FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Jacobs, JP
O'Brien, SM
Shahian, DM
Edwards, FH
Badhwar, V
Dokholyan, RS
Sanchez, JA
Morales, DL
Prager, RL
Wright, CD
Puskas, JD
Gammie, JS
Haan, CK
George, KM
Sheng, SB
Peterson, ED
Shewan, CM
Han, JM
Bongiorno, PA
Yohe, C
Williams, WG
Mayer, JE
Grover, FL
AF Jacobs, Jeffrey P.
O'Brien, Sean M.
Shahian, David M.
Edwards, Fred H.
Badhwar, Vinay
Dokholyan, Rachel S.
Sanchez, Juan A.
Morales, David L.
Prager, Richard L.
Wright, Cameron D.
Puskas, John D.
Gammie, James S.
Haan, Constance K.
George, Kristopher M.
Sheng, Shubin
Peterson, Eric D.
Shewan, Cynthia M.
Han, Jane M.
Bongiorno, Phillip A.
Yohe, Courtney
Williams, William G.
Mayer, John E.
Grover, Frederick L.
TI Successful linking of the Society of Thoracic Surgeons Database to
Social Security data to examine the accuracy of Society of Thoracic
Surgeons mortality data
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT International Mesothelioma Interest Group Congress
CY SEP 11-14, 2012
CL Boston, MA
ID CORONARY-ARTERY-BYPASS; LONG-TERM SURVIVAL; CARDIAC-SURGERY; PUMP
AB Objectives: The Society of Thoracic Surgeons Adult Cardiac Surgery Database has been linked to the Social Security Death Master File to verify "life status" and evaluate long-term surgical outcomes. The objective of this study is explore practical applications of the linkage of the Society of Thoracic Surgeons Adult Cardiac Surgery Database to Social Securtiy Death Master File, including the use of the Social Securtiy Death Master File to examine the accuracy of the Society of Thoracic Surgeons 30-day mortality data.
Methods: On January 1, 2008, the Society of Thoracic Surgeons Adult Cardiac Surgery Database began collecting Social Security numbers in its new version 2.61. This study includes all Society of Thoracic Surgeons Adult Cardiac Surgery Database records for operations with nonmissing Social Security numbers between January 1, 2008, and December 31, 2010, inclusive. To match records between the Society of Thoracic Surgeons Adult Cardiac Surgery Database and the Social Security Death Master File, we used a combined probabilistic and deterministic matching rule with reported high sensitivity and nearly perfect specificity.
Results: Between January 1, 2008, and December 31, 2010, the Society of Thoracic Surgeons Adult Cardiac Surgery Database collected data for 870,406 operations. Social Security numbers were available for 541,953 operations and unavailable for 328,453 operations. According to the Society of Thoracic Surgeons Adult Cardiac Surgery Database, the 30-day mortality rate was 17,757/541,953 = 3.3%. Linkage to the Social Security Death Master File identified 16,565 cases of suspected 30-day deaths (3.1%). Of these, 14,983 were recorded as 30-day deaths in the Society of Thoracic Surgeons database (relative sensitivity = 90.4%). Relative sensitivity was 98.8% (12,863/13,014) for suspected 30-day deaths occurring before discharge and 59.7% (2120/3551) for suspected 30-day deaths occurring after discharge.
Conclusions: Linkage to the Social Security Death Master File confirms the accuracy of data describing "mortality within 30 days of surgery" in the Society of Thoracic Surgeons Adult Cardiac Surgery Database. The Society of Thoracic Surgeons and Social Security Death Master File link reveals that capture of 30-day deaths occurring before discharge is highly accurate, and that these in-hospital deaths represent the majority (79% [13,014/16,565]) of all 30-day deaths. Capture of the remaining 30-day deaths occurring after discharge is less complete and needs improvement. Efforts continue to encourage Society of Thoracic Surgeons Database participants to submit Social Security numbers to the Database, thereby enhancing accurate determination of 30-day life status. The Society of Thoracic Surgeons and Social Security Death Master File linkage can facilitate ongoing refinement of mortality reporting. (J Thorac Cardiovasc Surg 2013;145:976-83)
C1 [Jacobs, Jeffrey P.] Univ S Florida, All Childrens Hosp, Johns Hopkins Childrens Heart Surg, St Petersburg, FL 33701 USA.
[Jacobs, Jeffrey P.] All Childrens Hosp, Johns Hopkins Childrens Heart Surg, Tampa, FL USA.
[Jacobs, Jeffrey P.] All Childrens Hosp, Johns Hopkins Childrens Heart Surg, Orlando, FL USA.
[Jacobs, Jeffrey P.] Florida Hosp Children, St Petersburg, FL USA.
[Jacobs, Jeffrey P.] Florida Hosp Children, Tampa, FL USA.
[Jacobs, Jeffrey P.] Florida Hosp Children, Orlando, FL USA.
[O'Brien, Sean M.; Dokholyan, Rachel S.; Sheng, Shubin; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Shahian, David M.; Wright, Cameron D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Edwards, Fred H.; Haan, Constance K.] Univ Florida, Coll Med Jacksonville, Shands Jacksonville, Jacksonville, FL USA.
[Badhwar, Vinay] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Sanchez, Juan A.] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
[Morales, David L.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Prager, Richard L.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Puskas, John D.] Emory Univ, Div Cardiothorac Surg, Atlanta, GA 30322 USA.
[Gammie, James S.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[George, Kristopher M.] Cardiac Surg Associates Florida, Orlando, FL USA.
[Shewan, Cynthia M.; Han, Jane M.; Bongiorno, Phillip A.; Yohe, Courtney] Soc Thorac Surg, Chicago, IL USA.
[Shewan, Cynthia M.; Han, Jane M.; Bongiorno, Phillip A.; Yohe, Courtney] Soc Thorac Surg, Washington, DC USA.
[Williams, William G.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Mayer, John E.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Grover, Frederick L.] Univ Colorado Denver, Sch Med, Aurora, CO USA.
RP Jacobs, JP (reprint author), Univ S Florida, All Childrens Hosp, Ctr Heart, 625 6th Ave South,Suite 475, St Petersburg, FL 33701 USA.
EM JeffJacobs@msn.com
RI O'Brien, Sean/H-6268-2013; Sanchez, Juan/I-1936-2016
OI Sanchez, Juan/0000-0002-6789-3208
NR 21
TC 5
Z9 5
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD APR
PY 2013
VL 145
IS 4
BP 976
EP 983
DI 10.1016/j.jtcvs.2012.11.094
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 114PA
UT WOS:000316753100015
PM 23497944
ER
PT J
AU Baruch, L
Sherman, O
AF Baruch, Lawrence
Sherman, Olga
TI Utilization of laboratory testing to optimize dabigatran dosing in 5
octogenarians: Focus on the 75-mg BID dose
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Meeting Abstract
C1 [Baruch, Lawrence; Sherman, Olga] James J Peters VA Med Ctr, Bronx, NY USA.
[Baruch, Lawrence] Mt Sinai Sch Med, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD APR
PY 2013
VL 35
IS 3
SI SI
BP 404
EP 405
PG 2
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 115OQ
UT WOS:000316822100032
ER
PT J
AU McDermott, S
Oliveira, GR
Wicky, S
Oklu, R
AF McDermott, Shaunagh
Oliveira, George R.
Wicky, Stephan
Oklu, Rahmi
TI Measurements of the Left Common Iliac Vein Diameter May Not Be
Consistent over Time
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Letter
C1 [McDermott, Shaunagh; Oliveira, George R.; Wicky, Stephan; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA.
RP McDermott, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, 55 Fruit St,290A Gray Bigelow, Boston, MA 02114 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD APR
PY 2013
VL 24
IS 4
BP 192
EP 193
DI 10.1016/j.jvir.2013.01.502
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 115QW
UT WOS:000316828000025
PM 23522166
ER
PT J
AU Misra, S
Lookstein, R
Rundback, J
Hirsch, AT
Hiatt, WR
Jaff, MR
White, CR
Conte, M
Geraghty, P
Patel, M
Rosenfield, K
AF Misra, Sanjay
Lookstein, Robert
Rundback, John
Hirsch, Alan T.
Hiatt, William R.
Jaff, Michael R.
White, Christopher R.
Conte, Michael
Geraghty, Patrick
Patel, Manesh
Rosenfield, Kenneth
TI Proceedings from the Society of Interventional Radiology Research
Consensus Panel on Critical Limb Ischemia
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID PERIPHERAL ARTERIAL-DISEASE; DRUG-ELUTING STENTS; THE-KNEE LESIONS;
INFRAPOPLITEAL ARTERIES; DOUBLE-BLIND; OUTCOMES; THERAPY;
RECANALIZATION; RUNOFF; CLAUDICATION
C1 [Misra, Sanjay] Mayo Clin, Dept Radiol, Div Vasc & Intervent Radiol, Rochester, MN 55905 USA.
[Lookstein, Robert] Mt Sinai Hosp, New York, NY 10029 USA.
[Rundback, John] Holy Name Hosp, Cardiovasc Dis Intervent Inst, Teaneck, NJ USA.
[Hirsch, Alan T.] Univ Minnesota, Sch Med, Lillehei Heart Inst, Vasc Med Program, Minneapolis, MN 55455 USA.
Univ Minnesota, Sch Med, Div Cardiovasc, Minneapolis, MN 55455 USA.
[Hiatt, William R.] Univ Colorado Denver, Sch Med, Div Cardiol, Aurora, CO USA.
[Hiatt, William R.] Univ Colorado Denver, Sch Med, CPC Clin Res, Aurora, CO USA.
[Jaff, Michael R.; Rosenfield, Kenneth] Massachusetts Gen Hosp, Vasc Med & Intervent Dept, Boston, MA 02114 USA.
[White, Christopher R.] Ochsner Med Ctr, John Ochsner Heart & Vasc Inst, New Orleans, LA USA.
[Conte, Michael] UCSF Heart & Vasc Ctr, San Francisco, CA USA.
[Geraghty, Patrick] Washington Univ St Louis, Sch Med, St Louis, MO USA.
[Patel, Manesh] Duke Univ Hlth Syst, Durham, NC USA.
RP Misra, S (reprint author), Mayo Clin, Dept Radiol, Div Vasc & Intervent Radiol, 200 1st St SW, Rochester, MN 55905 USA.
FU SIR Foundation; NIH [HL098967, HL109192, HL 88476]; Covidien/ev3;
NHLBI/Washington University; SIRtex; Abbott; EKOS; Flexmedics; Aastrom;
CeloNova; Abbott Vascular; Aastrom Biosciences; Sanofi-aventis
Partnership; Cytokinetics; Viromed; AstraZeneca; DNAVEC; Pluristem;
Takeda; ReNeuron; Tarix; Theravasc; NHBLI; Johnson and Johnson; Astra
Zeneca; Baxter Healthcare; AHRQ; Cordis; Lutonix/Bard; Atrium; IDEV
Technologies
FX This meeting was funded by the SIR Foundation.; S.M. received funding
from NIH (HL098967, HL109192, HL 88476). He is on the data safety
monitoring board for Arteriocyte and Flexstent. R.L. is a consultant for
Bayer Interventional, Cordis, and Boston Scientific. J.R. is a
consultant for Covidien/ev3, Biotronik, St. Jude, EKOS, Simbionix, and
CSI, is a speaker for Boston Scientific, Terumo, and Cook, and received
research support from Covidien/ev3, NHLBI/Washington University, SIRtex,
Abbott, EKOS, Flexmedics, Aastrom, and CeloNova. A.T H. received
research grants from Abbott Vascular, Aastrom Biosciences,
Sanofi-aventis Partnership, Cytokinetics, and Viromed, is on the
advisory board of AstraZeneca and Merck, and is a consultant for
Novartis, Pozen, Summit Doppler, and Shire HGT. W.R.H. received grant
income for trials in peripheral artery disease structured as a contract
between the sponsor and CPC Clinical Research (a nonprofit research
center affiliated with the University of Colorado) from Aastrom,
AstraZeneca, DNAVEC, Pluristem, Takeda, ReNeuron, Tarix and Theravasc.
M.R.J. is a consultant for Abbott Vascular (noncompensated), Becker
Venture Services Group, Bluegrass Vascular Therapies, Cordis Corporation
(noncompensated), Covidien (noncompensated), Hansen Medical, Medtronic
(noncompensated), Micell Incorporated, Primacea, Trivascular Inc., and
Vortex, and has equity in Access Closure Inc., Embolitech Inc., Hotspur
Inc., Icon Interventional Inc., I.C. Sciences Inc., Janacare Inc.,
Northwind Medical Inc., PQ Bypass Inc., Primacea, Sadra Medical,
TMI/Trireme Inc., and Vascular Therapies Inc., is a board member of VIVA
Physicians (not for profit), and is a 501(c) 3 Organization member
(www.vivapvd com). C.J.W. is a consultant for Baxter Cellular Therapies
and is a member of the PAD Guidelines Task Force (ACC/AHA). He is the
CARE Steering committee chair (NCDR/ACC) and president of the Society of
Cardiovascular Angiography and Interventions (SCAI). M.C. is on the
advisory board of Aastrom Biosciences and Humacyte Inc P.G. is a
scientific advisory board member of Bard/Lutonix and Bayer/Medrad He is
an equity holder and has stock options with Pulse Therapeutics. M.P. has
research grants with NHBLI, Johnson and Johnson, Astra Zeneca, Baxter
Healthcare, and AHRQ and is a consultant and is on the advisory board of
Bayer Healthcare, Baxter, Genzyme, Otsuka, and Cardiostem. K R. is a
consultant for Abbott Vascular, Accelmed, Becker Ventures, Micell,
Complete Conference Management, Vortex/AngioDynamics, Endospan,
Medicines Company, Shockwave Medical, and VuMedi. He has equity in
CardioMEMs, Contego, Endospan, Embolitech, Icon, JanaCare, Medical
Simulation Corporation, Micell, Primacea, PQ Bypass, Shockwave Medical,
and Vortex. He received research or fellowship support from Abbott
Vascular, Cordis, Lutonix/Bard, Atrium, and IDEV Technologies. He is a
board member of VIVA Physicians (www.vivapvd.com).
NR 44
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 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD APR
PY 2013
VL 24
IS 4
BP 451
EP 458
DI 10.1016/j.jvir.2012.10.028
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 115QW
UT WOS:000316828000001
PM 23522155
ER
PT J
AU Gallagher, KA
Tracci, MC
Scovell, SD
AF Gallagher, Katherine A.
Tracci, Margaret Clarke
Scovell, Sherry D.
TI Vascular arteritides in women
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID GIANT-CELL ARTERITIS; OBLITERANS BUERGERS-DISEASE; RHEUMATOLOGY 1990
CRITERIA; ANCA-ASSOCIATED VASCULITIS; PLACEBO-CONTROLLED TRIAL;
MEDIUM-VESSEL VASCULITIS; SPINAL-CORD STIMULATION;
WEGENERS-GRANULOMATOSIS; THROMBOANGIITIS-OBLITERANS; FIBROMUSCULAR
DYSPLASIA
AB The vasculitides are multiple clinical disease states that are characterized by inflammation of the wall of blood vessels. They are typically classified by the size of the vessel that is affected. Some of the vasculitides are more commonly identified in women, such as the large-vessel vasculitides. In addition, the incidence of some of the medium and small-vessel vasculitides in women has increased during the past several decades. These inflammatory conditions specifically affecting women will be reviewed here. The implications that pregnancy may have on various vasculitides will also be highlighted. (J Vasc Surg 2013;57:27S-36S.)
C1 [Gallagher, Katherine A.] Univ Michigan, Med Ctr, Div Vasc & Endovasc Surg, Ann Arbor, MI USA.
[Tracci, Margaret Clarke] Univ Virginia Hlth Syst, Div Vasc & Endovasc Surg, Charlottesville, VA USA.
[Scovell, Sherry D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA.
RP Scovell, SD (reprint author), MGH North Shore Ctr Outpatient Care, 104 Endicott St,Ste 200, Danvers, MA 01923 USA.
EM sscovell@partners.org
NR 100
TC 1
Z9 1
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD APR
PY 2013
VL 57
IS 4
SU S
BP 27S
EP 36S
DI 10.1016/j.jvs.2012.10.119
PG 10
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 113KF
UT WOS:000316665200005
PM 23522715
ER
PT J
AU Bachler, BC
Humbert, M
Palikuqi, B
Siddappa, NB
Lakhashe, SK
Rasmussen, RA
Ruprecht, RM
AF Bachler, Barbara C.
Humbert, Michael
Palikuqi, Brisa
Siddappa, Nagadenahalli B.
Lakhashe, Samir K.
Rasmussen, Robert A.
Ruprecht, Ruth M.
TI Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine
Protection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 TAT PROTEIN; BIMODAL AIDS VACCINE;
B-CELL EPITOPES; RHESUS MACAQUES; TYPE-1 TAT; NEUTRALIZING ANTIBODIES;
MONOCLONAL-ANTIBODIES; CYNOMOLGUS MONKEYS; PEPTIDE LIBRARIES
AB Identifying immune correlates of protection is important to develop vaccines against infectious diseases. We designed a novel, universally applicable strategy to profile the antibody (Ab) repertoire of protected vaccine recipients, using recombinant phages encoding random peptide libraries. The new approach, termed "protection-linked (PL) biopanning," probes the Ab paratopes of protected vaccinees versus those with vaccine failure. As proof of concept, we screened plasma samples from vaccinated rhesus macaques (RMs) that had completely resisted multiple mucosal challenges with R5-tropic simian-human immunodeficiency viruses (SHIVs). The animals had been immunized with a multicomponent vaccine (multimeric HIV-1 gp160, HIV-1 Tat, and SIV Gag-Pol particles). After PL biopanning, we analyzed the phagotopes selected for amino acid homologies; in addition to the expected Env mimotopes, one recurring motif reflected the neutralizing Ab epitope at the N terminus (NT) of HIV-1 Tat. Subsequent binding and functional assays indicated that anti-Tat NT Abs were present only in completely or partially protected RMs; peak viremia of the latter was inversely correlated with anti-Tat NT Ab titers. In contrast, highly viremic, unvaccinated controls did not develop detectable Abs against the same epitope. Based upon the protective effect observed in vivo, we suggest that Tat should be included in multicomponent HIV-1 vaccines. Our data highlight the power of the new PL-biopanning strategy to identify Ab responses with significant association to vaccine protection, regardless of the mechanism(s) or targets of the protective Abs. PL biopanning is also unbiased with regard to pathogens or disease model, making it a universal tool.
C1 [Bachler, Barbara C.; Humbert, Michael; Palikuqi, Brisa; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Rasmussen, Robert A.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Bachler, Barbara C.] Univ Vet Med Vienna, VetCore, Res Facil, Vienna, Austria.
[Humbert, Michael; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Rasmussen, Robert A.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM ruth_ruprecht@dfci.harvard.edu
RI Lakhashe, Samir/F-1150-2014;
OI Byrareddy, Siddappa /0000-0002-7423-1763
FU National Institutes of Health [P01 AI048240, R37 AI034266, R01
AI100703]; Harvard University [P30 AI060354]
FX This work was supported by National Institutes of Health grants P01
AI048240, R37 AI034266, and R01 AI100703 to R.M.R. and Harvard
University C.F.A.R grant P30 AI060354.
NR 69
TC 19
Z9 19
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2013
VL 87
IS 8
BP 4403
EP 4416
DI 10.1128/JVI.02888-12
PG 14
WC Virology
SC Virology
GA 113MC
UT WOS:000316671000026
PM 23388727
ER
PT J
AU Mallipattu, SK
Liu, RJ
Zhong, YF
Chen, EY
D'Agati, V
Kaufman, L
Ma'ayan, A
Klotman, PE
Chuang, PY
He, JC
AF Mallipattu, Sandeep K.
Liu, Ruijie
Zhong, Yifei
Chen, Ed Y.
D'Agati, Vivette
Kaufman, Lewis
Ma'ayan, Avi
Klotman, Paul E.
Chuang, Peter Y.
He, John C.
TI Expression of HIV transgene aggravates kidney injury in diabetic mice
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE diabetic nephropathy; glomerulopathy; HIV
ID ACQUIRED IMMUNODEFICIENCY SYNDROME; HIV-1-ASSOCIATED NEPHROPATHY;
INFECTED PATIENTS; RENAL-DISEASE; MOUSE KIDNEY; GLOMERULOSCLEROSIS;
GENES; PODOCYTES; PROTEIN; BIOPSY
AB With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy has decreased. Currently, HIV-infected patients live much longer and often suffer from comorbidities such as diabetes mellitus. Recent epidemiological studies suggest that concurrent HIV infection and diabetes mellitus may have a synergistic effect on the incidence of chronic kidney disease. To address this, we determined whether HIV-1 transgene expression accelerates diabetic kidney injury using a diabetic HIV-1 transgenic (Tg26) murine model. Diabetes was initially induced with low-dose streptozotocin in both Tg26 and wildtype mice on a C57BL/6 background, which is resistant to classic HIV-associated nephropathy. Although diabetic nephropathy is minimally observed on the C57BL/6 background, diabetic Tg26 mice exhibited a significant increase in glomerular injury compared with nondiabetic Tg26 mice and diabetic wild-type mice. Validation of microarray gene expression analysis from isolated glomeruli showed a significant upregulation of proinflammatory pathways in diabetic Tg26 mice. Thus, our study found that expression of HIV-1 genes aggravates diabetic kidney disease. Kidney International (2013) 83, 626-634; doi:10.1038/ki.2012.445; published online 16 January 2013
C1 [Mallipattu, Sandeep K.; Liu, Ruijie; Kaufman, Lewis; Chuang, Peter Y.; He, John C.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA.
[Liu, Ruijie; He, John C.] James J Peters VA Med Ctr, Renal Sect, New York, NY USA.
[Zhong, Yifei] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Nephrol, Shanghai, Peoples R China.
[Chen, Ed Y.; Ma'ayan, Avi; He, John C.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
[D'Agati, Vivette] Columbia Univ, Dept Pathol, New York, NY USA.
[Klotman, Paul E.] Baylor Coll Med, Houston, TX 77030 USA.
RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA.
EM cijiang.he@mssm.edu
RI Mallipattu , Sandeep/M-7009-2014
FU NIH/NIDDK [1R01DK078897-01, 2012CB517601, P01DK056492, 5K08DK082760, T32
DK07757-12, 1F32 DK094635-01]
FX We thank Dr A Gharavi for use of the backcrossed Tg26 mice. This work
was supported by funds from the NIH/NIDDK (1R01DK078897-01 and 973 fund
2012CB517601 to JCH, P01DK056492 to PEK and JCH, 5K08DK082760 to PYC,
and T32 DK07757-12 and 1F32 DK094635-01 to SKM).
NR 41
TC 19
Z9 19
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD APR
PY 2013
VL 83
IS 4
BP 626
EP 634
DI 10.1038/ki.2012.445
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 117HY
UT WOS:000316945400014
PM 23325078
ER
PT J
AU Bonawitz, SC
Duvvuri, U
AF Bonawitz, Steven C.
Duvvuri, Umamaheswar
TI Robotic-assisted FAMM flap for soft palate reconstruction
SO LARYNGOSCOPE
LA English
DT Article
DE FAMM flap; robotic; oropharyngeal
ID ARTERY MUSCULOMUCOSAL FLAP; NECK-CANCER; SURGERY TORS; HEAD; DEFECTS
AB Objectives/Hypothoses: TORS (Trans Oral Robotic Surgery) has been demonstrated to be an acceptable alternative to chemoradiation for the treatment of early stage malignant lesions of the oropharynx, with equivalent tumor control and enhanced functional outcomes. Surgical ablation of tumors of the oropharynx under conditions of limited access, however, creates the need to adapt the robotic platform to surgical reconstruction and to assess reconstructive outcomes. We present our experience with the Facial Artery Musculomucosal (FAMM) flap with robotic assistance for the reconstruction of defects of the soft palate. Methods: We reviewed the records of five patients who underwent combined robot-assisted resection of malignant lesions of the oropharynx with immediate reconstruction. The reconstructions included four ispilateral and one bilateral FAMM flaps. Patients were assessed for complications and functional results. Results: Successful closure of the defect was achieved in all five patients. There were no major complications; however, three patients developed minor wound dehiscence and two were revised at the time of planned subsequent lymphadenectomy. All five patients achieved a good functional outcome. Conclusions: The FAMM flap is reliable and easy to raise and transfer, with the surgical robot making it a good candidate for reconstruction of moderate-sized defects created by TORS applied to malignancies of the soft palate. Minor wound dehiscence is not infrequent, but reconstructive outcomes are nevertheless good. A unilateral FAMM flap will reach to the contralateral border of the uvula and is best limited to defects with a width of 2 cm or less.
C1 [Bonawitz, Steven C.] Johns Hopkins Univ, Sch Med, Dept Plast & Reconstruct Surg, Baltimore, MD USA.
[Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Syst, Dept Otolaryngol,Eye & Ear Inst, Pittsburgh, PA 15213 USA.
RP Duvvuri, U (reprint author), Univ Pittsburgh, Med Ctr, Dept Head & Neck Surg, Inst Eye & Ear, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM duvvuriu@upmc.edu
NR 17
TC 7
Z9 7
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD APR
PY 2013
VL 123
IS 4
BP 870
EP 874
DI 10.1002/lary.23578
PG 5
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 115KZ
UT WOS:000316812400012
PM 23529879
ER
PT J
AU Kleiss, IJ
Hohman, MH
Quatela, OE
Marres, HAM
Hadlock, TA
AF Kleiss, Ingrid J.
Hohman, Marc H.
Quatela, Olivia E.
Marres, Henri A. M.
Hadlock, Tessa A.
