie; Smith, Zachary D.; Meissner, Alex] Broad Inst, Cambridge, MA 02142 USA.
[Bock, Christoph; Jaeger, Natalie; Smith, Zachary D.; Rossi, Derrick J.; Meissner, Alex] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Bock, Christoph] Max Planck Inst Informat, D-66123 Saarbrucken, Germany.
[Gimelbrant, Alexander A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Kim, CF (reprint author), Childrens Hosp, Stem Cell Program, 300 Longwood Ave, Boston, MA 02115 USA.
EM carla.kim@childrens.harvard.edu
RI Bock, Christoph/B-6723-2008;
OI Bock, Christoph/0000-0001-6091-3088; Jaeger,
Natalie/0000-0002-9589-7580; Gazit, Roi/0000-0002-0548-2147
FU Ladies Auxiliary to the Veterans of Foreign Wars; National Defense
Science Engineering [RO1 HL090136, U01 HL100402]; American Cancer
Society [RSG-08-082-01-MGO]; V Foundation for Cancer Research; Basil
O'Conner March of Dimes Starter Award; Harvard Stem Cell Institute
FX We thank Kim Lab members for discussions; S. Temple, C. Dulac, C. Gregg,
D. Tenen, C. Hetherington, S. Eliedge, J. Luo, N. Solimini, M. Hemann,
C. Meacham, and B. Wilson for reagents and discussions; DFCI and CHB
HemOnc FACS facilities; CHB Molecular Genetics Core facility; R. Bronson
for histology; L. Zon, S. Orkin, and G. Daley for critical reading; and
M. Goodell for sharing unpublished data. This work was supported by the
Ladies Auxiliary to the Veterans of Foreign Wars (C.M.F.), the National
Defense Science & Engineering Graduate Fellowship (A.N.L.), RO1
HL090136, U01 HL100402, American Cancer Society Research Scholar Grant
#RSG-08-082-01-MGO, the V Foundation for Cancer Research, a Basil
O'Conner March of Dimes Starter Award, and the Harvard Stem Cell
Institute (C.F.K.).
NR 5
TC 62
Z9 63
U1 1
U2 9
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 SEP 2
PY 2011
VL 9
IS 3
BP 272
EP 280
DI 10.1016/j.stem.2011.07.007
PG 9
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 822DN
UT WOS:000295024200013
PM 21885022
ER
PT J
AU Sykes, SM
Lane, SW
Bullinger, L
Kalaitzidis, D
Yusuf, R
Saez, B
Ferraro, F
Mercier, F
Singh, H
Brumme, KM
Acharya, SS
Scholl, C
Tothova, Z
Attar, EC
Frohling, S
DePinho, RA
Armstrong, SA
Gilliland, DG
Scadden, DT
AF Sykes, Stephen M.
Lane, Steven W.
Bullinger, Lars
Kalaitzidis, Demetrios
Yusuf, Rushdia
Saez, Borja
Ferraro, Francesca
Mercier, Francois
Singh, Harshabad
Brumme, Kristina M.
Acharya, Sanket S.
Schoell, Claudia
Tothova, Zuzana
Attar, Eyal C.
Froehling, Stefan
DePinho, Ronald A.
Armstrong, Scott A.
Gilliland, D. Gary
Scadden, David T.
TI AKT/FOXO Signaling Enforces Reversible Differentiation Blockade in
Myeloid Leukemias
SO CELL
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; PROTEIN-KINASE-B; FORKHEAD TRANSCRIPTION
FACTOR; JUN ACTIVATION DOMAIN; OXIDATIVE STRESS; AKT PHOSPHORYLATION;
TUMOR SUPPRESSORS; INITIATING CELLS; INSULIN; FOXO
AB AKT activation is associated with many malignancies, where AKT acts, in part, by inhibiting FOXO tumor suppressors. We show a converse role for AKT/FOXOs in acute myeloid leukemia (AML). Rather than decreased FOXO activity, we observed that FOXOs are active in similar to 40% of AML patient samples regardless of genetic subtype. We also observe this activity in human MLL-AF9 leukemia allele-induced AML in mice, where either activation of Akt or compound deletion of FoxO1/3/4 reduced leukemic cell growth, with the latter markedly diminishing leukemia-initiating cell (LIC) function in vivo and improving animal survival. FOXO inhibition resulted in myeloid maturation and subsequent AML cell death. FOXO activation inversely correlated with JNK/c-JUN signaling, and leukemic cells resistant to FOXO inhibition responded to JNK inhibition. These data reveal a molecular role for AKT/FOXO and JNK/c-JUN in maintaining a differentiation blockade that can be targeted to inhibit leukemias with a range of genetic lesions.
C1 [Sykes, Stephen M.; Yusuf, Rushdia; Saez, Borja; Ferraro, Francesca; Mercier, Francois; Singh, Harshabad; Acharya, Sanket S.; Attar, Eyal C.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Sykes, Stephen M.; Yusuf, Rushdia; Saez, Borja; Ferraro, Francesca; Mercier, Francois; Singh, Harshabad; Acharya, Sanket S.; Attar, Eyal C.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Sykes, Stephen M.; Yusuf, Rushdia; Saez, Borja; Ferraro, Francesca; Mercier, Francois; Acharya, Sanket S.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Lane, Steven W.; Kalaitzidis, Demetrios; Brumme, Kristina M.; Armstrong, Scott A.] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston, Boston, MA 02115 USA.
[Tothova, Zuzana] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bullinger, Lars; Schoell, Claudia; Froehling, Stefan] Univ Hosp Ulm, Dept Internal Med 3, D-89081 Ulm, Germany.
[Gilliland, D. Gary] Merck Res Labs, N Wales, PA 19454 USA.
RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
EM dscadden@mgh.harvard.edu
RI Lane, Steven/C-3215-2012
OI Lane, Steven/0000-0002-8050-6209
FU NHLBI [5T32HL007623-24, U01HL100402]; Deutsche Forschungsgemeinschaft
[BU 1339/3-1]; Leukemia and Lymphoma Society; Alex Lemonade Stand
Foundation; Chamber of Industry and Commerce of the Government of Spain;
NCI [U01CA141508, CA140575]; NIH NHLBI [HL097794, HL097748, HL100402];
NIDDK [DK050234]; Ellison Foundation; Harvard Stem Cell Institute
FX We would like to thank Dr. Christine Ragu, Dr. Andrew Lane, and Dr.
David Sykes for critically reading the manuscript and providing valuable
suggestions. We would also like to thank Dr. Kira Gritsman and Dr.
Michael Kharas for donating the MSCV-IRES-GFP-myr-Akt construct. We
would also like to thank M. Milsom for donating the LoxP-STOP-LoxP-hCD34
expression plasmid. S.M.S. was supported by NHLBI 5T32HL007623-24. L.B.
was supported by the Deutsche Forschungsgemeinschaft
(Heisenberg-Stipendium BU 1339/3-1). R.Y. is supported by the Leukemia
and Lymphoma Society and the Alex Lemonade Stand Foundation. B.S. is
supported by the Chamber of Industry and Commerce of the Government of
Spain. F.F. is supported by NHLBI U01HL100402. R.A.D. was supported by
NCI U01CA141508. S.A.A. was supported by the Leukemia and Lymphoma
Society and NCI CA140575. D.T.S. is supported by the NIH NHLBI HL097794,
HL097748, and HL100402 and NIDDK DK050234, the Ellison Foundation, and
the Harvard Stem Cell Institute. D.G.G. is a full-time employee of Merck
& Company, Inc.
NR 39
TC 113
Z9 120
U1 2
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 SEP 2
PY 2011
VL 146
IS 5
BP 697
EP 708
DI 10.1016/j.cell.2011.07.032
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 814SM
UT WOS:000294477500011
PM 21884932
ER
PT J
AU Van Rechem, C
Black, JC
Abbas, T
Allen, A
Rinehart, CA
Yuan, GC
Dutta, A
Whetstine, JR
AF Van Rechem, Capucine
Black, Joshua C.
Abbas, Tarek
Allen, Andrew
Rinehart, Claire A.
Yuan, Guo-Cheng
Dutta, Anindya
Whetstine, Johnathan R.
TI The SKP1-Cul1-F-box and Leucine-rich Repeat Protein 4 (SCF-FbxL4)
Ubiquitin Ligase Regulates Lysine Demethylase 4A (KDM4A)/Jumonji
Domain-containing 2A (JMJD2A) Protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CELL-CYCLE PROGRESSION; MAMMALIAN-CELLS; HISTONE METHYLTRANSFERASE;
DYNAMIC REGULATION; GENE-EXPRESSION; S PHASE; DEGRADATION; REPLICATION;
CHROMATIN; PR-SET7
AB Chromatin-modifying enzymes play a fundamental role in regulating chromatin structure so that DNA replication is spatially and temporally coordinated. For example, the lysine demethylase 4A/Jumonji domain-containing2A(KDM4A/JMJD2A) is tightly regulated during the cell cycle. Overexpression of JMJD2A leads to altered replication timing and faster S phase progression. In this study, we demonstrate that degradation of JMJD2A is regulated by the proteasome. JMJD2A turnover is coordinated through the SKP1-Cul1-F-box ubiquitin ligase complex that contains cullin 1 and the F-box and leucine-rich repeat protein 4 (FbxL4). This complex interacted with JMJD2A. Ubiquitin overexpression restored turnover and blocked the JMJD2A-dependent faster S phase progression in a cullin 1-dependent manner. Furthermore, increased ubiquitin levels decreased JMJD2A occupancy and BrdU incorporation at target sites. This study highlights a finely tuned mechanism for regulating histone demethylase levels and emphasizes the need to tightly regulate chromatin modifiers so that the cell cycle occurs properly.
C1 [Van Rechem, Capucine; Black, Joshua C.; Allen, Andrew; Whetstine, Johnathan R.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA.
[Van Rechem, Capucine; Black, Joshua C.; Allen, Andrew; Whetstine, Johnathan R.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Abbas, Tarek; Dutta, Anindya] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
[Rinehart, Claire A.] Western Kentucky Univ, Dept Biol, Bowling Green, KY 42101 USA.
[Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Whetstine, JR (reprint author), Harvard Univ, Sch Med, Dept Med, Bldg 149,13th St,Rm 7-213, Charlestown, MA 02129 USA.
EM jwhetstine@hms.harvard.edu
RI Black, Joshua/Q-2484-2015; Dutta, Anindya/P-3203-2016;
OI Dutta, Anindya/0000-0002-4319-0073
FU Ellison Medical Foundation [CA059267]; National Institutes of Health
[R01CA60499, R01HG005085]; Jane Coffin Childs Memorial Fund for Medical
Research; NCI National Institutes of Health [KCA140774A]
FX This work was supported, in whole or in part, by the Ellison Medical
Foundation, Howard Goodman Fellowship, and Grant CA059267 (to J. R. W.).
This work was also supported by National Institutes of Health Grants
R01CA60499 (to A. D.) and R01HG005085 (to G. C. Y.). This work has also
been aided by grants from The Jane Coffin Childs Memorial Fund for
Medical Research (to J. C. B.) and from NCI National Institutes of
Health Grant KCA140774A (to T. A.).
NR 35
TC 30
Z9 30
U1 2
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 2
PY 2011
VL 286
IS 35
BP 30462
EP 30470
DI 10.1074/jbc.M111.273508
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 812HT
UT WOS:000294283600025
PM 21757720
ER
PT J
AU Su, XL
Qiu, WH
Gupta, ML
Pereira-Leal, JB
Reck-Peterson, SL
Pellman, D
AF Su, Xiaolei
Qiu, Weihong
Gupta, Mohan L., Jr.
Pereira-Leal, Jose B.
Reck-Peterson, Samara L.
Pellman, David
TI Mechanisms Underlying the Dual-Mode Regulation of Microtubule Dynamics
by Kip3/Kinesin-8
SO MOLECULAR CELL
LA English
DT Article
ID PLUS-END-TRACKING; MITOTIC SPINDLE; YEAST KINESIN-8; FISSION YEAST;
PROTEINS; ANAPHASE; MOTOR; KIP3; CELL; DEPOLYMERIZATION
AB The kinesin-8 family of microtubule motors plays a critical role in microtubule length control in cells. These motors have complex effects on microtubule dynamics: they destabilize growing microtubules yet stabilize shrinking microtubules. The budding yeast kinesin-8, Kip3, accumulates on plus ends of growing but not shrinking microtubules. Here we identify an essential role of the tail domain of Kip3 in mediating both its destabilizing and its stabilizing activities. The Kip3 tail promotes Kip3's accumulation at the plus ends and facilitates the destabilizing effect of Kip3. However, the Kip3 tail also inhibits microtubule shrinkage and is required for promoting microtubule rescue by Kip3. These effects of the tail domain are likely to be mediated by the tubulin- and microtubule-binding activities that we describe. We propose a concentration-dependent model for the coordination of the destabilizing and stabilizing activities of Kip3 and discuss its relevance to cellular microtubule organization.
C1 [Su, Xiaolei; Pellman, David] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Su, Xiaolei; Pellman, David] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Su, Xiaolei; Pellman, David] Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA.
[Su, Xiaolei; Qiu, Weihong; Reck-Peterson, Samara L.; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Gupta, Mohan L., Jr.] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA.
[Pereira-Leal, Jose B.] Inst Gulbenkian Ciencias, P-2781901 Oeiras, Portugal.
RP Pellman, D (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM david_pellman@dfci.harvard.edu
RI Pereira-Leal, Jose/C-5616-2012; Qiu, Weihong/F-6790-2012;
OI Pereira Leal, Jose/0000-0002-3111-7119; Qiu, Weihong/0000-0003-1413-1389
FU Howard Hughes Medical Institute; National Institutes of Health
[GM61345]; HMS/Portugal
FX We thank T. Mitchison, R. King, S. Gilbert, C. Moores, J. Al-Bassam, M.
Betterton, M. Kwon, N. Ganem, S. Godinho, and K. Knouse for discussions
and comments on the work. D.P. was supported by Howard Hughes Medical
Institute and a National Institutes of Health grant (GM61345). J.B.P.-L.
received support from the HMS/Portugal Program in Translational
Research.
NR 36
TC 53
Z9 53
U1 0
U2 3
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 SEP 2
PY 2011
VL 43
IS 5
BP 751
EP 763
DI 10.1016/j.molcel.2011.06.027
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 816JA
UT WOS:000294593300010
PM 21884976
ER
PT J
AU Yanagihara, H
Kobayashi, J
Tateishi, S
Kato, A
Matsuura, S
Tauchi, H
Yamada, K
Takezawa, J
Sugasawa, K
Masutani, C
Hanaoka, F
Weemaes, CM
Mori, T
Zou, L
Komatsu, K
AF Yanagihara, Hiromi
Kobayashi, Junya
Tateishi, Satoshi
Kato, Akihiro
Matsuura, Shinya
Tauchi, Hiroshi
Yamada, Kouichi
Takezawa, Jun
Sugasawa, Kaoru
Masutani, Chikahide
Hanaoka, Fumio
Weemaes, Corry M.
Mori, Toshio
Zou, Lee
Komatsu, Kenshi
TI NBS1 Recruits RAD18 via a RAD6-like Domain and Regulates Pol
eta-Dependent Translesion DNA Synthesis
SO MOLECULAR CELL
LA English
DT Article
ID NIJMEGEN-BREAKAGE-SYNDROME; DEFECTIVE POSTREPLICATION REPAIR;
REPLICATION PROTEIN-A; THYMINE DIMER BYPASS; IN-VIVO MUTATIONS;
POLYMERASE-ETA; HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; CELLS;
COMPLEX
AB Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6 and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are regulated by DNA damage is not fully understood. We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage. Disruption of NBS1 abolished RAD18-dependent PCNA ubiquitination and Pol eta focus formation, leading to elevated UV sensitivity and mutation. Unexpectedly, the RAD18-interacting domain of NBS1, which was mapped to its C terminus, shares structural and functional similarity with the RAD18-interacting domain of RAD6. These domains of NBS1 and RAD6 allow the two proteins to interact with RAD18 homodimers simultaneously and are crucial for Pol eta-dependent UV tolerance. Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis.
C1 [Yanagihara, Hiromi; Kobayashi, Junya; Kato, Akihiro; Komatsu, Kenshi] Kyoto Univ, Ctr Radiat Biol, Kyoto 6068501, Japan.
[Tateishi, Satoshi] Kumamoto Univ, Inst Mol Embryol & Genet, Kumamoto 8620976, Japan.
[Matsuura, Shinya] Hiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
[Tauchi, Hiroshi] Ibaraki Univ, Dept Biol Sci, Ibaraki 3108512, Japan.
[Yamada, Kouichi; Takezawa, Jun] Natl Inst Hlth & Nutr, Div Genet Biochem, Shinjuku Ku, Tokyo 1628636, Japan.
[Sugasawa, Kaoru] Kobe Univ, Biosignal Res Ctr, Org Adv Sci & Technol, Kobe, Hyogo 6578501, Japan.
[Masutani, Chikahide] Nagoya Univ, Environm Med Res Inst, Nagoya, Aichi 4648601, Japan.
[Hanaoka, Fumio] Gakushuin Univ, Fac Sci, Tokyo 1718588, Japan.
[Weemaes, Corry M.] Radboud Univ Nijmegen, Med Ctr, Dept Pediat, NL-6500 HB Nijmegen, Netherlands.
[Mori, Toshio] Nara Med Univ, Radioisotope Res Ctr, Nara 6348521, Japan.
[Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02129 USA.
RP Komatsu, K (reprint author), Kyoto Univ, Ctr Radiat Biol, Kyoto 6068501, Japan.
EM komatsu@house.rbc.kyoto-u.ac.jp
RI Weemaes, C.M.R./L-4747-2015; Masutani, Chikahide/I-6160-2014
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan
FX The authors wish to thank John Petrini, Dik C. van Gent, and Kanji
Ishizaki for providing Delta B/Delta B MEFs, Delta B/Delta B ESCs, and
retrovirus vector pCLXSL-hTERT. We also thank Yukiko Hayuka and Douglas
V.N.P. Oliveira for the excellent technical assistance and discussions.
This work was supported by grants from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan.
NR 46
TC 22
Z9 22
U1 0
U2 10
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 SEP 2
PY 2011
VL 43
IS 5
BP 788
EP 797
DI 10.1016/j.molcel.2011.07.026
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 816JA
UT WOS:000294593300013
PM 21884979
ER
PT J
AU Shen, DX
Li, J
Lepore, JJ
Anderson, TJT
Sinha, S
Lin, AY
Cheng, L
Cohen, ED
Roberts, JD
Dedhar, S
Parmacek, MS
Gerszten, RE
AF Shen, Dongxiao
Li, Jian
Lepore, John J.
Anderson, Thomas J. T.
Sinha, Sumita
Lin, Alexander Y.
Cheng, Lan
Cohen, Ethan David
Roberts, Jesse D., Jr.
Dedhar, Shoukat
Parmacek, Michael S.
Gerszten, Robert E.
TI Aortic Aneurysm Generation in Mice With Targeted Deletion of
Integrin-Linked Kinase in Vascular Smooth Muscle Cells
SO CIRCULATION RESEARCH
LA English
DT Article
DE integrin-linked kinase; smooth muscle cells; aortic aneurysm; actin
cytoskeleton; myocardin-related transcription factor-A
ID PROTEIN-KINASE; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; FOCAL ADHESIONS;
MARFAN-SYNDROME; ANGIOTENSIN-II; ACTIN; ILK; DIFFERENTIATION;
CONTRACTION
AB Rationale: Integrin-linked kinase (ILK) is located at focal adhesions and links the extracellular matrix (ECM) to the actin cytoskeleton via beta 1- and beta 3-integrins. ILK plays a role in the activation of kinases including protein kinase B/Akt and glycogen synthase kinase 3 beta and regulates cell proliferation, motility, and survival.
Objective: To determine the function of ILK in vascular smooth muscle cells (SMCs) in vivo.
Methods and Results: SM22Cre(+)Ilk(Fl/Fl) conditional mutant mice were generated in which the Ilk gene was selectively ablated in SMCs. SM22Cre(+)Ilk(Fl/Fl) conditional mutant mice survive to birth but die in the perinatal period exhibiting multiple vascular pathologies including aneurysmal dilatation of the aorta and patent ductus arteriosus (PDA). Defects in morphogenetic development of the aorta were observed as early as E12.5 in SM22Cre(+)Ilk(Fl/Fl) mutant embryos. By late gestation (E16.5 to 18.5), striking expansion of the thoracic aorta was observed in ILK mutant embryos. Histological analyses revealed that the structural organization of the arterial tunica media is severely disrupted with profound derangements in SMC morphology, cell-cell, and cell-matrix relationships, including disruption of the elastic lamellae. ILK deletion in primary aortic SMCs results in alterations of RhoA/cytoskeletal signaling transduced through aberrant localization of myocardin-related transcription factor (MRTF)-A repressing the transcription and expression of SMC genes, which are required for the maintenance of the contractile SMC phenotype.
Conclusions: These data identify a molecular pathway linking ILK signaling to the contractile SMC gene program. Activation of this pathway is required for morphogenetic development of the aorta and ductus arteriosus during embryonic and postnatal survival. (Circ Res. 2011;109:616-628.)
C1 [Shen, Dongxiao; Sinha, Sumita; Roberts, Jesse D., Jr.; Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Shen, Dongxiao; Anderson, Thomas J. T.; Sinha, Sumita; Lin, Alexander Y.; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
[Li, Jian; Cheng, Lan; Parmacek, Michael S.] Div Cardiovasc Med, Philadelphia, PA USA.
[Li, Jian; Cheng, Lan; Parmacek, Michael S.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Lepore, John J.] GlaxoSmithKline, Metab Pathways Ctr Excellence Drug Discovery, King Of Prussia, PA USA.
[Cohen, Ethan David] Univ Rochester, Sch Med & Dent, Div Endocrinol & Metab, Rochester, NY USA.
[Dedhar, Shoukat] Univ British Columbia, Dept Biochem & Mol Biol, BC Canc Res Ctr, Vancouver, BC V5Z 1M9, Canada.
RP Gerszten, RE (reprint author), Massachusetts Gen Hosp E 8307, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA.
EM rgerszten@partners.org
OI Parmacek, Michael/0000-0003-1449-4665; Anderson,
Thomas/0000-0002-2762-6703
FU National Institutes of Health [R01HL-65584, R01HL-96779, R01HL-094520,
R01HL-102968]
FX We gratefully acknowledge support from the National Institutes of Health
to R.E.G. (R01HL-65584), J.D.R. (R01HL-96779), and R01HL-094520 and
R01HL-102968 to M.S.P. We also acknowledge the excellent technical
assistance of Melinda J. Palma.
NR 51
TC 16
Z9 16
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD SEP 2
PY 2011
VL 109
IS 6
BP 616
EP U78
DI 10.1161/CIRCRESAHA.110.239343
PG 27
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 814SJ
UT WOS:000294477200007
PM 21778429
ER
PT J
AU Patti, JA
AF Patti, John A.
TI Planning for the Future Through Intersociety Collaboration
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 1
TC 1
Z9 1
U1 0
U2 0
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 SEP
PY 2011
VL 8
IS 9
BP 595
EP 595
DI 10.1016/j.jacr.2011.07.012
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KB
UT WOS:000306201700001
PM 21889741
ER
PT J
AU Brown, ML
Guiberteau, MJ
Oates, ME
Thrall, JH
AF Brown, Manuel L.
Guiberteau, Milton J.
Oates, M. Elizabeth
Thrall, James H.
CA ACR ABR Writing Grp
TI ACR/ABR Clinical Statement on Credentialing and Privileging of
Radiologists for Diagnostic Nuclear Medicine, Including Multimodality
Hybrid Imaging
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE ACR; ABR; credentialing; privileging; hybrid imaging; nuclear medicine;
diagnostic radiologists
AB Processes for credentialing physicians and criteria for delineating their practice-specific clinical privileges vary widely across the United States. The ACR and the ABR have jointly developed this resource document to define the requisite credentials for board-certified radiologists to be privileged to practice the full gamut of diagnostic nuclear medicine, including multimodality hybrid imaging. Through its initial certification of radiologists and maintenance of certification programs for practicing certificate holders, the ABR assesses the competence and ensures excellence of its professional diplomates for clinical practice. On the basis of their education, training, and clinical work experience, board-certified radiologists are imminently qualified to supervise, interpret, and report all diagnostic nuclear medicine studies, including radionuclide cardiovascular imaging, and uniquely so for all radionuclide-based, multimodality hybrid examinations. Optimum patient care is best served by an imaging physician with training and expertise in applying, interpreting, and correlating a broad spectrum of these diagnostic technologies.
C1 [Guiberteau, Milton J.] St Joseph Med Ctr, Dept Radiol, Houston, TX 77002 USA.
[Brown, Manuel L.] Henry Ford Hosp, Dept Diagnost Radiol, Detroit, MI 48202 USA.
[Guiberteau, Milton J.] Univ Texas Med Sch, Houston, TX USA.
[Oates, M. Elizabeth] Univ Kentucky, Dept Radiol, Lexington, KY USA.
[Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Guiberteau, MJ (reprint author), St Joseph Med Ctr, Dept Radiol, 1919 LaBranch St, Houston, TX 77002 USA.
EM guiberteau@theabr.org
NR 4
TC 7
Z9 7
U1 0
U2 0
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 SEP
PY 2011
VL 8
IS 9
BP 617
EP 621
DI 10.1016/j.jacr.2011.06.007
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KB
UT WOS:000306201700008
ER
PT J
AU Abujudeh, HH
Govindan, S
Narin, O
Johnson, JO
Thrall, JH
Rosenthal, DI
AF Abujudeh, Hani H.
Govindan, Siddharth
Narin, Ozden
Johnson, Jamlik Omani
Thrall, James H.
Rosenthal, Daniel I.
TI Automatically Inserted Technical Details Improve Radiology Report
Accuracy
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Radiology reports; automation; report headers; report accuracy
AB Purpose: To assess the effect of automatically inserted technical details on the concordance of a radiology report header with the actual procedure performed.
Methods and Materials: The study was IRB approved and informed consent was waived. We obtained radiology report audit data from the hospital's compliance office from the period of January 2005 through December 2009 spanning a total of 20 financial quarters. A "discordance percentage" was defined as the percentage of total studies in which a procedure code change was made during auditing. Using Chi-square analysis we compared discordance percentages between reports with manually inserted technical details (MITD) and automatically inserted technical details (AITD). The second quarter data of 2007 was not included in the analysis as the switch from MITD to AITD occurred during this quarter.
Results: The hospital's compliance office audited 9,110 studies from 2005-2009. Excluding the 564 studies in the second quarter of 2007, we analyzed a total of 8,546 studies, 3,948 with MITD and 4,598 with AITD. The discordance percentage in the MITD group was 3.95% (156/3,948, range per quarter, 1.5-6.1%). The AITD discordance percentage was 1.37% (63/4,598, range per quarter, 0.0-2.6%). A Chi-square analysis determined a statistically significant difference between the 2 groups (P < 0.001).
Conclusion: There was a statistically significant improvement in the concordance of a radiology report header with the performed procedure using automatically inserted technical details compared to manually inserted details.
C1 [Abujudeh, Hani H.; Govindan, Siddharth; Narin, Ozden; Thrall, James H.; Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Johnson, Jamlik Omani] Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA.
RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 213B, Boston, MA 02114 USA.
EM habujudeh@partners.org
NR 10
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD SEP
PY 2011
VL 8
IS 9
BP 635
EP 637
DI 10.1016/j.jacr.2011.02.009
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KB
UT WOS:000306201700012
PM 21889750
ER
PT J
AU Singh, S
Kalra, MK
Thrall, JH
Mahesh, M
AF Singh, Sarabjeet
Kalra, Mannudeep K.
Thrall, James H.
Mahesh, Mahadevappa
TI Pointers for Optimizing Radiation Dose in Chest CT Protocols
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
ID IMAGE QUALITY; REDUCTION; STRATEGIES
C1 [Mahesh, Mahadevappa] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
[Singh, Sarabjeet; Kalra, Mannudeep K.; Thrall, James H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Imaging, Boston, MA USA.
RP Mahesh, M (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, 601 N Caroline St, Baltimore, MD 21287 USA.
EM mmahesh@jhmi.edu
NR 14
TC 7
Z9 8
U1 0
U2 1
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 SEP
PY 2011
VL 8
IS 9
BP 663
EP 665
DI 10.1016/j.jacr.2011.06.009
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 971KB
UT WOS:000306201700019
PM 21889757
ER
PT J
AU Rider, EA
AF Rider, Elizabeth A.
TI Advanced Communication Strategies for Relationship-Centered Care
SO PEDIATRIC ANNALS
LA English
DT Article
ID PHYSICIAN COMMUNICATION; PATIENT SATISFACTION; MEDICAL-CARE; SKILLS;
COMPETENCES; AWARENESS; OUTCOMES; CHILDREN; PARENTS; EMPATHY
C1 [Rider, Elizabeth A.] Childrens Hosp Boston, Inst Professionalism & Eth Practice, Boston, MA USA.
[Rider, Elizabeth A.] Massachusetts Gen Hosp, John D Stoeckle Ctr Primary Care Innovat, Programs Commun Skills, Boston, MA 02114 USA.
[Rider, Elizabeth A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Rider, EA (reprint author), 1153 Ctr St,Suite 31, Boston, MA 02130 USA.
EM eliza-beth_rider@hms.harvard.edu
NR 41
TC 7
Z9 7
U1 0
U2 5
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0090-4481
J9 PEDIATR ANN
JI Pediatr. Annu.
PD SEP
PY 2011
VL 40
IS 9
BP 447
EP 453
DI 10.3928/00904481-20110815-08
PG 7
WC Pediatrics
SC Pediatrics
GA 965BV
UT WOS:000305742000009
PM 21902122
ER
PT J
AU Bergmark, RWJ
Guo, DP
Lin, HW
Faquin, WC
Young, GS
Saxon, KG
AF Bergmark, Regan W. J.
Guo, David P.
Lin, Harrison W.
Faquin, William C.
Young, Geoffrey S.
Saxon, Keith G.
TI Vagal Schwannoma
SO ENT-EAR NOSE & THROAT JOURNAL
LA English
DT Editorial Material
ID VAGUS NERVE
C1 [Bergmark, Regan W. J.; Guo, David P.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Young, Geoffrey S.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Saxon, Keith G.] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA.
RP Bergmark, RWJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA.
NR 5
TC 0
Z9 0
U1 0
U2 1
PU VENDOME GROUP LLC
PI NEW YORK
PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA
SN 0145-5613
J9 ENT-EAR NOSE THROAT
JI ENT-Ear Nose Throat J.
PD SEP
PY 2011
VL 90
IS 9
BP 410
EP 411
PG 2
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 964UE
UT WOS:000305721400005
PM 21938697
ER
PT J
AU Ku, TNK
Naseri, A
Han, Y
Porco, TC
Rutar, T
AF Ku, Tina K.
Naseri, Ayman
Han, Ying
Porco, Travis C.
Rutar, Tina
TI Effect of Timing and Duration of Tamsulosin Exposure on Complications in
Resident-Performed Phacoemulsification
SO OPHTHALMIC SURGERY LASERS & IMAGING
LA English
DT Article
ID FLOPPY-IRIS-SYNDROME; BENIGN PROSTATIC HYPERTROPHY; CATARACT-SURGERY;
CLINICAL FINDINGS; LEARNING-CURVE; IFIS; ASSOCIATION; EPINEPHRINE;
PROPHYLAXIS; MANAGEMENT
AB BACKGROUND AND OBJECTIVES: Tamsulosin can cause intraoperative floppy iris syndrome and increase the risk of phacoemulsification complications. This study evaluated whether the risk of complications was associated with the timing or duration of preoperative tamsulosin exposure.
PATIENTS AND METHODS: The current study was a retrospective review of electronic medical records of resident-performed phacoemulsification surgeries from 1998 to 2008 at a Veterans Administration Hospital. There were 73 eyes with recent tamsulosin exposure (within 30 days preoperatively) and 28 eyes with remote exposure (> 30 days preoperatively but within 3 years of surgery).
RESULTS: There was a trend toward more total complications in recent compared with remote tamsulosin exposure cases (31.5% vs 14.3%, P = .09). A longer duration of tamsulosin use was not statistically associated with an increased risk of total complications.
CONCLUSION: The authors were unable to detect a statistically significant effect of duration of tamsulosin use on the risk of intraoperative complications in phacoemulsification surgery.
C1 [Ku, Tina K.; Naseri, Ayman; Han, Ying; Porco, Travis C.; Rutar, Tina] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
[Naseri, Ayman; Porco, Travis C.] Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA USA.
[Naseri, Ayman] San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA USA.
[Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Prevent Med & Publ Hlth, San Francisco, CA 94143 USA.
RP Rutar, T (reprint author), Univ Calif San Francisco, Dept Ophthalmol, 10 Koret Way,K301, San Francisco, CA 94143 USA.
EM rutart@vision.ucsf.edu
FU Research to Prevent Blindness, New York, New York; University of
California, Bethesda, Maryland [NIH P30]
FX Supported in part by an unrestricted grant from Research to Prevent
Blindness, New York, New York, and by the University of California
Institutional Core Grant For Vision Research (NIH P30), Bethesda,
Maryland.
NR 33
TC 1
Z9 2
U1 0
U2 1
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 1542-8877
J9 OPHTHAL SURG LAS IM
JI Ophthalmic Surg. Lasers Imaging
PD SEP-OCT
PY 2011
VL 42
IS 5
BP 416
EP 422
DI 10.3928/15428877-20110602-01
PG 7
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 959UX
UT WOS:000305342100009
PM 21661666
ER
PT J
AU Impink, BG
Collinger, JL
Boninger, ML
AF Impink, Bradley G.
Collinger, Jennifer L.
Boninger, Michael L.
TI The Effect of Symptoms of Carpal Tunnel Syndrome on Ultrasonographic
Median Nerve Measures Before and After Wheelchair Propulsion
SO PM&R
LA English
DT Article
ID CROSS-SECTIONAL AREA; BODY-MASS INDEX; HIGH-RESOLUTION SONOGRAPHY; UPPER
EXTREMITY; CLINICAL IMPLICATIONS; PARAPLEGIC PATIENTS;
GENERAL-POPULATION; FUNCTIONAL STATUS; CANAL PRESSURE; DIAGNOSIS
AB Objective: To quantify median nerve characteristics before and after strenuous wheelchair propulsion and relate them to symptoms of carpal tunnel syndrome (CTS). We hypothesized that persons with and without symptoms of CTS would have significantly different nerve characteristics at baseline and after propulsion.
Design: A repeated-measures design was used to obtain ultrasound images of the median nerve at 3 levels of the wrist (radius, pisiform, and hamate) before and after wheelchair propulsion. Investigators were blinded to subject history related to CTS.
Setting: The 2007 and 2008 National Veterans Wheelchair Games and the Human Engineering Research Laboratories.
Participants: Fifty-four participants between the ages of 18 and 65 years with a nonprogressive disability who used a manual wheelchair as their primary means of mobility completed this study.
Methods: Participants completed questionnaires regarding demographics and the presence and severity of symptoms of CTS. Ultrasound images of the median nerve were obtained before and after a 15-minute strenuous wheelchair-propulsion task.
Main Outcome Measurements: Baseline values and post-propulsion changes were determined for median nerve cross-sectional area, flattening ratio, and swelling ratio. Differences in median nerve variables between symptomatic and asymptomatic groups were assessed.
Results: No significant differences between symptom groups were identified at baseline; however, persons with symptoms of CTS showed a significantly different percent change from baseline compared with the asymptomatic participants for cross-sectional area at pisiform (P = .014) and flattening ratio at hamate (P = .022), and they showed a strong trend toward a difference in swelling ratio (P = .0502). For each of these variables, the change in the symptomatic group was in the opposite direction of the change in the asymptomatic group.
Conclusions: We found several median nerve responses to wheelchair propulsion associated with symptoms of CTS. These responses occurred even though no baseline ultrasound difference was found based on symptoms. Future research is necessary to determine how propulsion characteristics (ie, force, repetition, and posture) affect the median nerve response. PM R 2011;3:803-810
C1 [Impink, Bradley G.; Collinger, Jennifer L.; Boninger, Michael L.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA.
[Impink, Bradley G.; Collinger, Jennifer L.; Boninger, Michael L.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA.
[Collinger, Jennifer L.; Boninger, Michael L.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA.
RP Boninger, ML (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,151R1-H,Bldg 4,East Wing, Pittsburgh, PA 15206 USA.
EM boninger@pitt.edu
OI Boninger, Michael/0000-0001-6966-919X
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development [B3142C]; National Institute on Disability
and Rehabilitation Research [H133E070024]; National Institutes of Health
[R21HD054529]; National Science Foundation [DGE0333420]
FX This material is based on work supported in part by the Department of
Veterans Affairs, Veterans Health Administration, Office of Research and
Development (B3142C), the National Institute on Disability and
Rehabilitation Research (H133E070024), the National Institutes of Health
(R21HD054529), and the National Science Foundation (DGE0333420). The
findings presented are the result of work supported with resources and
the use of facilities of the Human Engineering Research Laboratories, VA
Pittsburgh Healthcare System. The contents of this publication do not
represent the views of the Department of Veterans Affairs or the United
States Government.
NR 55
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Z9 5
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD SEP
PY 2011
VL 3
IS 9
BP 803
EP 810
DI 10.1016/j.pmrj.2011.04.009
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 961BE
UT WOS:000305438100004
PM 21944298
ER
PT J
AU Plow, EB
Obretenova, SN
Halko, MA
Kenkel, S
Jackson, ML
Pascual-Leone, A
Merabet, LB
AF Plow, Ela B.
Obretenova, Souzana N.
Halko, Mark A.
Kenkel, Sigrid
Jackson, Mary Lou
Pascual-Leone, Alvaro
Merabet, Lotfi B.
TI Combining Visual Rehabilitative Training and Noninvasive Brain
Stimulation to Enhance Visual Function in Patients With Hemianopia: A
Comparative Case Study
SO PM&R
LA English
DT Article
ID VISION RESTORATION THERAPY; TRANSCRANIAL MAGNETIC STIMULATION; MOTOR
CORTEX STIMULATION; CORTICAL STIMULATION; FIELD DEFECTS; STROKE
PATIENTS; IMPAIRMENT QUESTIONNAIRE; HOMONYMOUS HEMIANOPIA; CEREBRAL
BLINDNESS; CRITICAL-APPRAISAL
AB Objective: To standardize a protocol for promoting visual rehabilitative outcomes in post-stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT).
Design: A comparative case study assessing feasibility and safety.
Setting: A controlled laboratory setting.
Patients: Two patients, both with right hemianopia after occipital stroke damage.
Methods and Outcome Measurements: Both patients underwent an identical VRT protocol that lasted 3 months (30 minutes, twice a day, 3 days per week). In patient 1, anodal tDCS was delivered to the occipital cortex during VRT training, whereas in patient 2 sham tDCS with VRT was performed. The primary outcome, visual field border, was defined objectively by using high-resolution perimetry. Secondary outcomes included subjective characterization of visual deficit and functional surveys that assessed performance on activities of daily living. For patient 1, the neural correlates of visual recovery were also investigated, by using functional magnetic resonance imaging.
Results: Delivery of combined tDCS with VRT was feasible and safe. High-resolution perimetry revealed a greater shift in visual field border for patient 1 versus patient 2. Patient 1 also showed greater recovery of function in activities of daily living. Contrary to the expectation, patient 2 perceived greater subjective improvement in visual field despite objective high-resolution perimetry results that indicated otherwise. In patient I., visual function recovery was associated with functional magnetic resonance imaging activity in surviving peri-lesional and bilateral higher-order visual areas.
Conclusions: Results of preliminary case comparisons suggest that occipital cortical tDCS may enhance recovery of visual function associated with concurrent VRT through visual cortical reorganization. Future studies may benefit from incorporating protocol refinements such as those described here, which include global capture of function, control for potential confounds, and investigation of underlying neural substrates of recovery. PM R 2011;3:825-835
C1 [Plow, Ela B.; Obretenova, Souzana N.; Halko, Mark A.; Pascual-Leone, Alvaro; Merabet, Lotfi B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Med Sch, Boston, MA 02215 USA.
[Jackson, Mary Lou; Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Vis Rehabil Ctr, Boston, MA 02114 USA.
[Plow, Ela B.] Cleveland Clin Fdn, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA.
[Kenkel, Sigrid] NovaVis Zentrum Sehtherapie, Ctr Vis Therapy, Magdeburg, Germany.
[Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Inst Guttmann Neurorehabil, Badalona, Spain.
RP Merabet, LB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Med Sch, Boston, MA 02215 USA.
EM lotfi_merabet@meei.harvard.edu
RI Halko, Mark/G-8633-2016
OI Halko, Mark/0000-0002-7427-0789
FU investigator-initiated pilot grant from Novavision VRT Inc.; National
Institutes of Health [K23-EY016131]; investigator-initiated grant from
Novavision; Nexstim; Nova Vision VTR
FX This work was supported by an investigator-initiated pilot grant from
Novavision VRT Inc. and by the National Institutes of Health
(K23-EY016131 to L.B.M.).; 9, Postdoctoral Fellow on
investigator-initiated grant from Novavision; 2A, scientific and medical
advisory board of Novavision VRT Inc, Star lab, Neosync, Neuronix; 7,
grant from Nexstim and equipment support; 9, investigator-initiated
grant from Nova Vision VTR
NR 92
TC 18
Z9 18
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD SEP
PY 2011
VL 3
IS 9
BP 825
EP 835
DI 10.1016/j.pmrj.2011.05.026
PG 11
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 961BE
UT WOS:000305438100007
PM 21944300
ER
PT J
AU Akiyoshi, K
Dziennis, S
Palmateer, J
Ren, XF
Vandenbark, AA
Offner, H
Herson, PS
Hurn, PD
AF Akiyoshi, Kozaburo
Dziennis, Suzan
Palmateer, Julie
Ren, Xuefang
Vandenbark, Arthur A.
Offner, Halina
Herson, Paco S.
Hurn, Patricia D.
TI Recombinant T Cell Receptor Ligands Improve Outcome After Experimental
Cerebral Ischemia
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Article
DE Cerebral ischemia; Cerebral infarction; Inflammation; T lymphocyte;
Immunotherapy; Mouse; Middle cerebral artery occlusion; Stroke
ID EXPERIMENTAL STROKE; MULTIPLE-SCLEROSIS; INFARCT VOLUME; MICE;
ASSOCIATION; ARTHRITIS; SEVERITY
AB A key target for novel stroke therapy is the regulation of post-ischemic inflammatory mechanisms. Recent evidence emphasizes the role of T lymphocytes of differing subtypes in the evolution is ischemic brain damage. We have recently demonstrated the benefit of myelin antigen-specific immunodulatory agents known as recombinant T cell receptor ligands (RTLs) in a standard murine model of focal stroke. The aim of the current study was to extend this initial observation to RTL treatment in a therapeutically relevant timing after middle cerebral artery occlusion (MCAO) and verify functional benefit to complement histological outcome measures. We observed that the administration of mouse-specific RTL551 reduced infarct size and improved sensorimotor outcome when administered within a 3 h post-ischemic therapeutic window. RTL551 treatment reduced cortical, caudate putamen, and total infarct volume as compared to vehicle-treated mice. Using a standard behavioral testing repertoire, we observed that RTL551 reduced sensorimotor impairment 3 days after MCAO. Humanized RTL1000 (HLA-DR2 moiety linked to hMOG-35-55 peptide) also reduced infarct size in HLA-DR2 transgenic mice. These data indicate that this neuroantigen-specific immunomodulatory agent reduces damage when administered in a therapeutically relevant reperfusion timeframe.
C1 [Akiyoshi, Kozaburo; Dziennis, Suzan; Palmateer, Julie; Ren, Xuefang; Offner, Halina; Herson, Paco S.; Hurn, Patricia D.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA.
[Dziennis, Suzan; Ren, Xuefang; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, 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.
[Vandenbark, Arthur A.; Offner, Halina; Hurn, Patricia D.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
RP Herson, PS (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM hersonp@ohsu.edu
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Biomedical Laboratory Research and
Development
FX The authors thank Ms. Kathy Gage, grants and publications writer for the
Department of Anesthesiology and Perioperative Medicine, OHSU, for her
outstanding editorial work in the preparation of this paper. 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 US government.
NR 23
TC 12
Z9 12
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-4483
EI 1868-601X
J9 TRANSL STROKE RES
JI Transl. Stroke Res.
PD SEP
PY 2011
VL 2
IS 3
BP 404
EP 410
DI 10.1007/s12975-011-0085-1
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 943YH
UT WOS:000304163500021
PM 21961027
ER
PT J
AU Thomas, JJ
Keel, PK
Heatherton, TF
AF Thomas, J. J.
Keel, P. K.
Heatherton, T. F.
TI Disordered eating and injuries among adolescent ballet dancers
SO EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY
LA English
DT Article
DE Eating disorder; vomiting; fasting; laxative; injury; ballet dancers
ID ANOREXIA-NERVOSA; MUSCULOSKELETAL INJURIES; STRESS-FRACTURES;
BULIMIA-NERVOSA; STUDENTS; WEIGHT; RISK; DISTURBANCES; POPULATION;
BEHAVIORS
AB BACKGROUND: Ballet dancers are at elevated risk for eating disorders, but the extent to which disordered eating attitudes and behaviors represent a relatively benign adaptation to an environment that values extreme thinness, or a functionally impairing form of psychopathology, has sparked considerable debate. METHOD: To determine whether disordered eating is associated with role impairment in dancers, we evaluated its association with musculoskeletal injuries among 239 adolescent female ballet students. RESULTS: Dance students reported a variety of lifetime disordered eating behaviors to control weight including fasting (29.3%), vomiting (9.6%), and laxative use (4.2%). More than half (52.3%) reported a lifetime history of injury (stress fracture, broken bone, and/or medically treated tendonitis). A greater number of lifetime disordered eating behaviors was associated with a greater number of lifetime injuries (p=0.01). Moreover, vomiting history was associated with greater likelihood of injury (p=0.004) and increased time to recover from injury (median difference=22.8 days, p=0.006). CONCLUSION: Although the direction of causality cannot be determined from this retrospective design, these results suggest that disordered eating is associated with role-relevant functional impairment, even among members of a subculture that values extreme thinness. (Eating Weight Disord. 16: e216-e222, 2011). (C)2011, Editrice Kurtis
C1 [Thomas, J. J.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA.
[Thomas, J. J.] McLean Hosp, Klarman Eating Disorders Ctr, Belmont, MA 02178 USA.
[Thomas, J. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Keel, P. K.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA.
[Heatherton, T. F.] Dartmouth Coll, Dept Psychol & Brain Sci, Hanover, NH 03755 USA.
RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, WAC 816D,15 Parkman St, Boston, MA 02114 USA.
EM jjthomas@partners.org
FU Dartmouth College; Klarman Family Foundation
FX This study was supported by a research grant from Dartmouth College and
a Klarman Family Foundation post-doctoral fellowship to Dr. Thomas.
NR 40
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Z9 8
U1 4
U2 25
PU EDITRICE KURTIS S R L
PI MILAN
PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY
SN 1124-4909
J9 EAT WEIGHT DISORD-ST
JI Eat. Weight Disord.-Stud. Anorex.
PD SEP
PY 2011
VL 16
IS 3
BP E216
EP E222
PG 7
WC Psychiatry
SC Psychiatry
GA 930VR
UT WOS:000303170600012
PM 22290040
ER
PT J
AU Mattei, PL
Johnson, RR
Beachkofsky, TM
Wisco, OJ
Hivnor, CM
Murchland, MR
AF Mattei, Peter L.
Johnson, Ryan R.
Beachkofsky, Thomas M.
Wisco, Oliver J.
Hivnor, Chad M.
Murchland, Michael R.
TI Pruritic rash on trunk
SO JOURNAL OF FAMILY PRACTICE
LA English
DT Editorial Material
ID SYPHILIS; DISEASES
C1 [Johnson, Ryan R.; Hivnor, Chad M.; Murchland, Michael R.] Wilford Hall USAF Med Ctr, Dept Dermatol, Lackland AFB, TX USA.
[Beachkofsky, Thomas M.] Kunsan Air Base, Fighter Squadron 80, Kunsan, South Korea.
[Wisco, Oliver J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wisco, Oliver J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Mattei, PL (reprint author), 641 Bainbridge Dr, Mullica Hill, NJ 08062 USA.
EM peterlmattei@gmail.com
NR 14
TC 0
Z9 0
U1 0
U2 0
PU DOWDEN HEALTH MEDIA
PI MONTVALE
PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA
SN 0094-3509
J9 J FAM PRACTICE
JI J. Fam. Pract.
PD SEP
PY 2011
VL 60
IS 9
BP 539
EP 542
PG 4
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 930IM
UT WOS:000303132300013
PM 21901180
ER
PT J
AU Adler, LA
Shaw, DM
Spencer, TJ
Newcorn, JH
Sitt, DJ
Minerly, AE
Davidow, JV
Faraone, SV
AF Adler, Lenard A.
Shaw, David M.
Spencer, Thomas J.
Newcorn, Jeffrey H.
Sitt, David J.
Minerly, AnaChristina E.
Davidow, Jennifer V.
Faraone, Stephen V.
TI Preliminary Reliability and Validity of a New Time-Sensitive ADHD
Symptom Scale in Adolescents with ADHD
SO POSTGRADUATE MEDICINE
LA English
DT Article
DE ADHD; adolescents; classification; psychometrics; questionnaires
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; MIXED AMPHETAMINE SALTS; ONCE-DAILY ATOMOXETINE; DOUBLE-BLIND;
CHILDREN; ADULTS; METHYLPHENIDATE; COMORBIDITY; TOLERABILITY
AB Objectives: To validate the Time-Sensitive ADHD Symptom Scale (TASS) in the assessment of symptom change during the day in adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 40 participants with ADHD aged 13 to 17 years completed 1 or 2 visits, 1 to 9 weeks apart. The TASS and the ADHD Rating Scale-IV (ADHD-RS-IV) were completed twice at each visit: at the time of the clinic visit (in-clinic assessment) and 2 to 6 hours afterwards (evening assessment). Results: Internal consistency of the TASS was high, with Cronbach's alpha coefficients of 0.91 (in-clinic) and 0.90 (evening) for visit 1, and 0.88 (in-clinic) and 0.86 (evening) for visit 2. Pearson's correlation coefficients between the TASS and ADHD-RS-IV were significant at both visits (P < 0.0001). Stability analyses of the TASS found no significant effect between ratings performed at different visits (P = 0.936), but there was a significant effect of the assessment time within visits (P < 0.0001). There was not a significant visit by assessment time interaction (P = 0.924). Conclusions: The TASS showed high internal consistency and high concurrent validity with the ADHD-RS-IV. Results of this preliminary study indicate that the TASS is a valid and reliable self-report scale for adolescents with ADHD.
C1 [Adler, Lenard A.] NYU Sch Med, Adult ADHD Program, Dept Psychiat, New York, NY 10016 USA.
[Adler, Lenard A.] NYU Sch Med, Adult ADHD Program, Dept Child & Adolescent Psychiat, New York, NY 10016 USA.
[Adler, Lenard A.] NY VA Harbor Healthcare Syst, Psychiat Serv, New York, NY USA.
[Spencer, Thomas J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Spencer, Thomas J.] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA.
[Newcorn, Jeffrey H.] Mt Sinai Sch Med, Div Child & Adolescent Psychiat, New York, NY USA.
[Sitt, David J.] CUNY, Baruch Coll, Dept Psychol, New York, NY 10021 USA.
[Minerly, AnaChristina E.] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA.
[Davidow, Jennifer V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA.
RP Adler, LA (reprint author), NYU Sch Med, Adult ADHD Program, Dept Psychiat, 650 1st Ave,7th Floor, New York, NY 10016 USA.
EM lenard.adler@nyumc.org
OI Newcorn, Jeffrey /0000-0001-8993-9337; Adler, Len/0000-0002-9812-8234;
Faraone, Stephen/0000-0002-9217-3982
FU Shire Development, Inc., Wayne, PA; Bristol-Myers Squibb; Chelsea
Therapeutics; Eli Lilly Company; National Institute of Drug Abuse; Ortho
McNeil/Janssen/Johnson Johnson; Pfizer Inc; Shire Laboratories, Inc.;
NYU School of Medicine; Cephalon; GlaxoSmithKline; Janssen; McNeil
Pharmaceutical; NIMH; Novartis Pharmaceuticals; Ortho-McNeil-Janssen;
National Institutes of Health
FX This study was funded in part by an investigator-initiated research
grant from Shire Development, Inc., Wayne, PA. In compliance with the
Uniform Requirements for Manuscripts Submitted to Biomedical Journals,
established by the International Committee of Medical Journal Editors,
Shire Development, Inc. did not impose any impediment, directly or
indirectly, on the publication of the study's results. Employees of
Shire Development, Inc. were not involved in the study design, in the
collection, analysis, and interpretation of data, in the writing of the
manuscript, or in the decision to submit the manuscript for
publication.; Lenard A. Adler, MD has received grant/research support
from the following sources: Bristol-Myers Squibb, Chelsea Therapeutics,
Eli Lilly & Company, National Institute of Drug Abuse, Ortho
McNeil/Janssen/Johnson & Johnson, Pfizer Inc, and Shire Laboratories,
Inc. Dr. Adler has been a speaker or on the speakers' bureaus for the
following companies: Ortho McNeil/Janssen/Johnson & Johnson and Shire
Laboratories, Inc. Dr. Adler has served on the advisory board for Eli
Lilly & Company, i3 Research, Major League Baseball, Mindsite, Organon,
Ortho McNeil/Janssen/Johnson & Johnson, and Shire Laboratories, Inc. Dr.
Adler has consulted with Epi-Q, INC Research, Major League Baseball
Players Association, and United Biosource Corporation. Dr. Adler has
received royalty payments (as inventor) from the NYU School of Medicine
for license of adult ADHD scales and training materials since 2004.
Thomas J. Spencer, MD has received research support from the following
sources: Cephalon, Eli Lilly & Company, GlaxoSmithKline, Janssen, McNeil
Pharmaceutical, NIMH, Novartis Pharmaceuticals, Pfizer Inc, and Shire
Laboratories, Inc. Dr. Spencer has been a speaker or on a speaker's
bureau for the following pharmaceutical companies: Eli Lilly & Company,
GlaxoSmithKline, Janssen, McNeil Pharmaceutical, Novartis
Pharmaceuticals, and Shire Laboratories, Inc. Dr Spencer has been an
advisor or on an advisory board for the following pharmaceutical
companies: Cephalon, Eli Lilly & Company, GlaxoSmithKline, Janssen,
McNeil Pharmaceutical, Novartis Pharmaceuticals, Pfizer Inc, and Shire
Laboratories, Inc. Jeffrey H. Newcorn, MD has received research support
from the following sources: Eli Lilly & Company, Ortho-McNeil-Janssen,
and Shire Laboratories, Inc. Dr Newcorn has consulted with Eli Lilly &
Company, Ortho-McNeil-Janssen, and Shire Laboratories, Inc. Dr. Newcorn
has served on the advisory board for Eli Lilly & Company,
Ortho-McNeil-Janssen, Schering-Plough, and Shire Laboratories, Inc.
Stephen V. Faraone, PhD has consulted with, has served the advisory
board, or has been a speaker for the following pharmaceutical companies:
Eli Lilly & Company, Janssen, Novartis, Ortho-McNeil, McNeil, Pfizer
Inc, and Shire Laboratories, Inc. Dr. Faraone has received research
support from Eli Lilly & Company, the National Institutes of Health,
Pfizer Inc, and Shire Laboratories, Inc. David M. Shaw, BA, David J.
Sitt, PsyD, AnaChristina E. Minerly, PhD, and Jennifer V. Davidow, BS
disclose no conflicts of interest.
NR 41
TC 1
Z9 1
U1 2
U2 3
PU JTE MULTIMEDIA
PI BERWYN
PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA
SN 0032-5481
J9 POSTGRAD MED
JI Postgrad. Med.
PD SEP
PY 2011
VL 123
IS 5
BP 7
EP 13
DI 10.3810/pgm.2011.09.2455
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 934CQ
UT WOS:000303419900001
PM 21904082
ER
PT J
AU Spencer, TJ
Faraone, SV
Surman, CBH
Petty, C
Clarke, A
Batchelder, H
Wozniak, J
Biederman, J
AF Spencer, Thomas J.
Faraone, Stephen V.
Surman, Craig B. H.
Petty, Carter
Clarke, Allison
Batchelder, Holly
Wozniak, Janet
Biederman, Joseph
TI Toward Defining Deficient Emotional Self-Regulation in Children with
Attention-Deficit/Hyperactivity Disorder Using the Child Behavior
Checklist: A Controlled Study
SO POSTGRADUATE MEDICINE
LA English
DT Article
DE attention-deficit/hyperactivity disorder; affective symptoms; severity
of illness index; youth; emotional self-regulation
ID PEDIATRIC BIPOLAR DISORDER; CHARACTERISTIC CURVE ANALYSIS; HYPERACTIVITY
DISORDER; SOCIAL-ADJUSTMENT; ADHD; CBCL; PROFILE; SCALES; ADOLESCENTS;
PHENOTYPE
AB Objective: Deficient emotional self-regulation (DESR) is characterized by deficits in self-regulating the physiological arousal caused by strong emotions. We examined whether a unique profile of the Child Behavior Checklist (CBCL) would help identify DESR in children with attention-deficit/hyperactivity disorder (ADHD). Methods: Subjects included 197 children with ADHD and 224 children without ADHD. We defined DESR if a child had an aggregate cut-off score of > 180 but < 210 on the Anxiety/Depression, Aggression, and Attention scales of the CBCL (CBCL-DESR). This profile was selected because of: 1) its conceptual congruence with the clinical concept of DESR; and 2) because its extreme (> 210) form has been previously associated with severe forms of mood and behavioral dysregulation in children with ADHD. All subjects were comprehensively assessed with structured diagnostic interviews and a wide range of functional measures. Results: Forty-four percent of children with ADHD had a positive CBCL-DESR profile versus 2% of controls (P < 0.001). The CBCL-DESR profile was associated with elevated rates of anxiety and disruptive behavior disorders, as well as significantly more impairments in emotional and interpersonal functioning. Conclusions: The CBCL-DESR profile helped identify a subgroup of children with ADHD who had a psychopathological and functional profile consistent with the clinical concept of DESR.
C1 [Spencer, Thomas J.; Biederman, Joseph] Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA.
[Spencer, Thomas J.; Biederman, Joseph] Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA.
[Spencer, Thomas J.; Surman, Craig B. H.; Wozniak, Janet; Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA.
[Surman, Craig B. H.] Massachusetts Gen Hosp, Adult ADHD Program, Boston, MA 02114 USA.
[Petty, Carter; Clarke, Allison; Batchelder, Holly] Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA.
[Wozniak, Janet] Massachusetts Gen Hosp, Pediat Bipolar Disorder Res Program, Boston, MA 02114 USA.
RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, 55 Fruit St,YAW6A, Boston, MA 02114 USA.
EM tspencer@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU National Institutes of Health [R01 HD36317 R01 MH50657]; Shire
Pharmaceuticals; Pediatric Psychopharmacology Research Council;
Cephalon; Eli Lilly Company; GlaxoSmithKline; Janssen Pharmaceutical;
McNeil Pharmaceutical; Novartis Pharmaceuticals; Pfizer Inc; Shire
Laboratories, Inc.; National Institute of Mental Health; Shire; Janssen;
McNeil; Novartis; Abbott; Alza; Hilda and Preston Davis Foundation;
Merck and Co., Inc.; New River; Organon; Takeda; Janssen-Ortho; Johnson
and Johnson; Sepracor; Elminda; NextWave Pharmaceuticals; MGH Psychiatry
Academy; AstraZeneca; Fundacion Dr. Manuel Camelo A.C. in Monterrey
Mexico; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany);
Spanish Child Psychiatry Association; Bristol-Myers Squibb; Celltech;
Esai; Forest; Gliatech; NARSAD; NIDA; NICHD; Noven; Neurosearch; Otsuka;
Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma, Inc.;
Wyeth; adult ADHD scales
FX This manuscript was supported in part by grants to Joseph Biederman, MD
from the National Institutes of Health (R01 HD36317 R01 MH50657) and to
Thomas J. Spencer, MD from Shire Pharmaceuticals and the Pediatric
Psychopharmacology Research Council Fund. The study sponsors had no role
in the study design or conduct, collection, management, preparation, or
analysis of the data.; Thomas J. Spencer, MD has received research
support from, has been a speaker for or on a speakers' bureau for, or
has been an advisor or on an advisory board of the following sources:
Cephalon, Eli Lilly & Company, GlaxoSmithKline, Janssen Pharmaceutical,
McNeil Pharmaceutical, Novartis Pharmaceuticals, Pfizer Inc, Shire
Laboratories, Inc., the National Institute of Mental Health, and has
received royalties on adult ADHD scales (research support). In the past
year, Stephen V. Faraone, PhD received consulting fees and was on
advisory boards for Shire Development, and received research support
from Shire and the National Institutes of Health (NIH). In previous
years, he received consulting fees or was on advisory boards or
participated in CME education programs sponsored by: Eli Lilly &
Company, Janssen, McNeil, Novartis, Pfizer Inc, and Shire. In previous
years, he received research support from Eli Lilly & Company, the NIH,
Pfizer Inc, and Shire. Dr. Faraone receives royalties from a book
published by Guilford Press, Straight Talk About Your Child's Mental
Health. Craig B. H. Surman, MD has received research support from
Abbott, Alza, Cephalon, Eli Lilly & Company, the Hilda and Preston Davis
Foundation, McNeil, Merck and Co., Inc., New River, the NIH, Organon,
Pfizer Inc, Shire, and Takeda; has received support from Janssen-Ortho,
McNeil, Novartis, and Shire for speaking and other educational
activities; and has been a consultant/advisor for McNeil, Shire, and
Takeda. Dr. Surman has also received honoraria from Reed Medical
Education (a logistics collaborator for the MGH Psychiatry Academy).
Commercial entities supporting the MGH Psychiatry Academy are listed on
the Academy's Web site (www.mghcme.org). Janet Wozniak, MD is the author
of a book published by Bantam Books, Is Your Child Bipolar. She is a
speaker for Primedia/MGH Psychiatry Academy. She has received research
support from Janssen, Johnson and Johnson, McNeil, and Shire. Her
spouse, John Winkelman MD, PhD, is on the speakers' bureaus for
sanofi-aventis and Sepracor. He is a consultant or on advisory boards
for Covance, GlaxoSmithKline, Impax Laboratories, Luitpold
Pharmaceuticals, Neurogen, Pfizer Inc, UCB, and Zeo, Inc. He has
received research support from GlaxoSmithKline and Sepracor. Joseph
Biederman, MD is currently receiving research support from the following
sources: Elminda, Janssen, McNeil, NextWave Pharmaceuticals, and Shire.
In 2011, Dr. Biederman gave a single unpaid talk for Juste
Pharmaceutical Spain, and received honoraria from the MGH Psychiatry
Academy for a tuition-funded CME course. He also received an honorarium
from Cambridge University Press for a chapter publication. Dr. Biederman
received departmental royalties from a copyrighted rating scale used for
ADHD diagnoses, paid by Eli Lilly and Company, Shire, and AstraZeneca;
these royalties are paid to the Department of Psychiatry at MGH. In
2010, Dr. Joseph Biederman received a speaker's fee from a single talk
given at Fundacion Dr. Manuel Camelo A.C. in Monterrey Mexico. Dr.
Biederman provided single consultations for Shionogi Pharma, Inc. and
Cipher Pharmaceuticals, Inc.; the honoraria for these consultations were
paid to the Department of Psychiatry at the MGH. Dr. Biederman received
honoraria from the MGH Psychiatry Academy for a tuition-funded CME
course. In 2009, Dr. Joseph Biederman received a speaker's fee from the
following sources: Fundacion Areces (Spain), Medice Pharmaceuticals
(Germany), and the Spanish Child Psychiatry Association. In previous
years, Dr.; Biederman received research support, consultation fees, or
speaker's fees for/from the following additional sources: Abbott, Alza,
AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly and
Company, Esai, Forest, GlaxoSmithKline, Gliatech, Janssen, McNeil, Merck
and Co., Inc., NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven,
Neurosearch, Organon, Otsuka, Pfizer Inc, Pharmacia, The Prechter
Foundation, Shire, The Stanley Foundation, UCB Pharma, Inc., and Wyeth.
Carter Petty, MA, Allison Clarke, BA, and Holly Batchelder, BS disclose
no conflicts of interest.
NR 35
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Z9 33
U1 2
U2 22
PU JTE MULTIMEDIA
PI BERWYN
PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA
SN 0032-5481
J9 POSTGRAD MED
JI Postgrad. Med.
PD SEP
PY 2011
VL 123
IS 5
BP 50
EP 59
DI 10.3810/pgm.2011.09.2459
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 934CQ
UT WOS:000303419900005
PM 21904086
ER
PT J
AU Dubovsky, SL
Leonard, K
Griswold, K
Daurignac, E
Hewitt, B
Fox, C
Seymour, D
Dubovsky, AN
DeGruy, F
AF Dubovsky, Steven L.
Leonard, Kenneth
Griswold, Kim
Daurignac, Elsa
Hewitt, Burlleen
Fox, Chester
Seymour, Deborah
Dubovsky, Amelia N.
DeGruy, Frank
TI Bipolar Disorder is Common in Depressed Primary Care Patients
SO POSTGRADUATE MEDICINE
LA English
DT Article
DE depression; bipolar disorder; primary care; antidepressant; mood
stabilizer; diagnosis
ID COMORBIDITY SURVEY REPLICATION; SPECTRUM DISORDER; ANTIDEPRESSANT
TREATMENT; PSYCHIATRIC-DISORDERS; VALIDITY; QUESTIONNAIRE; PREVALENCE;
VALIDATION; DIAGNOSIS; INTERVIEW
AB Objective: To examine the prevalence and treatment of typical and subsyndromal bipolar disorder (BD) in depressed primary care patients. Methods: Patients with a diagnosis of a mood disorder being treated with antidepressants in 2 academic family practice clinics underwent a structured diagnostic interview (Mini International Neuropsychiatric Inventory) for manic and hypomanic symptoms. Results: Of 58 patients evaluated, 19% met full criteria for bipolar 1 disorder and 8.6% for bipolar 11 disorder; 31% had subsyndromal BD (ie, persistent elation or irritability accompanied by additional symptoms of hypomania but not enough symptoms to meet full criteria for bipolar I or 11 disorder). Only 5 patients with BD were receiving mood stabilizers, which had not been instituted in any patient by the primary care physician. Conclusions: The high prevalence of patients meeting full criteria for BD and the low rate of identification of BD in primary care patients are consistent with estimates using self-administered questionnaires, but the interview revealed a substantial additional population that could be considered to have subsyndromal BD. Because subsyndromal forms of BD are associated with significant impairment and comorbidity as well as progression to frank BD, recognition of both full and subthreshold BD in primary care practice should be improved.