TI Computer-Assisted Assessment of Ocular Synkinesis: A Comparison of
Methods
SO LARYNGOSCOPE
LA English
DT Article
DE Facial nerve; facial paralysis; ocular synkinesis; assessment;
objective; Facial Assessment by Computer Evaluation; Glasgow Facial
Palsy Scale
ID FACIAL-NERVE FUNCTION; GRADING SYSTEM; OBJECTIVE METHOD; MEASUREMENT
TOOL; CONTROLLED-TRIAL; BOTULINUM-TOXIN; HOUSE-BRACKMANN; MOVEMENT;
PARALYSIS; MOTION
AB Objectives/Hypothesis: To define an objective, easy to perform, rapid method for the assessment of ocular synkinesis by employing both the Facial Assessment by Computer Evaluation software and a modification of the Glasgow Facial Palsy Scale. Study Design: Retrospective study. Methods: Fifty normal subjects and 50 patients with known ocular synkinesis were studied. Measurements of ocular synkinesis were made using the semiautomated Facial Assessment by Computer Evaluation software, and a modification of the automated Glasgow Facial Palsy program. Results: The mean resting vertical palpebral fissure width of a normal eye was 10.17 mm (standard deviation [SD], 1.63 mm), and the degree of eye closure during smile was on average 21.56% (SD, 13.38%). Synkinetic eyes had a statistically significantly smaller resting palpebral fissure width on average (8.99 mm; SD, 1.61 mm; P < .001, t test), and a statistically significantly greater degree of narrowing during smiling (32.65%; SD, 13.68%; P < .001, t test). Using a modified synkinesis-determining application of the Glasgow Facial Palsy Scale did not consistently correlate with the Facial Assessment by Computer Evaluation program or clinical observations of eye closure during smiling (R = 0.251, Pearson correlation) and puckering (R = 0.253, Pearson correlation). Conclusions: The Facial Assessment by Computer Evaluation program yields rapid, consistent, palpebral fissure width measurements, and when combined with a subjective self-assessment questionnaire yields a comprehensive measure of ocular synkinesis. Our modified application of the Glasgow Facial Palsy Scale did not appear to be a reliable method for quantitative ocular synkinesis assessment.
C1 [Kleiss, Ingrid J.; Hohman, Marc H.; Quatela, Olivia E.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Kleiss, Ingrid J.; Marres, Henri A. M.] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, NL-6525 ED Nijmegen, Netherlands.
RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM tessa_hadlock@meei.harvard.edu
RI Marres, H.A.M./H-8071-2014
NR 28
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD APR
PY 2013
VL 123
IS 4
BP 879
EP 883
DI 10.1002/lary.23778
PG 5
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 115KZ
UT WOS:000316812400014
PM 23404714
ER
PT J
AU Dalal, SR
Shekelle, PG
Hempel, S
Newberry, SJ
Motala, A
Shetty, KD
AF Dalal, Siddhartha R.
Shekelle, Paul G.
Hempel, Susanne
Newberry, Sydne J.
Motala, Aneesa
Shetty, Kanaka D.
TI A Pilot Study Using Machine Learning and Domain Knowledge to Facilitate
Comparative Effectiveness Review Updating
SO MEDICAL DECISION MAKING
LA English
DT Review
DE machine learning; comparative effectiveness reviews; text classification
ID SYSTEMATIC REVIEWS; TEXT CATEGORIZATION; CONTROLLED-TRIAL; CONCEPT
DRIFT; DOUBLE-BLIND; OSTEOPOROSIS; OLANZAPINE; REGRESSION; MODELS
AB Background. Comparative effectiveness and systematic reviews require frequent and time-consuming updating. Results of earlier screening should be useful in reducing the effort needed to screen relevant articles. Methods. We collected 16,707 PubMed citation classification decisions from 2 comparative effectiveness reviews: interventions to prevent fractures in low bone density (LBD) and off-label uses of atypical antipsychotic drugs (AAP). We used previously written search strategies to guide extraction of a limited number of explanatory variables pertaining to the intervention, outcome, and study design. We empirically derived statistical models (based on a sparse generalized linear model with convex penalties [GLMnet] and a gradient boosting machine [GBM]) that predicted article relevance. We evaluated model sensitivity, positive predictive value (PPV), and screening workload reductions using 11,003 PubMed citations retrieved for the LBD and AAP updates. Results. GLMnet-based models performed slightly better than GBM-based models. When attempting to maximize sensitivity for all relevant articles, GLMnet-based models achieved high sensitivities (0.99 and 1.0 for AAP and LBD, respectively) while reducing projected screening by 55.4% and 63.2%. The GLMnet-based model yielded sensitivities of 0.921 and 0.905 and PPVs of 0.185 and 0.102 when predicting articles relevant to the AAP and LBD efficacy/effectiveness analyses, respectively (using a threshold of P >= 0.02). GLMnet performed better when identifying adverse effect relevant articles for the AAP review (sensitivity = 0.981) than for the LBD review (0.685). The system currently requires MEDLINE-indexed articles. Conclusions. We evaluated statistical classifiers that used previous classification decisions and explanatory variables derived from MEDLINE indexing terms to predict inclusion decisions. This pilot system reduced workload associated with screening 2 simulated comparative effectiveness review updates by more than 50% with minimal loss of relevant articles.
C1 [Dalal, Siddhartha R.; Shekelle, Paul G.; Hempel, Susanne; Newberry, Sydne J.; Motala, Aneesa; Shetty, Kanaka D.] RAND Corp, Southern Calif Evidence Based Practice Ctr, Santa Monica, CA 90401 USA.
[Shekelle, Paul G.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA.
RP Dalal, SR (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA.
EM sdalal@rand.org
FU RAND Corporation; Agency for Healthcare Research and Quality
[290-2007-10062-I]
FX Received 21 March 2012 from Southern California Evidence-based Practice
Center, RAND Corporation, Santa Monica, CA (SRD, PGS, SH, SJN, AM, KDS);
and the Greater Los Angeles Veterans Affairs Healthcare System, Los
Angeles, CA (PGS). This work was largely produced under Agency for
Healthcare Research and Quality Contract No. 290-2007-10062-I. The
funding agreement ensured the authors' independence in designing the
study, interpreting the data, and writing and publishing the report.
This work was also funded by an internal grant from the RAND
Corporation. The RAND Corporation played no role in the design or
conduct of the study. Revision accepted for publication 29 May 2012.
NR 40
TC 5
Z9 5
U1 1
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD APR
PY 2013
VL 33
IS 3
SI SI
BP 343
EP 355
DI 10.1177/0272989X12457243
PG 13
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 113RH
UT WOS:000316685000006
PM 22961102
ER
PT J
AU Saleem, F
Bouatra, S
Guo, AC
Psychogios, N
Mandal, R
Dunn, SM
Ametaj, BN
Wishart, DS
AF Saleem, Fozia
Bouatra, Souhaila
Guo, An Chi
Psychogios, Nikolaos
Mandal, Rupasri
Dunn, Suzanna M.
Ametaj, Burim N.
Wishart, David S.
TI The Bovine Ruminal Fluid Metabolome
SO METABOLOMICS
LA English
DT Article
DE Rumen fluid; Bovine Metabolome; Metabolomics; Nuclear magnetic
resonance; Mass spectrometry; ICP-MS
ID QUANTITATIVE METABOLOMICS; H-1-NMR SPECTROSCOPY; RUMEN MICROORGANISMS;
LINOLEIC-ACID; FATTY-ACIDS; DAIRY-COWS; NMR; DOMESTICATION; PERFORMANCE;
MANAGEMENT
AB The rumen is a unique organ that serves as the primary site for microbial fermentation of ingested plant material for domestic livestock such as cattle, sheep and goats. The chemical composition of ruminal fluid is thought to closely reflect the healthy/unhealthy interaction between rumen microflora and diet. Just as diet and feed quality is important for livestock production, rumen health is also critical to the growth and production of high quality milk and meat. Therefore a detailed understanding of the chemical composition of ruminal fluid and the influence of diet on its composition could help improve the efficiency and effectiveness of farming and veterinary practices. Consequently we have undertaken an effort to comprehensively characterize the bovine ruminal fluid metabolome. In doing so, we combined NMR spectroscopy, inductively coupled plasma mass-spectroscopy (ICP-MS), gas chromatography-mass spectrometry (GC-MS), direct flow injection (DFI) mass spectrometry and lipidomics with computer-aided literature mining to identify and quantify essentially all of the metabolites in bovine ruminal fluid that can be routinely detected (with today's technology). The use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these techniques. Tables containing the set of 246 ruminal fluid metabolites or metabolite species, their concentrations, related literature reference and links to their known diet associations for the bovine rumen metabolome are freely available at http://www.rumendb.ca.
C1 [Saleem, Fozia; Bouatra, Souhaila; Guo, An Chi; Mandal, Rupasri; Wishart, David S.] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E8, Canada.
[Psychogios, Nikolaos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Dunn, Suzanna M.; Ametaj, Burim N.] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB T6G 2E8, Canada.
[Wishart, David S.] Univ Alberta, Dept Comp Sci, Edmonton, AB T6G 2E8, Canada.
RP Wishart, DS (reprint author), Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E8, Canada.
EM burim.ametaj@ualberta.ca; dwishart@ualberta.ca
OI Psychogios, Nikolaos/0000-0002-2747-6012; Wishart, David
S/0000-0002-3207-2434
FU Alberta Agricultural Research Institute (AARI; Edmonton, Alberta,
Canada); Alberta Livestock and Meat Agency Ltd. (ALMA; Edmonton,
Alberta, Canada); Genome Alberta (Calgary, Alberta, Canada); Natural
Sciences and Engineering Research Council of Canada (NSERC; Ottawa,
Ontario, Canada)
FX Financial support for this work was provided by the Alberta Agricultural
Research Institute (AARI; Edmonton, Alberta, Canada), the Alberta
Livestock and Meat Agency Ltd. (ALMA; Edmonton, Alberta, Canada), Genome
Alberta (Calgary, Alberta, Canada) and the Natural Sciences and
Engineering Research Council of Canada (NSERC; Ottawa, Ontario, Canada).
We also are grateful to the technical staff of Dairy Research and
Technology Centre at the University of Alberta for their help in caring
for and monitoring the cows used in this study.
NR 45
TC 10
Z9 11
U1 10
U2 84
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1573-3882
J9 METABOLOMICS
JI Metabolomics
PD APR
PY 2013
VL 9
IS 2
BP 360
EP 378
DI 10.1007/s11306-012-0458-9
PG 19
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 116WG
UT WOS:000316913200009
ER
PT J
AU Ogino, S
Lochhead, P
Chan, AT
Nishihara, R
Cho, E
Wolpin, BM
Meyerhardt, JA
Meissner, A
Schernhammer, ES
Fuchs, CS
Giovannucci, E
AF Ogino, Shuji
Lochhead, Paul
Chan, Andrew T.
Nishihara, Reiko
Cho, Eunyoung
Wolpin, Brian M.
Meyerhardt, Jeffrey A.
Meissner, Alexander
Schernhammer, Eva S.
Fuchs, Charles S.
Giovannucci, Edward
TI Molecular pathological epidemiology of epigenetics: emerging integrative
science to analyze environment, host, and disease
SO MODERN PATHOLOGY
LA English
DT Review
DE CIMP; genetics; hypermethylation; molecular pathological epidemiology;
omics; personalized therapy; unique tumor principle
ID ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER RISK; BODY-MASS INDEX;
FATTY-ACID SYNTHASE; III COLON-CANCER; MICROSATELLITE INSTABILITY
STATUS; ONE-CARBON METABOLISM; POSTMENOPAUSAL HORMONE-THERAPY;
GENOME-WIDE ASSOCIATION; POPULATION-BASED SAMPLE
AB Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator phenotype, LINE-1 (long interspersed nucleotide element-1; also called long interspersed nuclear element-1; long interspersed element-1; L1) hypomethylation, etc), and host-disease interactions. In this article, we illustrate increasing contribution of modern pathology to broader public health sciences, which attests pivotal roles of pathologists in the new integrated MPE science towards our ultimate goal of personalized medicine and prevention. Modern Pathology (2013) 26, 465-484; doi:10.1038/modpathol.2012.214; published online 11 January 2013
C1 [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Ogino, Shuji; Chan, Andrew T.; Cho, Eunyoung; Schernhammer, Eva S.; Fuchs, Charles S.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA.
[Ogino, Shuji; Schernhammer, Eva S.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Ogino, Shuji; Lochhead, Paul; Nishihara, Reiko; Wolpin, Brian M.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.; Cho, Eunyoung; Schernhammer, Eva S.; Fuchs, Charles S.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Meissner, Alexander] Broad Inst MIT & Harvard Univ, Cambridge, MA USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Dept Epidemiol,Dept Pathol, 450 Brookline Ave,Room JF 215C, Boston, MA 02215 USA.
EM shuji_ogino@dfci.harvard.edu
FU USA National Institute of Health (NIH) [R01 CA151993, R01 CA137178, R01
CA136950, R01 CA149222, P50 CA127003, R01 CA124908, P01 CA87969, 1UM1
CA167552]
FX This work was supported by grants from USA National Institute of Health
(NIH) (R01 CA151993 (to SO), R01 CA137178 (to ATC), R01 CA136950 (to
EC), R01 CA149222 (to JAM), P50 CA127003 (to CSF), R01 CA124908 (to
CSF), P01 CA87969 (to SE Hankinson), and 1UM1 CA167552 (to WC Willett)).
PL is a Scottish Government Clinical Academic Fellow. ATC is a Damon
Runyon Clinical Investigator. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
NIH. Funding agencies did not have any role in the decision to submit
the manuscript for publication, or the writing of the manuscript.
NR 381
TC 97
Z9 97
U1 2
U2 86
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD APR
PY 2013
VL 26
IS 4
BP 465
EP 484
DI 10.1038/modpathol.2012.214
PG 20
WC Pathology
SC Pathology
GA 117GN
UT WOS:000316941600001
PM 23307060
ER
PT J
AU Ryan, RJH
Akin, C
Castells, M
Wills, M
Selig, MK
Nielsen, GP
Ferry, JA
Hornick, JL
AF Ryan, Russell J. H.
Akin, Cem
Castells, Mariana
Wills, Marcia
Selig, Martin K.
Nielsen, G. Petur
Ferry, Judith A.
Hornick, Jason L.
TI Mast cell sarcoma: a rare and potentially under-recognized diagnostic
entity with specific therapeutic implications
SO MODERN PATHOLOGY
LA English
DT Article
DE mast cell sarcoma; mastocytosis; urticaria pigmentosa; KIT mutation;
imatinib
ID MASTOCYTOSIS; IMATINIB; ADULTS
AB Mast cell sarcoma is a rare, aggressive neoplasm composed of cytologically malignant mast cells presenting as a solitary mass. Previous descriptions of mast cell sarcoma have been limited to single case reports, and the pathologic features of this entity are not well known. Here, we report three new cases of mast cell sarcoma and review previously reported cases. Mast cell sarcoma has a characteristic morphology of medium-sized to large epithelioid cells, including bizarre multinucleated cells, and does not closely resemble either normal mast cells or the spindle cells of systemic mastocytosis. One of our three cases arose in a patient with a remote history of infantile cutaneous mastocytosis, an association also noted in one previous case report. None of our three cases were correctly diagnosed as mast cell neoplasms on initial pathological evaluation, suggesting that this entity may be under-recognized. Molecular testing of mast cell sarcoma has not thus far detected the imatinib-resistant KIT D816V mutation, suggesting that recognition of these cases may facilitate specific targeted therapy. Modern Pathology (2013) 26, 533-543; doi:10.1038/modpathol.2012.199; published online 30 November 2012
C1 [Ryan, Russell J. H.; Selig, Martin K.; Nielsen, G. Petur; Ferry, Judith A.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Ryan, Russell J. H.; Selig, Martin K.; Nielsen, G. Petur; Ferry, Judith A.; Hornick, Jason L.] Harvard Univ, Sch Med, Boston, MA USA.
[Akin, Cem; Castells, Mariana; Hornick, Jason L.] Harvard Univ, Sch Med, Mastocytosis Ctr, Boston, MA USA.
[Akin, Cem; Castells, Mariana] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Wills, Marcia] Aurora Diagnost, Seacoast Pathol, Exeter, NH USA.
[Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Ryan, RJH (reprint author), Massachusetts Gen Hosp, Pathol Serv, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA.
EM rryan6@partners.org; jhornick@partners.org
OI Akin, Cem/0000-0001-6301-4520
NR 22
TC 10
Z9 10
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD APR
PY 2013
VL 26
IS 4
BP 533
EP 543
DI 10.1038/modpathol.2012.199
PG 11
WC Pathology
SC Pathology
GA 117GN
UT WOS:000316941600007
PM 23196796
ER
PT J
AU He, J
Shen, L
Wan, M
Taranova, O
Wu, H
Zhang, Y
AF He, Jin
Shen, Li
Wan, Ma
Taranova, Olena
Wu, Hao
Zhang, Yi
TI Kdm2b maintains murine embryonic stem cell status by recruiting PRC1
complex to CpG islands of developmental genes
SO NATURE CELL BIOLOGY
LA English
DT Article
ID POLYCOMB REPRESSIVE COMPLEX-2; HISTONE H3; MOUSE DEVELOPMENT; INK4A/ARF
LOCUS; TARGET GENES; HUMAN GENOME; CXXC DOMAIN; PLURIPOTENT; PROTEINS;
METHYLATION
AB Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, how PcG proteins are recruited to their target genes is largely unknown. Here, we show that the H3K36-specific histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4 and Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CxxC-ZF domain, which mediates its genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals an Oct4-Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining the undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression.
C1 [He, Jin; Shen, Li; Wan, Ma; Taranova, Olena; Wu, Hao; Zhang, Yi] Howard Hughes Med Inst, Boston, MA 02115 USA.
[He, Jin; Shen, Li; Wan, Ma; Taranova, Olena; Wu, Hao; Zhang, Yi] Program Cellular & Mol Med, Boston, MA 02115 USA.
[He, Jin; Shen, Li; Wan, Ma; Taranova, Olena; Wu, Hao; Zhang, Yi] Boston Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA.
[Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA.
RP Zhang, Y (reprint author), Howard Hughes Med Inst, WAB 149G,200 Longwood Ave, Boston, MA 02115 USA.
EM yzhang@genetics.med.harvard.edu
RI Wu, Hao/G-4145-2013
OI Wu, Hao/0000-0002-1256-6891
FU NIH [GM068804, U01DK089565]
FX We thank R. Klose for the plasmid pGEM3z-601. This project was supported
by NIH GM068804 and U01DK089565. Y.Z. is an investigator of the Howard
Hughes Medical Institute.
NR 59
TC 92
Z9 94
U1 1
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD APR
PY 2013
VL 15
IS 4
BP 373
EP +
DI 10.1038/ncb2702
PG 22
WC Cell Biology
SC Cell Biology
GA 118DX
UT WOS:000317004200008
PM 23502314
ER
PT J
AU Kokel, D
Cheung, CYJ
Mills, R
Coutinho-Budd, J
Huang, LY
Setola, V
Sprague, J
Jin, S
Jin, YN
Huang, XP
Bruni, G
Woolf, CJ
Roth, BL
Hamblin, MR
Zylka, MJ
Milan, DJ
Peterson, RT
AF Kokel, David
Cheung, Chung Yan J.
Mills, Robert
Coutinho-Budd, Jaeda
Huang, Liyi
Setola, Vincent
Sprague, Jared
Jin, Shan
Jin, Youngnam N.
Huang, Xi-Ping
Bruni, Giancarlo
Woolf, Clifford J.
Roth, Bryan L.
Hamblin, Michael R.
Zylka, Mark J.
Milan, David J.
Peterson, Randall T.
TI Photochemical activation of TRPA1 channels in neurons and animals
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; ION CHANNELS; GLUTAMATE-RECEPTOR;
REMOTE-CONTROL; COVALENT MODIFICATION; CAGED GLUTAMATE; OPTICAL CONTROL;
ZEBRAFISH; LIGHT; PHOTOSTIMULATION
AB Optogenetics is a powerful research tool because it enables high-resolution optical control of neuronal activity. However, current optogenetic approaches are limited to transgenic systems expressing microbial opsins and other exogenous photoreceptors. Here, we identify optovin, a small molecule that enables repeated photoactivation of motor behaviors in wild-type zebrafish and mice. To our surprise, optovin's behavioral effects are not visually mediated. Rather, photodetection is performed by sensory neurons expressing the cation channel TRPA1. TRPA1 is both necessary and sufficient for the optovin response. Optovin activates human TRPA1 via structure-dependent photochemical reactions with redox-sensitive cysteine residues. In animals with severed spinal cords, optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination. These studies identify a light-based strategy for controlling endogenous TRPA1 receptors in vivo, with potential clinical and research applications in nontransgenic animals, including humans.
C1 [Kokel, David; Cheung, Chung Yan J.; Mills, Robert; Jin, Shan; Jin, Youngnam N.; Bruni, Giancarlo; Milan, David J.; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA USA.
[Kokel, David; Cheung, Chung Yan J.; Mills, Robert; Jin, Shan; Jin, Youngnam N.; Bruni, Giancarlo; Milan, David J.; Peterson, Randall T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA.
[Kokel, David; Cheung, Chung Yan J.; Jin, Shan; Jin, Youngnam N.; Bruni, Giancarlo; Peterson, Randall T.] Broad Inst, Cambridge, MA USA.
[Coutinho-Budd, Jaeda; Zylka, Mark J.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC USA.
[Zylka, Mark J.] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC USA.
[Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Huang, Liyi; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, Peoples R China.
[Setola, Vincent; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA.
[Setola, Vincent; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA.
[Sprague, Jared; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Childrens Hosp Boston, Boston, MA 02115 USA.
[Sprague, Jared] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Hamblin, Michael R.] Harvard Massachusetts Inst Technol Div Hlth Sci &, Cambridge, MA USA.
RP Kokel, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA USA.
EM dkokel@cvrc.mgh.harvard.edu; peterson@cvrc.mgh.harvard.edu
RI Roth, Bryan/F-3928-2010;
OI Bruni, Giancarlo/0000-0003-2850-4633; kokel, david/0000-0002-1981-1511;
Hamblin, Michael/0000-0001-6431-4605
FU US National Institutes of Health (NIH) [K01MH091449, MH086867, MH085205,
P01 NS072040, R01 AI050875]; Charles and Ann Sanders Massachusetts
General Hospital; Michael Hooker Chair; NIMH PDSP; National Institute of
Neurological Disorders and Stroke (NINDS) [R01NS060725, R01NS067688];
NINDS [F31NS068038]; NIH [HL109004, DA026982]
FX We thank K. Kwan and D. Corey (Harvard Medical School), T. Miyamoto and
A. Patapoutian (Scripps Research Institute), and T. Numata and Y. Mori
(Kyoto University) for human TrpA1 constructs. A. Schier, D. Prober and
D. Robson (Harvard University) generously provided TrpA1 mutant
zebrafish. We thank R. Gaudet, A. Vakkasglu, B. Shoichet, T. Dunn, M.
Ahrens, F. Engert, R. Mazitschek and members of our research groups for
helpful advice. This work was supported by US National Institutes of
Health (NIH) grants K01MH091449 (D.K.), MH086867 and MH085205 (R.T.P.),
P01 NS072040 (C.J.W.), R01 AI050875 (L.H. and M.R.H.); the Charles and
Ann Sanders Massachusetts General Hospital Research Scholar award
(R.T.P.); and the Michael Hooker Chair and the NIMH PDSP (B.L.R.).
M.J.Z. was supported by grants from National Institute of Neurological
Disorders and Stroke (NINDS; R01NS060725, R01NS067688), J.C.-B. was
supported by a National Research Service Award training grant from NINDS
(F31NS068038) and D.J.M. was supported by NIH grants HL109004 and
DA026982.
NR 45
TC 22
Z9 23
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD APR
PY 2013
VL 9
IS 4
BP 257
EP 263
DI 10.1038/NCHEMBIO.1183
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 118LA
UT WOS:000317025800016
PM 23396078
ER
PT J
AU Pharoah, PDP
Tsai, YY
Ramus, SJ
Phelan, CM
Goode, EL
Lawrenson, K
Buckley, M
Fridley, BL
Tyrer, JP
Shen, H
Weber, R
Karevan, R
Larson, MC
Song, HL
Tessier, DC
Bacot, F
Vincent, D
Cunningham, JM
Dennis, J
Dicks, E
Katja, KA
Anton-Culver, H
Antonenkova, N
Armasu, SM
Baglietto, L
Bandera, EV
Beckmann, MW
Birrer, MJ
Bloom, G
Bogdanova, N
Brenton, JD
Brinton, LA
Brooks-Wilson, A
Brown, R
Butzow, R
Campbell, I
Carney, ME
Carvalho, RS
Chang-Claude, J
Chen, YA
Chen, ZH
Chow, WH
Cicek, MS
Coetzee, G
Cook, LS
Cramer, DW
Cybulski, C
Dansonka-Mieszkowska, A
Despierre, E
Doherty, JA
Doerk, T
du Bois, A
Duerst, M
Eccles, D
Edwards, R
Ekici, AB
Fasching, PA
Fenstermacher, D
Flanagan, J
Gao, YT
Garcia-Closas, M
Gentry-Maharaj, A
Giles, G
Gjyshi, A
Gore, M
Gronwald, J
Guo, Q
Halle, MK
Harter, P
Hein, A
Heitz, F
Hillemanns, P
Hoatlin, M
Hogdall, E
Hogdall, CK
Hosono, S
Jakubowska, A
Jensen, A
Kalli, KR
Karlan, BY
Kelemen, LE
Kiemeney, LA
Kjaer, SK
Konecny, GE
Krakstad, C
Kupryjanczyk, J
Lambrechts, D
Lambrechts, S
Le, ND
Lee, N
Lee, J
Leminen, A
Lim, BK
Lissowska, J
Lubinski, J
Lundvall, L
Lurie, G
Massuger, LFAG
Matsuo, K
McGuire, V
McLaughlin, JR
Menon, U
Modugno, F
Moysich, KB
Nakanishi, T
Narod, SA
Ness, RB
Nevanlinna, H
Nickels, S
Noushmehr, H
Odunsi, K
Olson, S
Orlow, I
Paul, J
Pejovic, T
Pelttari, LM
Permuth-Wey, J
Pike, MC
Poole, EM
Qu, XT
Risch, HA
Rodriguez-Rodriguez, L
Rossing, MA
Rudolph, A
Runnebaum, I
Rzepecka, IK
Salvesen, HB
Schwaab, I
Severi, G
Shen, H
Shridhar, V
Shu, XO
Sieh, W
Southey, MC
Spellman, P
Tajima, K
Teo, SH
Terry, KL
Thompson, PJ
Timorek, A
Tworoger, SS
van Altena, AM
van den Berg, D
Vergote, I
Vierkant, RA
Vitonis, AF
Wang-Gohrke, S
Wentzensen, N
Whittemore, AS
Wik, E
Winterhoff, B
Woo, YL
Wu, AH
Yang, HP
Zheng, W
Ziogas, A
Zulkifli, F
Goodman, MT
Hall, P
Easton, DF
Pearce, CL
Berchuck, A
Chenevix-Trench, G
Iversen, E
Monteiro, ANA
Gayther, SA
Schildkraut, JM
Sellers, TA
AF Pharoah, Paul D. P.
Tsai, Ya-Yu
Ramus, Susan J.
Phelan, Catherine M.
Goode, Ellen L.
Lawrenson, Kate
Buckley, Melissa
Fridley, Brooke L.
Tyrer, Jonathan P.
Shen, Howard
Weber, Rachel
Karevan, Rod
Larson, Melissa C.
Song, Honglin
Tessier, Daniel C.
Bacot, Francois
Vincent, Daniel
Cunningham, Julie M.
Dennis, Joe
Dicks, Ed
Aben, Katja K.
Anton-Culver, Hoda
Antonenkova, Natalia
Armasu, Sebastian M.
Baglietto, Laura
Bandera, Elisa V.
Beckmann, Matthias W.
Birrer, Michael J.
Bloom, Greg
Bogdanova, Natalia
Brenton, James D.
Brinton, Louise A.
Brooks-Wilson, Angela
Brown, Robert
Butzow, Ralf
Campbell, Ian
Carney, Michael E.
Carvalho, Renato S.
Chang-Claude, Jenny
Chen, Y. Anne
Chen, Zhihua
Chow, Wong-Ho
Cicek, Mine S.
Coetzee, Gerhard
Cook, Linda S.
Cramer, Daniel W.
Cybulski, Cezary
Dansonka-Mieszkowska, Agnieszka
Despierre, Evelyn
Doherty, Jennifer A.
Doerk, Thilo
du Bois, Andreas
Duerst, Matthias
Eccles, Diana
Edwards, Robert
Ekici, Arif B.
Fasching, Peter A.
Fenstermacher, David
Flanagan, James
Gao, Yu-Tang
Garcia-Closas, Montserrat
Gentry-Maharaj, Aleksandra
Giles, Graham
Gjyshi, Anxhela
Gore, Martin
Gronwald, Jacek
Guo, Qi
Halle, Mari K.
Harter, Philipp
Hein, Alexander
Heitz, Florian
Hillemanns, Peter
Hoatlin, Maureen
Hogdall, Estrid
Hogdall, Claus K.
Hosono, Satoyo
Jakubowska, Anna
Jensen, Allan
Kalli, Kimberly R.
Karlan, Beth Y.
Kelemen, Linda E.
Kiemeney, Lambertus A.
Kjaer, Susanne Kruger
Konecny, Gottfried E.
Krakstad, Camilla
Kupryjanczyk, Jolanta
Lambrechts, Diether
Lambrechts, Sandrina
Le, Nhu D.
Lee, Nathan
Lee, Janet
Leminen, Arto
Lim, Boon Kiong
Lissowska, Jolanta
Lubinski, Jan
Lundvall, Lene
Lurie, Galina
Massuger, Leon F. A. G.
Matsuo, Keitaro
McGuire, Valerie
McLaughlin, John R.
Menon, Usha
Modugno, Francesmary
Moysich, Kirsten B.
Nakanishi, Toru
Narod, Steven A.
Ness, Roberta B.
Nevanlinna, Heli
Nickels, Stefan
Noushmehr, Houtan
Odunsi, Kunle
Olson, Sara
Orlow, Irene
Paul, James
Pejovic, Tanja
Pelttari, Liisa M.
Permuth-Wey, Jenny
Pike, Malcolm C.
Poole, Elizabeth M.
Qu, Xiaotao
Risch, Harvey A.
Rodriguez-Rodriguez, Lorna
Rossing, Mary Anne
Rudolph, Anja
Runnebaum, Ingo
Rzepecka, Iwona K.
Salvesen, Helga B.
Schwaab, Ira
Severi, Gianluca
Shen, Hui
Shridhar, Vijayalakshmi
Shu, Xiao-Ou
Sieh, Weiva
Southey, Melissa C.
Spellman, Paul
Tajima, Kazuo
Teo, Soo-Hwang
Terry, Kathryn L.
Thompson, Pamela J.
Timorek, Agnieszka
Tworoger, Shelley S.
van Altena, Anne M.
van den Berg, David
Vergote, Ignace
Vierkant, Robert A.
Vitonis, Allison F.
Wang-Gohrke, Shan
Wentzensen, Nicolas
Whittemore, Alice S.
Wik, Elisabeth
Winterhoff, Boris
Woo, Yin Ling
Wu, Anna H.
Yang, Hannah P.
Zheng, Wei
Ziogas, Argyrios
Zulkifli, Famida
Goodman, Marc T.
Hall, Per
Easton, Douglas F.
Pearce, Celeste L.
Berchuck, Andrew
Chenevix-Trench, Georgia
Iversen, Edwin
Monteiro, Alvaro N. A.
Gayther, Simon A.
Schildkraut, Joellen M.
Sellers, Thomas A.
CA Australian Canc Study
Australian Ovarian Canc Study Grp
TI GWAS meta-analysis and replication identifies three new susceptibility
loci for ovarian cancer
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; RISK; GENE; EXPRESSION; CARCINOMA; NEBULETTE;
LEUKEMIA; CELLS; 19P13; MYC
AB Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 x 10(-9)) and 10p12 (rs1243180, P = 1.8 x 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 x 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
C1 [Pharoah, Paul D. P.; Tyrer, Jonathan P.; Song, Honglin; Dicks, Ed; Guo, Qi; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Pharoah, Paul D. P.; Dennis, Joe; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Tsai, Ya-Yu; Phelan, Catherine M.; Buckley, Melissa; Bloom, Greg; Chen, Y. Anne; Chen, Zhihua; Fenstermacher, David; Gjyshi, Anxhela; Permuth-Wey, Jenny; Qu, Xiaotao; Monteiro, Alvaro N. A.; Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33682 USA.
[Ramus, Susan J.; Lawrenson, Kate; Shen, Howard; Karevan, Rod; Lee, Nathan; Lee, Janet; Pike, Malcolm C.; van den Berg, David; Wu, Anna H.; Pearce, Celeste L.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Goode, Ellen L.; Fridley, Brooke L.; Cicek, Mine S.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
[Weber, Rachel; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
[Larson, Melissa C.; Armasu, Sebastian M.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
[Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel] McGill Univ, Ctr Technol, Montreal, PQ, Canada.
[Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel] McGill Univ, Montreal, PQ, Canada.
[Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Cunningham, Julie M.; Shridhar, Vijayalakshmi] Mayo Clin, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN USA.
[Aben, Katja K.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands.
[Aben, Katja K.; Kiemeney, Lambertus A.] Comprehens Canc Ctr Netherlands, Utrecht, Netherlands.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA.
[Antonenkova, Natalia] NN Aleksandrov Byelorussian Inst Oncol & Med Radi, Minsk, Byelarus.
[Baglietto, Laura; Giles, Graham; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Baglietto, Laura; Giles, Graham; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Bandera, Elisa V.; Rodriguez-Rodriguez, Lorna] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA.
[Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander] Univ Erlangen Nurnberg, Dept Gynecol & Obstet, Univ Hosp Erlangen, Ctr Comprehens Canc, D-91054 Erlangen, Germany.
[Birrer, Michael J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Bogdanova, Natalia; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Brenton, James D.] Li Ka Shing Ctr, Cambridge Res Inst, Cambridge, England.
[Brinton, Louise A.; Wentzensen, Nicolas; Yang, Hannah P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Brooks-Wilson, Angela] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Brown, Robert; Flanagan, James] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England.
[Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland.
[Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Campbell, Ian] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, Melbourne, Vic, Australia.
[Campbell, Ian] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[Carney, Michael E.; Lurie, Galina; Thompson, Pamela J.; Goodman, Marc T.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Chang-Claude, Jenny; Nickels, Stefan; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Chow, Wong-Ho] NCI, Div Canc Etiol & Genet, Bethesda, MD 20892 USA.
[Coetzee, Gerhard; Noushmehr, Houtan] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Microbiol & Prevent Med, Los Angeles, CA 90033 USA.
[Cook, Linda S.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA.
[Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.] Harvard Univ, Sch Med, Boston, MA USA.
[Cramer, Daniel W.; Poole, Elizabeth M.; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Cybulski, Cezary; Gronwald, Jacek; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Rzepecka, Iwona K.] Maria Sklodowska Curie Mem Canc Ctr, Dept Mol Pathol, Warsaw, Poland.
[Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Rzepecka, Iwona K.] Inst Oncol, Warsaw, Poland.
[Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace] Leuven Canc Inst, Dept Obstet & Gynaecol, Div Gynecol Oncol, Louvain, Belgium.
[Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Lebanon, NH USA.
[du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany.
[du Bois, Andreas; Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte Evang Huyssens Stiftung Knap, Dept Gynecol & Gynecol Oncol, Essen, Germany.
[Duerst, Matthias; Runnebaum, Ingo] Jena Univ Hosp, Dept Gynecol, Jena, Germany.
[Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp, Southampton SO9 5NH, Hants, England.
[Edwards, Robert; Modugno, Francesmary] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Edwards, Robert] Magee Womens Res Inst, Womens Canc Program, Pittsburgh, PA USA.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Fasching, Peter A.; Konecny, Gottfried E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London, England.
[Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Elizabeth Garrett Anderson Inst Womens Hlth, Gynaecol Canc Res Ctr, London, England.
[Giles, Graham] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Gore, Martin] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England.
[Halle, Mari K.; Krakstad, Camilla; Salvesen, Helga B.; Wik, Elisabeth] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway.
[Halle, Mari K.; Krakstad, Camilla; Salvesen, Helga B.; Wik, Elisabeth] Univ Bergen, Dept Clin Med, Bergen, Norway.
[Hillemanns, Peter] Hannover Med Sch, Clin Obstet, Hannover, Germany.
[Hillemanns, Peter] Hannover Med Sch, Clin Gynaecol, Hannover, Germany.
[Hoatlin, Maureen] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA.
[Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne Kruger] Danish Canc Soc Res Ctr, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Hogdall, Claus K.; Kjaer, Susanne Kruger; Lundvall, Lene] Rigshosp, Dept Obstet & Gynecol, Juliane Marie Ctr, DK-2100 Copenhagen, Denmark.
[Hosono, Satoyo; Matsuo, Keitaro; Tajima, Kazuo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan.
[Kalli, Kimberly R.] Mayo Clin, Dept Med Oncol, Rochester, MN USA.
[Karlan, Beth Y.] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, Calgary, AB, Canada.
[Kelemen, Linda E.] Univ Calgary, Dept Med Genet, Calgary, AB, Canada.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands.
[Lambrechts, Diether] Katholieke Univ Leuven, Vesalius Res Ctr, Louvain, Belgium.
[Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Lim, Boon Kiong; Woo, Yin Ling] Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur, Malaysia.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Massuger, Leon F. A. G.; van Altena, Anne M.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, NL-6525 ED Nijmegen, Netherlands.
[McGuire, Valerie; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[McLaughlin, John R.] Univ Toronto, Fac Med, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[McLaughlin, John R.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Modugno, Francesmary] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Moysich, Kirsten B.; Odunsi, Kunle] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Nakanishi, Toru] Aichi Canc Ctr Cent Hosp, Dept Gynecol Oncol, Nagoya, Aichi, Japan.
[Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
[Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Noushmehr, Houtan; Shen, Hui] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Epigenome Ctr, Los Angeles, CA 90033 USA.
[Olson, Sara; Orlow, Irene; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Paul, James] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Risch, Harvey A.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06520 USA.
[Risch, Harvey A.] Yale Univ, Sch Med, New Haven, CT USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA.
[Schwaab, Ira] Inst Human Genet & Anthropol, Wiesbaden, Germany.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Spellman, Paul] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Teo, Soo-Hwang; Zulkifli, Famida] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya, Malaysia.
[Teo, Soo-Hwang; Zulkifli, Famida] Univ Malaya, Med Ctr, Kuala Lumpur, Malaysia.
[Timorek, Agnieszka] Warsaw Med Univ, Fac Med 2, Dept Obstet Gynecol & Oncol, Warsaw, Poland.
[Timorek, Agnieszka] Brodnowski Hosp, Dept Obstet & Gynaecol, Warsaw, Poland.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynaecol, D-89069 Ulm, Germany.
[Winterhoff, Boris] Mayo Clin, Dept Obstet & Gynaecol, Rochester, MN USA.
[Hall, Per] Karolinska Istitutet, Dept Epidemiol & Biostat, Stockholm, Sweden.
[Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynaecol, Durham, NC USA.
[Chenevix-Trench, Georgia] Queensland Inst Med Res, Canc Div, Herston, Qld 4006, Australia.
[Iversen, Edwin] Duke Univ, Dept Stat, Durham, NC USA.
[Schildkraut, Joellen M.] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC USA.
RP Pharoah, PDP (reprint author), Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
EM paul.pharoah@medschl.cam.ac.uk
RI Hein, Alexander/F-6999-2010; Noushmehr, Houtan/C-9692-2013; Verdrengh,
Evelien/H-4571-2012; Ekici, Arif/C-3971-2013; McLaughlin,
John/E-4577-2013; Kiemeney, Lambertus/D-3357-2009; Tang,
Macy/B-9798-2014; Dork, Thilo/J-8620-2012; Whittemore,
Alice/F-9925-2014; Brooks-Wilson, Angela/E-9399-2012; Teo,
Soo-hwang/H-2353-2014; Bandera, Elisa/M-4169-2014; Massuger,
Leon/H-8072-2014; Jakubowska, Anna/O-8050-2014; campbell,
Ian/F-6006-2011; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat
/F-3871-2015; Brinton, Louise/G-7486-2015; Woo, Yin Ling/B-5198-2010;
van Altena, Anne/B-9824-2016; Aben, Katja/G-9686-2016; Bowtell,
David/H-1007-2016; Gronwald, Jacek/A-4576-2017; salvesen,
Helga/C-1187-2017
OI Hein, Alexander/0000-0003-2601-3398; Noushmehr,
Houtan/0000-0003-4051-8114; Kiemeney, Lambertus/0000-0002-2368-1326;
Brooks-Wilson, Angela/0000-0003-1009-6408; Bandera,
Elisa/0000-0002-8789-2755; Krakstad, Camilla/0000-0002-0174-8139; Giles,
Graham/0000-0003-4946-9099; Matsuo, Keitaro/0000-0003-1761-6314;
Rudolph, Anja/0000-0001-7520-2035; Brenton, James/0000-0002-5738-6683;
Tworoger, Shelley/0000-0002-6986-7046; Kjaer,
Susanne/0000-0002-8347-1398; Monteiro, Alvaro/0000-0002-8448-4801;
Ramus, Susan/0000-0003-0005-7798; Lissowska,
Jolanta/0000-0003-2695-5799; Dennis, Joe/0000-0003-4591-1214;
Nevanlinna, Heli/0000-0002-0916-2976; Halle, Mari/0000-0002-2660-8271;
Orlow, Irene/0000-0001-6234-6961; Fridley, Brooke/0000-0001-7739-7956;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Woo, Yin Ling/0000-0003-1742-1066; Aben,
Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525; Gronwald,
Jacek/0000-0002-3643-2871; salvesen, Helga/0000-0002-4438-8831
FU European Commission's Seventh Framework Programme [223175,
HEALTH-F22009-223175]; Ovarian Cancer Research Fund; Genetic
Associations and Mechanisms in Oncology (GAME-ON); National Cancer
Institute Cancer Post-GWAS Initiative [U19-CA148112]; Wellcome Trust
[076113]
FX We thank all the individuals who took part in this study and all the
researchers, clinicians and technical and administrative staff who made
possible the many studies contributing to this work (a full list is
provided in the Supplementary Note). The COGS project is funded through
a European Commission's Seventh Framework Programme grant (agreement
number 223175 - HEALTH-F22009-223175). The Ovarian Cancer Association
Consortium is supported by a grant from the Ovarian Cancer Research Fund
thanks to donations by the family and friends of Kathryn Sladek Smith
(PPD/RPCI.07). The scientific development and funding for this project
were supported in part by the Genetic Associations and Mechanisms in
Oncology (GAME-ON) and a National Cancer Institute Cancer Post-GWAS
Initiative (U19-CA148112). Details of the funding of individual
investigators and studies are provided in the Supplementary Note. This
study made use of data generated by the Wellcome Trust Case Control
consortium; funding for the project was provided by the Wellcome Trust
under award 076113. A full list of the investigators who contributed to
the generation of the data is available from the website (see URLs). The
results published here are based in part on data generated by The Cancer
Genome Atlas Pilot Project established by the National Cancer Institute
and National Human Genome Research Institute; information about The
Cancer Genome Atlas (TCGA) and the investigators and institutions who
constitute the TCGA research network can be found on the website (see
URLs).
NR 31
TC 144
Z9 146
U1 3
U2 48
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2013
VL 45
IS 4
BP 362
EP 370
DI 10.1038/ng.2564
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 115VS
UT WOS:000316840600006
PM 23535730
ER
PT J
AU Bojesen, SE
Pooley, KA
Johnatty, SE
Beesley, J
Michailidou, K
Tyrer, JP
Edwards, SL
Pickett, HA
Shen, HC
Smart, CE
Hillman, KM
Mai, PL
Lawrenson, K
Stutz, MD
Lu, Y
Karevan, R
Woods, N
Johnstonw, RL
French, JD
Chen, XQ
Weischer, M
Nielsen, SF
Maranian, MJ
Ghoussaini, M
Ahmed, S
Baynes, C
Bolla, MK
Wang, Q
Dennis, J
McGuffog, L
Barrowdale, D
Lee, A
Healey, S
Lush, M
Tessier, DC
Vincent, D
Bacot, F
Vergote, I
Lambrechts, S
Despierre, E
Risch, HA
Gonzaalez-Neira, A
Rossing, MA
Pita, G
Doherty, JA
Alvarez, N
Larson, MC
Fridley, BL
Schoof, N
Chang-Claude, J
Cicek, MS
Peto, J
Kalli, KR
Broeks, A
Armasu, SM
Schmidt, MK
Braaf, LM
Winterhoff, B
Nevanlinna, H
Konecny, GE
Lambrechts, D
Rogmann, L
Guenel, P
Teoman, A
Milne, RL
Garcia, JJ
Cox, A
Shridhar, V
Burwinkel, B
Marme, F
Hein, R
Sawyer, EJ
Haiman, CA
Wang-Gohrke, S
Andrulis, IL
Moysich, KB
Hopper, JL
Odunsi, K
Lindblom, A
Giles, GG
Brenner, H
Simard, J
Lurie, G
Fasching, PA
Carney, ME
Radice, P
Wilkens, LR
Swerdlow, A
Goodman, MT
Brauch, H
Garcia-Closas, M
Hillemanns, P
Winqvist, R
Durst, M
Devilee, P
Runnebaum, I
Jakubowska, A
Lubinski, J
Mannermaa, A
Butzow, R
Bogdanova, NV
Dork, T
Pelttari, LM
Zheng, W
Leminen, A
Anton-Culver, H
Bunker, CH
Kristensen, V
Ness, RB
Muir, K
Edwards, R
Meind, A
Heitz, F
Matsuo, K
du Bois, A
Wu, AH
Harter, P
Teo, SH
Schwaab, I
Shu, XO
Blot, W
Hosono, S
Kang, D
Nakanishi, T
Hartman, M
Yatabe, Y
Hamann, U
Karlan, BY
Sangrajrang, S
Kjaer, SK
Gaborieau, V
Jensen, A
Eccles, D
Hogdall, E
Shen, CY
Brown, J
Woo, YL
Shah, M
Azmi, MAN
Luben, R
Omar, SZ
Czene, K
Vierkant, RA
Nordestgaard, BG
Flyger, H
Vachon, C
Olson, JE
Wang, XS
Levine, DA
Rudolph, A
Weber, RP
Flesch-Janys, D
Iversen, E
Nickels, S
Schildkraut, JM
Silva, ID
Cramer, DW
Gibson, L
Terry, KL
Fletcher, O
Vitonis, AF
van der Schoot, CE
Poole, EM
Hogervorst, FBL
Tworoger, SS
Liu, JJ
Bandera, EV
Li, JM
Olson, SH
Humphreys, K
Row, I
Blomqvist, C
Rodriguez-Rodriguez, L
Aittomaki, K
Salvesen, HB
Muranen, TA
Wik, E
Brouwers, B
Krakstad, C
Wauters, E
Halle, MK
Wildiers, H
Kiemeney, LA
Mulot, C
Aben, KK
Laurent-Puig, P
Altena, AM
Truong, T
Massuger, LFAG
Benitez, J
Pejovic, T
Perez, JIA
Hoatlin, M
Zamora, MP
Cook, LS
Balasubramanian, SP
Kelemen, LE
Schneeweiss, A
Le, ND
Sohn, C
Brooks-Wilson, A
Tomlinson, I
Kerin, MJ
Miller, N
Cybulski, C
Henderson, BE
Menkiszak, J
Schumacher, F
Wentzensen, N
Le Marchand, L
Yang, HP
Mulligan, AM
Glendon, G
Engelholm, SA
Knight, JA
Hogdall, CK
Apicella, C
Gore, M
Tsimiklis, H
Song, HL
Southey, MC
Jager, A
den Ouweland, AMW
Brown, R
Martens, JWM
Flanagan, JM
Kriege, M
Paul, J
Margolin, S
Siddiqui, N
Severi, G
Whittemore, AS
Baglietto, L
McGuire, V
Stegmaier, C
Sieh, W
Muller, H
Arndt, V
Labreche, F
Gao, YT
Goldberg, MS
Yang, G
Dumont, M
McLaughlin, JR
Hartmann, A
Ekici, AB
Beckmann, MW
Phelan, CM
Lux, MP
Permuth-Wey, J
Peissel, B
Sellers, TA
Ficarazzi, F
Barile, M
Ziogas, A
Ashworth, A
Gentry-Maharaj, A
Jones, M
Ramus, SJ
Orr, N
Menon, U
Pearce, CL
Bruning, T
Pike, MC
Ko, YD
Lissowska, J
Figueroa, J
Kupryjanczyk, J
Chanock, SJ
Dansonka-Mieszkowska, A
Jukkola-Vuorinen, A
Rzepecka, IK
Pylkas, K
Bidzinski, M
Kauppila, S
Hollestelle, A
Seynaeve, C
Tollenaar, RAEM
Durda, K
Jaworska, K
Hartikainen, JM
Kosma, VM
Kataja, V
Antonenkova, NN
Long, JR
Shrubsole, M
Deming-Halverson, S
Lophatananon, A
Siriwanarangsan, P
Stewart-Brown, S
Ditsch, N
Lichtner, P
Schmutzler, RK
Ito, H
Iwata, H
Tajima, K
Tseng, CC
Stram, DO
van den Berg, D
Yip, CH
Ikrarn, MK
Teh, YC
Cai, H
Lu, W
Signorello, LB
Cai, QY
Noh, DY
Yoo, KY
Miao, H
Iau, PTC
Teo, YY
McKay, J
Shapiro, C
Ademuyiwa, F
Fountzilas, G
Hsiung, CN
Yu, JC
Hou, MF
Healey, CS
Luccarini, C
Peock, S
Stoppa-Lyonnet, D
Peterlongo, P
Rebbeck, TR
Piedmonte, M
Singer, CF
Friedman, E
Thomassen, M
Offit, K
Hansen, TVO
Neuhausen, SL
Szabo, CI
Blanco, I
Garber, J
Narod, SA
Weitzel, JN
Montagna, M
Olah, E
Godwin, AK
Yannoukakos, D
Goldgar, DE
Caldes, T
Imyanitov, EN
Tihomirova, L
Arun, BK
Campbell, I
Mensenkamp, AR
van Asperen, CJ
van Roozendaa, KEP
Meijers-Heijboer, H
Collee, JM
Oosterwijk, JC
Hooning, MJ
Rookus, MA
van der Luijt, RB
Os, TAM
Evans, DG
Frost, D
Fineberg, E
Barwell, J
Walker, L
Kennedy, MJ
Platte, R
Davidson, R
Ellis, SD
Cole, T
Bressac-de Paillerets, B
Buecher, B
Damiola, F
Faivre, L
Frenay, M
Sinilnikova, OM
Caron, O
Giraud, S
Mazoyer, S
Bonadona, V
Caux-Moncoutier, V
Toloczko-Grabarek, A
Gronwald, J
Byrski, T
Spurdle, AB
Bonanni, B
Zaffaroni, D
Giannini, G
Bernard, L
Dolcetti, R
Manoukian, S
Arnold, N
Engel, C
Deissler, H
Rhiem, K
Niederacher, D
Pendl, H
Sutter, C
Wappenschmidt, B
Borg, A
Mein, B
Rantala, J
Soller, M
Nathanson, KL
Domchek, SM
Rodriguez, GC
Salani, R
Kaulich, DG
Tea, MK
Paluch, SS
Laitman, Y
Skytte, AB
Kruse, TA
Jensen, UB
Robson, M
Gerdes, AM
Ejlertsen, B
Foretova, L
Savage, SA
Lesterm, J
Soucy, P
Kuchenbaecker, KB
Olswold, C
Cunningham, JM
Slager, S
Pankratz, VS
Dicks, E
Lakhani, SR
Couch, FJ
Hall, P
Monteiro, ANA
Gayther, SA
Pharoah, PDP
Reddel, RR
Goode, EL
Greene, MH
Easton, DF
Berchuck, A
Antoniou, AC
Chenevix-Trench, G
Dunning, AM
AF Bojesen, Stig E.