C1 [Dubovsky, Steven L.; Leonard, Kenneth] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA.
[DeGruy, Frank] Univ Colorado, Dept Family Med, Denver, CO 80202 USA.
[Hewitt, Burlleen] Radiant Res, Denver, CO USA.
[Dubovsky, Amelia N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Dubovsky, SL (reprint author), 462 Grider St,Room 1182, Buffalo, NY 14215 USA.
EM dubovsky@buffalo.edu
FU Pfizer Inc.; Eli Lilly; Otsuka; Sumitomo; National Institutes of Health
FX Steven L. Dubovsky, MD receives research support from Pfizer Inc., Eli
Lilly, Otsuka, and Sumitomo. Kenneth Leonard, PhD receives research
support from the National Institutes of Health. Burlleen Hewitt, BA is
an employee of Radiant Research, which receives grant support from
multiple manufacturers. Kim Griswold, MD, Elsa Daurignac, PhD, Chester
Fox, MD, Deborah Seymour, PhD, Amelia N. Dubovsky, MD, and Frank DeGruy,
MD disclose no conflicts of interest.
NR 30
TC 7
Z9 7
U1 2
U2 4
PU JTE MULTIMEDIA
PI BERWYN
PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA
SN 0032-5481
J9 POSTGRAD MED
JI Postgrad. Med.
PD SEP
PY 2011
VL 123
IS 5
BP 129
EP 133
DI 10.3810/pgm.2011.09.2468
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 934CQ
UT WOS:000303419900014
PM 21904095
ER
PT J
AU Mendez, MF
AF Mendez, Mario F.
TI Malapropisms, or "The Archie Bunker Syndrome," and Frontotemporal
Dementia
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Letter
C1 [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
[Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Mendez, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
EM mmendez@UCLA.edu
NR 5
TC 0
Z9 0
U1 0
U2 0
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 FAL
PY 2011
VL 23
IS 4
BP E3
EP E3
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 924XS
UT WOS:000302725200003
ER
PT J
AU Marques, L
Weingarden, HM
LeBlanc, NJ
Siev, J
Wilhelm, S
AF Marques, Luana
Weingarden, Hilary M.
LeBlanc, Nicole J.
Siev, Jedidiah
Wilhelm, Sabine
TI The relationship between perceived social support and severity of body
dysmorphic disorder symptoms: the role of gender
SO REVISTA BRASILEIRA DE PSIQUIATRIA
LA English
DT Article
DE Body dysmorphic disorders; Signs and symptoms; Gender; Social support
ID OBSESSIVE-COMPULSIVE DISORDER; STRESS SCALES DASS; QUALITY-OF-LIFE;
FOLLOW-UP; PSYCHOMETRIC PROPERTIES; FUNCTIONAL IMPAIRMENT;
CLINICAL-FEATURES; ADOLESCENT GIRLS; 200 INDIVIDUALS; DEPRESSION
AB Objective: Whether social support is associated with severity of body dysmorphic symptoms is unknown. To address this gap in the literature, the present study aims to examine the association between three domains of perceived social support (i.e., family, friends, and significant others) and severity of body dysmorphic disorder symptoms. Method: Participants (N = 400) with symptoms consistent with diagnosis of body dysmorphic disorder completed measures of symptomatology and social support via the internet. Results: More perceived social support from friends and significant others was associated with less severe body dysmorphic disorder symptoms for males, and more perceived social support from family and friends was associated with less severe body dysmorphic disorder symptoms among females. Additionally, gender moderated the association between perceived social support from significant others and symptom severity, such that perceived social support from a significant other was significantly negatively associated with body dysmorphic symptom severity in males, but not females. Conclusion: The present study implicates social support as an important area of future body dysmorphic disorder research.
C1 [Marques, Luana; Siev, Jedidiah; Wilhelm, Sabine] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Marques, Luana; Siev, Jedidiah] Harvard Univ, Sch Med, Boston, MA USA.
[Weingarden, Hilary M.; LeBlanc, Nicole J.; Wilhelm, Sabine] Massachusetts Gen Hosp, Obsess Compuls & Related Disorders Clin, Boston, MA 02114 USA.
[Weingarden, Hilary M.; LeBlanc, Nicole J.] Tufts Univ, Boston, MA 02111 USA.
RP Marques, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA.
EM lmarques@partners.org
NR 43
TC 3
Z9 3
U1 1
U2 12
PU ASSOC BRASILEIRA PSIQUIATRIA
PI SAO PAULO
PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO,
SP 04039-032 A, BRAZIL
SN 1516-4446
J9 REV BRAS PSIQUIATR
JI Rev. Bras. Psiquiatr.
PD SEP
PY 2011
VL 33
IS 3
BP 238
EP 244
PG 7
WC Psychiatry
SC Psychiatry
GA 908YF
UT WOS:000301528300006
PM 21971776
ER
PT J
AU Dewanwala, A
Chittenden, A
Rosenblatt, M
Mercado, R
Garber, JE
Syngal, S
Stoffel, EM
AF Dewanwala, Akriti
Chittenden, Anu
Rosenblatt, Margery
Mercado, Rowena
Garber, Judy E.
Syngal, Sapna
Stoffel, Elena M.
TI Attitudes toward childbearing and prenatal testing in individuals
undergoing genetic testing for Lynch Syndrome
SO FAMILIAL CANCER
LA English
DT Article
DE Lynch syndrome; Prenatal testing; Preimplantation genetic diagnosis;
Family; Genetic testing; Genetic counseling
ID NONPOLYPOSIS COLORECTAL-CANCER; FAMILIAL ADENOMATOUS POLYPOSIS;
COMPLEMENTARY MEDICINE USE; LI-FRAUMENI-SYNDROME; OVARIAN-CANCER;
HEREDITARY RETINOBLASTOMA; PREDISPOSITION SYNDROMES; MUTATION CARRIERS;
CYSTIC-FIBROSIS; DIAGNOSIS
AB To examine attitudes toward childbearing and prenatal genetic testing among individuals at risk for Lynch Syndrome (LS), the most common type of hereditary colorectal cancer. Individuals undergoing clinical genetic testing for mismatch repair (MMR) gene mutations completed written questionnaires before and after testing. 161 of 192 (84%) eligible individuals participated in the study. Mean age was 46 years (range 20-75), 71% were female, 53% had a personal diagnosis of cancer, and 68% had children. Eighty percent worried about their children's risk for developing cancer; however only 9% reported their decision to have children was affected by their family history of cancer. When asked whether providing prenatal testing to carriers of MMR gene mutations was ethical, 66% (86/ 130) of respondents agreed/ strongly agreed, 25% (32) were neutral and 9% (12) disagreed/ strongly disagreed. Of 48 individuals planning to have children in the future, 57% (27) intended to have children regardless of their genetic test result. If found to carry a MMR gene mutation that confirmed LS, 42% (20) would consider prenatal testing for a future pregnancy and 20% (7/ 35) of women would consider having children earlier in order to have prophylactic surgery to reduce their risk for gynecologic cancers. Individuals undergoing genetic testing for LS may utilize test results to make reproductive decisions. Clinicians should be prepared to discuss options of reproductive genetic technologies during counseling of LS patients of childbearing age.
C1 [Syngal, Sapna; Stoffel, Elena M.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Dewanwala, Akriti; Chittenden, Anu; Rosenblatt, Margery; Mercado, Rowena; Garber, Judy E.; Syngal, Sapna; Stoffel, Elena M.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA.
[Garber, Judy E.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Garber, Judy E.; Syngal, Sapna; Stoffel, Elena M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Stoffel, EM (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA.
EM estoffel@partners.org
FU National Cancer Institute [K07 CA 120448-04, K24 CA 113433]; American
Recovery and Reinvestment Act [3K07CA120448-03S1]; American College of
Gastroenterology Junior Faculty
FX The authors would like to thank Bridget Neville, MS, for her assistance
with statistical programming. The authors acknowledge the following
sources of grant support: National Cancer Institute K07 CA 120448-04
(Dr. Stoffel), American Recovery and Reinvestment Act 3K07CA120448-03S1
(Dr. Stoffel), American College of Gastroenterology Junior Faculty Award
(2004-Dr. Stoffel), National Cancer Institute K24 CA 113433 (Dr.
Syngal).
NR 53
TC 7
Z9 7
U1 1
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9600
J9 FAM CANCER
JI Fam. Cancer
PD SEP
PY 2011
VL 10
IS 3
SI SI
BP 549
EP 556
DI 10.1007/s10689-011-9448-8
PG 8
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 908RI
UT WOS:000301507400019
PM 21567236
ER
PT J
AU Kunik, M
AF Kunik, Mark
TI CBT for older adults with chronic medical illnesses and psychological
comorbidity
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Meeting Abstract
C1 [Kunik, Mark] Houston Vet Affairs Med Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD SEP
PY 2011
VL 23
SU 1
BP S68
EP S69
PG 2
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
Psychology
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA 889UX
UT WOS:000300101100114
ER
PT J
AU Mintzer, J
Brawman-Mintzer, O
Nietert, P
Vankirk, K
Longmire, CF
Jones, E
Stuckey, M
AF Mintzer, Jacobo
Brawman-Mintzer, O.
Nietert, P.
Vankirk, K.
Longmire, C. Flynn
Jones, E.
Stuckey, M.
TI Escitalopram in the treatment of non-depressed elderly patients with
generalized anxiety disorder
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Meeting Abstract
ID CONTROLLED-TRIAL
C1 [Mintzer, Jacobo; Brawman-Mintzer, O.; Nietert, P.; Jones, E.; Stuckey, M.] Ralph Johnson VA Med Ctr, N Charleston, SC USA.
[Mintzer, Jacobo; Brawman-Mintzer, O.; Nietert, P.; Vankirk, K.; Longmire, C. Flynn] Med Univ S Carolina, N Charleston, SC USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD SEP
PY 2011
VL 23
SU 1
BP S305
EP S306
PG 2
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
Psychology
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA 889UX
UT WOS:000300101100410
ER
PT J
AU Belanger, E
Henry, FP
Vallee, R
Randolph, MA
Kochevar, IE
Winograd, JM
Lin, CP
Cote, D
AF Belanger, E.
Henry, F. P.
Vallee, R.
Randolph, M. A.
Kochevar, I. E.
Winograd, J. M.
Lin, C. P.
Cote, D.
TI In vivo evaluation of demyelination and remyelination in a nerve crush
injury model
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID STOKES-RAMAN SCATTERING; MICROSCOPY; MYELIN; DEGENERATION; TISSUE;
MECHANISMS; CONTRAST; BIOLOGY
AB Nerves of the peripheral nervous system have, to some extent, the ability to regenerate after injury, particularly in instances of crush or contusion injuries. After a controlled crush injury of the rat sciatic nerve, demyelination and remyelination are followed with functional assessments and imaged both ex vivo and in vivo over the course of 4 weeks with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy. A new procedure compatible with live animal imaging is developed for performing histomorphometry of myelinated axons. This allows quantification of demyelination proximal and remyelination distal to the crush site ex vivo and in vivo respectively. (C) 2011 Optical Society of America
C1 [Belanger, E.; Vallee, R.; Cote, D.] Univ Laval, CRULRG, Quebec City, PQ G1J 2G3, Canada.
[Belanger, E.; Vallee, R.; Cote, D.] Univ Laval, COPL, Quebec City, PQ G1V 0A6, Canada.
[Henry, F. P.; Randolph, M. A.; Kochevar, I. E.; Winograd, J. M.; Lin, C. P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Belanger, E (reprint author), Univ Laval, CRULRG, Quebec City, PQ G1J 2G3, Canada.
EM daniel.cote@crulrg.ulaval.ca
OI Henry, Francis P./0000-0003-4170-7806
FU Plastic Surgery Educational Foundation (PSEF),; Bullock-Wellman
Fellowship; Canada Research Chair (CRC) program; National Science and
Engineering Research Council of Canada (NSERC); Multiple Sclerosis
Society of Canada (MSSOC)
FX The authors gratefully acknowledge funding from the Plastic Surgery
Educational Foundation (PSEF), Basic Science Grant 2007 and the
Bullock-Wellman Fellowship, the Canada Research Chair (CRC) program and
National Science and Engineering Research Council of Canada (NSERC).
This investigation was supported by a Dr. William J. McIlroy Studentship
from the Multiple Sclerosis Society of Canada (MSSOC) awarded to E.
Belanger.
NR 24
TC 32
Z9 32
U1 0
U2 9
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 SEP 1
PY 2011
VL 2
IS 9
BP 2698
EP 2708
PG 11
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 886VY
UT WOS:000299883200024
PM 22091449
ER
PT J
AU Kraker, J
Zivkovic, SA
AF Kraker, Jessica
Zivkovic, Sasa A.
TI Autoimmune Neuromuscular Disorders
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Article
DE Autoimmune; neuromuscular; neuropathy; myositis; myasthenia gravis;
treatment
ID INFLAMMATORY-DEMYELINATING POLYNEUROPATHY; EATON-MYASTHENIC-SYNDROME;
GUILLAIN-BARRE-SYNDROME; QUALITY STANDARDS SUBCOMMITTEE; MULTIFOCAL
MOTOR NEUROPATHY; LONG-TERM PROGNOSIS; FOLLOW-UP; MONOCLONAL GAMMOPATHY;
PLASMA-EXCHANGE; UNDETERMINED SIGNIFICANCE
AB Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular junction or muscle have a wide clinical spectrum with diverse pathogenetic mechanisms. Peripheral nervous system may be targeted in the context of complex immune reactions involving different cytokines, antigen-presenting cells, B cells and different types of T cells. Various immunomodulating and cytotoxic treatments block proliferation or activation of immune cells by different mechanisms attempting to control the response of the immune system and limit target organ injury. Most treatment protocols for autoimmune neuromuscular disorders are based on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with cytotoxic agents mostly used as steroid-sparing medications. More recently, development of specific monoclonal antibodies targeting individual cell types allowed a different approach targeting specific immune pathways, but these new treatments are also associated with various adverse effects and their long-term efficacy is still unknown.
C1 [Kraker, Jessica; Zivkovic, Sasa A.] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA.
[Zivkovic, Sasa A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Zivkovic, SA (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, 200 Lothrop St,PUH F878, Pittsburgh, PA 15213 USA.
EM zivkovics@upmc.edu
NR 71
TC 1
Z9 1
U1 1
U2 3
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-159X
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PD SEP
PY 2011
VL 9
IS 3
BP 400
EP 408
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 883HF
UT WOS:000299624100002
PM 22379454
ER
PT J
AU Hirsch, AE
Jha, RM
Yoo, AJ
Saxena, A
Ozonoff, A
Growney, MJ
Hirsch, JA
AF Hirsch, Ariel E.
Jha, Ruchira M.
Yoo, Albert J.
Saxena, Akriti
Ozonoff, Al
Growney, Marion J.
Hirsch, Joshua A.
TI The Use of Vertebral Augmentation and External Beam Radiation Therapy in
the Multimodal Management of Malignant Vertebral Compression Fractures
SO PAIN PHYSICIAN
LA English
DT Article
DE malignant compression fractures; palliation; vertebroplasty; radiation
therapy
ID INTERVENTIONAL PAIN MANAGEMENT; EVIDENCE-BASED MEDICINE;
CLINICAL-PRACTICE GUIDELINES; CT-GUIDED VERTEBROPLASTY; CHRONIC SPINAL
PAIN; PERCUTANEOUS VERTEBROPLASTY; SYSTEMATIC REVIEWS; RANDOMIZED-TRIAL;
CEMENT AUGMENTATION; METASTATIC-DISEASE
AB Background: Vertebral augmentation (VA) techniques such as vertebroplasty and kyphoplasty are increasingly performed minimally invasive procedures for osteoporotic or malignant compression fractures (MCFs) and involve injection of polymethylmethacrylate (PMMA) cement directly into a compressed vertebral body.
Objective: This article will evaluate the efficacy of VA in relieving fracture-related pain. We also intend to identify procedural and clinical variables that could potentially influence outcomes in this population. In the subset of patients with cancer who received both external beam radiation therapy (EBRT) and VA, we will assess the impact of the treatment sequence on pain outcomes.
Study Design: We performed a retrospective analysis of 201 cases of patients with cancer and MCFs who underwent one or more vertebral augmentation procedures at our institution between 2003 and 2009. The majority of cancers represented were multiple myeloma, metastatic lung cancer, and metastatic breast cancer. The primary outcome measure was pain relief, as measured by the Visual Analog Scale and a 4-point pain scale.
Setting: We present an institutional experience at an academic medical center of 201 cases of MCFs.
Methods: We compiled an institutional database of vertebroplasty and kyphoplasty cases using paper and electronic medical records. Our data collection methodology has been previously reported and includes variables such as procedure dates, gender, age, type of malignancy, fracture etiology, history of cancer treatment, type of procedure performed, vertebral level treated, the number of levels treated per procedure, complications, and follow-up information on pain response. The updated dataset incorporates new variables including information on pain medications and standardized questionnaires such as the Visual Analog Scale (VAS) for pain and the Roland Morris Disability Questionnaire (RMDQ).
Results: In the 201 cases of MCFs, a total of 316 vertebral levels were treated with either vertebroplasty or kyphoplasty. Follow-up data on pain relief was available for 190 out of 201 cases (95%). Among this subgroup, 168 cases (88%) with MCFs responded. Thirty-nine percent (39%) of the time patients experienced complete pain resolution. In only 4% of cases did patients report worsening of their fracture-related pain post-procedure. There was no difference in pain outcomes with regard to sequencing of EBRT and VA.
Limitations: One of the limitations of our analysis is that it did not evaluate the effect of pain improvement or resolution before and after EBRT alone and on activities of daily living in the majority of patients. However, one of the main goals of this analysis is to address previous limitations. We attempt to standardize outcome measures by using the Visual Analog Scale (VAS) for pain and the Roland Morris Disability Questionnaire (RMDQ).
Conclusion: A multimodality approach for the management of MCFs includes VA procedures. The majority of patients with MCFs have excellent palliation with this approach. In patients who receive both EBRT and VA, the sequence in which they are given does not affect pain improvement outcomes.
C1 [Hirsch, Ariel E.] Boston Univ, Med Ctr, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02118 USA.
[Jha, Ruchira M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Yoo, Albert J.; Growney, Marion J.; Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Neuroradiol, Boston, MA 02114 USA.
[Saxena, Akriti] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Ozonoff, Al] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA.
RP Hirsch, AE (reprint author), Boston Univ, Med Ctr, Massachusetts Gen Hosp, Dept Radiat Oncol, 830 Harrison Ave,Moakley Bldg LL, Boston, MA 02118 USA.
EM Ariel.hirsch@bmc.org
NR 71
TC 12
Z9 14
U1 1
U2 3
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 SEP-OCT
PY 2011
VL 14
IS 5
BP 447
EP 458
PG 12
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 885MW
UT WOS:000299784100013
PM 21927049
ER
PT J
AU Manchikanti, L
Falco, FJE
Hirsch, JA
AF Manchikanti, Laxmaiah
Falco, Frank J. E.
Hirsch, Joshua A.
TI Necessity and Implications of ICD-10: Facts and Fallacies
SO PAIN PHYSICIAN
LA English
DT Review
DE Diagnostic coding systems; International Statistical Classification of
Diseases and Related Health Problems (ICD); ICD-9-CM; ICD-10-CM;
regulations; growth; evidence-based literature; reimbursement; claims;
Health Insurance Portability and Accountability Act (HIPAA)
ID INTERVENTIONAL PAIN MANAGEMENT; EVIDENCE-BASED MEDICINE; CHRONIC SPINAL
PAIN; REFLEX SYMPATHETIC DYSTROPHY; CLINICAL-PRACTICE GUIDELINES;
AFFORDABLE CARE ACT; LOW-BACK-PAIN; ADMINISTRATIVE DATA; HEALTH-CARE;
SYSTEMATIC REVIEWS
AB The International Classification of Diseases-10 (ICD-10 is a new system that is expected to be implemented effective on October 1, 2013. This new system is a federally mandated change affecting all payers and providers, and is expected to exceed both the Health Insurance Portability and Accountability Act (HIPAA) and Y2K in terms of costs and risks. However, the Administration is poised to implement these changes at a rapid pace which could be problematic for health care in the United States.
In 2003, HIPAA named ICD-9 as the code set for supporting diagnoses and procedures in electronic administrative transactions. However, on January 16, 2009, the Department of Health and Human Services (HHS) published a regulation requiring the replacement of ICD-9 with ICD-10 as of October 1, 2013. While ICD-9 and 10 have a similar type of hierarchy in their structures, the ICD-10 is more complex and incorporates numerous changes. Overall, ICD-10 contains over 141,000 codes, a whopping 712% increase over the less than 20,000 codes in ICD-9, creating enormous complexities, confusion, and expense. Multiple published statistics illustrate that there are approximately 119 instances where a single ICD-9 code can map to more than 100 distinct ICD-10 codes, whereas there are 255 instances where a single ICD-9 code can map to more than 50 ICD-10 codes. To add to the confusion, there are 3,684 instances in the mapping for diseases where a single ICD-10 code can map to more than one ICD-9 code.
Proponents of the new ICD-10 system argue that the granularity should lead to improvements in the quality of health care, since more precise coding that more accurately reflects actual patient conditions will permit smarter and more effective disease management in pay-for-performance programs. This, in essence, encapsulates the benefits that supporters of this new system believe will be realized, even though many of these experts may not be involved in actual day-to-day medical practices.
Detractors of the system see the same granularity as burdensome. The estimated cost per physician is projected to range from $25,000 to $50,000. Further, they argue that the ICD-10 classification is extremely complicated, and expensive. Concerns exist that it is being implemented without establishing either the necessity or thinking through the unintended consequences. Opponents also argue that beyond financial expense, it is also costly in terms of human toll, hardware and software expenses and has the potential to delay reimbursement. There is also concern that an unintended consequence of granularity would be the potential for enhanced and unnecessary fraud and abuse investigations.
The authors of this article favor postponing the implementation of the ICD-10 until such time as its necessity is proven and implications are understood.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys Newark, Newark, DE USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 107
TC 25
Z9 25
U1 0
U2 22
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 SEP-OCT
PY 2011
VL 14
IS 5
BP E405
EP E425
PG 21
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 885MW
UT WOS:000299784100001
PM 21927055
ER
PT J
AU Felts, AS
Bates, BS
Rodriguez, AL
Menon, UN
Jadhav, S
Blobaum, AL
Byers, FW
Daniels, JS
Lawson, KP
Jones, CK
Conn, PJ
Lindsley, CW
Emmitte, KA
AF Felts, A. S.
Bates, B. S.
Rodriguez, A. L.
Menon, U. N.
Jadhav, S.
Blobaum, A. L.
Byers, F. W.
Daniels, J. S.
Lawson, K. P.
Jones, C. K.
Conn, P. J.
Lindsley, C. W.
Emmitte, K. A.
TI SAR and in vitro/vivo Evaluation of a Novel Series of Substituted Aryl
Ether Benzamides as Negative Allosteric Modulators of mGlu(5)
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Felts, A. S.; Bates, B. S.; Rodriguez, A. L.; Menon, U. N.; Jadhav, S.; Blobaum, A. L.; Byers, F. W.; Daniels, J. S.; Jones, C. K.; Conn, P. J.; Lindsley, C. W.; Emmitte, K. A.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
[Felts, A. S.; Bates, B. S.; Rodriguez, A. L.; Menon, U. N.; Jadhav, S.; Blobaum, A. L.; Byers, F. W.; Daniels, J. S.; Jones, C. K.; Conn, P. J.; Lindsley, C. W.; Emmitte, K. A.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA.
[Jones, C. K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN USA.
Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA.
RI Conn, Peter/D-7848-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-159X
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PD SEP
PY 2011
VL 9
SU 1
MA 55
BP 20
EP 20
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 883IJ
UT WOS:000299627200056
ER
PT J
AU Niswender, CM
Jones, CK
Hopkins, CR
Thompson, AD
Bubser, M
Engers, D
Gogliotti, RD
Blobaum, AL
Salovich, JM
Cheung, YY
Morrison, RD
Dawson, ES
Zamorano, R
Brewer, KA
Daniels, JS
Lindsley, CW
Conn, PJ
AF Niswender, C. M.
Jones, C. K.
Hopkins, C. R.
Thompson, A. D.
Bubser, M.
Engers, D.
Gogliotti, R. D.
Blobaum, A. L.
Salovich, J. M.
Cheung, Y. Y.
Morrison, R. D.
Dawson, E. S.
Zamorano, R.
Brewer, K. A.
Daniels, J. S.
Lindsley, C. W.
Conn, P. J.
TI mGlu4 Receptor Positive Allosteric Modulator Development for the
Treatment of CNS Disorders
SO CURRENT NEUROPHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Niswender, C. M.; Jones, C. K.; Hopkins, C. R.; Thompson, A. D.; Bubser, M.; Engers, D.; Gogliotti, R. D.; Blobaum, A. L.; Salovich, J. M.; Cheung, Y. Y.; Morrison, R. D.; Dawson, E. S.; Zamorano, R.; Brewer, K. A.; Daniels, J. S.; Lindsley, C. W.; Conn, P. J.] Vanderbilt Univ, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37212 USA.
[Niswender, C. M.; Jones, C. K.; Hopkins, C. R.; Thompson, A. D.; Bubser, M.; Engers, D.; Gogliotti, R. D.; Blobaum, A. L.; Salovich, J. M.; Cheung, Y. Y.; Morrison, R. D.; Dawson, E. S.; Zamorano, R.; Brewer, K. A.; Daniels, J. S.; Lindsley, C. W.; Conn, P. J.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37212 USA.
[Hopkins, C. R.; Lindsley, C. W.] Vanderbilt Univ, Dept Chem, Nashville, TN 37212 USA.
[Jones, C. K.] Vanderbilt Univ, US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA.
[Lindsley, C. W.] Vanderbilt Univ, Vanderbilt Inst Chem Biol, Nashville, TN 37212 USA.
RI Conn, Peter/D-7848-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-159X
J9 CURR NEUROPHARMACOL
JI Curr. Neuropharmacol.
PD SEP
PY 2011
VL 9
SU 1
MA 131
BP 48
EP 48
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 883IJ
UT WOS:000299627200131
ER
PT J
AU Welsh, CA
Flanagan, ME
Kiess, C
Doebbeling, BN
AF Welsh, Catherine Amber
Flanagan, Mindy E.
Kiess, Chris
Doebbeling, Bradley N.
TI Implementing the MRSA Bundle in ICUs: One Citywide Collaborative's Key
Lessons Learned
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID HEALTH-CARE; INNOVATIONS
AB Because bundle implementation in intensive care units to reduce methicillin-resistant Staphylococcus aureus is challenging, we conducted in-depth interviews with implementation teams at 5 participating hospitals. Key lessons learned across hospitals included the following: maintain management support, engage frontline staff, build the right multidisciplinary team, conduct process mapping, and commit to data collection and feedback. Infect Control Hosp Epidemiol 2011;32(9):918-921
C1 [Welsh, Catherine Amber; Flanagan, Mindy E.; Doebbeling, Bradley N.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA.
[Welsh, Catherine Amber] IU Purdue Univ Indianapolis, Sch Engn & Technol, Indianapolis, IN USA.
[Kiess, Chris; Doebbeling, Bradley N.] Regenstrief Inst Hlth Care, Indianapolis, IN USA.
[Doebbeling, Bradley N.] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Ctr Excellence, Indianapolis, IN USA.
[Doebbeling, Bradley N.] IU Sch Med, Dept Med, Indianapolis, IN USA.
RP Welsh, CA (reprint author), 799 W Michigan St, Indianapolis, IN 46202 USA.
EM amwelsh@hotmail.com
FU US Agency for Healthcare Research and Quality under Office of Management
and Budget [HHSA2902006000131]
FX US Agency for Healthcare Research and Quality (contract
HHSA2902006000131, under Office of Management and Budget control no.
0935-0168, expiration date September 30, 2012).
NR 7
TC 4
Z9 4
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD SEP
PY 2011
VL 32
IS 9
BP 918
EP 921
DI 10.1086/661101
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 876BW
UT WOS:000299083000014
PM 21828975
ER
PT J
AU Chae, CU
Derby, CA
AF Chae, Claudia U.
Derby, Carol A.
TI The Menopausal Transition and Cardiovascular Risk
SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Lipids; Blood pressure; Diabetes; Metabolic syndrome; Menopause;
Perimenopause
ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL
HORMONE-THERAPY; MIDDLE-AGED WOMEN; BODY-MASS INDEX; BLOOD-PRESSURE;
METABOLIC SYNDROME; HEALTHY WOMEN; MIDLIFE WOMEN; ENDOTHELIAL
DYSFUNCTION
AB The incidence of cardiovascular disease, which is the leading single cause of death among women, increases substantially after menopause. This may be related to adverse changes in cardiovascular risk factors that occur during the menopausal transition. Proatherogenic changes in lipid and apolipoprotein profiles seem to be specifically related to ovarian aging; unfavorable changes in other cardiovascular risk factors may be influenced more by chronologic aging. Whether these changes are due to aging or to menopause itself, increased attention to risk factor modification in the pre- and perimenopausal years will help reduce future cardiovascular disease risk among women.
C1 [Chae, Claudia U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02114 USA.
[Derby, Carol A.] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10461 USA.
[Derby, Carol A.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Derby, Carol A.] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10461 USA.
[Derby, Carol A.] Albert Einstein Coll Med, Dept Populat Hlth, Bronx, NY 10461 USA.
RP Chae, CU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, 55 Fruit St, Boston, MA 02114 USA.
EM cchae@partners.org
FU Bristol Meyers Squibb; National Institutes of Health [2U01AG012535-16, 5
UO1 AG12531-17]
FX Dr Derby receives research support from Bristol Meyers Squibb.;
Supported by Grant No. 2U01AG012535-16 (C.A.D.) and 5 UO1 AG12531-17
(C.U.C.) from the National Institutes of Health.
NR 71
TC 19
Z9 19
U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8545
J9 OBSTET GYN CLIN N AM
JI Obstet. Gynecol. Clin. N. Am.
PD SEP
PY 2011
VL 38
IS 3
BP 477
EP +
DI 10.1016/j.ogc.2011.05.005
PG 13
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 878DU
UT WOS:000299234700008
PM 21961715
ER
PT J
AU Thurston, RC
Joffe, N
AF Thurston, Rebecca C.
Joffe, Nadine
TI Vasomotor Symptoms and Menopause: Findings from the Study of Women's
Health across the Nation
SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Hot flashes; Hot flushes; Vasomotor symptoms; Menopause; Climacteric
symptoms; Menopausal symptoms
ID MIDDLE-AGED WOMEN; CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; HOT FLASHES;
MIDLIFE WOMEN; POSTMENOPAUSAL WOMEN; HORMONE-LEVELS; MULTIETHNIC
COMMUNITY; DEPRESSIVE SYMPTOMS; CARDIOVASCULAR-DISEASE
AB Vasomotor symptoms (VMS), or hot flashes and night sweats, are often considered the cardinal symptoms of menopause. SWAN, one of the largest and most ethnically diverse longitudinal studies of the menopausal transition, has allowed unique insights into VMS. Specifically, SWAN has helped yield important information about the prevalence of, racial/ethnic differences in, risk factors for, and implications of VMS for midlife women's mental and physical health. We have reviewed the literature on VMS, emphasizing findings that have emerged from SWAN and new areas of inquiry in the area of VMS.
C1 [Thurston, Rebecca C.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Thurston, Rebecca C.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Joffe, Nadine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Ctr Womens Mental Hlth, Boston, MA 02114 USA.
RP Thurston, RC (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM thurstonrc@upmc.edu
FU NIH [AG029216, NH082922]; Bayer Health Care Pharmaceuticals; Forest
Laboratories; GlaxoSmithKline
FX In addition to the SWAN funding described in the overview, this work was
also supported by NIH grants AG029216 (Thurston) and NH082922 (Joffe).;
Hadine Joffe has received research support from Bayer Health Care
Pharmaceuticals (co-Pl), Forest Laboratories (co-l), GlaxoSmithKline
(co-l), and served as an advisor/consultant to Sunovion.
NR 80
TC 49
Z9 52
U1 2
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 0889-8545
EI 1558-0474
J9 OBSTET GYN CLIN N AM
JI Obstet. Gynecol. Clin. N. Am.
PD SEP
PY 2011
VL 38
IS 3
BP 489
EP +
DI 10.1016/j.ogc.2011.05.006
PG 14
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 878DU
UT WOS:000299234700009
PM 21961716
ER
PT J
AU Lo, JC
Burnett-Bowie, SAM
Finkelstein, JS
AF Lo, Joan C.
Burnett-Bowie, Sherri-Ann M.
Finkelstein, Joel S.
TI Bone and the Perimenopause
SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Osteoporosis; Perimenopause; Menopause; Bone; Fractures
ID EARLY POSTMENOPAUSAL WOMEN; VITAMIN-D SUPPLEMENTATION; ESTROGEN
REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIALS; MINERAL DENSITY
CHANGES; CLINICAL RISK-FACTORS; HEALTHY OLDER WOMEN; LIFE-STYLE FACTORS;
MENOPAUSAL TRANSITION; BIOCHEMICAL MARKERS
AB Loss of ovarian function has a profound impact on female skeletal health. Bone mineral density findings from the Study of Women's Health Across the Nation demonstrate an accelerated rate of bone loss during the menopausal transition. The greatest reduction occurs in the year before the final menstrual period and the first 2 years thereafter. Clinical management includes maintenance of adequate dietary calcium and vitamin D intake, attention to modifiable risk factors, and osteoporosis screening. Indications, benefits, and risks of pharmacologic osteoporosis therapy should be assessed individually; there are currently no established guidelines addressing the treatment and prevention of osteoporosis in perimenopausal women.
C1 [Lo, Joan C.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA.
[Lo, Joan C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Burnett-Bowie, Sherri-Ann M.; Finkelstein, Joel S.] Harvard Univ, Sch Med, Dept Med, Endocrine Unit, Boston, MA 02114 USA.
[Burnett-Bowie, Sherri-Ann M.; Finkelstein, Joel S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Lo, JC (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA.
EM Joan.C.Lo@kp.org
OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X
FU Amgen, Inc.
FX Drs Lo and Burnett-Bowie have received research funding from Amgen, Inc.
NR 92
TC 16
Z9 17
U1 1
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8545
EI 1558-0474
J9 OBSTET GYN CLIN N AM
JI Obstet. Gynecol. Clin. N. Am.
PD SEP
PY 2011
VL 38
IS 3
BP 503
EP +
DI 10.1016/j.ogc.2011.07.001
PG 16
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 878DU
UT WOS:000299234700010
PM 21961717
ER
PT J
AU Kravitz, HM
Joffe, H
AF Kravitz, Howard M.
Joffe, Hadine
TI Sleep During the Perimenopause: A SWAN Story
SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Aging; Menopausal transition; Perimenopause; Psychosocial; Reproductive
hormones; Sleep
ID MIDDLE-AGED ADULTS; MENOPAUSAL TRANSITION; WOMENS HEALTH; MIDLIFE WOMEN;
QUALITY INDEX; INSOMNIA; SYMPTOMS; HORMONE; DISTURBANCE; PREVALENCE
AB Is there evidence for a perimenopausal sleep disorder? We address this question in our presentation of the Study of Women's Health Across the Nation (SWAN) "sleep story," in which we summarize and discuss data addressing sleep quality, objective measures of sleep patterns, and sleep disorders that have been published to date by the SWAN and the ancillary SWAN Sleep Study. We describe what has been learned about sleep during the perimenopause. Analyses exploring racial/ethnic diversity and the role of hot flashes and mood disturbance in sleep-perimenopause associations are described. Implications for clinical practice are considered.
C1 [Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA.
[Kravitz, Howard M.] Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA.
[Joffe, Hadine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Ctr Womens Mental Hlth, Boston, MA 02114 USA.
RP Kravitz, HM (reprint author), Rush Univ, Med Ctr, Dept Psychiat, 2150 W Harrison St,Room 275, Chicago, IL 60612 USA.
EM hkravitz@rush.edu
FU National Institute on Aging [AG019360, AG019361, AG019362, AG019363];
National Institute of Mental Health [5R01MH082922]; Bayer Health Care
Pharmaceuticals; Forest Laboratories; GlaxoSmithKline
FX Funding for the SWAN Sleep Study is from the National Institute on Aging
(Grants AG019360, AG019361, AG019362, AG019363). Support for this
manuscript was also provided in part by National Institute of Mental
Health (5R01MH082922; H. Joffe, PI). The content of this manuscript is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIA, NINR, ORWH or the NIH. The
authors also acknowledge the graphics assistance of Dr Imke Janssen in
preparing Fig. 7.; Dr Joffe discloses that over the past 12 months she
has served as a co-investigator on clinical trials supported by Bayer
Health Care Pharmaceuticals, Forest Laboratories, and GlaxoSmithKline,
and served as a consultant to Sunovion.
NR 48
TC 27
Z9 28
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 0889-8545
J9 OBSTET GYN CLIN N AM
JI Obstet. Gynecol. Clin. N. Am.
PD SEP
PY 2011
VL 38
IS 3
BP 567
EP +
DI 10.1016/j.ogc.2011.06.002
PG 21
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 878DU
UT WOS:000299234700013
PM 21961720
ER
PT J
AU Gordon, CR
Yaremchuk, MJ
AF Gordon, Chad R.
Yaremchuk, Michael J.
TI Temporal Augmentation With Methyl Methacrylate
SO AESTHETIC SURGERY JOURNAL
LA English
DT Article
DE temporal hollowing; temporal atrophy; temporal augmentation; methyl
methacrylate; facial contouring
ID FREE-FLAP; RECONSTRUCTION
AB Concavity in the temporal area reflects a deficiency in the bulk of the temporalis muscle or overlying temporal fat pad. It may be a reflection of senescence, low body fat, exaggerated adjacent skeletal or soft-tissue contours, idiopathic progressive atrophy, or postsurgical deformities. The authors describe the application of methyl methacrylate (MMA) to fill depressions in the temporal area. In instances in which no previous surgery has been performed or when the temporal area has served as a dissection plane for surgery in adjacent areas (eg, a subperiosteal facelift), the implant material is placed beneath the temporal muscle through a limited incision in the hair-bearing scalp. When previous reconstructive surgery has been performed in the temporal area, the area of depression is accessed through existing surgical incision scars to place MMA over the temporal muscle. These operative techniques have been reliable, durable, and relatively free of complications.
C1 [Gordon, Chad R.; Yaremchuk, Michael J.] Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Yaremchuk, MJ (reprint author), Harvard Univ, Sch Med, Div Plast & Reconstruct Surg, Dept Surg,Massachusetts Gen Hosp, 15 Parkman St,WACC 435, Boston, MA 02114 USA.
EM myaremchuk@partners.org
NR 15
TC 5
Z9 5
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1090-820X
J9 AESTHET SURG J
JI Aesthet. Surg. J.
PD SEP
PY 2011
VL 31
IS 7
BP 827
EP 833
DI 10.1177/1090820X11417425
PG 7
WC Surgery
SC Surgery
GA 864MK
UT WOS:000298244000012
PM 21908815
ER
PT J
AU Rokkam, D
LaFemina, MJ
Lee, JW
Matthay, MA
Frank, JA
AF Rokkam, Deepti
LaFemina, Michael J.
Lee, Jae Woo
Matthay, Michael A.
Frank, James A.
TI Claudin-4 Levels Are Associated with Intact Alveolar Fluid Clearance in
Human Lungs
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID RESPIRATORY-DISTRESS-SYNDROME; JUNCTION FIBRIL ARCHITECTURE; EPITHELIAL
BARRIER FUNCTION; PERFUSED HUMAN LUNGS; CHARGE SELECTIVITY; EXPRESSION;
INJURY; CELLS; PERMEABILITY; RESISTANCE
AB The removal of edema from the air spaces is a critical function of the alveolar barrier requiring intact tight junctions. Alveolar fluid clearance contributes to graft function after transplantation and is associated with survival in patients with acute lung injury. Claudin-4 concentrations are known to increase during lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice. This study was therefore undertaken to evaluate whether differences in lung expression of the tight junction protein claudin-4 are associated with alveolar fluid clearance or clinical measures of lung function. Alveolar fluid clearance rates were measured in ex vivo perfused human lungs not used for transplantation and were compared with histological lung injury and clinical measures of lung injury in the donors. Claudin-4 staining demonstrated a positive correlation with alveolar fluid clearance (Spearman rank correlation [r(s)] = 0.71; P < 0.003); however, claudin-4 staining was not strongly associated with histological measures of lung injury. The expression of other tight junction proteins (including ZO-1) was not associated with alveolar fluid clearance or claudin-4 levels. Claudin-4 staining was lower in lungs from donors with greater impairment in respiratory physiology. These data suggest that claudin-4 may promote alveolar fluid clearance and demonstrate that the amount of claudin-4 expressed may provide specific information regarding alveolar epithelial barrier function that strengthens the link between histological changes and physiological impairment. (Am J Pathol 2011, 179:1081-1087; DOI: 10.1016/j.ajpath.2011.05.017)
C1 [Frank, James A.] Univ Calif San Francisco, Cardiovasc Res Inst, No Calif Inst Res & Educ, San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Frank, JA (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, No Calif Inst Res & Educ, San Francisco VA Med Ctr, 4150 Clement St,Box 111D, San Francisco, CA 94121 USA.
EM james.frank@ucsf.edu
FU National Institutes of Health [HL88440]; National Heart, Lung and Blood
Institute [HL551856]
FX Supported by grants from the National Institutes of Health (HL88440 to
J.A.F.) and the National Heart, Lung and Blood Institute (HL551856 to
J.A.F. and M.A.M.).
NR 28
TC 31
Z9 31
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2011
VL 179
IS 3
BP 1081
EP 1087
DI 10.1016/j.ajpath.2011.05.017
PG 7
WC Pathology
SC Pathology
GA 865JN
UT WOS:000298307300002
PM 21741940
ER
PT J
AU Serrano-Pozo, A
Mielke, ML
Gomez-Isla, T
Betensky, RA
Growdon, JH
Frosch, MP
Hyman, BT
AF Serrano-Pozo, Alberto
Mielke, Matthew L.
Gomez-Isla, Teresa
Betensky, Rebecca A.
Growdon, John H.
Frosch, Matthew P.
Hyman, Bradley T.
TI Reactive Glia not only Associates with Plaques but also Parallels
Tangles in Alzheimer's Disease
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MILD COGNITIVE IMPAIRMENT;
AMYLOID-BETA; NEUROFIBRILLARY TANGLES; MICROGLIAL ACTIVATION; SYNAPSE
LOSS; MOUSE MODEL; TRANSGENIC MICE; SENILE PLAQUES; NEURONAL LOSS
AB Senile plaques are a prominent pathological feature of Alzheimer's disease (AD)), but little is understood about the association of glial cells with plaques or about the dynamics of glial responses through the disease course. We investigated the progression of reactive glial cells and their relationship with AD pathological hallmarks to test whether glial cells are linked only to amyloid deposits or also to tangle deposition, thus integrating both lesions as a marker of disease severity. We conducted a quantitative stereology-based post-mortem study on the temporal neocortex of 15 control subjects without dementia and 91 patients with AD, including measures of amyloid load, neurofibrillary tangles, reactive astrocytes, and activated microglia. We also addressed the progression of glial responses in the vicinity (<= 50 mu m) of dense-core plaques anti tangles. Although the amyloid load reached a plateau early after symptom onset, astrocytosis and microgliosis increased linearly throughout the disease course. Moreover, glial responses correlated positively with tangle burden, whereas astrocytosis correlated negatively with cortical thickness. However, neither correlated with amyloid load. Glial responses increased linearly around existing plaques and in the vicinity of tangles. These results indicate that the progression of astrocytosis and microgliosis diverges from that of amyloid deposition, arguing against a straightforward relationship between glial cells and plaques. They also suggest that reactive glia might contribute to the ongoing neurodegeneration. (Am J Pathol 2011, 179:1373-1384; DOI: 10.1016/j.ajpath.2011.05.047)
C1 [Serrano-Pozo, Alberto; Mielke, Matthew L.; Gomez-Isla, Teresa; Growdon, John H.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
[Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Betensky, Rebecca A.; Growdon, John H.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA USA.
[Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Inst Neurodegenerat Dis, 16th St,Bldg 114, Charlestown, MA 02129 USA.
EM bhyman@partners.org
RI SERRANO-POZO, ALBERTO/F-5119-2013;
OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530
FU NIH [P50AG05134, AG08487]; Foundation Alfonso Martin Escudero, Madrid,
Spain
FX Supported by grants from the NIH (P50AG05134 and AG08487) and a research
fellowship from the Foundation Alfonso Martin Escudero, Madrid, Spain
(AS.-P.).
NR 53
TC 77
Z9 78
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2011
VL 179
IS 3
BP 1373
EP 1384
DI 10.1016/j.ajpath.2011.05.047
PG 12
WC Pathology
SC Pathology
GA 865JN
UT WOS:000298307300031
PM 21777559
ER
PT J
AU Chen, CC
Pekow, J
Llado, V
Kanneganti, M
Lau, CW
Mizoguchi, A
Mino-Kenudson, M
Bissonnette, M
Mizoguchi, E
AF Chen, Chun-Chuan
Pekow, Joel
Llado, Victoria
Kanneganti, Manasa
Lau, Cindy W.
Mizoguchi, Atsushi
Mino-Kenudson, Mari
Bissonnette, Marc
Mizoguchi, Emiko
TI Chitinase 3-Like-1 Expression in Colonic Epithelial Cells as a
Potentially Novel Marker for Colitis-Associated Neoplasia
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; HUMAN CARTILAGE GLYCOPROTEIN-39;
COLORECTAL-CANCER; SERUM YKL-40; ARTICULAR CHONDROCYTES;
ULCERATIVE-COLITIS; PROTEIN FAMILY; MUTANT MICE; MACROPHAGES; CARCINOMA
AB Chitinase 3-like-1 (CHI3L1/YKL-40) is a protein secreted from restricted cell types including colonic epithelial cells (CECs) and macrophages. CHI3L1 is an inflammation-associated molecule, and its expression is enhanced in persons with colitis and colon cancer. The biological function of CHI3L1 on CECs is unclear. In this study, we investigated the role of CHI3L1 on CECs during the development of colitis-associated neoplasia. We analyzed colonic samples obtained from healthy persons and from persons with ulcerative colitis with or without premalignant or malignant changes. DNA microarray and RT-PCR analyses significantly increased CHI3L1 expression in non-dysplastic mucosa from patients with inflammatory bowel disease (IBD) who had dysplasia/adenocarcinoma compared with that in healthy persons and in patients with IBD who did not have dysplasia. As determined by MC, CHI3L1 was expressed in specific cell types in the crypts of colonic biopsies obtained from patients with ulcerative colitis who have remote dysplasia. Purified CHI3L1 efficiently activated the NF-kappa B signaling pathway and enhanced the secretion of IL-8 and TNF-alpha in SW480 human colon cancer cells. In addition, colon cancer cell proliferation and migration were significantly promoted in response to CHI3L1 in these cells. In summary, CHI3L1 may contribute to the proliferation, migration, and neoplastic progression of CECs under inflammatory conditions and could be a useful biomarker for neoplastic changes in patients with IBD. (Am J Pathol 2011, 179:1494-1503; DOI: 10.1016/j.ajpath.2011.05.038)
C1 [Chen, Chun-Chuan; Llado, Victoria; Kanneganti, Manasa; Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA.
[Lau, Cindy W.; Mizoguchi, Atsushi; Mino-Kenudson, Mari] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Mizoguchi, Atsushi; Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Pekow, Joel; Bissonnette, Marc] Univ Chicago, Div Gastroenterol, Dept Med, Chicago, IL 60637 USA.
Univ Chicago, Digest Dis Res Core Ctr, Chicago, IL 60637 USA.
RP Mizoguchi, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, GRJ 702,55 Fruit St, Boston, MA 02114 USA.
EM emizoguchi@partners.org
FU National Institutes of Health [DK80070, DK74454, DK64289, DK43351,
AI81807]; Eli and Edythe L. Broad Medical Foundation; American
Gastroenterological Association Foundation; Crohn's and Colitis
Foundation of America Inc.
FX Supported by grants from the National Institutes of Health (DK80070,
DK74454, DK64289, and DK43351 to E.M. and AI81807 to A.M.) and the Eli
and Edythe L. Broad Medical Foundation and American Gastroenterological
Association Foundation (E.M.). M.K. is the recipient of a 2010 Student
Research Fellowship Award from the Crohn's and Colitis Foundation of
America Inc.
NR 44
TC 28
Z9 28
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2011
VL 179
IS 3
BP 1494
EP 1503
DI 10.1016/j.ajpath.2011.05.038
PG 10
WC Pathology
SC Pathology
GA 865JN
UT WOS:000298307300042
PM 21763261
ER
PT J
AU Lai, GGY
Penson, RT
AF Lai, G. G. Y.
Penson, R. T.
TI BEVACIZUMAB AND OVARIAN CANCER
SO DRUGS OF TODAY
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; CELL
LUNG-CANCER; PHASE-III TRIAL; METRONOMIC ORAL CYCLOPHOSPHAMIDE;
COOPERATIVE-ONCOLOGY-GROUP; ADVANCED BREAST-CANCER; FALLOPIAN-TUBE
CANCER; EPITHELIAL OVARIAN; RECURRENT OVARIAN
AB Epithelial ovarian cancer is the most lethal of gynecologic malignancies in the United States, with a significant proportion of patients with advanced disease achieving clinical remission with conventional treatment approaches, but dying of recurrence. Bevacizumab is a first-in-class antiangiogenic. This recombinant humanized monoclonal antibody neutralizes vascular endothelial growth factor (VEGF) and inhibits endothelial and tumor cell activation and proliferation. It has a low clearance and long elimination half-life, supporting a convenient 2- or 3-weekly dosing schedule. It is generally well tolerated, although trials have highlighted some toxicity-related concerns, notably gastrointestinal perforation. Phase III trials that evaluate overall survival are not yet mature, and cost-effectiveness of bevacizumab is hotly debated. As more evidence for the role of anti-VEGF agents in augmenting therapy and inducing durable tumor dormancy continues to emerge, it is anticipated that antiangiogenic therapy will play an important role in the management ovarian malignancy.
C1 [Lai, G. G. Y.; Penson, R. T.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Yawkey 9066,55 Fruit St, Boston, MA 02114 USA.
EM rpenson@partners.org
FU Genentech; DARA BioSciences; MGI Pharma; Berlex Labs (Bayer HealthCare
Pharmaceuticals); CuraGen; PDL BioPharma; ImClone Systems; Endocyte;
Eisai; Amgen
FX R.T. Penson has received research funding from Genentech, DARA
BioSciences, MGI Pharma, Berlex Labs (Bayer HealthCare Pharmaceuticals),
CuraGen, PDL BioPharma, ImClone Systems, Endocyte, Eisai and Amgen. He
has also acted as a consultant for DARA BioSciences and Lilly, and has
served on the scientific advisory boards of Genentech, GlaxoSmithKline,
Abbott and AstraZeneca. G.G.Y. Lai states no conflicts of interest.
NR 126
TC 4
Z9 4
U1 0
U2 1
PU PROUS SCIENCE, SA-THOMSON REUTERS
PI BARCELONA
PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN
SN 1699-3993
J9 DRUG TODAY
JI Drugs Today
PD SEP
PY 2011
VL 47
IS 9
BP 669
EP 681
DI 10.1358/dot.2011.47.9.1673557
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 852SQ
UT WOS:000297378200003
PM 21971541
ER
PT J
AU Kanji, Z
Powe, CE
Wenger, JB
Huang, C
Ankers, E
Sullivan, DA
Collerone, G
Powe, NR
Tonelli, M
Bhan, I
Bernhardy, AJ
DiBartolo, S
Friedman, D
Genovese, G
Pollak, MR
Thadhani, R
AF Kanji, Z.
Powe, C. E.
Wenger, J. B.
Huang, C.
Ankers, E.
Sullivan, D. A.
Collerone, G.
Powe, N. R.
Tonelli, M.
Bhan, I.
Bernhardy, A. J.
DiBartolo, S.
Friedman, D.
Genovese, G.
Pollak, M. R.
Thadhani, R.
TI GENETIC VARIATION IN APOL1 AND AGE AT HEMODIALYSIS INITIATION IN AFRICAN
AMERICANS
SO ETHNICITY & DISEASE
LA English
DT Meeting Abstract
C1 [Kanji, Z.; Powe, C. E.; Wenger, J. B.; Huang, C.; Ankers, E.; Sullivan, D. A.; Collerone, G.; Bhan, I.; Thadhani, R.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Powe, N. R.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA.
[Tonelli, M.] Univ Alberta, Dept Med, Edmonton, AB, Canada.
[Bernhardy, A. J.; DiBartolo, S.; Friedman, D.; Genovese, G.; Pollak, M. R.] Harvard Univ, Sch Med, Boston, MA USA.
[Bernhardy, A. J.; DiBartolo, S.; Friedman, D.; Genovese, G.; Pollak, M. R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA.
[Pollak, M. R.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD FAL
PY 2011
VL 21
IS 4
MA 019
BP S11
EP S11
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 867FH
UT WOS:000298439800039
ER
PT J
AU Kapuku, G
Davis, H
Choksy, P
Januzzi, J
Harshfield, G
AF Kapuku, G.
Davis, H.
Choksy, P.
Januzzi, J.
Harshfield, G.
TI STRESS-INDUCED CHANGES IN DIASTOLIC FUNCTION IS PREDICTED BY BRAIN
NATRIURETIC HORMONE
SO ETHNICITY & DISEASE
LA English
DT Meeting Abstract
C1 [Kapuku, G.; Davis, H.; Choksy, P.; Harshfield, G.] Georgia Hlth Sci Univ, Georgia Prevent Inst, Dept Pediat & Med, Augusta, GA USA.
[Januzzi, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD FAL
PY 2011
VL 21
IS 4
MA 011
BP S6
EP S6
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 867FH
UT WOS:000298439800031
ER
PT J
AU Scott, JB
Chandler, P
Emmons, K
Fuchs, C
AF Scott, J. B.
Chandler, P.
Emmons, K.
Fuchs, C.
TI VITAMIN D SUPPLEMENTATION AND RISK OF HYPERCALCEMIA IN HYPERTENSIVE
BLACKS TAKING HYDROCHLOROTHIAZIDE
SO ETHNICITY & DISEASE
LA English
DT Meeting Abstract
C1 [Scott, J. B.; Emmons, K.; Fuchs, C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Scott, J. B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Chandler, P.] Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD FAL
PY 2011
VL 21
IS 4
MA 017
BP S9
EP S9
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 867FH
UT WOS:000298439800037
ER
PT J
AU Beadling, C
Heinrich, MC
Warrick, A
Forbes, EM
Nelson, D
Justusson, E
Levine, J
Neff, TL
Patterson, J
Presnell, A
McKinley, A
Winter, LJ
Dewey, C
Harlow, A
Barney, O
Druker, BJ
Schuff, KG
Corless, CL
AF Beadling, Carol
Heinrich, Michael C.
Warrick, Andrea
Forbes, Erin M.
Nelson, Dylan
Justusson, Emily
Levine, Judith
Neff, Tanaya L.
Patterson, Janice
Presnell, Ajia
McKinley, Arin
Winter, Laura J.
Dewey, Christie
Harlow, Amy
Barney, Oscar
Druker, Brian J.
Schuff, Kathryn G.
Corless, Christopher L.
TI Multiplex Mutation Screening by Mass Spectrometry Evaluation of 820
Cases from a Personalized Cancer Medicine Registry
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; CHRONIC
MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTOR; ABL TYROSINE KINASE; BRAF
MUTATIONS; IMATINIB MESYLATE; BETA-CATENIN; PHILADELPHIA-CHROMOSOME;
ENDOMETRIAL CARCINOMAS
AB There is an immediate and critical need for a rapid, broad-based genotyping method that can evaluate multiple mutations simultaneously in clinical cancer specimens and identify patients most likely to benefit from targeted agents now in use or in late-stage clinical development. We have implemented a prospective genotyping approach to characterize the frequency and spectrum of mutations amenable to drug targeting present in urothelial, colorectal, endometrioid, and thyroid carcinomas and in melanoma. Cancer patients were enrolled in a Personalized Cancer Medicine Registry that houses both clinical information and genotyping data, and mutation screening was performed using a multiplexed assay panel with mass spectrometry based analysis to detect 390 mutations across 30 cancer genes. Formalin fixed, paraffin-embedded specimens were evaluated from 820 Registry patients. The genes most frequently mutated across multiple cancer types were BRAF, PIK3C4, KRAS, and NRAS. Less common mutations were also observed in AKT1, CTNNB1, FGFR2, FGFR3, GNAQ, HRAS, and MAP2K1. Notably, 48 of 77 PIK3C4-mutant cases (62%) harbored at least one additional mutation in another gene, most often KRAS. Among melanomas, only 54 of 73 BRAF mutations (74%) were the V600E substitution. These findings demonstrate the diversity and complexity of mutations in druggable targets among the different cancer types and underscore the need for a broad-spectrum, prospective genotyping approach to personalized cancer medicine. (J Mol Diagn 2011, 13: 504-513; DOI: 10.1016/j.jmoldx.2011.04.003)
C1 [Corless, Christopher L.] OHSU, Dept Pathol, Knight Canc Inst, Portland, OR 97239 USA.
[Beadling, Carol; Heinrich, Michael C.] OHSU, Div Hematol Oncol, Portland, OR 97239 USA.
[Schuff, Kathryn G.] OHSU, Div Endocrinol, Portland, OR 97239 USA.
[Corless, Christopher L.] Portland VA Med Ctr, Portland, OR USA.
RP Corless, CL (reprint author), OHSU, Dept Pathol, Knight Canc Inst, Mailcode L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM corlessc@ohsu.edu
OI Patterson, Janice/0000-0002-8969-2933
FU Novartis Pharmaceuticals
FX This study was supported in part with funding from Novartis
Pharmaceuticals.
NR 65
TC 54
Z9 54
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD SEP
PY 2011
VL 13
IS 5
BP 504
EP 513
DI 10.1016/j.jmoldx.2011.04.003
PG 10
WC Pathology
SC Pathology
GA 865JG
UT WOS:000298306600006
PM 21726664
ER
PT J
AU Hurley, RA
Filley, CM
Taber, KH
AF Hurley, Robin A.
Filley, Christopher M.
Taber, Katherine H.
TI Central Pontine Myelinolysis: A Metabolic Disorder of Myelin
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Editorial Material
ID OSMOTIC DEMYELINATION SYNDROME; MAGNETIC-RESONANCE-SPECTROSCOPY;
EXTRAPONTINE MYELINOLYSIS; DIFFUSION; PATIENT; HYPONATREMIA;
MANIFESTATIONS; PLASMAPHERESIS; COMPLICATION; ALCOHOLISM
C1 [Hurley, Robin A.; Taber, Katherine H.] WG Hefner Vet Affairs Med Ctr, Vet Affairs Midatlantic Mental Illness Res Educ &, Salisbury, NC 28144 USA.
[Hurley, Robin A.; Taber, Katherine H.] WG Hefner Vet Affairs Med Ctr, Res & Educ Serv Line, Salisbury, NC USA.
[Hurley, Robin A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat, Winston Salem, NC USA.
[Hurley, Robin A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA.
[Hurley, Robin A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Filley, Christopher M.] Univ Colorado, Sch Med, Behav Sect, Denver, CO USA.
[Filley, Christopher M.] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA.
[Taber, Katherine H.] Edward Via Coll Osteopath Med, Div Biomed Sci, Blacksburg, VA USA.
[Taber, Katherine H.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA.
RP Hurley, RA (reprint author), Hefner VA Med Ctr, Salisbury, NC 28144 USA.
EM Robin.Hurley@va.gov
NR 56
TC 0
Z9 0
U1 0
U2 3
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 FAL
PY 2011
VL 23
IS 4
BP IV
EP 374
PG 7
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 875GT
UT WOS:000299019100001
ER
PT J
AU Wagner, PJ
Wortzel, HS
Frey, KL
Anderson, CA
Arciniegas, DB
AF Wagner, Peter J.
Wortzel, Hal S.
Frey, Kimberly L.
Anderson, C. Alan
Arciniegas, David B.
TI Clock-Drawing Performance Predicts Inpatient Rehabilitation Outcomes
After Traumatic Brain Injury
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID POSTTRAUMATIC AMNESIA; PRACTICAL SCALE; SEVERITY; MODERATE; BATTERY
AB The authors used clock-drawing performance to assess cognition and predict inpatient rehabilitation outcomes among persons with traumatic brain injury. Clock-drawing performance, as assessed with the Clock Drawing Interpretation Scale, predicts rehabilitation length of stay as well as Functional Independence Measure scores at the time of neurobehavioral assessment and rehabilitation discharge. (The Journal of Neuropsychiatry and Clinical Neurosciences 2011; 23:449-453)
C1 [Wagner, Peter J.; Wortzel, Hal S.; Frey, Kimberly L.; Anderson, C. Alan; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Psychiat, Neurobehav Disorders Program, Aurora, CO 80045 USA.
[Wortzel, Hal S.] Denver Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 19, Denver, CO USA.
[Anderson, C. Alan; Arciniegas, David B.] Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Aurora, CO USA.
[Anderson, C. Alan] Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA.
RP Arciniegas, DB (reprint author), Univ Colorado, Sch Med, Dept Psychiat, Neurobehav Disorders Program, Aurora, CO 80045 USA.
EM David.Arciniegas@UCDenver.edu
FU HCA/HealthONE Spalding Rehabilitation Hospital; VA VISN-19 Mental
Illness Research, Education, and Clinical Center
FX This work was supported in part by HCA/HealthONE Spalding Rehabilitation
Hospital and the VA VISN-19 Mental Illness Research, Education, and
Clinical Center.
NR 17
TC 5
Z9 5
U1 0
U2 1
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 FAL
PY 2011
VL 23
IS 4
BP 449
EP 453
PG 5
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 875GT
UT WOS:000299019100012
PM 22231317
ER
PT J
AU Zelenetz, AD
Ahmed, I
Braud, EL
Cross, JD
Davenport-Ennis, N
Dickinson, BD
Goldberg, SE
Gottlieb, S
Johnson, PE
Lyman, GH
Markus, R
Matulonis, UA
Reinke, D
Li, EC
DeMartino, J
Larsen, JK
Hoffman, JM
AF Zelenetz, Andrew D.
Ahmed, Islah
Braud, Edward Louis
Cross, James D.
Davenport-Ennis, Nancy
Dickinson, Barry D.
Goldberg, Steven E.
Gottlieb, Scott
Johnson, Philip E.
Lyman, Gary H.
Markus, Richard
Matulonis, Ursula A.
Reinke, Denise
Li, Edward C.
DeMartino, Jessica
Larsen, Jonathan K.
Hoffman, James M.
TI NCCN Biosimilars White Paper: Regulatory, Scientific, and Patient Safety
Perspectives
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
DE Biosimilars; follow-on biologics; health policy
ID DRUG-THERAPY; NAMES
AB Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval. (JNCCN 2011; 9[Suppl 4]: S1-S22)
C1 [Zelenetz, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Ahmed, Islah] Hospira Inc, Lake Forest, IL USA.
[Braud, Edward Louis] Springfield Reg Canc Ctr, Springfield, MO USA.
[Dickinson, Barry D.] Amer Med Assoc, Chicago, IL 60610 USA.
[Hoffman, James M.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Lyman, Gary H.] Duke Canc Inst, Durham, NC USA.
[Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Reinke, Denise] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Zelenetz, AD (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 30
TC 50
Z9 51
U1 0
U2 5
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD SEP
PY 2011
VL 9
SU 4
BP S1
EP S22
PG 22
WC Oncology
SC Oncology
GA 865XP
UT WOS:000298344500001
PM 21976013
ER
PT J
AU Spigner, C
Lyles, CR
Galvin, G
Sabin, J
Davis, C
Dick, A
Young, BA
AF Spigner, Clarence
Lyles, Courtney Rees
Galvin, Georgia
Sabin, Janice
Davis, Connie
Dick, Andre
Young, Bessie A.
TI A Qualitative Assessment of Personal and Social Responsibility for
Kidney Disease: The Increasing Kidney Disease Awareness Network
Transplant Project
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE kidney; transplant; race/ethnicity; physicians; patient self-management;
qualitative research
ID STAGE RENAL-DISEASE; SICK ROLE; ETHNIC-DIFFERENCES; PUBLIC-HEALTH;
UNITED-STATES; POPULATION; CARE; END; RACE; DISPARITIES
AB Introduction: Limited qualitative research has explored opinions of kidney disease health care providers regarding racial and ethnic disparities in access to and receipt of kidney transplantation.
Methods: Key informant interviews were conducted among transplant nephrologists, nephrologists, transplant social workers, and transplant coordinators to determine barriers to transplantation among African Americans compared to whites with end-stage renal disease (ESRD).
Analysis: Thirty-eight interviews were audio recorded and transcribed to hardcopy for content analysis. Grounded theory was used to determine dominant themes within the interviews. Reliability and validity were ensured by several coinvestigators independently sorting verbatim responses used for generating themes and subsequent explanations.
Results: Several major categories arose from analysis of the transcripts. Under the category of personal and social responsibility for kidney transplantation, interviews revealed 4 major themes: negative personal behaviors, acquisition of and lack of self-treatment of comorbid conditions, lack of individual responsibility, and the need for more social responsibility. Many providers perceived patients as being largely responsible for the development of ESRD, while some providers expressed the idea that more social responsibility was needed to improve poor health status and disparities in kidney transplantation rates.
Conclusion: Kidney disease health providers seemed torn between notions of patients' accountability and social responsibility for racial disparities in chronic kidney disease and ESRD. Further research is needed to clarify which aspects contribute most to disparities in access to transplantation.
C1 [Spigner, Clarence; Lyles, Courtney Rees; Young, Bessie A.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA.
[Sabin, Janice] Univ Washington, Dept Med Educ & Biomed Informat, Seattle, WA 98195 USA.
[Young, Bessie A.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
[Davis, Connie] Univ Washington, Div Nephrol & Transplantat, Seattle, WA 98195 USA.
[Galvin, Georgia; Young, Bessie A.] Puget Sound Hlth Care Syst, Vet Adm, Seattle, WA USA.
RP Young, BA (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,152-E, Seattle, WA 98108 USA.
EM youngb@u.wash-ington.edu
FU NIH [R01DK079745]; National Institute of Diabetes and Digestive and
Kidney Diseases; Veterans Affairs Puget Sound Health Care System,
Seattle, Washington
FX The project described was supported by Dr Young's NIH grant award
(R01DK079745) from the National Institute of Diabetes and Digestive and
Kidney Diseases. This material is also the result of work supported by
resources (Dr Young) from the Veterans Affairs Puget Sound Health Care
System, Seattle, Washington.
NR 37
TC 2
Z9 2
U1 2
U2 8
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD SEP-OCT
PY 2011
VL 103
IS 9-10
BP 879
EP 884
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 869BU
UT WOS:000298571500012
PM 22364056
ER
PT J
AU Andreotti, RF
Lee, SI
Allison, SOD
Bennett, GL
Brown, DL
Dubinsky, T
Glanc, P
Javitt, MC
Mitchell, DG
Podrasky, AE
Shipp, TD
Siegel, CL
Wong-You-Cheong, JJ
Zelop, CM
AF Andreotti, Rochelle F.
Lee, Susanna I.
Allison, Sandra O. DeJesus
Bennett, Genevieve L.
Brown, Douglas L.
Dubinsky, Theodore
Glanc, Phyllis
Javitt, Marcia C.
Mitchell, Donald G.
Podrasky, Ann E.
Shipp, Thomas D.
Siegel, Cary Lynn
Wong-You-Cheong, Jade J.
Zelop, Carolyn M.
TI ACR Appropriateness Criteria (R) Acute Pelvic Pain in the Reproductive
Age Group
SO ULTRASOUND QUARTERLY
LA English
DT Article
DE appropriateness criteria; pelvic pain; acute; imaging; diagnosis
ID DEEP VENOUS THROMBOSIS; HELICAL COMPUTED-TOMOGRAPHY; ACUTE APPENDICITIS;
ADNEXAL TORSION; INFLAMMATORY-DISEASE; PREGNANT PATIENTS; SUSPECTED
APPENDICITIS; SONOGRAPHIC FINDINGS; RADIATION-EXPOSURE; ECTOPIC
PREGNANCY
AB Premenopausal women who present with acute pelvic pain frequently pose a diagnostic dilemma, exhibiting nonspecific signs and symptoms, the most common being nausea, vomiting, and leukocytosis. Diagnostic considerations encompass multiple organ systems, including obstetric, gynecologic, urologic, gastrointestinal, and vascular etiologies. The selection of imaging modality is determined by the clinically suspected differential diagnosis. Thus, a careful evaluation of such a patient should be performed and diagnostic considerations narrowed before a modality is chosen. Transvaginal and transabdominal pelvic sonography is the modality of choice when an obstetric or gynecologic abnormality is suspected, and computed tomography is more useful when gastrointestinal or genitourinary pathology is more likely. Magnetic resonance imaging, when available in the acute setting, is favored over computed tomography for assessing pregnant patients for nongynecologic etiologies because of the lack of ionizing radiation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
C1 [Andreotti, Rochelle F.] Vanderbilt Univ, Med Ctr, Dept Radiol, Nashville, TN 37232 USA.
[Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Allison, Sandra O. DeJesus] Georgetown Univ Hosp, Dept Radiol, Washington, DC 20007 USA.
[Bennett, Genevieve L.] NYU Med Ctr, Dept Radiol, New York, NY 10016 USA.
[Brown, Douglas L.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Dubinsky, Theodore] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA.
[Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Dept Med Imaging, Toronto, ON M4N 3M5, Canada.
[Javitt, Marcia C.] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA.
[Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA.
[Podrasky, Ann E.] Baptist Hosp Miami, S Miami Ctr Women & Infants, Dept Radiol, Miami, FL USA.
[Shipp, Thomas D.] Amer Coll Obstetricians & Gynecologists, Washington, DC USA.
[Shipp, Thomas D.] Diagnost Ultrasound Associates, Boston, MA USA.
[Siegel, Cary Lynn] Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO USA.
[Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Dept Diagnost Radiol, Baltimore, MD 21201 USA.
[Zelop, Carolyn M.] Univ Connecticut, Sch Med, Dept Radiol, Farmington, CT USA.
RP Andreotti, RF (reprint author), Amer Coll Radiol, Dept Qual & Safety, 1891 Preston White Dr, Reston, VA 20191 USA.
EM acr_ac@acr.org
NR 53
TC 6
Z9 6
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-8771
J9 ULTRASOUND Q
JI Ultrasound Q.
PD SEP
PY 2011
VL 27
IS 3
BP 205
EP 210
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 854XF
UT WOS:000297527400008
PM 21873877
ER
PT J
AU Lam, A
Wolpin, S
Nguyen, J
Berry, DL
Kurth, A
Morisky, DE
AF Lam, Annie
Wolpin, Seth
Nguyen, Juliet
Berry, Donna L.
Kurth, Ann
Morisky, Donald E.
TI Is 60 seconds enough? Can talking pill bottles be used in the community
pharmacy setting?
SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION
LA English
DT Letter
C1 [Lam, Annie] Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
[Berry, Donna L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA.
[Kurth, Ann] NYU, Global Hlth Initiat, Coll Nursing, New York, NY USA.
[Morisky, Donald E.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA.
RP Lam, A (reprint author), Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
EM aylam@u.washington.edu
RI Kurth, Ann/A-1615-2013
NR 0
TC 0
Z9 0
U1 0
U2 2
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 SEP-OCT
PY 2011
VL 51
IS 5
BP 569
EP 570
DI 10.1331/JAPhA.2011.10096
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 857XD
UT WOS:000297757100004
PM 21896452
ER
PT J
AU Borg-Stein, JP
Fogelman, DJ
Ackerman, KE
AF Borg-Stein, Joanne P.
Fogelman, David J.
Ackerman, Kathryn E.
TI Exercise, Sports Participation, and Musculoskeletal Disorders of
Pregnancy and Postpartum
SO SEMINARS IN NEUROLOGY
LA English
DT Article
DE Pregnancy; orthopedic; musculoskeletal; exercise; sports
ID GESTATIONAL DIABETES-MELLITUS; RECREATIONAL PHYSICAL-ACTIVITY;
CARPAL-TUNNEL SYNDROME; NECROSIS-FACTOR-ALPHA; TRANSIENT OSTEOPOROSIS;
SYMPHYSIS PUBIS; BACK-PAIN; FETOPLACENTAL GROWTH; REGULAR EXERCISE;
BIRTH-WEIGHT
AB The benefits of rigorous physical activity have long been proclaimed by the medical community. However, consensus regarding exercise duration and intensity in pregnancy has been more difficult to achieve. Conservative exercise guidelines for pregnant women were issued broadly in the 1980s due to limited evidence regarding safety. More recent evidence has failed to demonstrate ill effects of physical activity during pregnancy, as any effects on the mother and the fetus have thus far shown to be positive. The physical discomfort experienced by virtually all women during pregnancy, nearly 25% of whom experience at least temporarily disabling symptoms, is often a barrier to participation in an exercise program. An approach to developing an exercise program during pregnancy will be discussed in this article, as well as the potential benefits of such a program for the maternal-fetal unit, and common pregnancy-related musculoskeletal conditions, including a discussion of the anatomy, physiology, diagnosis, and treatment of such disorders.
C1 [Borg-Stein, Joanne P.; Fogelman, David J.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA.
[Borg-Stein, Joanne P.] Newton Wellesley Hosp, Spine Ctr, Newton, MA USA.
[Borg-Stein, Joanne P.] Spaulding Rehabil Hosp Wellesley, Boston, MA 02114 USA.
[Fogelman, David J.] Spaulding Rehabil Hosp, Boston, MA USA.
[Ackerman, Kathryn E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Ackerman, Kathryn E.] Childrens Hosp Boston, Div Sports Med, Boston, MA USA.
[Ackerman, Kathryn E.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Borg-Stein, JP (reprint author), Spaulding Rehabil Hosp Wellesley, 125 Nashua St, Boston, MA 02114 USA.
EM jborgstein@partners.org
NR 75
TC 0
Z9 0
U1 4
U2 21
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0271-8235
EI 1098-9021
J9 SEMIN NEUROL
JI Semin. Neurol.
PD SEP
PY 2011
VL 31
IS 4
BP 413
EP 422
DI 10.1055/s-0031-1293541
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 856MF
UT WOS:000297645100009
PM 22113514
ER
PT J
AU Vaillant, G
AF Vaillant, George
TI A FIRST-RATE MADNESS: Uncovering the Links Between Leadership and Mental
Illness
SO AMERICAN SCHOLAR
LA English
DT Book Review
C1 [Vaillant, George] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Vaillant, George] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vaillant, George] Harvard Univ, Study Adult Dev, Hlth Serv, Cambridge, MA 02138 USA.
RP Vaillant, G (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU PHI BETA KAPPA SOC
PI WASHINGTON
PA 1785 MASSACHUSETTS AVENUE, N W FOURTH FL,, WASHINGTON, DC 20036 USA
SN 0003-0937
J9 AM SCHOLAR
JI Am. Sch.
PD FAL
PY 2011
VL 80
IS 4
BP 125
EP 127
PG 3
WC Humanities, Multidisciplinary
SC Arts & Humanities - Other Topics
GA 856RM
UT WOS:000297661100036
ER
PT J
AU Bauer, M
Demyttenaere, K
El-Khalili, N
Thase, M
Papakostas, GI
Szamosi, J
Earley, W
Eriksson, H
AF Bauer, M.
Demyttenaere, K.
El-Khalili, N.
Thase, M.
Papakostas, G. I.
Szamosi, J.
Earley, W.
Eriksson, H.
TI Efficacy of adjunct quetiapine extended-release in major depressive
disorder: a pooled analysis of SSRI and SNRI patient subgroups
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 24th Congress Meeting of European-College-of-Neuropsychopharmacology
CY SEP 03-07, 2011
CL Paris, FRANCE
SP European Coll Neuropsychopharmacol
ID DOUBLE-BLIND; ANTIDEPRESSANT; THERAPY
C1 [Bauer, M.] Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, Dresden, Germany.
[Demyttenaere, K.] Univ Hosp Gasthuisberg, Dept Psychiat, B-3000 Louvain, Belgium.
[Thase, M.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Papakostas, G. I.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Szamosi, J.; Eriksson, H.] AstraZeneca, R&D, Sodertalje, Sweden.
NR 3
TC 1
Z9 1
U1 2
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2011
VL 21
SU 3
BP S441
EP S442
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 852US
UT WOS:000297383600483
ER
PT J
AU Papakostas, GI
AF Papakostas, G. I.
TI No time to lose: rethinking treatment options in MDD
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 24th Congress Meeting of European-College-of-Neuropsychopharmacology
CY SEP 03-07, 2011
CL Paris, FRANCE
SP European Coll Neuropsychopharmacol
ID MAJOR DEPRESSIVE DISORDER; METAANALYSIS; PLACEBO
C1 [Papakostas, G. I.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
NR 3
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2011
VL 21
SU 3
BP S629
EP S630
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 852US
UT WOS:000297383600804
ER
PT J
AU Tran, P
Bradshaw, M
McKinney, A
Bymaster, F
Skolnick, P
Czobor, P
Huang, N
Manthis, J
Fava, M
AF Tran, P.
Bradshaw, M.
McKinney, A.
Bymaster, F.
Skolnick, P.
Czobor, P.
Huang, N.
Manthis, J.
Fava, M.
TI A placebo-controlled study of EB-1010, a novel triple re-uptake
inhibitor, in patients with major depressive disorder
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 24th Congress Meeting of European-College-of-Neuropsychopharmacology
CY SEP 03-07, 2011
CL Paris, FRANCE
SP European Coll Neuropsychopharmacol
C1 [Tran, P.; Bymaster, F.; Manthis, J.] Euthym Biosci Inc, Res & Dev, Cambridge, MA USA.
[Bradshaw, M.] Global Consulting Partners LLC, Res & Dev, Princeton, NJ USA.
[McKinney, A.] Euthym Biosci Inc, Management, Cambridge, MA USA.
[Skolnick, P.; Czobor, P.] DOV Pharmaceut, Res & Dev, Somerset, NJ USA.
[Huang, N.] QRx Pharma, Res & Dev, Bedminster, NJ USA.
[Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 1
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD SEP
PY 2011
VL 21
SU 3
BP S384
EP S385
PG 2
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 852US
UT WOS:000297383600386
ER
PT J
AU Bamboat, ZM
DePeralta, D
Dursun, A
Berger, DL
Bordeianou, L
AF Bamboat, Zubin M.
DePeralta, Danielle
Dursun, Abdulmetin
Berger, David L.
Bordeianou, Liliana
TI Factors affecting lymph node yield from patients undergoing colectomy
for cancer
SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
LA English
DT Article
DE Lymph node yield; Colon cancer; Colectomy; Pathologist training
ID COMPLETE MESOCOLIC EXCISION; AMERICAN JOINT COMMITTEE; COLON-CANCER;
COLORECTAL-CANCER; PROGNOSTIC-FACTORS; MINIMUM NUMBER; SURVIVAL;
SURGERY; PATHOLOGISTS; RESECTION
AB Purpose Lymph node (LN) yield is a critical component of colon cancer staging and is often a surrogate for quality assessment in surgery. We investigated the impact of pathologists' training on LN harvest.
Methods This is a retrospective review on 137 patients undergoing elective colectomy for adenocarcinoma at a single institution from 2008 to 2009. We studied surgeon-, patient- and pathologist-derived factors, and identified independent variables affecting LN yield using logistic regression.
Results LN yield was similar between open and laparoscopic resections (21 versus 23, p=0.54). Similarly, nodal counts were independent of tumor location (p=0.08) and no difference was noted between colorectal and general surgeons (24 versus 21, p=0.31). Strikingly, the number of LNs reported by PGY-1 pathology residents was significantly higher than those with two or more years of training (24 versus 19, p=0.02). On logistic regression, only the reporting pathologists' year in training remained a significant predictor of the number of nodes reported (OR=5.28, p=0.0001).
Conclusions LN retrieval in patients with colon cancer is inversely related to the interpreting pathologists' level of training.
C1 [Bamboat, Zubin M.; DePeralta, Danielle; Dursun, Abdulmetin; Berger, David L.; Bordeianou, Liliana] Massachusetts Gen Hosp, Div Gastrointestinal Surg, Boston, MA 02114 USA.
[Bamboat, Zubin M.; DePeralta, Danielle; Dursun, Abdulmetin; Berger, David L.; Bordeianou, Liliana] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Div Gastrointestinal Surg, Boston, MA 02114 USA.
EM lbordeianou@partners.org
NR 30
TC 14
Z9 14
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0179-1958
J9 INT J COLORECTAL DIS
JI Int. J. Colorectal Dis.
PD SEP
PY 2011
VL 26
IS 9
BP 1163
EP 1168
DI 10.1007/s00384-011-1240-6
PG 6
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 851CS
UT WOS:000297246500011
PM 21573900
ER
PT J
AU Beauchamp, JP
Cesarini, D
Johannesson, M
van der Loos, MJHM
Koellinger, PD
Groenen, PJF
Fowler, JH
Rosenquist, JN
Thurik, AR
Christakis, NA
AF Beauchamp, Jonathan P.
Cesarini, David
Johannesson, Magnus
van der Loos, Matthijs J. H. M.
Koellinger, Philipp D.
Groenen, Patrick J. F.
Fowler, James H.
Rosenquist, J. Niels
Thurik, A. Roy
Christakis, Nicholas A.
TI Molecular Genetics and Economics
SO JOURNAL OF ECONOMIC PERSPECTIVES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HUMAN HEIGHT; INDIVIDUAL-DIFFERENCES; MISSING
HERITABILITY; MONOAMINE-OXIDASE; DICTATOR GAME; RISK-TAKING; BEHAVIOR;
DETERMINANTS; STRATIFICATION
C1 [Beauchamp, Jonathan P.; Rosenquist, J. Niels; Christakis, Nicholas A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Cesarini, David] NYU, Ctr Expt Social Sci, New York, NY USA.
[Cesarini, David] Inst Ind Econ IFN, Stockholm, Sweden.
[Johannesson, Magnus] Stockholm Sch Econ, S-11383 Stockholm, Sweden.
[van der Loos, Matthijs J. H. M.; Koellinger, Philipp D.; Groenen, Patrick J. F.; Thurik, A. Roy] Erasmus Sch Econ, Rotterdam, Netherlands.
[Fowler, James H.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Rosenquist, J. Niels] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Cambridge, MA USA.
[Rosenquist, J. Niels] Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA.
RP Beauchamp, JP (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
EM beauchamp.jonathan.pierre@gmail.com
RI Fowler, James/C-2750-2008; Thurik, Roy/A-9386-2012; Johannesson,
Magnus/E-9680-2011; Groenen, Patrick/D-3667-2009;
OI Fowler, James/0000-0001-7795-1638; Thurik, Roy/0000-0002-0242-6908;
Johannesson, Magnus/0000-0001-8759-6393; Groenen,
Patrick/0000-0001-6683-8971; Koellinger, Philipp/0000-0001-7413-0412;
Cesarini, David/0000-0002-0043-009X
FU NIA NIH HHS [P01 AG031093, P01 AG031093-04]; NIGMS NIH HHS [P41
GM103504]
NR 102
TC 33
Z9 34
U1 1
U2 27
PU AMER ECONOMIC ASSOC
PI NASHVILLE
PA 2014 BROADWAY, STE 305, NASHVILLE, TN 37203 USA
SN 0895-3309
J9 J ECON PERSPECT
JI J. Econ. Perspect.
PD FAL
PY 2011
VL 25
IS 4
BP 57
EP 82
DI 10.1257/jep.25.4.57
PG 26
WC Economics
SC Business & Economics
GA 851IX
UT WOS:000297262800003
PM 22427719
ER
PT J
AU Arriaga, AF
Elbardissi, AW
Regenbogen, SE
Greenberg, CC
Berry, WR
Lipsitz, S
Moorman, D
Kasser, J
Warshaw, AL
Zinner, MJ
Gawande, AA
AF Arriaga, Alexander F.
Elbardissi, Andrew W.
Regenbogen, Scott E.
Greenberg, Caprice C.
Berry, William R.
Lipsitz, Stuart
Moorman, Donald
Kasser, James
Warshaw, Andrew L.
Zinner, Michael J.
Gawande, Atul A.
TI A Policy-Based Intervention for the Reduction of Communication
Breakdowns in Inpatient Surgical Care: Results From a Harvard Surgical
Safety Collaborative EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB After technical errors, the most common cause of avoidable adverse events during inpatient surgical care is communication-related breakdowns. Lapses in communication have been associated with delays in care and increased patient morbidity. A previous study conducted at 4 academic medical centers examined surgical resident and attending surgeon communication practices and identified errors in communication for more than 30% of identified critical events. The data in that study also showed that residents and attending surgeons had not discussed the plan of care for 15% of randomly selected patients and that more than 20% of weekend patients had not been seen for more than 48 hours by an attending surgeon.
This nonrandomized study was designed to investigate whether development and implementation of an interventional policy in surgical departments would lead to improved resident-attending communication practices, increased frequency of attending-patient interactions, and reduced failures in communication associated with critical patient events. Communication practices were compared before and after implementation of the policy according to the following 3 measures: (1) transfer into the intensive unit; (2) unplanned intubation or ventilatory support; and (3) cardiac arrest, new arrhythmia, or hemodynamic instability. The results of intervention were examined for a 19-month period. Specific measures to reinforce use of the policies included a resident-pocket information card and periodic reminders. Medical charts and audit information of randomly selected surgical services and care units for surgical patients were reviewed; repeat audits were conducted.
Information on resident and attending surgeon communication practices for 211 critical events and 1360 patients were reviewed. After the policy was implemented, the proportion of critical events not conveyed by a resident to an attending surgeon decreased from 33% (26/80) to 2% (1/47), gaps in the frequency of reporting of patient status on weekends by the attending surgeon were virtually eliminated (P < 0.0001), and the percentage of patients not visited by an attending surgeon for more than 24 hours on a weekend decreased from 61% to 33% (P = 0.0002). Improvements in resident-attending communication led to changes in patient management in one third of cases.
These findings show that implementation of this policy significantly improved resident-attending communication practices, reduced the incidence of potentially harmful communication breakdowns, and led to changes in patient management in inpatient surgical care.
C1 [Arriaga, Alexander F.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
RP Arriaga, AF (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD SEP
PY 2011
VL 66
IS 9
BP 535
EP 537
DI 10.1097/OGX.0b013e31823b6056
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 851EQ
UT WOS:000297251600003
ER
PT J
AU Buscher, A
Hartman, C
Kallen, MA
Giordano, TP
AF Buscher, April
Hartman, Christine
Kallen, Michael A.
Giordano, Thomas P.
TI Validity of Self-Report Measures in Assessing Antiretroviral Adherence
of Newly Diagnosed, HAART-Naive, HIV Patients
SO HIV CLINICAL TRIALS
LA English
DT Article
DE adherence; cohort study; HIV; self-report; Spanish
ID THERAPY ADHERENCE; VIRAL SUPPRESSION; CLINICAL-PRACTICE; QUESTIONNAIRE;
TRIALS
AB Purpose: To compare the performance of self-report instruments assessing adherence to antiretroviral therapy (ART) in patients starting ART for the first time and in a predominately Hispanic population. Methods: Of 184 patients in a prospective observational cohort study of newly diagnosed, minority patients of low socioeconomic status, 54 were given Medication Event Monitoring System (MEMS) caps for their boosted protease inhibitor (RI) or non-nucleoside reverse transcriptase inhibitor (NNRTI). They completed a 4-week recall visual analogue scale (VAS), the Adult AIDS Clinical Trial Group (AACTG) 4-day recall instrument, and a 1-month recall qualitative single-item measure every 3 months for up to 18 months in English or Spanish. Electronic pharmacy records recorded refill dates. Spearman correlation coefficients were calculated to compare self-report measures with MEMS data and pharmacy data. Results: Of 46 patients with MEMS data, mean adherence was 84.7% (SD 35.6) by MEMS, 84.5% (SD 15.1) by pharmacy, 95.4% (SD 11.9) by VAS, 95.8% (SD 17.2) by AACTG, and 87.6% (SD 28.2) by qualitative single item. The correlation coefficient (CC) of VAS with MEMS was 0.37 (P < .01), and with pharmacy it was 0.34 (P < .01). The CC of the AACTG with MEMS was 0.32 (P < .01), and with pharmacy it was 0.28 (P < .01). The qualitative single item had a CC with MEMS of 0.24 (P < .01) and with pharmacy of 0.32 (P < .01). Spanish-speaking patients' VAS adherence had a CC of 0.40 (P < .01) with MEMS. Conclusions: The VAS, AACTG, and qualitative single-item measures correlated significantly with MEMS and pharmacy data. Our data support self-administration of the VAS, even in Spanish speakers.
C1 [Buscher, April; Hartman, Christine; Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Buscher, April; Hartman, Christine; Giordano, Thomas P.] Michael E DeBakey VA Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA.
[Kallen, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Houston, TX 77030 USA.
RP Giordano, TP (reprint author), Michael E DeBakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM tpg@bcm.tmc.edu
FU National Institute of Mental Health (NIMH) [R34MH074360]; Agency for
Healthcare Research and Quality (AHRQ) [U18HS016093]; Baylor/UT Houston
Center for AIDS [P30AI036211]; NIH HIV [T32AI07456]
FX Supported by National Institute of Mental Health (NIMH) grant
R34MH074360, Agency for Healthcare Research and Quality (AHRQ) grant
U18HS016093, the Baylor/UT Houston Center for AIDS Research grant
P30AI036211, NIH HIV T32AI07456, and the facilities and resources of the
Harris County Hospital District and the Michael E. DeBakey VA Medical
Center. Dr. Giordano is a researcher at the Michael E. DeBakey VA
Medical Center Health Services Research and Development Center of
Excellence, Houston, Texas. The views expressed in this article are
those of the authors and do not necessarily represent the views of the
US Department of Veterans Affairs.
NR 25
TC 22
Z9 22
U1 0
U2 5
PU THOMAS LAND PUBLISHERS, INC
PI ST LOUIS
PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA
SN 1528-4336
J9 HIV CLIN TRIALS
JI HIV Clin. Trials
PD SEP-OCT
PY 2011
VL 12
IS 5
BP 244
EP 254
DI 10.1310/hct1205-244
PG 11
WC Infectious Diseases; Pharmacology & Pharmacy
SC Infectious Diseases; Pharmacology & Pharmacy
GA 847UT
UT WOS:000296998700002
PM 22180522
ER
PT J
AU Haas, DW
Kuritzkes, DR
Ritchie, MD
Amur, S
Gage, BF
Maartens, G
Masys, D
Fellay, J
Phillips, E
Ribaudo, HJ
Freedberg, KA
Petropoulos, C
Manolio, TA
Gulick, RM
Haubrich, R
Kim, P
Dehlinger, M
Abebe, R
Telenti, A
AF Haas, David W.
Kuritzkes, Daniel R.
Ritchie, Marylyn D.
Amur, Shashi
Gage, Brian F.
Maartens, Gary
Masys, Dan
Fellay, Jacques
Phillips, Elizabeth
Ribaudo, Heather J.
Freedberg, Kenneth A.
Petropoulos, Christos
Manolio, Teri A.
Gulick, Roy M.
Haubrich, Richard
Kim, Peter
Dehlinger, Marjorie
Abebe, Rahel
Telenti, Amalio
CA Participants Workshop Pharmacogeno
TI Pharmacogenomics of HIV Therapy: Summary of a Workshop Sponsored by the
National Institute of Allergy and Infectious Diseases
SO HIV CLINICAL TRIALS
LA English
DT Article
DE HIV therapy; pharmacogenetics; pharmacogenomics; workshop
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ANTIRETROVIRAL THERAPY;
PLASMA-CONCENTRATIONS; HIV-1-INFECTED INDIVIDUALS; SLCO1B1
POLYMORPHISMS; EFAVIRENZ; HYPERSENSITIVITY; NEVIRAPINE; CYP2B6; ABACAVIR
AB Approximately 1 million people in the United States and over 30 million worldwide are living with human immunodeficiency virus type 1 (HIV-1). While mortality from untreated infection approaches 100%, survival improves markedly with use of contemporary antiretroviral therapies (ART). In the United States, 25 drugs are approved for treating HIV-1, and increasing numbers are available in resource-limited countries. Safe and effective ART is a cornerstone in the global struggle against the acquired immunodeficiency syndrome. Variable responses to ART are due at least in part to human genetic variants that affect drug metabolism, drug disposition, and off-site drug targets. Defining effects of human genetic variants on HIV treatment toxicity, efficacy, and pharmacokinetics has far-reaching implications. In 2010, the National Institute of Allergy and Infectious Diseases sponsored a workshop entitled, Pharmacogenomics A Path Towards Personalized HIV Care. This article summarizes workshop objectives, presentations, discussions, and recommendations derived from this meeting.
C1 [Haas, David W.; Ritchie, Marylyn D.; Masys, Dan] Vanderbilt Univ, Sch Med, Nashville, TN 37204 USA.
[Kuritzkes, Daniel R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kuritzkes, Daniel R.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA.
[Amur, Shashi] US FDA, Silver Spring, MD USA.
[Gage, Brian F.] Washington Univ, St Louis, MO USA.
[Maartens, Gary] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Fellay, Jacques; Telenti, Amalio] Univ Lausanne, Lausanne, Switzerland.
[Phillips, Elizabeth] Murdoch Univ, Royal Perth Hosp, Sir Charles Gairdner Hosp, Perth, WA, Australia.
[Phillips, Elizabeth] Univ Western Australia, Perth, WA 6009, Australia.
[Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Stat Data Anal Ctr, Boston, MA 02115 USA.
[Freedberg, Kenneth A.] Massachussetts Gen Hosp, Boston, MA USA.
[Petropoulos, Christos] Monogram Biosci, San Francisco, CA USA.
[Manolio, Teri A.] Natl Genome Res Inst, NIH, Bethesda, MD USA.
[Gulick, Roy M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Haubrich, Richard] Univ Calif San Diego, San Diego, CA 92103 USA.
[Kim, Peter; Dehlinger, Marjorie] NIAID, NIH, Bethesda, MD 20892 USA.
[Abebe, Rahel] Henry M Jackson Fdn DAIDS, Bethesda, MD USA.
RP Haas, DW (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Hlth 1 Hundred Oaks,719 Thompson Lane,, Nashville, TN 37204 USA.
EM david.w.haas@vanderbilt.edu
RI Ritchie, Marylyn/C-1114-2012; Maartens, Gary/F-3836-2014; Fellay,
Jacques/A-6681-2009
OI Maartens, Gary/0000-0003-3080-6606; Fellay, Jacques/0000-0002-8240-939X
FU National Institute of Allergies and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200800014C]; Bristol Myers Squibb; Boehringer Ingelheim; Merck;
Gilead Sciences; Abbott; Avexa; Boehringer-Ingelheim; Gilead;
GlaxoSmithKline (GSK); Oncolys; Roche; Siemens; Tobira; Vertex; ViiV;
Viro-Statics; VIRxSYS; ViiV Australia; Merck Pty Ltd; Tibotec; Pfizer;
Bristol-Myers Squibb; GSK; Monogram; GlaxoSmithKline; National Institute
of Allergy and Infectious Diseases; NIH Office of AIDS Research; AIDS
Clinical Trials Group [AI68636, AI38858, AI68634, AI38855]; Swiss
National Foundation [324730-124943, HL097036, AI64086, AI36214,
AI69432]; CHRP [MC08-SD-700, AI069472, HL065962, AI077505, AI42006,
AI085736]; [AI069439]; [RR024975]; [AI54999]; [AI51966];
[RR024996]; [RR69419]
FX The views expressed in written conference materials or publications and
by speakers and moderators at HHS-sponsored conferences do not
necessarily reflect the official policies of the US Department of Health
and Human Services nor does mention of trade names, commercial
practices, or organizations imply endorsement by the US Government. This
project has been funded in whole or in part with federal funds from the
National Institute of Allergies and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
contract no. HHSN272200800014C.; David W. Haas: Principal Investigator
for research grants to Vanderbilt from Bristol Myers Squibb, Boehringer
Ingelheim, Merck, Gilead Sciences. Daniel Kuritzkes: Consultant to
and/or received research support from Abbott, Avexa,
Boehringer-Ingelheim, Gilead, GlaxoSmithKline (GSK), Merck, Oncolys,
Roche, Siemens, Tobira, Vertex, ViiV, Viro-Statics and VIRxSYS. Marylyn
D. Ritchie: Consultant for Boehringer Ingelheim. Elizabeth Phillips:
Honoraria and consulting fees from ViiV Australia, Merck Pty Ltd, and
Tibotec. Christos Petropoulos: Employee of Monogram Biosciences, South
San Francisco, CA. Roy M. Gulick: Ad hoc consultant for Bristol-Myers,
Gilead, GSK, MedImmune, ViiV, and Virostatics, and as Principal
Investigator for research grants to Weill Cornell from Merck and Pfizer.
Richard Haubrich: Received honoraria or consultant fees from Abbott,
Bristol-Myers Squibb, Gilead Sciences, GSK, Merck, Monogram, Pfizer,
Roche, Tibotec, and ViiV and research support (to UCSD) from Abbott,
GlaxoSmithKline, Merck, Pfizer, and ViiV. No potential conflicts of
interest: Shashi Amur, Brian Gage, Gary Maartens, Dan Masys, Jacques
Fellay, Heather J. Ribaudo, Kenneth A. Freedberg, Ten A. Manolio, Peter
Kim, Marjorie Dehlinger, Rahel Abebe, and Amalio Telenti.; The workshop
entitled, Pharmacogenomics - A Path Towards Personalized HIV Care, was
supported by the National Institute of Allergy and Infectious Diseases
and the NIH Office of AIDS Research. This work was supported in part by
the AIDS Clinical Trials Group (grants AI68636, AI38858, AI68634, and
AI38855). Participants were also supported by the following: grants
AI069439, RR024975, and AI54999 (DWH); AI51966 (RMG); RR024996 (Cornell
CTSC); RR69419 (CTU); Swiss National Foundation 324730-124943 (AT);
HL097036 (BFG); AI64086, AI36214, AI69432, and CHRP MC08-SD-700 (RH);
AI069472 (DK); HL065962 and AI077505 (MDR); AI42006 and AI085736 (KAF).
NR 34
TC 8
Z9 9
U1 0
U2 4
PU THOMAS LAND PUBLISHERS, INC
PI ST LOUIS
PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA
SN 1528-4336
J9 HIV CLIN TRIALS
JI HIV Clin. Trials
PD SEP-OCT
PY 2011
VL 12
IS 5
BP 277
EP 285
DI 10.1310/hct1205-277
PG 9
WC Infectious Diseases; Pharmacology & Pharmacy
SC Infectious Diseases; Pharmacology & Pharmacy
GA 847UT
UT WOS:000296998700006
PM 22180526
ER
PT J
AU Mankey, VL
AF Mankey, Vaughn L.
TI Using Multimodal and Multimedia Tools in the Psychiatric Education of
Diverse Learners: Examples From the Mental Status Exam
SO ACADEMIC PSYCHIATRY
LA English
DT Editorial Material
ID LEARNING STYLES; WORKING-MEMORY; COGNITIVE LOAD; CAPACITY; INFORMATION;
STUDENTS; ATTENTION; LIMITS
C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Mankey, VL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM vmankey@gmail.com
NR 29
TC 1
Z9 1
U1 1
U2 6
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 SEP-OCT
PY 2011
VL 35
IS 5
BP 335
EP 339
PG 5
WC Education & Educational Research; Psychiatry
SC Education & Educational Research; Psychiatry
GA 846JF
UT WOS:000296892500015
PM 22007095
ER
PT J
AU Shin, JH
Chao, ST
Angelov, L
AF Shin, J. H.
Chao, S. T.
Angelov, L.
TI Stereotactic radiosurgery for spinal metastases: update on treatment
strategies
SO JOURNAL OF NEUROSURGICAL SCIENCES
LA English
DT Article
DE Spine; Radiosurgery; Neoplasm metastases; Radiation oncology
ID INTENSITY-MODULATED RADIOTHERAPY; CORD COMPRESSION; CONVENTIONAL
RADIOTHERAPY; PREOPERATIVE EVALUATION; PROGNOSTIC-FACTORS; PARASPINAL
TUMORS; BODY RADIOTHERAPY; SCORING SYSTEM; RADIATION; DISEASE
AB Metastatic tumors are the most common tumors that affect the spinal column and are the source of significant pain and disability in cancer patients. The management of symptomatic spinal metastases presents unique challenges to surgeons as a number of considerations specific to the underlying tumor histology, extent of disease, the functional status of the patient and response to systemic therapy often affect the role, timing and effectiveness of any surgical intervention. As surgical techniques have evolved, the focus of therapy has shifted towards minimizing the morbidity associated with treatments for patients in whom limited nutrition and functional reserve impact their overall survival. As such, stereotactic spinal radiosurgery (SRS) has emerged as a powerful adjunct to surgery as well as a stand-alone treatment option for patients with metastatic disease. Recent technological innovations such as intensity-modulated radiation therapy, image-guidance, and non-invasive spine immobilization have made significant improvements to the delivery of highly conformal radiation to spinal tumors. In this article, current treatment strategies utilizing SRS in the multidisciplinary management of spinal metastases are discussed.
C1 [Shin, J. H.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, Boston, MA 02114 USA.
[Chao, S. T.] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA.
[Angelov, L.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA.
RP Shin, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Sch Med, 55 Fruit St,WAC 745, Boston, MA 02114 USA.
EM johnhongshin@gmail.com
NR 59
TC 5
Z9 5
U1 0
U2 1
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0390-5616
J9 J NEUROSURG SCI
JI J. Neurosurg. Sci.
PD SEP
PY 2011
VL 55
IS 3
BP 197
EP 209
PG 13
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 837TH
UT WOS:000296225600005
PM 21968584
ER
PT J
AU Vachharajani, TJ
Moossavi, S
Salman, L
Wu, S
Dwyer, AC
Ross, J
Dukkipati, R
Maya, ID
Yevzlin, AS
Agarwal, A
Abreo, KD
Work, J
Asif, A
AF Vachharajani, Tushar J.
Moossavi, Shahriar
Salman, Loay
Wu, Steven
Dwyer, Amy C.
Ross, Jamie
Dukkipati, Ramanath
Maya, Ivan D.
Yevzlin, Alexander S.
Agarwal, Anil
Abreo, Kenneth D.
Work, Jack
Asif, Arif
TI Dialysis Vascular Access Management by Interventional Nephrology
Programs at University Medical Centers in the United States
SO SEMINARS IN DIALYSIS
LA English
DT Article
ID MULTIDISCIPLINARY APPROACH; HEALTH-CARE
AB The development of interventional nephrology has undoubtedly led to an improvement in patient care at many facilities across the United States. However, these services have traditionally been offered by interventional nephrologists in the private practice arena. While interventional nephrology was born in the private practice setting, several academic medical centers across the United States have now developed interventional nephrology programs. University Medical Centers (UMCs) that offer interventional nephrology face challenges, such as smaller dialysis populations, limited financial resources, and real or perceived political "turf'' issues.'' Despite these hurdles, several UMCs have successfully established interventional nephrology as an intricate part of a larger nephrology program. This has largely been accomplished by consolidating available resources and collaborating with other specialties irrespective of the size of the dialysis population. The collaboration with other specialties also offers an opportunity to perform advanced procedures, such as application of excimer laser and endovascular ultrasound. As more UMCs establish interventional nephrology programs, opportunities for developing standardized training centers will improve, resulting in better quality and availability of nephrology-related procedures, and providing an impetus for research activities.
C1 [Vachharajani, Tushar J.; Moossavi, Shahriar] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med Nephrol, Dialysis Access Grp, Winston Salem, NC 27157 USA.
[Salman, Loay; Asif, Arif] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Wu, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Dwyer, Amy C.] Univ Louisville, Louisville, KY 40292 USA.
[Ross, Jamie] Univ Calif, Davis Sch Med, Vasc Access Unit, Sacramento, CA USA.
[Dukkipati, Ramanath] Harbor UCLA Med Ctr, Div Nephrol, Torrance, CA 90509 USA.
[Maya, Ivan D.] Univ Alabama, Birmingham, AL USA.
[Yevzlin, Alexander S.] Univ Wisconsin, Madison, WI USA.
[Agarwal, Anil] Ohio State Univ, Columbus, OH 43210 USA.
[Abreo, Kenneth D.] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA.
[Work, Jack] Emory Univ, Atlanta, GA 30322 USA.
RP Vachharajani, TJ (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med Nephrol, Dialysis Access Grp, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM tvachhar@wfubmc.edu
NR 23
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-0959
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD SEP-OCT
PY 2011
VL 24
IS 5
BP 564
EP 569
DI 10.1111/j.1525-139X.2011.00985.x
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 835GW
UT WOS:000296025300017
PM 21999740
ER
PT J
AU Swearingen, B
Wu, N
Chen, SY
Pulgar, S
Biller, BMK
AF Swearingen, Brooke
Wu, Ning
Chen, Shih-Yin
Pulgar, Sonia
Biller, Beverly M. K.
TI HEALTH CARE RESOURCE USE AND COSTS AMONG PATIENTS WITH GUSHING DISEASE
SO ENDOCRINE PRACTICE
LA English
DT Article
ID CUSHINGS-DISEASE; TRANSSPHENOIDAL SURGERY; CARDIOVASCULAR RISK;
CONSENSUS STATEMENT; MORTALITY; COMPLICATIONS; PERSISTENT; REMISSION;
MASS; CURE
AB Objective: To assess health care costs associated with Cushing disease and to determine changes in overall and comorbidity-related costs after surgical treatment.
Methods: In this retrospective cohort study, patients with Cushing disease were identified from insurance claims databases by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for Cushing syndrome (255.0) and either benign pituitary adenomas (227.3) or hypophysectomy (07.6x) between 2004 and 2008. Each patient with Cushing disease was age- and sex-matched with 4 patients with nonfunctioning pituitary adenomas and 10 population control subjects. Comorbid conditions and annual direct health care costs were assessed within each calendar year. Postoperative changes in health care costs and comorbidity-related costs were compared between patients presumed to be in remission and those with presumed persistent disease.
Results: Of 877 identified patients with Cushing disease, 79% were female and the average age was 43.4 years. Hypertension, diabetes mellitus, and hyperlipidemia were more common among patients with Cushing disease than in patients with nonfunctioning pituitary adenomas or in control patients (P<.01). For every calendar year studied, patients with Cushing disease had significantly higher total health care costs (2008: $26440 [Cushing disease] vs $13708 [nonfunctioning pituitary adenomas] vs $5954 [population control], P<.01). Annual outpatient costs decreased significantly for patients in remission after surgery, and there was a trend towards improvement in overall disease-related costs with remission. A significant increase in postoperative health care costs was observed in those patients not in remission.
Conclusions: Patients with Cushing disease had more comorbidities than patients with nonfunctioning pituitary adenomas or control patients and incurred significantly higher annual health care costs; these costs decreased after successful surgery and increased after unsuccessful surgery. (Endocr Pract. 2011;17:681-690)
C1 [Swearingen, Brooke] Massachusetts Gen Hosp, Neurosurg Serv, Neuroendocrine Clin Ctr, Boston, MA 02114 USA.
[Wu, Ning; Chen, Shih-Yin] United BioSource Corp, Lexington, MA USA.
[Pulgar, Sonia] Novartis Pharmaceut, Florham Pk, NJ USA.
RP Swearingen, B (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Neuroendocrine Clin Ctr, 15 Parkman St, Boston, MA 02114 USA.
EM BSwearingen@partners.org
FU Novartis Pharmaceuticals Corporation
FX Funding for this project was provided by Novartis Pharmaceuticals
Corporation. Dr. Swearingen has served as a consultant for Novartis. Ms.
Pulgar is an employee of Novartis. Dr. Biller has served as a consultant
and principal investigator for Novartis and as a principal investigator
for Corcept. Dr. Wu and Dr. Chen have no multiplicity of interest to
declare.
NR 26
TC 15
Z9 15
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 SEP-OCT
PY 2011
VL 17
IS 5
BP 681
EP 690
DI 10.4158/EP10368.OR
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 838TJ
UT WOS:000296314800001
PM 21454233
ER
PT J
AU Daniels, GH
AF Daniels, Gilbert H.
TI WHAT IF MANY FOLLICULAR VARIANT PAPILLARY THYROID CARCINOMAS ARE NOT
MALIGNANT? A REVIEW OF FOLLICULAR VARIANT PAPILLARY THYROID CARCINOMA
AND A PROPOSAL FOR A NEW CLASSIFICATION
SO ENDOCRINE PRACTICE
LA English
DT Review
ID FINE-NEEDLE-ASPIRATION; FOLLOW-UP; MACROFOLLICULAR VARIANT;
DIFFERENTIAL-DIAGNOSIS; OBSERVER VARIATION; CLINICAL-FEATURES; PATTERNED
LESIONS; RAS MUTATIONS; PAX8-PPAR-GAMMA REARRANGEMENT; GENETIC
ALTERATIONS
AB Objectives: To review the relevant literature concerning follicular variant of papillary thyroid carcinoma (FVPTC) with an emphasis on the heterogeneity of this disorder and to propose a new classification for FVPTC on the basis of molecular diagnostics and apply the classification to a typical case.
Methods: English-language articles pertaining to FVPTC published between January 1990 and December 2010 were reviewed.
Results: FVPTC is particularly vexing. The criteria for diagnosing FVPTC appear to have changed over the years. Pathologists often disagree about the diagnosis of FVPTC. The clinical behavior of these tumors is variable. Molecular diagnostic studies suggest that FVPTC represents a heterogeneous group of disorders rather than a single entity.
Conclusions: On the basis of the available data, it is proposed that individual cases of FVPTC be reclassified as papillary thyroid carcinoma, follicular thyroid carcinoma, or follicular adenomas, after appropriate molecular biologic studies have been completed. Long-term follow-up studies to validate this classification are necessary. (Endocr Pract. 2011;17:768-787)
C1 [Daniels, Gilbert H.] Harvard Univ, Thyroid Unit, Massachusetts Gen Hosp, Canc Ctr,Med Sch, Boston, MA 02114 USA.
[Daniels, Gilbert H.] Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Daniels, GH (reprint author), Harvard Univ, Thyroid Unit, Massachusetts Gen Hosp, Canc Ctr,Med Sch, ACC 730, Boston, MA 02114 USA.
EM gdaniels@partners.org
NR 135
TC 14
Z9 14
U1 0
U2 4
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
J9 ENDOCR PRACT
JI Endocr. Pract.
PD SEP-OCT
PY 2011
VL 17
IS 5
BP 768
EP 787
DI 10.4158/EP10407.RA
PG 20
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 838TJ
UT WOS:000296314800011
PM 21940284
ER
PT J
AU Schoenfeld, JD
Dranoff, G
AF Schoenfeld, Jonathan D.
Dranoff, Glenn
TI Anti-angiogenic immunotherapy
SO HUMAN VACCINES
LA English
DT Editorial Material
DE angiogenesis; vaccine; immunotherapy; GM-CSF; angiopoietin
ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-INFILTRATING LYMPHOCYTES; IMMATURE
MYELOID CELLS; REGULATORY T-CELLS; ANTITUMOR IMMUNITY; OVARIAN-CANCER;
METASTATIC MELANOMA; COLORECTAL-CANCER; FACTOR RECEPTOR-2; THERAPEUTIC
IMPLICATIONS
C1 [Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Schoenfeld, Jonathan D.; Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA.
[Schoenfeld, Jonathan D.] Harvard Radiat Oncol Program, Boston, MA USA.
RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM glenn_dranoff@dfci.harvard.edu
FU Howard Hughes Medical Institute; NCI NIH HHS [R01 CA111506, R01
CA143083, CA78378, CA111506, P01 CA078378]; NIAID NIH HHS [AI29530, U19
AI029530, P01 AI029530]
NR 96
TC 9
Z9 9
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8600
EI 1554-8619
J9 HUM VACCINES
JI Hum. Vaccines
PD SEP
PY 2011
VL 7
IS 9
BP 976
EP 981
DI 10.4161/hv.7.9.16407
PG 6
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA 832VN
UT WOS:000295837200023
PM 21860259
ER
PT J
AU Urdaneta, RA
Daher, S
Leary, J
Emanuel, K
Chuang, SK
AF Urdaneta, Rainier A.
Daher, Shadi
Leary, Joseph
Emanuel, Kimberly
Chuang, Sung-Kiang
TI Factors Associated with Crestal Bone Gain on Single-Tooth Locking-Taper
Implants: The Effect of Nonsteroidal Anti-Inflammatory Drugs
SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS
LA English
DT Article
DE dental implants; nonsteroidal anti-inflammatory drugs; peri-implant bone
gain; prospective cohort study; risk factors
ID DENTAL IMPLANTS; RADIOGRAPHIC EVALUATION; BRANEMARK IMPLANTS; TITANIUM
IMPLANTS; WIDE-DIAMETER; REPLACEMENT; RATS; INHIBITION; DICLOFENAC;
MECHANISM
AB Purpose: To identify factors associated with crestal bone gain around single-tooth implants. Materials and Methods: A retrospective cohort study was conducted. More than 90 different local and systemic factors were documented. Descriptive statistics and univariate and multivariate mixed-effects regression models, adjusted for multiple implants in the same patient, were used to identify predictors of crestal bone gain after insertion of definitive restorations. Results: Eighty-one subjects who received 326 Bicon implants were followed for an average of 70.7 months. Eighty-one implants in 46 patients showed varying degrees of apparent bone gain over time. Variables associated with peri-implant bone gain in the first multivariate model were: type of opposing structure, tooth (P = .02); type of restoration, crown cemented on a prefabricated titanium abutment with a spherical base (P = .006); hydroxyapatite coating (P = .0005); implant size 5 x 8 mm (P = .02); and daily intake of nonsteroidal anti-inflammatory drugs (NSAIDs) (P =. 04). NSAIDs remained significantly correlated to crestal bone gain in the second multivariate analysis; an implant was significantly more likely to gain bone if the patient was taking NSAIDs daily (P = .02), but this effect was specific to hydroxyapatite-coated implants (P = .01). Conclusion: Daily doses of NSAIDs were correlated with a significant increase in crestal bone levels around single-tooth hydroxyapatite-coated implants following crown insertion. INT J ORAL MAXILLOFAC IMPLANTS 2011;26:1063-1078
C1 [Urdaneta, Rainier A.; Daher, Shadi; Emanuel, Kimberly] Implant Dent Ctr, Boston, MA USA.
[Daher, Shadi] Boston Univ, Dept Oral & Maxillofacial Surg, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA.
[Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Leary, Joseph] Private Practice Ltd Periodont, Norwood, MA USA.
RP Urdaneta, RA (reprint author), 25 Prairie Ave, Auburndale, MA 02466 USA.
EM rainieru@yahoo.com
NR 46
TC 12
Z9 12
U1 0
U2 2
PU QUINTESSENCE PUBLISHING CO INC
PI HANOVER PARK
PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA
SN 0882-2786
J9 INT J ORAL MAX IMPL
JI Int. J. Oral Maxillofac. Implants
PD SEP-OCT
PY 2011
VL 26
IS 5
BP 1063
EP 1078
PG 16
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 837WB
UT WOS:000296237700021
PM 22010091
ER
PT J
AU Tobin, MJ
AF Tobin, Martin J.
TI The new irrationalism in weaning A nova irracionalidade no desmame
SO JORNAL BRASILEIRO DE PNEUMOLOGIA
LA English
DT Editorial Material
ID MECHANICAL VENTILATION; SUPPORT
C1 [Tobin, Martin J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA.
[Tobin, Martin J.] Loyola Univ Chicago, Stritch Sch Med, Hines, IL USA.
RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA.
NR 16
TC 3
Z9 3
U1 0
U2 0
PU SOC BRASILEIRA PNEUMOLOGIA TISIOLOGIA
PI BRASILIA DF
PA SEPS 714-719, BLOCO E ASA SUL, SALAS 220-223, BRASILIA DF, CEP70390-145,
BRAZIL
SN 1806-3713
J9 J BRAS PNEUMOL
JI J. Bras. Pneumol.
PD SEP-OCT
PY 2011
VL 37
IS 5
BP 571
EP 573
PG 3
WC Respiratory System
SC Respiratory System
GA 837PA
UT WOS:000296214500001
PM 22042386
ER
PT J
AU Kradin, R
AF Kradin, Richard
TI THE PLACEBO RESPONSE an attachment strategy that counteracts the effects
of stress-related dysfunction
SO PERSPECTIVES IN BIOLOGY AND MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; MECHANISM; BRAIN;
EXPECTATION; MEDICINE; DISEASE; FMRI; LIFE
AB The placebo response represents an enigmatic element of therapeutics. The potency of placebo effects is highlighted by the fact that the current gold standard for determining therapeutic efficacy, the randomized controlled clinical trial, is based on identifying treatment responses that are statistically superior to those elicited by a placebo. Although much has been written concerning the phenomenology of placebos, little is known concerning how they are elicited, although recent research has demonstrated that placebo effects are mediated via objective physiological pathways. I have previously argued that the placebo response is a developmental achievement, rooted in implicit procedural memories that are linked to background affects of wellbeing evoked by a relational dynamic with a caregiver. This article develops this idea further, suggesting that placebo response represents a nervous-system response aimed at countering the dysphoric effects attributable to chronic stress, and that it is dependent on developmental attachment dynamics. A range of behaviors by caregivers that mimic those achieved during secure attachment are suggested to promote placebo responses.
C1 [Kradin, Richard] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kradin, Richard] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kradin, Richard] Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA.
RP Kradin, R (reprint author), Massachusetts Gen Hosp, Dept Med, Warren 253, Boston, MA 02114 USA.
EM rkradin@partners.org
NR 74
TC 1
Z9 1
U1 3
U2 5
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0031-5982
J9 PERSPECT BIOL MED
JI Perspect. Biol. Med.
PD FAL
PY 2011
VL 54
IS 4
BP 438
EP 454
PG 17
WC History & Philosophy Of Science; Medicine, Research & Experimental
SC History & Philosophy of Science; Research & Experimental Medicine
GA 835YV
UT WOS:000296074100002
PM 22019533
ER
PT J
AU Flores-Moreno, JM
Furlong, C
Rosowski, JJ
Harrington, E
Cheng, JT
Scarpino, C
Santoyo, FM
AF Flores-Moreno, J. M.
Furlong, Cosme
Rosowski, John J.
Harrington, Ellery
Cheng, Jeffrey T.
Scarpino, C.
Mendoza Santoyo, F.
TI Holographic Otoscope for Nanodisplacement Measurements of Surfaces Under
Dynamic Excitation
SO SCANNING
LA English
DT Article
DE optoelectronic holography; digital holography; otology; middle-ear
ID TYMPANIC-MEMBRANE; STROBOSCOPIC HOLOGRAPHY; MOTION; INTERFEROMETRY;
COMPONENTS; VIBRATION
AB We describe a novel holographic otoscope system for measuring nanodisplacements of objects subjected to dynamic excitation. Such measurements are necessary to quantify the mechanical deformation of surfaces in mechanics, acoustics, electronics, biology, and many other fields. In particular, we are interested in measuring the sound-induced motion of biological samples, such as an eardrum. Our holographic otoscope system consists of laser illumination delivery (IS), optical head (OH), and image processing computer (IP) systems. The IS delivers the object beam (OB) and the reference beam (RB) to the OH. The back-scattered light coming from the object illuminated by the OB interferes with the RB at the camera sensor plane to be digitally recorded as a hologram. The hologram is processed by the IP using the Fresnel numerical reconstruction algorithm, where the focal plane can be selected freely. Our holographic otoscope system is currently deployed in a clinic, and is packaged in a custom design. It is mounted in a mechatronic positioning system to increase its maneuverability degrees to be conveniently positioned in front of the object to be measured. We present representative results highlighting the versatility of our system to measure deformations of complex elastic surfaces in the wavelength scale including a copper foil membrane and postmortem tympanic membrane. SCANNING 33: 342-352, 2011. (C) 2011 Wiley Periodicals, Inc.
C1 [Flores-Moreno, J. M.; Furlong, Cosme; Harrington, Ellery] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA.
[Flores-Moreno, J. M.; Furlong, Cosme; Harrington, Ellery] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA.
[Flores-Moreno, J. M.; Mendoza Santoyo, F.] Ctr Invest Opt AC, Leon, Gto, Mexico.
[Furlong, Cosme; Rosowski, John J.; Cheng, Jeffrey T.; Scarpino, C.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Furlong, Cosme; Rosowski, John J.; Cheng, Jeffrey T.; Scarpino, C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Rosowski, John J.] MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA.
RP Flores-Moreno, JM (reprint author), Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA.
EM mflores@wpi.edu
OI Mendoza-Santoyo, Fernando/0000-0002-4596-3316
FU U.S. National Institute for Deafness and other Communicative Disorders;
Worcester Polytechnic Institute (WPI); Centro de Investigaciones en
Optica, A.C. (CIO); Massachusetts Eye and Ear Infirmary (MEEI); Lakshmi
Mittal Fund
FX Contract grant sponsors: U.S. National Institute for Deafness and other
Communicative Disorders; Worcester Polytechnic Institute (WPI); Centro
de Investigaciones en Optica, A.C. (CIO); Massachusetts Eye and Ear
Infirmary (MEEI); Lakshmi Mittal Fund.
NR 27
TC 9
Z9 9
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0161-0457
J9 SCANNING
JI Scanning
PD SEP-OCT
PY 2011
VL 33
IS 5
SI SI
BP 342
EP 352
DI 10.1002/sca.20283
PG 11
WC Instruments & Instrumentation; Microscopy
SC Instruments & Instrumentation; Microscopy
GA 839QZ
UT WOS:000296385000009
PM 21898459
ER
PT J
AU Devaraj, NK
Weissleder, R
AF Devaraj, Neal K.
Weissleder, Ralph
TI Biomedical Applications of Tetrazine Cycloadditions
SO ACCOUNTS OF CHEMICAL RESEARCH
LA English
DT Review
ID GROWTH-FACTOR RECEPTOR; LIVING CELLS; CLICK CHEMISTRY; BUILDING-BLOCKS;
CANCER-CELLS; REACTIVITY; SYSTEMS; MOLECULES; LIGATION; PROBES
AB Disease mechanisms are increasingly being resolved at the molecular level. Biomedical success at this scale creates synthetic opportunities for combining specifically designed orthogonal reactions In applications such as imaging, diagnostics, and therapy. For practical reasons, it would be helpful If bioorthogonal coupling reactions proceeded with extremely rapid kinetics (k>10(3) M(-1) s(-1)) and high specificity. Improving kinetics would minimize both the time and amount of labeling agent required to maintain high coupling yields. In this Account, we discuss our recent efforts to design extremely rapid bioorthogonal coupling reactions between tetrazines and strained alkenes.
These selective reactions were first used to covalently couple conjugated tetrazine near-Infrared-emitting fluorophores to dienophile-modifed extracellular proteins on living cancer cells. Confocal fluorescence microscopy demonstrated efficient and selective labeling, and control experiments showed minimal background fluorescence. Multistep techniques were optimized to work with nanomolar concentrations of labeling agent over a time scale of minutes: the result was successful real-time imaging of covalent modification. We subsequently discovered fluorogenic probes that Increase in fluorescence Intensity after the chemical reaction, leading to an improved signal-to-background ratio. Fluorogenic probes were used for Intracellular imaging of dienophiles. We further developed strategies to react and image chemotherapeutics, such as trans-cyclooctene taxol analogues, inside living cells. Because the coupling partners are small molecules (<300 Da), they offer unique steric advantages in multistep amplification.
We also describe recent success in using tetrazine reactions to label biomarkers on cells with magneto-fluorescent nanoparticles. Two-step protocols that use bioorthogonal chemistry can significantly amplify signals over both one-step labeling procedures as well as two-step procedures that use more sterically hindered biotin avidin interactions. Nanoparticles can be detected with fluorescence or magnetic resonance techniques. These strategies are now being routinely used on clinical samples for biomarker profiling to predict malignancy and patient outcome.
Finally, we discuss recent results with tetrazine reactions used for in vivo molecular imaging applications. Rapid tetrazine cycloadditions allow modular labeling of small molecules with the most commonly used positron emission tomography isotope, (18)F. Additionally, recent work has applied this reaction directly in vivo for the pretargeted imaging of solid tumors. Future work with tetrazine cycloadditions will undoubtedly lead to optimized protocols, improved probes, and additional biomedical applications.
C1 [Devaraj, Neal K.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
RP Devaraj, NK (reprint author), Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
EM ndevaraj@ucsd.edu; rweissleder@mgh.harvard.edu
RI Devaraj, Neal/B-4712-2014
FU NIH [P50CA86355, R01EB010011, K01EB010078, T32CA079443]
FX The authors gratefully acknowledge S. A. Hilderbrand, J. B. Haun, G. M.
Thurber, C. Castro, T. Reiner, N. Keliher, and R. Mazitschek for their
contributions to the above-discussed research as well as for their many
helpful discussions and suggestions. This work was funded in part by NIH
Grants P50CA86355, R01EB010011, K01EB010078, and T32CA079443.
NR 48
TC 179
Z9 180
U1 17
U2 201
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0001-4842
J9 ACCOUNTS CHEM RES
JI Accounts Chem. Res.
PD SEP
PY 2011
VL 44
IS 9
SI SI
BP 816
EP 827
DI 10.1021/ar200037t
PG 12
WC Chemistry, Multidisciplinary
SC Chemistry
GA 835ZH
UT WOS:000296075300017
PM 21627112
ER
PT J
AU Anderson, ICW
Sedaghat, AR
McGinley, BM
Redett, RJ
Boss, EF
Ishman, SL
AF Anderson, Iee Ching W.
Sedaghat, Ahmad R.
McGinley, Brian M.
Redett, Richard J.
Boss, Emily F.
Ishman, Stacey L.
TI Prevalence and Severity of Obstructive Sleep Apnea and Snoring in
Infants With Pierre Robin Sequence
SO CLEFT PALATE-CRANIOFACIAL JOURNAL
LA English
DT Article; Proceedings Paper
CT 66th Annual Meeting of the
American-Cleft-Palate-Craniofacial-Association
CY APR 20-25, 2009
CL Scottsdale, AZ
SP Amer Cleft Palate Craniofacial Assoc
DE infants; OSA; Pierre Robin sequence; snoring
ID CHILDREN; MANAGEMENT
AB Objective: To evaluate the prevalence and severity of obstructive sleep apnea in infants with Pierre Robin sequence prior to airway intervention and determine whether snoring correlates with the presence of obstructive sleep apnea in this population.
Design: Retrospective case series.
Setting: Urban tertiary care teaching hospital.
Participants/Methods: Review of infants with Pierre Robin sequence who underwent polysomnography in the first year of life from 2002 to 2007. Only results from the initial polysomnography were analyzed. A subgroup of consecutive prospectively tested patients was also evaluated.
Results: A total of 33 infants with Pierre Robin sequence were identified. Of these, 13 (39%), 11 girls and two boys, underwent polysomnography in the first year of life. The mean age at evaluation was 48 days (range, 7 to 214 days). Seven nonconsecutive and six consecutive patients were included, and no significant differences were seen between groups. Obstructive sleep apnea was identified in 11 of 13 (85%) infants. The mean obstructive apnea-hypopnea index was 33.5 (range, 0 to 85.7). Obstructive sleep apnea severity was mild in 2 of 11 (18%), moderate in 3 of 11 (27%), and severe in 6 of 11 (55%). Mean endtidal Pco(2) measurements were elevated at 59 mm Hg (range, 47 to 76 mm Hg). Mean oxygen saturation nadir was decreased at 80% (range, 68% to 93%). Snoring occurred in only 7 of 13 (54%). Of the subjects with obstructive sleep apnea, snoring occurred in 6 of 11 (55%).
Conclusion: The high incidence of obstructive sleep apnea in this group suggests that polysomnography should be promptly performed in children with Pierre Robin sequence. Although snoring was seen in the majority, the absence of snoring did not exclude the presence of obstructive sleep apnea.
C1 [Boss, Emily F.; Ishman, Stacey L.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA.
[Anderson, Iee Ching W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA USA.
[McGinley, Brian M.] Johns Hopkins Sch Med, Dept Pediat, Eudowood Div Pediat Pulmonol, Baltimore, MD 21287 USA.
[Redett, Richard J.] Johns Hopkins Sch Med, Dept Surg, Div Plast Surg, Baltimore, MD 21287 USA.
RP Ishman, SL (reprint author), Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St,Room 6231, Baltimore, MD 21287 USA.
EM sishman1@jhmi.edu
OI Ishman, Stacey/0000-0003-0997-9692
NR 19
TC 28
Z9 30
U1 1
U2 2
PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS
PI LAWRENCE
PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA
SN 1545-1569
J9 CLEFT PALATE-CRAN J
JI Cleft Palate-Craniofac. J.
PD SEP
PY 2011
VL 48
IS 5
BP 614
EP 618
DI 10.1597/10-100
PG 5
WC Dentistry, Oral Surgery & Medicine; Surgery
SC Dentistry, Oral Surgery & Medicine; Surgery
GA 835FK
UT WOS:000296020700017
PM 20815709
ER
PT J
AU Spicka, I
Mateos, MV
Redman, K
Dimopoulos, MA
Richardson, PG
AF Spicka, Ivan
Mateos, M. V.
Redman, K.
Dimopoulos, M. A.
Richardson, P. G.
TI An overview of the VISTA trial: newly diagnosed, untreated patients with
multiple myeloma ineligible for stem cell transplantation
SO IMMUNOTHERAPY
LA English
DT Editorial Material
DE bortezomib; multiple myeloma; peripheral neuropathy; proteasome
inhibition; treatment-naive older patients
ID BORTEZOMIB PLUS MELPHALAN; RANDOMIZED CONTROLLED-TRIAL; PERIPHERAL
NEUROPATHY; INITIAL TREATMENT; ELDERLY-PATIENTS; PHASE-3 VISTA; WORKING
GROUP; PREDNISONE; THERAPY; THALIDOMIDE
AB Multiple myeloma, a plasma cell neoplasm, is the second most common hematologic malignancy after non-Hodgkins lymphoma and is responsible for 2% of cancer deaths. Melphalan and prednisone (MP) has been the standard treatment in elderly patients for many decades. The VISTA study evaluated the effect of this combination with or without the first-in-class proteasome inhibitor bortezomib in newly diagnosed myeloma patients who were not candidates for autologous stem cell transplantation. Altogether 682 patients were enrolled and prospectively randomized in this trial. All patients received nine 6-week cycles of oral melphalan (9 mg/m(2)) and prednisone (60 mg/m(2)) on days 1-4, either alone or with bortezomib administered intravenously (1.3 mg/m(2) on days 1, 4, 8, 11, 22, 25, 29 and 32 during the first four cycles and on days 1, 8, 22, 29 during remaining course of therapy). Median time to progression (the primary end point of the trial) was 24 months in the bortezomib-containing group compared with 16.6 months in the control group (p < 0.001). Response was evaluated in 337 patients receiving bortezomib compared with 331 patients in the control group who received MP alone; the percentages of partial response or better was 71 vs 35% (p < 0.001), with complete response seen in 30 vs 4%, respectively (p < 0.001). Median response duration in both groups was 19.9 versus 13.1 months, respectively. Median overall survival has not been reached in VMP group compared with 43 months in the MP group (p < 0.001), and this benefit is maintained after long term follow-up and subsequent antimyeloma therapies. Hematological adverse events (AEs) were similar in both groups, although patients in the bortezomib group experienced more frequent peripheral sensory neuropathy (including 13% grade 3, with less than 1% grade 4). Overall, the occurrence of grade 3 AEs was higher in patients receiving bortezomib (53 vs 44%, p = 0.02), but the risk of grade 4 AEs was identical (28 vs 27%). These results confirm the superiority of MP plus bortezomib combination over MP therapy in treatment-naive patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.
C1 [Mateos, M. V.] Hosp Univ Salamanca, Salamanca, Spain.
[Redman, K.; Richardson, P. G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Dimopoulos, M. A.] Univ Athens, Sch Med, GR-11527 Athens, Greece.
RP Spicka, I (reprint author), Charles Univ Prague, Fac Med 1, Dept Med 1, Dept Clin Haematol, U Nemocnice 2, Prague 12808 2, Czech Republic.
EM spicka@cesnet.cz
RI 2011, Secribsal/D-9425-2012
NR 33
TC 3
Z9 4
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
EI 1750-7448
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PD SEP
PY 2011
VL 3
IS 9
BP 1033
EP 1040
DI 10.2217/IMT.11.104
PG 8
WC Immunology
SC Immunology
GA 838LS
UT WOS:000296293800006
PM 21913826
ER
PT J
AU Reiman, EM
McKhann, GM
Albert, MS
Sperling, RA
Petersen, RC
Blacker, D
AF Reiman, Eric M.
McKhann, Guy M.
Albert, Marilyn S.
Sperling, Reisa A.
Petersen, Ronald C.
Blacker, Deborah
TI Alzheimer's Disease: Implications of the Updated Diagnostic and Research
Criteria
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Editorial Material
ID MILD COGNITIVE IMPAIRMENT; ASSOCIATION WORKGROUPS; NATIONAL INSTITUTE;
RECOMMENDATIONS; GUIDELINES; DEMENTIA
C1 [Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA.
[McKhann, Guy M.; Albert, Marilyn S.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sperling, Reisa A.; Blacker, Deborah] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Reiman, EM (reprint author), Banner Alzheimers Inst, Phoenix, AZ USA.