Pooley, Karen A.
Johnatty, Sharon E.
Beesley, Jonathan
Michailidou, Kyriaki
Tyrer, Jonathan P.
Edwards, Stacey L.
Pickett, Hilda A.
Shen, Howard C.
Smart, Chanel E.
Hillman, Kristine M.
Mai, Phuong L.
Lawrenson, Kate
Stutz, Michael D.
Lu, Yi
Karevan, Rod
Woods, Nicholas
Johnstonw, Rebecca L.
French, Juliet D.
Chen, Xiaoqing
Weischer, Maren
Nielsen, Sune F.
Maranian, Melanie J.
Ghoussaini, Maya
Ahmed, Shahana
Baynes, Caroline
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
McGuffog, Lesley
Barrowdale, Daniel
Lee, Andrew
Healey, Sue
Lush, Michael
Tessier, Daniel C.
Vincent, Daniel
Bacot, Francis
Vergote, Ignace
Lambrechts, Sandrina
Despierre, Evelyn
Risch, Harvey A.
Gonzalez-Neira, Anna
Rossing, Mary Anne
Pita, Guillermo
Doherty, Jennifer A.
Alvarez, Nuria
Larson, Melissa C.
Fridley, Brooke L.
Schoof, Nils
Chang-Claude, Jenny
Cicek, Mine S.
Peto, Julian
Kalli, Kimberly R.
Broeks, Annegien
Armasu, Sebastian M.
Schmidt, Marjanka K.
Braaf, Linde M.
Winterhoff, Boris
Nevanlinna, Heli
Konecny, Gottfried E.
Lambrechts, Diether
Rogmann, Lisa
Guenel, Pascal
Teoman, Attila
Milne, Roger L.
Garcia, Joaquin J.
Cox, Angela
Shridhar, Vijayalakshmi
Burwinkel, Barbara
Marme, Frederik
Hein, Rebecca
Sawyer, Elinor J.
Haiman, Christopher A.
Wang-Gohrke, Shan
Andrulis, Irene L.
Moysich, Kirsten B.
Hopper, John L.
Odunsi, Kunle
Lindblom, Annika
Giles, Graham G.
Brenner, Hermann
Simard, Jacques
Lurie, Galina
Fasching, Peter A.
Carney, Michael E.
Radice, Paolo
Wilkens, Lynne R.
Swerdlow, Anthony
Goodman, Marc T.
Brauch, Hiltrud
Garcia-Closas, Montserrat
Hillemanns, Peter
Winqvist, Robert
Durst, Matthias
Devilee, Peter
Runnebaum, Ingo
Jakubowska, Anna
Lubinski, Jan
Mannermaa, Arto
Butzow, Ralf
Bogdanova, Natalia V.
Doerk, Thilo
Pelttari, Liisa M.
Zheng, Wei
Leminen, Arto
Anton-Culver, Hoda
Bunker, Clareann H.
Kristensen, Vessela
Ness, Roberta B.
Muir, Kenneth
Edwards, Robert
Meindl, Alfons
Heitz, Florian
Matsuo, Keitaro
du Bois, Andreas
Wu, Anna H.
Harter, Philipp
Teo, Soo-Hwang
Schwaab, Ira
Shu, Xiao-Ou
Blot, William
Hosono, Satoyo
Kang, Daehee
Nakanishi, Toru
Hartman, Mikael
Yatabe, Yasushi
Hamann, Ute
Karlan, Beth Y.
Sangrajrang, Suleeporn
Kjaer, Susanne Kruger
Gaborieau, Valerie
Jensen, Allan
Eccles, Diana
Hogdall, Estrid
Shen, Chen-Yang
Brown, Judith
Woo, Yin Ling
Shah, Mitul
Azmi, Mat Adenan Noor
Luben, Robert
Omar, Siti Zawiah
Czene, Kamila
Vierkant, Robert A.
Nordestgaard, Borge G.
Flyger, Henrik
Vachon, Celine
Olson, Janet E.
Wang, Xianshu
Levine, Douglas A.
Rudolph, Anja
Weber, Rachel Palmieri
Flesch-Janys, Dieter
Iversen, Edwin
Nickels, Stefan
Schildkraut, Joellen M.
Silva, Isabel Dos Santos
Cramer, Daniel W.
Gibson, Lorna
Terry, Kathryn L.
Fletcher, Olivia
Vitonis, Allison F.
van der Schoot, C. Ellen
Poole, Elizabeth M.
Hogervorst, Frans B. L.
Tworoger, Shelley S.
Liu, Jianjun
Bandera, Elisa V.
Li, Jingmei
Olson, Sara H.
Humphreys, Keith
Row, Irene
Blomqvist, Carl
Rodriguez-Rodriguez, Lorna
Aittomaki, Kristiina
Salvesen, Helga B.
Muranen, Taru A.
Wik, Elisabeth
Brouwers, Barbara
Krakstad, Camilla
Wauters, Els
Halle, Mari K.
Wildiers, Hans
Kiemeney, Lambertus A.
Mulot, Claire
Aben, Katja K.
Laurent-Puig, Pierre
Altena, Anne Mvan
Therese Truong
Massuger, Leon F. A. G.
Benitez, Javier
Pejovic, Tanja
Arias Perez, Jose Ignacio
Hoatlin, Maureen
Zamora, M. Pilar
Cook, Linda S.
Balasubramanian, Sabapathy P.
Kelemen, Linda E.
Schneeweiss, Andreas
Le, Nhu D.
Sohn, Christof
Brooks-Wilson, Angela
Tomlinson, Ian
Kerin, Michael J.
Miller, Nicola
Cybulski, Cezary
Henderson, Brian E.
Menkiszak, Janusz
Schumacher, Fredrick
Wentzensen, Nicolas
Marchand, Loic Le
Yang, Hannah P.
Mulligan, Anna Marie
Glendon, Gord
Engelholm, Svend Aage
Knight, Julia A.
Hogdall, Claus K.
Apicella, Carmel
Gore, Martin
Tsimiklis, Helen
Song, Honglin
Southey, Melissa C.
Jager, Agnes
den Ouweland, Ans M. Wvan
Brown, Robert
Martens, John W. M.
Flanagan, James M.
Kriege, Mieke
Paul, James
Margolin, Sara
Siddiqui, Nadeem
Severi, Gianluca
Whittemore, Alice S.
Baglietto, Laura
McGuire, Valerie
Stegmaier, Christa
Sieh, Weiva
Mueller, Heiko
Arndt, Volker
Labreche, France
Gao, Yu-Tang
Goldberg, Mark S.
Yang, Gong
Dumont, Martine
McLaughlin, John R.
Hartmann, Arndt
Ekici, Arif B.
Beckmann, Matthias W.
Phelan, Catherine M.
Lux, Michael P.
Permuth-Wey, Jenny
Peissel, Bernard
Sellers, Thomas A.
Ficarazzi, Filomena
Barile, Monica
Ziogas, Argyrios
Ashworth, Alan
Gentry-Maharaj, Aleksandra
Jones, Michael
Ramus, Susan J.
Orr, Nick
Menon, Usha
Pearce, Celeste L.
Bruening, Thomas
Pike, Malcolm C.
Ko, Yon-Dschun
Lissowska, Jolanta
Figueroa, Jonine
Kupryjanczyk, Jolanta
Chanock, Stephen J.
Dansonka-Mieszkowska, Agnieszka
Jukkola-Vuorinen, Arja
Rzepecka, Iwona K.
Pylkas, Katri
Bidzinski, Mariusz
Kauppila, Saila
Hollestelle, Antoinette
Seynaeve, Caroline
Tollenaar, Rob A. E. M.
Durda, Katarzyna
Jaworska, Katarzyna
Hartikainen, Jaana M.
Kosma, Veli-Matti
Kataja, Vesa
Antonenkova, Natalia N.
Long, Jirong
Shrubsole, Martha
Deming-Halverson, Sandra
Lophatananon, Artitaya
Siriwanarangsan, Pornthep
Stewart-Brown, Sarah
Ditsch, Nina
Lichtner, Peter
Schmutzler, Rita K.
Ito, Hidemi
Iwata, Hiroji
Tajima, Kazuo
Tseng, Chiu-Chen
Stram, Daniel O.
van den Berg, David
Yip, Cheng Har
Ikrarn, M. Kamran
Teh, Yew-Ching
Cai, Hui
Lu, Wei
Signorello, Lisa B.
Cai, Qiuyin
Noh, Dong-Young
Yoo, Keun-Young
Miao, Hui
Iau, Philip Tsau-Choong
Teo, Yik Ying
McKay, James
Shapiro, Charles
Ademuyiwa, Foluso
Fountzilas, George
Hsiung, Chia-Ni
Yu, Jyh-Cherng
Hou, Ming-Feng
Healey, Catherine S.
Luccarini, Craig
Peock, Susan
Stoppa-Lyonnet, Dominique
Peterlongo, Paolo
Rebbeck, Timothy R.
Piedmonte, Marion
Singer, Christian F.
Friedman, Eitan
Thomassen, Mads
Offit, Kenneth
Hansen, Thomas V. O.
Neuhausen, Susan L.
Szabo, Csilla I.
Blanco, Ignacio
Garber, Judy
Narod, Steven A.
Weitzel, Jeffrey N.
Montagna, Marco
Olah, Edith
Godwin, Andrew K.
Yannoukakos, Drakoulis
Goldgar, David E.
Caldes, Trinidad
Imyanitov, Evgeny N.
Tihomirova, Laima
Arun, Banu K.
Campbell, Ian
Mensenkamp, Arjen R.
van Asperen, Christi J.
van Roozendaa, Kees E. P.
Meijers-Heijboer, Hanne
Collee, J. Margriet
Oosterwijk, Jan C.
Hooning, Maartje J.
Rookus, Matti A.
van der Luijt, Rob B.
Os, Theo A. Mvan
Evans, D. Gareth
Frost, Debra
Fineberg, Elena
Barwell, Julian
Walker, Lisa
Kennedy, M. John
Platte, Radka
Davidson, Rosemarie
Ellis, Steve D.
Cole, Trevor
Bressac-de Paillerets, Brigitte
Buecher, Bruno
Damiola, Francesca
Faivre, Laurence
Frenay, Marc
Sinilnikova, Olga M.
Caron, Olivier
Giraud, Sophie
Mazoyer, Sylvie
Bonadona, Valerie
Caux-Moncoutier, Virginie
Toloczko-Grabarek, Aleksandra
Gronwald, Jacek
Byrski, Tomasz
Spurdle, Amanda B.
Bonanni, Bernardo
Zaffaroni, Daniela
Giannini, Giuseppe
Bernard, Loris
Dolcetti, Riccardo
Manoukian, Siranoush
Arnold, Norbert
Engel, Christoph
Deissler, Helmut
Rhiem, Kerstin
Niederacher, Dieter
Pendl, Hansjoerg
Sutter, Christian
Wappenschmidt, Barbara
Borg, Ake
Mein, Beatrice
Rantala, Johanna
Soller, Maria
Nathanson, Katherine L.
Domchek, Susan M.
Rodriguez, Gustavo C.
Salani, Ritu
Kaulich, Daphne Gschwantler
Tea, Muy-Kheng
Paluch, Shani Shimon
Laitman, Yael
Skytte, Anne-Bine
Kruse, Torben A.
Jensen, Uffe Birk
Robson, Mark
Gerdes, Anne-Marie
Ejlertsen, Bent
Foretova, Lenka
Savage, Sharon A.
Lesterm, Jenny
Soucy, Penny
Kuchenbaecker, Karoline B.
Olswold, Curtis
Cunningham, Julie M.
Slager, Susan
Pankratz, Vernon S.
Dicks, Ed
Lakhani, Sunil R.
Couch, Fergus J.
Hall, Per
Monteiro, Alvaro N. A.
Gayther, Simon A.
Pharoah, Paul D. P.
Reddel, Roger R.
Goode, Ellen L.
Greene, Mark H.
Easton, Douglas F.
Berchuck, Andrew
Antoniou, Antonis C.
Chenevix-Trench, Georgia
Dunning, Alison M.
CA Australian Canc Study
Australian Ovarian Canc Study
Kathleen Cuningham Fdn Consortium
Gene Environm Interactimi Breast
Swedish Breast Canc Study SWE-BRCA
Hereditary Breast Ovarian Canc Res
Epidemiological Study BRCA1
Genetic Modifiers Canc Risk BRCA1
TI Multiple independent variants at the TERT locus are associated with
telomere length and risks of breast and ovarian cancer
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; REVERSE-TRANSCRIPTASE HTERT; SUSCEPTIBILITY
LOCI; TERT-CLPTM1L LOCUS; GENETIC-VARIATION; COMMON VARIANTS; BUCCAL
CELLS; FIBROBLASTS; CARCINOMA; METAANALYSIS
AB TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
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[Brown, Robert; Flanagan, James M.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London, England.
[Paul, James] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland.
[Margolin, Sara] Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
[Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynecol Oncol, Glasgow G4 0SF, Lanark, Scotland.
[Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Labreche, France] Univ Montreal, Fac Med, Dept Environm & Occupat Hlth, Montreal, PQ H3C 3J7, Canada.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Goldberg, Mark S.] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada.
[McLaughlin, John R.] Univ Toronto, Fac Med, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Hartmann, Arndt] Univ Erlangen Nurnberg, Inst Pathol, Univ Hosp Erlangen, Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Peissel, Bernard; Zaffaroni, Daniela; Manoukian, Siranoush] Fdn IRCCS INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
[Ficarazzi, Filomena; Bernard, Loris] Cogentech Canc Genet Test Lab, Milan, Italy.
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[Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA.
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[Bruening, Thomas] Ruhr Univ Bochum, Inst Prevent & Occupat Med, German Social Accid Insurance, Bochum, Germany.
[Ko, Yon-Dschun] Johanniter Krankenhaus, Evangel Kliniken Bonn, Dept Internal Med, Bonn, Germany.
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[Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland.
[Bidzinski, Mariusz] Maria Sklodowska Curie Mem Canc Ctr, Dept Gynecol Oncol, Warsaw, Poland.
[Kauppila, Saila] Univ Oulu, Dept Pathol, Oulu Univ Hosp, Oulu, Finland.
[Tollenaar, Rob A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands.
[Jaworska, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland.
[Antonenkova, Natalia N.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Siriwanarangsan, Pornthep] Minist Publ Hlth, Bangkok, Thailand.
[Ditsch, Nina] Univ Munich, Dept Gynecol & Obstet, Munich, Germany.
[Lichtner, Peter] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany.
[Schmutzler, Rita K.; Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Dept Gynaecol & Obstet, Cologne, Germany.
[Schmutzler, Rita K.; Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany.
[Iwata, Hiroji] Aichi Canc Ctr Hosp, Dept Breast Oncol, Nagoya, Aichi, Japan.
[Ikrarn, M. Kamran] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
[Lu, Wei] Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China.
[Shapiro, Charles] Ohio State Univ, Div Oncol, Wexner Med Ctr, Columbus, OH 43210 USA.
[Ademuyiwa, Foluso] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Fountzilas, George] Aristotle Univ Thessaloniki, Sch Med, Dept Med Oncol, Papageorgiou Hosp, GR-54006 Thessaloniki, Greece.
[Yu, Jyh-Cherng] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Chung Ho Mem Hosp, Ctr Canc, Kaohsiung, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Chung Ho Mem Hosp, Dept Surg, Kaohsiung, Taiwan.
[Stoppa-Lyonnet, Dominique; Buecher, Bruno; Caux-Moncoutier, Virginie] Inst Curie, Dept Tumor Biol, Paris, France.
[Stoppa-Lyonnet, Dominique] INSERM, Inst Curie, U830, Paris, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France.
[Rebbeck, Timothy R.; Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Basser Res Ctr, Philadelphia, PA USA.
[Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Piedmonte, Marion] Roswell Pk Canc Inst, Gynecol Oncol Grp Stat, Buffalo, NY 14263 USA.
[Piedmonte, Marion] Roswell Pk Canc Inst, Ctr Data, Buffalo, NY 14263 USA.
[Singer, Christian F.; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Vienna, Austria.
[Friedman, Eitan; Paluch, Shani Shimon; Laitman, Yael] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel.
[Friedman, Eitan; Paluch, Shani Shimon; Laitman, Yael] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel.
[Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Offit, Kenneth; Robson, Mark] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA.
[Hansen, Thomas V. O.] Rigshosp, Copenhagen Univ Hosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark.
[Neuhausen, Susan L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA.
[Szabo, Csilla I.] Univ Delaware, Dept Biol Sci, Ctr Translat Canc Res, Newark, DE USA.
[Blanco, Ignacio] Inst Invest Biomed Bellvitge Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain.
[Garber, Judy] Dana Farber Canc Inst, Ctr Canc Genet & Prevent, Boston, MA 02115 USA.
[Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
[Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Clin Canc Genet, Duarte, CA USA.
[Montagna, Marco] IRCCS, Ist Oncol Veneto IOV, Immunol & Mol Oncol Unit, Padua, Italy.
[Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Yannoukakos, Drakoulis] Aghia Paraskevi Attikis, Mol Diagnost Lab, Inst Radioisotopes & Radiodiagnost Prod, Natl Ctr Sci Res Demokritos, Athens, Greece.
[Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA.
[Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Caldes, Trinidad] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
[Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg, Russia.
[Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Campbell, Ian] Peter MacCallum Canc Ctr, Victorian Breast Canc Res Consortium Canc Genet L, Melbourne, Vic, Australia.
[Mensenkamp, Arjen R.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands.
[van Roozendaa, Kees E. P.] Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands.
[Meijers-Heijboer, Hanne] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Oosterwijk, Jan C.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Os, Theo A. Mvan] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Barwell, Julian] Univ Hosp Leicester NHS Trust, Leicestershire Clin Genet Serv, Leicester, Leics, England.
[Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England.
[Kennedy, M. John] Trinity Coll Dublin, Acad Unit Clin & Mol Oncol, Dublin, Ireland.
[Kennedy, M. John] St James Hosp, Dublin 8, Ireland.
[Davidson, Rosemarie] So Gen Hosp, Lab Med, Glasgow G51 4TF, Lanark, Scotland.
[Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England.
[Bressac-de Paillerets, Brigitte] Fdn Jean Dausset, INSERM, U946, Paris, France.
[Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Serv Genet, Villejuif, France.
[Damiola, Francesca; Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon 1, INSERM, U1052, CNRS,UMR 5286,Ctr Rech Cancerol Lyon, F-69365 Lyon, France.
[Faivre, Laurence] Univ Bourgogne, CHU Dijon, Ctr Genet, Dijon, France.
[Faivre, Laurence] Ctr Georges Francois Leclerc, Dijon, France.
[Frenay, Marc] Ctr Antoine Lacassagne, Nice, France.
[Sinilnikova, Olga M.; Giraud, Sophie] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France.
[Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France.
[Bonadona, Valerie] Ctr Leon Berard, Unite Prevent & Epiderniol Genet, F-69373 Lyon, France.
[Bonadona, Valerie] Univ Lyon 1, CNRS, UMR 5558, F-69365 Lyon, France.
[Giannini, Giuseppe] Univ Roma La Sapienza, Dept Mol Med, Rome, Italy.
Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy.
[Dolcetti, Riccardo] IRCCS, Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Aviano, Italy.
[Arnold, Norbert] Univ Hosp Schleswig Holstein, Dept Gynecol & Obstet, Kiel, Germany.
[Arnold, Norbert] Univ Kiel, Kiel, Germany.
[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Univ Med Ctr, Dept Obstet & Gynecol, D-40225 Dusseldorf, Germany.
[Pendl, Hansjoerg] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel, Germany.
[Sutter, Christian] Heidelberg Univ, Inst Human Genet, Heidelberg, Germany.
[Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden.
[Mein, Beatrice] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Rantala, Johanna] Karolinska Hosp, Dept Clin Genet, S-10401 Stockholm, Sweden.
[Soller, Maria] Univ Lund Hosp, Univ & Reg Labs, Dept Clin Genet, S-22185 Lund, Sweden.
[Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Rodriguez, Gustavo C.] Univ Chicago, North Shore Univ Hlth Syst, Div Gynecol Oncol, Evanston, IL USA.
[Salani, Ritu] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Skytte, Anne-Bine] Vejle Hosp, Dept Clin Genet, Vejle, Denmark.
[Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark.
[Gerdes, Anne-Marie] Rigshosp, Copenhagen Univ Hosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark.
[Ejlertsen, Bent] Rigshosp, Copenhagen Univ Hosp, Dept Oncol, DK-2100 Copenhagen, Denmark.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Lakhani, Sunil R.] Royal Brisbane & Womens Hosp, Pathol Queensland, Herston, Qld, Australia.
[Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
RP Bojesen, SE (reprint author), Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
EM stig.egil.bojesen@regionh.dk; Georgia.Trench@qimr.edu.au;
amd24@medschl.cam.ac.uk
RI Spurdle, Amanda/A-4978-2011; Peissel, Bernard/E-8187-2017; Mensenkamp,
A.R./L-4520-2015; laurent-puig, pierre/B-2226-2013; Savage,
Sharon/B-9747-2015; Aben, Katja/G-9686-2016; Bowtell, David/H-1007-2016;
Bruning, Thomas/G-8120-2015; Edwards, Stacey/A-4980-2011; Menkiszak,
Janusz/I-4036-2014; Johnatty, Sharon/R-8890-2016; Gronwald,
Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; salvesen,
Helga/C-1187-2017; manoukian, siranoush/E-7132-2017; Bandera,
Elisa/M-4169-2014; Massuger, Leon/H-8072-2014; Jakubowska,
Anna/O-8050-2014; Yip, Cheng-Har/B-1909-2010; campbell, Ian/F-6006-2011;
Gonzalez-Neira, Anna/C-5791-2015; Fridley, Brooke/D-8315-2015;
Garcia-Closas, Montserrat /F-3871-2015; montagna, marco/E-2225-2012;
Woo, Yin Ling/B-5198-2010; Shrubsole, Martha/K-5052-2015; Hartikainen,
Jaana/E-6256-2015; Dolcetti, Riccardo/O-3832-2015; Blanco,
Ignacio/D-2565-2013; Salani, Ritu/E-4008-2011; Dork, Thilo/J-8620-2012;
Ditsch, Nina/F-6267-2014; Whittemore, Alice/F-9925-2014; Oosterwijk, Jan
C./G-5770-2011; Brooks-Wilson, Angela/E-9399-2012; Teo,
Soo-hwang/H-2353-2014; Hartman, Mikael/B-4324-2011; Noh,
Dong-Young/G-5531-2011; Bernard, Loris/K-5953-2014; Arnold,
Norbert/E-3012-2010; BYRSKI, Tomasz/I-2844-2014; Giannini,
Giuseppe/B-5672-2013; Verdrengh, Evelien/H-4571-2012; Kerin,
Michael/D-6748-2013; Radice, Paolo/O-3119-2013; Reddel,
Roger/A-6635-2014; Knight, Julia/A-6843-2012; Kiemeney,
Lambertus/D-3357-2009; Andrulis, Irene/E-7267-2013; Smart,
Chanel/C-9583-2011; Ekici, Arif/C-3971-2013; French, Juliet/A-4982-2011;
Li, Jingmei/I-2904-2012; McLaughlin, John/E-4577-2013; Tang,
Macy/B-9798-2014;
OI Lissowska, Jolanta/0000-0003-2695-5799; Arias Perez, Jose
Ignacio/0000-0003-4500-397X; Dennis, Joe/0000-0003-4591-1214; Luben,
Robert/0000-0002-5088-6343; Nevanlinna, Heli/0000-0002-0916-2976; Cox,
Angela/0000-0002-5138-1099; Halle, Mari/0000-0002-2660-8271;
Yannoukakos, Drakoulis/0000-0001-7509-3510; Orlow,
Irene/0000-0001-6234-6961; Dunning, Alison Margaret/0000-0001-6651-7166;
Tworoger, Shelley/0000-0002-6986-7046; Devilee,
Peter/0000-0002-8023-2009; Kjaer, Susanne/0000-0002-8347-1398; Monteiro,
Alvaro/0000-0002-8448-4801; Ramus, Susan/0000-0003-0005-7798; Spurdle,
Amanda/0000-0003-1337-7897; Barrowdale, Daniel/0000-0003-1661-3939;
Peissel, Bernard/0000-0001-9233-3571; Hollestelle,
Antoinette/0000-0003-1166-1966; Nathanson,
Katherine/0000-0002-6740-0901; Rudolph, Anja/0000-0001-7520-2035; Lux,
Michael Patrick/0000-0002-2781-2178; Robson, Mark/0000-0002-3109-1692;
Czene, Kamila/0000-0002-3233-5695; laurent-puig,
pierre/0000-0001-8475-5459; Savage, Sharon/0000-0001-6006-0740; Aben,
Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525; Bruning,
Thomas/0000-0001-9560-5464; Johnatty, Sharon/0000-0002-7888-1966;
Gronwald, Jacek/0000-0002-3643-2871; Brenner,
Hermann/0000-0002-6129-1572; salvesen, Helga/0000-0002-4438-8831;
manoukian, siranoush/0000-0002-6034-7562; Bandera,
Elisa/0000-0002-8789-2755; Fridley, Brooke/0000-0001-7739-7956;
Garcia-Closas, Montserrat /0000-0003-1033-2650; montagna,
marco/0000-0002-4929-2150; Woo, Yin Ling/0000-0003-1742-1066; Shrubsole,
Martha/0000-0002-5591-7575; Dolcetti, Riccardo/0000-0003-1625-9853;
Blanco, Ignacio/0000-0002-7414-7481; Brooks-Wilson,
Angela/0000-0003-1009-6408; Arnold, Norbert/0000-0003-4523-8808;
Giannini, Giuseppe/0000-0003-0299-4056; Reddel,
Roger/0000-0002-6302-6107; Kiemeney, Lambertus/0000-0002-2368-1326; Li,
Jingmei/0000-0001-8587-7511; Krakstad, Camilla/0000-0002-0174-8139;
ADEMUYIWA, FOLUSO/0000-0002-6766-2258; Ikram, Mohammad
Kamran/0000-0003-0173-9571; Giles, Graham/0000-0003-4946-9099; Muranen,
Taru/0000-0002-5895-1808; Skytte, Anne-Bine/0000-0002-0067-9557; Matsuo,
Keitaro/0000-0003-1761-6314; Arndt, Volker/0000-0001-9320-8684; Evans,
Gareth/0000-0002-8482-5784
FU European Commission's Seventh Framework Programme [223175,
HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/Al2014];
European Union Cooperation in Science and Technology (COST) [BM0606];
Cancer Research UK; Canadian Institutes of Health Research (CIHR);
Ministry of Economic Development, Innovation and Export Trade of Quebec
[PSR-SIIRI-701]; Genetic Associations and Mechanisms in Oncology
[U19-CA148112]; US National Institutes of Health [CAl28978]; National
Cancer Institute (NCI) [CA116201]; US Department of Defense Ovarian
Cancer Idea [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen
Foundation for the Cure; Wellcome Trust Case Control Consortium;
Wellcome Trust [076113]
FX We thank all the individuals who took part in these studies and all the
researchers, clinicians, technicians and administrative staff who have
enabled this work to be carried out. COGS is funded through a grant from
the European Commission's Seventh Framework Programme (agreement 223175
HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK
(C1287/A10118 and C1287/Al2014). BCAC meetings have been funded by the
European Union Cooperation in Science and Technology (COST) programme
(BM0606). Telomere length measurement and analysis were funded by Cancer
Research UK project grant C1287/A9540 and Chief Physician Johan Boserup
and Lise Boserup's Fund. CIMBA data management and analysis were
supported by Cancer Research UK grants C12292/A11174 and C1287/A10118.