FU NIA NIH HHS [P50 AG005146, P30 AG019610]
NR 16
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U1 0
U2 10
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD SEP
PY 2011
VL 72
IS 9
BP 1190
EP 1196
DI 10.4088/JCP.10087colc
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 828LO
UT WOS:000295502700005
PM 21951985
ER
PT J
AU Gurrera, RJ
Caroff, SN
Cohen, A
Carroll, BT
DeRoos, F
Francis, A
Frucht, S
Gupta, S
Levenson, JL
Mahmood, A
Mann, SC
Policastro, MA
Rosebush, PI
Rosenberg, H
Sachdev, PS
Trollor, JN
Velamoor, VR
Watson, CB
Wilkinson, JR
AF Gurrera, Ronald J.
Caroff, Stanley N.
Cohen, Abigail
Carroll, Brendan T.
DeRoos, Francis
Francis, Andrew
Frucht, Steven
Gupta, Sanjay
Levenson, James L.
Mahmood, Ahsan
Mann, Stephan C.
Policastro, Michael A.
Rosebush, Patricia I.
Rosenberg, Henry
Sachdev, Perminder S.
Trollor, Julian N.
Velamoor, Varadaraj R.
Watson, Charles B.
Wilkinson, Jayne R.
TI An International Consensus Study of Neuroleptic Malignant Syndrome
Diagnostic Criteria Using the Delphi Method
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID SYMPTOMS; SCALE
AB Objective: The lack of generally accepted diagnostic criteria for neuroleptic malignant syndrome (NMS) impedes research and clinical management of patients receiving antipsychotic medications The purpose of this study was to develop NMS diagnostic criteria reflecting a broad consensus among clinical knowledge experts, represented by an international multispecialty physician panel.
Participants: Eleven psychiatrists, 2 neurologists, 2 anesthesiologists, and 2 emergency medicine specialists participated in a formal Delphi consensus procedure.
Evidence: A core bibliography consisting of 12 prominent, current reviews of the NMS literature was identified by an objective, comprehensive electronic search strategy. Each panel member was given a copy of these references and asked to examine them before commencing the survey process.
Consensus Process: After reviewing the core bibliography, panel members were asked to list any clinical signs or symptoms or diagnostic studies that they believed, on the basis of their knowledge and clinical experience, were useful in making a diagnosis of NMS. In subsequent survey rounds, panel members assigned priority points to these items, and items that failed to receive a minimum priority score were eliminated from the next round. Information about individual panel member responses was fed back to the group anonymously in the form of the group median or mean and the number of members who had ranked or scored each survey item. The a priori consensus endpoint was defined operationally as a change of 10% or less in the mean priority score for any individual item, and an average absolute value change of 5% or less across all items, between consecutive rounds. The survey was conducted from January 2009 through September 2009.
Results: Consensus was reached on the fifth round regarding the following criteria: recent dopamine antagonist exposure, or dopamine agonist withdrawal; hyperthermia; rigidity; mental status alteration; creatine kinase elevation; sympathetic nervous system lability; tachycardia plus tachypnea; and a negative work-up for other causes. The panel also reached a consensus on the relative importance of these criteria and on the following critical values for quantitative criteria: hyperthermia, > 100.4 degrees F or > 38.0 degrees C on at least 2 occasions; creatine kinase elevation, at least 4 times the upper limit of normal; blood pressure elevation, >= 25% above baseline; blood pressure fluctuation, >= 20 mm Hg (diastolic) or >= 25 mm Hg (systolic) change within 24 hours; tachycardia, >= 25% above baseline; and tachypnea, >= 50% above baseline.
Conclusions: These diagnostic criteria significantly advance the field because they represent the consensus of an international multispecialty expert panel, include critical values, provide guidance regarding the relative importance of individual elements, and are less influenced by particular theoretical biases than most previously published criteria. They require validation before being applied in clinical settings. J Clin Psychiatry 2011;72(9):1222-1228 (C) Copyright 2011 Physicians Postgraduate Press, Inc.
C1 [Gurrera, Ronald J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Gurrera, Ronald J.] Vet Affairs VA Boston Healthcare Syst, Boston, MA USA.
[Caroff, Stanley N.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Cohen, Abigail] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[DeRoos, Francis] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA.
[Wilkinson, Jayne R.] Univ Penn, Sch Med, Dept Clin Neurol, Philadelphia, PA 19104 USA.
[Caroff, Stanley N.; DeRoos, Francis; Wilkinson, Jayne R.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Carroll, Brendan T.] Ohio Univ, Coll Osteopath Med, Athens, OH 45701 USA.
[Carroll, Brendan T.] Chillicothe VA Med Ctr, Chillicothe, OH USA.
[Francis, Andrew] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA.
[Frucht, Steven] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Gupta, Sanjay] SUNY Syracuse, Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Gupta, Sanjay; Mahmood, Ahsan] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA.
[Levenson, James L.] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23284 USA.
[Mahmood, Ahsan] Buffalo Psychiat Ctr, Buffalo, NY USA.
[Mann, Stephan C.] Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA.
[Mann, Stephan C.] Cent Montgomery Mental Hlth & Mental Retardat Ctr, Norristown, PA USA.
[Policastro, Michael A.] Wright State Univ, Boonshoft Sch Med, Dept Emergency Med, Dayton, OH 45435 USA.
[Policastro, Michael A.] Good Samaritan Hosp, Cincinnati, OH USA.
[Rosebush, Patricia I.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada.
[Rosenberg, Henry] St Barnabas Hosp, Dept Med Educ, Livingston, NJ USA.
[Rosenberg, Henry] St Barnabas Hosp, Dept Clin Res, Livingston, NJ USA.
[Rosenberg, Henry] Malignant Hyperthermia Assoc US, Sherburne, NY USA.
[Sachdev, Perminder S.; Trollor, Julian N.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia.
[Trollor, Julian N.] Univ New S Wales, Dept Dev Disabil Neuropsychiat, Sydney, NSW, Australia.
[Sachdev, Perminder S.] Prince Wales Hosp, Inst Neuropsychiat, Randwick, NSW 2031, Australia.
[Velamoor, Varadaraj R.] Univ Western Ontario, Dept Psychiat, Schulich Sch Med & Dent, London, ON N6A 3K7, Canada.
[Watson, Charles B.] Yale New Haven Hlth Syst, Bridgeport Hosp, Dept Anesthesia, Bridgeport, CT USA.
RP Gurrera, RJ (reprint author), Vet Affairs Boston Healthcare Syst, 940 Belmont St,116A, Brockton, MA 02301 USA.
EM ronald.gurrera@va.gov
RI Cohen, Abigail/K-9180-2013;
OI Cohen, Abigail/0000-0002-7425-7218; Sachdev,
Perminder/0000-0002-9595-3220; Trollor, Julian/0000-0002-7685-2977
FU Eli Lilly; GlaxoSmithKline; AstraZeneca; Pfizer; Takeda; Forest; Myriad;
Ono; NMSIS; AstraZeneca Pharmaceuticals LP [48804]; National Center for
Research Resources [UL1-RR024134]; VA Boston Healthcare System; American
Academy of Child & Adolescent Psychiatry; Malignant Hyperthermia
Association of the United States
FX Dr Gurrera has served as a volunteer consultant for the Neuroleptic
Malignant Syndrome Information Service (NMSIS) and is a member of the
NMSIS Professional Advisory Council. Dr Caroff has served as a
consultant for Eli Lilly and is a member of the NMSIS Professional
Advisory Council. Dr Carroll has received speakers bureau honoraria from
Eli Lilly and Pfizer and is an NMSIS hotline volunteer consultant. Dr
Francis is a member of the NMSIS Professional Advisory Council. Dr
Frucht has served as a consultant for UCB Pharma, Lundbeck, GE
Healthcare, Gerson Lehrman Group, and Guidepoint Global and is a member
of the NMSIS Professional Advisory Council. Dr Gupta has been a
consultant for Eli Lilly; has received research support from Eli Lilly,
GlaxoSmithKline, AstraZeneca, Pfizer, Takeda, Forest, Myriad, and Ono;
has served on advisory panels for Eli Lilly and Pamlab; has received
speakers bureau honoraria from Eli Lilly, GlaxoSmithKline, Novartis,
Forest, Merck, and AstraZeneca; and is a member of the NMSIS
Professional Advisory Council. Dr Levenson is a member of the NMSIS
Professional Advisory Council. Dr Mann is an NMSIS hotline volunteer
consultant. Dr Policastro has been an employee of Qualified Emergency
Specialists, Cincinnati, Ohio; has been a consultant to the US Drug
Enforcement Administration and Dyax Corporation; has received honoraria
from the Malignant Hyperthermia Association of the United States and
NMSIS; and has served as an advisory panel member for Dyax Corporation
and the Malignant Hyperthermia Association of the United States. Drs
Rosebush and Rosenberg are members of the NMSIS Professional Advisory
Council. Drs Sachdev and Trollor are NMSIS International Partners. Dr
Velamoor is a member of the NMSIS Professional Advisory Council. Dr
Watson is an NMSIS hotline volunteer consultant. Drs Cohen, DeRoos,
Mahmood, and Wilkinson report no financial relationships with any
commercial interest. All expert panel members received a small
honorarium from NMSIS for their participation.; This study received
administrative support from NMSIS (www.nmsis.org) and received financial
support from the Shah Educational Awareness Fund of NMSIS and from an
independent educational grant (#48804) from AstraZeneca Pharmaceuticals
LP to NMSIS. Dr. Cohen was supported by the Outcomes Measurement Methods
Core of the Center for Translational Science Award, National Center for
Research Resources grant number UL1-RR024134. This work was also
supported by the resources of and the use of the facilities at the VA
Boston Healthcare System.; The authors thank Jeffrey R. Strawn, MD, of
the Department of Psychiatry and Behavioral Neuroscience, University of
Cincinnati College of Medicine, Cincinnati, Ohio, for his assistance in
assembling the core bibliography for the expert panel and Marilyn Green
Larach, MD, FAAP, who is affiliated with the North American Malignant
Hyperthermia Registry of the Malignant Hyperthermia Association of the
United States, Pittsburgh, Pennsylvania, for her helpful comments about
the Delphi consensus process. Dr Strawn has received research support
from the American Academy of Child & Adolescent Psychiatry and Eli Lilly
and has received honoraria from Qualcom Medical Media. Dr Larach has
received a consulting fee from the Malignant Hyperthermia Association of
the United States to develop an ambulatory surgery center
transfer-of-care document for malignant hyperthermia patients and has
been reimbursed by the Association for travel expenses to attend
scientific conferences.
NR 29
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U2 5
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD SEP
PY 2011
VL 72
IS 9
BP 1222
EP 1228
DI 10.4088/JCP.10m06438
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 828LO
UT WOS:000295502700009
PM 21733489
ER
PT J
AU Kontos, N
AF Kontos, Nicholas
TI The Rise and Fall of the Biopsychosocial Model: Reconciling Art and
Science in Psychiatry
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Book Review
C1 [Kontos, Nicholas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RP Kontos, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
EM nkontos@partners.org
NR 1
TC 0
Z9 0
U1 1
U2 11
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD SEP
PY 2011
VL 72
IS 9
BP 1287
EP 1288
DI 10.4088/JCP.11bk07158
PG 2
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 828LO
UT WOS:000295502700024
ER
PT J
AU Denisenko, O
Lin, BY
Bagby, S
AF Denisenko, Oleg
Lin, Baoyu
Bagby, Susan
TI Maternal Malnutrition Upregulates Expression and Alters Splicing of
Angiotensin II Receptor Gene, AT1R, in Prenatal and Neonatal Kidneys
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Meeting Abstract
C1 [Denisenko, Oleg] Univ Washington, Seattle, WA 98195 USA.
[Bagby, Susan] Portland VA Med Ctr, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD SEP
PY 2011
VL 2
SU 1
BP S25
EP S25
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 837CK
UT WOS:000296168500078
ER
PT J
AU DuPriest, EA
Kupfer, P
Lin, B
Sekiguchi, K
Morgan, TK
Saunders, KE
Chatkupt, TT
Purnell, JQ
Bagby, SP
AF DuPriest, E. A.
Kupfer, P.
Lin, B.
Sekiguchi, K.
Morgan, T. K.
Saunders, K. E.
Chatkupt, T. T.
Purnell, J. Q.
Bagby, S. P.
TI Prevention of Accelerated Growth in Nutritionally Programmed Offspring
Does Not Ameliorate Adipose Tissue Dysfunction
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Meeting Abstract
C1 [DuPriest, E. A.; Kupfer, P.; Lin, B.; Sekiguchi, K.; Morgan, T. K.; Saunders, K. E.; Chatkupt, T. T.; Purnell, J. Q.; Bagby, S. P.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[DuPriest, E. A.; Kupfer, P.; Lin, B.; Sekiguchi, K.; Bagby, S. P.] Portland VA Med Ctr, Portland, OR USA.
[DuPriest, E. A.] Warner Pacific Coll, Portland, OR USA.
NR 0
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U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD SEP
PY 2011
VL 2
SU 1
BP S60
EP S60
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 837CK
UT WOS:000296168500198
ER
PT J
AU DuPriest, EA
Kupfer, P
Lin, BY
Sekiguchi, K
Morgan, TK
Saunders, KE
Chatkupt, TT
Purnell, JQ
Bagby, SP
AF DuPriest, Elizabeth A.
Kupfer, Philipp
Lin, Baoyu
Sekiguchi, Kaiu
Morgan, Terry K.
Saunders, Kim E.
Chatkupt, Tom T.
Purnell, Jonathan Q.
Bagby, Susan P.
TI Altered Adipocyte Structure and Function in Nutritionally Programmed
Microswine Offspring
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Meeting Abstract
C1 [DuPriest, Elizabeth A.; Kupfer, Philipp; Lin, Baoyu; Sekiguchi, Kaiu; Morgan, Terry K.; Saunders, Kim E.; Chatkupt, Tom T.; Purnell, Jonathan Q.; Bagby, Susan P.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[DuPriest, Elizabeth A.; Kupfer, Philipp; Lin, Baoyu; Sekiguchi, Kaiu; Bagby, Susan P.] Portland VA Med Ctr, Portland, OR USA.
[DuPriest, Elizabeth A.] Warner Pacific Coll, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD SEP
PY 2011
VL 2
SU 1
BP S54
EP S54
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 837CK
UT WOS:000296168500179
ER
PT J
AU Isganaitis, E
Radford, E
Lytras, A
Chen, M
Schroeder, J
Sharma, A
Ferguson-Smith, A
Patti, ME
AF Isganaitis, Elvira
Radford, Elizabeth
Lytras, Aristides
Chen, Michael
Schroeder, Joshua
Sharma, Aparna
Ferguson-Smith, Anne
Patti, Mary-Elizabeth
TI Paternal History of Exposure to Prenatal Undernutrition Alters Placental
Expression of Nutrient Transporters and mTor Targets in F2 Offspring:
Potential Contribution to Intergenerational Transmission of Diabetes and
Obesity Risk
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Meeting Abstract
C1 [Isganaitis, Elvira; Lytras, Aristides; Chen, Michael; Schroeder, Joshua; Sharma, Aparna] Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA.
[Radford, Elizabeth; Ferguson-Smith, Anne; Patti, Mary-Elizabeth] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 1TN, England.
RI Ferguson-Smith, Anne/G-7534-2011
NR 0
TC 1
Z9 1
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD SEP
PY 2011
VL 2
SU 1
BP S4
EP S4
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 837CK
UT WOS:000296168500009
ER
PT J
AU Kirchner, JE
Farmer, MS
Shue, VM
Blevins, D
Sullivan, G
AF Kirchner, Joann E.
Farmer, Mary Sue
Shue, Valorie M.
Blevins, Dean
Sullivan, Greer
TI Partnering With Communities to Address the Mental Health Needs of Rural
Veterans
SO JOURNAL OF RURAL HEALTH
LA English
DT Article
DE clergy; criminal justice; education; mental health; rural veterans
ID POSTTRAUMATIC-STRESS-DISORDER; COMORBIDITY SURVEY REPLICATION;
UNITED-STATES; URBAN DIFFERENCES; SERVICES UTILIZATION; DEPRESSION;
CARE; PREVALENCE; AFGHANISTAN; OUTCOMES
AB Purpose: Many veterans who face mental illness and live in rural areas never obtain the mental health care they need. To address these needs, it is important to reach out to community stakeholders who are likely to have frequent interactions with veterans, particularly those returning from Operations Enduring and Iraqi Freedom (OEF/OIF).
Methods: Three community stakeholder groups-clergy, postsecondary educators, and criminal justice personnel-are of particular importance for OEF/OIF veterans living in rural areas and may be more likely to come into contact with rural veterans struggling with mental illness or substance abuse than the formal health care system. This article briefly describes the conceptualization, development, initial implementation, and early evaluation of a Veterans Affairs (VA) medical center-based program designed to improve engagement in, and access to, mental health care for veterans returning to rural areas.
Findings: One year since initial funding, 90 stakeholders have attended formal training workshops (criminal justice personnel = 36; educators = 31; clergy = 23). Two training formats (a 2-hour workshop and an intensive 2.5-day workshop) have been developed and provided to clergy in 1 rural county with another county scheduled for training. A veteran outreach initiative, which has received 32 referrals for various student services, has been established on 4 rural college campuses. A Veterans Treatment Court also has been established with 16 referrals for eligibility assessments.
Conclusions: While this pilot program is in the early stages of evaluation, its success to date has encouraged program and VA clinical leadership to expand beyond the original sites.
C1 [Kirchner, Joann E.] US Dept Vet Affairs, Mental Hlth Qual Enhancement Res Initiat, N Little Rock, AR USA.
[Farmer, Mary Sue; Blevins, Dean; Sullivan, Greer] US Dept Vet Affairs, Mental Illness Res Educ Clin Ctr, N Little Rock, AR USA.
[Kirchner, Joann E.; Shue, Valorie M.; Blevins, Dean; Sullivan, Greer] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Kirchner, Joann E.; Blevins, Dean; Sullivan, Greer] US Dept Vet Affairs, Hlth Serv Res & Dev Ctr Mental Healthcare & Outco, N Little Rock, AR USA.
RP Kirchner, JE (reprint author), VA HSR & Ctr Mental Healthcare & Outcomes Res, 2200 Ft Roots Dr,Bldg 58, N Little Rock, AR 72114 USA.
EM kirchnerjoanne@uams.edu
FU United States Department of Veterans Affairs Office of Rural Health;
South Central Mental Illness Research Education Clinical Center
FX We would like to thank the clinicians, OEF-OIF Veterans, and clinical
teams who made this work possible. Specifically, we would like to
acknowledge Michael T. Lambert, LCSW; Bridgett Larkin, MBA (OEF-IOF
Veteran); William M. Moore, PhD; Jamie Mucciarelli, MA (OEF/OIF
Veteran); Vince Roca, PhD; Steve Sullivan, M.Div, Th.M; Elizabeth White,
LMSW; and Linda Worley, MD. This project was supported by the United
States Department of Veterans Affairs Office of Rural Health and South
Central Mental Illness Research Education Clinical Center. The views
expressed in this article are those of the authors and do not
necessarily represent the views of the Department of Veterans Affairs.
For further information contact: JoAnn E. Kirchner, MD, VA HSR & D
Center for Mental Healthcare and Outcomes Research, 2200 Fort Roots
Drive, Bldg 58, North Little Rock, AR 72114; e-mail
kirchnerjoanne@uams.edu.
NR 70
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U1 3
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0890-765X
J9 J RURAL HEALTH
JI J. Rural Health
PD FAL
PY 2011
VL 27
IS 4
BP 416
EP 424
DI 10.1111/j.1748-0361.2011.00362.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 833HU
UT WOS:000295875200011
PM 21967386
ER
PT J
AU Bauman, WA
Emmons, RR
Cirnigliaro, CM
Kirshblum, SC
Spungen, AM
AF A. Bauman, William
Emmons, Racine R.
Cirnigliaro, Christopher M.
Kirshblum, Steven C.
Spungen, Ann M.
TI An effective oral vitamin D replacement therapy in persons with spinal
cord injury
SO JOURNAL OF SPINAL CORD MEDICINE
LA English
DT Article
DE Vitamin D deficiency; Nutritional supplementation; Calcium; Vitamin D;
Osteoporosis; Spinal cord injuries; Bone loss; Cholecalciferol;
Paraplegia; Tetraplegia; Veterans
ID BONE-MINERAL DENSITY; D DEFICIENCY; COLORECTAL-CANCER; RISK; DISEASE;
MORTALITY; CALCIUM; HEALTH; ADULTS; INDIVIDUALS
AB Background/objective: Vitamin D deficiency is prevalent in chronic spinal cord injury (SCI). A 3-month course of oral vitamin D-3 to 'normalize' serum vitamin D levels was investigated.
Design: Prospective drug-intervention study.
Setting: VA Medical Center; private rehabilitation facility.
Methods: Seven individuals with chronic SCI and vitamin D deficiency completed 3 months of oral vitamin D-3 (i.e. cholecalciferol) supplementation. At screening, baseline, and months 1 and 3, blood was collected for serum calcium, 25 hydroxyvitamin D [25(OH) D], intact parathyroid hormone (iPTH), and N-telopeptide (NTx); 24-hour urine for calcium, creatinine, and NTx was performed. Oral vitamin D-3 (2000 IU daily) and elemental calcium (1.3 g daily) were prescribed for 90 days. The results are expressed as mean +/- standard deviation (SD). Analysis of variance with a Fisher's post-hoc analysis was performed to test for differences between study visits. Subjects were classified as deficient (<20 ng/ml), relatively deficient (20-30 ng/ml), or not deficient (>30 ng/ml) in 25(OH) D.
Results: Serum 25(OH) D levels were greater at months 1 and 3 than at baseline (26 +/- 6 and 48 +/- 17 vs. 14 +/- 2 ng/ml; P = 0.005). Six of seven subjects were no longer deficient [25(OH) D >30 ng/ml] by month 3. Serum iPTH levels were significantly decreased at month 1 and month 3; serum NTx levels were significantly lower at month 3 than at baseline. Serum and urinary calcium levels remained within the normal range.
Conclusion: A daily prescription of 2000 IU of oral vitamin D-3 for 3 months safely raised serum 25(OH) D levels into the normal range in persons with chronic SCI on calcium supplementation.
C1 [A. Bauman, William; Emmons, Racine R.; Cirnigliaro, Christopher M.; Spungen, Ann M.] James J Peters VA Med Ctr, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Med Consequences, Bronx, NY 10468 USA.
[A. Bauman, William; Spungen, Ann M.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[A. Bauman, William; Spungen, Ann M.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA.
[Emmons, Racine R.] Columbia Univ Teachers Coll, New York, NY 10027 USA.
[Kirshblum, Steven C.] Kessler Inst Rehabil, W Orange, NJ USA.
[Kirshblum, Steven C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07103 USA.
RP Bauman, WA (reprint author), James J Peters VA Med Ctr, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Med Consequences, Room 7A-13,130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM william.bauman@va.gov
NR 43
TC 5
Z9 6
U1 1
U2 12
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1079-0268
EI 2045-7723
J9 J SPINAL CORD MED
JI J. Spinal Cord. Med.
PD SEP
PY 2011
VL 34
IS 5
BP 455
EP 460
DI 10.1179/2045772311Y.0000000032
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 835OS
UT WOS:000296046300003
PM 22118252
ER
PT J
AU Stroud, MW
Bombardier, CH
Dyer, JR
Rimmele, CT
Esselman, PC
AF Stroud, Michael W.
Bombardier, Charles H.
Dyer, Joshua R.
Rimmele, Carl T.
Esselman, Peter C.
TI Preinjury alcohol and drug use among persons with spinal cord injury:
Implications for rehabilitation
SO JOURNAL OF SPINAL CORD MEDICINE
LA English
DT Article
DE Alcohol; Drug; Substance-related disorders; Spinal cord injuries;
Rehabilitation; Paraplegia; Tetraplegia; Toxicology screening
ID TRAUMATIC BRAIN-INJURY; SUBSTANCE-ABUSE; CHANGE QUESTIONNAIRE; USE
DISORDERS; READINESS; RISK; INTERVENTIONS; COMPLICATIONS; MAGNITUDE;
DRINKERS
AB Context/objective: To describe preinjury alcohol and drug use and opportunities for secondary prevention among persons with recent spinal cord injury (SCI).
Design: Survey.
Setting: Acute inpatient rehabilitation program.
Participants: Participants were 118 (84.8%) of 139 consecutive admissions who met inclusion criteria and were screened for preinjury alcohol and drug use.
Interventions: None.
Outcome measures: Alcohol and drug use, toxicology results, alcohol problems, readiness to change, and treatment preferences.
Results: Participants were on average 37 years old, 84% were men, and 85% were white. Fifty-one percent of the sample was considered 'at-risk' drinkers. Significant lifetime alcohol-related problems were reported by 38% of the total sample. Thirty-three percent reported recent illicit drug use and 44% of the 82 cases with toxicology results were positive for illicit drugs. Seventy-one percent of at-risk drinkers reported either considering changes in alcohol use or already taking action. Forty-one percent reported interest in trying substance abuse treatment or Alcoholics Anonymous (AA). Motivation to change alcohol use was significantly and positively associated with self-reported indicators of alcohol problem severity.
Conclusion: Preinjury alcohol and drug abuse are common among persons with recent SCI. Substance abuse screening is feasible and detects not only salient clinical problems but also significant motivation to change and interest in AA or treatment, all of which represent an important window of opportunity for appropriate brief interventions and referrals. In contrast with the idea that alcoholism is a 'disease of denial', the majority of at-risk drinkers with new onset SCI indicate they are considering making changes.
C1 [Bombardier, Charles H.] Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Seattle, WA 98104 USA.
[Stroud, Michael W.] Vet Adm Med Ctr, Denver, CO USA.
[Rimmele, Carl T.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Rimmele, Carl T.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Bombardier, CH (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Sch Med, Box 359612,325 9th Ave, Seattle, WA 98104 USA.
EM chb@uw.edu
FU Northwest Regional Spinal Cord Injury System; National Institute on
Disability and Rehabilitation Research [H133N50025, H133N060033]
FX This research was supported by the Northwest Regional Spinal Cord Injury
System grant and funded by the National Institute on Disability and
Rehabilitation Research (H133N50025; H133N060033). The contents of this
paper are solely the responsibility of the authors and do not represent
the official views of the granting agency. No commercial party having a
direct financial interest in the results of the research has or will
confer a benefit upon the authors or upon any organization with which
the authors are associated.
NR 45
TC 3
Z9 4
U1 2
U2 5
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1079-0268
J9 J SPINAL CORD MED
JI J. Spinal Cord. Med.
PD SEP
PY 2011
VL 34
IS 5
BP 461
EP 472
DI 10.1179/2045772311Y.0000000033
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 835OS
UT WOS:000296046300004
PM 22118253
ER
PT J
AU Turner, PV
Brabb, T
Pekow, C
Vasbinder, MA
AF Turner, Patricia V.
Brabb, Thea
Pekow, Cynthia
Vasbinder, Mary Ann
TI Administration of Substances to Laboratory Animals: Routes of
Administration and Factors to Consider
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Editorial Material
ID HYDRODYNAMIC GENE DELIVERY; INBRED MOUSE STRAINS; DRUG-DELIVERY;
INTRAPERITONEAL INJECTIONS; INTRAMUSCULAR INJECTION; SELF-MUTILATION;
GASTROINTESTINAL ABSORPTION; INTRAARTERIAL INJECTION;
PARENTERAL-NUTRITION; EPIDURAL ANALGESIA
AB Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. For all species, many different routes are available for administration of substances. The research team and IACUC members should be aware of reasons for selecting specific routes and of training and competency necessary for personnel to use these routes effectively. Once a route is selected, issues such as volume of administration, site of delivery, pH of the substance, and other factors must be considered to refine the technique. Inadequate training or inattention to detail during this aspect of a study may result in unintentional adverse effects on experimental animals and confounded results.
C1 [Turner, Patricia V.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada.
[Brabb, Thea] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA.
[Pekow, Cynthia] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Vasbinder, Mary Ann] GlaxoSmithKline, Platform Technol & Sci Qual & Risk Management, Res Triangle Pk, NC USA.
RP Turner, PV (reprint author), Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada.
EM pvturner@uoguelph.ca
NR 145
TC 86
Z9 89
U1 10
U2 41
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 600
EP 613
PG 14
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000001
PM 22330705
ER
PT J
AU Turner, PV
Pekow, C
Vasbinder, MA
Brabb, T
AF Turner, Patricia V.
Pekow, Cynthia
Vasbinder, Mary Ann
Brabb, Thea
TI Administration of Substances to Laboratory Animals: Equipment
Considerations, Vehicle Selection, and Solute Preparation
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Editorial Material
ID VASCULAR ACCESS PORTS; BIOMEDICAL-RESEARCH; RHESUS-MONKEYS; RESTRAINT;
CATHETER; PATENCY; RAT; DIMETHYLSULFOXIDE; CYCLODEXTRIN; FORMULATIONS
AB Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. The equipment selected to deliver substances to animals depends on the length of the study and the nature of the material being administered. This selection provides a significant opportunity for refining animal treatment. Similarly, when substances are administered as solutions or suspensions, attention should be given to selection of vehicles and methods used for preparing the solutions and suspensions. The research team, veterinarian, technical personnel, and IACUC members should be aware of reasons underlying selection of equipment for substance delivery and should consider carefully how substances will be prepared and stored prior to administration to animals. Failure to consider these factors during experimental planning may result in unintentional adverse effects on experimental animals and confounded results.
C1 [Turner, Patricia V.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada.
[Pekow, Cynthia] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Brabb, Thea] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA.
[Vasbinder, Mary Ann] GlaxoSmithKline, Platform Technol & Sci Qual & Risk Management, Res Triangle Pk, NC USA.
RP Turner, PV (reprint author), Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada.
EM pvturner@uoguelph.ca
NR 89
TC 32
Z9 33
U1 3
U2 15
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 614
EP 627
PG 14
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000002
PM 22330706
ER
PT J
AU Huang, P
Samuel, R
Chen, Y
Fukumura, D
Jain, RK
Duda, DG
AF Huang, P.
Samuel, R.
Chen, Y.
Fukumura, D.
Jain, R. K.
Duda, D. G.
TI The Development of Diethylnitrosamine-Induced Carcinogenesis in Mouse
Models is Gender and Genetic Strain Dependent
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Meeting Abstract
C1 [Huang, P.; Samuel, R.; Chen, Y.; Fukumura, D.; Jain, R. K.; Duda, D. G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 743
EP 744
PG 2
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000112
ER
PT J
AU Mikkola, A
Debrace, MO
Brown, D
AF Mikkola, A.
Ocampo Debrace, M.
Brown, D.
TI Affordable Laboratory Animal Clinical Pathology for Emerging Economies
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Meeting Abstract
C1 [Mikkola, A.; Brown, D.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA.
[Ocampo Debrace, M.] Univ Republ Oriental Uruguay, Montevideo, Uruguay.
[Brown, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 759
EP 759
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000180
ER
PT J
AU Hall, C
Gibbons, C
Jarrell, DM
AF Hall, C.
Gibbons, C.
Jarrell, D. M.
TI Improving Onboarding of New Husbandry Staff via Lean Management
Principles
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Meeting Abstract
C1 [Hall, C.; Gibbons, C.; Jarrell, D. M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 762
EP 762
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000195
ER
PT J
AU Hankenson, FC
Cooper, DR
Weigler, BJ
AF Hankenson, F. C.
Cooper, D. R.
Weigler, B. J.
TI A National Assessment of Occupational Health Programs for Animal Care
and Research Personnel in the United States
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Meeting Abstract
C1 [Hankenson, F. C.] Univ Penn, Philadelphia, PA 19104 USA.
[Cooper, D. R.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA.
[Weigler, B. J.] Washington Natl Primate Res Ctr, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 767
EP 767
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000217
ER
PT J
AU Swanson, LK
Beckman, WJ
Dehlinger, K
AF Swanson, L. K.
Beckman, W. J.
Dehlinger, K.
TI Characterization of Prairie Vole (Microtus ochrogaster) Pup Development
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Meeting Abstract
C1 [Swanson, L. K.; Beckman, W. J.; Dehlinger, K.] Portland VA Med Ctr, Vet Med Unit, Portland, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 776
EP 776
PG 1
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000259
ER
PT J
AU Campbell, S
AF Campbell, S.
TI Standardizing Nonhuman Primate Dietary Instructions with Visual Cues
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Meeting Abstract
C1 [Campbell, S.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD SEP
PY 2011
VL 50
IS 5
BP 782
EP 783
PG 2
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 835XJ
UT WOS:000296070000290
ER
PT J
AU Bonn-Miller, MO
Vujanovic, AA
Drescher, KD
AF Bonn-Miller, Marcel O.
Vujanovic, Anka A.
Drescher, Kent D.
TI Cannabis Use Among Military Veterans After Residential Treatment for
Posttraumatic Stress Disorder
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE posttraumatic stress disorder; trauma; cannabis; marijuana; relapse;
treatment
ID SELF-MEDICATION HYPOTHESIS; ADMINISTERED PTSD SCALE; USE COPING MOTIVES;
SUBSTANCE USE; PSYCHOMETRIC PROPERTIES; DRUG-USE; ABUSE; DEPENDENCE;
MARIJUANA; SEVERITY
AB The present investigation prospectively evaluated whether treatment changes in PTSD symptom severity, among military Veterans in residential PTSD treatment, were related to cannabis use 4 months after discharge from residential rehabilitation. The sample was comprised of 432 male military Veteran patients (M(age) = 51.06 years, SD = 4.17), who had a primary diagnosis of PTSD and were admitted to a VA residential rehabilitation program for PTSD. Results demonstrated that lower levels of change in PCL-M scores between treatment intake and discharge were significantly predictive of greater frequency of cannabis use at 4-month follow-up (p < .05), even after accounting for the effects of length of treatment stay and frequency of cannabis use during the 2 months before treatment intake. Furthermore, post hoc analyses revealed that less change in PTSD avoidance/numbing and hyperarousal symptom severity during treatment was significantly predictive of a greater frequency of cannabis use at 4-month follow-up, after controlling for relevant covariates. Notably, these effects were specific to cannabis and were not found for the other substances examined among this sample, including alcohol and opiates. Implications of the findings are discussed with regard to the extant literature and future directions.
C1 [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk Div 152, Menlo Pk, CA 94025 USA.
[Drescher, Kent D.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA.
[Vujanovic, Anka A.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Vujanovic, Anka A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA.
RP Bonn-Miller, MO (reprint author), VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk Div 152, 795 Willow Rd, Menlo Pk, CA 94025 USA.
EM Marcel.Bonn-Miller@va.gov
RI Schueter, nicos/A-3625-2014
NR 40
TC 32
Z9 32
U1 4
U2 15
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD SEP
PY 2011
VL 25
IS 3
BP 485
EP 491
DI 10.1037/a0021945
PG 7
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA 827CP
UT WOS:000295404100011
PM 21261407
ER
PT J
AU Cougle, JR
Bonn-Miller, MO
Vujanovic, AA
Zvolensky, MJ
Hawkins, KA
AF Cougle, Jesse R.
Bonn-Miller, Marcel O.
Vujanovic, Anka A.
Zvolensky, Michael J.
Hawkins, Kirsten A.
TI Posttraumatic Stress Disorder and Cannabis Use in a Nationally
Representative Sample
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE cannabis; marijuana; posttraumatic stress disorder; trauma; anxiety
ID USE COPING MOTIVES; SUBSTANCE-ABUSE; COMORBIDITY SURVEY; CAUSAL
PATHWAYS; DEPENDENCE; PTSD; VETERANS; RATES
AB The present study examined the relations between posttraumatic stress disorder (PTSD) and cannabis use in a large representative survey of adults (N = 5,672) from the United States (Kessler et al., 2004). After adjusting for sociodemographic variables (i.e., age, marital status, ethnicity, education, income, and sex), alcohol use disorders, and nicotine dependence, lifetime and current (past year) PTSD diagnoses were associated with increased odds of lifetime history of cannabis use as well as past year daily cannabis use. Lifetime, but not current, PTSD diagnosis also was uniquely associated with increased risk for any past year cannabis use. Additional analyses revealed that the relations between PTSD (lifetime and current) and lifetime cannabis use remained statistically significant when adjusting for co-occurring anxiety and mood disorders and trauma type frequency. Overall, these findings add to the emerging literature demonstrating a possibly important relationship between PTSD and cannabis use.
C1 [Cougle, Jesse R.; Hawkins, Kirsten A.] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA.
[Bonn-Miller, Marcel O.] Natl Ctr PTSD, Palo Alto, CA USA.
[Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA.
[Vujanovic, Anka A.] VA Boston Healthcare, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA.
[Vujanovic, Anka A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA.
RP Cougle, JR (reprint author), Florida State Univ, Dept Psychol, POB 3064301, Tallahassee, FL 32306 USA.
EM cougle@psy.fsu.edu
FU NIMH NIH HHS [1 R01 MH076629-01]
NR 20
TC 46
Z9 47
U1 2
U2 8
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD SEP
PY 2011
VL 25
IS 3
BP 554
EP 558
DI 10.1037/a0023076
PG 5
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA 827CP
UT WOS:000295404100019
PM 21480682
ER
PT J
AU Sales, AE
Lapham, GG
Squires, J
Hutchinson, A
Almenoff, P
Sharp, ND
Lowy, E
Li, YF
AF Sales, Anne E.
Lapham, Gwendolyn G.
Squires, Janet
Hutchinson, Alison
Almenoff, Peter
Sharp, Nancy D.
Lowy, Elliott
Li, Yu-Fang
TI Organizational Factors Associated With Decreased Mortality Among
Veterans Affairs Patients With an ICU Stay
SO CIN-COMPUTERS INFORMATICS NURSING
LA English
DT Article
DE Electronic record; Hospital organization; In-hospital mortality;
Intensive care
ID INTENSIVE-CARE UNITS; ILL HOSPITALIZED ADULTS; OUTCOMES; QUALITY; IMPACT
AB In-hospital mortality rates associated with an ICU stay are high and vary widely among units. This variation may be related to organizational factors such as staffing patterns, ICU structure, and care processes. We aimed to identify organizational factors associated with variation in in-hospital mortality for patients with an ICU stay. This was a retrospective observational cross-sectional study using administrative data from 34 093 patients from 171 ICUs in 119 Veterans Health Administration hospitals. Staffing and patient data came from Veterans Health Administration national databases. ICU characteristics came from a survey in 2004 of ICUs within the Veterans Health Administration. We conducted multilevel multivariable estimation with patient-, unit-, and hospital-level data. The primary outcome was in-hospital mortality. Of 34 093 patients, 2141 (6.3%) died in the hospital. At the patient level, risk of complications and having a medical diagnosis were significantly associated with a higher risk of mortality. At the unit level, having an interface with the electronic medical record was significantly associated with a lower risk of mortality. The finding that electronic medical records integrated with ICU information systems are associated with lower in-hospital mortality adds support to existing evidence on organizational characteristics associated with in-hospital mortality among ICU patients.
C1 [Sales, Anne E.; Squires, Janet; Hutchinson, Alison] Univ Alberta, Fac Nursing, Edmonton, AB T6G 2T4, Canada.
[Lapham, Gwendolyn G.; Sharp, Nancy D.; Lowy, Elliott; Li, Yu-Fang] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Almenoff, Peter] VA Cent Off, Washington, DC USA.
RP Sales, AE (reprint author), Univ Alberta, Fac Nursing, Edmonton, AB T6G 2T4, Canada.
EM anne.sales@ualberta.ca
RI Sales, Anne/D-9678-2012;
OI Sales, Anne/0000-0001-9360-3334
FU Office of Research and Development, Health Services R&D Service,
Department of Veterans Affairs [IIR 01-160]
FX This study was supported by the Office of Research and Development,
Health Services R&D Service, Department of Veterans Affairs (project
number IIR 01-160).
NR 18
TC 5
Z9 5
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1538-2931
J9 CIN-COMPUT INFORM NU
JI CIN-Comput. Inform. Nurs.
PD SEP
PY 2011
VL 29
IS 9
BP 496
EP 501
DI 10.1097/NCN.0b013e3182148c47
PG 6
WC Computer Science, Interdisciplinary Applications; Medical Informatics;
Nursing
SC Computer Science; Medical Informatics; Nursing
GA 833IR
UT WOS:000295878200004
PM 21983432
ER
PT J
AU Numis, AL
Yellen, MB
Chu-Shore, CJ
Pfeifer, HH
Thiele, EA
AF Numis, Adam L.
Yellen, Margaret B.
Chu-Shore, Catherine J.
Pfeifer, Heidi H.
Thiele, Elizabeth A.
TI The relationship of ketosis and growth to the efficacy of the ketogenic
diet in infantile spasms
SO EPILEPSY RESEARCH
LA English
DT Article
DE Ketogenic diet; West syndrome; Refractory epilepsy; Ketone bodies;
Anthropometry
ID CHILDREN; EXPERIENCE; EPILEPSY
AB The ketogenic diet (KO) is a treatment of infantile spasms (IS). Here, we examine the efficacy of KD in medically refractory IS, examine its impact on growth in infants, and explore its mechanism of action. At 1-3 months after the initiation of the KD, 46% of twenty-six patients had a greater than 90% reduction in IS. No significant relationships between reduction in IS and serum p-hydroxybutyrate, or glucose levels were identified. Also, the KD had not significantly altered patient's growth parameters. Thus, in corroborating with prior studies, we demonstrate the KD is a well-tolerated and efficacious treatment of IS. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, Boston, MA 02114 USA.
RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Pediat Epilepsy Program, Dept Neurol, 175 Cambridge St,Suite 340, Boston, MA 02114 USA.
EM ethiele@partners.org
FU Carol and James Herscot Center for Tuberous Sclerosis Complex
FX This study was supported by the Carol and James Herscot Center for
Tuberous Sclerosis Complex.
NR 12
TC 18
Z9 22
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-1211
J9 EPILEPSY RES
JI Epilepsy Res.
PD SEP
PY 2011
VL 96
IS 1-2
BP 172
EP 175
DI 10.1016/j.eplepsyres.2011.05.012
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 831CQ
UT WOS:000295706700023
PM 21700429
ER
PT J
AU Blanke, C
Rankin, C
Benjamin, RS
Raymond, AK
Heinrich, MC
Fletcher, CDM
Crowley, J
Borden, EC
Demetri, GD
Baker, LH
AF Blanke, C.
Rankin, C.
Benjamin, R. S.
Raymond, A. K.
Heinrich, M. C.
Fletcher, C. D. M.
Crowley, J.
Borden, E. C.
Demetri, G. D.
Baker, L. H.
TI Long-term Survival on S0033-a Phase III Randomized, Intergroup Trial
Assessing Imatinib Mesylate at Two Dose Levels in Patients With
Unresectable or Metastatic Gastrointestinal Stromal Tumours (GISTs)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Blanke, C.] BC Canc Agcy, Med Oncol, Vancouver, BC, Canada.
[Rankin, C.; Crowley, J.] SW Oncol Grp, Seattle, WA USA.
[Benjamin, R. S.; Raymond, A. K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Heinrich, M. C.] OHSU, Portland, OR USA.
[Fletcher, C. D. M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Borden, E. C.] Cleveland Clin, Cleveland, OH 44106 USA.
[Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Baker, L. H.] Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 1
Z9 1
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 SEP
PY 2011
VL 47
SU 1
BP S664
EP S664
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752802343
ER
PT J
AU Bruno, R
Jonsson, F
Zaki, M
Jacques, C
Richardson, P
Rajkumar, VS
Claret, L
AF Bruno, R.
Jonsson, F.
Zaki, M.
Jacques, C.
Richardson, P.
Rajkumar, V. S.
Claret, L.
TI Simulation of Clinical Endpoints (Survival, PFS) in Patients With
Refractory Multiple Myeloma Treated With Pomalidomide Based on Interim
Week 8 M-protein Response
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Bruno, R.; Claret, L.] Consulting Serv, Marseille, France.
[Jonsson, F.] Consulting Serv, Stockholm, Sweden.
[Zaki, M.; Jacques, C.] Celgene, Clin Res & Dev, Summit, NJ USA.
[Richardson, P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Rajkumar, V. S.] Mayo Clin, Dept Internal Med, Rochester, MN USA.
NR 0
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 SEP
PY 2011
VL 47
SU 1
BP S647
EP S647
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752802287
ER
PT J
AU Cella, D
Bushmakin, AG
Cappelleri, JC
Charbonneau, C
Sandin, R
Negriers, S
Figlin, RA
Michaelson, MD
Davis, MP
Motzer, RJ
AF Cella, D.
Bushmakin, A. G.
Cappelleri, J. C.
Charbonneau, C.
Sandin, R.
Negriers, S.
Figlin, R. A.
Michaelson, M. D.
Davis, M. P.
Motzer, R. J.
TI Comparison of Health-related Quality of Life (HRQoL) in Patients
Reporting the Same Adverse Event (AE) Fatigue on Different Treatments
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Cella, D.] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA.
[Bushmakin, A. G.; Cappelleri, J. C.] Pfizer Oncol, Global Res & Dev, New London, CT USA.
[Charbonneau, C.] Pfizer Oncol, Global Outcomes Res, New York, NY USA.
[Sandin, R.] Pfizer Oncol, Global Hlth Econ & Outcomes Res, Sollentuna, Sweden.
[Negriers, S.] Ctr Leon Berard, F-69373 Lyon, France.
[Figlin, R. A.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Davis, M. P.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
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 SEP
PY 2011
VL 47
SU 1
BP S233
EP S233
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800803
ER
PT J
AU Davis, MP
Goldstein, D
George, S
Casali, PG
Li, S
Perkins, J
Demetri, GD
AF Davis, M. P.
Goldstein, D.
George, S.
Casali, P. G.
Li, S.
Perkins, J.
Demetri, G. D.
TI Asthenia and Fatigue as Predictors of Sunitinib Efficacy In
Gastrointestinal Stromal Tumour (GIST)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Davis, M. P.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA.
[Goldstein, D.] Prince Wales Hosp, Dept Med Oncol, Randwick, NSW 2031, Australia.
[George, S.; Demetri, G. D.] Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA USA.
[Casali, P. G.] Ist Nazl Tumori, Dept Canc Med, I-20133 Milan, Italy.
[Li, S.] Pfizer Oncol, Clin Stat, Shanghai, Peoples R China.
[Perkins, J.] Pfizer Oncol, Oncol, New York, NY USA.
NR 0
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 SEP
PY 2011
VL 47
SU 1
BP S135
EP S136
PG 2
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800477
ER
PT J
AU Donskov, F
von Mehren, M
Carus, A
George, S
Casali, PG
Li, S
Perkins, J
Demetri, GD
AF Donskov, F.
von Mehren, M.
Carus, A.
George, S.
Casali, P. G.
Li, S.
Perkins, J.
Demetri, G. D.
TI Neutropenia as a Biomarker of Sunitinib Efficacy in Patients (Pts) With
Gastrointestinal Stromal Tumour (GIST)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Donskov, F.; Carus, A.] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark.
[von Mehren, M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[George, S.; Demetri, G. D.] Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA USA.
[Casali, P. G.] Ist Nazl Tumori, Dept Canc Med, I-20133 Milan, Italy.
[Li, S.] Pfizer Oncol, Clin Stat, Shanghai, Peoples R China.
[Perkins, J.] Pfizer Oncol, Oncol, New York, NY USA.
NR 0
TC 4
Z9 4
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 SEP
PY 2011
VL 47
SU 1
BP S135
EP S135
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800475
ER
PT J
AU Flaherty, K
AF Flaherty, K.
TI Melanoma Therapy - Realising the Potential In Targeted Therapy
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Flaherty, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 SEP
PY 2011
VL 47
SU 1
BP S31
EP S32
PG 2
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800109
ER
PT J
AU Gamez, C
Flamen, P
Holmes, E
Robles, J
Gebhart, G
Di Cosimo, S
Eidtmann, H
Piccart-Gebhart, M
Baselga, J
De Azambuja, E
AF Gamez, C.
Flamen, P.
Holmes, E.
Robles, J.
Gebhart, G.
Di Cosimo, S.
Eidtmann, H.
Piccart-Gebhart, M.
Baselga, J.
De Azambuja, E.
TI FDG-PET/CT for Early Prediction of Response to Neoadjuvant Lapatinib,
Trastuzumab, and Their Combination in HER2-positive Breast Cancer
Patients: the Neo-ALTTO Study Results
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Gamez, C.; Robles, J.] Univ Hosp Bellvitge, PET Unit IDI IDIBELL, Barcelona, Spain.
[Flamen, P.] Univ Libre Bruxelles, Inst Jules Bordet, Dept Nucl Med, Brussels, Belgium.
[Holmes, E.] Frontier Sci, Inverness, Scotland.
[Di Cosimo, S.] Vail dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain.
[Di Cosimo, S.] SOLTI, Med Oncol Serv, Barcelona, Spain.
[Eidtmann, H.] Univ Hosp Kiel, Univ Klinikum Schleswig Holstein, Dept Gynecol & Obstet, Kiel, Germany.
[Piccart-Gebhart, M.; De Azambuja, E.] Univ Libre Bruxelles, Dept Med, Inst Jules Bordet, Brussels, Belgium.
[Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA.
NR 0
TC 1
Z9 1
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 SEP
PY 2011
VL 47
SU 1
BP S333
EP S334
PG 2
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752801181
ER
PT J
AU Johnson, BE
Kris, MG
Kwiatkowski, DJ
Wistuba, II
Engelman, JA
Pao, W
Rudin, CM
Berry, L
Minna, JD
Bunn, PA
AF Johnson, B. E.
Kris, M. G.
Kwiatkowski, D. J.
Wistuba, I. I.
Engelman, J. A.
Pao, W.
Rudin, C. M.
Berry, L.
Minna, J. D.
Bunn, P. A.
TI Identification of Driver Mutations in Tumour Specimens From 1000
Patients With Lung Adenocarcinoma for the Lung Cancer Mutation
Consortium (LCMC)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Johnson, B. E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kris, M. G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Kwiatkowski, D. J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wistuba, I. I.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Engelman, J. A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Pao, W.; Berry, L.] Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN USA.
[Rudin, C. M.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Minna, J. D.] Harold C Simmons Comprehens Canc Ctr, Dallas, TX USA.
[Bunn, P. A.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 8
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 SEP
PY 2011
VL 47
SU 1
BP S597
EP S597
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752802125
ER
PT J
AU Kwak, EL
Shapiro, GI
Cohen, SM
Becerra, CR
Lenz, HJ
Gooden, S
Robohn, M
Le-Maulf, F
Chand, VK
Iafrate, AJ
AF Kwak, E. L.
Shapiro, G. I.
Cohen, S. M.
Becerra, C. R.
Lenz, H. J.
Gooden, S.
Robohn, M.
Le-Maulf, F.
Chand, V. K.
Iafrate, A. J.
TI A Phase II Trial of Afatinib (BIBW 2992) in Patients With Tumours
Prospectively Screened for EGFR And/or HER2 Gene Amplification or EGFR
Activating Mutations
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Kwak, E. L.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Shapiro, G. I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cohen, S. M.] St Lukes Roosevelt Hosp, New York, NY USA.
[Becerra, C. R.] USON Texas Oncol, Sammons Canc Ctr, Dallas, TX USA.
[Lenz, H. J.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA USA.
[Gooden, S.; Robohn, M.; Chand, V. K.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
[Le-Maulf, F.] Boehringer Ingelheim Pharmaceut Inc, Reims, France.
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 SEP
PY 2011
VL 47
SU 1
BP S174
EP S174
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800604
ER
PT J
AU Levanon, K
Hirsch, M
Miron, A
Ligon, A
Birrer, M
Drapkin, R
AF Levanon, K.
Hirsch, M.
Miron, A.
Ligon, A.
Birrer, M.
Drapkin, R.
TI Foxo3a Loss is a Key Event in High-grade Pelvic Serous Carcinogenesis
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Levanon, K.] Chaim Sheba Med Ctr, Ramat Gan, Israel.
[Hirsch, M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ligon, A.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Birrer, M.] NCI, NIH, Bethesda, MD 20892 USA.
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
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 SEP
PY 2011
VL 47
SU 1
BP S113
EP S114
PG 2
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800398
ER
PT J
AU Lu, J
Kuchimanchi, M
Tang, R
Deng, H
Kindler, H
Fuchs, C
Suzuki, S
Gansert, J
Loh, E
Zhu, M
AF Lu, J.
Kuchimanchi, M.
Tang, R.
Deng, H.
Kindler, H.
Fuchs, C.
Suzuki, S.
Gansert, J.
Loh, E.
Zhu, M.
TI Phase 3 Dose Selection for Ganitumab (AMG 479) in Pancreatic Cancer
Based on Clinical Pharmacokinetics and Pharmacokinetic/Pharmacodynamic
Assessments
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Lu, J.; Kuchimanchi, M.; Zhu, M.] Amgen Inc, Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA.
[Tang, R.; Deng, H.] Amgen Inc, Biostat, Thousand Oaks, CA 91320 USA.
[Kindler, H.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Fuchs, C.] Dana Farber Canc Inst, Ctr Gastrointestinal Canc, Boston, MA 02115 USA.
[Suzuki, S.] Amgen Inc, Biostat, San Francisco, CA USA.
[Gansert, J.] Amgen Inc, Oncol, Thousand Oaks, CA 91320 USA.
[Loh, E.] Amgen Inc, Oncol, San Francisco, CA USA.
NR 0
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 SEP
PY 2011
VL 47
SU 1
BP S468
EP S468
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752801625
ER
PT J
AU Lyons, J
Smyth, T
Curry, J
Fletcher, JA
Wallis, N
Thompson, N
AF Lyons, J.
Smyth, T.
Curry, J.
Fletcher, J. A.
Wallis, N.
Thompson, N.
TI AT13387, a Heat Shock Protein 90 Inhibitor in a Phase I Study Exhibits
Potent Activity in GIST Models
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Lyons, J.; Smyth, T.; Curry, J.; Wallis, N.; Thompson, N.] Astex Therapeut Ltd, Biol, Cambridge, England.
[Fletcher, J. A.] Dana Farber Canc Inst, Cambridge, MA USA.
NR 0
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 SEP
PY 2011
VL 47
SU 1
BP S665
EP S665
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752802346
ER
PT J
AU Margolin, K
Hodi, FS
McDermott, DF
Lawrence, DP
Hamid, O
Puzanov, I
Thompson, JA
Ernstoff, MS
Michener, TL
Heller, KN
AF Margolin, K.
Hodi, F. S.
McDermott, D. F.
Lawrence, D. P.
Hamid, O.
Puzanov, I.
Thompson, J. A.
Ernstoff, M. S.
Michener, T. L.
Heller, K. N.
TI Safety and Efficacy of Ipilimumab-treated Patients With Melanoma and
Brain Metastases
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Margolin, K.] Univ Washington, Div Med Oncol, Seattle, WA 98195 USA.
[Hodi, F. S.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[McDermott, D. F.] Beth Israel Deaconess Med Ctr, Dept Cell Biol, Boston, MA 02215 USA.
[Lawrence, D. P.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA USA.
[Hamid, O.] Angeles Clin & Res Inst, Neurooncol Clin, Santa Monica, CA USA.
[Puzanov, I.] Vanderbilt Univ, Med Ctr, Dept Oncol, Nashville, TN USA.
[Thompson, J. A.] Univ Washington, SCCA Melanoma Clin, Seattle, WA USA.
[Ernstoff, M. S.] Dartmouth Hitchcock Med Ctr, Dept Hematol Oncol, Lebanon, NH 03766 USA.
[Michener, T. L.] Bristol Myers Squibb Co, Collaborat Sci Ctr Excellence, Plainsboro, NJ USA.
NR 0
TC 0
Z9 0
U1 2
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 SEP
PY 2011
VL 47
SU 1
BP S654
EP S654
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752802310
ER
PT J
AU Negrier, S
Bushmakin, AG
Cappelleri, JC
Charbonneau, C
Sandin, R
Michaelson, MD
Figlin, RA
Motzer, RJ
AF Negrier, S.
Bushmakin, A. G.
Cappelleri, J. C.
Charbonneau, C.
Sandin, R.
Michaelson, M. D.
Figlin, R. A.
Motzer, R. J.
TI Assessment of Progression-free Survival as a Surrogate Endpoint for
Overall Survival in Patients With Metastatic Renal Cell Carcinoma
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Negrier, S.] Ctr Leon Berard, F-69373 Lyon, France.
[Bushmakin, A. G.; Cappelleri, J. C.] Pfizer Oncol, Global Res & Dev, New London, CT USA.
[Charbonneau, C.] Pfizer Oncol, Global Outcomes Res, New York, NY USA.
[Sandin, R.] Pfizer Oncol, Global Hlth Econ & Outcomes Res, Sollentuna, Sweden.
[Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Figlin, R. A.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
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 SEP
PY 2011
VL 47
SU 1
BP S163
EP S163
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800569
ER
PT J
AU Ngwa, W
AF Ngwa, W.
TI Feasibility of Boosting Local Dose to Tumour Endothelial Cells Using
Vascular-targeted Bismuth Nanoparticles During Radiotherapy
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Ngwa, W.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 2
U2 10
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 SEP
PY 2011
VL 47
SU 1
BP S212
EP S213
PG 2
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800736
ER
PT J
AU O'Shaughnessy, J
Telli, M
Swain, S
Gralow, J
Rugo, H
Litton, J
Charpentier, E
Smith, J
Blackwood-Chirchir, A
Winer, E
AF O'Shaughnessy, J.
Telli, M.
Swain, S.
Gralow, J.
Rugo, H.
Litton, J.
Charpentier, E.
Smith, J.
Blackwood-Chirchir, A.
Winer, E.
TI Phase 3 Study of Iniparib (I) Plus Gemcitabine (G) and Carboplatin (C)
in Metastatic Triple-negative Breast Cancer (mTNBC) - Results of an
Exploratory Analysis by Prior Therapy
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [O'Shaughnessy, J.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA.
[Telli, M.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Swain, S.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
[Gralow, J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Rugo, H.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Litton, J.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Charpentier, E.] Sanofi Aventis Oncol, Dept Stat, Cambridge, MA 02138 USA.
[Smith, J.] BiPar Sci, Dept Stat, San Francisco, CA USA.
[Winer, E.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
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 SEP
PY 2011
VL 47
SU 1
BP S338
EP S338
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752801193
ER
PT J
AU Oudard, S
Smith, M
Karsh, L
Egerdie, B
Van Veldhuizen, P
Gomez-Veiga, F
Dearnaley, D
Ye, Z
Dansey, R
Goessl, C
AF Oudard, S.
Smith, M.
Karsh, L.
Egerdie, B.
Van Veldhuizen, P.
Gomez-Veiga, F.
Dearnaley, D.
Ye, Z.
Dansey, R.
Goessl, C.
TI Denosumab and Bone Metastasis-free Survival in Men With
Castrate-resistant Prostate Cancer - Subgroup Analyses From an
International, Double-blind, Randomized, Phase 3 Trial
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Oudard, S.] Georges Pompidou Hosp, Paris, France.
[Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Karsh, L.] Urol Ctr Colorado, Dept Clin Res, Denver, CO USA.
[Egerdie, B.] Urol Associates, Urol Med Res, Med Res, Kitchener, ON, Canada.
[Van Veldhuizen, P.] Kansas City VA Med Ctr, Kansas City, MO USA.
[Gomez-Veiga, F.] Hosp Univ Juan Canalejo, La Coruna, Spain.
[Dearnaley, D.] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England.
[Ye, Z.] Amgen Inc, Gobal Biostat Sci, Thousand Oaks, CA 91320 USA.
[Dansey, R.; Goessl, C.] Amgen Inc, Hematol Oncol, Thousand Oaks, CA 91320 USA.
NR 0
TC 1
Z9 1
U1 1
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 SEP
PY 2011
VL 47
SU 1
BP S484
EP S485
PG 2
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752801680
ER
PT J
AU Puzanov, I
Michaelson, D
Cohen, D
Li, S
Burnett, P
Desai, J
AF Puzanov, I.
Michaelson, D.
Cohen, D.
Li, S.
Burnett, P.
Desai, J.
TI Evaluation of Hand-foot Syndrome (HFS) as a Potential Biomarker of
Sunitinib (SU) Efficacy in Patients (pts) With Metastatic Renal Cell
Carcinoma (mRCC) and Gastrointestinal Stromal Tumour (GIST)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Puzanov, I.] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA.
[Michaelson, D.] Massachusetts Gen Hosp Canc, Genitourinary Canc Ctr, Boston, MA USA.
[Cohen, D.] Pfizer Oncol, La Jolla, CA USA.
[Li, S.] Pfizer Oncol, Shanghai, Peoples R China.
[Burnett, P.] Vanderbilt Univ, Med Ctr, Genitourinary Canc Ctr, Boston, MA USA.
[Desai, J.] Royal Melbourne Hosp, Dept Med Oncol, Parkville, Vic 3050, Australia.
NR 0
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2011
VL 47
SU 1
BP S182
EP S182
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800631
ER
PT J
AU Reichardt, P
Kang, YK
Rutkowski, P
Schuette, J
Rosen, LS
Seddon, B
Yalcin, S
Chen, L
Fly, K
Demetri, GD
AF Reichardt, P.
Kang, Y. K.
Rutkowski, P.
Schuette, J.
Rosen, L. S.
Seddon, B.
Yalcin, S.
Chen, L.
Fly, K.
Demetri, G. D.
TI Optimizing Management of Sunitinib Treatment in a Worldwide
Treatment-use Trial of Patients (Pts) With Advanced Gastrointestinal
Stromal Tumour (GIST)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Reichardt, P.] Helios Klinikum Bad Saarow, Innere Med Klin 3, Bad Saarow Pieskow, Germany.
[Kang, Y. K.] Asan Med Ctr, Dept Oncol, Seoul, South Korea.
[Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland.
[Schuette, J.] Marien Hosp Duesseldorf, Dept Hematol & Oncol, Dusseldorf, Germany.
[Seddon, B.] Univ Coll Hosp, Dept Oncol, London, England.
[Chen, L.] Pfizer Oncol, Biostat, New York, NY USA.
[Fly, K.] Pfizer Oncol, Oncol, New London, CT USA.
[Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA.
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 SEP
PY 2011
VL 47
SU 1
BP S669
EP S669
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752802360
ER
PT J
AU Seki, H
Hayashida, T
Jinno, H
Hirose, S
Takahashi, M
Maheswaran, S
Mukai, M
Kitagawa, Y
AF Seki, H.
Hayashida, T.
Jinno, H.
Hirose, S.
Takahashi, M.
Maheswaran, S.
Mukai, M.
Kitagawa, Y.
TI HOXB9, a Gene Promoting Tumour Angiogenesis and Proliferation, is a
Novel Prognostic Biomarker in Human Breast Cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Seki, H.; Hayashida, T.; Jinno, H.; Hirose, S.; Takahashi, M.; Mukai, M.; Kitagawa, Y.] Keio Univ, Sch Med, Tokyo, Japan.
[Maheswaran, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Maheswaran, S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
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 SEP
PY 2011
VL 47
SU 1
BP S182
EP S183
PG 2
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800632
ER
PT J
AU Shulman, L
AF Shulman, L.
TI Electronic Health Records and Other Health Information Technology and
Their Ability to Measure and Improve Cancer Care
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Shulman, L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
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 SEP
PY 2011
VL 47
SU 1
BP S43
EP S43
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752800154
ER
PT J
AU Small, EJ
Higano, CS
Kantoff, PW
Whitmore, JB
Frohlich, MW
Petrylak, DP
AF Small, E. J.
Higano, C. S.
Kantoff, P. W.
Whitmore, J. B.
Frohlich, M. W.
Petrylak, D. P.
TI Time to Disease-related Pain After Sipuleucel-T in Asymptomatic Patients
With Metastatic Castrate Resistant Prostate Cancer (mCRPC): Results From
3 Randomized Phase III Trials
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Small, E. J.] UCSF Comprehens Canc Ctr, San Francisco, CA USA.
[Higano, C. S.] Univ Washington, Seattle, WA 98195 USA.
[Kantoff, P. W.] Dana Farber Canc Inst, Div Solid Tumour Oncol, Boston, MA 02115 USA.
[Whitmore, J. B.; Frohlich, M. W.] Dendreon Corp, Seattle, WA USA.
[Petrylak, D. P.] Columbia Univ, Med Ctr, Div Hematol Oncol, New York, NY USA.
NR 0
TC 3
Z9 3
U1 1
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 SEP
PY 2011
VL 47
SU 1
BP S484
EP S484
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752801679
ER
PT J
AU Wolpin, BM
O'Reilly, EM
Ko, YJ
Lima, MSR
Spratlin, JL
Macarulla, T
Pezet, D
Hartford, A
Jackson, LS
Hidalgo, M
AF Wolpin, B. M.
O'Reilly, E. M.
Ko, Y. J.
Lima, M. S. Rocha
Spratlin, J. L.
Macarulla, T.
Pezet, D.
Hartford, A.
Jackson, L. S.
Hidalgo, M.
TI Improved 6-month Survival Rate in Subjects With Prostate Stem Cell
Antigen (PSCA) Positive Tumours in a Global, Randomized Phase 2 Trial
Comparing Gemcitabine Vs. Gemcitabine + Ags-1c4d4 (asp6182) in
Metastatic Pancreatic Cancer (mPC)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT European Multidisciplinary Cancer Congress on Integrating Basic and
Translational Science, Surgery, Radiotherapy, Medical oncology, Advocacy
and Care
CY SEP 23-27, 2011
CL Stockholm, SWEDEN
C1 [Wolpin, B. M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[O'Reilly, E. M.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Ko, Y. J.] Univ Toronto, Dept Med, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Lima, M. S. Rocha] Univ Miami, Sylvester Comprehens Canc Ctr, Dept Oncol, Miami, FL USA.
[Spratlin, J. L.] Cross Canc Inst, Dept Med, Edmonton, AB T6G 1Z2, Canada.
[Macarulla, T.] Hosp Vail dHebron, Dept Med, Barcelona, Spain.
[Pezet, D.] Chu Estaing, Dept Digest Surg & Oncol, Clermont Ferrand, France.
[Hartford, A.; Jackson, L. S.] Agensys Inc, Dept Clin Res & Dev, Santa Monica, CA USA.
[Hidalgo, M.] Ctr Integral Oncol Clara Campal, Dept Med, Madrid, Spain.
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 SEP
PY 2011
VL 47
SU 1
BP S469
EP S469
PG 1
WC Oncology
SC Oncology
GA 831TA
UT WOS:000295752801628
ER
PT J
AU Zhang, Y
Nateras, OS
Peng, Q
Kuranov, RV
Harrison, JM
Milner, TE
Duong, TQ
AF Zhang, Yi
Nateras, Oscar San Emeterio
Peng, Qi
Kuranov, Roman V.
Harrison, Joseph M.
Milner, Thomas E.
Duong, Timothy Q.
TI Lamina-Specific Anatomic Magnetic Resonance Imaging of the Human Retina
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; MANGANESE-ENHANCED MRI; BLOOD-FLOW;
IN-VIVO; FUNCTIONAL MRI; RAT RETINA; 7 TESLA; QUANTIFICATION;
RESOLUTION; THICKNESS
AB PURPOSE. Magnetic resonance imaging (MRI) of the human retina faces two major challenges: eye movement and hardware limitation that could preclude human retinal MRI with adequate spatiotemporal resolution. This study investigated eye-fixation stability and high-resolution anatomic MRI of the human retina on a 3-Tesla (T) MRI scanner. Comparison was made with optical coherence tomography (OCT) on the same subjects.
METHODS. Eye-fixation stability of protocols used in MRI was evaluated on four normal volunteers using an eye tracker. High-resolution MRI (100 x 200 x 2000 mu m) protocol was developed on a 3-T scanner. Subjects were instructed to maintain stable eye fixation on a target with cued blinks every 8 seconds during MRI. OCT imaging of the retina was performed. Retinal layer thicknesses measured with MRI and OCT were analyzed for matching regions of the same eyes close to the optic nerve head.
RESULTS. The temporal SDs of the horizontal and vertical displacements were 78 +/- 51 and 130 +/- 51 mu m (+/- SD, n = 4), respectively. MRI detected three layers within the human retina, consistent with MRI findings in rodent, feline, and baboon retinas. The hyperintense layer 1 closest to the vitreous likely consisted of nerve fiber, ganglion cell, and inner nuclear layer; the hypointense layer 2, the outer nuclear layer and the inner and outer segments; and the hyperintense layer 3, the choroid. The MRI retina/choroid thickness was 711 +/- 37 mu m, 19% (P < 0.05) thicker than OCT thickness (579 +/- 34 mu m).
CONCLUSIONS. This study reports high-resolution MRI of laminaspecific structures in the human retina. These initial results are encouraging. Further improvement in spatiotemporal resolution is warranted. (Invest Ophthalmol Vis Sci. 2011;52:7232-7237) DOI:10.1167/iovs.11-7623
C1 [Zhang, Yi; Nateras, Oscar San Emeterio; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Zhang, Yi; Nateras, Oscar San Emeterio; Peng, Qi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Kuranov, Roman V.; Harrison, Joseph M.; 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.
[Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 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 duongt@uthscsa.edu
RI Duong, Timothy/B-8525-2008
FU Clinical Translational Science Award; Translational Technology Resource
Grant [UL1RR025767]; National Institutes of Health/National Eye
Institute [R01 EY014211, EY018855]; Department of Veterans Affairs
FX Supported in part by a Clinical Translational Science Award Pilot grant
(TQD) and a Translational Technology Resource Grant UL1RR025767 (QP),
National Institutes of Health/National Eye Institute Grants R01 EY014211
and EY018855, and Department of Veterans Affairs Merit awards (TQD).
NR 46
TC 20
Z9 20
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2011
VL 52
IS 10
BP 7232
EP 7237
DI 10.1167/iovs.11-7623
PG 6
WC Ophthalmology
SC Ophthalmology
GA 827YU
UT WOS:000295467200027
PM 21828153
ER
PT J
AU Wang, LQ
Jeong, KJ
Chiang, HH
Zurakowski, D
Behlau, I
Chodosh, J
Dohlman, CH
Langer, R
Kohane, DS
AF Wang, Liqiang
Jeong, Kyung Jae
Chiang, Homer H.
Zurakowski, David
Behlau, Irmgard
Chodosh, James
Dohlman, Claes H.
Langer, Robert
Kohane, Daniel S.
TI Hydroxyapatite for Keratoprosthesis Biointegration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID COATINGS; TRANSPLANTATION; HYDROXYLAPATITE; ENDOPHTHALMITIS;
CHROMATOGRAPHY; SUBSTRATE; PROTEINS; SURVIVAL; TITANIUM; ADHESION
AB PURPOSE. Integration of keratoprosthesis with the surrounding cornea is very important in preventing bacterial invasion, which may cause ocular injury. Here the authors investigated whether hydroxyapatite (HAp) coating can improve keratoprosthesis (KPro) biointegration, using polymethyl methacrylate (PMMA)-the principal component of the Boston KPro-as a model polymer.
METHODS. HAp coatings were induced on PMMA discs after treatment with concentrated NaOH and coating with polydopamine (PDA) or polydopamine and then with 11-mercaptoundecanoic acid (11-MUA). Coatings were characterized chemically (Fourier transform infrared spectroscopy [FTIR], energy dispersive X-ray spectroscopy [EDX]) and morphologically (SEM) and were used as substrates for keratocyte growth in vitro. Cylinders of coated PMMA were implanted in porcine corneas ex vivo for 2 weeks, and the force required to pull them out was measured. The inflammatory reaction to coated discs was assessed in the rabbit cornea in vivo.
RESULTS. FTIR of the coatings showed absorption bands characteristic of phosphate groups, and EDX showed that the Ca/P ratios were close to those of HAp. By SEM, each method resulted in morphologically distinct HAp films; the 11-MUA group had the most uniform coating. The hydroxyapatite coatings caused comparable enhancement of keratocyte proliferation compared with unmodified PMMA surfaces. HAp coating significantly increased the force and work required to pull PMMA cylinders out of porcine corneas ex vivo. HAp coating of implants reduced the inflammatory response around the PMMA implants in vivo.
CONCLUSIONS. These results are encouraging for the potential of HAp-coated surfaces for use in keratoprostheses. (Invest Ophthalmol Vis Sci. 2011;52:7392-7399) DOI:10.1167/iovs.11-7601
C1 [Jeong, Kyung Jae; Chiang, Homer H.; Kohane, Daniel S.] Harvard Univ, Childrens Hosp, Lab Biomat & Drug Delivery, Dept Anesthesiol,Div Crit Care Med,Sch Med, Boston, MA 02115 USA.
[Wang, Liqiang; Behlau, Irmgard; Chodosh, James; Dohlman, Claes H.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
[Wang, Liqiang] Chinese Peoples Liberat Army Gen Hosp, Dept Ophthalmol, Beijing, Peoples R China.
[Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
RP Kohane, DS (reprint author), Harvard Univ, Childrens Hosp, Lab Biomat & Drug Delivery, Dept Anesthesiol,Div Crit Care Med,Sch Med, Boston, MA 02115 USA.
EM daniel.kohane@childrens.harvard.edu
FU National Institute of General Medical Sciences [GM073626]; Massachusetts
Eye and Ear Infirmary
FX Supported by National Institute of General Medical Sciences Grant
GM073626 (DSK) and the Boston KPro Fund, Massachusetts Eye and Ear
Infirmary (DSK).
NR 35
TC 12
Z9 14
U1 1
U2 18
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 SEP
PY 2011
VL 52
IS 10
BP 7392
EP 7399
DI 10.1167/iovs.11-7601
PG 8
WC Ophthalmology
SC Ophthalmology
GA 827YU
UT WOS:000295467200047
PM 21849419
ER
PT J
AU Sobrin, L
Green, T
Sim, X
Jensen, RA
Tai, ES
Tay, WT
Wang, JJ
Mitchell, P
Sandholm, N
Liu, YY
Hietala, K
Iyengar, SK
Brooks, M
Buraczynska, M
Van Zuydam, N
Smith, AV
Gudnason, V
Doney, ASF
Morris, AD
Leese, GP
Palmer, CNA
Swaroop, A
Taylor, HA
Wilson, JG
Penman, A
Chen, CJ
Groop, PH
Saw, SM
Aung, T
Klein, BE
Rotter, JI
Siscovick, DS
Cotch, MF
Klein, R
Daly, MJ
Wong, TY
AF Sobrin, Lucia
Green, Todd
Sim, Xueling
Jensen, Richard A.
Tai, E. Shyong
Tay, Wan Ting
Wang, Jie Jin
Mitchell, Paul
Sandholm, Niina
Liu, Yiyuan
Hietala, Kustaa
Iyengar, Sudha K.
Brooks, Matthew
Buraczynska, Monika
Van Zuydam, Natalie
Smith, Albert V.
Gudnason, Vilmundur
Doney, Alex S. F.
Morris, Andrew D.
Leese, Graham P.
Palmer, Colin N. A.
Swaroop, Anand
Taylor, Herman A., Jr.
Wilson, James G.
Penman, Alan
Chen, Ching J.
Groop, Per-Henrik
Saw, Seang-Mei
Aung, Tin
Klein, Barbara E.
Rotter, Jerome I.
Siscovick, David S.
Cotch, Mary Frances
Klein, Ronald
Daly, Mark J.
Wong, Tien Y.
CA Family Invest Nephropathy Diabet-E
Wellcome Trust Case Control Consor
TI Candidate Gene Association Study for Diabetic Retinopathy in Persons
with Type 2 Diabetes: The Candidate Gene Association Resource (CARe)
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; COMMON VARIANTS;
RISK-FACTORS; ERYTHROPOIETIN GENE; LINKAGE ANALYSES; BLOOD-PRESSURE;
UNITED-STATES; FTO GENE; COMPLICATIONS
AB PURPOSE. To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate gene Association Resource (CARe).
METHODS. Persons with T2D who were enrolled in the study (n = 2691) had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades >= 14 and >= 30. The chi(2) analyses for each CARe cohort were combined by Cochran-Mantel- Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple hypothesis testing. Logistic regression was performed with adjustment for other DR risk factors. Results from replication in independent cohorts were analyzed with CMH meta-analysis methods.
RESULTS. Among 39 genes previously associated with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni correction). These associations remained significant after adjustment for DR risk factors. Among other genes examined, several variants were associated with DR with significant P values, including rs6856425 tagging alpha-Liduronidase (IDUA) (P = 2.1 X 10(-5), after Bonferroni correction). However, replication in independent cohorts did not reveal study-wide significant effects. The P values after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively.
CONCLUSIONS. Genes associated with DN, T2D, and vascular diseases do not appear to be consistently associated with DR. A few genetic variants associated with DR, particularly those in SELP and near IDUA, should be investigated in additional DR cohorts. (Invest Ophthalmol Vis Sci. 2011;52:7593-7602) DOI:10.1167/iovs.11-7510
C1 [Sobrin, Lucia] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Green, Todd; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Green, Todd; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Sim, Xueling] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore.
[Tai, E. Shyong] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore.
[Tai, E. Shyong; Saw, Seang-Mei] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore.
[Aung, Tin; Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore.
[Jensen, Richard A.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Tai, E. Shyong] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore.
[Tay, Wan Ting; Aung, Tin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia.
[Wang, Jie Jin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Sandholm, Niina; Groop, Per-Henrik] Univ Helsinki, Dept Med, Div Nephrol, Helsinki, Finland.
[Sandholm, Niina; Hietala, Kustaa; Groop, Per-Henrik] Biomedicum Helsinki, Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland.
[Liu, Yiyuan; Van Zuydam, Natalie; Palmer, Colin N. A.] Univ Dundee, Inst Biomed Res, Dundee, Scotland.
[Hietala, Kustaa] Univ Helsinki, Cent Hosp, Dept Ophthalmol, Helsinki, Finland.
[Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Brooks, Matthew; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Buraczynska, Monika] Med Univ Lublin, Lab DNA Anal & Mol Diagnost, Dept Nephrol, Lublin, Poland.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Doney, Alex S. F.; Morris, Andrew D.; Leese, Graham P.] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med & Therapeut, Populat Pharmacogenet Grp, Dundee DD1 9SY, Scotland.
[Taylor, Herman A., Jr.; Penman, Alan] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Penman, Alan] Univ Mississippi, Med Ctr, Dept Biostat, Jackson, MS 39216 USA.
[Chen, Ching J.] Univ Mississippi, Med Ctr, Dept Ophthalmol, Jackson, MS 39216 USA.
[Klein, Barbara E.; Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
RP Sobrin, L (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM lucia_sobrin@meei.harvard.edu
RI Nelson, Robert/B-1470-2012; Palmer, Colin/C-7053-2008; Wang, Jie
Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Blackwell,
Jenefer/H-3015-2015; Gudnason, Vilmundur/K-6885-2015; Smith,
Albert/K-5150-2015; Study, GoDARTS/K-9448-2016;
OI Swaroop, Anand/0000-0002-1975-1141; Gillman,
Matthew/0000-0002-2340-6930; Plomin, Robert/0000-0002-0756-3629; Klein,
Ronald/0000-0002-4428-6237; Tai, E Shyong/0000-0003-2929-8966; Palmer,
Colin/0000-0002-6415-6560; Wang, Jie Jin/0000-0001-9491-4898; Gudnason,
Vilmundur/0000-0001-5696-0084; Cotch, Mary Frances/0000-0002-2046-4350;
Smith, Albert/0000-0003-1942-5845; Sandholm, Niina/0000-0003-4322-6942;
Potter, Simon/0000-0003-4208-4102
FU National Eye Institute [K12-EY16335]; Research to Prevent Blindness
Career Development Award; Massachusetts Lions Eye Research Fund; Sara
Elizabeth O'Brien Trust; Harvard Catalyst/The Harvard Clinical and
Translational Science Center; National Institutes of Health [UL1 RR
025758]; Harvard University; affiliated academic health care centers;
National Heart, Lung Blood Institute (NHLBI) [N01-HC-65226];
Atherosclerosis Risk in Communities (ARIC) Study,; Cardiovascular Health
Study (CHS); Jackson Heart Study (JHS); Multi-ethnic Study of
Atherosclerosis (MESA)
FX Supported by National Eye Institute Grant K12-EY16335; a Research to
Prevent Blindness Career Development Award; the Massachusetts Lions Eye
Research Fund; the Sara Elizabeth O'Brien Trust; and Harvard
Catalyst/The Harvard Clinical and Translational Science Center, National
Institutes of Health Award Grant UL1 RR 025758 and financial
contributions from Harvard University and its affiliated academic health
care centers. The National Heart, Lung Blood Institute (NHLBI) Grant
N01-HC-65226 has supported genotyping and has created a
genotype-phenotype database with data and samples from nine cohorts as
part of Candidate Gene Association Resource (CARe). Please see the
Supplementary Material
(http://www.iovs.org/lookup/suppl/doi:10.1167/iovs.11-7510/-/DC
Supplemental), as well as http://public.nhlbi.nih.gov/Genetics
Genomics/home/care.aspx for detailed information about the grants
supporting the four cohorts in this study: Atherosclerosis Risk in
Communities (ARIC) Study, Cardiovascular Health Study (CHS), Jackson
Heart Study (JHS), and Multi-ethnic Study of Atherosclerosis (MESA).
Please see the Supplementary Material
(http://www.iovs.org/lookup/suppl/doi: 10.1167/iovs.11-7510/-/DC
Supplemental) for detailed information about the grants supporting the
replication cohorts.
NR 69
TC 34
Z9 34
U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2011
VL 52
IS 10
BP 7593
EP 7602
DI 10.1167/iovs.11-7510
PG 10
WC Ophthalmology
SC Ophthalmology
GA 827YU
UT WOS:000295467200072
PM 21873659
ER
PT J
AU Yu, YG
Zhu, HT
Miller, DT
Gusella, JF
Platt, OS
Wu, BL
Shen, YP
AF Yu, Yongguo
Zhu, Haitao
Miller, David T.
Gusella, James F.
Platt, Orah S.
Wu, Bai-Lin
Shen, Yiping
CA Children's Hosp Boston Genotype
TI Age- and gender-dependent obesity in individuals with 16p11.2 deletion
SO JOURNAL OF GENETICS AND GENOMICS
LA English
DT Article
DE Obesity; Chromosome deletion; 16p11.2; Developmental delay; Autism
spectrum disorders; Chromosomal microarray analysis; Genetic testing
ID AUTISM SPECTRUM DISORDER; BODY-MASS INDEX; PERVASIVE DEVELOPMENTAL
DISORDERS; MENTAL-RETARDATION; CHROMOSOME 16P11.2; FEMALE-CHILDREN;
MICRODELETION; ASSOCIATION; PHENOTYPE; GENES
AB Recurrent genomic imbalances at 16p11.2 are genetic risk factors of variable penetrance for developmental delay and autism. Recently, 16p11.2 (chr16:29.5 Mb-30.1 Mb) deletion has also been detected in individuals with early-onset severe obesity. The penetrance of 16p11.2 deletion as a genetic risk factor for obesity is unknown. We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2 (chr16: 29.5 Mbe30.1 Mb) deletion originally ascertained for their developmental disorders by reviewing their medical records. We found that nine individuals could be classified as obese and six as overweight. These individuals generally had early feeding and growth difficulties, and started to gain excessive weight around 5-6 years of age. Thirteen out of the 18 deletion carriers aged 5 years and older (72%) were overweight or obese, whereas only two of 10 deletion carriers (20%) younger than five were overweight or obese. Males exhibited more severe obesity than females. Thus, the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset, exhibited an age-and gender-dependent penetrance. 16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader-Willi syndrome (PWS). Early detection of this deletion will provide opportunity to prevent obesity.
C1 [Yu, Yongguo; Zhu, Haitao; Miller, David T.; Platt, Orah S.; Wu, Bai-Lin; Shen, Yiping] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
[Gusella, James F.; Shen, Yiping] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Miller, David T.; Gusella, James F.; Platt, Orah S.; Wu, Bai-Lin; Shen, Yiping] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Yu, Yongguo; Shen, Yiping] Shanghai Jiao Tong Univ, Shanghai Childrens Med Ctr, Shanghai 200127, Peoples R China.
[Zhu, Haitao; Wu, Bai-Lin] Fudan Univ, Childrens Hosp, Shanghai 201102, Peoples R China.
[Zhu, Haitao; Wu, Bai-Lin] Fudan Univ, Inst Biomed Sci, Shanghai 201102, Peoples R China.
RP Wu, BL (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM Bai-lin.Wu@childrens.harvard.edu; yiping.shen@childrens.harvard.edu
OI yu, yongguo/0000-0002-4472-0910
FU Chinese National Natural Science Foundation [81000346]; Center for
Clinical Nutrition Study [SCMC-YP-HOPE-KY-0905]; social development
branch of Pudong New District [PW2009D-9]; Simons Foundation;
Developmental Genome Anatomy Project [P01 GM061354]; Chinese National
"973" Project on Population and Health [2010CB529601]; Science and
Technology Council of Shanghai [09JC1402400]; Children's Tumor
Foundation; Harvard Medical School
FX This work was supported by the Chinese National Natural Science
Foundation (No. 81000346, Y.G.Y.); foundation grant from the Center for
Clinical Nutrition Study (SCMC-YP-HOPE-KY-0905 for Y.G.Y); Health
Science grant from the social development branch of Pudong New District
(PW2009D-9 for Y.G.Y); the Simons Foundation (J.F.G.), Autism Speaks
(J.F.G.) and Developmental Genome Anatomy Project (P01 GM061354);
Chinese National "973" Project on Population and Health (No.
2010CB529601, B.-L. W.); Science and Technology Council of Shanghai (No.
09JC1402400 (B.-L. W.); Y. Shen holds a Young Investigator Award from
the Children's Tumor Foundation and Catalyst Award from Harvard Medical
School. We would like to thank Joel Hirschhorn MD, PhD for helpful
discussion and review of the manuscript. We gratefully acknowledge the
assistance by our colleagues from the DNA Diagnostics Lab: Va Lip,
Xiaoming Sheng, Ann Reinhard, Hong Fang, Siv Tang, Hong Shao, Sam Tang,
and Andrew Cheng for technical support of array CGH.
NR 28
TC 7
Z9 9
U1 1
U2 14
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 1673-8527
J9 J GENET GENOMICS
JI J. Genet. Genomics
PD SEP
PY 2011
VL 38
IS 9
BP 403
EP 409
DI 10.1016/j.jgg.2011.08.003
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 831LT
UT WOS:000295732900003
PM 21930099
ER
PT J
AU Amariglio, RE
Townsend, MK
Grodstein, F
Sperling, RA
Rentz, DM
AF Amariglio, Rebecca England
Townsend, Mary K.
Grodstein, Francine
Sperling, Reisa A.
Rentz, Dorene M.
TI Specific Subjective Memory Complaints in Older Persons May Indicate Poor
Cognitive Function
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE memory complaints; cognitive function; aging
ID ALZHEIMERS-DISEASE; IMPAIRMENT; COMMUNITY; PERFORMANCE; DEMENTIA
AB OBJECTIVES: To examine the association between the type and number of subjective memory complaints (SMCs) and performance on objective cognitive tests.
DESIGN: Cross-sectional.
SETTING: Nurses' Health Study.
PARTICIPANTS: Sixteen thousand nine hundred sixty-four women (mean age 74) who provided information on SMCs.
MEASUREMENTS: Telephone cognitive assessments and seven questions regarding SMCs were administered. Cognitive impairment was defined as a score of less than 31 on the Telephone Interview for Cognitive Status (TICS) and below the 10th percentile on other cognitive measures. To assess associations with SMCs, multivariable logistic regression was used to calculate odds ratios for cognitive impairment and multivariable linear regression to calculate mean differences in cognitive test scores, adjusting for age and depressive symptoms.
RESULTS: Some SMCs, such as trouble following a group conversation or finding one's way around familiar streets, were more highly associated than others with odds of cognitive impairment. The complaint of forgetting things from one second to the next, generally considered part of normal aging, was not associated with cognitive impairment. In addition, there were strong, linear trends of increasingly worse scores on cognitive tests with increasing numbers of memory complaints. For each additional SMC endorsed, the odds of cognitive impairment increased approximately 20% when each SMC was weighted equally.
CONCLUSION: SMCs are associated with objective cognitive status and may be considered by primary care physicians in determining whether follow-up is warranted. J Am Geriatr Soc 59: 1612-1617, 2011.
C1 [Amariglio, Rebecca England] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA.
[Townsend, Mary K.; Grodstein, Francine] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Townsend, Mary K.; Grodstein, Francine] Harvard Univ, Sch Med, Boston, MA USA.
[Sperling, Reisa A.; Rentz, Dorene M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Grodstein, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Amariglio, RE (reprint author), Brigham & Womens Hosp, Div Cognit & Behav Neurol, Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA.
EM rengland@partners.org
FU National Institutes of Health [CA87969, AG15424]; Yerby Postdoctoral
Fellowship Program
FX This research was supported by Grants CA87969 and AG15424 from the
National Institutes of Health. Dr. Townsend was supported by the Yerby
Postdoctoral Fellowship Program.
NR 21
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U1 1
U2 15
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 SEP
PY 2011
VL 59
IS 9
BP 1612
EP 1617
DI 10.1111/j.1532-5415.2011.03543.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 829WD
UT WOS:000295615000006
PM 21919893
ER
PT J
AU Pham, AN
Datta, SK
Weber, TJ
Walter, LC
Colon-Emeric, CS
AF Pham, Annalise N.
Datta, Santanu K.
Weber, Thomas J.
Walter, Louise C.
Colon-Emeric, Cathleen S.
TI Cost-Effectiveness of Oral Bisphosphonates for Osteoporosis at Different
Ages and Levels of Life Expectancy
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE osteoporosis; bisphosphonates; cost-effectiveness
ID FRACTURE INTERVENTION TRIAL; VERTEBRAL FRACTURES; HIP FRACTURE;
UNITED-STATES; BONE-DENSITY; OLDER WOMEN; ALENDRONATE; RISK;
RISEDRONATE; MORTALITY
AB OBJECTIVES: To evaluate the cost-effectiveness of oral bisphosphonate therapy for osteoporosis in women at different ages and life expectancies.
DESIGN: A Markov model was used to analyze oral bisphosphonate treatment for 5 years compared to no intervention. Women at each age were divided into life expectancy quartiles: the lowest 1% to 25% (sickest group), the two middle 26% to 75% (average health group), and the highest 76% to 100% of life expectancy (healthiest group). Simulations were performed for hypothetical cohorts at 5-year intervals with starting ages between 50 and 90 and for each life expectancy group and followed for up to 100 years or until death. Data sources included published fracture rates, costs, utility values, and mortality risks.
SETTING: Computer simulation using a societal perspective.
PARTICIPANTS: Hypothetical cohort of women with various life expectancies beginning osteoporosis treatment between the age of 50 and 90 years.
MEASUREMENTS: Cost per quality-adjusted life years (QALY) gained for 5 years of bisphosphonate therapy compared to no treatment. Cost-effectiveness was defined at a willingness-to-pay of $50,000.
RESULTS: In the healthiest group, all costs were less than $18,000 per QALY. In the median quartiles of life expectancy, lifetime costs per QALY were less than $27,000 for patients at all ages; treatment became cost-saving at a starting age of 75 and remained so through a starting age of 85. Even in the sickest group, although osteoporosis treatment was not cost-saving, it remained cost-effective through a starting age of 90 with lifetime costs of less than $43,000 per QALY.
CONCLUSION: Treatment with an oral bisphosphonate for 5 years was cost-effective for all women, regardless of quartile of life expectancy. Advanced age should not prevent consideration of osteoporosis treatment based on cost effectiveness, and strategies to improve care, such as nurseled screening programs or electronic medical record tools, are needed. J Am Geriatr Soc 59: 1642-1649, 2011.
C1 [Colon-Emeric, Cathleen S.] Duke Univ, Div Geriatr, Med Ctr, Durham, NC 27705 USA.
[Weber, Thomas J.] Duke Univ, Div Endocrinol, Med Ctr, Durham, NC 27705 USA.
[Datta, Santanu K.] Duke Univ, Div Gen Internal Med, Med Ctr, Durham, NC 27705 USA.
[Pham, Annalise N.] Canberra Hosp, Dept Endocrinol, Canberra, ACT, Australia.
[Colon-Emeric, Cathleen S.] Durham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA.
[Datta, Santanu K.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res, Durham, NC USA.
[Walter, Louise C.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94143 USA.
RP Colon-Emeric, CS (reprint author), Duke Univ, Div Geriatr, Med Ctr, 508 Fulton St,GRECC 182, Durham, NC 27705 USA.
EM colon001@mc.duke.edu
FU Presidential Poster Award in Geriatric Syndromes; Novartis; Amgen; Eli
Lilly; Wyeth; Pfizer
FX Presented as a poster at the Annual Scientific Meeting of the American
Geriatrics Society, May 2010, and recipient of the Presidential Poster
Award in Geriatric Syndromes.; Dr. Pham received an educational grant
from Novartis in 2009 for medical research at Duke University. Dr. Weber
receives funding from Amgen, Eli Lilly, and Novartis and is a consultant
for Proctor and Gamble and GlaxoSmithKline. Dr. Colon-Emeric receives
research funding from Novartis, Wyeth, and Pfizer for
osteoporosis-related studies and is a consultant for Novartis and Amgen.
NR 43
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U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD SEP
PY 2011
VL 59
IS 9
BP 1642
EP 1649
DI 10.1111/j.1532-5415.2011.03571.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 829WD
UT WOS:000295615000010
PM 21883116
ER
PT J
AU Latourelle, JC
Hendricks, AE
Pankratz, N
Wilk, JB
Halter, C
Nichols, WC
Gusella, JF
Destefano, AL
Myers, RH
Foroud, T
AF Latourelle, Jeanne C.
Hendricks, Audrey E.
Pankratz, Nathan
Wilk, Jemma B.
Halter, Cheryl
Nichols, William C.
Gusella, James F.
Destefano, Anita L.
Myers, Richard H.
Foroud, Tatiana
CA PSG Progeni GenePD Investigators
TI Genomewide Linkage Study of Modifiers of LRRK2-Related Parkinson's
Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; leucine-rich repeat kinase 2; linkage
ID LRRK2 MUTATION; ONSET AGE; ASSOCIATION; GENE; G2019S; FAMILIES;
HETEROZYGOSITY; RELEVANCE; MAPS
AB Mutations in the leucine-rich repeat kinase 2 gene, located at 12q12, are the most common known genetic causes of Parkinson's disease. Studies of leucine-rich repeat kinase 2 mutation carriers have shown incomplete and age-dependent penetrance, and previous studies have suggested that inherited susceptibility factors may modify the penetrance of leucine-rich repeat kinase 2 mutations. Genomewide linkage to age of onset of leucine-rich repeat kinase 2-related Parkinson's disease was evaluated in a sample of 113 leucine-rich repeat kinase 2 mutation carriers from 64 families using single-nucleotide polymorphism data from the Illumina HumanCNV370 genotyping array. Association between onset age and single-nucleotide polymorphisms under suggestive linkage peaks was also evaluated. The top logarithmic odds score for onset age (logarithmic odds score = 2.43) was in the chromosome 1q32.1 region. Moderate linkage to onset was also identified at 16q12.1 (logarithmic odds score = 1.58). Examination of single-nucleotide polymorphism association to Parkinson's disease onset under the linkage peaks revealed no statistically significant single-nucleotide polymorphism associations. The 2 novel genomic regions identified may harbor modifiers of leucine-rich repeat kinase 2-related Parkinson's disease onset age or penetrance, and further study of these regions may provide important insight into leucine-rich repeat kinase 2-related Parkinson's disease. (C) 2011 Movement Disorder Society
C1 [Latourelle, Jeanne C.; Wilk, Jemma B.; Destefano, Anita L.; Myers, Richard H.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Hendricks, Audrey E.; Destefano, Anita L.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Pankratz, Nathan; Halter, Cheryl; Foroud, Tatiana] Indiana Univ Sch Med, Indianapolis, IN USA.
[Nichols, William C.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Nichols, William C.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Gusella, James F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gusella, James F.] Harvard Univ, Sch Med, Boston, MA USA.
RP Latourelle, JC (reprint author), 72 E Concord St,B-617, Boston, MA 02119 USA.
EM jlatoure@bu.edu
RI Hendricks, Audrey/I-4127-2016;
OI Hendricks, Audrey/0000-0002-7152-0287; Latourelle,
Jeanne/0000-0002-4218-9572; Myers, Richard/0000-0002-8365-2674
FU Robert P. & Judith N. Goldberg Foundation; Bumpus Foundation; Harvard
NeuroDiscovery Center; Department of Medicine at Boston University
School of Medicine; Boston Medical Center; National Institutes of Health
[HHSN268200782096C]; Italian Telethon [GTB07001]; Fondazione Grigioni
per il Morbo di Parkinson; [R01 NS37167]; [R01 NS036711]
FX This project was supported by R01 NS37167, R01 NS036711, the Robert P. &
Judith N. Goldberg Foundation, the Bumpus Foundation, and the Harvard
NeuroDiscovery Center. A portion of this research was conducted using
the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine, and Boston Medical Center. Genotyping
services were provided by the Center for Inherited Disease Research
(CIDR), fully funded through a federal contract from the National
Institutes of Health to Johns Hopkins University (contract
HHSN268200782096C).; This study used samples from the NINDS Human
Genetics Resource Center DNA and Cell Line Repository
(http://ccr.coriell.org/ninds), as well as clinical data. DNA samples
contributed by the Parkinson Institute-Istituti Clinici di
Perfezionamento, Milan, Italy, were from the Human Genetic Bank of
Patients Affected by PD and Parkinsonisms, supported by Italian Telethon
grant number GTB07001, and by the Fondazione Grigioni per il Morbo di
Parkinson. We particularly thank Drs. Kimberly Doheny and Elizabeth Pugh
from CIDR and Mr. Justin Paschall from NCBI for their assistance. The
data used in this study are available at
http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap through dbGaP accession
number phs000126.v1.p1. We thank the subjects for their participation in
this research study.
NR 35
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD SEP
PY 2011
VL 26
IS 11
BP 2039
EP 2044
DI 10.1002/mds.23781
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 827VF
UT WOS:000295456300014
PM 21661047
ER
PT J
AU Morley, JF
Weintraub, D
Mamikonyan, E
Moberg, PJ
Siderowf, AD
Duda, JE
AF Morley, James F.
Weintraub, Daniel
Mamikonyan, Eugenia
Moberg, Paul J.
Siderowf, Andrew D.
Duda, John E.
TI Olfactory Dysfunction Is Associated with Neuropsychiatric Manifestations
in Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; olfaction; nonmotor symptoms; psychiatric symptoms;
cognitive symptoms
ID MINI-MENTAL-STATE; MILD COGNITIVE IMPAIRMENT; NONMOTOR SYMPTOMS; ODOR
IDENTIFICATION; DE-NOVO; DEFICITS; RISK; COMMON; APATHY; TESTS
AB Hyposmia, psychiatric disorders, and cognitive problems are common nonmotor manifestations in Parkinson's disease, but how they are related remains unclear. We investigated the relationship between olfactory dysfunction and neuropsychiatric manifestations and performed a cross-sectional study of 248 patients at two movement disorders clinics at academic medical centers. Psychiatric measures were the Geriatric Depression Scale-15, Inventory of Depressive Symptomatology, State Anxiety Inventory, Apathy Scale, and Parkinson's Psychosis Rating Scale. Cognitive measures were the Mini-Mental State Examination, Hopkins Verbal Learning Test-Revised, Digit Span, Tower of London-Drexel, and the Stroop Color Word Test. Olfaction was tested with the University of Pennsylvania Smell Identification Test. There was no significant association between olfaction and mood measures, but psychotic symptoms were more common in patients with olfaction scores below the median (30% vs. 12%; P < 0.001). Worse olfaction was associated with poorer memory (Hopkins Verbal Learning Test-Revised delayed recall items: mean [standard deviation], 6.2 [3.2] vs. 8.4 [2.8]; P < 0.001) and executive performance (Tower of London total moves, 52 [38] vs. 34 [21]; P < 0.001). Odor-identification score was a significant predictor of abnormal performance on these cognitive tests after adjustment for age, sex, and disease characteristics in logistic regression models. The relationship between hyposmia, psychosis, and specific cognitive impairments may reflect the anatomic distribution of Lewy pathology and suggests that olfactory dysfunction could be a biomarker of additional extranigral disease. Future prospective studies are warranted to assess whether hyposmia, a very early feature of Parkinson's disease, might be used to predict the appearance of other common nonmotor symptoms. (C) 2011 Movement Disorder Society
C1 [Morley, James F.; Weintraub, Daniel; Moberg, Paul J.; Siderowf, Andrew D.; Duda, John E.] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA.
[Morley, James F.; Weintraub, Daniel; Moberg, Paul J.; Siderowf, Andrew D.; Duda, John E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Weintraub, Daniel; Mamikonyan, Eugenia; Moberg, Paul J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA.
RP Duda, JE (reprint author), Philadelphia Vet Adm Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM John.Duda@va.gov
FU NIH [K23 MH067894, NINDS U10 NS044451-023, NINDS P50 NS053488-01, NINDS
R43NS0636071, NINDS R01NS065087]; Teva Pharmaceutical Industries Ltd.;
Avid Radiopharmaceuticals, Inc.; Boehringer Ingelheim; National
Institutes of Health [NIMH K23 MH067894]; NINDS [P50 NS053488-01,
R01NS065087]; NIA [RO1AG031348]; Michael J. Fox Foundation for
Parkinson's Research; Institute for Neurodegenerative Disorders; U.S.
Department of Veterans Affairs; Michael J. Fox Foundation; Samueli
Institute; C.R. Bard, Inc.; Celgene; Clarient, Inc.; Johnson Johnson
FX This work was supported by NIH grant K23 MH067894 (to D.W.).; Dr. Morley
has received travel funding from Teva Pharmaceutical Industries Ltd. Dr.
Weintraub has served on a scientific advisory board for Boehringer
Ingelheim; serves on the editorial board of Movement Disorders; has
received speaker honoraria from Boehringer Ingelheim, ACADIA
Pharmaceuticals, Novartis, Osmotica Pharmaceutical Corp., BrainCells
Inc., Merck Serono, Sanofi-aventis, and Pfizer Inc; and has
received/receives research support from Avid Radiopharmaceuticals, Inc.,
Boehringer Ingelheim, National Institutes of Health (NIMH K23 MH067894
[PI], NINDS P50 NS053488-01 [coinvestigator], NIA RO1AG031348 [site PI],
and NINDS R01NS065087 [coinvestigator]), and from the Michael J. Fox
Foundation for Parkinson's Research. Ms. Mamikonyan reports no
disclosures. Dr. Siderowf serves on a scientific advisory board for, and
has received speaker honoraria from, Teva Pharmaceutical Industries
Ltd.; serves as a consultant for Supernus Pharmaceuticals, Inc.; and
receives research support from Avid Radiopharmaceuticals, Inc., the NIH
(NINDS U10 NS044451-023 [Site PI], NINDS P50 NS053488-01 [cocore leader
and project leader], NINDS R43NS0636071 [site PI], and NINDS R01NS065087
coinvestigator]), and from the Institute for Neurodegenerative
Disorders. Dr. Duda serves on a grant review panel for the Michael J.
Fox Foundation for Parkinson's Research; receives research support from
the U.S. Department of Veterans Affairs (Merit Award [PI]), the Michael
J. Fox Foundation, and the Samueli Institute; and holds stock in C.R.
Bard, Inc., Celgene, Clarient, Inc., and Johnson & Johnson.
NR 53
TC 30
Z9 33
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD SEP
PY 2011
VL 26
IS 11
BP 2051
EP 2057
DI 10.1002/mds.23792
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 827VF
UT WOS:000295456300016
PM 21611985
ER
PT J
AU Sharma, N
Armata, IA
Multhaupt-Buell, TJ
Ozelius, LJ
Xin, WN
Sims, KB
AF Sharma, Nutan
Armata, Ioanna A.
Multhaupt-Buell, Trisha J.
Ozelius, Laurie J.
Xin, Winnie
Sims, Katherine B.
TI Mutation in 5 ' Upstream Region of GCHI Gene Causes Familial
Dopa-Responsive Dystonia
SO MOVEMENT DISORDERS
LA English
DT Letter
C1 [Sharma, Nutan; Armata, Ioanna A.; Multhaupt-Buell, Trisha J.; Xin, Winnie; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
[Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Xin, Winnie; Sims, Katherine B.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Sharma, N (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM nsharma@partners.org
FU NCRR NIH HHS [R21 RR026123]; NINDS NIH HHS [P50 NS037409, R01 NS046340,
5P50NS037409, R01 NS058949, P50 NS037409-11]
NR 5
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD SEP
PY 2011
VL 26
IS 11
BP 2140
EP 2140
DI 10.1002/mds.23786
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 827VF
UT WOS:000295456300035
PM 21674621
ER
PT J
AU Brun, R
Surjanhata, B
Kuo, B
AF Brun, R.
Surjanhata, B.
Kuo, B.
TI pH profiles of gi tract by wireless motility capsule (WMC) in healthy
(H), gastroparetics (GP) and constipated (C)
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Brun, R.; Surjanhata, B.; Kuo, B.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD SEP
PY 2011
VL 23
SU 1
SI SI
MA 48
BP 15
EP 15
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 822NL
UT WOS:000295055100049
ER
PT J
AU Brun, R
Michalek, W
Kuo, B
AF Brun, R.
Michalek, W.
Kuo, B.
TI Cephalic phase of small bowel fed response as measured by wireless
motility capsule (WMC)
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Brun, R.; Michalek, W.; Kuo, B.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 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 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD SEP
PY 2011
VL 23
SU 1
SI SI
MA 47
BP 15
EP 15
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 822NL
UT WOS:000295055100048
ER
PT J
AU Leung, FW
AF Leung, F. W.
TI Treatment of fecal incontinence (FI) by injection of bulking agent into
peri-anal tissue - review of observational studies (OS) and randomized
controlled trials (RCT)
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Leung, F. W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Med Serv, North Hills, CA USA.
[Leung, F. W.] VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res Serv, North Hills, CA USA.
[Leung, F. W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD SEP
PY 2011
VL 23
SU 1
SI SI
MA 68
BP 21
EP 21
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 822NL
UT WOS:000295055100069
ER
PT J
AU Brun, R
Surjanhata, B
Michalek, W
Baker, JR
Wilding, G
Hasler, W
Kuo, B
AF Brun, R.
Surjanhata, B.
Michalek, W.
Baker, J. R.
Wilding, G.
Hasler, W.
Kuo, B.
TI Mild and severe gastroparesis (gp) as defined by wireless motility
capsule (wmc) - comparison of clinical characteristics and pressure
profiles
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Brun, R.; Surjanhata, B.; Michalek, W.; Kuo, B.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA.
[Baker, J. R.; Hasler, W.] Univ Michigan, GI Unit, Ann Arbor, MI 48109 USA.
[Wilding, G.] SUNY Buffalo, Buffalo, NY 14260 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 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD SEP
PY 2011
VL 23
SU 1
SI SI
MA 127
BP 37
EP 37
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 822NL
UT WOS:000295055100127
ER
PT J
AU Chaudhury, A
He, XD
Goyal, RK
AF Chaudhury, A.
He, X. D.
Goyal, R. K.
TI Myosin Va plays a key role in enteric purinergic neurotransmission by
transporting purinergic secretory vesicles to the varicosity membrane
for exocytosis
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 VA Boston HealthCare Syst, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD SEP
PY 2011
VL 23
SU 1
SI SI
MA 163
BP 47
EP 47
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 822NL
UT WOS:000295055100163
ER
PT J
AU Mata, IF
Wilhoite, GJ
Yearout, D
Bacon, JA
Cornejo-Olivas, M
Mazzetti, P
Marca, V
Ortega, O
Acosta, O
Cosentino, C
Torres, L
Medina, AC
Perez-Pastene, C
Diaz-Grez, F
Vilarino-Guell, C
Venegas, P
Miranda, M
Trujillo-Godoy, O
Layson, L
Avello, R
Dieguez, E
Raggio, V
Micheli, F
Perandones, C
Alvarez, V
Segura-Aguilar, J
Farrer, MJ
Zabetian, CP
Ross, OA
AF Mata, Ignacio F.
Wilhoite, Greggory J.
Yearout, Dora
Bacon, Justin A.
Cornejo-Olivas, Mario
Mazzetti, Pilar
Marca, Victoria
Ortega, Olimpio
Acosta, Oscar
Cosentino, Carlos
Torres, Luis
Medina, Angel C.
Perez-Pastene, Carolina
Diaz-Grez, Fernando
Vilarino-Gueell, Carles
Venegas, Pablo
Miranda, Marcelo
Trujillo-Godoy, Osvaldo
Layson, Luis
Avello, Rodrigo
Dieguez, Elena
Raggio, Victor
Micheli, Federico
Perandones, Claudia
Alvarez, Victoria
Segura-Aguilar, Juan
Farrer, Matthew J.
Zabetian, Cyrus P.
Ross, Owen A.
TI Lrrk2 p.Q1111H substitution and Parkinson's disease in Latin America
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson disease; Lrrk2; Latin America
ID COMPREHENSIVE ANALYSIS; MUTATIONS; FAMILIES; RISK; GENE
AB Mutations in the LRRK2 gene are the most common genetic cause of Parkinson's disease, with frequencies displaying a high degree of population-specificity. Although more than 100 coding substitutions have been identified, only seven have been proven to be highly penetrant pathogenic mutations. Studies however are lacking in non-white populations. Recently, Lrrk2 p.Q1111H (rs78365431) was identified in two affected Hispanic brothers and absent in 386 non-Hispanic white healthy controls. We therefore screened this variant in 1460 individuals (1150 PD patients and 310 healthy controls) from 4 Latin American countries (Peru, Chile, Uruguay and Argentina).
In our case-control series from Peru and Chile we observed an increased frequency of Lrrk2 p.Q1111H in patients (7.9%) compared to controls (5.4%) although the difference did not reach significance (OR 1.38; p = 0.10).
In addition, the frequency of Lrrk2 p.Q1111H varied greatly between populations and further screening in a set of pure Amerindian and pure Spanish controls suggested that this variant likely originated in an Amerindian population. Further studies in other Latin American populations are warranted to assess its role as a risk factor for Parkinson's disease. Screening in Parkinson's disease patients from under-represented populations will increase our understanding of the role of LRRK2 variants in disease risk worldwide. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Mata, Ignacio F.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182, Seattle, WA 98108 USA.
[Mata, Ignacio F.; Yearout, Dora; Zabetian, Cyrus P.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
[Wilhoite, Greggory J.; Bacon, Justin A.; Vilarino-Gueell, Carles; Farrer, Matthew J.; Ross, Owen A.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
[Cornejo-Olivas, Mario; Mazzetti, Pilar; Marca, Victoria; Ortega, Olimpio; Segura-Aguilar, Juan] Inst Nacl Ciencias Neurol, Neurogenet Unit, Lima, Peru.
[Acosta, Oscar] Univ Nacl Mayor San Marcos, Sch Med, Lima 14, Peru.
[Medina, Angel C.] Univ Nacl Altiplano, Puno, Peru.
[Perez-Pastene, Carolina; Diaz-Grez, Fernando] Univ Chile, Fac Med, ICBM, Santiago 7, Chile.
[Vilarino-Gueell, Carles; Farrer, Matthew J.] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada.
[Miranda, Marcelo] Clin Las Condes, Santiago, Chile.
[Layson, Luis] Hosp Barros Luco, Santiago, Chile.
[Dieguez, Elena] Univ Republica, Fac Med, Dept Neurol, Montevideo, Uruguay.
[Raggio, Victor] Univ Republica, Fac Med, Dept Genet, Montevideo, Uruguay.
[Micheli, Federico; Perandones, Claudia] Hosp Clin Buenos Aires, Dept Neurol, Buenos Aires, DF, Argentina.
[Alvarez, Victoria] Hosp Univ Cent Asturias, Inst Invest Nefrol IRSINFRIAT, Lab Genet Mol, Oviedo, Spain.
RP Mata, IF (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM nachofm@u.washington.edu
RI Micheli, Federico/A-8358-2012; Ross, Owen/D-7573-2013; Vilarino-Guell,
Carles/D-8628-2011; Segura-Aguilar, Juan/H-8839-2013;
OI Vilarino-Guell, Carles/0000-0002-5612-5940; Segura-Aguilar,
Juan/0000-0002-1018-673X; Fernandez Mata, Ignacio/0000-0003-1198-0633;
Zabetian, Cyrus/0000-0002-7739-4306; Cornejo-Olivas, Mario
/0000-0001-6313-5680
FU National Institutes of Health [R01 NS065070, P50 NS062684, P50
NS072187]; Department of Veterans Affairs [1101BX000531]; FONDECYT
[1061083]; Parkinson's Disease Foundation; Michael J. Fox Foundation;
family of Carl and Susan Bolch; NIH [R24 TW007988]
FX This work was supported by the National Institutes of Health (R01
NS065070, P50 NS062684, P50 NS072187), Department of Veterans Affairs
(1101BX000531), FONDECYT (#1061083), Parkinson's Disease Foundation,
Michael J. Fox Foundation, and the family of Carl and Susan Bolch. Dr
Cornejo-Olivas is the recipient of an NIH Fogarty International Clinical
Research Fellowship at Vanderbilt University (R24 TW007988).
NR 12
TC 3
Z9 4
U1 1
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD SEP
PY 2011
VL 17
IS 8
BP 629
EP 631
DI 10.1016/j.parkreldis.2011.05.003
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 831WE
UT WOS:000295761000010
PM 21632271
ER
PT J
AU Stengel, A
Goebel-Stengel, M
Jawien, J
Kobelt, P
Tache, Y
Lambrecht, NWG
AF Stengel, Andreas
Goebel-Stengel, Miriam
Jawien, Janusz
Kobelt, Peter
Tache, Yvette
Lambrecht, Nils W. G.
TI Lipopolysaccharide increases gastric and circulating NUCB2/nesfatin-1
concentrations in rats
SO PEPTIDES
LA English
DT Article
DE Endotoxin; Ghrelin; Nucleobindin2; Stomach; X/A-like cell
ID REGULATED TRANSCRIPT PEPTIDE; EDINGER-WESTPHAL NUCLEUS; FASTED PLASMA
GHRELIN; FOOD-INTAKE; NESFATIN-1 NEURONS; BODY-WEIGHT; IMMUNOREACTIVITY;
BRAIN; EXPRESSION; RECEPTOR
AB Bacterial lipopolysaccharide (LPS) is an established animal model to study the innate immune response to Gram-negative bacteria mimicking symptoms of infection including reduction of food intake. LPS decreases acyl ghrelin associated with decreased concentrations of circulating ghrelin-O-acyltransferase (GOAT) likely contributing to the anorexigenic effect. We also recently described the prominent expression of the novel anorexigenic hormone, nucleobindin2 (NUCB2)/nesfatin-1 in gastric X/A-like cells co-localized with ghrelin in different pools of vesicles. To investigate whether LPS would affect gastric and circulating NUCB2/nesfatin-1 concentration, ad libitum fed rats were equipped with an intravenous (iv) catheter. LPS was injected intraperitoneally (ip, 100 mu g/kg) and blood was withdrawn before and at 2, 5, 7 and 24 h post injection and processed for NUCB2/nesfatin-1 radioimmunoassay. Gastric corpus was collected to measure NUCB2 mRNA expression by RT-qPCR and NUCB2/nesfatin-1 protein concentration by Western blot. Injection of LPS increased plasma NUCB2/nesfatin-1 concentrations by 43%, 78% and 62% compared to vehicle at 2 h, 5 h and 7 h post injection respectively (p < 0.05) and returned to baseline at 24 h. The plasma NUCB2/nesfatin-1 increase at 2 h was associated with increased corpus NUCB2 mRNA expression (p < 0.01), whereas NUCB2 mRNA was not detectable in white blood cells. Likewise, gastric NUCB2 protein concentration was increased by 62% after LPS compared to vehicle (p < 0.01). These data show that gastric NUCB2 production and release are increased in response to LPS. These changes are opposite to those of ghrelin in response to LPS supporting a differential gastric regulation of NUCB2/nesfatin-1 and ghrelin expression derived from the same cell by immune challenge. (C) 2011 Published by Elsevier Inc.
C1 [Stengel, Andreas; Goebel-Stengel, Miriam; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA.
[Stengel, Andreas; Goebel-Stengel, Miriam; Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA.
[Stengel, Andreas; Kobelt, Peter] Univ Med Berlin, Dept Med, Div Psychosomat Med & Psychotherapy, Charite, Berlin, Germany.
[Goebel-Stengel, Miriam] Martin Luther Krankenhaus, Dept Med, Berlin, Germany.
[Goebel-Stengel, Miriam] Martin Luther Krankenhaus, Inst Neurogastroenterol, Berlin, Germany.
[Lambrecht, Nils W. G.] Vet Affairs Long Beach Healthcare Syst, Gastrointestinal Endocrinol, Long Beach, CA 90822 USA.
RP Lambrecht, NWG (reprint author), VA Long Beach HCS, 5901 E 7th St,Bldg 1,Rm 200M, Long Beach, CA 90822 USA.
EM Nils.Lambrecht2@va.gov
OI Lambrecht, Nils/0000-0002-1275-1384
FU Department of Veterans Affairs; VA Research Career Scientist Award; NIH
[DK-33061]; Center [DK-41301]
FX This work was supported by Department of Veterans Affairs Merit Awards
(N.W.G.L. and Y.T.), VA Research Career Scientist Award (Y.T.), NIH
DK-33061 (Y.T.) and Center grant DK-41301 (Animal Core, Y.T.).
NR 45
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Z9 13
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
EI 1873-5169
J9 PEPTIDES
JI Peptides
PD SEP
PY 2011
VL 32
IS 9
BP 1942
EP 1947
DI 10.1016/j.peptides.2011.07.006
PG 6
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 831YQ
UT WOS:000295767400022
PM 21782869
ER
PT J
AU Anguera, MC
Ma, WY
Clift, D
Namekawa, S
Kelleher, RJ
Lee, JT
AF Anguera, Montserrat C.
Ma, Weiyuan
Clift, Danielle
Namekawa, Satoshi
Kelleher, Raymond J., III
Lee, Jeannie T.
TI Tsx Produces a Long Noncoding RNA and Has General Functions in the
Germline, Stem Cells, and Brain
SO PLOS GENETICS
LA English
DT Article
ID X-CHROMOSOME INACTIVATION; TESTIS-SPECIFIC GENE; DOSAGE COMPENSATION;
SYNAPTIC PLASTICITY; MOUSE EMBRYOS; TSIX; MEMORY; MICE; SPERMATOGENESIS;
HIPPOCAMPUS
AB The Tsx gene resides at the X-inactivation center and is thought to encode a protein expressed in testis, but its function has remained mysterious. Given its proximity to noncoding genes that regulate X-inactivation, here we characterize Tsx and determine its function in mice. We find that Tsx is actually noncoding and the long transcript is expressed robustly in meiotic germ cells, embryonic stem cells, and brain. Targeted deletion of Tsx generates viable offspring and X-inactivation is only mildly affected in embryonic stem cells. However, mutant embryonic stem cells are severely growth-retarded, differentiate poorly, and show elevated cell death. Furthermore, male mice have smaller testes resulting from pachytene-specific apoptosis and a maternal-specific effect results in slightly smaller litters. Intriguingly, male mice lacking Tsx are less fearful and have measurably enhanced hippocampal short-term memory. Combined, our study indicates that Tsx performs general functions in multiple cell types and links the noncoding locus to stem and germ cell development, learning, and behavior in mammals.
C1 [Anguera, Montserrat C.; Clift, Danielle; Lee, Jeannie T.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Anguera, Montserrat C.; Clift, Danielle; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Anguera, Montserrat C.; Clift, Danielle; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Ma, Weiyuan; Kelleher, Raymond J., III] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Ma, Weiyuan; Kelleher, Raymond J., III] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Namekawa, Satoshi] Cincinnati Childrens Hosp Med Ctr, Div Reprod Sci, Cincinnati, OH USA.
RP Anguera, MC (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA.
EM lee@molbio.mgh.harvard.edu
FU NIH; HHMI
FX This work was supported by the NIH and HHMI. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 41
TC 45
Z9 49
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2011
VL 7
IS 9
AR e1002248
DI 10.1371/journal.pgen.1002248
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100007
PM 21912526
ER
PT J
AU Boger, CA
Gorski, M
Li, M
Hoffmann, MM
Huang, CM
Yang, Q
Teumer, A
Krane, V
O'Seaghdha, CM
Kutalik, Z
Wichmann, HE
Haak, T
Boes, E
Coassin, S
Coresh, J
Kollerits, B
Haun, M
Paulweber, B
Kottgen, A
Li, G
Shlipak, MG
Powe, N
Hwang, SJ
Dehghan, A
Rivadeneira, F
Uitterlinden, A
Hofman, A
Beckmann, JS
Kramer, BK
Witteman, J
Bochud, M
Siscovick, D
Rettig, R
Kronenberg, F
Wanner, C
Thadhani, RI
Heid, IM
Fox, CS
Kao, WH
AF Boeger, Carsten A.
Gorski, Mathias
Li, Man
Hoffmann, Michael M.
Huang, Chunmei
Yang, Qiong
Teumer, Alexander
Krane, Vera
O'Seaghdha, Conall M.
Kutalik, Zoltan
Wichmann, H. -Erich
Haak, Thomas
Boes, Eva
Coassin, Stefan
Coresh, Josef
Kollerits, Barbara
Haun, Margot
Paulweber, Bernhard
Koettgen, Anna
Li, Guo
Shlipak, Michael G.
Powe, Neil
Hwang, Shih-Jen
Dehghan, Abbas
Rivadeneira, Fernando
Uitterlinden, Andre
Hofman, Albert
Beckmann, Jacques S.
Kraemer, Bernhard K.
Witteman, Jacqueline
Bochud, Murielle
Siscovick, David
Rettig, Rainer
Kronenberg, Florian
Wanner, Christoph
Thadhani, Ravi I.
Heid, Iris M.
Fox, Caroline S.
Kao, W. H.
CA CKDGen Consortium
TI Association of eGFR-Related Loci Identified by GWAS with Incident CKD
and ESRD
SO PLOS GENETICS
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE;
DIABETIC-NEPHROPATHY; GENERAL-POPULATION; AFRICAN-AMERICANS; RISK;
PROGRESSION; MORTALITY; VARIANTS
AB Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
C1 [Boeger, Carsten A.] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany.
[Gorski, Mathias; Heid, Iris M.] Univ Hosp Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Gorski, Mathias; Wichmann, H. -Erich; Heid, Iris M.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Li, Man; Koettgen, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hoffmann, Michael M.] Univ Freiburg, Univ Med Ctr Freiburg, Freiburg, Germany.
[Huang, Chunmei; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Krane, Vera; Wanner, Christoph] Univ Wurzburg, Div Nephrol, Dept Med 1, Univ Hosp Wurzburg, Wurzburg, Germany.
[O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBIs Framingham Heart Study, Framingham, MA USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Haak, Thomas] Diabet Klin Bad Mergentheim, Bad Mergentheim, Germany.
[Boes, Eva; Coassin, Stefan; Kollerits, Barbara; Haun, Margot; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria.
[Coresh, Josef; Kao, W. H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Coresh, Josef; Kao, W. H.] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Paulweber, Bernhard] Paracelsus Med Univ, Dept Internal Med 1, Salzburg, Austria.
[Koettgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany.
[Li, Guo] Univ Washington, Dept Med, Seattle, WA USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Dept Med Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Powe, Neil] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA.
[Dehghan, Abbas; Hofman, Albert; Witteman, Jacqueline] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Kraemer, Bernhard K.] Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany.
[Bochud, Murielle] CHU Vaudois, Univ Inst Social & Prevent Med, CH-1011 Lausanne, Switzerland.
[Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Boger, CA (reprint author), Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany.
EM foxca@nhlbi.nih.gov; wkao@jhsph.edu
RI Beckmann, Jacques S /A-9772-2008; Kronenberg, Florian/B-1736-2008;
Kottgen, Anna/D-2920-2012; Li, Guo/E-5613-2012; Yang, Qiong/G-5438-2014;
Hoffmann, Michael/D-4074-2015; Colaus, PsyColaus/K-6607-2013;
Rivadeneira, Fernando/O-5385-2015; Bochud, Murielle/A-3981-2010
OI Beckmann, Jacques S /0000-0002-9741-1900; Kronenberg,
Florian/0000-0003-2229-1120; Dehghan, Abbas/0000-0001-6403-016X;
Hoffmann, Michael/0000-0001-8459-6080; Rivadeneira,
Fernando/0000-0001-9435-9441; Bochud, Murielle/0000-0002-5727-0218
FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
R01HL087641, R01HL59367, R01HL086694, N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health [HHSN268200625226C]; NIH
Roadmap for Medical Research [UL1RR025005]; German Research Foundation;
National Institute of Neurological Disorders and Stroke; National Center
for Research Resources [M01RR00425]; National Institute of Diabetes and
Digestive and Kidney Diseases [DK063491]; GlaxoSmithKline; Faculty of
Biology and Medicine of Lausanne; Swiss National Science Foundation
[33CSCO-122661, 3200BO-111361/2, 3100AO-116323/1, 310000-112552]; Swiss
School of Public Health Plus; Giorgi-Cavaglieri Foundation; European
Framework Project 6 (EuroDia, AnEuploidy and Hypergenes projects);
National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195, N02-HL-6-4278]; Robert Dawson Evans Endowment of the
Department of Medicine at Boston University School of Medicine and
Boston Medical Center; NIH, Children's Hospital, Boston, US [1 R01
DK075787-01A1]; German National Genome Research Net [01GS0823, A3,
01GS0834]; Munich Center of Health Sciences (MC Health); Else
Kroner-Fresenius-Stiftung [P48/08//A11/08]; Regensburg University
Medical Center, Germany; University of Ulm, Germany; Helmholtz Zentrum
Munchen; German Research Center for Environmental Health; German Federal
Ministry of Education and Research; State of Bavaria; University of
Regensburg for the Department of Epidemiology and Preventive Medicine at
the Regensburg University Medical Center; Netherlands Organisation of
Scientific Research NWO Investments [175.010.2005.011, 911-03-012];
Research Institute for Diseases in the Elderly [014-93-015, RIDE2];
Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy
Aging (NCHA) [050-060-810]; Erasmus University Medical Center;
Netherlands Organisation for Health Research and Development (ZonMw);
Research Institute for Diseases in the Elderly (RIDE); Ministry of
Education, Culture, and Science, the Ministry for Health, Welfare, and
Sports; European Commission; Municipality of Rotterdam; German
Bundesministerium fur Forschung und Technologie [01 AK 803 A-H, 01 IG
07015]; NWO [918-76-619]; Federal Ministry of Education and Research
[01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs;
Social Ministry of the Federal State of Mecklenburg-West Pomerania;
Siemens Healthcare, Germany; Federal State of Mecklenburg-West
Pomerania; Kamillo Eisner Stiftung; Genomics Of Lipid-associated
Disorders (GOLD) of the Austrian Genome Research Programme GEN-AU;
Interdisziplinares Zentrum fur Klinische Forschung (IZKF);
Bundesministerium fuer Bildung und Forschung (BMBF); Comprehensive Heart
Failure Center; Pfizer; NIH [DK071674, DK084974, 5T32DK007540-25];
National Institute of Diabetes, Digestive and Kidney Diseases
[R01DK080123, R01DK059616]; Agency for Health Care Research and Quality
[R01HS008365]; Dr Robert Pfleger-Stiftung; University of Regensburg;
KfH-Stiftung Praventivmedizin e.V.
FX The Atherosclerosis Risk in Communities Study (ARIC) was supported by
National Heart, Lung, and Blood Institute contracts N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01HL087641, R01HL59367, and R01HL086694; National Human
Genome Research Institute contract U01HG004402; and National Institutes
of Health contract HHSN268200625226C. Infrastructure was partly
supported by grant number UL1RR025005 from NIH Roadmap for Medical
Research. AK was supported by the Emmy Noether Programme of the German
Research Foundation. The Cardiovascular Health Study (CHS) research was
supported by contract numbers N01-HC-85079 through N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
grant numbers U01 HL080295 and R01 HL087652, and R01 AG027002 from the
National Heart, Lung, and Blood Institute, with additional contributions
from the National Institute of Neurological Disorders and Stroke. DNA
handling and genotyping was supported in part by National Center for
Research Resources grant M01RR00425 to the Cedars-Sinai General Clinical
Research Center Genotyping Core and National Institute of Diabetes and
Digestive and Kidney Diseases grant DK063491 to the Southern California
Diabetes Endocrinology Research Center. The CoLaus study received
financial contributions from GlaxoSmithKline, the Faculty of Biology and
Medicine of Lausanne, the Swiss National Science Foundation
(33CSCO-122661, 3200BO-111361/2, 3100AO-116323/1, 310000-112552), the
Swiss School of Public Health Plus, the Giorgi-Cavaglieri Foundation,
and the European Framework Project 6 (EuroDia, AnEuploidy and Hypergenes
projects). The Framingham Heart Study (FHS): This research was conducted
in part using data and resources from the Framingham Heart Study of the
National Heart Lung and Blood Institute of the National Institutes of
Health and Boston University School of Medicine. The analyses reflect
intellectual input and resource development from the Framingham Heart
Study investigators participating in the SNP Health Association Resource
(SHARe) project. This work was partially supported by the National
Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195)
and its contract with Affymetrix for genotyping services
(N02-HL-6-4278). A portion of this research utilized the Linux Cluster
for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine and Boston Medical Center. KORA cohorts: The genetic
epidemiological work was funded by the NIH subcontract from the
Children's Hospital, Boston, US (HEW, IMH; prime grant 1 R01
DK075787-01A1), the German National Genome Research Net NGFN2 and
NGFNplus (HEW, 01GS0823; WK, project A3, number 01GS0834), the Munich
Center of Health Sciences (MC Health) as part of LMUinnovativ, and by
the Else Kroner-Fresenius-Stiftung (CAB, BKK; P48/08//A11/08). The
kidney parameter measurements in F3 were funded by the Else
Kroner-Fresenius-Stiftung (CAB, BKK) and the Regensburg University
Medical Center, Germany; in F4 by the University of Ulm, Germany (WK).
The Else Kroner-Fresenius-Stiftung funded de novo and (in part)
genome-wide genotyping in F3 and F4 (CAB, BKK). The KORA research
platform and the MONICA Augsburg studies were initiated and financed by
the Helmholtz Zentrum Munchen, German Research Center for Environmental
Health, by the German Federal Ministry of Education and Research and by
the State of Bavaria.; Genotyping was performed in the Genome Analysis
Center (GAC) of the Helmoltz Zentrum Munchen. The LINUX platform for
computation was funded by the University of Regensburg for the
Department of Epidemiology and Preventive Medicine at the Regensburg
University Medical Center. The Rotterdam Study: The GWAS was funded by
the Netherlands Organisation of Scientific Research NWO Investments
(175.010.2005.011, 911-03-012), the Research Institute for Diseases in
the Elderly (014-93-015; RIDE2), and the Netherlands Genomics Initiative
(NGI)/Netherlands Consortium for Healthy Aging (NCHA) project
050-060-810. The Rotterdam Study is funded by the Erasmus University
Medical Center, the Netherlands Organisation for Health Research and
Development (ZonMw), the Research Institute for Diseases in the Elderly
(RIDE), the Ministry of Education, Culture, and Science, the Ministry
for Health, Welfare, and Sports, the European Commission (DG XII), and
the Municipality of Rotterdam. The national German MediGRID and
Services@MediGRID, part of the German D-Grid provided access to their
grid resources, both funded by the German Bundesministerium fur
Forschung und Technologie under grants #01 AK 803 A-H and # 01 IG 07015
G. AD is supported by NWO grant (vici, 918-76-619). The Study of Health
in Pomerania (SHIP) is part of the Community Medicine Research net of
the University of Greifswald, Germany, which is funded by the Federal
Ministry of Education and Research (01ZZ9603, 01ZZ0103, and 01ZZ0403),
the Ministry of Cultural Affairs, and the Social Ministry of the Federal
State of Mecklenburg-West Pomerania. Genome-wide data have been
supported by the Federal Ministry of Education and Research (03ZIK012)
and a joint grant from Siemens Healthcare, Germany, and the Federal
State of Mecklenburg-West Pomerania. The University of Greifswald is a
member of the 'Center of Knowledge Interchange' program of the Siemens
AG. The SAPHIR study was partially supported by a grant from the Kamillo
Eisner Stiftung to BP and by grants from the Genomics Of
Lipid-associated Disorders (GOLD) of the Austrian Genome Research
Programme GEN-AU to FK. Genotyping was funded by the Else
Kroner-Fresenius-Stiftung (CAB, BKK; P48/08//A11/08). 4D Study: The
Interdisziplinares Zentrum fur Klinische Forschung (IZKF) provided an
intramural grant and the Bundesministerium fuer Bildung und Forschung
(BMBF) sponsored Comprehensive Heart Failure Center supported
subanalyses in the 4D study. Genotyping was funded by the Else
Kroner-Fresenius-Stiftung (CAB, BKK; P48/08//A11/08). The original study
was supported by Pfizer. ArMORR received funding from the NIH
(DK071674). RT is supported by NIH grant DK084974 and CH by
5T32DK007540-25. CHOICE was supported by grants R01DK080123 and
R01DK059616 from the National Institute of Diabetes, Digestive and
Kidney Diseases, grant R01HL62985 from the National Heart Lung and Blood
Institute, and grant R01HS008365 from the Agency for Health Care
Research and Quality. The Family Heart and Kidney Study (FHKS) was
partially supported by a grant from GOLD to FK. Genotyping was funded by
the Else Kroner-Fresenius-Stiftung (CAB, BKK; P48/08//A11/08). GENDIAN
has received funding from the Dr Robert Pfleger-Stiftung, the Else
Kroner-Fresenius-Stiftung, the University of Regensburg's intramural
grants ReForM A, B, and C, and from the KfH-Stiftung Praventivmedizin
e.V. The Mild to Moderate Kidney Disease (MMKD) Study was partially
supported by a grant from GOLD to FK. Genotyping was funded by the Else
Kroner-Fresenius-Stiftung (CAB, BKK; P48/08//A11/08).; The funders had
no rol in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 53
TC 60
Z9 62
U1 2
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2011
VL 7
IS 9
AR e1002292
DI 10.1371/journal.pgen.1002292
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100041
PM 21980298
ER
PT J
AU Butterworth, AS
Braund, PS
Farrall, M
Hardwick, RJ
Saleheen, D
Peden, JF
Soranzo, N
Chambers, JC
Sivapalaratnam, S
Kleber, ME
Keating, B
Qasim, A
Klopp, N
Erdmann, J
Assimes, TL
Ball, SG
Balmforth, AJ
Barnes, TA
Basart, H
Baumert, J
Bezzina, CR
Boerwinkle, E
Boehm, BO
Brocheton, J
Bugert, P
Cambien, F
Clarke, R
Codd, V
Collins, R
Couper, D
Cupples, LA
de Jong, JS
Diemert, P
Ejebe, K
Elbers, CC
Elliott, P
Fornage, M
Franzosi, MG
Frossard, P
Garner, S
Goel, A
Goodall, AH
Hengstenberg, C
Hunt, SE
Kastelein, JJP
Klungel, OH
Kluter, H
Koch, K
Konig, IR
Kooner, AS
Laaksonen, R
Lathrop, M
Li, MY
Liu, K
McPherson, R
Musameh, MD
Musani, S
Nelson, CP
O'Donnell, CJ
Ongen, H
Papanicolaou, G
Peters, A
Peters, BJM
Potter, S
Psaty, BM
Qu, LM
Rader, DJ
Rasheed, A
Rice, C
Scott, J
Seedorf, U
Sehmi, JS
Sotoodehnia, N
Stark, K
Stephens, J
van der Schoot, CE
van der Schouw, YT
Thorsteinsdottir, U
Tomaszewski, M
van der Harst, P
Vasan, RS
Wilde, AAM
Willenborg, C
Winkelmann, BR
Zaidi, M
Zhang, WH
Ziegler, A
de Bakker, PIW
Koenig, W
Marz, W
Trip, MD
Reilly, MP
Kathiresan, S
Schunkert, H
Hamsten, A
Hall, AS
Kooner, JS
Thompson, SG
Thompson, JR
Deloukas, P
Ouwehand, WH
Watkins, H
Danesh, J
Samani, NJ
AF Butterworth, Adam S.