OCAC is supported by a grant from the Ovarian Cancer Research Fund
thanks to the family and friends of Kathryn Sladek Smith (PPD/RPCI.07).
Genotyping of the iCOGS array was funded by the European Union
(HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian
Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks
of Breast Cancer program (J.S. and D.E.) and the Ministry of Economic
Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701;
J.S., D.E. and P. Hall). Scientific development and funding of the OCAC
portion of this project were supported by Genetic Associations and
Mechanisms in Oncology (GAME-ON; U19-CA148112). CIMBA genotyping was
supported by US National Institutes of Health (NIH) grant CAl28978, a
National Cancer Institute (NCI) Specialized Program of Research
Excellence (SPORE) in Breast Cancer (CA116201), a US Department of
Defense Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the
Breast Cancer Research Foundation and the Komen Foundation for the Cure.
This study made use of data generated by The Wellcome Trust Case Control
Consortium (funding was provided by Wellcome Trust award 076113) and the
TCGA Pilot Project established by NCI and the National Human Genome
Research Institute.
NR 70
TC 211
Z9 216
U1 15
U2 171
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2013
VL 45
IS 4
BP 371
EP 384
DI 10.1038/ng.2566
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 115VS
UT WOS:000316840600007
PM 23535731
ER
PT J
AU Eeles, RA
Al Olama, AA
Benlloch, S
Saunders, EJ
Leongamornlert, DA
Tymrakiewicz, M
Ghoussaini, M
Luccarini, C
Dennis, J
Jugurnauth-Little, S
Dadaev, T
Neal, DE
Hamdy, FC
Donovan, JL
Muir, K
Giles, GG
Severi, G
Wiklund, F
Gronberg, H
Haiman, CA
Schumacher, F
Henderson, BE
Le Marchand, L
Lindstrom, S
Kraft, P
Hunter, DJ
Gapstur, S
Chanock, SJ
Berndt, SI
Albanes, D
Andriole, G
Schleutker, J
Weischer, M
Canzian, F
Riboli, E
Key, TJ
Travis, RC
Campa, D
Ingles, SA
John, EM
Hayes, RB
Pharoah, PDP
Pashayan, N
Khaw, KT
Stanford, JL
Ostrander, EA
Signorello, LB
Thibodeau, SN
Schaid, D
Maier, C
Vogel, W
Kibel, AS
Cybulski, C
Lubhiski, J
Cannon-Albright, L
Brenner, H
Park, JY
Kaneva, R
Batra, J
Spurdle, AB
Clements, JA
Teixeira, MR
Dicks, E
Lee, A
Dunning, AM
Baynes, C
Conroy, D
Maranian, MJ
Ahmed, S
Govindasami, K
Guy, M
Wilkinson, RA
Sawyer, EJ
Morgan, A
Dearnaley, DP
Horwich, A
Huddart, RA
Khoo, VS
Parker, CC
Van As, NJ
Woodhouse, CJ
Thompson, A
Dudderidge, T
Ogden, C
Cooper, CS
Lophatananon, A
Cox, A
Southey, MC
Hopper, JL
English, DR
Aly, M
Adolfsson, J
Xu, JF
Zheng, SL
Yeager, M
Kaaks, R
Diver, WR
Gaudet, MM
Stern, MC
Corral, R
Joshi, AD
Shahabi, A
Wahlfors, T
Tammela, TLJ
Auvinen, A
Virtamo, J
Klarskov, P
Nordestgaard, BG
Roder, MA
Nielsen, SF
Bojesen, SE
Siddiq, A
FitzGerald, LM
Kolb, S
Kwon, EM
Karyadi, DM
Blot, WJ
Zheng, W
Cai, QY
McDonnell, SK
Rinckleb, AE
Drake, B
Colditz, G
Wokolorczyk, D
Stephenson, RA
Teerlink, C
Muller, H
Rothenbacher, D
Sellers, TA
Lin, HY
Slavov, C
Mitev, V
Lose, F
Srinivasan, S
Maia, S
Paulo, P
Lange, E
Cooney, KA
Antoniou, AC
Vincent, D
Bacot, F
Tessier, DC
Kote-Jarai, Z
Easton, DF
AF Eeles, Rosalind A.
Al Olama, Ali Amin
Benlloch, Sara
Saunders, Edward J.
Leongamornlert, Daniel A.
Tymrakiewicz, Malgorzata
Ghoussaini, Maya
Luccarini, Craig
Dennis, Joe
Jugurnauth-Little, Sarah
Dadaev, Tokhir
Neal, David E.
Hamdy, Freddie C.
Donovan, Jenny L.
Muir, Ken
Giles, Graham G.
Severi, Gianluca
Wiklund, Fredrik
Gronberg, Henrik
Haiman, Christopher A.
Schumacher, Fredrick
Henderson, Brian E.
Le Marchand, Loic
Lindstrom, Sara
Kraft, Peter
Hunter, David J.
Gapstur, Susan
Chanock, Stephen J.
Berndt, Sonja I.
Albanes, Demetrius
Andriole, Gerald
Schleutker, Johanna
Weischer, Maren
Canzian, Federico
Riboli, Elio
Key, Tim J.
Travis, Ruth C.
Campa, Daniele
Ingles, Sue A.
John, Esther M.
Hayes, Richard B.
Pharoah, Paul D. P.
Pashayan, Nora
Khaw, Kay-Tee
Stanford, Janet L.
Ostrander, Elaine A.
Signorello, Lisa B.
Thibodeau, Stephen N.
Schaid, Dan
Maier, Christiane
Vogel, Walther
Kibel, Adam S.
Cybulski, Cezary
Lubhiski, Jan
Cannon-Albright, Lisa
Brenner, Hermann
Park, Jong Y.
Kaneva, Radka
Batra, Jyotsna
Spurdle, Amanda B.
Clements, Judith A.
Teixeira, Manuel R.
Dicks, Ed
Lee, Andrew
Dunning, Alison M.
Baynes, Caroline
Conroy, Don
Maranian, Melanie J.
Ahmed, Shahana
Govindasami, Koveela
Guy, Michelle
Wilkinson, Rosemary A.
Sawyer, Emma J.
Morgan, Angela
Dearnaley, David P.
Horwich, Alan
Huddart, Robert A.
Khoo, Vincent S.
Parker, Christopher C.
Van As, Nicholas J.
Woodhouse, Christopher J.
Thompson, Alan
Dudderidge, Tim
Ogden, Chris
Cooper, Colin S.
Lophatananon, Artitaya
Cox, Angela
Southey, Melissa C.
Hopper, John L.
English, Dallas R.
Aly, Markus
Adolfsson, Jan
Xu, Jiangfeng
Zheng, Siqun L.
Yeager, Meredith
Kaaks, Rudolf
Diver, W. Ryan
Gaudet, Mia M.
Stern, Mariana C.
Corral, Roman
Joshi, Amit D.
Shahabi, Ahva
Wahlfors, Tiina
Tammela, Teuvo L. J.
Auvinen, Anssi
Virtamo, Jarmo
Klarskov, Peter
Nordestgaard, Borge G.
Roder, M. Andreas
Nielsen, Sune F.
Bojesen, Stig E.
Siddiq, Afshan
FitzGerald, Liesel M.
Kolb, Suzanne
Kwon, Erika M.
Karyadi, Danielle M.
Blot, William J.
Zheng, Wei
Cai, Qiuyin
McDonnell, Shannon K.
Rinckleb, Antje E.
Drake, Bettina
Colditz, Graham
Wokolorczyk, Dominika
Stephenson, Robert A.
Teerlink, Craig
Muller, Heiko
Rothenbacher, Dietrich
Sellers, Thomas A.
Lin, Hui-Yi
Slavov, Chavdar
Mitev, Vanio
Lose, Felicity
Srinivasan, Srilakshmi
Maia, Sofia
Paulo, Paula
Lange, Ethan
Cooney, Kathleen A.
Antoniou, Antonis C.
Vincent, Daniel
Bacot, Francois
Tessier, Daniel C.
Kote-Jarai, Zsofia
Easton, Douglas F.
CA COGS-Canc Res UK GWAS-ELLIPSE Part
Australian Prostate Canc
UK Genetic Prostate Canc Study
UK ProtecT Prostate Testing Canc
PRACTICAL Prostate Canc Assoc Grp
TI Identification of 23 new prostate cancer susceptibility loci using the
iCOGS custom genotyping array
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; VARIANTS; RISK; HOXB13; PREDISPOSITION;
MUTATIONS; MEN
AB Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom II lumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genomewide significance (P < 5 x 10(-8)). More than 70 prostate cancer susceptibility loci, explaining similar to 30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
C1 [Eeles, Rosalind A.; Saunders, Edward J.; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Jugurnauth-Little, Sarah; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Wilkinson, Rosemary A.; Sawyer, Emma J.; Morgan, Angela; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Cooper, Colin S.; Kote-Jarai, Zsofia] Inst Canc Res, Sutton, Surrey, England.
[Eeles, Rosalind A.; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas J.; Woodhouse, Christopher J.; Thompson, Alan; Dudderidge, Tim; Ogden, Chris] Royal Marsden Natl Hlth Serv NHS Fdn, London, England.
[Eeles, Rosalind A.; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas J.; Woodhouse, Christopher J.; Thompson, Alan; Dudderidge, Tim; Ogden, Chris] Royal Marsden Natl Hlth Serv NHS Fdn, Sutton, Surrey, England.
[Al Olama, Ali Amin; Benlloch, Sara; Ghoussaini, Maya; Luccarini, Craig; Dennis, Joe; Pharoah, Paul D. P.; Pashayan, Nora; Dicks, Ed; Lee, Andrew; Dunning, Alison M.; Baynes, Caroline; Conroy, Don; Maranian, Melanie J.; Ahmed, Shahana; Antoniou, Antonis C.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Neal, David E.] Univ Cambridge, Addenbrookes Hosp, Cambridge CB2 2QQ, England.
[Neal, David E.] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge, England.
[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
[Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford OX3 9DU, England.
[Donovan, Jenny L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Muir, Ken; Lophatananon, Artitaya] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Muir, Ken] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
[Giles, Graham G.; Severi, Gianluca; English, Dallas R.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca; Hopper, John L.; English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Wiklund, Fredrik; Gronberg, Henrik; Aly, Markus] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.; Ingles, Sue A.; Stern, Mariana C.; Corral, Roman; Joshi, Amit D.; Shahabi, Ahva] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Lindstrom, Sara; Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Gapstur, Susan; Diver, W. Ryan; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Chanock, Stephen J.; Berndt, Sonja I.; Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
[Albanes, Demetrius] NCI, Nutr Epidemiol Branch, US NIH, Bethesda, MD 20892 USA.
[Andriole, Gerald; Drake, Bettina; Colditz, Graham] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Schleutker, Johanna; Wahlfors, Tiina] Univ Tampere, Inst Biomed Technol BioMediTech, FIN-33101 Tampere, Finland.
[Schleutker, Johanna; Wahlfors, Tiina] FimLab Labs, Tampere, Finland.
[Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland.
[Weischer, Maren; Nordestgaard, Borge G.; Nielsen, Sune F.; Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.
[Canzian, Federico; Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Key, Tim J.; Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Hayes, Richard B.] NYU, Dept Environm Med, Langone Med Ctr, Div Epidemiol, New York, NY 10016 USA.
[Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England.
[Stanford, Janet L.; FitzGerald, Liesel M.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Ostrander, Elaine A.; Kwon, Erika M.; Karyadi, Danielle M.] NHGRI, US NIH, Bethesda, MD 20892 USA.
[Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Signorello, Lisa B.; Blot, William J.; Zheng, Wei; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Dept Med,Div Epidemiol, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN 37212 USA.
[Thibodeau, Stephen N.; McDonnell, Shannon K.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Schaid, Dan] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
[Maier, Christiane; Rinckleb, Antje E.] Univ Hosp Ulm, Dept Urol, Ulm, Germany.
[Maier, Christiane; Vogel, Walther; Rinckleb, Antje E.] Univ Hosp Ulm, Inst Human Genet, Ulm, Germany.
[Kibel, Adam S.] Brigham & Womens Hosp, Div Urol Surg, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Cybulski, Cezary; Lubhiski, Jan; Wokolorczyk, Dominika] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Cannon-Albright, Lisa; Teerlink, Craig] Univ Utah, Sch Med, Dept Med, Div Genet Epidemiol, Salt Lake City, UT USA.
[Cannon-Albright, Lisa; Stephenson, Robert A.] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA.
[Brenner, Hermann; Muller, Heiko; Rothenbacher, Dietrich] DKFZ, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Park, Jong Y.; Sellers, Thomas A.; Lin, Hui-Yi] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA.
[Kaneva, Radka; Mitev, Vanio] Med Univ Sofia, Mol Med Ctr, Dept Med Chem & Biochem, Sofia, Bulgaria.
[Batra, Jyotsna; Clements, Judith A.; Srinivasan, Srilakshmi] Queensland Univ Technol, Australian Prostate Canc Res Ctr, Queensland Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Batra, Jyotsna; Clements, Judith A.; Srinivasan, Srilakshmi] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4001, Australia.
[Spurdle, Amanda B.; Lose, Felicity] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Teixeira, Manuel R.; Maia, Sofia; Paulo, Paula] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal.
[Teixeira, Manuel R.; Maia, Sofia; Paulo, Paula] Univ Porto, Abel Salazar Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal.
[Cooper, Colin S.] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England.
[Cox, Angela] Univ Sheffield, Canc Res UK Yorkshire Canc Res Sheffield Canc Res, Sheffield, S Yorkshire, England.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia.
[Aly, Markus] Karolinska Inst, Danderyd Hosp, Div Urol, Dept Clin Sci, Stockholm, Sweden.
[Adolfsson, Jan] Karolinska Inst, Reg Canc Ctr, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
[Xu, Jiangfeng] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Zheng, Siqun L.] Wake Forest Univ Hlth Sci, Ctr Canc Genom, Genom Genotyping Lab, Winston Salem, NC USA.
[Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick, US NIH, Gaithersburg, MD USA.
[Kaaks, Rudolf] DKFZ, Div Canc Epidemiol, Heidelberg, Germany.
[Tammela, Teuvo L. J.] Tampere Univ Hosp, Dept Urol, Tampere, Finland.
[Tammela, Teuvo L. J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Auvinen, Anssi] Univ Tampere, Dept Epidemiol, Sch Hlth Sci, FIN-33101 Tampere, Finland.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Klarskov, Peter] Copenhagen Univ Hosp, Herlev Hosp, Dept Urol, Herlev, Denmark.
[Roder, M. Andreas] Copenhagen Univ Hosp, Rigshosp, Dept Urol, Copenhagen, Denmark.
[Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Stephenson, Robert A.] Huntsman Canc Inst, Salt Lake City, UT USA.
[Slavov, Chavdar] Med Univ Sofia, Alexandrovska Univ Hosp, Dept Urol, Sofia, Bulgaria.
[Lange, Ethan] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Cooney, Kathleen A.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Div Hematol Oncol, Ann Arbor, MI USA.
[Vincent, Daniel; Bacot, Francois; Tessier, Daniel C.] McGill Univ, Montreal, PQ, Canada.
[Vincent, Daniel; Bacot, Francois; Tessier, Daniel C.] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
RP Eeles, RA (reprint author), Inst Canc Res, Sutton, Surrey, England.
EM rosalind.eeles@icr.ac.uk
RI Spurdle, Amanda/A-4978-2011; Batra, Jyotsna/B-4130-2011; Albanes,
Demetrius/B-9749-2015; Paulo, Paula/F-1441-2016; Teixeira,
Manuel/E-4885-2011; Campa, Daniele/K-1617-2016; Colditz,
Graham/A-3963-2009; Brenner, Hermann/B-4627-2017;
OI albright, lisa/0000-0003-2602-3668; Cox, Angela/0000-0002-5138-1099;
Drake, Bettina/0000-0001-9340-5848; Dunning, Alison
Margaret/0000-0001-6651-7166; Giles, Graham/0000-0003-4946-9099;
Clements, Judith/0000-0001-6026-1964; English,
Dallas/0000-0001-7828-8188; Ostrander, Elaine/0000-0001-6075-9738;
Eeles, Rosalind/0000-0002-3698-6241; Lose, Felicity/0000-0001-8337-3547;
Roder, Martin Andreas/0000-0002-0019-5333; Spurdle,
Amanda/0000-0003-1337-7897; Adolfsson, Jan/0000-0003-2992-1869; Dennis,
Joe/0000-0003-4591-1214; Teerlink, Craig/0000-0002-1992-2326; Neal,
David/0000-0002-6033-5086; Leongamornlert, Daniel/0000-0002-3486-3168;
Hayes, Richard/0000-0002-0918-661X; van As,
Nicholas/0000-0001-6829-8788; Paulo, Paula/0000-0001-8387-2127;
Teixeira, Manuel/0000-0002-4896-5982; Campa,
Daniele/0000-0003-3220-9944; Colditz, Graham/0000-0002-7307-0291;
Brenner, Hermann/0000-0002-6129-1572; Dadaev,
Tokhir/0000-0002-8268-0438; Auvinen, Anssi/0000-0003-1125-4818;
Saunders, Ed/0000-0003-4343-3570
FU Cancer Research UK [10118, 10124, 10588, 11174, 13065, 14136];
Intramural NIH HHS [Z99 CA999999, ZIA CP010195-06]; Medical Research
Council [G0401527, G0900871, G1000143]; NCATS NIH HHS [TL1 TR000132];
NCI NIH HHS [P30 CA042014, P30 CA076292, R01 CA056678, R01 CA082664, R01
CA092447, R01 CA092579]; Prostate Cancer UK [G2011/36]
NR 29
TC 228
Z9 229
U1 4
U2 61
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2013
VL 45
IS 4
BP 385
EP 391
DI 10.1038/ng.2560
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 115VS
UT WOS:000316840600008
PM 23535732
ER
PT J
AU Garcia-Closas, M
Couch, FJ
Lindstrom, S
Michailidouo, K
Schmidt, MK
Brook, MN
Orr, N
Rhie, SK
Riboli, E
Feigelson, HS
Le Marchand, L
Buring, JE
Eccles, D
Miron, P
Fasching, PA
Brauch, H
Chang-Claude, J
Carpenter, J
Godwin, AK
Nevanlinna, H
Giles, GG
Cox, A
Hopper, JL
Bolla, MK
Wang, Q
Dennis, J
Dicks, E
Howat, WJ
Schoof, N
Bojesen, SE
Lambrechts, D
Broeks, A
Andrulis, IL
Guenel, P
Burwinkel, B
Sawyer, EJ
Hollestelle, A
Fletcher, O
Winqvist, R
Brenner, H
Mannermaa, A
Hamann, U
Meindl, A
Lindblom, A
Zheng, W
Devillee, P
Goldberg, MS
Lubinski, J
Kristensen, V
Swerdlow, A
Anton-Culver, H
Doerk, T
Muir, K
Matsuo, K
Wu, AH
Radice, P
Teo, SH
Shu, XO
Blot, W
Kang, D
Hartman, M
Sangrajrang, S
Shen, CY
Southey, MC
Park, DJ
Hammet, F
Stone, J
Van't Veer, LJ
Rutgers, EJ
Lophatananon, A
Stewart-Brown, S
Siriwanarangsan, P
Peto, J
Schrauder, MG
Ekici, AB
Beckmann, MW
Silva, ID
Johnson, N
Warren, H
Tomlins, I
Kerin, MJ
Miller, N
Marme, F
Schneeweiss, A
Sohn, C
Truong, T
Laurent-Puig, P
Kerbrat, P
Nordestgaard, BG
Nielsen, SF
Flyger, H
Milne, RL
Perez, JIA
Menendez, P
Muller, H
Arndt, V
Stegmaier, C
Lichtner, P
Lochmann, M
Justenhoven, C
Ko, YD
Muranen, TA
Aittomaki, K
Blomqvist, C
Greco, D
Heikkinen, T
Ito, H
Iwata, H
Yatabe, Y
Antonenkova, NN
Margolin, S
Kataja, V
Kosma, VM
Hartikainen, JM
Balleine, R
Tseng, CC
Van den Berg, D
Stram, DO
Neven, P
Dieudonne, AS
Leunen, K
Rudolph, A
Nickels, S
Flesch-Janys, D
Peterlongo, P
Peissel, B
Bernard, L
Olson, JE
Wang, XS
Stevens, K
Severi, G
Baglietto, L
McLean, C
Coetzee, GA
Feng, Y
Henderson, BE
Schumacher, F
Bogdanova, NV
Labreche, F
Dumont, M
Yip, CH
Taib, NAM
Cheng, CY
Shrubsole, M
Long, JR
Pylkas, K
Jukkola-Vuorinen, A
Kauppila, S
Knight, JA
Glendon, G
Mulligan, AM
Tollenaar, RAEM
Seynaeve, CM
Kriege, M
Hooning, MJ
van den Ouweland, AMW
van Deurzen, CHM
Lu, W
Gao, YT
Cai, H
Balasubramanian, SP
Cross, SS
Reed, MWR
Signorello, L
Cai, QY
Shah, M
Miao, H
Chan, CW
Chia, KS
Jakubowska, A
Jaworska, K
Durda, K
Hsiung, CN
Wu, P
Yu, JC
Ashworth, A
Jones, M
Tessier, DC
Gonzalez-Neira, A
Pita, G
Alonso, MR
Vincent, D
Bacot, F
Ambrosone, CB
Bandera, EV
John, EM
Chen, GK
Hu, JJ
Rodriguez-Gil, JL
Bernstein, L
Press, MF
Ziegler, RG
Millikan, RM
Deming-Halverson, SL
Nyante, S
Ingles, SA
Waisfisz, Q
Tsimiklis, H
Makalic, E
Schmidt, D
Bui, M
Gibson, L
Muller-Myhsok, B
Schmutzler, RK
Hein, R
Dahmen, N
Beckmann, L
Aaltonen, K
Czene, K
Irwanto, A
Liu, JJ
Turnbull, C
Rahman, N
Meijers-Heijboer, H
Uitterlinden, AG
Rivadeneira, F
Olswold, C
Slager, S
Pilarski, R
Ademuyiwa, F
Konstantopoulou, I
Martin, NG
Montgomery, GW
Slamon, DJ
Rauh, C
Lux, MP
Jud, SM
Bruning, T
Weaver, J
Harma, P
Pathak, H
Tapper, W
Gerty, S
Durcan, L
Trichopoulos, D
Tumino, R
Peeters, PH
Kaaks, R
Campa, D
Canzian, F
Weiderpass, E
Johansson, M
Khaw, KT
Travis, R
Clavel-Chapelon, F
Kolonel, LN
Chen, C
Beck, A
Hankinson, SE
Berg, CD
Hoover, RN
Lissowska, J
Figueroa, JD
Chasman, DI
Gaudet, MM
Diver, WR
Willett, WC
Hunter, DJ
Simard, J
Benitez, J
Dunning, AM
Sherman, ME
Chenevix-Trench, G
Chanock, SJ
Hall, P
Pharoah, PDP
Vachon, C
Easton, DF
Haiman, CA
Kraft, P
AF Garcia-Closas, Montserrat
Couch, Fergus J.
Lindstrom, Sara
Michailidouo, Kyriaki
Schmidt, Marjanka K.
Brook, Mark N.
Orr, Nick
Rhie, Suhn Kyong
Riboli, Elio
Feigelson, Heather S.
Le Marchand, Loic
Buring, Julie E.
Eccles, Diana
Miron, Penelope
Fasching, Peter A.
Brauch, Hiltrud
Chang-Claude, Jenny
Carpenter, Jane
Godwin, Andrew K.
Nevanlinna, Heli
Giles, Graham G.
Cox, Angela
Hopper, John L.
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Dicks, Ed
Howat, Will J.
Schoof, Nils
Bojesen, Stig E.
Lambrechts, Diether
Broeks, Annegien
Andrulis, Irene L.
Guenel, Pascal
Burwinkel, Barbara
Sawyer, Elinor J.
Hollestelle, Antoinette
Fletcher, Olivia
Winqvist, Robert
Brenner, Hermann
Mannermaa, Arto
Hamann, Ute
Meindl, Alfons
Lindblom, Annika
Zheng, Wei
Devillee, Peter
Goldberg, Mark S.