Braund, Peter S.
Farrall, Martin
Hardwick, Robert J.
Saleheen, Danish
Peden, John F.
Soranzo, Nicole
Chambers, John C.
Sivapalaratnam, Suthesh
Kleber, Marcus E.
Keating, Brendan
Qasim, Atif
Klopp, Norman
Erdmann, Jeanette
Assimes, Themistocles L.
Ball, Stephen G.
Balmforth, Anthony J.
Barnes, Timothy A.
Basart, Hanneke
Baumert, Jens
Bezzina, Connie R.
Boerwinkle, Eric
Boehm, Bernhard O.
Brocheton, Jessy
Bugert, Peter
Cambien, Francois
Clarke, Robert
Codd, Veryan
Collins, Rory
Couper, David
Cupples, L. Adrienne
de Jong, Jonas S.
Diemert, Patrick
Ejebe, Kenechi
Elbers, Clara C.
Elliott, Paul
Fornage, Myriam
Franzosi, Maria-Grazia
Frossard, Philippe
Garner, Stephen
Goel, Anuj
Goodall, Alison H.
Hengstenberg, Christian
Hunt, Sarah E.
Kastelein, John J. P.
Klungel, Olaf H.
Klueter, Harald
Koch, Kerstin
Koenig, Inke R.
Kooner, Angad S.
Laaksonen, Reijo
Lathrop, Mark
Li, Mingyao
Liu, Kiang
McPherson, Ruth
Musameh, Muntaser D.
Musani, Solomon
Nelson, Christopher P.
O'Donnell, Christopher J.
Ongen, Halit
Papanicolaou, George
Peters, Annette
Peters, Bas J. M.
Potter, Simon
Psaty, Bruce M.
Qu, Liming
Rader, Daniel J.
Rasheed, Asif
Rice, Catherine
Scott, James
Seedorf, Udo
Sehmi, Joban S.
Sotoodehnia, Nona
Stark, Klaus
Stephens, Jonathan
van der Schoot, C. Ellen
van der Schouw, Yvonne T.
Thorsteinsdottir, Unnur
Tomaszewski, Maciej
van der Harst, Pim
Vasan, Ramachandran S.
Wilde, Arthur A. M.
Willenborg, Christina
Winkelmann, Bernhard R.
Zaidi, Moazzam
Zhang, Weihua
Ziegler, Andreas
de Bakker, Paul I. W.
Koenig, Wolfgang
Maerz, Winfried
Trip, Mieke D.
Reilly, Muredach P.
Kathiresan, Sekar
Schunkert, Heribert
Hamsten, Anders
Hall, Alistair S.
Kooner, Jaspal S.
Thompson, Simon G.
Thompson, John R.
Deloukas, Panos
Ouwehand, Willem H.
Watkins, Hugh
Danesh, John
Samani, Nilesh J.
CA IBC 50K CAD Consortium
TI Large-Scale Gene-Centric Analysis Identifies Novel Variants for Coronary
Artery Disease
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCI;
RISK; ATHEROSCLEROSIS; METAANALYSIS; LIPOPROTEIN
AB Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in similar to 2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5x10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other similar to 4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.
C1 [Butterworth, Adam S.; Saleheen, Danish; Thompson, Simon G.; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Braund, Peter S.; Hardwick, Robert J.; Barnes, Timothy A.; Codd, Veryan; Goodall, Alison H.; Musameh, Muntaser D.; Nelson, Christopher P.; Tomaszewski, Maciej; van der Harst, Pim; Samani, Nilesh J.] Univ Leicester, Dept Cardiovas Sci, Glenfield Gen Hosp, Leicester, Leics, England.
[Braund, Peter S.; Hardwick, Robert J.; Barnes, Timothy A.; Codd, Veryan; Goodall, Alison H.; Musameh, Muntaser D.; Nelson, Christopher P.; Tomaszewski, Maciej; van der Harst, Pim; Samani, Nilesh J.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res Biomed Res Unit Card, Leicester LE3 9QP, Leics, England.
[Farrall, Martin; Peden, John F.; Goel, Anuj; Ongen, Halit; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Farrall, Martin; Peden, John F.; Goel, Anuj; Ongen, Halit; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Hardwick, Robert J.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
[Saleheen, Danish; Frossard, Philippe; Rasheed, Asif; Zaidi, Moazzam] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Soranzo, Nicole; Hunt, Sarah E.; Potter, Simon; Rice, Catherine; Deloukas, Panos; Ouwehand, Willem H.] Wellcome Trust Sanger Inst, Hinxton, England.
[Chambers, John C.; Zhang, Weihua] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.
[Sivapalaratnam, Suthesh; Basart, Hanneke; Kastelein, John J. P.; Trip, Mieke D.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Kleber, Marcus E.] LURIC Non Profit LLC, Freiburg, Germany.
[Keating, Brendan] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Qasim, Atif; Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Med Ctr, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Klopp, Norman; Baumert, Jens; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Erdmann, Jeanette; Diemert, Patrick; Willenborg, Christina; Schunkert, Heribert] Univ Lubeck, Med Klin 2, Lubeck, Germany.
[Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Ball, Stephen G.] Univ Leeds, Fac Med & Hlth, LIGHT Res Inst, Leeds, W Yorkshire, England.
[Balmforth, Anthony J.] Univ Leeds, Div Cardiovasc & Diabet Res, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England.
[Bezzina, Connie R.; de Jong, Jonas S.; Wilde, Arthur A. M.; Trip, Mieke D.] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, Dept Clin & Expt Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Boehm, Bernhard O.] Univ Ulm, Div Endocrinol & Diabet, Ctr Excellence Metab Dis, Dept Internal Med, Ulm, Germany.
[Brocheton, Jessy; Cambien, Francois] Univ Paris 06, INSERM, UMRS 937, Paris, France.
[Brocheton, Jessy; Cambien, Francois] Sch Med, Paris, France.
[Bugert, Peter; Klueter, Harald] Univ Heidelberg, Inst Transfus Med & Immunol, Germany Red Cross Blood Serv, Baden Wurttemberg Hessen gGmbH,Med Fac Mannheim, D-6800 Mannheim, Germany.
[Clarke, Robert; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford, England.
[Clarke, Robert; Collins, Rory] Univ Oxford, Epidemiol Studies Unit, Oxford, England.
[Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ejebe, Kenechi; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ejebe, Kenechi; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Ejebe, Kenechi; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA.
[Elbers, Clara C.; van der Schouw, Yvonne T.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Elbers, Clara C.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Div Biomed Genet, Dept Med Genet, Utrecht, Netherlands.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London, England.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA.
[Franzosi, Maria-Grazia] Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
[Garner, Stephen; Koch, Kerstin; Stephens, Jonathan; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England.
[Garner, Stephen; Koch, Kerstin; Stephens, Jonathan; Ouwehand, Willem H.] NHS Blood & Transplant, Cambridge, England.
[Hengstenberg, Christian; Stark, Klaus] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany.
[Klungel, Olaf H.; Peters, Bas J. M.] Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands.
[Koenig, Inke R.; Ziegler, Andreas] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany.
[Kooner, Angad S.; Scott, James; Sehmi, Joban S.; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England.
[Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland.
[Lathrop, Mark] CEA, Inst Genom, Ctr Natl Genotypage, F-91057 Evry, France.
[Lathrop, Mark] Fdn Jean Dausset CEPH, F-75010 Paris, France.
[Li, Mingyao; Qu, Liming] Univ Penn, Med Ctr, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[McPherson, Ruth] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada.
[Musani, Solomon] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA.
[Papanicolaou, George; Reilly, Muredach P.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Seedorf, Udo] Univ Munster, Leibniz Inst Arterioskleroseforsch, Munster, Germany.
[Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA.
[van der Schoot, C. Ellen] Sanquin Res, Dept Expt Immunohematol, Amsterdam, Netherlands.
[Thorsteinsdottir, Unnur] deCODE Genet, IS-101 Reykjavik, Iceland.
[Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Echocardiog Vasc Lab, Framingham, MA USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Dept Med, Prevent Med & Epidemiol Sect, Framingham, MA USA.
[Winkelmann, Bernhard R.] Cardiol Grp Frankfurt Sachsenhausen, Frankfurt, Germany.
[Winkelmann, Bernhard R.] Clin Phen GmbH, Frankfurt, Germany.
[de Bakker, Paul I. W.; Kathiresan, Sekar] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.
[Maerz, Winfried] Synlab Serv GmbH, Mannheim, Germany.
[Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Maerz, Winfried] Univ Heidelberg, Inst Publ Heath Social Med & Epidemiol, Med Fac Mannheim, D-6800 Mannheim, Germany.
[Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Unit, Dept Med Solna, Stockholm, Sweden.
[Hall, Alistair S.] Univ Leeds, Inst Genet Hlth & Therapeut, Multidisciplinary Cardiovasc Res Ctr, Div Cardiovasc & Neuronal Remodelling, Leeds, W Yorkshire, England.
[Thompson, Simon G.] Med Res Council Biostat Unit, Cambridge, England.
[Thompson, Simon G.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
RP Butterworth, AS (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
EM hugh.watkins@cardiov.ox.ac.uk; jd292@medschl.cam.ac.uk;
njs@leicester.ac.uk
RI Leander, Karin/C-7261-2017; Smith, Albert Vernon/K-5150-2015; Morgan,
Tom/C-3478-2012; de Bakker, Paul/B-8730-2009; Laaksonen,
Reijo/D-6323-2014; Strawbridge, Rona/H-5422-2012; Boehm,
Bernhard/F-8750-2015; Peters, Annette/A-6117-2011; Ejebe,
Kenechi/I-9238-2016; Martinelli, Nicola/J-5622-2016; Klungel,
Olaf/I-9563-2016; Konig, Inke/A-4544-2009; Stark, Klaus/D-3813-2009;
Willenborg, Christina/D-2668-2012; Deloukas, Panos/B-2922-2013; Erdmann,
Jeanette/A-4417-2009; Erdmann, Jeanette/P-7513-2014;
OI Ouwehand, Willem/0000-0002-7744-1790; Kleber,
Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Sabater
Lleal, Maria/0000-0002-0128-379X; Leander, Karin/0000-0002-1404-9222;
Meisinger, Christa/0000-0002-9026-6544; ELOSUA,
ROBERTO/0000-0001-8235-0095; Hunt, Sarah/0000-0002-8350-1235; Smith,
Albert Vernon/0000-0003-1942-5845; Stewart,
Alexandre/0000-0003-2673-9164; Seedorf, Udo/0000-0003-4652-5358;
Ramachandran, Vasan/0000-0001-7357-5970; de Bakker,
Paul/0000-0001-7735-7858; Strawbridge, Rona/0000-0001-8506-3585; Ejebe,
Kenechi/0000-0002-6090-8657; Martinelli, Nicola/0000-0001-6465-5119;
Stark, Klaus/0000-0002-7832-1942; Willenborg,
Christina/0000-0001-5217-6882; Deloukas, Panos/0000-0001-9251-070X;
Erdmann, Jeanette/0000-0002-4486-6231; Peyvandi,
Flora/0000-0001-7423-9864; Soranzo, Nicole/0000-0003-1095-3852; Gieger,
Christian/0000-0001-6986-9554; Wijmenga, Cisca/0000-0002-5635-1614;
Ziegler, Andreas/0000-0002-8386-5397; Ferguson,
Jane/0000-0001-6896-1025; Nothen, Markus/0000-0002-8770-2464; Watkins,
Hugh/0000-0002-5287-9016; Jones, Gregory T/0000-0002-6950-4210
FU British Heart Foundation (BHF); UK Medical Research Council; Leicester
NIHR Biomedical Research Unit in Cardiovascular Disease; AMC (The
Netherlands); LURIC (Germany); University of Cambridge (UK); Wellcome
Trust Sanger Institute (UK); Bloodomics [LSHM-CT-2004-503485]; British
Heart Foundation [RG/09/12/28096]; National Institute for Health
Research [RP-PG-0310-1002]; Netherlands Heart Foundation [2001D019,
2003T302, 2007B202]; Leducq Foundation [05-CVD]; Center for
Translational Molecular Medicine (CTMM COHFAR); Interuniversity
Cardiology Institute of The Netherlands; LURIC [LSHM-CT-2004-503485];
European Union [201668, LSHM-CT-2006-037593]; National Heart, Lung, and
Blood Institute; Helmholtz Zentrum Munchen; German Research Center for
Environmental Health; Neuherberg, Germany; German Federal Ministry of
Education and Research (BMBF); German National Genome Research Network
[01GS0834]; University of Ulm; Munich Center of Health Sciences (MC
Health); Penn Cardiovascular Institute; GlaxoSmithKline; British Heart
Foundation; European Community [LSHM-CT-2007-037273]; AstraZeneca;
Wellcome Trust; United Kingdom Medical Research Council; Swedish
Heart-Lung Foundation; Swedish Medical Research Council; Knut and Alice
Wallenberg Foundation; Torsten and Ragnar Soderberg Foundation;
Karolinska Institutet and Stockholm County Council; Foundation for
Strategic Research; Stockholm County Council [560283]; University of
Cambridge and in Pakistan; EU Framework 6-funded Bloodomics Integrated
Project [LSHM-CT-2004-503485]; Yousef Jameel Foundation; European
Commission (SANCO); Dutch Ministry of Health; Dutch Cancer Society;
ZonMW; Netherlands Organisation for Health Research and Development;
World Cancer Research Fund (WCRF); NL Agency [IGE 05012]; Organization
for Scientific Research (NWO); Netherlands Heart Foundation (NHS)
[2001.064]; TI Pharma [T6-101]; Novo Nordisk; Top Institute Pharma;
Dutch Medicines Evaluation Board
FX BHF-FHS: Recruitment of CAD cases for the BHF-FHS study was supported by
the British Heart Foundation (BHF) and the UK Medical Research Council.
Controls were provided by the Wellcome Trust Case Control Consortium.
Genotyping of the IBC 50K array for the BHF-FHS study was funded by the
BHF. NJS and SGB hold personal chairs supported by the BHF. The work
described in this paper forms part of the portfolio of translational
research supported by the Leicester NIHR Biomedical Research Unit in
Cardiovascular Disease. BLOODOMICS: The Bloodomics partners from AMC
(The Netherlands), LURIC (Germany), the University of Cambridge (UK),
and the Wellcome Trust Sanger Institute (UK) received funding through
the 6th Framework funded Integrated Project Bloodomics (grant
LSHM-CT-2004-503485). The University of Cambridge group in the
Department of Haematology also received programme grant funding from the
British Heart Foundation (RG/09/12/28096) and the National Institute for
Health Research (RP-PG-0310-1002). BLOODOMICS-Dutch: This study was
supported by research grants from The Netherlands Heart Foundation
(grants 2001D019, 2003T302 and 2007B202), the Leducq Foundation (grant
05-CVD), the Center for Translational Molecular Medicine (CTMM COHFAR),
and the Interuniversity Cardiology Institute of The Netherlands (project
27). BLOODOMICS-German: LURIC has received funding through the 6th
Framework Program (integrated project Bloodomics, grant
LSHM-CT-2004-503485) and 7th Framework Program (integrated project
Atheroremo, Grant Agreement number 201668) of the European Union. CARe
Consortium: CARe was performed with the support of the National Heart,
Lung, and Blood Institute and acknowledges the contributions of the
research institutions, study investigators, and field staff in creating
this resource for biomedical research. Full details of the studies in
the CARe Consortium can be found in Text S1. LOLIPOP: Genotyping of the
IBC 50K array for the LOLIPOP Study was funded by the British Heart
Foundation. Paul Elliott is a National Institute for Health Research
Senior Investigator. MONICA-KORA: The MONICA/KORA Augsburg studies were
financed by the Helmholtz Zentrum Munchen, German Research Center for
Environmental Health, Neuherberg, Germany, and supported by grants from
the German Federal Ministry of Education and Research (BMBF). Part of
this work was financed by the German National Genome Research Network
(NGFNPlus, project number 01GS0834) and through additional funds from
the University of Ulm. Furthermore, the research was supported within
the Munich Center of Health Sciences (MC Health) as part of LMU
innovative. PennCATH: Muredach P Reilly and Daniel J Rader have been
supported by the Penn Cardiovascular Institute and GlaxoSmithKline.
PROCARDIS: The PROCARDIS study has been supported by the British Heart
Foundation, the European Community Sixth Framework Program
(LSHM-CT-2007-037273), AstraZeneca, the Wellcome Trust, the United
Kingdom Medical Research Council, the Swedish Heart-Lung Foundation, the
Swedish Medical Research Council, the Knut and Alice Wallenberg
Foundation, the Torsten and Ragnar Soderberg Foundation, the Strategic
Cardiovascular Program of Karolinska Institutet and Stockholm County
Council, the Foundation for Strategic Research and the Stockholm County
Council (560283). PROMIS: Epidemiological field work in PROMIS was
supported by unrestricted grants to investigators at the University of
Cambridge and in Pakistan.; Genotyping for this study was funded by the
Wellcome Trust and the EU Framework 6-funded Bloodomics Integrated
Project(LSHM-CT-2004-503485). The British Heart Foundation has supported
some biochemical assays. The Yousef Jameel Foundation supported D
Saleheen. The cardiovascular disease epidemiology group of J Danesh is
underpinned by programme grants from the British Heart Foundation and
the UK Medical Research Council. EPIC-NL: The EPIC-NL study was funded
by "Europe against Cancer'' Programme of the European Commission
(SANCO); the Dutch Ministry of Health; the Dutch Cancer Society; ZonMW
the Netherlands Organisation for Health Research and Development; World
Cancer Research Fund (WCRF). We thank the institute PHARMO for follow-up
data on diabetes. Genotyping was funded by IOP Genomics grant IGE 05012
from NL Agency. UCP: The project was funded by Veni grant Organization
for Scientific Research (NWO), Grant no. 2001.064 Netherlands Heart
Foundation (NHS), and TI Pharma Grant T6-101 Mondriaan. Cardiogenics:
Cardiogenics was funded through the 6th Framework Programme (integrated
project Cardiogenics, grant LSHM-CT-2006-037593) of the European Union.
None of the sponsors had any role in the design and conduct of the
study; collection, management, analysis, and interpretation of the data;
or preparation, review, or approval of the manuscript.; Muredach P
Reilly and Daniel J Rader have a research grant from GlaxoSmithKline.
The division of Pharmacoepidemiology and Clinical Pharmacology employing
Bas Peters, Olaf Klungel, Anthonius de Boer, and Anke-Hilse Maitland-van
der Zee has received unrestricted funding for pharmacoepidemiological
research from GlaxoSmithKline, Novo Nordisk, the private-public funded
Top Institute Pharma (www.tipharma.nl ,includes co-funding from
universities, government, and industry), the Dutch Medicines Evaluation
Board, and the Dutch Ministry of Health. Arthur AM Wilde is a consultant
for Transgenomics (Familion test) and Sorin. No other disclosures were
reported.
NR 32
TC 15
Z9 15
U1 0
U2 38
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2011
VL 7
IS 9
AR e1002260
DI 10.1371/journal.pgen.1002260
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100015
ER
PT J
AU Dewey, FE
Chen, R
Cordero, SP
Ormond, KE
Caleshu, C
Karczewski, KJ
Whirl-Carrillo, M
Wheeler, MT
Dudley, JT
Byrnes, JK
Cornejo, OE
Knowles, JW
Woon, M
Sangkuhl, K
Gong, L
Thorn, CF
Hebert, JM
Capriotti, E
David, SP
Pavlovic, A
West, A
Thakuria, JV
Ball, MP
Zaranek, AW
Rehm, HL
Church, GM
West, JS
Bustamante, CD
Snyder, M
Altman, RB
Klein, TE
Butte, AJ
Ashley, EA
AF Dewey, Frederick E.
Chen, Rong
Cordero, Sergio P.
Ormond, Kelly E.
Caleshu, Colleen
Karczewski, Konrad J.
Whirl-Carrillo, Michelle
Wheeler, Matthew T.
Dudley, Joel T.
Byrnes, Jake K.
Cornejo, Omar E.
Knowles, Joshua W.
Woon, Mark
Sangkuhl, Katrin
Gong, Li
Thorn, Caroline F.
Hebert, Joan M.
Capriotti, Emidio
David, Sean P.
Pavlovic, Aleksandra
West, Anne
Thakuria, Joseph V.
Ball, Madeleine P.
Zaranek, Alexander W.
Rehm, Heidi L.
Church, George M.
West, John S.
Bustamante, Carlos D.
Snyder, Michael
Altman, Russ B.
Klein, Teri E.
Butte, Atul J.
Ashley, Euan A.
TI Phased Whole-Genome Genetic Risk in a Family Quartet Using a Major
Allele Reference Sequence
SO PLOS GENETICS
LA English
DT Article
ID VII-ACTIVATING PROTEASE; MARBURG-I POLYMORPHISM; VENOUS THROMBOSIS;
RECOMBINATION HOTSPOTS; MEIOTIC RECOMBINATION; PERSONAL GENOME;
FACTOR-V; DISEASE; MUTATIONS; GENOTYPE
AB Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (< 1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.
C1 [Dewey, Frederick E.; Caleshu, Colleen; Wheeler, Matthew T.; Knowles, Joshua W.; Pavlovic, Aleksandra; Ashley, Euan A.] Stanford Univ, Div Cardiovasc Med, Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA.
[Chen, Rong; Dudley, Joel T.; Butte, Atul J.] Stanford Univ, Dept Pediat, Sch Med, Div Syst Med, Stanford, CA 94305 USA.
[Cordero, Sergio P.; Karczewski, Konrad J.; Dudley, Joel T.] Stanford Univ, Sch Med, Biomed Informat Grad Training Program, Stanford, CA 94305 USA.
[Ormond, Kelly E.; Karczewski, Konrad J.; Whirl-Carrillo, Michelle; Byrnes, Jake K.; Cornejo, Omar E.; Woon, Mark; Sangkuhl, Katrin; Gong, Li; Thorn, Caroline F.; Hebert, Joan M.; Capriotti, Emidio; David, Sean P.; Bustamante, Carlos D.; Snyder, Michael; Altman, Russ B.; Klein, Teri E.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Ormond, Kelly E.] Stanford Univ, Ctr Biomed Eth, Stanford, CA 94305 USA.
[West, Anne] Wellesley Coll, Wellesley, MA 02181 USA.
[Thakuria, Joseph V.] Massachusetts Gen Hosp, Div Genet, Boston, MA 02114 USA.
[Ball, Madeleine P.; Zaranek, Alexander W.; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Rehm, Heidi L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[West, John S.] Personalis, Palo Alto, CA USA.
[Altman, Russ B.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
RP Dewey, FE (reprint author), Stanford Univ, Div Cardiovasc Med, Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA.
EM euan@stanford.edu
RI Sincan, Murat /A-3794-2010; Knowles, Josh/C-9241-2013; Capriotti,
Emidio/D-9318-2011;
OI Capriotti, Emidio/0000-0002-2323-0963; David, Sean/0000-0002-4922-2603;
Karczewski, Konrad/0000-0003-2878-4671
FU NIH/NHLBI [T32 HL094274-01A2, KO8 HL083914]; Stanford University School
of Medicine; NIH National Research Service [F32 HL097462]; NHGRI
[U01HG005715]; NIH/NIGMS [U01 GM61374, R01 GM079719]; NIH/NHGRI [5 P50
HG003389-05]; Lucile Packard Foundation for Children's Health; Hewlett
Packard Foundation; NIH/NLM [T15 LM007033]; NIH [OD004613]; Breetwor
Family Foundation; Novartis; 23andMe; Lilly; NuMedii; Johnson and
Johnson; Genstruct; Tercica; Prevendia
FX FED was supported by NIH/NHLBI training grant T32 HL094274-01A2 and the
Stanford University School of Medicine Dean's Postdoctoral Fellowship.
MTW was supported by NIH National Research Service Award fellowship F32
HL097462. JKB, OEC, and CDB were supported by NHGRI grant U01HG005715.
CFT, JMH, KS, LG, MW-C, MW, and RBA were supported by grants from the
NIH/NIGMS U01 GM61374. KEO was supported by NIH/NHGRI 5 P50 HG003389-05.
AJB was supported by the Lucile Packard Foundation for Children's
Health, Hewlett Packard Foundation, and NIH/NIGMS R01 GM079719. JTD and
KJK were supported by NIH/NLM T15 LM007033. EAA was supported by
NIH/NHLBI KO8 HL083914, NIH New Investigator DP2 Award OD004613, and a
grant from the Breetwor Family Foundation. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.; JVT and AWZ are founders, consultants,
and equity holders in Clinical Future; GMC has advisory roles in and
research sponsorships from several companies involved in genome
sequencing technology and personal genomics (see
http://arep.med.harvard.edu/gmc/tech.html); MS is on the scientific
advisory board of DNA Nexus and holds stock in Personalis; RBA has
received consultancy fees from Novartis and 23andMe and holds stock in
Personalis; AJB is a scientific advisory board member and founder for
NuMedii and Genstruct, a scientific advisory board member for Johnson
and Johnson, has received consultancy fees from Lilly, NuMedii, Johnson
and Johnson, Genstruct, Tercica, and Prevendia and honoraria from Lilly
and Siemens, and holds stock in NuMedii, Genstruct, and Personalis. EAA
holds stock in Personalis.
NR 53
TC 64
Z9 65
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2011
VL 7
IS 9
AR e1002280
DI 10.1371/journal.pgen.1002280
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100031
PM 21935354
ER
PT J
AU Gouzi, JY
Moressis, A
Walker, JA
Apostolopoulou, AA
Palmer, RH
Bernards, A
Skoulakis, EMC
AF Gouzi, Jean Y.
Moressis, Anastasios
Walker, James A.
Apostolopoulou, Anthi A.
Palmer, Ruth H.
Bernards, Andre
Skoulakis, Efthimios M. C.
TI The Receptor Tyrosine Kinase Alk Controls Neurofibromin Functions in
Drosophila Growth and Learning
SO PLOS GENETICS
LA English
DT Article
ID ANAPLASTIC LYMPHOMA KINASE; ADENYLYL-CYCLASE; MUSHROOM BODY; MOUSE
MODEL; PC12 CELLS; IN-VIVO; PROTEIN; GENE; MEMORY; NF1
AB Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in several cancers, but with largely unknown physiological functions. We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant phenotypes. These results identify dAlk as an upstream activator of dNf1-regulated Ras signaling responsible for several dNf1 defects, and they implicate human Alk as a potential therapeutic target in NF1.
C1 [Gouzi, Jean Y.; Moressis, Anastasios; Apostolopoulou, Anthi A.; Skoulakis, Efthimios M. C.] Biomed Sci Res Ctr Alexander Fleming, Inst Cellular & Dev Biol, Vari, Greece.
[Moressis, Anastasios] Univ Athens, Dept Basic Sci, Sch Hlth Sci, Athens 11528, Greece.
[Walker, James A.; Bernards, Andre] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Walker, James A.; Bernards, Andre] Harvard Univ, Sch Med, Charlestown, MA USA.
[Palmer, Ruth H.] Umea Univ, Dept Mol Biol, Umea, Sweden.
RP Gouzi, JY (reprint author), Biomed Sci Res Ctr Alexander Fleming, Inst Cellular & Dev Biol, Vari, Greece.
EM skoulakis@fleming.gr
OI Apostolopoulou, Anthi/0000-0002-8174-4372
FU Ministere Francais des Affaires Etrangeres et Europeennes; Children's
Tumor Foundation; Greek National Scholarships Foundation; Biomedical
Sciences Research Center; NIH/NGMS [1-R01 GM084220]
FX JYG was supported by a post-doctoral fellowship from the "Programme
Lavoisier - Ministere Francais des Affaires Etrangeres et Europeennes"
and by a Young Investigator Award from the Children's Tumor Foundation.
AM was supported by scholarships from the Greek National Scholarships
Foundation (IKY) and from the Biomedical Sciences Research Center
"Alexander Fleming." AB and JAW were supported by NIH/NGMS grant 1-R01
GM084220 and by an anonymous donor. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 67
TC 25
Z9 27
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2011
VL 7
IS 9
AR e1002281
DI 10.1371/journal.pgen.1002281
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100032
PM 21949657
ER
PT J
AU Hendel, A
Krijger, PHL
Diamant, N
Goren, Z
Langerak, P
Kim, J
Reissner, T
Lee, KY
Geacintov, NE
Carell, T
Myung, K
Tateishi, S
D'Andrea, A
Jacobs, H
Livneh, Z
AF Hendel, Ayal
Krijger, Peter H. L.
Diamant, Noam
Goren, Zohar
Langerak, Petra
Kim, Jungmin
Reissner, Thomas
Lee, Kyoo-young
Geacintov, Nicholas E.
Carell, Thomas
Myung, Kyungjae
Tateishi, Satoshi
D'Andrea, Alan
Jacobs, Heinz
Livneh, Zvi
TI PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA
Synthesis in Mammalian Cells
SO PLOS GENETICS
LA English
DT Article
ID POLYMERASE-ETA; 2-POLYMERASE MECHANISMS; MONOUBIQUITINATED PCNA;
XERODERMA-PIGMENTOSUM; GENOMIC INSTABILITY; REPLICATION FORK; BINDING
DOMAINS; NUCLEAR ANTIGEN; MUTATION LOAD; POL-ETA
AB Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the specialized polymerases to the damaged site through their ubiquitin-binding domain. In mammals, however, there is a debate on the requirement for ubiquitinated PCNA (PCNA-Ub) in TLS. We show that UV-induced Rpa foci, indicative of single-stranded DNA (ssDNA) regions caused by UV, accumulate faster and disappear more slowly in Pcna(K164R/K164R) cells, which are resistant to PCNA ubiquitination, compared to Pcna(+/+) cells, consistent with a TLS defect. Direct analysis of TLS in these cells, using gapped plasmids with site-specific lesions, showed that TLS is strongly reduced across UV lesions and the cisplatin-induced intrastrand GG crosslink. A similar effect was obtained in cells lacking Rad18, the E3 ubiquitin ligase which monoubiquitinates PCNA. Consistently, cells lacking Usp1, the enzyme that de-ubiquitinates PCNA exhibited increased TLS across a UV lesion and the cisplatin adduct. In contrast, cells lacking the Rad5-homologs Shprh and Hltf, which polyubiquitinate PCNA, exhibited normal TLS. Knocking down the expression of the TLS genes Rev3L, PolH, or Rev1 in Pcna(K164R/K164R) mouse embryo fibroblasts caused each an increased sensitivity to UV radiation, indicating the existence of TLS pathways that are independent of PCNA-Ub. Taken together these results indicate that PCNA-Ub is required for maximal TLS. However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity.
C1 [Hendel, Ayal; Diamant, Noam; Goren, Zohar; Livneh, Zvi] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
[Krijger, Peter H. L.; Langerak, Petra; Jacobs, Heinz] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands.
[Kim, Jungmin; D'Andrea, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol & Pediat Oncol, Boston, MA 02115 USA.
[Reissner, Thomas; Carell, Thomas] Univ Munich, Dept Chem & Biochem, Munich, Germany.
[Lee, Kyoo-young; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Geacintov, Nicholas E.] NYU, Dept Chem, New York, NY 10003 USA.
[Tateishi, Satoshi] Kumamoto Univ, Inst Mol Embryol & Genet, Kumamoto, Japan.
RP Hendel, A (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
EM h.jacobs@nki.nl; zvi.livneh@weizmann.ac.il
RI Carell, Thomas/G-4799-2012;
OI Krijger, Peter/0000-0003-1702-348X; Jacobs, Heinz/0000-0001-6227-9850;
Carell, Thomas/0000-0001-7898-2831
FU Flight Attendant Medical Research Institute; Leona M. and Harry B.
Helmsley Charitable Trust; Israel Science Foundation [1136/08];
Netherlands Organization for Scientific Research; Dutch Cancer
Foundation [917.56.328, 2008-4112]; NIH USA [CA099194]
FX ZL is the incumbent of the Maxwell Ellis Professorial Chair in
Biomedical Research. This work was supported by grants to ZL from the
Flight Attendant Medical Research Institute, the Leona M. and Harry B.
Helmsley Charitable Trust, and the Israel Science Foundation (no.
1136/08); to HJ from The Netherlands Organization for Scientific
Research and the Dutch Cancer Foundation (VIDI program 917.56.328 and
KWF 2008-4112); and to NEG from NIH USA (no. CA099194). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 50
TC 49
Z9 50
U1 0
U2 8
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 SEP
PY 2011
VL 7
IS 9
AR e1002262
DI 10.1371/journal.pgen.1002262
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100017
PM 21931560
ER
PT J
AU Le, MTN
Shyh-Chang, N
Khaw, SL
Chin, LZ
Teh, C
Tay, J
O'Day, E
Korzh, V
Yang, H
Lal, A
Lieberman, J
Lodish, HF
Lim, B
AF Le, Minh T. N.
Shyh-Chang, Ng
Khaw, Swea Ling
Chin, Lingzi
Teh, Cathleen
Tay, Junliang
O'Day, Elizabeth
Korzh, Vladimir
Yang, Henry
Lal, Ashish
Lieberman, Judy
Lodish, Harvey F.
Lim, Bing
TI Conserved Regulation of p53 Network Dosage by MicroRNA-125b Occurs
through Evolving miRNA-Target Gene Pairs
SO PLOS GENETICS
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; NEGATIVE
REGULATOR; ESCHERICHIA-COLI; BAK1 EXPRESSION; CANCER CELLS; C-ELEGANS;
MIR-125B; PROLIFERATION; CANALIZATION
AB MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain-and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA-target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis.
C1 [Le, Minh T. N.; Shyh-Chang, Ng; Khaw, Swea Ling; Chin, Lingzi; Tay, Junliang; Lim, Bing] Genome Inst Singapore, Singapore, Singapore.
[Le, Minh T. N.; O'Day, Elizabeth; Lal, Ashish; Lieberman, Judy] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA USA.
[Le, Minh T. N.; O'Day, Elizabeth; Lal, Ashish; Lieberman, Judy] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA.
[Le, Minh T. N.; Lodish, Harvey F.; Lim, Bing] Singapore MIT Alliance, Computat & Syst Biol, Singapore, Singapore.
[Shyh-Chang, Ng] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Khaw, Swea Ling; Korzh, Vladimir] NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore.
[Teh, Cathleen] Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore.
[Yang, Henry] Singapore Immunol Network, Bioinformat Grp, Singapore, Singapore.
[Lal, Ashish] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Lodish, Harvey F.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Lodish, Harvey F.] MIT, Dept Biol, Cambridge, MA USA.
[Lim, Bing] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Le, MTN (reprint author), Genome Inst Singapore, Singapore, Singapore.
EM lodish@wi.mit.edu; limb1@gis.a-star.edu.sg
RI ASTAR, IMCB/E-2320-2012; Xie, Huangming/B-2260-2012; Le,
Minh/D-7651-2013; Lieberman, Judy/A-2717-2015; Korzh,
Vladimir/H-1596-2011;
OI Shyh-Chang, Ng/0000-0003-3138-9525; Korzh, Vladimir/0000-0002-6580-7986;
LE, Thi Nguyet Minh/0000-0002-6077-1566
FU ASTAR, Singapore; SMA [C-382-641-001-091]; NIH [R01 DK068348]
FX MTNL, NS-C, SLK, LC, JT, CT, VK, and BL were supported by ASTAR,
Singapore. MTNL was a L'Oreal Singapore for Women in Science National
Fellow. BL and HFL were partially supported by SMA grant
C-382-641-001-091. HFL was supported by NIH grant R01 DK068348. JL, EO,
MTNL, and AL were supported by NIH. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 51
TC 65
Z9 71
U1 0
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2011
VL 7
IS 9
AR e1002242
DI 10.1371/journal.pgen.1002242
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100005
PM 21935352
ER
PT J
AU Liu, CT
Garnaas, MK
Tin, A
Kottgen, A
Franceschini, N
Peralta, CA
de Boer, IH
Lu, XN
Atkinson, E
Ding, JZ
Nalls, M
Shriner, D
Coresh, J
Kutlar, A
Bibbins-Domingo, K
Siscovick, D
Akylbekova, E
Wyatt, S
Astor, B
Mychaleckjy, J
Li, M
Reilly, MP
Townsend, RR
Adeyemo, A
Zonderman, AB
de Andrade, M
Turner, ST
Mosley, TH
Harris, TB
Rotimi, CN
Liu, YM
Kardia, SLR
Evans, MK
Shlipak, MG
Kramer, H
Flessner, MF
Dreisbach, AW
Goessling, W
Cupples, LA
Kao, WL
Fox, CS
AF Liu, Ching-Ti
Garnaas, Maija K.
Tin, Adrienne
Kottgen, Anna
Franceschini, Nora
Peralta, Carmen A.
de Boer, Ian H.
Lu, Xiaoning
Atkinson, Elizabeth
Ding, Jingzhong
Nalls, Michael
Shriner, Daniel
Coresh, Josef
Kutlar, Abdullah
Bibbins-Domingo, Kirsten
Siscovick, David
Akylbekova, Ermeg
Wyatt, Sharon
Astor, Brad
Mychaleckjy, Josef
Li, Man
Reilly, Muredach P.
Townsend, Raymond R.
Adeyemo, Adebowale
Zonderman, Alan B.
de Andrade, Mariza
Turner, Stephen T.
Mosley, Thomas H.
Harris, Tamara B.
Rotimi, Charles N.
Liu, Yongmei
Kardia, Sharon L. R.
Evans, Michele K.
Shlipak, Michael G.
Kramer, Holly
Flessner, Michael F.
Dreisbach, Albert W.
Goessling, Wolfram
Cupples, L. Adrienne
Kao, W. Linda
Fox, Caroline S.
CA CKDGen Consortium
TI Genetic Association for Renal Traits among Participants of African
Ancestry Reveals New Loci for Renal Function
SO PLOS GENETICS
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE;
DIABETIC-NEPHROPATHY; UNITED-STATES; ZEBRAFISH; POPULATIONS;
PROGRESSION; SUSCEPTIBILITY; PREDICTORS; MUTATIONS
AB Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR,60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR>30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3x10(-7)) and FNDC1 (p-value = 3.0x10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6x10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.
C1 [Liu, Ching-Ti; Lu, Xiaoning; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Garnaas, Maija K.; Goessling, Wolfram] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Garnaas, Maija K.; Goessling, Wolfram; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Garnaas, Maija K.; Goessling, Wolfram; Kao, W. Linda] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Tin, Adrienne; Kottgen, Anna; Li, Man] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Kottgen, Anna] Univ Hosp Freiburg, Div Renal, Freiburg, Germany.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Peralta, Carmen A.] Univ Calif San Francisco, Sch Med, Div Nephrol, San Francisco, CA USA.
[Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
[Atkinson, Elizabeth; de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Ding, Jingzhong] Wake Forest Univ Hlth Sci, J Paul Sticht Ctr Aging, Winston Salem, NC USA.
[Nalls, Michael] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Kutlar, Abdullah] Med Coll Georgia, Augusta, GA 30912 USA.
[Siscovick, David] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Akylbekova, Ermeg] Jackson State Univ, Jackson, MS USA.
[Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA.
[Astor, Brad] Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Mychaleckjy, Josef] Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Townsend, Raymond R.] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
[Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Dept Internal Med, Rochester, MN USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Kramer, Holly] Loyola Univ, Maywood, IL 60153 USA.
[Flessner, Michael F.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
[Dreisbach, Albert W.] Univ Mississippi, Div Nephrol, Jackson, MS 39216 USA.
[Goessling, Wolfram] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA.
[Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Boston, MA USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Liu, CT (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
EM wgoessling@partners.org; wkao@jhsph.edu; foxca@nhlbi.nih.gov
RI Kottgen, Anna/D-2920-2012;
OI Zonderman, Alan B/0000-0002-6523-4778; Cupples, L.
Adrienne/0000-0003-0273-7965; Kramer, Holly/0000-0002-6374-837X;
Adeyemo, Adebowale/0000-0002-3105-3231; Goessling,
Wolfram/0000-0001-9972-1569
FU NHLBI [R01-HL087660]; NIA [N01AG62101, N01AG62103, N01AG62106,
1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C,
S06GM008016-320107, S06GM008016-380111, 2M01RR010284]; NIH, National
Institute on Aging. Howard University Family Study; Center for Research
on Genomics and Global Health; National Human Genome Research Institute;
National Institute of Diabetes and Digestive and Kidney Diseases; Center
for Information Technology; Office of the Director at the National
Institutes of Health [Z01HG200362]; NIH, National Institute on Aging;
National Center on Minority Health and Health Disparities [Z01-AG000513,
2009-149]; National Heart, Lung, and Blood Institute
FX The following nine parent studies have contributed parent study data,
ancillary study data, and DNA samples through the Massachusetts
Institute of Technology - Broad Institute (N01-HC-65226) to create this
genotype/phenotype data base for wide dissemination to the biomedical
research community: Atherosclerotic Risk in Communities (ARIC):
University of North Carolina at Chapel Hill (N01-HC-55015), Baylor
Medical College (N01-HC-55016), University of Mississippi Medical Center
(N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins
University (N01-HC-55020), University of Texas Houston (N01-HC-55022),
University of North Carolina Forsyth County (N01-HC-55018);
Cardiovascular Health Study (CHS): University of Washington
(N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins
University (N01-HC-85081), University of Pittsburgh (N01-HC-85082),
University of California Davis (N01-HC-85083), University of California
Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085),
University of Vermont (N01-HC-85086), Georgetown University
(N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of
Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of
Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study (CFS):
Case Western Reserve University (NIH HL 46380, M01RR00080); Cooperative
Study of Sickle Cell Disease (CSSCD): University of Illinois
(N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991,
N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke
University (N01-HB-72993), George Washington University (N01-HB-72994),
University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University
(N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia
(N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998,
N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060),
Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and
Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and
Hospitals of the City of Boston (N01-HB-73003), Children's
Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi
(N01-HB-73005), St. Luke's Hospital-New York (N01-HB-73006), Alta
Bates-Herrick Hospital (N01-HB-97051), Columbia University
(N01-HB97058), St.; Jude's Children's Research Hospital (N01-HB-97066),
Research Foundation of the State University of New York-Albany
(N01-HB-97068, N01-HB-97069), New England Research Institute
(N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085);
Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at
Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048),
Northwestern University (N01-HC-48049), Kaiser Foundation Research
Institute (N01-HC-48050), University of Alabama at Birmingham
(N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake
Forest University (N01-HC45205), Harbor-UCLA Research and Education
Institute (N01-HC-05187), University of California Irvine (N01-HC-45134,
N01-HC-95100); Framingham Heart Study (FHS): Boston University
(N01-HC-25195, R01HL092577-01A1, RO1 HL076784, R01 AG028321); Jackson
Heart Study (JHS): Jackson State University (N01-HC-95170), University
of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172);
Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington
(N01-HC-95159), Regents of the University of California (N01-HC-95160),
Columbia University (N01-HC-95161), Johns Hopkins University
(N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163),
Northwestern Universiy (N01-HC-95164), Wake Forest University
(N01-HC-95165), University of Vermont (N01-HC-95166), New England
Medical Center (N01-HC-95167), Harbor-UCLA Research and Education
Institute (N01-HC-95169), Cedars-Sinai Medical Center (R01-HL-071205),
University of Virginia (subcontract to R01-HL-071205); Sleep Heart
Health Study (SHHS): Johns Hopkins University (U01 HL064360), Case
Western University (U01 HL063463), University of California, Davis (U01
HL053916), University of Arizona (U01 HL053938), University of Minnesota
(relocating in 2006 to Univ Arizona) (U01 HL053934), University of
Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar
Research Institute (U01 HL063429), Johns Hopkins University (U01
HL053937). GENOA: The GENOA Study genome-wide association study was
funded by NHLBI R01-HL087660. HABC: This research was supported by NIA
contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide
association study was funded by NIA grant 1R01AG032098-01A1 to Wake
Forest University Health Sciences and genotyping services were provided
by the Center for Inherited Disease Research (CIDR). CIDR is fully
funded through a federal contract from the National Institutes of Health
to The Johns Hopkins University, contract number HHSN268200782096C. This
research was supported in part by the Intramural Research Program of the
NIH, National Institute on Aging. Howard University Family Study: The
Howard University Family Study was supported by National Institutes of
Health grants S06GM008016-320107 and S06GM008016-380111. Enrollment was
carried out at the Howard University General Clinical Research Center,
supported by National Institutes of Health grant 2M01RR010284. This
research was supported in part by the Intramural Research Program of the
Center for Research on Genomics and Global Health. The Center for
Research on Genomics and Global Health is supported by the National
Human Genome Research Institute, the National Institute of Diabetes and
Digestive and Kidney Diseases, the Center for Information Technology,
and the Office of the Director at the National Institutes of Health
(Z01HG200362). Genotyping support was provided by the Coriell Institute
for Medical Research. We thank the participants of the Howard University
Family Study.; The contents of this publicationare solely the
responsibility of the authors and do not necessarily represent the
official view of the National Institutes of Health. HANDLS: This
research was supported by the Intramural Research Program of the NIH,
National Institute on Aging and the National Center on Minority Health
and Health Disparities (Intramural Project # Z01-AG000513 and human
subjects protocol # 2009-149). Data analyses for the HANDLS study
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, MD.
(http://biowulf.nih.gov). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.; The authors wish 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 authors wish to
thank Andrea Calhoun and Dr. Susan Hagen at the Electron Microscopy Core
Facility at Beth Israel Deaconess Medical Center for expert assistance
with electron microscopy and Drs. Dirk Hentschel and Helmut Rennke at
Brigham and Women's Hospital for advice on electron microscopy images.
We thank Dr. Iain Drummond at Massachusetts General Hospital and Dr.
Rebecca Wingert at the University of Notre Dame for in situ probes.
NR 42
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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 SEP
PY 2011
VL 7
IS 9
AR e1002264
DI 10.1371/journal.pgen.1002264
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100018
PM 21931561
ER
PT J
AU Rizki, G
Iwata, TN
Li, J
Riedel, CG
Picard, CL
Jan, M
Murphy, CT
Lee, SS
AF Rizki, Gizem
Iwata, Terri Naoko
Li, Ji
Riedel, Christian G.
Picard, Colette Lafontaine
Jan, Max
Murphy, Coleen T.
Lee, Siu Sylvia
TI The Evolutionarily Conserved Longevity Determinants HCF-1 and
SIR-2.1/SIRT1 Collaborate to Regulate DAF-16/FOXO
SO PLOS GENETICS
LA English
DT Article
ID ELEGANS LIFE-SPAN; FOXO TRANSCRIPTION FACTORS; CAENORHABDITIS-ELEGANS;
C-ELEGANS; EXPRESSION PATTERNS; PROTEIN INTERACTS; FAMILY-MEMBER;
CELL-CYCLE; MLL FAMILY; FAT-BODY
AB The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.
C1 [Rizki, Gizem; Iwata, Terri Naoko; Lee, Siu Sylvia] Cornell Univ, Dept Mol Biol & Genet, Field Comparat Biomed Sci, Ithaca, NY 14853 USA.
[Riedel, Christian G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Simches Res Ctr, Boston, MA 02114 USA.
[Jan, Max; Murphy, Coleen T.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
RP Rizki, G (reprint author), Cornell Univ, Dept Mol Biol & Genet, Field Comparat Biomed Sci, Ithaca, NY 14853 USA.
EM sylvia.lee@cornell.edu
OI Riedel, Christian/0000-0002-3689-8022
FU National Institute on Aging [AG024425]; Ellison Medical Foundation;
Cornell Center of Vertebrate Genomics; Juvenile Diabetes Research
Foundation; National Institute of Child Health and Human Development
[T32HD052471]; European Molecular Biology Organization; Human Frontier
Science Program
FX This work was supported by R01 grant AG024425 from the National
Institute on Aging, a Senior Scholar in Aging award from the Ellison
Medical Foundation, a seed grant from the Cornell Center of Vertebrate
Genomics, and an innovation award from the Juvenile Diabetes Research
Foundation awarded to SSL. TNI was supported by a Reproductive Genomic
Training grant T32HD052471 from the National Institute of Child Health
and Human Development. CGR was supported by long-term fellowships from
the European Molecular Biology Organization and the Human Frontier
Science Program. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 76
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U1 2
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2011
VL 7
IS 9
AR e1002235
DI 10.1371/journal.pgen.1002235
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 827HH
UT WOS:000295419100004
PM 21909281
ER
PT J
AU Wei, MH
Querques, J
Stern, TA
AF Wei, Marlynn H.
Querques, John
Stern, Theodore A.
TI Teaching Trainees about the Practice of Consultation-Liaison Psychiatry
in the General Hospital
SO PSYCHIATRIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Consultation-Liaison Psychiatry; Psychosomatic Medicine; Teaching
Psychiatry; Education; Teaching Rounds
ID ADULT LEARNING-THEORY; MEDICAL-EDUCATION; RANDOMIZED-TRIAL; CYNICAL
HUMOR; GUIDELINES; EFFICACY; ROUNDS; PERCEPTIONS; SERVICES; FEEDBACK
AB Teaching trainees about the practice of consultation-liaison (C-L) psychiatry involves formal didactics, bedside rounds, reviewing the literature, and the demonstration of specific skills (eg, critical thinking and self-awareness [autognosis]). Effective teaching (based on adult learning theory) about psychosomatic medicine uses problem-oriented approaches, integrates knowledge into real-life situations, and makes trainees responsible for their decisions. Discussions of differential diagnoses, work-ups, formulations (that involve biological, psychological, sociocultural, and existential perspectives) and treatment of myriad conditions seen in the general hospital create a solid foundation. Teaching C-L psychiatry is most effective with a layered approach, tailored to specific teaching forums and learning styles of trainees.
C1 [Wei, Marlynn H.; Querques, John; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Stern, TA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren Bldg,Room 605, Boston, MA 02114 USA.
EM TStern@Partners.org
NR 53
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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 0193-953X
EI 1558-3147
J9 PSYCHIAT CLIN N AM
JI Psychiatr. Clin. North Amer.
PD SEP
PY 2011
VL 34
IS 3
BP 689
EP +
DI 10.1016/j.psc.2011.05.009
PG 20
WC Psychiatry
SC Psychiatry
GA 829RL
UT WOS:000295601900014
PM 21889687
ER
PT J
AU Theurl, I
Schroll, A
Sonnweber, T
Nairz, M
Theurl, M
Willenbacher, W
Eller, K
Wolf, D
Lin, H
Weiss, G
AF Theurl, Igor
Schroll, Andrea
Sonnweber, Thomas
Nairz, Manfred
Theurl, Milan
Willenbacher, Wolfgang
Eller, Kathrin
Wolf, Dominik
Lin, Herbert
Weiss, Guenter
TI Pharmacologic inhibition of hepcidin expression reverses anemia of
chronic disease in rats
SO WIENER KLINISCHE WOCHENSCHRIFT
LA English
DT Meeting Abstract
C1 [Theurl, Igor; Schroll, Andrea; Sonnweber, Thomas; Nairz, Manfred; Theurl, Milan; Weiss, Guenter] Med Univ Innsbruck, Ctr Internal Med, Dept Internal Med 1, Innsbruck, Austria.
[Willenbacher, Wolfgang; Wolf, Dominik] Med Univ Innsbruck, Ctr Internal Med, Dept Internal Med Hematol & Oncol 5, Innsbruck, Austria.
[Eller, Kathrin] Med Univ Innsbruck, Ctr Internal Med, Dept Internal Med Nephrol & Hypertensiol 4, Innsbruck, Austria.
[Lin, Herbert] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Cambridge, MA 02138 USA.
NR 0
TC 0
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U1 1
U2 1
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0043-5325
J9 WIEN KLIN WOCHENSCHR
JI Wien. Klin. Wochen.
PD SEP
PY 2011
VL 123
IS 17-18
BP A71
EP A71
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 833HZ
UT WOS:000295875800176
ER
PT J
AU Hagan, MP
Saleh, H
Moore, M
Williamson, J
AF Hagan, Michael P.
Saleh, Habeeb
Moore, Mary
Williamson, Jeffrey
TI Regulatory evaluation of prostate volume implants: Pitfalls of a
retrospective assessment
SO BRACHYTHERAPY
LA English
DT Article
DE Prostate; Brachytherapy; Volume implant; Evaluation; Medical event
ID POSTIMPLANT DOSIMETRY; COMPUTED-TOMOGRAPHY; TREATMENT DELIVERY; SEED
LOCALIZATION; BRACHYTHERAPY; ULTRASOUND; CANCER; EDEMA; RECOMMENDATIONS;
QUALITY
AB PURPOSE: Evaluate for regulatory compliance the prostate implants from the Philadelphia Veterans Medical Center applying both an activity-based and volume-corrected D(90) (the maximum dose delivered to 90% of the prostate volume) metrics.
METHODS AND MATERIALS: Dosimetry from 107 prostate implants performed at the Philadelphia Veterans Medical Center used immediate postprocedural CT image sets. D(90) values were adjusted for volume differences from planning volumes. Medical events (MEs) determined from the volume-corrected data were compared with an activity-based metric.
RESULTS: Examination of images using original and third-party reviewed prostate contours revealed 56 and 62 cases with D(90) values <80% of the prescription close, respectively. Because postprocedural prostate volumes were on average 55.7% larger than the planned volume, clinical nomogram-based doses using the implanted activity and actual volumes found 34-47 implants failing to achieve closes greater than 80% of the prescription dose.
Volume correction identified 20 MEs, 9 cases with D(90) values within 4% of the ME threshold and 11 significantly inferior cases with median D(90) values <52% of the prescribed dose.
Eleven implants also had 20% or more seeds beyond the treatment site according to an activity metric recommended by the VHA Blue Ribbon Panel. Ten of these 11 cases were also identified by volume-corrected D(90) metric. The remaining 96 cases, however, had 95% (+/-6%) of seeds placed within the treatment site.
CONCLUSIONS: Of the cases reported to the United States Nuclear Regulatory Commission (NRC) on the basis of Day-1 D(90) values, many appear to have been acceptable implants relative to standard-of-practice clinical criteria. The activity-based dose metric, endorsed by the NRC Advisory Committee on the Medical Uses of Isotopes in 2005 and recommended by the VHA Blue Ribbon Panel for Prostate Brachytherapy yields a more robust determination of ME for this population of implants. Published by Elsevier Inc. All rights reserved.
C1 [Hagan, Michael P.; Saleh, Habeeb; Williamson, Jeffrey] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA 23298 USA.
[Hagan, Michael P.] Vet Hlth Agcy, Dept Vet Affairs, Natl Radiat Oncol Program Off, Richmond, VA USA.
[Moore, Mary] Philadelphia VA Med Ctr, Radiat Safety Off, Philadelphia, PA USA.
RP Hagan, MP (reprint author), Virginia Commonwealth Univ, Dept Radiat Oncol, 401 Coll St, Richmond, VA 23298 USA.
EM michael.hagan@va.gov
NR 35
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U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1538-4721
J9 BRACHYTHERAPY
JI Brachytherapy
PD SEP-OCT
PY 2011
VL 10
IS 5
BP 385
EP 394
DI 10.1016/j.brachy.2011.01.005
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 826IB
UT WOS:000295346700007
PM 21349777
ER
PT J
AU MacConaill, LE
Van Hummelen, P
Meyerson, M
Hahn, WC
AF MacConaill, Laura E.
Van Hummelen, Paul
Meyerson, Matthew
Hahn, William C.
TI Clinical Implementation of Comprehensive Strategies to Characterize
Cancer Genomes: Opportunities and Challenges
SO CANCER DISCOVERY
LA English
DT Review
ID CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; METASTATIC
COLORECTAL-CANCER; GROWTH-FACTOR RECEPTOR; CHRONIC MYELOID-LEUKEMIA;
IN-SITU HYBRIDIZATION; TYROSINE KINASE JAK2; BREAST-CANCER;
GENE-EXPRESSION; ONCOGENIC MUTATIONS
AB An increasing number of anticancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Recent evidence suggests that the selection of patients whose tumors harbor specific genetic alterations identifies the subset of patients who are most likely to benefit from the use of such agents. As the number of genetic alterations that provide diagnostic and/or therapeutic information increases, the comprehensive characterization of cancer genomes will be necessary to understand the spectrum of distinct genomic alterations in cancer, to identify patients who are likely to respond to particular therapies, and to facilitate the selection of treatment modalities. Rapid developments in new technologies for genomic analysis now provide the means to perform comprehensive analyses of cancer genomes. In this article, we review the current state of cancer genome analysis and discuss the challenges and opportunities necessary to implement these technologies in a clinical setting.
Significance: Rapid advances in sequencing technologies now make it possible to contemplate the use of genome scale interrogation in clinical samples, which is likely to accelerate efforts to match treatments to patients. However, major challenges in technology, clinical trial design, legal and social implications, healthcare information technology, and insurance and reimbursement remain. Identifying and addressing these challenges will facilitate the implementation of personalized cancer medicine. Cancer Discovery; 1(4): 297-311. (C) 2011 AACR.
C1 [MacConaill, Laura E.; Van Hummelen, Paul; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[MacConaill, Laura E.; Van Hummelen, Paul; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA.
[MacConaill, Laura E.; Van Hummelen, Paul; Meyerson, Matthew; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA.
[MacConaill, Laura E.; Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Hahn, William C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Meyerson, Matthew; Hahn, William C.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Meyerson, Matthew; Hahn, William C.] MIT, Cambridge, MA 02139 USA.
RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM william_hahn@dfci.harvard.edu
RI Meyerson, Matthew/E-7123-2012
FU Novartis
FX No potential conflicts of interest were disclosed by L. E. MacConaill
and P. Van Hummelen. M. Meyerson is a consultant for and received
research support from Novartis; the founding advisor of, consultant for,
and equity holder in Foundation Medicine; a coinventor and patent holder
on the use of EGFR mutations for lung cancer diagnosis, licensed to
Genzyme Genetics/Labcorp. W. C. Hahn is a consultant for Novartis and
Thermo-Fisher and has received research support from Novartis.
NR 161
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U1 1
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD SEP
PY 2011
VL 1
IS 4
BP 297
EP 311
DI 10.1158/2159-8290.CD-11-0110
PG 15
WC Oncology
SC Oncology
GA 832ET
UT WOS:000295785800017
PM 21935500
ER
PT J
AU Faber, AC
Corcoran, RB
Ebi, H
Sequist, LV
Waltman, BA
Chung, EH
Incio, J
Digumarthy, SR
Pollack, SF
Song, YC
Muzikansky, A
Lifshits, E
Roberge, S
Coffman, EJ
Benes, CH
Gomez, HL
Baselga, J
Arteaga, CL
Rivera, MN
Dias-Santagata, D
Jain, RK
Engelman, JA
AF Faber, Anthony C.
Corcoran, Ryan B.
Ebi, Hiromichi
Sequist, Lecia V.
Waltman, Belinda A.
Chung, Euiheon
Incio, Joao
Digumarthy, Subba R.
Pollack, Sarah F.
Song, Youngchul
Muzikansky, Alona
Lifshits, Eugene
Roberge, Sylvie
Coffman, Erik J.
Benes, Cyril H.
Gomez, Henry L.
Baselga, Jose
Arteaga, Carlos L.
Rivera, Miguel N.
Dias-Santagata, Dora
Jain, Rakesh K.
Engelman, Jeffrey A.
TI BIM Expression in Treatment-Naive Cancers Predicts Responsiveness to
Kinase Inhibitors
SO CANCER DISCOVERY
LA English
DT Article
ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; MET AMPLIFICATION; INDUCED
APOPTOSIS; BREAST-CANCER; PHASE-II; GEFITINIB; EGFR; MUTATIONS;
ACTIVATION
AB Cancers with specific genetic mutations are susceptible to selective kinase inhibitors. However, there is a wide spectrum of benefit among cancers harboring the same sensitizing genetic mutations. Herein, we measured apoptotic rates among cell lines sharing the same driver oncogene following treatment with the corresponding kinase inhibitor. There was a wide range of kinase inhibitor-induced apoptosis despite comparable inhibition of the target and associated downstream signaling pathways. Surprisingly, pretreatment RNA levels of the BH3-only pro-apoptotic BIM strongly predicted the capacity of EGFR, HER2, and PI3K inhibitors to induce apoptosis in EGFR-mutant, HER2-amplified, and PIK3CA-mutant cancers, respectively, but BIM levels did not predict responsiveness to standard chemotherapies. Furthermore, BIM RNA levels in EGFR-mutant lung cancer specimens predicted response and duration of clinical benefit from EGFR inhibitors. These findings suggest assessment of BIM levels in treatment-naive tumor biopsies may indicate the degree of benefit from single-agent kinase inhibitors in multiple oncogene-addiction paradigms.
SIGNIFICANCE: In several oncogene-addiction paradigms, assessment of BIM RNA levels identifies those cancers that fail to have substantial apoptotic responses to kinase inhibitors. BIM RNA levels may be assessed in diagnostic cancer specimens to predict which patients will receive less benefit from single-agent kinase inhibitors. Cancer Discovery: 1(4); 352-65. (C) 2011 AACR.
C1 [Faber, Anthony C.; Corcoran, Ryan B.; Ebi, Hiromichi; Sequist, Lecia V.; Waltman, Belinda A.; Pollack, Sarah F.; Song, Youngchul; Muzikansky, Alona; Lifshits, Eugene; Coffman, Erik J.; Benes, Cyril H.; Baselga, Jose; Rivera, Miguel N.; Dias-Santagata, Dora; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA.
[Rivera, Miguel N.; Dias-Santagata, Dora] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA.
[Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA.
[Faber, Anthony C.; Corcoran, Ryan B.; Ebi, Hiromichi; Sequist, Lecia V.; Waltman, Belinda A.; Digumarthy, Subba R.; Pollack, Sarah F.; Song, Youngchul; Lifshits, Eugene; Coffman, Erik J.; Benes, Cyril H.; Baselga, Jose; Rivera, Miguel N.; Dias-Santagata, Dora; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Chung, Euiheon; Incio, Joao; Roberge, Sylvie; Jain, Rakesh K.] Massachusetts Gen Hosp, Steele Lab Tumor Biol, Charlestown, MA USA.
[Chung, Euiheon; Incio, Joao; Roberge, Sylvie; Jain, Rakesh K.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Arteaga, Carlos L.] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Arteaga, Carlos L.] Vanderbilt Univ, Breast Canc Res Program, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Gomez, Henry L.] Inst Nacl Enfermedades Neoplas, Lima, Peru.
RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Boston, MA 02129 USA.
EM jengelman@partners.org
OI Incio, Joao/0000-0002-0259-1356; Gomez, Henry/0000-0003-2660-1843; Ebi,
Hiromichi/0000-0003-3155-7576
FU National Institutes of Health NIH [R01CA137008-01, R01CA140594,
R01CA135257-01]; National Cancer Institute Lung SPORE [P50CA090578];
DF/HCC Gastrointestinal Cancer SPORE [P50 CA127003]; American Lung
Cancer Association; V Foundation; Ellison Foundation; Aid for Cancer
Research Postdoctoral Fellowship; [CA120060-01]
FX This study is supported by grants from the National Institutes of Health
NIH R01CA137008-01 (J.A. Engelman), R01CA140594 (J.A. Engelman),
R01CA135257-01 (J.A. Engelman), National Cancer Institute Lung SPORE
P50CA090578 (J.A. Engelman), DF/HCC Gastrointestinal Cancer SPORE P50
CA127003 (J.A. Engelman), K08 grant CA120060-01 (J.A. Engelman), the
American Lung Cancer Association Lung Cancer Discovery Award (J.A.
Engelman), the V Foundation (J.A. Engelman), the Ellison Foundation
Scholar (J.A. Engelman), and an Aid for Cancer Research Postdoctoral
Fellowship (A.C. Faber).
NR 53
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Z9 130
U1 2
U2 16
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 SEP
PY 2011
VL 1
IS 4
BP 352
EP 365
DI 10.1158/2159-8290.CD-11-0106
PG 14
WC Oncology
SC Oncology
GA 832ET
UT WOS:000295785800021
PM 22145099
ER
PT J
AU Chen, WY
AF Chen, Wendy Y.
TI Postmenopausal Hormone Therapy and Breast Cancer Risk: Current Status
and Unanswered Questions
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Article
DE Menopause; Hormone therapy; Breast cancer; Estrogen
ID ESTROGEN-PLUS-PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; REPLACEMENT
THERAPY; MILLION WOMEN; EQUINE ESTROGEN; FAMILY-HISTORY; MENOPAUSE;
HEALTH; COHORT; MAMMOGRAPHY
AB Many women take hormone therapy (HT) for menopausal symptom relief. Studies have tried to clarify whether various factors can modify the risk of HT, such as the age at initiation, dose, duration, or type of HT, or characteristics of the individual, such as family history or body mass index. The relative risks of breast cancer associated with HT across various subgroups of women should be considered similar, but absolute risks can vary significantly among women and this may inform individual decision making. For breast cancer survivors, systemic HT should be discouraged.
C1 [Chen, Wendy Y.] Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Chen, Wendy Y.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Chen, WY (reprint author), Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, 181 Longwood Ave, Boston, MA 02115 USA.
EM wendy.chen@channing.harvard.edu
FU NCI NIH HHS [P01 CA087969, P01 CA087969-11]
NR 49
TC 5
Z9 6
U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8529
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD SEP
PY 2011
VL 40
IS 3
BP 509
EP +
DI 10.1016/j.ecl.2011.05.006
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 829RN
UT WOS:000295602100006
PM 21889717
ER
PT J
AU Ibarra, JM
Quinones, MP
Estrada, CA
Jimenez, F
Martinez, HG
Ahuja, SS
AF Ibarra, Jessica M.
Quinones, Marlon P.
Estrada, Carlos A.
Jimenez, Fabio
Martinez, Hernan G.
Ahuja, Seema S.
TI CD8 alpha(+) dendritic cells improve collagen-induced arthritis in CC
chemokine receptor (CCR)-2 deficient mice
SO IMMUNOBIOLOGY
LA English
DT Article
DE CCR2; Dendritic cells; CD8 alpha(+) DC; Arthritis; SKG
ID REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE ARTHRITIS;
TRANSPLANT TOLERANCE; DIFFERENT MECHANISMS; LEISHMANIA-MAJOR; LIGAND;
DIFFERENTIATION; CYTOKINES; RESPONSES
AB Objective: Dendritic cells (DCs) have long been recognized as potential therapeutic targets of rheumatoid arthritis (RA). Increasing evidence has showed that DCs are capable of suppressing autoimmunity by expanding FoxP3(+) regulatory T cells (T g), which in turn exert immunosuppression by increasing TGF beta-1. In the SKG mice, activated DC prime autoreactive T cells causing autoantibody production and an inflammatory arthritic response. Recently, we reported that CC-chemokine receptor-2 deficient (Ccr2(-/-)) mice had impaired DCs migration and reduced CD8 alpha(+) DCs in the C57B1/6J mice strain and that these mice were more susceptible to collagen antibody-induced arthritis (CAIA), compared to wild type mice. To examine the mechanism by which DCs contribute to the increased susceptibility of arthritis in Ccr2(-/-)mice, we tested the hypothesis that CD8 alpha(+) DCs are protective (tolerogenic) against autoimmune arthritis by examining the role of CD8 alpha(+) DCs in Ccr2(-/-) and SKG mice.
Methods: To examine the mechanism by which DCs defects lead to the development of arthritis, we used two murine models of experimental arthritis: collagen-induced arthritis (CIA) in DBA1/J mice and zymosan-induced arthritis in SKG mice. DBA1/J mice received recombinant fms-like tyrosine kinase 3 ligand (Flt3L) injections to expand endogenous DCs populations or adoptive transfers of CD8 alpha(+) DCs.
Results: Flt3L-mediated expansion of endogenous CD8 alpha(+) DCs resulted in heightened susceptibility of CIA. In contrast, supplementation with exogenous CD8 alpha(+) DCs ameliorated arthritis in Ccr2(-/-) mice and enhanced TGF beta 1 production by T cells. Furthermore, SKG mice with genetic inactivation of CCR2 did not affect the numbers of DCs nor improve the arthritis phenotype.
Conclusion: CD8 alpha(+) DCs were tolerogenic to the development of arthritis. CD8 alpha(+) DCs deficiency heightened the sensitivity to arthritis in Ccr2(-/-) mice. Ccr2 deficiency did not alter the arthritic phenotype in SKG mice suggesting the arthritis in Ccr2(-/-) mice was T cell-independent. Published by Elsevier GmbH.
C1 [Ibarra, Jessica M.; Quinones, Marlon P.; Estrada, Carlos A.; Jimenez, Fabio; Martinez, Hernan G.; Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Quinones, Marlon P.; Estrada, Carlos A.; Jimenez, Fabio; Martinez, Hernan G.; Ahuja, Seema S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Adm Ctr Res AIDS & HIV Infect 1, San Antonio, TX USA.
RP Ahuja, SS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM ahuja@uthscsa.edu
FU National Institutes of Health (NIH) [AI48644, AR052755]
FX This work was supported in part by the National Institutes of Health
(NIH)grants (AI48644 and AR052755) and VA Merit to S.S.A.
NR 30
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD SEP
PY 2011
VL 216
IS 9
BP 971
EP 978
DI 10.1016/j.imbio.2011.03.012
PG 8
WC Immunology
SC Immunology
GA 829TG
UT WOS:000295606600001
PM 21531476
ER
PT J
AU Ford, L
Bloom, K
Nowak-Wegrzyn, A
Shreffler, W
Masilamani, M
Sampson, H
AF Ford, Lara
Bloom, Katherine
Nowak-Wegrzyn, Anna
Shreffler, Wayne
Masilamani, Madhan
Sampson, Hugh
TI IDENTIFICATION OF BIOMARKERS TO DISTINGUISH VARIOUS LEVELS OF COW'S MILK
TOLERANCE
SO INTERNAL MEDICINE JOURNAL
LA English
DT Meeting Abstract
C1 [Ford, Lara; Bloom, Katherine; Nowak-Wegrzyn, Anna; Masilamani, Madhan; Sampson, Hugh] Mt Sinai Sch Med, New York, NY USA.
[Shreffler, Wayne] Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM lford@med.usyd.edu.au
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1444-0903
J9 INTERN MED J
JI Intern. Med. J.
PD SEP
PY 2011
VL 41
SU 4
SI SI
BP 7
EP 7
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 828RQ
UT WOS:000295520600022
ER
PT J
AU McNulty, EJ
Ng, W
Spertus, JA
Zaroff, JG
Yeh, RW
Ren, XSM
Lundstrom, RJ
AF McNulty, Edward J.
Ng, William
Spertus, John A.
Zaroff, Jonathan G.
Yeh, Robert W.
Ren, Xiushi M.
Lundstrom, Robert J.
TI Surgical Candidacy and Selection Biases in Nonemergent Left Main
Stenting Implications for Observational Studies
SO JACC-CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE bias; bypass; comparative effectiveness; risk factors; stents
ID PERCUTANEOUS CORONARY INTERVENTION; DRUG-ELUTING STENTS; ARTERY-BYPASS
SURGERY; LONG-TERM OUTCOMES; HEART-ASSOCIATION GUIDELINES;
CARDIAC-SURGERY; AMERICAN-COLLEGE; FOLLOW-UP; REVASCULARIZATION
REGISTRY; GRAFTING SURGERY
AB Objectives This study sought to characterize reasons for surgical ineligibility in patients undergoing nonemergent unprotected left main (ULM) percutaneous coronary intervention (PCI) and to assess the potential for these reasons to confound comparative effectiveness studies of coronary revascularization.
Background Although both PCI and coronary artery bypass graft surgery are treatments for ULM disease, some patients are not eligible for both treatments, which may result in treatment selection biases.
Methods In 101 consecutive patients undergoing nonemergent ULM PCI, mixed methods were used to determine the prevalence of treatment selection dictated by surgical ineligibility and to identify the reasons cited for avoiding coronary artery bypass graft surgery. We then determined whether these reasons were captured by the ACC-NCDR (American College of Cardiology-National Cardiovascular Data Registry) Cath-PCI dataset to assess the ability of this registry to account for biases in treatment selection. Finally, the association of surgical eligibility with long-term outcomes after ULM PCI was assessed.
Results Treatment selection was dictated by surgical ineligibility in over half the ULM PCI cohort with the majority having reasons for ineligibility not captured by the ACC-NCDR. Surgical ineligibility was a significant predictor of mortality after adjustment for Society of Thoracic Surgeons (hazard ratio [HR]: 5.4, 95% confidence interval [CI]: 1.2 to 25), EuroSCORE (European System for Cardiac Operative Risk Evaluation) (HR: 5.9, 95% CI: 1.3 to 27), or NCDR mortality scores (HR: 6.2, 95% CI: 1.4 to 27).
Conclusions Surgical ineligibility dictating treatment selection is common in patients undergoing nonemergent ULM PCI, occurs on the basis of risk factors not captured by the ACC-NCDR, and is independently associated with worse long-term outcomes after adjusting for standard risk scores. (J Am Coll Cardiol Intv 2011;4:1020-7) (C) 2011 by the American College of Cardiology Foundation
C1 [McNulty, Edward J.; Ng, William; Zaroff, Jonathan G.; Lundstrom, Robert J.] Kaiser Permanente Med Ctr, Div Cardiol, San Francisco, CA 94115 USA.
[McNulty, Edward J.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA.
[Ren, Xiushi M.] Kaiser Permanente Med Ctr, Div Cardiol, Redwood City, CA USA.
[Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA.
[Spertus, John A.] St Lukes Mid Amer Heart Inst, Div Cardiol, Kansas City, MO USA.
[Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP McNulty, EJ (reprint author), Kaiser Permanente Med Ctr, Div Cardiol, 2350 Geary Blvd, San Francisco, CA 94115 USA.
EM edward.j.mcnulty@kp.org
FU Community Benefits Grant; Kaiser Foundation Research Institute; Graduate
Medical Education Program; Northern California Kaiser Permanente;
National Institutes of Health; American Heart Association; Amgen;
Johnson , Johnson; Atherotech; Roche Diagnostics
FX From the *Division of Cardiology, Kaiser Permanente Medical Center, San
Francisco, California; dagger Department of Medicine, University of
California, San Francisco School of Medicine, San Francisco, California;
double dagger Division of Cardiology, Kaiser Permanente Medical Center,
Redwood City, California; Division of Cardiology, Saint Luke's Mid
America Heart Institute and the University of Missouri-Kansas City,
Kansas City, Missouri; and the parallel to Division of Cardiology,
Massachusetts General Hospital, Harvard Medical School, Boston,
Massachusetts. This study was supported by grants from the Community
Benefits Grant, Kaiser Foundation Research Institute (to Dr. Lundstrom)
and Graduate Medical Education Program, Northern California Kaiser
Permanente (to Dr. Ng). Drs. McNulty, Ng, Ren, and Lundstrom are
employees of The Permanente Medical Group, Inc. Dr. McNulty receives
grant support from the National Institutes of Health. Dr. Sperms has a
research contract with American College of Cardiology Foundation; has
received grants from American Heart Association, Amgen, Johnson &,
Johnson, and National Institutes of Health; has received grant support
from Atherotech and Roche Diagnostics; and is a consultant for Novartis,
United Healthcare, and St. Jude Medical. Drs. Zaroff and Lundstrom
receive grant support from the Kaiser Foundation Research Institute. Dr.
Yeh is a consultant for the Kaiser Permanente Division of Research and
the Harvard Clinical Research Institute. All other authors have reported
that they have no relationships relevant to the contents of this paper
to disclose.
NR 48
TC 26
Z9 27
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-8798
J9 JACC-CARDIOVASC INTE
JI JACC-Cardiovasc. Interv.
PD SEP
PY 2011
VL 4
IS 9
BP 1020
EP 1027
DI 10.1016/j.jcin.2011.06.010
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 829RU
UT WOS:000295602800011
PM 21939943
ER
PT J
AU Kong, YCM
Brown, NK
Flynn, JC
McCormick, DJ
Brusic, V
Morris, GP
David, CS
AF Kong, Yi-chi M.
Brown, Nicholas K.
Flynn, Jeffrey C.
McCormick, Daniel J.
Brusic, Vladimir
Morris, Gerald P.
David, Chella S.
TI Efficacy of HLA-DRB1*03:01 and H2E transgenic mouse strains to correlate
pathogenic thyroglobulin epitopes for autoimmune thyroiditis
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Autoimmune thyroiditis; HLA-DR3; H2E; Transgenic mice; Thyroglobulin
peptides
ID CLASS-II TRANSGENES; REGULATORY T-CELLS; HLA-DR; PEPTIDE-BINDING;
E-ALPHA; MURINE THYROIDITIS; MICE LACKING; MOLECULES; SUSCEPTIBILITY;
GENES
AB Thyroglobulin (Tg), a homodimer of 660 kD comprising 2748 amino acids, is the largest autoantigen known. The prevalence of autoimmune thyroid disease, including Hashimoto's thyroiditis and Graves' disease, has provided the impetus for identifying pathogenic T cell epitopes from human Tg over two decades. With no known dominant epitopes, the search has long been a challenge for investigators. After identifying HLA-DRB1*03:01 (HLA-DR3) and H2E(b) as susceptibility alleles for Tg-induced experimental autoimmune thyroiditis in transgenic mouse strains, we searched for naturally processed T cell epitopes with MHC class II-binding motif anchors and tested the selected peptides for pathogenicity in these mice. The thyroiditogenicity of one peptide, hTg2079, was confirmed in DR3 transgenic mice and corroborated in clinical studies. In H2E(b)-expressing transgenic mice, we identified three T cell epitopes from mouse Tg, mTg179, mTg409 and mTg2342, based on homology to epitopes hTg179, hTg410 and hTg2344, respectively, which we and others have found stimulatory or pathogenic in both DR3- and H2E-expressing mice. The high homology among these peptides with shared presentation by DR3. H2E(b) and H2E(k) molecules led us to examine the binding pocket residues of these class II molecules. Their similar binding characteristics help explain the pathogenic capacity of these T cell epitopes. Our approach of using appropriate human and murine MHC class II transgenic mice, combined with the synthesis and testing of potential pathogenic Tg peptides predicted from computational models of MHC-binding motifs, should continue to provide insights into human autoimmune thyroid disease. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Kong, Yi-chi M.; Brown, Nicholas K.; Flynn, Jeffrey C.; Morris, Gerald P.] Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA.
[McCormick, Daniel J.] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[Brusic, Vladimir] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[David, Chella S.] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN 55905 USA.
RP Kong, YCM (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, 540 E Canfield Ave, Detroit, MI 48201 USA.
EM ykong@med.wayne.edu
RI Morris, Gerald/I-3680-2016
OI Morris, Gerald/0000-0002-1097-4453
FU NIDDK [DK45950]; DOD [BC098075]
FX This work was supported by DK45950 from NIDDK and DOD BC098075 (YMK).
NR 77
TC 4
Z9 4
U1 0
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD SEP
PY 2011
VL 37
IS 2
SI SI
BP 63
EP 70
DI 10.1016/j.jaut.2011.05.010
PG 8
WC Immunology
SC Immunology
GA 831UE
UT WOS:000295755800002
PM 21683551
ER
PT J
AU Hasturk, H
Kantarci, A
Ghattas, M
Schmidt, M
Giordano, RA
Ashman, A
Diekwisch, TG
Van Dyke, T
AF Hasturk, Hatice
Kantarci, Alpdogan
Ghattas, Mazen
Schmidt, Marcella
Giordano, Russell A.
Ashman, Arthur
Diekwisch, Thomas G.
Van Dyke, Thomas
TI The Use of Light/Chemically Hardened Polymethylmethacrylate,
Polyhydroxyethylmethacrylate, and Calcium Hydroxide Graft Material in
Combination With Polyanhydride Around Implants in Minipigs: Part I:
Immediate Stability and Function
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE Alveolar ridge augmentation; bone replacement material; dental implants;
models; animal; tooth extraction
ID CONTROLLED CLINICAL-TRIALS; ALVEOLAR BONE LOSS; DENTAL IMPLANTS;
FOLLOW-UP; EXTRACTION SOCKETS; RESORBABLE MEMBRANE; OSTEOTOME TECHNIQUE;
BARRIER MEMBRANES; TITANIUM IMPLANTS; MOLAR FURCATIONS
AB Background: The present study is designed as a proof-of-concept study to evaluate light/chemical hardening technology and a newly formulated polymethylmethacrylate, polyhydroxyethylmethacrylate, and calcium hydroxide (PPCH) plus polyanhydride (PA) (PPCH-PA) composite graft material as a bone substitute compared to positive and negative controls in a minipig model.
Methods: PPCH-PA (composite graft); PPCH alone (positive control), PA alone (positive control), and no graft (negative control) were compared. Four mandibular premolar teeth per quadrant were extracted; a total of 48 implants were placed into sockets in three minipigs. Abutments were placed protruding into the oral cavity 4 mm in height for immediate loading. Crestal areas and intrabony spaces were filled with PPCH-PA, PPCH, or PA using a three-phase delivery system in which all graft materials were hardened by a light cure. In the negative control group, implant sites were left untreated. At 12 weeks, block sections containing implants were obtained. Evaluations included periodontal probing, pullout-force load, and stability measurements to determine implant stability, radiographs to examine bone levels, and scanning electron microscopy (SEM)-energy-dispersed spectroscopy to determine bone-to-implant contact.
Results: Probing measurements did not reveal any pathologic pocket formation or bone loss. Radiographs revealed that immediate implant placement and loading resulted in bone at or slightly apical to the first thread of the implant in all groups at 12 weeks. Stability test values showed a relative clinical stability for all implants (range: -7 to +1); however, implants augmented with PPCH-PA exhibited a statistically significantly greater stability compared to all other groups (P <0.05). The newly formed bone in PPCH-PA-treated sites was well organized with less marrow spaces and well-distributed osteocytes. SEM revealed a tighter implant-socket interface in the PPCH-PA group compared to other groups with reduced microfissures and implant-bone interface fractures during pullout testing, whereas implants treated with PA or no graft showed approximate to 10-mu m microfissures between the implant and bone with fractures of the intrathread bone.
Conclusions: The newly formulated chemically hardened graft material PPCH-PA was useful in immediate implant placement after tooth extraction and resulted in greater stability and a well-organized implant-bone interface with immediate loading, especially in those areas where cancellous bone was present. The results of this proof-of-concept study warranted further research investigating different healing times and longer durations. J Periodontol 2011;82:1339-1352.
C1 [Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA.
[Ghattas, Mazen] Boston Univ, Dept Periodontol & Oral Biol, Sch Dent Med, Boston, MA 02215 USA.
[Giordano, Russell A.] Boston Univ, Dept Restorat Sci Biomat, Boston, MA 02215 USA.
[Schmidt, Marcella; Diekwisch, Thomas G.] Univ Illinois, Coll Dent, Dept Oral Biol, Brodie Lab Craniofacial Genet, Chicago, IL USA.
[Ashman, Arthur] NYU, Coll Dent, Dept Periodontol & Implant Dent, New York, NY USA.
RP Hasturk, H (reprint author), Forsyth Inst, Dept Periodontol, 245 1st St,Suite 1757, Cambridge, MA 02142 USA.
EM hhasturk@forsyth.org
FU Bioplant R&D, Westport, Connecticut; United States Public Health
Service, NIH, Bethesda, Maryland [DE019938]
FX This study was supported, in part, by Bioplant R&D, Westport,
Connecticut and the United States Public Health Service, NIH, Bethesda,
Maryland (grant DE019938; to Dr. Van Dyke). The authors thank Dr. Devon
A. Shipp, Department of Chemistry and Biomolecular Science, Clarkson
University, Potsdam, New York; the veterinary and animal care personnel,
Mimi Crowley, Sharron Kirchain, Michelle Callihan, Rosa Yip, and Sergio
Maura at the BUMC LASC; and Ronald L'Herault, laboratory supervisor,
Boston University School of Dental Medicine Biomaterials Laboratory,
Boston, Massachusetts, for their technical assistance during the study.
Implants and the implant equipment were kindly donated by Biomet 3i,
Palm Beach Gardens, Florida. Specialty surgical instruments were a gift
from Hu-Friedy, Chicago, Illinois. Dr. Ashman, chief executive officer
of Bioplant R&D, is the inventor of and has issued patents on the light
and chemically cured materials (PPCH-PA [composite graft of hard tissue
replacement and polyanhydride with light/chemical hardening technology])
tested in this study. Drs. Hasturk, Kantarci, Ghattas, Schmidt,
Giordano, Diekwisch, and Van Dyke declare no financial interests related
to this study.
NR 66
TC 5
Z9 6
U1 0
U2 7
PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
J9 J PERIODONTOL
JI J. Periodont.
PD SEP
PY 2011
VL 82
IS 9
BP 1339
EP 1352
DI 10.1902/jop.2011.100617
PG 14
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 831JI
UT WOS:000295726000013
PM 21342001
ER
PT J
AU Parikh, CR
Devarajan, P
Zappitelli, M
Sint, K
Thiessen-Philbrook, H
Li, S
Kim, RW
Koyner, JL
Coca, SG
Edelstein, CL
Shlipak, MG
Garg, AX
Krawczeski, CD
AF Parikh, Chirag R.
Devarajan, Prasad
Zappitelli, Michael
Sint, Kyaw
Thiessen-Philbrook, Heather
Li, Simon
Kim, Richard W.
Koyner, Jay L.
Coca, Steven G.
Edelstein, Charles L.
Shlipak, Michael G.
Garg, Amit X.
Krawczeski, Catherine D.
CA TRIBE-AKI Consortium
TI Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes
after Pediatric Cardiac Surgery
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GELATINASE-ASSOCIATED LIPOCALIN; ACUTE-RENAL-FAILURE; CONGENITAL
HEART-DISEASE; ROC CURVE; NGAL; CHILDREN; MARKERS; INCREASES; DIALYSIS;
THERAPY
AB Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.
C1 [Parikh, Chirag R.; Sint, Kyaw; Coca, Steven G.] Yale Univ, Sch Med, Nephrol Sect, New Haven, CT USA.
[Parikh, Chirag R.; Sint, Kyaw; Coca, Steven G.] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT 06516 USA.
[Devarajan, Prasad; Krawczeski, Catherine D.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Zappitelli, Michael] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat,Div Nephrol, Montreal, PQ H3H 1P3, Canada.
[Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada.
[Li, Simon] Yale Univ, Sch Med, Dept Pediat, Div Pediat Crit Care Med, New Haven, CT 06510 USA.
[Kim, Richard W.] Yale Univ, Sch Med, Div Pediat Cardiac Surg, New Haven, CT USA.
[Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA.
[Edelstein, Charles L.] Univ Colorado, Div Renal Dis, Denver, CO 80202 USA.
[Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Room 21, West Haven, CT 06516 USA.
EM chirag.parikh@yale.edu
FU American Heart Association; National Heart, Lung, and Blood Institute
[R01 HL-085757]; National Center for Research Resources [UL1 RR024139]
FX The research reported in this article was supported by the American
Heart Association Clinical Development Award, Grant R01 HL-085757 from
the National Heart, Lung, and Blood Institute. The study was also
supported by CTSA Grant Number UL1 RR024139 from the National Center for
Research Resources. This work is Clinical Trials.gov number NCT00774137.
The urine biomarker assays were donated by Abbott Diagnostics. Plasma
NGAL was donated by Biosite, Inc.
NR 36
TC 140
Z9 141
U1 1
U2 7
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD SEP
PY 2011
VL 22
IS 9
BP 1737
EP 1747
DI 10.1681/ASN.2010111163
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 831CH
UT WOS:000295705800021
PM 21836147
ER
PT J
AU Parikh, CR
Coca, SG
Thiessen-Philbrook, H
Shlipak, MG
Koyner, JL
Wang, Z
Edelstein, CL
Devarajan, P
Patel, UD
Zappitelli, M
Krawczeski, CD
Passik, CS
Swaminathan, M
Garg, AX
AF Parikh, Chirag R.
Coca, Steven G.
Thiessen-Philbrook, Heather
Shlipak, Michael G.
Koyner, Jay L.
Wang, Zhu
Edelstein, Charles L.
Devarajan, Prasad
Patel, Uptal D.
Zappitelli, Michael
Krawczeski, Catherine D.
Passik, Cary S.
Swaminathan, Madhav
Garg, Amit X.
CA TRIBE-AKI Consortium
TI Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes
after Adult Cardiac Surgery
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GELATINASE-ASSOCIATED LIPOCALIN; ACUTE-RENAL-FAILURE; ACUTE CORONARY
SYNDROMES; MORTALITY; RISK; RECLASSIFICATION; ASSOCIATION; DYSFUNCTION;
MARKERS; MICE
AB Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery. (Clinical Trials.gov number, NCT00774137).
C1 [Parikh, Chirag R.; Coca, Steven G.; Wang, Zhu] Yale Univ, Sch Med, Nephrol Sect, New Haven, CT USA.
[Parikh, Chirag R.; Coca, Steven G.; Wang, Zhu] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT USA.
[Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada.
[Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA.
[Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA.
[Edelstein, Charles L.] Univ Colorado, Div Renal Dis, Denver, CO 80202 USA.
[Devarajan, Prasad; Krawczeski, Catherine D.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
[Swaminathan, Madhav] Duke Univ, Sch Med, Dept Anesthesiol, Div Cardiothorac Anesthesiol & Crit Care Med, Durham, NC USA.
[Zappitelli, Michael] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat,Div Nephrol, Montreal, PQ H3H 1P3, Canada.
[Passik, Cary S.] Danbury Hosp, Dept Cardiothorac Surg, Danbury, CT USA.
[Passik, Cary S.] Univ Vermont, Coll Med, Burlington, VT USA.
RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35 A,Room 21, West Haven, CT 06516 USA.
EM chirag.parikh@yale.edu
FU American Heart Association from the National Heart, Lung, and Blood
Institute [R01 HL-085757]; National Center for Research Resources [UL1
RR024139]; Abbott Diagnostics; Biosite, Inc.
FX We would also like to thank the nursing and support staff of the
preadmission clinic, anesthesia units, and the cardiac care units at all
of the participating centers. The research reported in this article was
supported by the American Heart Association Clinical Development award
(grant R01 HL-085757) from the National Heart, Lung, and Blood
Institute. The study was also supported by a Clinical and Translational
Science Award grant (UL1 RR024139) from the National Center for Research
Resources. The urine biomarker assays were donated by Abbott
Diagnostics, and plasma NGAL was donated by Biosite. The granting
agencies, Abbott Diagnostics and Biosite, Inc., did not participate in
the protocol development, analysis, or interpretation of the results.
NR 36
TC 188
Z9 190
U1 1
U2 12
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD SEP
PY 2011
VL 22
IS 9
BP 1748
EP 1757
DI 10.1681/ASN.2010121302
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 831CH
UT WOS:000295705800022
PM 21836143
ER
PT J
AU Vladutiu, GD
Isackson, PJ
Kaufman, K
Harley, JB
Cobb, B
Christopher-Stine, L
Wortmann, RL
AF Vladutiu, Georgirene D.
Isackson, Paul J.
Kaufman, Kenneth
Harley, John B.
Cobb, Beth
Christopher-Stine, Lisa
Wortmann, Robert L.
TI Genetic risk for malignant hyperthermia in non-anesthesia-induced
myopathies
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Malignant hyperthermia; Statin myopathy; RYR1 gene mutations; Metabolic
muscle disease; Coexisting genetic risk
ID DEPENDENT CALCIUM-CHANNEL; CENTRAL CORE DISEASE; SKELETAL-MUSCLE;
RYANODINE RECEPTOR; EXERTIONAL RHABDOMYOLYSIS; SUSCEPTIBILITY LOCUS;
CONGENITAL MYOPATHY; MOLECULAR-BASIS; RYR1 MUTATIONS; FAMILIES
AB Malignant hyperthermia (MH) is a pharmacogenetic, autosomal dominantly inherited disorder of skeletal muscle triggered by volatile anesthetics and infrequently by extreme exertion and heat exposure. MH has variable penetrance with an incidence ranging from 1 in 5000 to 1 in 50,000-100,000 anesthesias. Mutations in the ryanodine receptor gene, RYR1, are found in 50-70% of cases. We hypothesized that a portion of patients with drug-induced muscle diseases, unrelated to anesthesia, such as severe statin myopathy, have underlying genetic liability that may include RYR1 gene mutations. DNA samples were collected from 885 patients in 4 groups: severe statin myopathy (n = 197), mild statin myopathy (n = 163), statin-tolerant controls (n = 133), and non-drug-induced myopathies of unknown etiology characterized by exercise-induced muscle pain and weakness (n = 392). Samples were screened for 105 mutations and variants in 26 genes associated with 7 categories of muscle disease including 34 mutations and variants in the RYR1 gene. Disease-causing mutations or variants in RYR1 were present in 3 severe statin myopathy cases, 1 mild statin myopathy case, 8 patients with non-drug-induced myopathy, and none in controls. These results suggest that disease-causing mutations and certain variants in the RYR1 gene may contribute to underlying genetic risk for non-anesthesia-induced myopathies and should be included in genetic susceptibility screening in patients with severe statin myopathy and in patients with non-statin-induced myopathies of unknown etiology. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Vladutiu, Georgirene D.; Isackson, Paul J.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14203 USA.
[Vladutiu, Georgirene D.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Neurol, Buffalo, NY 14203 USA.
[Vladutiu, Georgirene D.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pathol & Anat Sci, Buffalo, NY 14203 USA.
[Kaufman, Kenneth] Univ Oklahoma, Oklahoma Med Res Fdn, Hlth Sci Ctr, Oklahoma City, OK USA.
[Kaufman, Kenneth] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA.
[Harley, John B.; Cobb, Beth] Cincinnati Childrens Hosp, Dept Med, Cincinnati, OH USA.
[Christopher-Stine, Lisa] Johns Hopkins Univ, Dept Med, Johns Hopkins Sch Med, Myositis Ctr, Baltimore, MD USA.
[Wortmann, Robert L.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA.
RP Vladutiu, GD (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, 100 High St, Buffalo, NY 14203 USA.
EM gdv@buffalo.edu
FU NHLBI [1R41HL093956-01, RO1HL085800]; UB Office of the Vice President
for Research
FX This work was supported by grants from the NHLBI (1R41HL093956-01 and
RO1HL085800; GDV) and an Interdisciplinary Research and Creative
Activities Award from the UB Office of the Vice President for Research
(GDV). We are especially grateful to Dr. Nyamkhishig Sambuughin for her
assistance in the interpretation of RYR1 gene variant data. We thank Dr.
Henry Rosenberg for his helpful comments during the preparation of this
manuscript. We thank Ms. Shanping Huang for technical assistance with
preparation, organization and individual genotyping of genomic DNA
samples and Ms. Catherine Kern for coordination of collaborating centers
and maintenance of the participant database. We also are grateful to
physicians and their patients from medical centers including the Mayo
Clinic, Rochester, MN; Cedars Sinai Medical Center, Los Angeles, CA;
Texas Children's Hospital, Houston, TX; Walter Reed Army Medical Center,
Washington, DC; the Oregon Health 8: Science University, Portland, OR;
Yale-New Haven Medical Center, New Haven, CT; McMaster University,
Hamilton, Ontario, Canada; and the VA Western New York Healthcare
System, Buffalo, NY.
NR 38
TC 24
Z9 24
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD SEP-OCT
PY 2011
VL 104
IS 1-2
SI SI
BP 167
EP 173
DI 10.1016/j.ymgme.2011.07.001
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 823UF
UT WOS:000295151300027
PM 21795085
ER
PT J
AU Arar, N
Seo, J
Abboud, HE
Parchman, M
Noel, P
AF Arar, Nedal
Seo, Joann
Abboud, Hanna E.
Parchman, Michael
Noel, Polly
TI Veterans' experience in using the online Surgeon General's family health
history tool
SO PERSONALIZED MEDICINE
LA English
DT Article
DE family health history; genomic services; Surgeon General's online tool
ID GENOMIC MEDICINE; PRIMARY-CARE; SATISFACTION; INFORMATION; DISEASE;
POPULATION; PREVENTION; COMMUNITY; INTERNET; DELIVERY
AB Aim: To assess veterans' experience and satisfaction in using the Surgeon General's (SG) online family health history (FHH) tool, and determine the perceived facilitators and barriers to using the online SG-FHH tool. Materials & methods: A mixed-method using both qualitative and quantitative approaches was employed in this study. A total of 35 veterans at the VA Medical Center in San Antonio, Texas, USA were invited to enter their FHH information using the online SG-FHH tool, complete the study's satisfaction survey and participate in a short semi-structured interview. The goal of the semi-structured interviews was to assess participants perceived facilitators and barriers to using the online SG-FHH tool. All participants were also provided with a printed copy of their pedigree, which was generated by the SG-FHH tool and were encouraged to share it with their relatives and providers. Results: The majority of participants (91%) said that they had access to a computer with internet capability and 77% reported that they knew how to use a computer. More than two-thirds of the participants felt that items on the SG-FHH tool were easy to read and felt that FHH categories were relevant to their family's health. Approximately 94% of participants viewed the SG-FHH tool as useful, and the majority of participants (97%) indicated that they were likely to recommend the tool to others. Content analysis of the semi-structured interviews highlighted several barriers to veterans' use of the SG-FHH tool and their FHH information. These included: lack of patients' knowledge regarding their relatives' FHH, and privacy and confidentiality concerns. Conclusion: This study provides information on the performance and functionality of an inexpensive and widely accessible method for FHH collection. Furthermore, our findings highlight several opportunities and challenges facing the utilization of FHH information as a clinical and genomic tool at the Veterans Health Administration (VHA). The results suggest that strategies that improve veterans' knowledge regarding the importance of their FHH information and that address their concerns about privacy and confidentiality may enhance the successful implementation of FHH information into VHA clinical practice. Implications: identifying a locally accepted method for FHH collection and documentation which can be conducted outside of the patient visit will reduce time burdens for providers and patients and allow for a focus on other important topics during clinic visits. Improvement in familial risk screening and assessment will enable the VHA to be prepared for personalized medicine and focus their resources on promoting critically important health behaviors for populations with the highest risk of developing chronic diseases and their complications.
C1 [Arar, Nedal; Seo, Joann; Abboud, Hanna E.; Parchman, Michael; Noel, Polly] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Arar, Nedal; Seo, Joann; Abboud, Hanna E.; Parchman, Michael; Noel, Polly] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Arar, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM ararn@uthscsa.edu
OI Parchman, Michael/0000-0001-7129-2889
FU VHA-HSR and D [DNA 08-129, PPO 09-241]; NIH [UL1RR025767]
FX This work was supported by the VHA-HSR and D (DNA 08-129 and PPO 09-241,
PI: Nedal Arar). This study was partly funded by the Clinical and
Translational Science Award (CTSA) - NIH grant (UL1RR025767). The
authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 35
TC 7
Z9 7
U1 1
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1741-0541
J9 PERS MED
JI Pers. Med.
PD SEP
PY 2011
VL 8
IS 5
BP 523
EP 532
DI 10.2217/PME.11.53
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 832JX
UT WOS:000295802100010
PM 22076122
ER
PT J
AU Dileepan, T
Linehan, JL
Moon, JJ
Pepper, M
Jenkins, MK
Cleary, PP
AF Dileepan, Thamotharampillai
Linehan, Jonathan L.
Moon, James J.
Pepper, Marion
Jenkins, Marc K.
Cleary, Patrick P.
TI Robust Antigen Specific Th17 T Cell Response to Group A Streptococcus Is
Dependent on IL-6 and Intranasal Route of Infection
SO PLOS PATHOGENS
LA English
DT Article
ID LYMPHOID-TISSUE; HOST-DEFENSE; M1 PROTEIN; IN-VITRO; PATHOGENESIS;
PYOGENES; HYALURONAN; GENERATION; PLASTICITY; INDUCTION
AB Group A streptococcus (GAS, Streptococcus pyogenes) is the cause of a variety of clinical conditions, ranging from pharyngitis to autoimmune disease. Peptide-major histocompatibility complex class II (pMHCII) tetramers have recently emerged as a highly sensitive means to quantify pMHCII-specific CD4(+) helper T cells and evaluate their contribution to both protective immunity and autoimmune complications induced by specific bacterial pathogens. In lieu of identifying an immunodominant peptide expressed by GAS, a surrogate peptide (2W) was fused to the highly expressed M1 protein on the surface of GAS to allow in-depth analysis of the CD4(+) helper T cell response in C57BL/6 mice that express the I-A(b) MHCII molecule. Following intranasal inoculation with GAS-2W, antigen-experienced 2W:I-A(b)-specific CD4(+) T cells were identified in the nasal-associated lymphoid tissue (NALT) that produced IL-17A or IL-17A and IFN-gamma if infection was recurrent. The dominant Th17 response was also dependent on the intranasal route of inoculation; intravenous or subcutaneous inoculations produced primarily IFN-gamma(+) 2W:I-A(b+) CD4(+) T cells. The acquisition of IL-17A production by 2W: I-A(b)-specific T cells and the capacity of mice to survive infection depended on the innate cytokine IL-6. IL-6-deficient mice that survived infection became long-term carriers despite the presence of abundant IFN-gamma-producing 2W:I-A(b)-specific CD4(+) T cells. Our results suggest that an imbalance between IL-17- and IFN-gamma-producing CD4(+) T cells could contribute to GAS carriage in humans.
C1 [Dileepan, Thamotharampillai; Linehan, Jonathan L.; Pepper, Marion; Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
[Moon, James J.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Cambridge, MA USA.
RP Dileepan, T (reprint author), Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
EM dile0003@umn.edu
RI Jenkins, Marc/G-1063-2012
OI Jenkins, Marc/0000-0001-8009-7655
FU National Institutes of Health [AI059533, AI39614]; [P30 CA77598]
FX This work was supported by National Institutes of Health Grant AI059533
to P. P. C and National Institutes of Health Grant AI39614 to M.K.J. We
would like to acknowledge the assistance of the Flow Cytometry Core
Facility of the Masonic Cancer Center, a comprehensive cancer center
designated by the National Cancer Institute, supported in part by P30
CA77598. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 43
TC 33
Z9 33
U1 0
U2 5
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 SEP
PY 2011
VL 7
IS 9
AR e1002252
DI 10.1371/journal.ppat.1002252
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 827DY
UT WOS:000295409000052
PM 21966268
ER
PT J
AU Gnanakaran, S
Bhattacharya, T
Daniels, M
Keele, BF
Hraber, PT
Lapedes, AS
Shen, TY
Gaschen, B
Krishnamoorthy, M
Li, H
Decker, JM
Salazar-Gonzalez, JF
Wang, SY
Jiang, CL
Gao, F
Swanstrom, R
Anderson, JA
Ping, LH
Cohen, MS
Markowitz, M
Goepfert, PA
Saag, MS
Eron, JJ
Hicks, CB
Blattner, WA
Tomaras, GD
Asmal, M
Letvin, NL
Gilbert, PB
DeCamp, AC
Magaret, CA
Schief, WR
Ban, YEA
Zhang, M
Soderberg, KA
Sodroski, JG
Haynes, BF
Shaw, GM
Hahn, BH
Korber, B
AF Gnanakaran, S.
Bhattacharya, Tanmoy
Daniels, Marcus
Keele, Brandon F.
Hraber, Peter T.
Lapedes, Alan S.
Shen, Tongye
Gaschen, Brian
Krishnamoorthy, Mohan
Li, Hui
Decker, Julie M.
Salazar-Gonzalez, Jesus F.
Wang, Shuyi
Jiang, Chunlai
Gao, Feng
Swanstrom, Ronald
Anderson, Jeffrey A.
Ping, Li-Hua
Cohen, Myron S.
Markowitz, Martin
Goepfert, Paul A.
Saag, Michael S.
Eron, Joseph J.
Hicks, Charles B.
Blattner, William A.
Tomaras, Georgia D.
Asmal, Mohammed
Letvin, Norman L.
Gilbert, Peter B.
DeCamp, Allan C.
Magaret, Craig A.
Schief, William R.
Ban, Yih-En Andrew
Zhang, Ming
Soderberg, Kelly A.
Sodroski, Joseph G.
Haynes, Barton F.
Shaw, George M.
Hahn, Beatrice H.
Korber, Bette
TI Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins
Associated with either Early or Chronic Infections
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODY-RESPONSES; N-LINKED
GLYCOSYLATION; SUBTYPE-C INFECTION; CYTOPLASMIC TAIL; CROSS-VALIDATION;
IMMUNE EVASION; HETEROSEXUAL TRANSMISSION; SELECTIVE TRANSMISSION;
VACCINE DEVELOPMENT
AB Here we have identified HIV-1 B clade Envelope (Env) amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.
C1 [Gnanakaran, S.; Bhattacharya, Tanmoy; Daniels, Marcus; Hraber, Peter T.; Lapedes, Alan S.; Shen, Tongye; Gaschen, Brian; Krishnamoorthy, Mohan; Zhang, Ming; Korber, Bette] Los Alamos Natl Lab, Los Alamos, NM USA.
[Bhattacharya, Tanmoy; Korber, Bette] Santa Fe Inst, Santa Fe, NM 87501 USA.
[Keele, Brandon F.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Keele, Brandon F.; Li, Hui; Decker, Julie M.; Salazar-Gonzalez, Jesus F.; Wang, Shuyi; Goepfert, Paul A.; Saag, Michael S.; Shaw, George M.; Hahn, Beatrice H.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Keele, Brandon F.; Li, Hui; Decker, Julie M.; Salazar-Gonzalez, Jesus F.; Wang, Shuyi; Goepfert, Paul A.; Saag, Michael S.; Shaw, George M.; Hahn, Beatrice H.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Shen, Tongye] Univ Tennessee, Ctr Biophys Mol, Knoxville, TN USA.
[Shen, Tongye] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN USA.
[Jiang, Chunlai] Jilin Univ, Sch Life Sci, Natl Engn Lab AIDS Vaccine, Changchun 130023, Peoples R China.
[Jiang, Chunlai; Gao, Feng; Hicks, Charles B.; Tomaras, Georgia D.; Soderberg, Kelly A.; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Jiang, Chunlai; Gao, Feng; Hicks, Charles B.; Tomaras, Georgia D.; Soderberg, Kelly A.; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Jiang, Chunlai; Gao, Feng; Hicks, Charles B.; Tomaras, Georgia D.; Soderberg, Kelly A.; Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA.
[Swanstrom, Ronald; Anderson, Jeffrey A.; Ping, Li-Hua; Cohen, Myron S.; Eron, Joseph J.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA.
[Swanstrom, Ronald; Anderson, Jeffrey A.; Ping, Li-Hua; Cohen, Myron S.; Eron, Joseph J.] Univ N Carolina, Div Infect Dis, Ctr AIDS Res, Chapel Hill, NC USA.
[Markowitz, Martin] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA.
[Blattner, William A.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Asmal, Mohammed; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Letvin, Norman L.] Harvard Univ, Sch Med, Dept Med, Div Viral Pathogenesis, Boston, MA USA.
[Gilbert, Peter B.; DeCamp, Allan C.; Magaret, Craig A.] Fred Hutchinson Canc Res Ctr, Vaccine Infect Dis Div, Seattle, WA 98104 USA.
[Schief, William R.; Ban, Yih-En Andrew] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Ban, Yih-En Andrew] Arzeda Corp, Seattle, WA USA.
[Zhang, Ming] Univ Georgia, Coll Publ Hlth, Dept Epidemiol & Biostat, Athens, GA 30602 USA.
[Sodroski, Joseph G.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
RP Gnanakaran, S (reprint author), Los Alamos Natl Lab, Los Alamos, NM USA.
EM btk@lanl.gov
RI Shen, Tongye/A-9718-2008; Bhattacharya, Tanmoy/J-8956-2013; Tomaras,
Georgia/J-5041-2016;
OI Shen, Tongye/0000-0003-1495-3104; Bhattacharya,
Tanmoy/0000-0002-1060-652X; Gnanakaran, S/0000-0002-9368-3044; Korber,
Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897
FU Division of AIDS, NIAID, NIH for the Center for HIV/AIDS Vaccine
Immunology (CHAVI) [AI06785]
FX This work was funded by the a grant from the Division of AIDS, NIAID,
NIH for the Center for HIV/AIDS Vaccine Immunology (CHAVI) AI06785. This
study was undertaken as part of our response to the CHAVI call, however,
and in this sense it was at the request of the NIH that we initiated
this work, but it was implemented, details were designed, and the
specific experiments and analyses undertaken by CHAVI consortium. The
supercomputing facility at Los Alamos National Laboratory also
contributed computational resources. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 122
TC 63
Z9 64
U1 3
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2011
VL 7
IS 9
AR e1002209
DI 10.1371/journal.ppat.1002209
PG 19
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 827DY
UT WOS:000295409000017
PM 21980282
ER
PT J
AU Jain, FA
Brooks, JO
Larsen, KA
Kelly, SE
Bode, RH
Sweeney, GA
Stern, TA
AF Jain, Felipe A.
Brooks, John O., III
Larsen, Kenneth A.
Kelly, Susan E.
Bode, Robert H.
Sweeney, Gerard A.
Stern, Theodore A.
TI Individual Risk Profiles for Postoperative Delirium after Joint
Replacement Surgery
SO PSYCHOSOMATICS
LA English
DT Article
ID MENTAL-STATE-EXAMINATION; ELDERLY-PATIENTS; HIP FRACTURE; BIPOLAR
DISORDER; PREDICTIVE MODEL; CONTROLLED-TRIAL; BLOOD-PRESSURE;
PREVENTION; VALIDATION; DONEPEZIL
AB Background: Delirium occurs in nearly half of older patients after joint replacement surgery. However, risk profiles for developing delirium have not been established. Objective: We sought to identify risk profiles for delirium in patients following joint replacement surgery. Method: Based on data from a randomized, double-blind, placebo-controlled trial of olanzapine (10 mg) as delirium prophylaxis in 400 patients (67-81 years old) undergoing hip or knee replacement surgery, we performed a signal detection analysis to develop risk profiles for postsurgical delirium (using baseline patient characteristics, iatrogenic factors, and physiologic response parameters). Results: Olanzapine reduced the incidence of delirium by 63% relative to placebo. Among patients receiving placebo, those with an ASA class = 3 and age >= 74 years had a 64% risk of delirium. Those with ASA class < 3 still had a 67% risk of delirium if postoperative oxygen saturation was < 95%. Patients who received olanzapine had an 83% risk of developing delirium if they received >= 42.5 mg equivalents of intra-operative morphine, were a 74 years old, and had a mean arterial pressure (MAP) < 90 mm Hg at the presurgical screening visit. Patients with the lowest risk (6%) of developing delirium received olanzapine had a hematocrit >= 28%, and a presurgical MAP >= 90. Conclusion: Although use of prophylactic olanzapine reduced the incidence of delirium, subsets of patients remained likely to develop delirium. The risk of developing delirium may be reduced through prophylactic dispensation of olanzapine, maintaining optimal perfusion and oxygenation, and limiting intra-operative opioids. (Psychosomatics 2011; 52:410-416)
C1 [Jain, Felipe A.; Brooks, John O., III] UCLA Semel Inst Neurosci & Human Behav, Dept Psychiat, Boston, MA USA.
New England Baptist Hosp, Boston, MA USA.
[Larsen, Kenneth A.; Kelly, Susan E.; Sweeney, Gerard A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Bode, Robert H.] Beth Israel Deaconess Med Ctr, Dept Anesthesiol, Boston, MA 02215 USA.
[Kelly, Susan E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Brooks, JO (reprint author), 760 Westwood Plaza,B8-267, Los Angeles, CA 90024 USA.
EM john.brooks@ucla.edu
FU Doris Duke Charitable Foundation; Pfizer
FX This work was supported by a grant from the Doris Duke Charitable
Foundation to Harvard Medical School to fund a Clinical Research
Fellowship awarded to FAJ. TAS has been a consultant to, and has been on
the speaker's bureau of; Eli Lilly and has been a consultant to, and
shareholder of WiFiMed, the company that designed the Tablet PC data
management software. JOB is on the speaker's bureau for Merck, Sunovion,
and Pfizer, and has received research funding from Pfizer. No other
authors reported conflicts of interest.
NR 36
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD SEP-OCT
PY 2011
VL 52
IS 5
BP 410
EP 416
PG 7
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 825BD
UT WOS:000295245000002
PM 21907058
ER
PT J
AU Greer, JA
Solis, JM
Temel, JS
Lennes, IT
Prigerson, HG
Maciejewski, PK
Pirl, WF
AF Greer, Joseph A.
Solis, Jessica M.
Temel, Jennifer S.
Lennes, Inga T.
Prigerson, Holly G.
Maciejewski, Paul K.
Pirl, William F.
TI Anxiety Disorders in Long-Term Survivors of Adult Cancers
SO PSYCHOSOMATICS
LA English
DT Article
ID NATIONAL-COMORBIDITY-SURVEY; POSTTRAUMATIC-STRESS-DISORDER; SUPPORTIVE
CARE NEEDS; SURVEY REPLICATION; DEPRESSION; DIAGNOSIS; SAMPLE
AB Background: Little is known about the prevalence of anxiety disorders among long-term survivors of adult cancers. Using data from the National Comorbidity Survey Replication (NCS-R), we compared rates of anxiety disorders between long-term cancer survivors and individuals without a histoty of cancer. Methods: A nationally representative sample of 9282 adults participated in a household survey to assess the prevalence of DSM-IV psychiatric disorders, a subset of whom also answered questions about medical comorbidities, including cancer. Long-term survivors were defined as those who received an adult cancer diagnosis at least 5 years before the survey. Multiple logistic regression analyses were used to examine associations between cancer histoty and anxiety disorders in the past year. Results: The NCS-R sample consisted of 225 long-term cancer survivors and 5337 people without a history of cancer. Controlling for socio-demographic variables, long-term cancer survivors were more likely to have an anxiety disorder (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.04-2.13), including specific phobia (OR: 1.59, 95% CI: 1.06-2.44) and medical phobia (OR: 3.45, 95% CI: 1.15-10.0), during the past 12 months compared with those without cancer histories. Rates for social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, panic disorder, and agoraphobia were not significantly different between groups. Conclusion: Longterm survivors of adult cancers were more likely to have an anxiety disorder diagnosis, namely specific phobia, in the past 12 months compared with the general public. Further longitudinal study is needed to clarify the timing and course of anxiety relative to the cancer diagnosis. (Psychosomatics 2011; 52:417-423)
C1 [Greer, Joseph A.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Canc, Boston, MA 02114 USA.
[Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Prigerson, Holly G.; Maciejewski, Paul K.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Greer, JA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Canc, WACC 812,15 Parkman St, Boston, MA 02114 USA.
EM jgreer2@partners.org
FU NIH/NCI [R03 CA 128478, K23 CA 115908]
FX This study was supported by NIH/NCI R03 CA 128478 (Greet) and K23 CA
115908 (Pin).
NR 23
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U1 3
U2 6
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD SEP-OCT
PY 2011
VL 52
IS 5
BP 417
EP 423
PG 7
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 825BD
UT WOS:000295245000003
PM 21907059
ER
PT J
AU Legesse, B
Freudenreich, O
Murray, E
Price, B
AF Legesse, Benalfew
Freudenreich, Oliver
Murray, Evan
Price, Bruce
TI A Case Report of Confusional Psychosis with Abrupt Onset and Rapid
Resolution of Symptoms
SO PSYCHOSOMATICS
LA English
DT Article
ID CYCLOID PSYCHOSES; CONCORDANCE
C1 [Legesse, Benalfew; Murray, Evan; Price, Bruce] Harvard Univ, Sch Med, McLean Hosp, Dept Neurol, Belmont, MA 02478 USA.
[Freudenreich, Oliver] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.
RP Legesse, B (reprint author), Harvard Univ, Sch Med, McLean Hosp, Dept Neurol, 115 Mill St, Belmont, MA 02478 USA.
EM blegesse@partners.org
NR 16
TC 1
Z9 1
U1 0
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD SEP-OCT
PY 2011
VL 52
IS 5
BP 468
EP 471
PG 4
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 825BD
UT WOS:000295245000012
PM 21907068
ER
PT J
AU Moore, MA
Wallace, EC
Westra, SJ
AF Moore, Michael A.
Wallace, E. Christine
Westra, Sjirk J.
TI Chest Trauma in Children: Current Imaging Guidelines and Techniques
SO RADIOLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Trauma; Chest; Pediatric; CT; Radiography; Ultrasound; Algorithms;
Techniques
ID BLUNT THORACIC TRAUMA; SEVERELY INJURED PATIENTS; COMPUTED-TOMOGRAPHY;
PULMONARY CONTUSION; RIB FRACTURES; PEDIATRIC-PATIENTS; X-RAY; BRONCHIAL
RUPTURE; AORTIC RUPTURE; HELICAL CT
AB Given the heterogeneous nature of pediatric chest trauma, the optimal imaging approach is tailored to the specific patient. Chest radiography remains the most important imaging modality for initial triage. The decision to perform a chest computed tomography scan should be based on the nature of the trauma, the child's clinical condition, and the initial radiographic findings, taking the age-related pretest probabilities of serious injury into account. The principles of as low as reasonably achievable and Image Gently should be followed. The epidemiology and pathophysiology, imaging techniques, characteristic findings, and evidence-based algorithms for pediatric chest trauma are discussed.
C1 [Westra, Sjirk J.] Harvard Univ, Sch Med, Div Pediat Radiol, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Moore, Michael A.] Cork Univ Hosp, Dept Radiol, Cork, Ireland.
[Wallace, E. Christine] Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Dept Radiol, Worcester, MA 01655 USA.
RP Westra, SJ (reprint author), Harvard Univ, Sch Med, Div Pediat Radiol, Dept Radiol,Massachusetts Gen Hosp, 55 Fruit St,White 246, Boston, MA 02114 USA.
EM swestra@partners.org
NR 114
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U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-8389
EI 1557-8275
J9 RADIOL CLIN N AM
JI Radiol. Clin. N. Am.
PD SEP
PY 2011
VL 49
IS 5
BP 949
EP +
DI 10.1016/j.rcl.2011.06.002
PG 21
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 826WY
UT WOS:000295387500008
PM 21889016
ER
PT J
AU Kurth, J
DeFeo, E
Cheng, LL
AF Kurth, Johannes
DeFeo, Elita
Cheng, Leo L.
TI Magnetic resonance spectroscopy: A promising tool for the diagnostics of
human prostate cancer?
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article
DE Human prostate cancer; Metabolomics; Spectroscopy; MRS; MRSI; HRMAS
ID HR-MAS SPECTROSCOPY; PROTON NMR; PERIPHERAL ZONE; RESOLUTION; TISSUE;
OUTCOMES; MR; OVERDIAGNOSIS; METABOLITES; SPERMINE
AB Background: Prostate Cancer (CaP) is one of the topmost diagnosed malignant diseases worldwide. In developed countries, early cancer detection methods have led to an increase of incidence rates over the last decades; however, with great variance of the prognosis. There is no diagnostic tool for an exact prediction of tumor aggressiveness, thus there is a lack of adequate and optimal treatment planning.
Methods: Electronic databases (Medline, PubMed) were scanned for scientific literature. Basic concepts of magnetic resonance spectroscopy (MRS), important results and its clinical applications were extracted and reviewed in this article.
Conclusions: MRS provides crucial information about the metabolic status of human prostate samples while preserving the specimens for further investigations. Single metabolites and metabolomic profiles can be quantified to distinguish benign from malignant tissue and to predict aggressiveness, such as the recurrence rates of CaP. Studies are also anticipating that MRS might be beneficially applicable for in vivo investigations in the future. (C) 2011 Elsevier Inc. All rights reserved.
C1 [DeFeo, Elita; Cheng, Leo L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
[DeFeo, Elita; Cheng, Leo L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Charlestown, MA 02129 USA.
[Kurth, Johannes] Charite, D-13353 Berlin, Germany.
RP Cheng, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
EM cheng@nmr.mgh.harvard.edu
FU NIH [CA 115746, CA115746S2, CA141139]
FX This work was supported in part by NIH grants (CA 115746, CA115746S2,
and CA141139).
NR 37
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Z9 3
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
EI 1873-2496
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD SEP-OCT
PY 2011
VL 29
IS 5
BP 562
EP 571
DI 10.1016/j.urolonc.2011.05.016
PG 10
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 829UE
UT WOS:000295609000016
PM 21930088
ER
PT J
AU Robinson, CM
Rajaiya, J
Zhou, XH
Singh, G
Dyer, DW
Chodosh, J
AF Robinson, Christopher M.
Rajaiya, Jaya
Zhou, Xiaohong
Singh, Gurdeep
Dyer, David W.
Chodosh, James
TI The E3 CR1-gamma gene in human adenoviruses associated with epidemic
keratoconjunctivitis
SO VIRUS RESEARCH
LA English
DT Article
DE Human adenovirus type 37; CR1-gamma; 31.6K; E3 transcription unit;
Epidemic keratoconjunctivitis
ID BIOINFORMATICS ANALYSIS; GENITAL INFECTIONS; DOWN-MODULATE; SUBGROUP-D;
PROTEIN; APOPTOSIS; IDENTIFICATION; RECEPTOR; TYPE-2; REGION
AB Human adenovirus species D type 37 (HAdV-D37) is an important etiologic agent of epidemic keratoconjunctivitis. Annotation of the whole genome revealed an open reading frame (ORF) in the E3 transcription unit predicted to encode a 31.6 kDa protein. This ORF, also known as CR1-gamma, is predicted to be an integral membrane protein containing N-terminal signal sequence, luminal, transmembrane, and cytoplasmic domains. HAdV-D19 (C), another viral pathogen causing epidemic keratoconjunctivitis, contains an ORF 100% identical to its HAdV-D37 homologue but only 66% identical to other HAdV-D homologues. Kinetics of RNA expression and confirmation of splicing to the adenovirus tripartite leader sequence suggest a role for the protein product of CR1-gamma in the late stages of the viral replication cycle. Confocal microscopy is consistent with expression in the cytoplasm. Sequence analysis reveals a hypervariable luminal domain and a conserved cytoplasmic domain. The luminal domain is predicted to contain multiple N-glycosylation sites. The cytoplasmic domain contains a putative protein kinase C phosphorylation site and potential YXX phi and dileucine (LL) motifs suggesting a potential role in modification of host proteins. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Robinson, Christopher M.; Rajaiya, Jaya; Zhou, Xiaohong; Singh, Gurdeep; Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Howe Lab, Boston, MA 02114 USA.
[Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA.
RP Chodosh, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Howe Lab, 243 Charles St, Boston, MA 02114 USA.
EM james_chodosh@meei.harvard.edu
FU NIH [EY013124, P30EY014104]; Department of Ophthalmology, Harvard
Medical School from Research to Prevent Blindness, Inc.
FX Supported by NIH grants EY013124 and P30EY014104, and an unrestricted
grant to the Department of Ophthalmology, Harvard Medical School from
Research to Prevent Blindness, Inc. The funding sponsors played no role
in any aspect of the study.
NR 38
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Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD SEP
PY 2011
VL 160
IS 1-2
BP 120
EP 127
DI 10.1016/j.virusres.2011.05.022
PG 8
WC Virology
SC Virology
GA 826HQ
UT WOS:000295345600015
PM 21683743
ER
PT J
AU Verma, P
Randhawa, I
Klaustermeyer, WB
AF Verma, Prashant
Randhawa, Inderpal
Klaustermeyer, William B.
TI Clinical efficacy of omalizumab in an elderly veteran population with
severe asthma
SO ALLERGY AND ASTHMA PROCEEDINGS
LA English
DT Article
ID SEVERE ALLERGIC-ASTHMA; ANTIIMMUNOGLOBULIN-E THERAPY; SEVERE PERSISTENT
ASTHMA; E ANTIBODY OMALIZUMAB; IGE ANTIBODY; ADULTS; EXACERBATIONS;
TOLERABILITY; MANAGEMENT; VALIDITY
AB Severe asthma in elderly patients is underdiagnosed, difficult to treat, and often accompanied by atopy. This study was designed to compare clinical outcomes of omalizumab therapy in an elderly veteran population with severe allergic asthma. A retrospective, observational data analysis was performed over 2 years. Cohort outcome measures 1 year before omalizumab therapy were compared with 1 year of active treatment. Statistical analysis included two sample t-tests. The total number of patients enrolled was 17 with median age of 60 years. Omalizumab therapy was associated with a significant reduction in acute asthma exacerbations requiring prednisone treatment (p < 0.01), a significant improvement in forced expiratory volume in 1 second of 0.28 L (p < 0.01), and significantly higher Asthma Control Test (ACT) scores at 3 (p = 0.043), 6 (p = 0.039), and 12 months of therapy (p < 0.01). Two of five patients on daily prednisone for >6 months were able to discontinue systemic steroid use within 3 months of omalizumab treatment. Our study suggests elderly patients with severe atopic asthma show a significant positive clinical response to oinalizumab. (Allergy Asthma Proc 32:346-350, 2011; doi: 10.2500/aap.2011.32.3467)
C1 [Verma, Prashant; Randhawa, Inderpal; Klaustermeyer, William B.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med, Div Allergy Immunol, Los Angeles, CA 90073 USA.
RP Verma, P (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Med, Div Allergy Immunol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM verma.allergy@gmail.com
NR 36
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Z9 15
U1 0
U2 0
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 SEP-OCT
PY 2011
VL 32
IS 5
BP 346
EP 350
DI 10.2500/aap.2011.32.3467
PG 5
WC Allergy
SC Allergy
GA 828JN
UT WOS:000295497400004
PM 22195686
ER
PT J
AU Konstantinidis, IT
Warshaw, AL
Lauwers, GY
Sahani, DV
Gan, SI
Ferrone, CR
AF Konstantinidis, Ioannis T.
Warshaw, Andrew L.
Lauwers, Gregory Y.
Sahani, Dushyant V.
Gan, S. Ian
Ferrone, Cristina R.
TI A Duodenal Duplication Cyst Causing Recurrent Pancreatitis in a Young
Patient
SO AMERICAN SURGEON
LA English
DT Article
C1 [Konstantinidis, Ioannis T.; Warshaw, Andrew L.; Lauwers, Gregory Y.; Sahani, Dushyant V.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gan, S. Ian] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
RP Konstantinidis, IT (reprint author), Univ Arizona, 1500 N Campbell Ave,POB 245058, Tucson, AZ 85724 USA.
EM ikonstan@email.arizona.edu
NR 5
TC 0
Z9 0
U1 0
U2 2
PU SOUTHEASTERN SURGICAL CONGRESS
PI ATLANTA
PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA
SN 0003-1348
J9 AM SURGEON
JI Am. Surg.
PD SEP
PY 2011
VL 77
IS 9
BP 1267
EP 1269
PG 3
WC Surgery
SC Surgery
GA 826GX
UT WOS:000295343700024
PM 21944639
ER
PT J
AU Almashat, S
Sepehr, A
AF Almashat, Salwan
Sepehr, Alireza
TI Obstructive and Inflammatory Gastric Heterotopic Pancreatic Tissue
SO ARCHIVES OF IRANIAN MEDICINE
LA English
DT Article
DE heterotopic pancreas
AB Heterotopic pancreas is defined as pancreatic tissue arising ectopically with no vascular or anatomic contiguity with the pancreas proper and is believed to arise embryologically during rotation of the foregut and fusion of the dorsal and ventral pancreatic buds. We report a case of gastric heterotopic pancreas presenting as an obstructive inflammatory mass with the clinical differential diagnosis of gastric carcinoma. A 54 year-old woman presented with a history of four days of severe, acute-onset abdominal pain. Abdominal ultrasound showed a gastric antral mass. This was confirmed on computerized tomography, which revealed a hypo-dense mass with heterogeneous enhancement in the gastric antrum and multiple ill-defined hypo-dense areas in the liver suspicious for metastases. A preoperative diagnosis of malignant neoplasm was strongly favored, and a subtotal gastrectomy was performed. Microscopic examination of the specimen revealed submucosal and deeply seated intra-muscular and mural heterotopic pancreatic tissue, comprised of both ductal and acinar structures, surrounded by exuberant acute and chronic inflammation. The ducts were inflamed and showed marked cytologic atypia, favored to be of reactive nature. There was overlying mucosal ulceration with marked acute and chronic full-thickness gastric mural inflammatory response with abscess formation. This is the second reported case of obstructive gastric heterotopic pancreas, presenting as an inflammatory mural gastric mass.
C1 [Almashat, Salwan; Sepehr, Alireza] Harvard Univ, Sch Med, BIDMC, Dept Pathol, Boston, MA 02215 USA.
RP Sepehr, A (reprint author), Harvard Univ, Sch Med, BIDMC, Dept Pathol, East Campus,330 Brookline Ave E1061, Boston, MA 02215 USA.
EM asepehr@bidmc.harvard.edu
NR 6
TC 5
Z9 6
U1 0
U2 1
PU ACAD MEDICAL SCIENCES I R IRAN
PI TEHRAN
PA PO BOX 19395-5655, TEHRAN, 00000, IRAN
SN 1029-2977
J9 ARCH IRAN MED
JI Arch. Iran. Med.
PD SEP
PY 2011
VL 14
IS 5
BP 357
EP 358
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 828FJ
UT WOS:000295486600012
PM 21888463
ER
PT J
AU Holmes, LB
Westgate, MN
AF Holmes, Lewis B.
Westgate, Marie-Noel
TI Inclusion and Exclusion Criteria for Malformations in Newborn Infants
Exposed to Potential Teratogens
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
DE exclusion criteria; malformations; teratogens
ID PRENATAL-DIAGNOSIS; CONGENITAL-MALFORMATIONS; MINOR ANOMALIES;
PREDICTIVE VALUE; MOTHERS; COHORT; TRENDS
AB BACKGROUND: The surveillance of newborn infants exposed to potential teratogens often relies on the findings in routine physicians' examinations to identify malformations. Exposed newborn infants can have a wide variety of physical features, including malformations, birth marks, positional deformities, and minor anomalies. The routine physician's findings are not standardized. Some physicians record a wide variety of physical features and others do not. The purpose of this study was to develop criteria and definitions for identifying malformations and for identifying the more common and less severe physical features that would be excluded as not being malformations. METHODS: The physical features recorded by the examining pediatricians were obtained from a review of the medical records of a consecutive sample of 1000 liveborn and stillborn infants and elective terminations for fetal anomalies. RESULTS: A malformation, defined as a structural abnormality with surgical, medical or cosmetic importance, was present in 18 (2.8%) of the infants; 222 other recorded features were identified and excluded: malformations attributed to dominant or recessive genes (4) or chromosome abnormalities (6), minor anomalies and normal variations (65), birth marks (110), positional deformities (6), prematurity-related features (5), physiologic findings (4) and findings identified by prenatal ultrasound (but not by the examining pediatrician) (20), functional abnormalities (1) and findings in newborn screening (1). CONCLUSIONS: Investigators should establish, in advance, the exclusion criteria to be used in programs, such as malformation surveillance programs or pregnancy registries, whose findings are based on a review of the routine examinations in medical records. It is essential that the same criteria be used in evaluating the drug-exposed and the unexposed comparison group. Birth Defects Research (Part A) 91:807-812, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Holmes, Lewis B.] Harvard Univ, Genet Unit, MassGen Hosp Children, Med Sch,Dept Pediat, Boston, MA 02114 USA.