Lubinski, Jan
Kristensen, Vessela
Swerdlow, Anthony
Anton-Culver, Hoda
Doerk, Thilo
Muir, Kenneth
Matsuo, Keitaro
Wu, Anna H.
Radice, Paolo
Teo, Soo Hwang
Shu, Xiao-Ou
Blot, William
Kang, Daehee
Hartman, Mikael
Sangrajrang, Suleeporn
Shen, Chen-Yang
Southey, Melissa C.
Park, Daniel J.
Hammet, Fleur
Stone, Jennifer
Van't Veer, Laura J.
Rutgers, Emiel J.
Lophatananon, Artitaya
Stewart-Brown, Sarah
Siriwanarangsan, Pornthep
Peto, Julian
Schrauder, Michael G.
Ekici, Arif B.
Beckmann, Matthias W.
Silva, Isabel dos Santos
Johnson, Nichola
Warren, Helen
Tomlins, Ian
Kerin, Michael J.
Miller, Nicola
Marme, Federick
Schneeweiss, Andreas
Sohn, Christof
Therese Truong
Laurent-Puig, Pierre
Kerbrat, Pierre
Nordestgaard, Borge G.
Nielsen, Sune F.
Flyger, Henrik
Milne, Roger L.
Arias Perez, Jose Ignacio
Menendez, Primitiva
Mueller, Heiko
Arndt, Volker
Stegmaier, Christa
Lichtner, Peter
Lochmann, Magdalena
Justenhoven, Christina
Ko, Yon-Dschun
Muranen, Taru A.
Aittomaki, Kristiina
Blomqvist, Carl
Greco, Dario
Heikkinen, Tuomas
Ito, Hidemi
Iwata, Hiroji
Yatabe, Yasushi
Antonenkova, Natalia N.
Margolin, Sara
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Balleine, Rosemary
Tseng, Chiu-Chen
Van den Berg, David
Stram, Daniel O.
Neven, Patrick
Dieudonne, Anne-Sophie
Leunen, Karin
Rudolph, Anja
Nickels, Stefan
Flesch-Janys, Dieter
Peterlongo, Paolo
Peissel, Bernard
Bernard, Loris
Olson, Janet E.
Wang, Xianshu
Stevens, Kristen
Severi, Gianluca
Baglietto, Laura
McLean, Catriona
Coetzee, Gerhard A.
Feng, Ye
Henderson, Brian E.
Schumacher, Fredrick
Bogdanova, Natalia V.
Labreche, France
Dumont, Martine
Yip, Cheng Har
Taib, Nur Aishah Mohd
Cheng, Ching-Yu
Shrubsole, Martha
Long, Jirong
Pylkas, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Knight, Julia A.
Glendon, Gord
Mulligan, Anna Marie
Tollenaar, Robertus A. E. M.
Seynaeve, Caroline M.
Kriege, Mieke
Hooning, Maartje J.
van den Ouweland, Ans M. W.
van Deurzen, Carolien H. M.
Lu, Wei
Gao, Yu-Tang
Cai, Hui
Balasubramanian, Sabapathy P.
Cross, Simon S.
Reed, Malcolm W. R.
Signorello, Lisa
Cai, Qiuyin
Shah, Mitul
Miao, Hui
Chan, Ching Wan
Chia, Kee Seng
Jakubowska, Anna
Jaworska, Katarzyna
Durda, Katarzyna
Hsiung, Chia-Ni
Wu, Peiei
Yu, Jyh-Cherng
Ashworth, Alan
Jones, Michael
Tessier, Daniel C.
Gonzalez-Neira, Anna
Pita, Guillermo
Alonso, M. Rosario
Vincent, Daniel
Bacot, Francois
Ambrosone, Christine B.
Bandera, Elisa V.
John, Esther M.
Chen, Gary K.
Hu, Jennifer J.
Rodriguez-Gil, Jorge L.
Bernstein, Leslie
Press, Michael F.
Ziegler, Regina G.
Millikan, Robert M.
Deming-Halverson, Sandra L.
Nyante, Sarah
Ingles, Sue A.
Waisfisz, Quinten
Tsimiklis, Helen
Makalic, Enes
Schmidt, Daniel
Bui, Minh
Gibson, Lorna
Mueller-Myhsok, Bertram
Schmutzler, Rita K.
Hein, Rebecca
Dahmen, Norbert
Beckmann, Lars
Aaltonen, Kirsimari
Czene, Kamila
Irwanto, Astrid
Liu, Jianjun
Turnbull, Clare
Rahman, Nazneen
Meijers-Heijboer, Hanne
Uitterlinden, Andre G.
Rivadeneira, Fernando
Olswold, Curtis
Slager, Susan
Pilarski, Robert
Ademuyiwa, Foluso
Konstantopoulou, Irene
Martin, Nicholas G.
Montgomery, Grant W.
Slamon, Dennis J.
Rauh, Claudia
Lux, Michael P.
Jud, Sebastian M.
Bruning, Thomas
Weaver, JoEllen
Harma, Priyanka
Pathak, Harsh
Tapper, Will
Gerty, Sue
Durcan, Lorraine
Trichopoulos, Dimitrios
Tumino, Rosario
Peeters, Petra H.
Kaaks, Rudolf
Campa, Daniele
Canzian, Federico
Weiderpass, Elisabete
Johansson, Mattias
Khaw, Kay-Tee
Travis, Ruth
Clavel-Chapelon, Francoise
Kolonel, Laurence N.
Chen, Constance
Beck, Andy
Hankinson, Susan E.
Berg, Christine D.
Hoover, Robert N.
Lissowska, Jolanta
Figueroa, Jonine D.
Chasman, Daniel I.
Gaudet, Mia M.
Diver, W. Ryan
Willett, Walter C.
Hunter, David J.
Simard, Jacques
Benitez, Javier
Dunning, Alison M.
Sherman, Mark E.
Chenevix-Trench, Georgia
Chanock, Stephen J.
Hall, Per
Pharoah, Paul D. P.
Vachon, Celine
Easton, Douglas F.
Haiman, Christopher A.
Kraft, Peter
CA Gene ENvironm Interaction Breast
KConFab Investigators
Familial Breast Canc Study FBCS
Australian Breast Canc Tissue Bank
TI Genome-wide association studies identify four ER negative-specific
breast cancer risk loci
SO NATURE GENETICS
LA English
DT Article
ID BODY-MASS INDEX; COMMON VARIANT; SUSCEPTIBILITY; EXPRESSION; ESTROGEN;
GENE
AB Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
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[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Gaudet, Mia M.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Benitez, Javier] CNIO, Human Genet Grp, Madrid, Spain.
[Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Madrid, Spain.
[Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia.
RP Garcia-Closas, M (reprint author), Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
EM montse.garciaclosas@icr.ac.uk
RI Brenner, Hermann/B-4627-2017; Peissel, Bernard/E-8187-2017; Bandera,
Elisa/M-4169-2014; Jakubowska, Anna/O-8050-2014; Yip,
Cheng-Har/B-1909-2010; Gonzalez-Neira, Anna/C-5791-2015; Garcia-Closas,
Montserrat /F-3871-2015; Pilarski, Robert/E-3871-2011; Shrubsole,
Martha/K-5052-2015; Hartikainen, Jaana/E-6256-2015; Montgomery,
Grant/B-7148-2008; laurent-puig, pierre/B-2226-2013; Bruning,
Thomas/G-8120-2015; Campa, Daniele/K-1617-2016; Weiderpass,
Elisabete/M-4029-2016; Bernard, Loris/K-5953-2014; Verdrengh,
Evelien/H-4571-2012; Andrulis, Irene/E-7267-2013; Ekici,
Arif/C-3971-2013; Kerin, Michael/D-6748-2013; Cheng,
Ching-Yu/K-7017-2013; Radice, Paolo/O-3119-2013; Knight,
Julia/A-6843-2012; Dork, Thilo/J-8620-2012; Clavel-Chapelon,
Francoise/G-6733-2014; Teo, Soo-hwang/H-2353-2014; Hartman,
Mikael/B-4324-2011; Berg , Christine/K-1047-2014
OI Muranen, Taru/0000-0002-5895-1808; Matsuo, Keitaro/0000-0003-1761-6314;
Arndt, Volker/0000-0001-9320-8684; Martin, Nicholas/0000-0003-4069-8020;
Dennis, Joe/0000-0003-4591-1214; Dunning, Alison
Margaret/0000-0001-6651-7166; Brook, Mark/0000-0002-8969-2378;
Rivadeneira, Fernando/0000-0001-9435-9441; Nevanlinna,
Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798;
Cox, Angela/0000-0002-5138-1099; Bui, Minh/0000-0002-9099-6870; Park,
Daniel/0000-0002-6354-0931; ADEMUYIWA, FOLUSO/0000-0002-6766-2258;
Giles, Graham/0000-0003-4946-9099; Brenner, Hermann/0000-0002-6129-1572;
Peissel, Bernard/0000-0001-9233-3571; Hollestelle,
Antoinette/0000-0003-1166-1966; Konstantopoulou,
Irene/0000-0002-0470-0309; Rudolph, Anja/0000-0001-7520-2035; Greco,
Dario/0000-0001-9195-9003; Lux, Michael Patrick/0000-0002-2781-2178;
Czene, Kamila/0000-0002-3233-5695; Cross, Simon/0000-0003-2044-1754;
Lissowska, Jolanta/0000-0003-2695-5799; Arias Perez, Jose
Ignacio/0000-0003-4500-397X; Bandera, Elisa/0000-0002-8789-2755;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Shrubsole,
Martha/0000-0002-5591-7575; Montgomery, Grant/0000-0002-4140-8139;
laurent-puig, pierre/0000-0001-8475-5459; Bruning,
Thomas/0000-0001-9560-5464; Campa, Daniele/0000-0003-3220-9944;
Weiderpass, Elisabete/0000-0003-2237-0128; Cheng,
Ching-Yu/0000-0003-0655-885X;
FU Cancer Research UK [C1287/A10118, C1287/Al2014]; European Community's
Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; European
Union European Cooperation in Science and Technology (COST) [BM0606]; US
National Cancer Institute [U01-CA98233, U01-CA98710, U01CA98216,
U01-CA98758]; Intramural Research Program of the US National Institutes
of Health (NIH)/National Cancer Institute, Division of Cancer
Epidemiology and Genetics; Mayo Clinic Breast Cancer Study (MCBCS); US
NIH [CA122340, CA116201]; Komen Foundation; European Union
[HEALTH-F2-2009223175]; Breast Cancer Research Foundation; Canadian
Institutes of Health Research (CIHR); Ministry of Economic Development,
Innovation and Export Trade of Quebec [PSR-SIIRI701]; US NIH Cancer
Post-Cancer GWAS initiative [U19 CA 148065-01]
FX The authors wish to thank all the individuals who took part in these
studies and all the researchers, clinicians and administrative staff who
have enabled this work to be carried out. We are very grateful to
Illumina, in particular J. Stone, S. McBean, J. Hadlington, A. Mustafa
and K. Cook, for their help with designing the array. BCAC is funded by
Cancer Research UK (C1287/A10118 and C1287/Al2014) and by the European
Community's Seventh Framework Programme under grant agreement 223175
(HEALTH-F2-2009-223175) (COGS). Meetings of BCAC have been funded by the
European Union European Cooperation in Science and Technology (COST)
programme (BM0606). BPC3 is funded by US National Cancer Institute
cooperative agreements U01-CA98233, U01-CA98710, U01CA98216 and
U01-CA98758 and the Intramural Research Program of the US National
Institutes of Health (NIH)/National Cancer Institute, Division of Cancer
Epidemiology and Genetics. TNBCC is supported by Mayo Clinic Breast
Cancer Study (MCBCS) (US NIH grants CAl22340 and a Specialized Program
of Research Excellence (SPORE) in Breast Cancer (CA116201)), grants from
the Komen Foundation for the Cure and the Breast Cancer Research
Foundation. Genotyping on the iCOGS array was funded by the European
Union (HEALTH-F2-2009223175), Cancer Research UK (C1287/A10710), US NIH
grant CAl22340, the Komen Foundation for the Cure, the Breast Cancer
Research Foundation, the Canadian Institutes of Health Research (CIHR)
for the CIHR Team in Familial Risks of Breast Cancer program (J. Simiard
and D.E.) and Ministry of Economic Development, Innovation and Export
Trade of Quebec grant PSR-SIIRI701 (J. Simiard, D.E. and P.H.). J.
Simiard holds the Canada Research Chair in Oncogenetics. Combination of
the GWAS data was supported in part by US NIH Cancer Post-Cancer GWAS
initiative grant U19 CA 148065-01 (DRIVE, part of the GAME-ON
initiative) and Breakthrough Breast Cancer Research.
NR 17
TC 174
Z9 177
U1 9
U2 98
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2013
VL 45
IS 4
BP 392
EP 398
DI 10.1038/ng.2561
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 115VS
UT WOS:000316840600009
PM 23535733
ER
PT J
AU Codd, V
Nelson, CP
Albrecht, E
Mangino, M
Deelen, J
Buxton, JL
Hottenga, JJ
Fischer, K
Esko, T
Surakka, I
Broer, L
Nyholt, DR
Leach, IM
Salo, P
Hagg, S
Matthews, MK
Palmen, J
Norata, GD
O'Reilly, PF
Saleheen, D
Amin, N
Balmforth, AJ
Beekman, M
de Boer, RA
Bohringer, S
Braund, PS
Burton, PR
de Craen, AJM
Denniff, M
Dong, YB
Douroudis, K
Dubinina, E
Eriksson, JG
Garlaschelli, K
Guo, DH
Hartikainen, AL
Henders, AK
Houwing-Duistermaat, JJ
Kananen, L
Karssen, LC
Kettunen, J
Klopp, N
Lagou, V
van Leeuwen, EM
Madden, PA
Magi, R
Magnusson, PKE
Mannisto, S
McCarthy, MI
Medland, SE
Mihailov, E
Montgomery, GW
Oostra, B
Palotie, A
Peters, A
Pollard, H
Pouta, A
Prokopenko, I
Ripatti, S
Salomaa, V
Suchiman, HED
Valdes, AM
Verweij, N
Vinuela, A
Wang, XL
Wichmann, HE
Widen, E
Willemsen, G
Wright, MJ
Xia, K
Xiao, XJ
van Veldhuisen, DJ
Catapano, AL
Tobin, MD
Hall, AS
Blakemore, AIF
van Gilst, WH
Zhu, HD
Erdmann, J
Reilly, MP
Kathiresan, S
Schunkert, H
Talmud, PJ
Pedersen, NL
Perola, M
Ouwehand, W
Kaprio, J
Martin, NG
van Duijn, CM
Hovatta, I
Gieger, C
Metspalu, A
Boomsma, DI
Jarvelin, MR
Slagboom, PE
Thompson, JR
Spector, TD
van der Harst, P
Samani, NJ
AF Codd, Veryan
Nelson, Christopher P.
Albrecht, Eva
Mangino, Massimo
Deelen, Joris
Buxton, Jessica L.
Hottenga, Jouke Jan
Fischer, Krista
Esko, Tonu
Surakka, Ida
Broer, Linda
Nyholt, Dale R.
Leach, Irene Mateo
Salo, Perttu
Hagg, Sara
Matthews, Mary K.
Palmen, Jutta
Norata, Giuseppe D.
O'Reilly, Paul F.
Saleheen, Danish
Amin, Najaf
Balmforth, Anthony J.
Beekman, Marian
de Boer, Rudolf A.
Bohringer, Stefan
Braund, Peter S.
Burton, Paul R.
de Craen, Anton J. M.
Denniff, Matthew
Dong, Yanbin
Douroudis, Konstantinos
Dubinina, Elena
Eriksson, Johan G.
Garlaschelli, Katia
Guo, Dehuang
Hartikainen, Anna-Liisa
Henders, Anjali K.
Houwing-Duistermaat, Jeanine J.
Kananen, Laura
Karssen, Lennart C.
Kettunen, Johannes
Klopp, Norman
Lagou, Vasiliki
van Leeuwen, Elisabeth M.
Madden, Pamela A.
Maegi, Reedik
Magnusson, Patrik K. E.
Mannisto, Satu
McCarthy, Mark I.
Medland, Sarah E.
Mihailov, Evelin
Montgomery, Grant W.
Oostra, Ben A.
Palotie, Aarno
Peters, Annette
Pollard, Helen
Pouta, Anneli
Prokopenko, Inga
Ripatti, Samuli
Salomaa, Veikko
Suchiman, H. Eka D.
Valdes, Ana M.
Verweij, Niek
Vinuela, Ana
Wang, Xiaoling
Wichmann, H-Erich
Widen, Elisabeth
Willemsen, Gonneke
Wright, Margaret J.
Xia, Kai
Xiao, Xiangjun
van Veldhuisen, Dirk J.
Catapano, Alberico L.
Tobin, Martin D.
Hall, Alistair S.
Blakemore, Alexandra I. F.
van Gilst, Wiek H.
Zhu, Haidong
Erdmann, Jeanette
Reilly, Muredach P.
Kathiresan, Sekar
Schunkert, Heribert
Talmud, Philippa J.
Pedersen, Nancy L.
Perola, Markus
Ouwehand, Willem
Kaprio, Jaakko
Martin, Nicholas G.
van Duijn, Cornelia M.
Hovatta, Iris
Gieger, Christian
Metspalu, Andres
Boomsma, Dorret I.
Jarvelin, Marjo-Riitta
Slagboom, P. Eline
Thompson, John R.
Spector, Tim D.
van der Harst, Pim
Samani, Nilesh J.
CA CARDIoGRAM Consortium
TI Identification of seven loci affecting mean telomere length and their
association with disease
SO NATURE GENETICS
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; RISK; CANCER;
ATHEROSCLEROSIS; SUSCEPTIBILITY; FIBROBLASTS; DYSFUNCTION; VARIANTS;
STRESS
AB Interindividual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases. We report here a genome-wide meta-analysis of 37,684 individuals with replication of selected variants in an additional 10,739 individuals. We identified seven loci, including five new loci, associated with mean LTL (P < 5 x 10(-8)). Five of the loci contain candidate genes (TERC, TERT, NAF1, OBFC1 and RTEL1) that are known to be involved in telomere biology. Lead SNPs at two loci (TERC and TERT) associate with several cancers and other diseases, including idiopathic pulmonary fibrosis. Moreover, a genetic risk score analysis combining lead variants at all 7 loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of coronary artery disease (21% (95% confidence interval, 5-35%) per standard deviation in LTL, P = 0.014). Our findings support a causal role of telomere-length variation in some age-related diseases.
C1 [Codd, Veryan; Nelson, Christopher P.; Matthews, Mary K.; Braund, Peter S.; Denniff, Matthew; Dubinina, Elena; Pollard, Helen; van der Harst, Pim; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Codd, Veryan; Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Gen Hosp, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England.
[Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Mangino, Massimo; Valdes, Ana M.; Vinuela, Ana; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Deelen, Joris; Beekman, Marian; Suchiman, H. Eka D.; Slagboom, P. Eline] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Leiden, Netherlands.
[Deelen, Joris; Broer, Linda; Beekman, Marian; Houwing-Duistermaat, Jeanine J.; van Duijn, Cornelia M.; Slagboom, P. Eline] Leiden Univ, Med Ctr, Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Buxton, Jessica L.; Blakemore, Alexandra I. F.] Univ London Imperial Coll Sci Technol & Med, Sect Invest Med, London, England.
[Hottenga, Jouke Jan; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Fischer, Krista; Esko, Tonu; Douroudis, Konstantinos; Maegi, Reedik; Mihailov, Evelin; Perola, Markus; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Surakka, Ida; Kettunen, Johannes; Ripatti, Samuli; Widen, Elisabeth; Perola, Markus; Kaprio, Jaakko] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
[Surakka, Ida; Salo, Perttu; Eriksson, Johan G.; Kettunen, Johannes; Mannisto, Satu; Ripatti, Samuli; Salomaa, Veikko; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland.
[Broer, Linda; Amin, Najaf; Karssen, Lennart C.; van Leeuwen, Elisabeth M.; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Broer, Linda; van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands.
[Nyholt, Dale R.; Henders, Anjali K.; Medland, Sarah E.; Montgomery, Grant W.; Wright, Margaret J.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Leach, Irene Mateo; de Boer, Rudolf A.; Verweij, Niek; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Hagg, Sara; Magnusson, Patrik K. E.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Palmen, Jutta; Talmud, Philippa J.] UCL, Inst Cardiovasc Sci, London, England.
[Norata, Giuseppe D.; Catapano, Alberico L.] Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy.
[Norata, Giuseppe D.; Garlaschelli, Katia] Bassini Hosp, Ctr Soc Italiana Studio Aterosclerosi, Cinisello Balsamo, Italy.
[Norata, Giuseppe D.] Queen Mary Univ, Barts & London Sch Med & Dent, Blizard Inst, London, England.
[O'Reilly, Paul F.; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.
[O'Reilly, Paul F.; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC, Hlth Protect Agcy Ctr Environm & Hlth, London, England.
[Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Balmforth, Anthony J.; Hall, Alistair S.] Univ Leeds, Sch Med, Div Epidemiol, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England.
[Bohringer, Stefan; Houwing-Duistermaat, Jeanine J.] Leiden Univ, Med Ctr, Sect Med Stat, Leiden, Netherlands.
[Burton, Paul R.; Tobin, Martin D.; Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Dong, Yanbin; Guo, Dehuang; Wang, Xiaoling; Zhu, Haidong] Georgia Hlth Sci Univ, Georgia Prevent Inst, Augusta, GA USA.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Inst Clin Med Obstet & Gynecol, Oulu, Finland.
[Kananen, Laura; Hovatta, Iris] Univ Helsinki, Biomedicum Helsinki, Res Programs Unit, Helsinki, Finland.
[Kananen, Laura; Hovatta, Iris] Univ Helsinki, Dept Med Genet, Haartman Inst, Helsinki, Finland.
[Klopp, Norman; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Klopp, Norman] Hannover Med Sch, Hanover Unified Biobank, Hannover, NH, Germany.
[Lagou, Vasiliki; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Madden, Pamela A.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford OX3 7LJ, England.
[Palotie, Aarno; Ripatti, Samuli; Ouwehand, Willem] Wellcome Trust Sanger Inst, Hinxton, England.
[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Palotie, Aarno] Helsinki Univ Hosp, Helsinki, Finland.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Peters, Annette] Munich Heart Alliance, Munich, Germany.
[Pouta, Anneli] Natl Inst Hlth & Welf, Oulu, Finland.
[Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany.
[Xia, Kai] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Xiao, Xiangjun] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Catapano, Alberico L.] Inst Ricovero & Cura Carattere Sci Multimed, Milan, Italy.
[Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Ouwehand, Willem] Univ Cambridge, Dept Hematol, Cambridge, England.
[Ouwehand, Willem] Natl Hlth Serv Blood & Transplant, Cambridge, England.
[Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Kaprio, Jaakko; Hovatta, Iris] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Lifecourse & Serv, Oulu, Finland.
[van der Harst, Pim] Univ Groningen, Univ Med Ctr, Dept Genet, Groningen, Netherlands.
RP Samani, NJ (reprint author), Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
EM njs@le.ac.uk
RI Peters, Annette/A-6117-2011; Burton, Paul/H-7527-2016; mangino,
massimo/F-5134-2011; Slagboom, P. Eline/R-4790-2016; Verweij,
Niek/A-4499-2017; Magnusson, Patrik/C-4458-2017; Suchiman, H. Eka
D./F-5024-2017; Nyholt, Dale/C-8384-2013; Buxton, Jessica/I-4033-2014;
Hovatta, Iiris/D-6871-2012; Medland, Sarah/C-7630-2013; Ripatti,
Samuli/H-9446-2014; Montgomery, Grant/B-7148-2008; Prokopenko,
Inga/H-3241-2014; Wright, Margaret/A-4560-2016; Vinuela,
Ana/J-9326-2012; Lagou, Vasiliki/N-8451-2013; Xia, Kai/B-7214-2014; van
Veldhuisen, Dirk Jan/E-8967-2014; Erdmann, Jeanette/P-7513-2014;
OI mangino, massimo/0000-0002-2167-7470; Slagboom, P.
Eline/0000-0002-2875-4723; Suchiman, H. Eka D./0000-0002-7168-5516;
Magi, Reedik/0000-0002-2964-6011; Deelen, Joris/0000-0003-4483-3701;
Vinuela, Ana/0000-0003-3771-8537; Talmud, Philippa/0000-0002-5560-1933;
Beekman, Marian/0000-0003-0585-6206; Buxton,
Jessica/0000-0002-0918-9335; Hovatta, Iiris/0000-0002-5990-7892;
Medland, Sarah/0000-0003-1382-380X; Ripatti, Samuli/0000-0002-0504-1202;
Montgomery, Grant/0000-0002-4140-8139; Prokopenko,
Inga/0000-0003-1624-7457; Wright, Margaret/0000-0001-7133-4970;
Ouwehand, Willem/0000-0002-7744-1790; Kaprio,
Jaakko/0000-0002-3716-2455; Karssen, Lennart C./0000-0002-1959-342X;
Martin, Nicholas/0000-0003-4069-8020; Esko, Tonu/0000-0003-1982-6569;
Erdmann, Jeanette/0000-0002-4486-6231; Norata, Giuseppe
Danilo/0000-0002-6081-1257; Mannisto, Satu/0000-0002-8668-3046; Gieger,
Christian/0000-0001-6986-9554; Verweij, Niek/0000-0002-4303-7685;
Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Eriksson,
Johan/0000-0002-2516-2060; Catapano, Alberico Luigi/0000-0002-7593-2094
FU European Union Framework 7 ENGAGE Project [HEALTH-F4-2007-201413]
FX This study was undertaken under the framework of European Union
Framework 7 ENGAGE Project (HEALTH-F4-2007-201413).
NR 39
TC 222
Z9 226
U1 6
U2 62
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2013
VL 45
IS 4
BP 422
EP 427
DI 10.1038/ng.2528
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 115VS
UT WOS:000316840600013
PM 23535734
ER
PT J
AU Fritsche, LG
Chen, W
Schu, M
Yaspan, BL
Yu, Y
Thorleifsson, G
Zack, DJ
Arakawa, S
Cipriani, V
Ripke, S
Igo, RP
Buitendijk, GHS
Sim, XL
Weeks, DE
Guymer, RH
Merriam, JE
Francis, PJ
Hannum, G
Agarwal, A
Armbrecht, AM
Audo, I
Aung, T
Barile, GR
Benchaboune, M
Bird, AC
Bishop, PN
Branham, KE
Brooks, M
Brucker, AJ
Cade, WH
Cain, MS
Campochiaroll, PA
Chan, CC
Cheng, CY
Chew, EY
Chin, KA
Chowers, I
Clayton, DG
Cojocaru, R
Conley, YP
Cornes, BK
Daly, MJ
Dhillon, B
Edwards, A
Evangelou, E
Fagemess, J
Ferreyra, HA
Friedman, JS
Geirsdottir, A
George, RJ
Gieger, C
Gupta, N
Hagstrom, SA
Harding, SP
Haritoglou, C
Heckenlively, JR
Hoz, FG
Hughes, G
Ioannidis, JPA
Ishibashi, T
Joseph, P
Jun, G
Kamatani, Y
Katsanis, N
Keilhauer, CN
Khan, JC
Kim, IK
Kiyohara, Y
Klein, BEK
Klein, R
Kovach, JL
Kozak, I
Lee, CJ
Lee, KE
Lichtner, P
Lotery, AJ
Meitinger, T
Mitchell, P
Mohand-Said, S
Moore, AT
Morgan, DJ
Margaux, AM
Myers, CE
Naj, AC
Nakamura, Y
Okada, Y
Orlin, A
Ortube, MC
Othman, MI
Pappas, C
Park, KH
Pauer, GJT
Peachey, NS
Poch, O
Priya, RR
Reynolds, R
Richardson, AJ
Ripp, R
Rudolph, G
Ryu, E
Sahel, JA
Schaumberg, DA
Scholl, HPN
Schwartz, SG
Scott, WK
Shahid, H
Sigurdsson, H
Silvestri, G
Sivakumaran, TA
Smith, RT
Sobrin, L
Souied, EH
Stambolian, DE
Stefansson, H
Sturgill-Short, GM
Takahashi, A
Tosakulwong, N
Truitt, BJ
Tsironi, EE
Uitterlinden, AG
van Duijn, CM
Vijaya, L
Vingerling, JR
Vithana, EN
Webster, AR
Wichmann, HE
Winkler, TW
Wong, TY
Wright, AF
Zelenika, D
Zhang, M
Zhao, L
Zhang, K
Klein, ML
Hageman, GS
Lathrop, GM
Stefansson, K
Allikmets, R
Baird, PN
Gorin, MB
Wang, JJ
Klaver, CCW
Seddon, JM
Pericak-Vance, MA
Iyengar, SK
Yates, JRW
Swaroop, A
Weber, BHF
Kubo, M
DeAngelis, MM
Leveillard, T
Thorsteinsdottir, U
Haines, JL
Farrer, LA
Heid, IM
Abecasis, GR
AF Fritsche, Lars G.
Chen, Wei
Schu, Matthew
Yaspan, Brian L.
Yu, Yi
Thorleifsson, Gudmar
Zack, Donald J.
Arakawa, Satoshi
Cipriani, Valentina
Ripke, Stephan
Igo, Robert P., Jr.
Buitendijk, Gabrielle H. S.
Sim, Xueling
Weeks, Daniel E.
Guymer, Robyn H.
Merriam, Joanna E.
Francis, Peter J.
Hannum, Gregory
Agarwal, Anita
Armbrecht, Ana Maria
Audo, Isabelle
Aung, Tin
Barile, Gaetano R.
Benchaboune, Mustapha
Bird, Alan C.
Bishop, Paul N.
Branham, Kari E.
Brooks, Matthew
Brucker, Alexander J.
Cade, William H.
Cain, Melinda S.
Campochiaroll, Peter A.
Chan, Chi-Chao
Cheng, Ching-Yu
Chew, Emily Y.
Chin, Kimberly A.
Chowers, Itay
Clayton, David G.
Cojocaru, Radu
Conley, Yvette P.
Cornes, Belinda K.
Daly, Mark J.
Dhillon, Baljean
Edwards, Albert
Evangelou, Evangelos
Fagemess, Jesen
Ferreyra, Henry A.
Friedman, James S.
Geirsdottir, Asbjorg
George, Ronnie J.
Gieger, Christian
Gupta, Neel
Hagstrom, Stephanie A.
Harding, Simon P.
Haritoglou, Christos
Heckenlively, John R.
Hoz, Frank G.
Hughes, Guy
Ioannidis, John P. A.
Ishibashi, Tatsuro
Joseph, Peronne
Jun, Gyungah
Kamatani, Yoichiro
Katsanis, Nicholas
Keilhauer, Claudia N.
Khan, Jane C.
Kim, Ivana K.
Kiyohara, Yutaka
Klein, Barbara E. K.
Klein, Ronald
Kovach, Jaclyn L.
Kozak, Igor
Lee, Clara J.
Lee, Kristine E.
Lichtner, Peter
Lotery, Andrew J.
Meitinger, Thomas
Mitchell, Paul
Mohand-Saied, Saddek
Moore, Anthony T.
Morgan, Denise J.
Morrison, Margaux A.
Myers, Chelsea E.
Naj, Adam C.
Nakamura, Yusuke
Okada, Yukinori
Orlin, Anton
Ortube, M. Carolina
Othman, Mohammad I.
Pappas, Chris
Park, Kyu Hyung
Pauer, Gayle J. T.
Peachey, Neal S.
Poch, Olivier
Priya, Rinki Ratna
Reynolds, Robyn
Richardson, Andrea J.
Ripp, Raymond
Rudolph, Guenther
Ryu, Euijung
Sahel, Jose-Alain
Schaumberg, Debra A.
Scholl, Hendrik P. N.
Schwartz, Stephen G.
Scott, William K.
Shahid, Humma
Sigurdsson, Haraldur
Silvestri, Giuliana
Sivakumaran, Theru A.
Smith, R. Theodore
Sobrin, Lucia
Souied, Eric H.
Stambolian, Dwight E.
Stefansson, Hreinn
Sturgill-Short, Gwen M.
Takahashi, Atsushi
Tosakulwong, Nirubol
Truitt, Barbara J.
Tsironi, Evangelia E.
Uitterlinden, Andre G.
van Duijn, Cornelia M.
Vijaya, Lingam
Vingerling, Johannes R.
Vithana, Eranga N.
Webster, Andrew R.
Wichmann, H-Erich
Winkler, Thomas W.
Wong, Tien Y.
Wright, Alan F.
Zelenika, Diana
Zhang, Ming
Zhao, Ling
Zhang, Kang
Klein, Michael L.
Hageman, Gregory S.
Lathrop, G. Mark
Stefansson, Kari
Allikmets, Rando
Baird, Paul N.
Gorin, Michael B.
Wang, Jie Jin
Klaver, Caroline C. W.
Seddon, Johanna M.
Pericak-Vance, Margaret A.
Iyengar, Sudha K.
Yates, John R. W.
Swaroop, Anand
Weber, Bernhard H. F.
Kubo, Michiaki
DeAngelis, Margaret M.
Leveillard, Thierry
Thorsteinsdottir, Unnur
Haines, Jonathan L.
Farrer, Lindsay A.
Heid, Iris M.
Abecasis, Goncalo R.
CA AMD Gene Consortium
TI Seven new loci associated with age-related macular degeneration
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMPLEMENT FACTOR-H; GENOTYPE IMPUTATION;
APOLIPOPROTEIN-E; INFLUENCES RISK; SUSCEPTIBILITY; GENE; VARIANTS;
DISEASES; CFH
AB Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 x 10(-8) These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 x 10-8 for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.
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[Schu, Matthew; Jun, Gyungah; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Sect Biomed Genet, Boston, MA 02118 USA.
[Schu, Matthew; Jun, Gyungah; Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med, Sect Biomed Genet, Boston, MA USA.
[Yaspan, Brian L.; Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA.
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[Zack, Donald J.; Sahel, Jose-Alain; Leveillard, Thierry] Univ Paris 06, Dept Genet, Inst Vis, UMRS 968, Paris, France.
[Zack, Donald J.; Campochiaroll, Peter A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Neurosci, Baltimore, MD 21205 USA.
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[Ripke, Stephan; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
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[Sahel, Jose-Alain; Leveillard, Thierry] INSERM, U968, Paris, France.
[Mohand-Saied, Saddek; Sahel, Jose-Alain; Leveillard, Thierry] CNRS, UMR 7210, Paris, France.
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[Sahel, Jose-Alain] Fdn Ophtalmol Adolphe Rothschild, Paris, France.
[Sahel, Jose-Alain] Acad Sci Inst France, Paris, France.
[Schaumberg, Debra A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Shahid, Humma] Addenbrookes Hosp, Dept Ophthalmol, Cambridge, England.
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[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Wichmann, H-Erich] Deutsch Forschungszentrum Gesundheit & Umwelt, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Gorin, Michael B.] Univ Munich, Inst Med Informat, Munich, Germany.
[Wichmann, H-Erich; Gorin, Michael B.] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany.
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[Zelenika, Diana; Lathrop, G. Mark] Ctr Energie Atom, Inst Genom, Ctr Natl Genotypage, Evry, France.
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[Iyengar, Sudha K.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA.
[Iyengar, Sudha K.] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA.
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[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Abecasis, GR (reprint author), Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
EM jonathan@chgr.mc.vanderbilt.edu; farrer@bu.edu;
iris.heid@klinik.uni-regensburg.de; goncalo@umich.edu
RI Kubo, Michiaki/N-7947-2015; Abecasis, Goncalo/B-7840-2010; Sahel,
Jose-Alain/F-3172-2017; Cipriani, Valentina/A-8549-2012; Cheng,
Ching-Yu/K-7017-2013; Wang, Jie Jin/P-1499-2014; Mitchell,
Paul/P-1498-2014; Zhao, Ling/D-9005-2015; DeAngelis, e/J-7863-2015;
Meitinger, Thomas/O-1318-2015; Klaver, Caroline/A-2013-2016; Kamatani,
Yoichiro/N-5513-2015;
OI Farrer, Lindsay/0000-0001-5533-4225; george, ronnie/0000-0001-7368-0252;
Baird, Paul/0000-0002-1305-3502; Zack, Don/0000-0002-7966-1973;
Abecasis, Goncalo/0000-0003-1509-1825; Harding,
Simon/0000-0003-4676-1158; Swaroop, Anand/0000-0002-1975-1141; Gieger,
Christian/0000-0001-6986-9554; Stefansson, Hreinn/0000-0002-9331-6666;
Klein, Ronald/0000-0002-4428-6237; Bishop, Paul/0000-0001-7937-7932;
Cipriani, Valentina/0000-0002-0839-9955; Cheng,
Ching-Yu/0000-0003-0655-885X; Wang, Jie Jin/0000-0001-9491-4898; Jun,
Gyungah/0000-0002-3230-8697; Evangelou, Evangelos/0000-0002-5488-2999;
smith, theodore/0000-0002-1693-943X; Weeks, Daniel/0000-0001-9410-7228;
Katsanis, Nicholas/0000-0002-2480-0171
FU Medical Research Council [G0000067, MC_U127584475, MR/K006584/1]; NEI
NIH HHS [P30 EY014800, R01 EY013435, R01 EY022005]; NHGRI NIH HHS [R01
HG007022]
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2013
VL 45
IS 4
BP 433
EP 439
DI 10.1038/ng.2578
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 115VS
UT WOS:000316840600015
PM 23455636
ER
PT J
AU Pillai, S
AF Pillai, Shiv
TI Love the one you're with: the HIV, B cell and T-FH cell triangle
SO NATURE MEDICINE
LA English
DT Editorial Material
ID FOLLICULAR HELPER-CELLS; INFECTION
AB Many HIV-infected people show impaired humoral immune responses, but it is unclear why. A new view into this conundrum may be provided with the recent discovery of altered interactions between follicular helper T (T-FH) cells and germinal center B cells from HIV-infected individuals. This leads to inadequate T-FH cell help for germinal center B cells and decreased B cell antibody responses (pages 494-499).
C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
EM pillai@helix.mgh.harvard.edu
NR 9
TC 4
Z9 4
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD APR
PY 2013
VL 19
IS 4
BP 401
EP 402
DI 10.1038/nm.3141
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 119PF
UT WOS:000317109100017
PM 23558623
ER
PT J
AU Cubas, RA
Mudd, JC
Savoye, AL
Perreau, M
van Grevenynghe, J
Metcalf, T
Connick, E
Meditz, A
Freeman, GJ
Abesada-Terk, G
Jacobson, JM
Brooks, AD
Crotty, S
Estes, JD
Pantaleo, G
Lederman, MM
Haddad, EK
AF Cubas, Rafael A.
Mudd, Joseph C.
Savoye, Anne-Laure
Perreau, Matthieu
van Grevenynghe, Julien
Metcalf, Talibah
Connick, Elizabeth
Meditz, Amie
Freeman, Gordon J.
Abesada-Terk, Guillermo, Jr.
Jacobson, Jeffrey M.
Brooks, Ari D.
Crotty, Shane
Estes, Jacob D.
Pantaleo, Giuseppe
Lederman, Michael M.
Haddad, Elias K.
TI Inadequate T follicular cell help impairs B cell immunity during HIV
infection
SO NATURE MEDICINE
LA English
DT Article
ID ACTIVE-ANTIRETROVIRAL-THERAPY; HUMORAL IMMUNITY; VIRAL-INFECTION; SIV
INFECTION; LYMPH-NODES; C-MAF; MEMORY; RESPONSES; INDIVIDUALS;
ANTIBODIES
AB The majority of HIV-infected individuals fail to produce protective antibodies and have diminished responses to new immunizations(1-3). We report here that even though there is an expansion of follicular helper T (T-FH) cells in HIV-infected individuals, the cells are unable to provide adequate B cell help. We found a higher frequency of programmed cell death ligand 1 (PD-L1)(+) germinal center B cells from lymph nodes of HIV-infected individuals suggesting a potential role for PD-1-PD-L1 interaction in regulating T-FH cell function. In fact, we show that engagement of PD-1 on T-FH cells leads to a reduction in cell proliferation, activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine secretion. Blocking PD-1 signaling enhances HIV-specific immunoglobulin production in vitro. We further show that at least part of this defect involves IL-21, as addition of this cytokine rescues antibody responses and plasma cell generation in vitro. Our results suggest that deregulation of T-FH cell-mediated B cell help diminishes B cell responses during HIV infection and may be related to PD-1 triggering on T-FH cells. These results demonstrate a role for T-FH cell impairment in HIV pathogenesis and suggest that enhancing their function could have a major impact on the outcome and control of HIV infection, preventing future infections and improving immune responses to vaccinations.
C1 [Cubas, Rafael A.; van Grevenynghe, Julien; Metcalf, Talibah; Haddad, Elias K.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA.
[Mudd, Joseph C.; Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis, Ctr AIDS Res, Univ Hosp,Case Med Ctr, Cleveland, OH 44106 USA.
[Savoye, Anne-Laure; Perreau, Matthieu; Pantaleo, Giuseppe] Univ Lausanne, Lausanne Univ Hosp, Swiss Vaccine Res Inst, Div Immunol & Allergy, Lausanne, Switzerland.
[Connick, Elizabeth; Meditz, Amie] Univ Colorado Denver, Div Infect Dis, Denver, CO USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Abesada-Terk, Guillermo, Jr.] Martin Mem Hlth Syst, Robert & Carol Weissman Canc Ctr, Stuart, FL USA.
[Jacobson, Jeffrey M.] Drexel Univ, Coll Med, Div Infect Dis & HIV Med, Philadelphia, PA 19104 USA.
[Brooks, Ari D.] Drexel Univ, Coll Med, Dept Surg, Philadelphia, PA 19104 USA.
[Crotty, Shane] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA.
[Crotty, Shane] Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA USA.
[Estes, Jacob D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Haddad, EK (reprint author), Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA.
EM ehaddad@vgtifl.org
RI Pantaleo, Giuseppe/K-6163-2016; Perreau, Matthieu/D-6309-2017
FU US National Institutes of Health (NIH) [HHSN272201100017C, NIH-1P01
AI080192, U19AI082630, 2P01 AI056299, R01 AI096966]; Case Western
Reserve University Center for AIDS Research [AI 36219]; Cleveland
Immunopathogenesis Consortium [AI 76174]
FX We thank W. Ryzner, R. Bordi and D. Brown for sample collection. We also
thank K. Kusser and Y. Shi from the Flow Cytometry Core at Vaccine &
Gene Therapy Institute Florida for their help with sorting all the
samples. We are grateful to R. Debernardo (Case Western Reserve
University and University Hospitals Case Medical Center) for obtaining
the HIV-uninfected lymph nodes and to B. Rodriguez for his help with the
infected lymph node samples. This study was supported in part by US
National Institutes of Health (NIH) contract HHSN272201100017C, NIH-1P01
AI080192, U19AI082630, 2P01 AI056299 and R01 AI096966. This work was
also supported by the Case Western Reserve University Center for AIDS
Research (AI 36219) and by the Cleveland Immunopathogenesis Consortium
(AI 76174).
NR 40
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U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD APR
PY 2013
VL 19
IS 4
BP 494
EP +
DI 10.1038/nm.3109
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 119PF
UT WOS:000317109100036
PM 23475201
ER
PT J
AU Kennedy, PJ
Feng, J
Robison, AJ
Maze, I
Badimon, A
Mouzon, E
Chaudhury, D
Damez-Werno, DM
Haggarty, SJ
Han, MH
Bassel-Duby, R
Olson, EN
Nestler, EJ
AF Kennedy, Pamela J.
Feng, Jian
Robison, A. J.
Maze, Ian
Badimon, Ana
Mouzon, Ezekiell
Chaudhury, Dipesh
Damez-Werno, Diane M.
Haggarty, Stephen J.
Han, Ming-Hu
Bassel-Duby, Rhonda
Olson, Eric N.
Nestler, Eric J.
TI Class I HDAC inhibition blocks cocaine-induced plasticity by targeted
changes in histone methylation
SO NATURE NEUROSCIENCE
LA English
DT Article
ID NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; DEACETYLASE INHIBITORS;
LOCOMOTOR SENSITIZATION; SYNAPTIC PLASTICITY; MEMORY FORMATION;
DELTA-FOSB; AMPHETAMINE; EXPRESSION; MICE
AB Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the acetylation of histone tails, but little is known about the functional specificity of different HDAC isoforms in the development and maintenance of cocaine-induced plasticity, and previous studies of HDAC inhibitors report conflicting effects on cocaine-elicited behavioral adaptations. Here we demonstrate that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior, an effect mediated in part through a chromatin-mediated suppression of GABA(A) receptor subunit expression and inhibitory tone on NAc neurons. Our findings suggest a new mechanism by which prolonged and selective HDAC inhibition can alter behavioral and molecular adaptations to cocaine and inform the development of therapeutics for cocaine addiction.
C1 [Kennedy, Pamela J.; Feng, Jian; Robison, A. J.; Badimon, Ana; Mouzon, Ezekiell; Damez-Werno, Diane M.; Nestler, Eric J.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY USA.
[Kennedy, Pamela J.; Feng, Jian; Robison, A. J.; Badimon, Ana; Mouzon, Ezekiell; Damez-Werno, Diane M.; Nestler, Eric J.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA.
[Maze, Ian] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10021 USA.
[Chaudhury, Dipesh; Han, Ming-Hu] Mt Sinai Sch Med, Friedman Brain Inst, Dept Pharmacol & Syst Therapeut, New York, NY USA.
[Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Neurol, Boston, MA USA.
[Bassel-Duby, Rhonda; Olson, Eric N.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
RP Nestler, EJ (reprint author), Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY USA.
EM eric.nestler@mssm.edu
OI Maze, Ian/0000-0003-1490-7781; Robison, Alfred/0000-0002-4150-9570;
Haggarty, Stephen J./0000-0002-7872-168X
FU US National Institute on Drug Abuse; US National Institute of Mental
Health; Canadian Institutes for Health Research [MFE 90086]
FX The authors would like to thank R. Neve (Massachusetts Institute of
Technology) for viral vectors and M. Baxter for statistical expertise.
This work was supported by grants from the US National Institute on Drug
Abuse and National Institute of Mental Health (E.J.N.) and the Canadian
Institutes for Health Research (P.J.K.; MFE 90086).
NR 45
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Z9 64
U1 1
U2 31
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD APR
PY 2013
VL 16
IS 4
BP 434
EP U95
DI 10.1038/nn.3354
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 114EM
UT WOS:000316723700013
PM 23475113
ER
PT J
AU Gellhorn, AC
Katz, JN
Suri, P
AF Gellhorn, Alfred C.
Katz, Jeffrey N.
Suri, Pradeep
TI Osteoarthritis of the spine: the facet joints
SO NATURE REVIEWS RHEUMATOLOGY
LA English
DT Review
ID LOW-BACK-PAIN; BONE-MARROW LESIONS; LUMBAR ZYGAPOPHYSEAL JOINTS;
COMMUNITY-BASED POPULATION; CERVICAL-SPINE; DISC DEGENERATION;
LONGITUDINAL ASSESSMENT; KNEE OSTEOARTHRITIS; CLINICAL-FEATURES;
PREVALENCE
AB Osteoarthritis (OA) of the spine involves the facet joints, which are located in the posterior aspect of the vertebral column and, in humans, are the only true synovial joints between adjacent spinal levels. Facet joint osteoarthritis (FJ OA) is widely prevalent in older adults, and is thought to be a common cause of back and neck pain. The prevalence of facet-mediated pain in clinical populations increases with increasing age, suggesting that FJ OA might have a particularly important role in older adults with spinal pain. Nevertheless, to date FJ OA has received far less study than other important OA phenotypes such as knee OA, and other features of spine pathoanatomy such as degenerative disc disease. This Review presents the current state of knowledge of FJ OA, including relevant anatomy, biomechanics, epidemiology, and clinical manifestations. We present the view that the modern concept of FJ OA is consonant with the concept of OA as a failure of the whole joint, and not simply of facet joint cartilage. Gellhorn, A. C. et al. Nat. Rev. Rheumatol. 9, 216-224 (2013); published online 13 November 2012; doi:10.1038/nrrheum.2012.199
C1 [Gellhorn, Alfred C.] Univ Washington, Dept Rehabil Med, Med Ctr, Seattle, WA 98105 USA.
[Katz, Jeffrey N.] Harvard Univ, Dept Orthoped Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Suri, Pradeep] VA Puget Sound Healthcare Syst, Div Rehabil Care Serv, Seattle, WA 98108 USA.
RP Suri, P (reprint author), VA Puget Sound Healthcare Syst, Div Rehabil Care Serv, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM pradeep.suri@va.gov
FU NIH National Institute of Arthritis and Musculoskeletal and Skin
Diseases [P60 AR 47782]
FX J. N. Katz's work is supported in part by a grant (P60 AR 47782) from
the NIH National Institute of Arthritis and Musculoskeletal and Skin
Diseases.
NR 97
TC 34
Z9 36
U1 5
U2 42
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4790
J9 NAT REV RHEUMATOL
JI Nat. Rev. Rheumatol.
PD APR
PY 2013
VL 9
IS 4
BP 216
EP 224
DI 10.1038/nrrheum.2012.199
PG 9
WC Rheumatology
SC Rheumatology
GA 117KR
UT WOS:000316952600005
PM 23147891
ER
PT J
AU Kittner, SJ
Singhal, AB
AF Kittner, Steven J.
Singhal, Aneesh B.
TI Premature atherosclerosis A major contributor to early-onset ischemic
stroke
SO NEUROLOGY
LA English
DT Editorial Material
ID YOUNG-ADULTS; REGISTRY
C1 [Kittner, Steven J.] Baltimore Vet Adm Med Ctr, Dept Neurol, Baltimore, MD 21201 USA.
Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Kittner, SJ (reprint author), Baltimore Vet Adm Med Ctr, Dept Neurol, Baltimore, MD 21201 USA.
EM SKittner@som.umaryland.edu
FU NINDS NIH HHS [U01 NS069208-01]
NR 15
TC 7
Z9 9
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR
PY 2013
VL 80
IS 14
BP 1272
EP 1273
DI 10.1212/WNL.0b013e31828ab3a4
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 118AW
UT WOS:000316995800006
PM 23468547
ER
PT J
AU Hedden, T
Oh, H
Younger, AP
Patel, TA
AF Hedden, Trey
Oh, Hwamee
Younger, Alayna P.
Patel, Tanu A.
TI Meta-analysis of amyloid-cognition relations in cognitively normal older
adults
SO NEUROLOGY
LA English
DT Review
ID PRECLINICAL ALZHEIMERS-DISEASE; WHITE-MATTER; A-BETA; EXECUTIVE
FUNCTION; IN-VIVO; DECLINE; BURDEN; IMPAIRMENT; DEMENTIA; MEMORY
AB Objective: We conducted a meta-analysis of relationships between amyloid burden and cognition in cognitively normal, older adult humans.
Methods: Methods of assessing amyloid burden included were CSF or plasma assays, histopathology, and PET ligands. Cognitive domains examined were episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Sixty-four studies representing 7,140 subjects met selection criteria, with 3,495 subjects from 34 studies representing independent cohorts. Weighted effect sizes were obtained for each study. Primary analyses were conducted limiting to independent cohort studies using only the most common assessment method (Pittsburgh compound B). Exploratory analyses included all assessment methods.
Results: Episodic memory (r = 0.12) had a significant relationship to amyloid burden. Executive function and global cognition did not have significant relationships to amyloid in the primary analysis of Pittsburgh compound B (r = 0.05 and r = 0.08, respectively), but did when including all assessment methods (r = 0.08 and r = 0.09, respectively). The domains of working memory, processing speed, visuospatial function, and semantic memory did not have significant relationships to amyloid. Differences in the method of amyloid assessment, study design (longitudinal vs cross-sectional), or inclusion of control variables (age, etc.) had little influence.