Harvard Univ, Active Malformat Surveillance Program, Dept Newborn Med, Brigham & Womens Hosp,Med Sch, Boston, MA 02114 USA.
RP Holmes, LB (reprint author), Harvard Univ, Genet Unit, MassGen Hosp Children, Med Sch,Dept Pediat, 175 Cambridge St,5th Floor, Boston, MA 02114 USA.
EM holmes.lewis@mgh.harvard.edu
FU Center for Birth Defects Research and Prevention in the Massachusetts
Department of Public Health
FX The authors received salary support from a subcontract from the Center
for Birth Defects Research and Prevention in the Massachusetts
Department of Public Health. The funding agency had no role in the
conduction of the study or in the analysis of the findings.
NR 32
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Z9 12
U1 0
U2 3
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 SEP
PY 2011
VL 91
IS 9
BP 807
EP 812
DI 10.1002/bdra.20842
PG 6
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 827BP
UT WOS:000295400900001
PM 21800414
ER
PT J
AU Danzer, KM
McLean, PJ
AF Danzer, Karin M.
McLean, Pamela J.
TI Drug Targets from Genetics: Alpha-Synuclein
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Alpha-synuclein; Parkinson's disease; chaperones; oligomers; heat shock
proteins; oxidative stress; degradation; neurodegeneration
ID HEAT-SHOCK PROTEINS; CHAPERONE-MEDIATED AUTOPHAGY; DELAYS DISEASE
PROGRESSION; SOLUBLE AMYLOID OLIGOMERS; INCLUSION-BODY FORMATION;
DOPAMINERGIC NEURON LOSS; A-BETA BURDEN; PARKINSONS-DISEASE;
ALZHEIMERS-DISEASE; LEWY BODIES
AB One of the critical issues in Parkinson disease (PD) research is the identity of the specific toxic, pathogenic moiety. In PD, mutations in alpha-synuclein (alpha syn) or multiplication of the SNCA gene encoding alpha syn, result in a phenotype of cellular inclusions, cell death, and brain dysfunction. While the historical point of view has been that the macroscopic aggregates containing alpha syn are the toxic species, in the last several years evidence has emerged that suggests instead that smaller soluble species - likely oligomers containing misfolded alpha syn - are actually the toxic moiety and that the fibrillar inclusions may even be a cellular detoxification pathway and less harmful. If soluble misfolded species of alpha syn are the toxic moieties, then cellular mechanisms that degrade misfolded alpha syn would be neuroprotective and a rational target for drug development. In this review we will discuss the fundamental mechanisms underlying alpha syn toxicity including oligomer formation, oxidative stress, and degradation pathways and consider rational therapeutic strategies that may have the potential to prevent or halt alpha syn induced pathogenesis in PD.
C1 [Danzer, Karin M.; McLean, Pamela J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA.
RP McLean, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, 114 16th St, Charlestown, MA 02129 USA.
EM pmclean@partners.org
FU NIH [NS063963]; Michael J. Fox Foundation for Parkinson's Disease
research
FX PJM is supported by NIH NS063963 and research grants from the Michael J.
Fox Foundation for Parkinson's Disease research.
NR 200
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U1 0
U2 7
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD SEP
PY 2011
VL 10
IS 6
BP 712
EP 723
PG 12
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 827CO
UT WOS:000295404000009
PM 21838671
ER
PT J
AU Dollinger, M
Kobler, J
Berry, DA
Mehta, DD
Luegmair, G
Bohr, C
AF Doellinger, Michael
Kobler, James
Berry, David A.
Mehta, Daryush D.
Luegmair, Georg
Bohr, Christopher
TI Experiments on Analysing Voice Production: Excised (Human, Animal) and
In Vivo (Animal) Approaches
SO CURRENT BIOINFORMATICS
LA English
DT Article
DE Larynx; hemilarynx; vocal fold; dynamics; laryngeal flow; acoustics
ID VOCAL FOLD VIBRATION; INVIVO CANINE MODEL; LARYNGEAL NERVE-STIMULATION;
PHONATION THRESHOLD FLOW; MEDIAL SURFACE DYNAMICS;
FUNDAMENTAL-FREQUENCY; LAMINA PROPRIA; AIR-FLOW; VIDEOSTROBOSCOPIC
ANALYSIS; EMPIRICAL EIGENFUNCTIONS
AB Experiments on human and on animal excised specimens as well as in vivo animal preparations are so far the most realistic approaches to simulate the in vivo process of human phonation. These experiments do not have the disadvantage of limited space within the neck and enable studies of the actual organ necessary for phonation, i.e., the larynx. The studies additionally allow the analysis of flow, vocal fold dynamics, and resulting acoustics in relation to well-defined laryngeal alterations.
Purpose of Review: This paper provides an overview of the applications and usefulness of excised (human/animal) specimen and in vivo animal experiments in voice research. These experiments have enabled visualization and analysis of dehydration effects, vocal fold scarring, bifurcation and chaotic vibrations, three-dimensional vibrations, aerodynamic effects, and mucosal wave propagation along the medial surface. Quantitative data will be shown to give an overview of measured laryngeal parameter values. As yet, a full understanding of all existing interactions in voice production has not been achieved, and thus, where possible, we try to indicate areas needing further study.
Recent Findings: A further motivation behind this review is to highlight recent findings and technologies related to the study of vocal fold dynamics and its applications. For example, studies of interactions between vocal tract airflow and generation of acoustics have recently shown that airflow superior to the glottis is governed by not only vocal fold dynamics but also by subglottal and supraglottal structures. In addition, promising new methods to investigate kinematics and dynamics have been reported recently, including dynamic optical coherence tomography, X-ray stroboscopy and three-dimensional reconstruction with laser projection systems. Finally, we touch on the relevance of vocal fold dynamics to clinical laryngology and to clinically-oriented research.
C1 [Doellinger, Michael; Luegmair, Georg] Univ Hosp Erlangen, Sch Med, Lab Computat Med, Dept Phoniatr & Pediat Audiol, D-91054 Erlangen, Germany.
[Kobler, James; Mehta, Daryush D.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Berry, David A.] Univ Calif Los Angeles, Sch Med, Laryngeal Dynam Lab, Div Head & Neck Surg, Los Angeles, CA 90095 USA.
[Bohr, Christopher] Univ Hosp Erlangen, Sch Med, ENT Hosp, D-91054 Erlangen, Germany.
RP Dollinger, M (reprint author), Univ Hosp Erlangen, Sch Med, Lab Computat Med, Dept Phoniatr & Pediat Audiol, Bohlenpl 21, D-91054 Erlangen, Germany.
EM Michael.doellinger@uk-erlangen.de
FU Deutsche Forschungsgemeinschaft (DFG) [FOR 894/2]; NIH [R01 DC03072, R01
DC007640]; Institute for Laryngology and Voice Restoration; Eugene B.
Casey Foundation
FX This work was made possible by Deutsche Forschungsgemeinschaft (DFG)
grant no. FOR 894/2 "Stromungsphysikalische Grundlagen der Menschlichen
Stimmgebung". Dr. Berry's contributions to this investigation were
supported by NIH grant no. R01 DC03072. Drs. Kobler and Mehta
acknowledge support from the Institute for Laryngology and Voice
Restoration, the Eugene B. Casey Foundation and NIH grant no. R01
DC007640. We thank all colleagues for providing the figures.
NR 119
TC 12
Z9 12
U1 1
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1574-8936
J9 CURR BIOINFORM
JI Curr. Bioinform.
PD SEP
PY 2011
VL 6
IS 3
BP 286
EP 304
PG 19
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 827ET
UT WOS:000295411100003
PM 26581597
ER
PT J
AU Isci, S
Ozturk, C
Jones, J
Otu, H
AF Isci, Senol
Ozturk, Cengihan
Jones, Jon
Otu, Hasan
TI Bayesian network based pathway analysis of microarray data
SO CURRENT OPINION IN BIOTECHNOLOGY
LA English
DT Meeting Abstract
CT European Biotechnology Congress
CY SEP 28-OCT 01, 2011
CL Istanbul, TURKEY
SP European Biotechnol Themat Network Assoc
C1 [Isci, Senol; Ozturk, Cengihan] Bogazici Univ, Inst Biomed Engn, TR-34342 Istanbul, Turkey.
[Jones, Jon] Johannes Gutenberg Univ Mainz, Dept Urol, D-55131 Mainz, Germany.
[Otu, Hasan] Harvard Univ, Sch Med, Dept Med, BIDMC Genom Ctr, Boston, MA USA.
[Otu, Hasan] Istanbul Bilgi Univ, Dept Bioengn, Istanbul, Turkey.
EM hotu@bidmc.harvard.edu
RI isci, senol/E-7024-2012; Ozturk, Cengizhan/A-6177-2016
OI Ozturk, Cengizhan/0000-0002-6966-0774
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0958-1669
J9 CURR OPIN BIOTECH
JI Curr. Opin. Biotechnol.
PD SEP
PY 2011
VL 22
SU 1
BP S22
EP S22
DI 10.1016/j.copbio.2011.05.034
PG 1
WC Biochemical Research Methods; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 825VS
UT WOS:000295310800029
ER
PT J
AU Friedman, MJ
Resick, PA
Bryant, RA
Strain, J
Horowitz, M
Spiegel, D
AF Friedman, Matthew J.
Resick, Patricia A.
Bryant, Richard A.
Strain, James
Horowitz, Mardi
Spiegel, David
TI CLASSIFICATION OF TRAUMA AND STRESSOR-RELATED DISORDERS IN DSM-5
SO DEPRESSION AND ANXIETY
LA English
DT Review
DE trauma; stress; stressor; dissociation; dissociative disorders; anxiety
disorders; adjustment disorders; PTSD; ASD; posttraumatic stress
disorder
ID DISSOCIATIVE IDENTITY DISORDER; MENTAL-HEALTH PROBLEMS; COMBAT-RELATED
PTSD; POSTTRAUMATIC-STRESS; LIFE EVENTS; PANIC DISORDER; PERITRAUMATIC
DISSOCIATION; PSYCHIATRIC OUTPATIENTS; INTERNALIZING SUBTYPES; TERRORIST
ATTACKS
AB This review examines the question of whether there should be a cluster of disorders, including the adjustment disorders (ADs), acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and the dissociative disorders (DDs), in a section devoted to abnormal responses to stress and trauma in the DSM-5. Environmental risk factors, including the individual's developmental experience, would thus become a major diagnostic consideration. The relationship of these disorders to one another is examined and also their relationship to other anxiety disorders to determine whether they are better grouped with anxiety disorders or a new specific grouping of trauma and stressor-related disorders. First how stress responses have been classified since DSM-III is reviewed. The major focus is on PTSD because it has received the most attention, regarding its proper placement among the psychiatric diagnoses. It is discussed whether PTSD should be considered an anxiety disorder, a stress-induced fear circuitry disorder, an internalizing disorder, or a trauma and stressor-related disorder. Then, ASD, AD, and DD are considered from a similar perspective. Evidence is examined pro and con, and a concision is offered recommending inclusion of this cluster of disorders in a section entitled "Trauma and Stressor-Related Disorders." The recommendation to shift ASD and PTSD out of the anxiety disorders section reflects increased recognition of trauma as a precipitant, emphasizing common etiology over common phenomenology. Similar considerations are addressed with regard to AD and DD. Depression and Anxiety 28:737-749, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Spiegel, David] Dept Psychiat & Behav Sci, Stanford, CA USA.
[Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, VA Med Ctr, White River Jct, VT USA.
[Friedman, Matthew J.] Dartmouth Med Sch, Dept Psychiat, Hanover, NH USA.
[Friedman, Matthew J.] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH USA.
[Resick, Patricia A.] VA Ctr Natl Ctr PTSD, White River Jct, VT USA.
[Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA.
[Bryant, Richard A.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia.
[Strain, James] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Horowitz, Mardi] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
RP Spiegel, D (reprint author), Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA.
EM dspiegel@stanford.edu
OI Bryant, Richard/0000-0002-9607-819X
NR 114
TC 72
Z9 74
U1 10
U2 52
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD SEP
PY 2011
VL 28
IS 9
SI SI
BP 737
EP 749
DI 10.1002/da.20845
PG 13
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 823EK
UT WOS:000295105100002
PM 21681870
ER
PT J
AU Friedman, MJ
Resick, PA
Bryant, RA
Brewin, CR
AF Friedman, Matthew J.
Resick, Patricia A.
Bryant, Richard A.
Brewin, Chris R.
TI CONSIDERING PTSD FOR DSM-5
SO DEPRESSION AND ANXIETY
LA English
DT Review
DE PTSD; DSM-IV; DSM-V; diagnostic criteria; posttraumatic; syndromes
ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS;
COGNITIVE-PROCESSING THERAPY; MOTOR-VEHICLE ACCIDENTS; SEPTEMBER-11
TERRORIST ATTACKS; VIETNAM COMBAT VETERANS; CHILDHOOD SEXUAL-ABUSE;
FEMALE CRIME VICTIMS; TRAUMA-RELATED GUILT; MENTAL-HEALTH
AB This is a review of the relevant empirical literature concerning the DSM-IV-TR diagnostic criteria for PTSD. Most of this work has focused on Criteria A1 and A2, the two components of the A (Stressor) Criterion. With regard to A1, the review considers: (a) whether A1 is etiologically or temporally related to the PTSD symptoms; (b) whether it is possible to distinguish "traumatic" from "non-traumatic" stressors; and (c) whether A1 should be eliminated from DSM-5. Empirical literature regarding the utility of the A2 criterion indicates that there is little support for keeping the A2 criterion in DSM-5. The B (reexperiencing), C (avoidance/numbing) and D (hyperarousal) criteria are also reviewed. Confirmatory factor analyses suggest that the latent structure of PTSD appears to consist of four distinct symptom clusters rather than the three-cluster structure found in DSM-IV. It has also been shown that in addition to the fear-based symptoms emphasized in DSM-IV; traumatic exposure is also followed by dysphoric, anhedonic symptoms, aggressive/externalizing symptoms, guilt/shame symptoms, dissociative symptoms, and negative appraisals about oneself and the world. A new set of diagnostic criteria is proposed for DSM-5 that: (a) attempts to sharpen the A1 criterion; (b) eliminates the A2 criterion; (c) proposes four rather than three symptom clusters; and (d) expands the scope of the B-E criteria beyond a fear-based context. The final sections of this review consider: (a) partial/subsyndromal PTSD; (b) disorders of extreme stress not otherwise specified (DESNOS)/complex PTSD; (c) cross- cultural factors; (d) developmental factors; and (e) subtypes of PTSD. Depression and Anxiety 28:750-769, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, VA Med Ctr, White River Jct, VT 05009 USA.
[Friedman, Matthew J.] Dartmouth Med Sch, Hanover, NH USA.
[Resick, Patricia A.] VA Boston Healthcare Syst, Boston, MA USA.
[Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Bryant, Richard A.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia.
[Brewin, Chris R.] UCL, London, England.
RP Friedman, MJ (reprint author), US Dept Vet Affairs, Natl Ctr PTSD, VA Med Ctr, 215 N Main St, White River Jct, VT 05009 USA.
EM Matthew.Friedman@Dartmouth.edu
RI Brewin, Chris/C-4566-2008;
OI Brewin, Chris/0000-0002-7462-4460; Bryant, Richard/0000-0002-9607-819X
NR 185
TC 186
Z9 187
U1 16
U2 111
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD SEP
PY 2011
VL 28
IS 9
SI SI
BP 750
EP 769
DI 10.1002/da.20767
PG 20
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 823EK
UT WOS:000295105100003
PM 21910184
ER
PT J
AU Hinton, DE
Lewis-Fernandez, R
AF Hinton, Devon E.
Lewis-Fernandez, Roberto
TI THE CROSS-CULTURAL VALIDITY OF POSTTRAUMATIC STRESS DISORDER:
IMPLICATIONS FOR DSM-5
SO DEPRESSION AND ANXIETY
LA English
DT Review
DE DSM-5; culture; classification diagnostic criteria; PTSD; trauma
ID ATAQUES-DE-NERVIOS; NATIONAL COMORBIDITY SURVEY; DOSE-EFFECT
RELATIONSHIPS; COMMON MENTAL-DISORDERS; FOCUSED PANIC-ATTACKS; CAMBODIAN
REFUGEES; 12-MONTH PREVALENCE; TIBETAN REFUGEES; VIETNAM VETERANS;
PSYCHIATRIC-DISORDERS
AB Background: There is considerable debate about the cross-cultural applicability of the posttraumatic stress disorder (PTSD) category as currently specified. Concerns include the possible status of PTSD as a Western culture-bound disorder and the validity of individual items and criteria thresholds. This review examines various types of cross-cultural validity of the PTSD criteria as defined in DSM-IV-TR, and presents options and preliminary recommendations to be considered for DSM-5. Methods: Searches were conducted of the mental health literature, particularly since 1994, regarding cultural-, race-, or ethnicity-related factors that might limit the universal applicability of the diagnostic criteria of PTSD in DSM-IV-TR and the possible criteria for DSM-5 Results: Substantial evidence of the cross-cultural validity of PTSD was found. However, evidence of cross-cultural variability in certain areas suggests the need for further research: the relative salience of avoidance/numbing symptoms, the role of the interpretation of trauma-caused symptoms in shaping symptomatology, and the prevalence of somatic symptoms. This review also indicates the need to modify certain criteria, such as the items on distressing dreams and on foreshortened future, to increase their cross-cultural applicability. Text additions are suggested to increase the applicability of the manual across cultural contexts: specifying that cultural syndromes-such as those indicated in the DSM-IV-TR Glossary-may be a prominent part of the trauma response in certain cultures, and that those syndromes may influence PTSD symptom salience and comorbidity. Conclusions: The DSM-IV-TR PTSD category demonstrates various types of validity. Criteria modification and textual clarifications are suggested to further improve its cross-cultural applicability. Depression and Anxiety 28:783-801, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Hinton, Devon E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
[Lewis-Fernandez, Roberto] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[Lewis-Fernandez, Roberto] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
RP Hinton, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA.
EM devon_hinton@hms.harvard.edu; rlewis@nyspi.cpmc.columbia.edu
NR 171
TC 83
Z9 84
U1 12
U2 55
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD SEP
PY 2011
VL 28
IS 9
SI SI
BP 783
EP 801
DI 10.1002/da.20753
PG 19
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 823EK
UT WOS:000295105100005
PM 21910185
ER
PT J
AU Strain, JJ
Friedman, MJ
AF Strain, James J.
Friedman, Matthew J.
TI CONSIDERING ADJUSTMENT DISORDERS AS STRESS RESPONSE SYNDROMES FOR DSM-5
SO DEPRESSION AND ANXIETY
LA English
DT Review
ID NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSION; MODERATION; RELEVANCE;
ANXIETY; GENE
C1 [Strain, James J.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Friedman, Matthew J.] US Dept Vet Affairs, Natl Ctr PTSD, Washington, DC USA.
[Friedman, Matthew J.] Dartmouth Med Sch, Hanover, NH USA.
RP Friedman, MJ (reprint author), VA Med Ctr, Natl Ctr PTSD 116D, 215 N Main St, White River Jct, VT 05009 USA.
EM matthew.friedman@dartmouth.edu
NR 33
TC 27
Z9 27
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD SEP
PY 2011
VL 28
IS 9
SI SI
BP 818
EP 823
DI 10.1002/da.20782
PG 6
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 823EK
UT WOS:000295105100007
PM 21254314
ER
PT J
AU Ling, MF
Luster, AD
AF Ling, Morris F.
Luster, Andrew D.
TI Novel approach to inhibiting chemokine function
SO EMBO MOLECULAR MEDICINE
LA English
DT Editorial Material
DE CCL2; chemokine; glutaminyl cyclase; inflammatory disease; MCP-1;
monocyte
ID PROGRESSION; RECEPTORS; ARTHRITIS; DISEASE; CCR2
C1 [Ling, Morris F.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02115 USA.
RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02115 USA.
EM aluster@mgh.harvard.edu
OI Ling, Morris/0000-0002-9657-8960
NR 12
TC 1
Z9 1
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD SEP
PY 2011
VL 3
IS 9
BP 510
EP 512
DI 10.1002/emmm.201100161
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 827KK
UT WOS:000295427200003
PM 21882341
ER
PT J
AU Pittet, MJ
Swirski, FK
AF Pittet, Mikael J.
Swirski, Filip K.
TI Monocytes link atherosclerosis and cancer
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Atherosclerosis; Cancer; Monocyte
ID TUMOR-ASSOCIATED MACROPHAGES; SUPPRESSOR-CELLS; LESION FORMATION;
CCR2(-/-) MICE; INFLAMMATION; SUBSETS; ATHEROGENESIS; ACCUMULATION;
HYPERCHOLESTEROLEMIA; INTERLEUKIN-1
AB From many perspectives, cardiovascular diseases and cancers are fundamentally different. On the one hand, atherosclerosis is a disease of lipid accumulation driven by diet and lifestyle, whereas cancer is an attack "from within'' driven by mutations. Nevertheless, studies over the past 20 years have forced us to re-evaluate such a view. We are learning that, among other factors, the immune system is indispensable for the development and progression of both diseases. Its components are not only reactive but can also orchestrate both tumor and atherosclerotic lesion growth. In this Viewpoint, we explore how monocytes, which are key constituents of the immune system, forge links between cardiovascular diseases and cancers.
C1 [Pittet, Mikael J.; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Pittet, Mikael J.; Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA.
EM mpittet@mgh.harvard.edu; fswirski@mgh.harvard.edu
FU NHLBI NIH HHS [R01 HL095612]; NIAID NIH HHS [R01 AI084880]
NR 48
TC 15
Z9 16
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD SEP
PY 2011
VL 41
IS 9
BP 2519
EP 2522
DI 10.1002/eji.201141727
PG 4
WC Immunology
SC Immunology
GA 825HC
UT WOS:000295260800014
PM 21952809
ER
PT J
AU Luteijn, R
Sciaranghella, G
van Lunzen, J
Nolting, A
Dugast, AS
Ghebremichael, MS
Altfeld, M
Alter, G
AF Luteijn, Rutger
Sciaranghella, Gaia
van Lunzen, Jan
Nolting, Anne
Dugast, Anne-Sophie
Ghebremichael, Musie S.
Altfeld, Marcus
Alter, Galit
TI Early viral replication in lymph nodes provides HIV with a means by
which to escape NK-cell-mediated control
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE HIV; Innate immunity; Lymph nodes; NK cells
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATURAL-KILLER-CELLS; EXPOSED UNINFECTED
INDIVIDUALS; CD8 T-CELLS; RECEPTOR EXPRESSION; DENDRITIC CELLS; IN-VIVO;
CHEMOKINE RECEPTORS; TYPE-1 INFECTION; PD-1 EXPRESSION
AB Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR(+) NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR(+) NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK-cell-mediated innate pressure.
C1 [Luteijn, Rutger; Sciaranghella, Gaia; Nolting, Anne; Dugast, Anne-Sophie; Ghebremichael, Musie S.; Altfeld, Marcus; Alter, Galit] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA.
[van Lunzen, Jan] Univ Klinikum Hamburg Eppendorf, Sekt Infektiol, Med Klin 1, Hamburg, Germany.
[van Lunzen, Jan] Univ Klinikum Hamburg Eppendorf, Ambulanzzentrum UKE, Hamburg, Germany.
[Ghebremichael, Musie S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Ghebremichael, Musie S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Alter, G (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, 149 13th St, Boston, MA 02129 USA.
EM galter@partners.org
RI Dugast, AnneSophie/L-9541-2015
FU NIAID NIH HHS [R01 AI080289]
NR 63
TC 13
Z9 13
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD SEP
PY 2011
VL 41
IS 9
BP 2729
EP 2740
DI 10.1002/eji.201040886
PG 12
WC Immunology
SC Immunology
GA 825HC
UT WOS:000295260800038
PM 21630248
ER
PT J
AU Gros, DF
Frueh, BC
Magruder, KM
AF Gros, Daniel F.
Frueh, B. Christopher
Magruder, Kathryn M.
TI Prevalence and features of panic disorder and comparison to
posttraumatic stress disorder in VA primary care
SO GENERAL HOSPITAL PSYCHIATRY
LA English
DT Article
DE Panic disorder; Posttraumatic stress disorder; Veterans; Comorbidity;
Health care utilization
ID US VETERANS; DSM-IV; PTSD; COMORBIDITY; SYMPTOMS; CLINICS
AB Objective: Although panic disorder (PD) is a highly prevalent condition in both community and community primary care settings, little is known about PD in veteran populations, especially in comparison to posttraumatic stress disorder (PTSD). The present study investigated prevalence, comorbidity, physical and mental health impairment, and health care utilization of veterans with PD and PTSD.
Method: A total of 884 veterans participated in a cross-sectional investigation in primary care clinics in four Veteran Affairs Medical Centers (VAMCs). Participants completed diagnostic interviews and self-report questionnaires, and a chart review was completed to assess their VAMC health care utilization.
Results: A large number of veterans (8.3%) met the diagnostic criteria for PD and reported significantly more severe physical health impairment (pain, general health), mental health impairment (emotional well-being, role limitations) and social functioning than veterans without PD. Veterans with PD also had increased health care utilization for mental health. Further, PD was highly comorbid with PTSD, with similar symptoms across all measures.
Conclusions: These findings demonstrate the high prevalence and severe impairment associated with PD in veterans and highlight the need for improved recognition, assessment and specialized treatments for PD in VAMCs and other care settings. Published by Elsevier Inc.
C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA.
[Gros, Daniel F.; Magruder, Kathryn M.] Med Univ S Carolina, Charleston, SC 29403 USA.
[Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA.
[Frueh, B. Christopher] Menninger Clin, Houston, TX 77080 USA.
RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA.
EM grosd@musc.edu
RI Schueter, nicos/A-3625-2014
FU Veterans Affairs Health Services Research and Development
[VCR-99-010-2]; Ralph H. Johnson VAMC Research Enhancement Award Program
[REA08-261]
FX This work was partially supported by a grant from Veterans Affairs
Health Services Research and Development (VCR-99-010-2). In addition,
the authors are members of the Ralph H. Johnson VAMC Research
Enhancement Award Program (REA08-261; principal investigator: Leonard
Egede, M.D.). The views expressed in this article are those of the
authors and do not necessarily reflect the position or policy of the
Department of Veterans Affairs or the US government. There are no
conflicts of interest to disclose.
NR 25
TC 24
Z9 24
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-8343
J9 GEN HOSP PSYCHIAT
JI Gen. Hosp. Psych.
PD SEP-OCT
PY 2011
VL 33
IS 5
BP 482
EP 488
DI 10.1016/j.genhosppsych.2011.06.005
PG 7
WC Psychiatry
SC Psychiatry
GA 824MP
UT WOS:000295206300012
PM 21816481
ER
PT J
AU Huffman, JC
Chang, TE
Durham, LE
Weiss, AP
AF Huffman, Jeff C.
Chang, Trina E.
Durham, Lauren E.
Weiss, Anthony P.
TI Antipsychotic polytherapy on an inpatient psychiatric unit: how does
clinical practice coincide with Joint Commission guidelines?
SO GENERAL HOSPITAL PSYCHIATRY
LA English
DT Article
DE Antipsychotics; Polypharmacy; Quality; Inpatient; Psychosis
ID ATYPICAL ANTIPSYCHOTICS; DOUBLE-BLIND; SCHIZOPHRENIA; QUETIAPINE;
DISORDER; POLYPHARMACY; ANTIDEPRESSANTS; AUGMENTATION; METAANALYSIS;
RISPERIDONE
AB Objective: A recently developed quality measure set for inpatient psychiatric care includes measurement of antipsychotic polytherapy at discharge. Our objective was to use detailed chart reviews to assess the use of antipsychotic polytherapy and place this use in the context of these measures.
Methods: Patients (N=75) discharged on multiple antipsychotics and a comparable set (N=114) of comparison patients (a randomly selected set of all admitted inpatients) were identified from consecutive admissions to a psychiatric inpatient unit. Medical records were reviewed to ascertain the clinical rationale for antipsychotic polytherapy and assess differences in characteristics between these groups.
Results: Patients discharged on antipsychotic polytherapy were more likely to have public insurance, longer lengths of stay, psychotic illness, more prior admissions, and state-funded services for persons with chronic mental illness. We identified subgroups of patients based on the clinical rationale for the antipsychotic co-prescription (refractory illness, regimen unchanged from admission and use of antipsychotic for nonpsychosis symptoms). Some, but not all, such rationales appeared to be clinically justified.
Conclusions: The majority of patients discharged on antipsychotic polytherapy had justifiable clinical rationales that were concordant with the new quality measures. However, two additional subsets were identified, one where quality improvement efforts may be warranted and another where revision of existing quality measure definitions should be considered. Given the implications of public reporting of quality measures, further study and refinement of these measures are required to provide meaningful information to all concerned stakeholders. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Huffman, Jeff C.; Chang, Trina E.; Durham, Lauren E.; Weiss, Anthony P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Huffman, Jeff C.; Chang, Trina E.; Weiss, Anthony P.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM jhuffman@partners.org
NR 23
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-8343
J9 GEN HOSP PSYCHIAT
JI Gen. Hosp. Psych.
PD SEP-OCT
PY 2011
VL 33
IS 5
BP 501
EP 508
DI 10.1016/j.genhosppsych.2011.05.012
PG 8
WC Psychiatry
SC Psychiatry
GA 824MP
UT WOS:000295206300014
PM 21762994
ER
PT J
AU Tischkowitz, M
Bahubeshi, A
Hamel, N
Pasini, B
Asioli, S
Baynam, G
Overkov, A
Frieder, RP
Dishop, M
Graf, N
Ekim, M
Bouron-Dal Soglio, D
Arseneau, J
Young, RH
Sabbaghian, N
Srivastava, A
Priest, JR
Foulkes, WD
AF Tischkowitz, Marc
Bahubeshi, A.
Hamel, N.
Pasini, B.
Asioli, S.
Baynam, G.
Overkov, A.
Frieder, R. P.
Dishop, M.
Graf, N.
Ekim, M.
Bouron-Dal Soglio, D.
Arseneau, J.
Young, R. H.
Sabbaghian, N.
Srivastava, A.
Priest, J. R.
Foulkes, W. D.
TI Extending the Benign and Malignant Phenotypes Associated with Germline
DICER1 Mutations
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Meeting Abstract
CT British Human Genetics Conference
CY SEP 05-07, 2011
CL Univ Warwick, Coventry, ENGLAND
HO Univ Warwick
C1 [Tischkowitz, Marc; Bahubeshi, A.; Hamel, N.; Sabbaghian, N.; Srivastava, A.; Foulkes, W. D.] McGill Univ, Program Canc Genet, Dept Oncol, Montreal, PQ, Canada.
[Tischkowitz, Marc; Bahubeshi, A.; Hamel, N.; Sabbaghian, N.; Srivastava, A.; Foulkes, W. D.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Tischkowitz, Marc; Bahubeshi, A.; Sabbaghian, N.; Srivastava, A.; Foulkes, W. D.] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Hamel, N.; Foulkes, W. D.] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada.
[Pasini, B.] Univ Turin, Dept Genet Biol & Biochem, I-10124 Turin, Italy.
[Asioli, S.] Univ Turin, Dept Biomed Sci & Human Oncol, I-10124 Turin, Italy.
[Baynam, G.; Overkov, A.] Univ Western Australia, Sch Pediat & Child Hlth, Nedlands, WA 6009, Australia.
[Frieder, R. P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA.
[Dishop, M.] Childrens Hosp, Dept Pathol, Aurora, CO USA.
[Graf, N.] Childrens Hosp Westmead, Dept Pathol, Sydney, NSW, Australia.
[Ekim, M.] Ankara Univ, Sch Med, Dept Pediat Nephrol, TR-06100 Ankara, Turkey.
[Bouron-Dal Soglio, D.] CHU St Justine, Dept Pathol, Montreal, PQ, Canada.
[Arseneau, J.] McGill Univ, Dept Pathol, Montreal, PQ, Canada.
[Young, R. H.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA.
[Priest, J. R.] Childrens Hosp & Clin Minnesota, Int Pleuropulm Blastoma Registry, Minneapolis, MN USA.
EM marc.tischkowitz@mcgill.ca
RI Ekim, Mesiha/L-9398-2014
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 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD SEP
PY 2011
VL 48
SU 1
BP S103
EP S103
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 823DY
UT WOS:000295103800225
ER
PT J
AU Hutt, E
Ruscin, JM
Linnebur, SA
Fish, DN
Oman, KS
Fink, RM
Radcliff, TA
Van Dorsten, B
Liebrecht, D
Fish, R
McNulty, MC
AF Hutt, Evelyn
Ruscin, J. Mark
Linnebur, Sunny A.
Fish, Douglas N.
Oman, Kathleen S.
Fink, Regina M.
Radcliff, Tiffany A.
Van Dorsten, Brent
Liebrecht, Debra
Fish, Ron
McNulty, Monica C.
TI A Multifaceted Intervention to Implement Guidelines Did Not Affect
Hospitalization Rates for Nursing Home-Acquired Pneumonia
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
DE Nursing home; pneumonia; hospitalization; guidelines; care processes
ID RANDOMIZED CONTROLLED-TRIAL; TERM-CARE FACILITIES; RESIDENTS;
MANAGEMENT; PROGRAM; REDUCE; IMPACT
AB Objective: Determine whether a comprehensive approach to implementing national consensus guidelines for nursing home acquired pneumonia (NHAP) affected hospitalization rates.
Design: Quasi-experimental, mixed-methods, multifaceted, unblinded intervention trial.
Setting: Sixteen nursing homes (NHs) from 1 corporation: 8 in metropolitan Denver, CO; 8 in Kansas and Missouri during 3 influenza seasons, October to April 2004 to 2007.
Participants: Residents with 2 or more signs and symptoms of systemic lower respiratory tract infection (LRTI); NH staff and physicians were eligible.
Intervention: Multifaceted, including academic detailing to clinicians, within-facility nurse change agent, financial incentives, and nursing education.
Measurements: Subjects' NH medical records were reviewed for resident characteristics, disease severity, and care processes. Bivariate analysis compared hospitalization rates for subjects with stable and unstable vital signs between intervention and control NHs and time periods. Qualitative interviews were analyzed using content coding.
Results: Hospitalization rates for stable residents in both NH groups remained low throughout the study. Few critically ill subjects in the intervention NHs were hospitalized in either the baseline or intervention period. In control NHs, 8.7% of subjects with unstable vital signs were hospitalized during the baseline and 33% in intervention year 2, but the difference was not statistically significant (P = .10). Interviews with nursing staff and leadership confirmed there were significant pressures for, and enablers of, avoiding hospitalization for treatment of acute infections.
Conclusions: Secular pressures to avoid hospitalization and the challenges of reaching NH physicians via academic detailing are likely responsible for the lack of intervention effect on hospitalization rates for critically ill NH residents. (J Am Med Dir Assoc 2011; 12: 499-507)
C1 [Hutt, Evelyn; Radcliff, Tiffany A.] Univ Colorado Denver, Denver VA Med Ctr, Denver, CO 80220 USA.
[Hutt, Evelyn; Ruscin, J. Mark; Linnebur, Sunny A.; Fish, Douglas N.; Oman, Kathleen S.; Fink, Regina M.; Radcliff, Tiffany A.; Van Dorsten, Brent; Liebrecht, Debra; Fish, Ron; McNulty, Monica C.] Univ Colorado Denver, Aurora, CO USA.
RP Hutt, E (reprint author), Univ Colorado Denver, Denver VA Med Ctr, 1055 Clermont St,151, Denver, CO 80220 USA.
EM evelyn.hutt@ucdenver.edu
NR 20
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD SEP
PY 2011
VL 12
IS 7
BP 499
EP 507
DI 10.1016/j.jamda.2010.03.011
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 827QJ
UT WOS:000295442700005
PM 21450174
ER
PT J
AU Shofner, JD
Lipworth, A
Tannous, Z
Avram, MM
AF Shofner, Joshua D.
Lipworth, Adam
Tannous, Zeina
Avram, Mathew M.
TI When Not to Treat Cutaneous Vascular Lesions With the Pulsed Dye Laser
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE pulsed dye laser; telangiectasia; petechiae
ID TELANGIECTASIA; DERMATOMYOSITIS; MELANOMA; ERYTHEMA; ROSACEA; DISEASE;
UPDATE; NM
AB The availability of effective laser treatment for cutaneous vascular lesions has risen dramatically in recent years. At the same time, there has been a proliferation of laser providers with varying amounts of training-both medical and nonmedical. We report a series of four cases where patients presented for cosmetic evaluation of vascular lesions and were discovered to have more significant pathologic disease. In presenting these cases, we hope to illuminate a basic differential diagnosis that exists for cutaneous vascular lesions and remind healthcare providers that not all "cosmetic" concerns are benign in origin. There is a differential diagnosis that exists for cutaneous vascular lesions that is worth reviewing, and it should be considered in all patients presenting for laser treatment. Lasers Surg. Med. 43:792-796, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Avram, Mathew M.] Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, MGH Laser & Cosmet Ctr,Med Sch, Boston, MA 02114 USA.
[Lipworth, Adam] Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Sch Med, Boston, MA 02114 USA.
RP Avram, MM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, MGH Laser & Cosmet Ctr,Med Sch, 50 Staniford St,250, Boston, MA 02114 USA.
EM mavram@partners.org
NR 27
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD SEP
PY 2011
VL 43
IS 8
BP 792
EP 796
DI 10.1002/lsm.21119
PG 5
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 824WG
UT WOS:000295232300002
PM 21956626
ER
PT J
AU Haedersdal, M
Katsnelson, J
Sakamoto, FH
Farinelli, WA
Doukas, AG
Tam, J
Anderson, RR
AF Haedersdal, M.
Katsnelson, J.
Sakamoto, F. H.
Farinelli, W. A.
Doukas, A. G.
Tam, J.
Anderson, R. R.
TI Enhanced Uptake and Photoactivation of Topical Methyl Aminolevulinate
After Fractional CO2 Laser Pretreatment
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE drug delivery; fractional laser ablation; methyl 5-aminolevulinic acid;
photodynamic therapy; photosensitizer; porphyrins
ID BASAL-CELL CARCINOMA; NONMELANOMA SKIN-CANCER; PROTOPORPHYRIN-IX
FLUORESCENCE; ACID-PHOTODYNAMIC THERAPY; ACTINIC KERATOSIS; ENDOGENOUS
PROTOPORPHYRIN; 5-AMINOLEVULINIC ACID; PHOTOTHERMOLYSIS;
PHOTOSENSITIZER; EPIDEMIOLOGY
AB Background and Objectives: Photodynamic therapy (PDT) of thick skin lesions is limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates vertical channels that may facilitate topical PDT drug penetration and improve PDT-response in deep skin layers. The purpose of this study was to evaluate whether pre-treating the skin with AFR before topically applied methyl aminolevulinate (MAL) could enable a deep PDT-response.
Materials and Methods: Yorkshire swine were treated under general anesthesia with a fractional CO2 laser using stacked single pulses of 3 milliseconds, 91.6 mJ per pulse and subsequent topical MAL application for 3 hours (Metvix (R)). Red light (LED arrays) was then delivered at fluences of 37 and 200 J/cm(2). Fluorescent photography and microscopy was used to quantify MAL-induced porphyrin distribution and PDT-induced photobleaching at the skin surface and five specific depths down to 1,800 mu m.
Results: Laser-ablated channels were approximately 1,850 mu m deep, which significantly increased topical MAL-induced porphyrin fluorescence (hair follicles, dermis, P < 0.0001) and PDT response, both superficially and deep, versus topical MAL application alone. The fraction of porphyrin fluorescence lost by photobleaching was slightly less after 37 J/cm(2) than after 200 J/cm(2) (overall median values 67-90%; 37 vs. 200 J/cm(2), P > 0.05 for all but one comparison). Photobleaching was steady throughout skin layers and did not vary significantly with skin depth at either LED fluence (P > 0.05).
Conclusions: AFR greatly facilitates topical MAL-induced porphyrins and the fraction of photobleached porphyrins is similar for superficial and deep skin. These observations are consistent with AFR-enhanced uptake of MAL, increased porphyrin synthesis, and photodynamic activation of deep porphyrins even at the lower fluence of 37 J/cm(2), widely used in clinical practice. AFR appears to be a clinically practical means for improving PDT deep into the skin. Clinical studies are suggested to evaluate selectivity in targeting dysplastic cell types. Lasers Surg. Med. 43:804-813, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Haedersdal, M.; Katsnelson, J.; Sakamoto, F. H.; Farinelli, W. A.; Doukas, A. G.; Tam, J.; Anderson, R. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Haedersdal, M.] Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen, Denmark.
[Sakamoto, F. H.] Univ Fed Sao Paulo, Escola Paulista Med, Dept Dermatol, BR-04023900 Sao Paulo, Brazil.
RP Haedersdal, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, BHX 630-55 Fruit St, Boston, MA 02114 USA.
EM mhaedersdal@dadlnet.dk
FU Photocure/Galderma; Danish Council for Independent Research/Medical
Sciences (FSS); Aage Bang Foundation; A.P Moller Foundation for the
Advancement of Medical Science
FX M.H. has received fee from Photocure/Galderma for speaking and is on the
advisory board for Galderma International regarding photodynamic therapy
of organ transplant recipients. None of the other listed authors have
any conflict of interest regarding this publication.; Contract grant
sponsor: Danish Council for Independent Research/Medical Sciences (FSS);
Contract grant sponsor: Aage Bang Foundation; Contract grant sponsor:
A.P Moller Foundation for the Advancement of Medical Science.
NR 32
TC 55
Z9 56
U1 0
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD SEP
PY 2011
VL 43
IS 8
BP 804
EP 813
DI 10.1002/lsm.21096
PG 10
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 824WG
UT WOS:000295232300004
PM 21956628
ER
PT J
AU Sharma, SK
Kharkwal, GB
Sajo, M
Huang, YY
De Taboada, L
McCarthy, T
Hamblin, MR
AF Sharma, Sulbha K.
Kharkwal, Gitika B.
Sajo, Mari
Huang, Ying-Ying
De Taboada, Luis
McCarthy, Thomas
Hamblin, Michael R.
TI Dose Response Effects of 810 nm Laser Light on Mouse Primary Cortical
Neurons
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE low level laser therapy; LLLT; photobiomodulation; cultured cortical
neurons; near-infra red laser; reactive oxygen species; nitric oxide;
mitochondrial membrane potential; intracellular calcium; ATP; biphasic
dose response
ID HELIUM-NEON LASER; TERM NEUROLOGICAL DEFICITS; TRAUMATIC BRAIN-INJURY;
HUMAN SKIN FIBROBLASTS; NITRIC-OXIDE; PROMOTES REGENERATION; FUNCTIONAL
RECOVERY; ISCHEMIC-STROKE; INFRARED LIGHT; ATP SYNTHESIS
AB Background and Objectives: In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from embryonic mouse brains.
Study Design/Materials and Methods: Neurons were irradiated with fluences of 0.03, 0.3, 3, 10, or 30 J/cm(2) of 810-nm laser delivered over varying times at 25 mW/cm(2) and intracellular levels of reactive oxygen species (ROS), nitric oxide and calcium were measured using fluorescent probes within 5 minutes of the end of irradiation. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP).
Results: Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluences. ROS was significantly induced at low fluences, followed by a decrease and a second larger increase at 30 J/cm(2). Nitric oxide levels showed a similar pattern of a double peak but values were less significant compared to ROS.
Conclusions: The results suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling processes which in turn may be responsible for the beneficial stimulatory effects of the low level laser. At higher fluences beneficial mediators are reduced and high levels of Janus-type mediators such as ROS and NO (beneficial at low concentrations and harmful at high concentrations) may be responsible for the damaging effects of high-fluence light and the overall biphasic dose response. Lasers Surg. Med. 43:851-859, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Sharma, Sulbha K.; Kharkwal, Gitika B.; Sajo, Mari; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Sharma, Sulbha K.; Kharkwal, Gitika B.; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Sajo, Mari] Univ Tokyo, Grad Sch Pharmaceut, Tokyo, Japan.
[Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China.
[De Taboada, Luis; McCarthy, Thomas] Photothera Inc, Carlsbad, CA USA.
[Hamblin, Michael R.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA.
EM hamblin@helix.mgh.harvard.edu
RI Huang, Ying-ying/G-3153-2011;
OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin,
Michael/0000-0001-6431-4605
FU Photothera, Inc.; Photothera; NIH [R01AI050875]; Center for Integration
of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program
in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research
[FA9950-04-1-0079]
FX This study was partly supported by a sponsored research agreement from
Photothera, Inc. Luis De Taboada and Thomas McCarthy are employees and
stockholders in Photothera, Inc. Michael R Hamblin has received research
support, loan of equipment and consulting fees from Photothera.;
Contract grant sponsor: NIH; Contract grant number: R01AI050875;
Contract grant sponsor: Center for Integration of Medicine and
Innovative Technology; Contract grant number: DAMD17-02-2-0006; Contract
grant sponsor: CDMRP Program in TBI; Contract grant number:
W81XWH-09-1-0514; Contract grant sponsor: Air Force Office of Scientific
Research; Contract grant number: FA9950-04-1-0079.
NR 63
TC 40
Z9 41
U1 1
U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD SEP
PY 2011
VL 43
IS 8
BP 851
EP 859
DI 10.1002/lsm.21100
PG 9
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 824WG
UT WOS:000295232300010
PM 21956634
ER
PT J
AU Mershon-Shier, KL
Vasuthasawat, A
Takahashi, K
Morrison, SL
Beenhouwer, DO
AF Mershon-Shier, Kileen L.
Vasuthasawat, Alex
Takahashi, Kazue
Morrison, Sherie L.
Beenhouwer, David O.
TI In vitro C3 deposition on Cryptococcus capsule occurs via multiple
complement activation pathways
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Cryptococcus; Complement
ID MANNAN-BINDING LECTINS; CLASSICAL PATHWAY; MICE DEFICIENT; COMPONENT C3;
NEOFORMANS; INFECTION; SERUM; PROTECTION; INNATE; GATTII
AB Complement can be activated via three pathways: classical, alternative, and lectin. Cryptococcus gattii and Cryptococcus neoformans are closely related fungal pathogens possessing a polysaccharide capsule composed mainly of glucuronoxylomannan (GXM), which serves as a site for complement activation and deposition of complement components. We determined 0 deposition on Cryptococcus spp. by flow cytometry and confocal microscopy after incubation with serum from C57BL/6J mice as well as mice deficient in complement components C4, C3, factor B, and mannose binding lectin (MBL). C. gattii and C. neoformans activate complement in EGTA-treated serum indicating that they can activate the alternative pathway. However, complement activation was seen with factor B(-/-) serum suggesting activation could also take place in the absence of a functional alternative pathway. Furthermore, we uncovered a role for C4 in the alternative pathway activation by Cryptococcus spp. We also identified an unexpected and complex role for MBL in complement activation by Cryptococcus spp. No complement activation occurred in the absence of MBL-A and -C proteins although activation took place when the lectin binding activity of MBL was disrupted by calcium chelation. In addition, alternative pathway activation by C. neoformans required both MBL-A and -C, while either MBL-A or -C was sufficient for alternative pathway activation by C. gattii. Thus, complement activation by Cryptococcus spp. can take place through multiple pathways and complement activation via the alternative pathway requires the presence of C4 and MBL proteins. Published by Elsevier Ltd.
C1 [Beenhouwer, David O.] Vet Affairs Greater Angeles Healthcare Syst, Div Infect Dis 111F, Los Angeles, CA 90073 USA.
[Mershon-Shier, Kileen L.; Vasuthasawat, Alex; Morrison, Sherie L.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA.
[Mershon-Shier, Kileen L.; Vasuthasawat, Alex; Morrison, Sherie L.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA.
[Takahashi, Kazue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA.
[Morrison, Sherie L.; Beenhouwer, David O.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Beenhouwer, DO (reprint author), Vet Affairs Greater Angeles Healthcare Syst, Div Infect Dis 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM dbeenhou@ucla.edu
FU Ford Foundation; NIH [R01 AI51415, R01 AI071025, CA-16042, AI-28697];
Veterans Affairs Merit Award; Jonsson Cancer Center; UCLA AIDS
Institute; UCLA School of Medicine; UCLA MIMG Department; UCLA Muscular
Dystrophy Translational Research Consortium
FX This work was supported by a Ford Foundation Pre-Doctoral Fellowship
awarded to K.L.M.-s., NIH grants R01 AI51415 (S.L.M.) and R01 AI071025
(D.O.B.), and a Veterans Affairs Merit Award (D.O.B.). Flow cytometry
was performed in the UCLA Jonsson Comprehensive Cancer Center and Center
for AIDS Research Flow Cytometry Core Facility that is supported by the
National Institutes of Health Awards CA-16042 and AI-28697, by the
Jonsson Cancer Center, the UCLA AIDS Institute, and the UCLA School of
Medicine. Flow cytometry was also supported through funds provided by
UCLA MIMG Department and the UCLA Muscular Dystrophy Translational
Research Consortium.
NR 34
TC 6
Z9 6
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD SEP
PY 2011
VL 48
IS 15-16
BP 2009
EP 2018
DI 10.1016/j.molimm.2011.06.215
PG 10
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 826ZY
UT WOS:000295395300033
PM 21723612
ER
PT J
AU Landau, M
Kurella-Tamura, M
Shlipak, MG
Kanaya, A
Strotmeyer, E
Koster, A
Satterfield, S
Simsonick, EM
Goodpaster, B
Newman, AB
Fried, LF
AF Landau, Michael
Kurella-Tamura, Manjula
Shlipak, Michael G.
Kanaya, Alka
Strotmeyer, Elsa
Koster, Annemarie
Satterfield, Suzanne
Simsonick, Eleanor M.
Goodpaster, Bret
Newman, Anne B.
Fried, Linda F.
CA Hlth Aging Body Composition Study
TI Correlates of insulin resistance in older individuals with and without
kidney disease
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE chronic kidney disease; cystatin C; insulin resistance; subcutaneous fat
ID CHRONIC-RENAL-FAILURE; GLOMERULAR-FILTRATION-RATE; METABOLIC SYNDROME;
ADIPOSE-TISSUE; PLASMA ADIPONECTIN; MUSCLE COMPOSITION; ABDOMINAL
OBESITY; BODY-COMPOSITION; VISCERAL FAT; SENSITIVITY
AB Background. Chronic kidney disease (CKD) is associated with insulin resistance (IR). Prior studies have found that in individuals with CKD, leptin is associated with fat mass but resistin is not and the associations with adiponectin are conflicting. This suggests that the mechanism and factors associated with IR in CKD may differ.
Methods. Of the 2418 individuals without reported diabetes at baseline, participating in the Health, Aging and Body Composition study, a study in older individuals aged 70-79 years, 15.6% had CKD defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m(2) based on cystatin C. IR was defined as the upper quartile of the homeostasis model assessment. The association of visceral and subcutaneous abdominal fat, percent body fat, muscle fat, lipids, inflammatory markers and adiponectin were tested with logistic regression. Interactions were checked to assess whether the factors associated with IR were different in those with and without CKD.
Results. Individuals with IR had a lower eGFR (80.7 +/- 20.9 versus 75.6 +/- 19.6, P < 0.001). After multivariable adjustment, eGFR (odds ratio per 10 mL/min/1.73m(2) 0.92, 95% confidence interval 0.87-0.98) and CKD (1.41, 1.04-1.92) remained independently associated with IR. In individuals with and without CKD, the significant predictors of IR were male sex, black race, higher visceral fat, abdominal subcutaneous fat and triglycerides. In individuals without CKD, IR was associated with lower high-density lipoprotein and current nonsmoking status in multivariate analysis. In contrast, among individuals with CKD, interleukin-6 (IL-6) was independently associated with IR. There was a significant interaction of eGFR with race and IL-6 with a trend for adionectin but no significant interactions with CKD (P > 0.1). In the fully adjusted model, there was a trend for an interaction with adiponectin for eGFR (P = 0.08) and significant for CKD (P = 0.04), where adiponectin was associated with IR in those without CKD but not in those with CKD.
Conclusions. In mainly Stage 3 CKD, kidney function is associated with IR; except for adiponectin, the correlates of IR are similar in those with and without CKD.
C1 [Strotmeyer, Elsa; Newman, Anne B.; Fried, Linda F.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Landau, Michael] Cleveland Clin, Dept Pathol, Cleveland, OH 44106 USA.
[Kurella-Tamura, Manjula] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
[Shlipak, Michael G.] San Francisco VA, Gen Internal Med Sect, San Francisco, CA USA.
[Shlipak, Michael G.; Kanaya, Alka] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shlipak, Michael G.; Kanaya, Alka] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA.
[Shlipak, Michael G.; Kanaya, Alka] Univ Calif San Francisco, Dept Biostat, San Francisco, CA USA.
[Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Koster, Annemarie] Sch Publ Hlth & Primary Care CAPHRI, Maastricht, Netherlands.
[Koster, Annemarie] Maastricht Univ, Dept Internal Med, Maastricht, Netherlands.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Simsonick, Eleanor M.] NIA, NIH, Baltimore, MD 21224 USA.
[Goodpaster, Bret; Newman, Anne B.; Fried, Linda F.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA.
[Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
RP Fried, LF (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
EM linda.fried@va.gov
RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; Strotmeyer,
Elsa/F-3015-2014; Kurella Tamura, Manjula/C-8284-2014;
OI Newman, Anne/0000-0002-0106-1150; Kurella Tamura,
Manjula/0000-0001-5227-2479; Strotmeyer, Elsa/0000-0002-4093-6036
FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIH, National
Institute on Aging
FX The Health, Aging and Body Composition Study is supported by NIA
contract numbers of all participating centers (N01-AG-6-2101;
N01-AG-6-2103; N01-AG-6-2106). This research was supported in part by
the Intramural Research Program of the NIH, National Institute on Aging.
The contents do not represent the views of the Department of Veterans
Affairs or the United States Government. The results presented in this
paper have not been published previously in whole or part.
NR 45
TC 19
Z9 19
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD SEP
PY 2011
VL 26
IS 9
BP 2814
EP 2819
DI 10.1093/ndt/gfq817
PG 6
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 824VZ
UT WOS:000295231600016
PM 21248294
ER
PT J
AU O'Seaghdha, CM
Hwang, SJ
Muntner, P
Melamed, ML
Fox, CS
AF O'Seaghdha, Conall M.
Hwang, Shih-Jen
Muntner, Paul
Melamed, Michal L.
Fox, Caroline S.
TI Serum phosphorus predicts incident chronic kidney disease and end-stage
renal disease
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE CKD; ESRD; phosphorus
ID GLOMERULAR-FILTRATION-RATE; DIETARY-PROTEIN; CARDIOVASCULAR-DISEASE;
RISK-FACTOR; PHOSPHATE; INSUFFICIENCY; PROGRESSION; MORTALITY; INJURY;
HYPERTENSION
AB Background. Elevations in serum phosphorus are associated with renal decline in animal models and progression of established chronic kidney disease (CKD) in human observational studies. We examined whether serum phosphorus levels increase the risk of incident CKD or end-stage renal disease (ESRD) in two population-based prospective cohort studies.
Methods. Overall, 2269 participants free of CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73(2)] from the Framingham Heart Study (FHS; mean age 42 years; 53% women) and 13 372 participants from the Third National Health and Nutrition Examination Survey (NHANES III; mean age 44.3 years, 52% women) contributed to the present study. In the FHS, we evaluated the relationship between baseline phosphorus category (< 2.5 mg/dL, 2.5-3.49 mg/dL, 3.5-3.99 mg/dL and >= 4 mg/dL) and incident CKD (n 267). In NHANES, we examined the relationship between phosphorus below and above 4 mg/dL in relation to incident ESRD (n 65).
Results. FHS participants in the highest phosphorus category had an increased risk of CKD [odds ratio 2.14; 95% confidence interval (CI), 1.07-4.28; P = 0.03] in multivariable-adjusted models when compared to the referent group (2.5-3.49 mg/dL). Similarly, NHANES III participants with phosphorus levels >= 4 mg/dL demonstrated an increased risk of incident ESRD compared to those < 4 mg/dL (relative risk 1.90; 95% CI 1.03-3.53; P = 0.04).
Conclusions. In prospective studies of the general population, serum phosphorus levels in the upper-normal range were associated with a doubling in the risk of developing incident CKD and ESRD.
C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Div Renal, Boston, MA 02114 USA.
[O'Seaghdha, Conall M.] Harvard Univ, Sch Med, Boston, MA USA.
[Muntner, Paul] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA.
[Muntner, Paul] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA.
[Melamed, Michal L.] Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10467 USA.
[Melamed, Michal L.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
EM foxca@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; [K23- DK
078774]
FX The Framingham Offspring Study is supported by the National Heart, Lung,
and Blood Institute (N01-HC-25195). M.L.M. is supported by grant K23- DK
078774.
NR 47
TC 30
Z9 31
U1 0
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
EI 1460-2385
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD SEP
PY 2011
VL 26
IS 9
BP 2885
EP 2890
DI 10.1093/ndt/gfq808
PG 6
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 824VZ
UT WOS:000295231600025
PM 21292817
ER
PT J
AU Pirl, WF
Traeger, L
Greer, JA
Bemis, H
Gallagher, E
Lennes, I
Sequist, L
Heist, R
Temel, JS
AF Pirl, William F.
Traeger, Lara
Greer, Joseph A.
Bemis, Heather
Gallagher, Emily
Lennes, Inga
Sequist, Lecia
Heist, Rebecca
Temel, Jennifer S.
TI Tumor Epidermal Growth Factor Receptor Genotype and Depression in Stage
IV Non-Small Cell Lung Cancer
SO ONCOLOGIST
LA English
DT Article
DE Non-small cell; Genotyping; Epidermal growth factor receptor;
Depression; Major depressive disorder
ID FACTOR-ALPHA; CLINICAL-TRIALS; MAJOR DEPRESSION; EGFR MUTATIONS;
DOUBLE-BLIND; GENE; AMPHIREGULIN; GEFITINIB; SYMPTOMS; BEHAVIOR
AB Introduction. Depression appears to be associated with worse survival from cancer, but underlying mechanisms for this association are unknown. In the present study, we explored the degree to which tumor genotype may be associated with depression in patients with non-small cell lung cancer (NSCLC). We examined differences in depression severity and rates of positive screens for major depressive disorder among newly diagnosed patients with stage IV NSCLC and known epidermal growth factor receptor (EGFR) genotype.
Methods. Newly diagnosed patients (n = 53) with metastatic NSCLC attending an initial thoracic oncology consultation completed self-report questionnaires regarding demographics, smoking behavior, and depression before meeting with their oncologist. Biopsy samples were subsequently genotyped, including screening for EGFR mutations. We conducted a retrospective chart review to obtain clinical data, including tumor stage, performance status, and EGFR genotype.
Results. Twelve patients (22.6%) tested positive for EGFR mutation. No EGFR mutation-positive cases met the screening criteria for major depressive disorder, in comparison with 29.3% of patients with wild-type EGFR (p = .03). Mutations of EGFR were also associated with lower depression severity than with wild-type EGFR, independent of gender, performance status, and smoking history (p < .05). This finding persisted for both the cognitive-affective and somatic domains of depression symptoms.
Conclusions. EGFR mutations were associated with lower depression severity and lower rates of probable major depressive disorder in patients with metastatic NSCLC, based on mood screening performed before results of genotyping were known. Findings support further work to explore the directionality of the associations and potential biological pathways to depression. The Oncologist 2011;16:1299-1306
C1 [Pirl, William F.; Traeger, Lara; Greer, Joseph A.; Bemis, Heather] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA.
[Gallagher, Emily; Lennes, Inga; Sequist, Lecia; Heist, Rebecca; Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Thorac Oncol, Boston, MA 02114 USA.
RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA.
EM wpirl@partners.org
RI Inov Farmaceutica, Inct/K-2313-2013
FU NIH [CA115908]
FX This work was supported by NIH grant CA115908 (Pirl). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIH. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 52
TC 6
Z9 6
U1 0
U2 2
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD SEP
PY 2011
VL 16
IS 9
BP 1299
EP 1306
DI 10.1634/theoncologist.2011-0116
PG 8
WC Oncology
SC Oncology
GA 825EP
UT WOS:000295254100011
PM 21807767
ER
PT J
AU Schorge, JO
Garrett, LA
Goodman, A
AF Schorge, John O.
Garrett, Leslie A.
Goodman, Annekathryn
TI Cytoreductive Surgery for Advanced Ovarian Cancer: Quo Vadis?
SO ONCOLOGY-NEW YORK
LA English
DT Article
ID GYNECOLOGIC-ONCOLOGY-GROUP; NEOADJUVANT CHEMOTHERAPY; SURGICAL
CYTOREDUCTION; STAGE-III; PROGNOSTIC-FACTORS; DEBULKING SURGERY;
IMPROVES SURVIVAL; RESIDUAL DISEASE; PROGRESSION-FREE; STEM-CELLS
AB Two-thirds of women who are newly diagnosed with invasive epithelial ovarian cancer present with stage III or IV disease. The preferred initial treatment has traditionally consisted of primary surgical debulking followed by platinum-based chemotherapy. However, recent data suggesting comparable efficacy for neoadjuvant Chemotherapy and interval debulking have challenged this conventional dogma. Most patients with advanced ovarian cancer will achieve remission regardless of initial treatment, but 80% to 90% of patients will ultimately relapse. The timing and clinical benefit of a second debulking operation for recurrent disease is even more contentious. This article focuses on the recent debate regarding when-or whether-patients with ovarian cancer should undergo aggressive surgical resection.
C1 [Schorge, John O.; Garrett, Leslie A.; Goodman, Annekathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv,Div Gynecol Oncol, Boston, MA 02114 USA.
RP Schorge, JO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet & Gynecol Serv,Div Gynecol Oncol, Boston, MA 02114 USA.
NR 45
TC 12
Z9 14
U1 0
U2 0
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD SEP
PY 2011
VL 25
IS 10
BP 928
EP 934
PG 7
WC Oncology
SC Oncology
GA 826KI
UT WOS:000295352600009
PM 22010391
ER
PT J
AU Heidel, FH
Wang, Z
Feng, Z
Armstrong, SA
AF Heidel, F. H.
Wang, Z.
Feng, Z.
Armstrong, S. A.
TI Genetic and pharmacologic inhibition of beta-Catenin (Ctnnb1) targets
imatinib resistant leukemia stem cells in CML
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Heidel, F. H.] Univ Magdeburg, Klin Haematol Onkol, D-39106 Magdeburg, Germany.
[Heidel, F. H.; Wang, Z.; Feng, Z.; Armstrong, S. A.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA.
[Armstrong, S. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Armstrong, S. A.] Harvard Stem Cell Inst HSCI, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD SEP
PY 2011
VL 34
SU 6
BP 29
EP 30
PG 2
GA 823XG
UT WOS:000295160600070
ER
PT J
AU Koch, R
Diering, N
Lahmann, M
Demant, M
Aung, T
Chapuy, B
Becker, S
Sinzig, U
Trumper, L
Wulf, G
AF Koch, R.
Diering, N.
Lahmann, M.
Demant, M.
Aung, T.
Chapuy, B.
Becker, S.
Sinzig, U.
Truemper, L.
Wulf, G.
TI Homeostasis of lymphoma side population cells in aggressive B-cell
lymphoma
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Koch, R.; Diering, N.; Lahmann, M.; Demant, M.; Aung, T.; Becker, S.; Sinzig, U.; Truemper, L.; Wulf, G.] Univ Med Gottingen, Gottingen, Germany.
[Chapuy, B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD SEP
PY 2011
VL 34
SU 6
BP 190
EP 190
PG 1
GA 823XG
UT WOS:000295160600502
ER
PT J
AU Rummel, M
Kuter, D
Mandanas, R
Giagounidis, A
Wang, X
Matthias, SD
Deuson, R
AF Rummel, M.
Kuter, D.
Mandanas, R.
Giagounidis, A.
Wang, X.
Matthias, S. D.
Deuson, R.
TI Quality of Life (QOL) in nonsplenectomized Immune Thrombocytopenia (ITP)
patients receiving romiplostim or Standard of Care (SOC)
SO ONKOLOGIE
LA English
DT Meeting Abstract
C1 [Rummel, M.] Klinikum Justus Liebig Univ, Giessen, Germany.
[Kuter, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mandanas, R.] Integris Canc Inst Oklahoma, Oklahoma City, OK USA.
[Giagounidis, A.] St Johannes Hosp, Duisburg, Germany.
[Wang, X.; Deuson, R.] Amgen Inc, Thousand Oaks, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-584X
J9 ONKOLOGIE
JI Onkologie
PD SEP
PY 2011
VL 34
SU 6
BP 239
EP 240
PG 2
GA 823XG
UT WOS:000295160600640
ER
PT J
AU Desai, KH
Tan, CS
Leek, JT
Maier, RV
Tompkins, RG
Storey, JD
AF Desai, Keyur H.
Tan, Chuen Seng
Leek, Jeffrey T.
Maier, Ronald V.
Tompkins, Ronald G.
Storey, John D.
CA Inflammation Host Response Injury
TI Dissecting Inflammatory Complications in Critically Injured Patients by
Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics
Study
SO PLOS MEDICINE
LA English
DT Article
ID NF-KAPPA-B; MULTIPLE ORGAN FAILURE; RESPONSE SYNDROME; SYSTEMIC
INFLAMMATION; NOSOCOMIAL INFECTION; DR EXPRESSION; SEPTIC SHOCK; TRAUMA;
SEPSIS; MORTALITY
AB Background: Trauma is the number one killer of individuals 1-44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition.
Methods and Findings: We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring,400 clinical variables and longitudinally profiling leukocyte gene expression with similar to 800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40-80 h window post-injury.
Conclusions: The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions.
C1 [Desai, Keyur H.; Tan, Chuen Seng; Storey, John D.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
[Leek, Jeffrey T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA.
[Tompkins, Ronald G.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Storey, John D.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
RP Desai, KH (reprint author), Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
EM jstorey@princeton.edu
RI Tan, Chuen Seng/K-1078-2013;
OI Tan, Chuen Seng/0000-0002-6513-2309; Leek, Jeffrey/0000-0002-2873-2671
FU NIH [U54 GM-62119]
FX This research is supported in part by NIH grant U54 GM-62119 (PI: Ronald
Tompkins). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 45
TC 21
Z9 23
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD SEP
PY 2011
VL 8
IS 9
AR e1001093
DI 10.1371/journal.pmed.1001093
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 825ZW
UT WOS:000295321900009
PM 21931541
ER
PT J
AU King, BS
Sturtevant, OJ
Kao, G
AF King, B. S.
Sturtevant, O. J.
Kao, G.
TI Using Novel Parameters in Predicting Stem Cell Mobilization
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 22-25, 2011
CL San Diego, CA
SP AABB
C1 [Sturtevant, O. J.; Kao, G.] Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02115 USA.
EM bking3@partners.org
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2011
VL 51
SU 3
SI SI
BP 220A
EP 220A
PG 1
WC Hematology
SC Hematology
GA 822YC
UT WOS:000295085500565
ER
EF