Conclusions: Based on this meta-analytic survey of the literature, increased amyloid burden has small but nontrivial associations with specific domains of cognitive performance in individuals who are currently cognitively normal. These associations may be useful for identifying preclinical Alzheimer disease or developing clinical outcome measures. Neurology (R) 2013;80:1341-1348
C1 [Hedden, Trey; Younger, Alayna P.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Hedden, Trey] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Younger, Alayna P.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Oh, Hwamee; Patel, Tanu A.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
RP Hedden, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM hedden@nmr.mgh.harvard.edu
FU National Institute on Aging [P01 AG036694, R01 AG034556, R01 AG034570,
K01 AG040197]; Alzheimer's Association; Center for Functional
Neuroimaging Technologies [RR14075]; Biomedical Technology Program of
the National Center for Research Resources, NIH; NIH [P01 AG036694, R01
AG034556, R01 AG034570, K01 AG040197]
FX This work was supported in part by the National Institute on Aging
(grant numbers P01 AG036694, R01 AG034556, R01 AG034570, and K01
AG040197); and by the Alzheimer's Association. This research was
performed in part at the Athinoula A. Martinos Center for Biomedical
Imaging at the Massachusetts General Hospital, using resources provided
by the Center for Functional Neuroimaging Technologies (grant number P41
RR14075), a P41 Regional Resource supported by the Biomedical Technology
Program of the National Center for Research Resources, NIH.; T. Hedden
received funding from NIH grants K01 AG040197, P01 AG036694, and R01
AG034556. H. Oh received funding from the Alzheimer's Association and
NIH grant R01 AG034570. A. P. Younger has received funding from NIH
grants P01 AG036694 and R01 AG034556. T. A. Patel reports no
disclosures. Go to Neurology.org for full disclosures.
NR 51
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U1 1
U2 25
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR
PY 2013
VL 80
IS 14
BP 1341
EP 1348
DI 10.1212/WNL.0b013e31828ab35d
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 118AW
UT WOS:000316995800019
PM 23547267
ER
PT J
AU Gonda, DD
Akers, JC
Kim, R
Kalkanis, SN
Hochberg, FH
Chen, CC
Carter, BS
AF Gonda, David D.
Akers, Johnny C.
Kim, Ryan
Kalkanis, Steven N.
Hochberg, Fred H.
Chen, Clark C.
Carter, Bob S.
TI Neuro-oncologic Applications of Exosomes, Microvesicles, and Other
Nano-Sized Extracellular Particles
SO NEUROSURGERY
LA English
DT Review
DE Biomarkers; Extracellular vesicles; Exosomes; Microvesicles
ID TUMOR-DERIVED MICROVESICLES; CANCER-CELL-LINES; GLIOBLASTOMA-MULTIFORME;
PILOCYTIC ASTROCYTOMAS; INTERCELLULAR TRANSFER; T-CELLS;
PROGNOSTIC-SIGNIFICANCE; BEARING MICROVESICLES; TRANSFERRIN RECEPTOR;
SHEEP RETICULOCYTES
AB The discovery that tumor-derived proteins and nucleic acids can be detected in nano-sized vesicles in the plasma and cerebrospinal fluid of patients afflicted with brain tumors has expanded opportunities for biomarker and therapeutic discovery. Through delivery of their contents to surrounding cells, exosomes, microvesicles, and other nano-sized extracellular vesicles secreted by tumors modulate their environment to promote tumor growth and survival. In this review, we discuss the biological processes mediated by these extracellular vesicles and their applications in terms of brain tumor diagnosis, monitoring, and therapy. We review the normal physiology of these extracellular vesicles, their pertinence to tumor biology, and directions for research in this field.
C1 [Gonda, David D.; Kim, Ryan; Chen, Clark C.; Carter, Bob S.] Univ Calif San Diego, Dept Neurosurg, San Diego, CA 92103 USA.
[Gonda, David D.; Akers, Johnny C.; Kim, Ryan; Chen, Clark C.; Carter, Bob S.] Univ Calif San Diego, Ctr Theoret & Appl Neurooncol, San Diego, CA 92103 USA.
[Kalkanis, Steven N.] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI USA.
[Hochberg, Fred H.] Massachusetts Gen Hosp, Pappas Ctr, Boston, MA 02114 USA.
RP Chen, CC (reprint author), 3855 Hlth Sci Dr,0987, La Jolla, CA 92093 USA.
EM clarkchen@ucsd.edu
FU Exosome Diagnostic; ABC2 foundation
FX Dr Carter reports receiving consulting fees and grant support from
Exosome Diagnostic and ABC2 foundation. The other authors have no
personal financial or institutional interest in any of the drugs,
materials, or devices described in this article.
NR 102
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Z9 13
U1 1
U2 33
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD APR
PY 2013
VL 72
IS 4
BP 501
EP 510
DI 10.1227/NEU.0b013e3182846e63
PG 10
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 113KU
UT WOS:000316667000018
PM 23277376
ER
PT J
AU Nagler, RH
Viswanath, K
AF Nagler, Rebekah H.
Viswanath, Kasisomayajula
TI Implementation and Research Priorities for FCTC Articles 13 and 16:
Tobacco Advertising, Promotion, and Sponsorship and Sales to and by
Minors
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Review
ID YOUTH SMOKING PREVENTION; SURVEY GYTS DATA; POINT-OF-SALE;
FRAMEWORK-CONVENTION; UNITED-STATES; YOUNG-ADULTS; CONTROL POLICY;
LATIN-AMERICA; CIGARETTE ADS; CIVIL-SOCIETY
AB Introduction: Article 13 of the Framework Convention on Tobacco Control (FCTC) calls for a comprehensive ban on tobacco advertising, promotion, and sponsorship (TAPS), and Article 16 calls for prohibition of tobacco sales to and by minors. Although these mandates are based on sound science, many countries have found provision implementation to be rife with challenges.
Objective: This paper reviews the history of tobacco marketing and minor access restrictions in high-, middle-, and low-income countries, identifying past challenges and successes. We consider current challenges to FCTC implementation, how these barriers can be addressed, and what research is necessary to support such efforts. Specifically, we identify implementation and research priorities for FCTC Articles 13 and 16.
Discussion: Although a solid evidence base underpins the FCTC's call for TAPS bans and minor access restrictions, we know substantially less about how best to implement these restrictions. Drawing on the regulatory experiences of high-, middle-, and low-income countries, we discern several implementation and research priorities, which are organized into 4 categories: policy enactment and enforcement, human capital expertise, the effects of FCTC marketing and youth access policies, and knowledge exchange and transfer among signatories. Future research should provide detailed case studies on implementation successes and failures, as well as insights into how knowledge of successful restrictions can be translated into tobacco control policy and practice and shared among different stakeholders.
Conclusion: Tobacco marketing surveillance, sales-to-minors compliance checks, enforcement and evaluation of restriction policies, and capacity building and knowledge transfer are likely to prove central to effective implementation.
C1 [Nagler, Rebekah H.; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Nagler, Rebekah H.; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA.
[Viswanath, Kasisomayajula] Dana Farber Canc Inst, McGraw Patterson Ctr Populat Sci, Boston, MA 02215 USA.
RP Nagler, RH (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW 601, Boston, MA 02215 USA.
EM rebekah_nagler@dfci.harvard.edu
FU Tobacco Disparities Research Network; National Cancer Institute;
American Legacy Foundation; Harvard School of Public Health's Lung
Cancer Disparities Center [3 P50-CA148596]; Dana-Farber/Harvard Cancer
Center [P30-CA006516]; National Cancer Institute by the Harvard
Education Program in Cancer Prevention and Control [5 R25-CA057711]
FX This work was supported by the Tobacco Disparities Research Network
(jointly funded by the National Cancer Institute and American Legacy
Foundation), the Harvard School of Public Health's Lung Cancer
Disparities Center (3 P50-CA148596), and the Dana-Farber/Harvard Cancer
Center (P30-CA006516). Funding support for RHN was also provided through
the National Cancer Institute by the Harvard Education Program in Cancer
Prevention and Control (5 R25-CA057711).
NR 107
TC 14
Z9 14
U1 3
U2 22
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD APR
PY 2013
VL 15
IS 4
BP 832
EP 846
DI 10.1093/ntr/nts331
PG 15
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 114XQ
UT WOS:000316776700008
PM 23291641
ER
PT J
AU Bradford, LS
Boruta, DM
AF Bradford, Leslie S.
Boruta, David M.
TI Laparoendoscopic Single-Site Surgery in Gynecology: A Review of the
Literature, Tools, and Techniques
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Article
ID ASSISTED VAGINAL HYSTERECTOMY; PORT LAPAROSCOPIC SURGERY; PERIOPERATIVE
OUTCOMES; INITIAL-EXPERIENCE; ENDOMETRIAL CANCER; SURGICAL OUTCOMES;
LEARNING-CURVE; LESS; SALPINGECTOMY; PREGNANCY
AB Recent decades have witnessed a tremendous shift from laparotomy to laparoscopy as the surgical approach of choice in gynecology. Completion of increasingly complicated procedures has been facilitated by technical advances in instrumentation. Lately, increasing attention has been paid to reducing both the number and size of laparoscopic incisions, with the ultimate goal being the absence of any visible scar. Laparoendoscopic single-site surgery (LESS), or single-incision laparoscopy, describes the use of 1 small skin incision to complete laparoscopic surgical procedures where traditionally multiple incisions were created. In addition to examining the developing literature related to LESS in gynecology, the aims of this review were to describe the technical challenges encountered during performance of LESS and to provide practical solutions for instrumentation and surgical techniques that allow them to be overcome.
Target Audience: Obstetricians and gynecologists, family physicians
Learning Objectives: After completing this CME activity, physicians should be better able to identify potential benefits of LESS, and implement practical solutions for instrumentation and surgical techniques to overcome technical challenges faced during LESS.
C1 [Bradford, Leslie S.] Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Boruta, David M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Boruta, DM (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 9E,55 Fruit St, Boston, MA 02114 USA.
EM dboruta@partners.org
NR 46
TC 5
Z9 6
U1 0
U2 4
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 APR
PY 2013
VL 68
IS 4
BP 295
EP 304
DI 10.1097/OGX.0b013e318286f673
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 117JB
UT WOS:000316948300019
PM 23943039
ER
PT J
AU Barroilhet, L
Van Hanegem, L
Bernstein, M
Feldman, S
AF Barroilhet, Lisa
Van Hanegem, Lennie
Bernstein, Marilyn
Feldman, Sarah
TI Potential Effects of Updated Pap Test Screening Guidelines and
Adenocarcinoma In Situ of the Cervix
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; PAPANICOLAOU SMEAR SENSITIVITY; ATYPICAL
GLANDULAR CELLS; UTERINE CERVIX; HUMAN-PAPILLOMAVIRUS; YOUNGER WOMEN;
UNITED-STATES; POPULATION; CANCER; PREVENTION
AB OBJECTIVE: To review cases of adenocarcinoma in situ (AIS) at our institution to examine how updated guidelines affect the timing of diagnosis.
METHODS: We identified patients with AIS diagnosed between 1998 and 2010 using the International Classification of Diseases, 9th Revision, Clinical Modification, code 233.1. Diagnosis was confirmed by pathology review. We abstracted demographic data, dysplasia history, and modalities utilized for diagnosis and treatment.
RESULTS: We identified 242 patients who met selection criteria. Two hundred eight (86%) had Pap test abnormalities at presentation. One hundred thirty-seven out of 208 (66%) patients with abnormal Pap test results had a squamous, rather than glandular, abnormality. The mean time from abnormal Pap test to diagnosis of AIS was 29 months in patients older than 30 years and was 21 months in patients 30 years or younger. In patients younger than 21 years, 16 out of 17 had abnormal screening Pap test results showing squamous lesions. Their subsequent treatment for squamous dysplasia ultimately led to the diagnosis of AIS.
CONCLUSION: Updated screening guidelines may prevent the expeditious diagnosis of AIS in females younger than 21 years and those aged 21-29 years, many of whom had normal Pap test results within 3 years of diagnosis. (Obstet Gynecol 2013;121:759-64) DOI: http://10.1097/AOG.0b013e3182887cad
C1 Univ Wisconsin, Madison, WI USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
RP Barroilhet, L (reprint author), UW Hosp, H4-658 CSC,600 Highland Ave, Madison, WI 53792 USA.
EM barroilhet@wisc.edu
NR 27
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD APR
PY 2013
VL 121
IS 4
BP 759
EP 764
DI 10.1097/AOG.0b013e3182887cad
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 112RJ
UT WOS:000316610000010
PM 23635675
ER
PT J
AU Murji, A
Patel, VI
Leyland, N
Choi, M
AF Murji, Ally
Patel, Virendra I.
Leyland, Nicholas
Choi, Matthew
TI Single-Incision Laparoscopy in Gynecologic Surgery A Systematic Review
and Meta-analysis
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Review
ID ASSISTED VAGINAL HYSTERECTOMY; RANDOMIZED-CONTROLLED-TRIAL; SITE
SURGERY; CONVENTIONAL LAPAROSCOPY; PERIOPERATIVE OUTCOMES; SURGICAL
OUTCOMES; PORT LAPAROSCOPY; ADNEXAL DISEASE; SALPINGECTOMY; PREGNANCY
AB OBJECTIVE: To evaluate surgical outcomes for gynecologic surgery performed by single-incision laparoscopy compared with conventional multi-incision laparoscopy.
DATA SOURCES: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through August 2012. We also screened reference lists of retrieved articles and manually searched abstracts from conference proceedings.
METHODS OF STUDY SELECTION: We included randomized control trials (RCTs) and high-quality observational studies that compared outcomes for single-incision laparoscopy and conventional laparoscopy for gynecologic surgery in patients. Included studies met predefined quality criteria and reported, at minimum, on complications, conversions, and operative time.
TABULATION, INTEGRATION, RESULTS: Six RCTs and 15 observational studies met inclusion criteria, with a total of 2,085 patients (899 single-incision laparoscopies and 1,186 conventional laparoscopies). In the pooled analysis, there was no significant difference in the risk of total complications between single-incision laparoscopy and conventional laparoscopy groups (relative risk 1.01, 95% confidence interval [CI] 0.72-1.40; P=.97, random effects model). The meta-analysis was powered to detect a 5% difference in complications (power=0.8, alpha=0.05). Mean operative time for adnexal surgery performed by single-incision laparoscopy was 6.97 minutes longer than conventional laparoscopy (95% CI 0.16-13.77; P=.045; I-2=47.2; random effects based on three RCTs). There was no significant difference in mean operative time for hysterectomy procedures performed by single-incision laparoscopy (8.29 minutes, 95% CI -5.85 to 22.43; P=.251; I-2=83.6; random effects based on three RCTs). Clinical outcomes of postoperative pain, change in hemoglobin, length of hospital stay, and scar cosmesis could not be pooled because of paucity of data and lack of uniform reporting.
CONCLUSION: There was no difference in the risk of complications between single-incision laparoscopy and conventional laparoscopy approaches in gynecologic surgery. Studies with imprecise effect sizes suggest that single-incision laparoscopy may have longer operative time for adnexal surgery, but not for hysterectomy. Effects on other surgical outcomes remain uncertain. (Obstet Gynecol 2013;121:819-28) DOI: http://10.1097/AOG.0b013e318288828c
C1 McMaster Univ, Dept Obstet & Gynecol, Hamilton, ON, Canada.
McMaster Univ, Dept Surg, Hamilton, ON L8S 4L8, Canada.
Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Murji, A (reprint author), Hamilton Hlth Sci, 1280 Main St West HSC 2F39, Hamilton, ON L8S 4K1, Canada.
EM ally.murji@gmail.com
RI Murji, Ally/C-1442-2016
NR 31
TC 14
Z9 14
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD APR
PY 2013
VL 121
IS 4
BP 819
EP 828
DI 10.1097/AOG.0b013e318288828c
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 112RJ
UT WOS:000316610000018
PM 23635683
ER
PT J
AU Li, Q
Yang, XH
Xu, F
Sharma, C
Wang, HX
Knoblich, K
Rabinovitz, I
Granter, SR
Hemler, ME
AF Li, Q.
Yang, X. H.
Xu, F.
Sharma, C.
Wang, H-X
Knoblich, K.
Rabinovitz, I.
Granter, S. R.
Hemler, M. E.
TI Tetraspanin CD151 plays a key role in skin squamous cell carcinoma
SO ONCOGENE
LA English
DT Article
DE tetraspanin CD151; skin squamous cell carcinoma; chemical
carcinogenesis; integrin alpha 6 beta 4; STAT3; PKC alpha
ID TRANSMEMBRANE 4 SUPERFAMILY; KERATINOCYTE STEM-CELLS; ALPHA-6-BETA-4
INTEGRIN; IN-VIVO; BETA-4 INTEGRIN; MICE LACKING; ALPHA-3-BETA-1
INTEGRIN; MALIGNANT PROGRESSION; PROSTATE-CANCER; TYROSINE KINASE
AB Here we provide the first evidence that tetraspanin CD151 can support de novo carcinogenesis. During two-stage mouse skin chemical carcinogenesis, CD151 reduces tumor lag time and increases incidence, multiplicity, size and progression to malignant squamous cell carcinoma (SCC), while supporting both cell survival during tumor initiation and cell proliferation during the promotion phase. In human skin SCC, CD151 expression is selectively elevated compared with other skin cancer types. CD151 support of keratinocyte survival and proliferation may depend on activation of transcription factor STAT3 (signal transducers and activators of transcription), a regulator of cell proliferation and apoptosis. CD151 also supports protein kinase C (PKC)alpha-alpha 6 beta 4 integrin association and PKC-dependent beta 4 S1424 phosphorylation, while regulating alpha 6 beta 4 distribution. CD151-PKC alpha effects on integrin beta 4 phosphorylation and subcellular localization are consistent with epithelial disruption to a less polarized, more invasive state. CD151 ablation, while minimally affecting normal cell and normal mouse functions, markedly sensitized mouse skin and epidermoid cells to chemicals/drugs including 7,12-dimethylbenz[alpha]anthracene (mutagen) and camptothecin (topoisomerase inhibitor), as well as to agents targeting epidermal growth factor receptor, PKC, Jak2/Tyk2 and STAT3. Hence, CD151 'co-targeting' may be therapeutically beneficial. These findings not only support CD151 as a potential tumor target, but also should apply to other cancers utilizing CD151/laminin-binding integrin complexes. Oncogene (2013) 32, 1772-1783; doi: 10.1038/onc.2012.205; published online 23 July 2012
C1 [Li, Q.; Xu, F.; Sharma, C.; Wang, H-X; Knoblich, K.; Hemler, M. E.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Li, Q.; Xu, F.; Sharma, C.; Wang, H-X; Knoblich, K.; Rabinovitz, I.; Hemler, M. E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Yang, X. H.] Univ Kentucky, Dept Mol & Biomed Pharmacol, Lexington, KY USA.
[Rabinovitz, I.] Beth Israel Deaconess Med Ctr, Div Canc Biol & Angiogenesis, Dept Pathol, Boston, MA 02215 USA.
[Granter, S. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Room D1430,44 Binney St, Boston, MA 02115 USA.
EM martin_hemler@dfci.harvard.edu
RI Knoblich, Konstantin/B-5980-2009; Li, Qinglin/K-2570-2015
OI Knoblich, Konstantin/0000-0002-5646-837X; Li,
Qinglin/0000-0002-4125-1944
FU NIH [CA42368]; SG Komen Career Catalyst Award
FX We thank Dr R Bronson for assistance with mouse histopathology, Dr Julie
Aldridge for assistance with statistical analyses, and Drs David Frank,
Sarah Walker and coworkers for nifuroxazide, ST3-01, assistance with
STAT3 functional assay and helpful discussions. This work was supported
by NIH grant CA42368 (to MEH), and a SG Komen Career Catalyst Award (to
XHY).
NR 77
TC 23
Z9 24
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD APR
PY 2013
VL 32
IS 14
BP 1772
EP 1783
DI 10.1038/onc.2012.205
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 118RQ
UT WOS:000317043900004
PM 22824799
ER
PT J
AU Martins, F
de Oliveira, MA
Wang, Q
Sonis, S
Gallottini, M
George, S
Treister, N
AF Martins, Fabiana
de Oliveira, Marcio Augusto
Wang, Qian
Sonis, Stephen
Gallottini, Marina
George, Suzanne
Treister, Nathaniel
TI A review of oral toxicity associated with mTOR inhibitor therapy in
cancer patients
SO ORAL ONCOLOGY
LA English
DT Review
DE mTOR inhibitors; Stomatitis; Mucositis; Cancer; Toxicities
ID ADVANCED SOLID TUMORS; RENAL-CELL CARCINOMA; PHASE-II TRIAL; REFRACTORY
HEMATOLOGIC MALIGNANCIES; EVERY 2 WEEKS; MAMMALIAN TARGET; TEMSIROLIMUS
CCI-779; RAPAMYCIN INHIBITOR; DEFOROLIMUS AP23573; BREAST-CANCER
AB Aphthous-like stomatitis has been identified as one of the most common dose-limiting toxicities associated with mTOR inhibitor therapy in cancer patients. The objective of this study was to summarize the cumulative oral toxicities associated with mTOR inhibitors in published oncology trials with respect to dose, schedule, and need for dose modifications. A review of all oncology-related clinical trials of mTOR inhibitors was conducted and standardized data was abstracted from each study. 44 studies were included in the analysis with a total of 2822 patients treated with temsirolimus (19 studies), everolimus (20 studies), and ridaforolimus (five studies) for a wide range of malignancies. At least one adverse event (AE) occurred in 74.4% of patients. Mucositis was the most frequent AE overall (73.4%), the third most frequent severe AE (20.7%), accounting for 27.3% dose reductions and 13.1% of discontinuations, and the most frequent dose limiting toxicity (52.5%). Mucositis typically occurred during the first cycle of therapy and was graded as mild to moderate in approximately 90% of the patients; severe mucositis generally occurred at higher doses. There were no clear differences in mucositis among the three agents and in most cases lesions resolved spontaneously. Oral mucositis is a frequent complication of mTOR inhibitor therapy and a significant cause of dose reductions and discontinuations in oncology trials. Prevention and management strategies should be investigated to improve tolerability and better permit effective long-term regimens. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Martins, Fabiana; de Oliveira, Marcio Augusto; Gallottini, Marina] Univ Sao Paulo, Dept Oral Pathol, Sch Dent, Sao Paulo, Brazil.
[Wang, Qian] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Sonis, Stephen; Treister, Nathaniel] Dana Farber Brigham & Womens Canc Ctr, Div Oral Med & Dent, Boston, MA USA.
[Sonis, Stephen; Treister, Nathaniel] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[George, Suzanne] Dana Farber Canc Inst, Dept Med Oncol, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
RP Treister, N (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,Suite BC 3-028, Boston, MA 02120 USA.
EM ntreister@partners.org
RI gallottini, marina/B-8893-2011
OI gallottini, marina/0000-0001-6071-5110
NR 55
TC 38
Z9 41
U1 1
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD APR
PY 2013
VL 49
IS 4
BP 293
EP 298
DI 10.1016/j.oraloncology.2012.11.008
PG 6
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 114JL
UT WOS:000316736800006
PM 23312237
ER
PT J
AU Kang, WS
Shim, BS
Lee, KS
AF Kang, Woo Seok
Shim, Byoung Soo
Lee, Kwang-Sun
TI Audiologic Performance After Cochlear Implantation in Children With
X-Linked Deafness: Comparison With Deaf Children With a Normal Inner Ear
Structure
SO OTOLOGY & NEUROTOLOGY
LA English
DT Article
DE Cochlear implantation; Incomplete partition type III; Inner ear anomaly;
X-linked deformity
ID CLASSIFICATION; MUTATIONS; SURGERY
AB Objective: To compare audiologic performances of cochlear implantation (CI) in children with X-linked deafness with those of CI in age-and sex-matched children with normal cochleae.
Patients: We identified 4 patients with X-linked deafness and selected 10 age-and sex-matched deaf patients with normal cochleae between April 1999 and April 2012.
Main Outcome Measures: Auditory brainstem responses, Categories of Auditory Performance (CAP), and Meaningful Auditory Integration Scale (MAIS).
Results: The ages of patients with X-linked deafness at the time of implantation ranged between 1.3 and 13.6 years, with a mean age of 5.3 years. All patients were male subjects and showed severe-to-profound hearing loss. Patient 1 lacked ABR in both ears. Patients 2, 3, and 4 showed ABR in the contralateral ear, at 70, 70, and 90 dB nHL, respectively. All 4 patients had bilateral X-linked cochlear anomaly and experienced cerebrospinal fluid (CSF) gushers. Straight electrodes were used in Patients 1 and 3, with perimodiolar electrodes used in the others. Patients 2 and 3, who were about the same age, had CAP scores of 6 or more at 18 months after activation of the implant despite the use of different electrode arrays. There were no statistically significant differences in MAIS and CAP scores between each patient with X-linked deafness and the control group.
Conclusion: The audiologic performances of patient with Xlinked deafness after CI are comparable to those of patients with normal inner ear structure after CI.
C1 [Kang, Woo Seok] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Kang, Woo Seok] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Shim, Byoung Soo; Lee, Kwang-Sun] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Otolaryngol, Seoul 138736, South Korea.
RP Lee, KS (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Otolaryngol, 388-1 Pungnap 2Dong, Seoul 138736, South Korea.
EM kslee2@amc.seoul.kr
NR 22
TC 5
Z9 5
U1 0
U2 1
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 APR
PY 2013
VL 34
IS 3
BP 544
EP 548
DI 10.1097/MAO.0b013e3182839864
PG 5
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 110NZ
UT WOS:000316452300033
PM 23470556
ER
PT J
AU Morasco, BJ
Lovejoy, TI
Lu, M
Turk, DC
Lewis, L
Dobscha, SK
AF Morasco, Benjamin J.
Lovejoy, Travis I.
Lu, Mary
Turk, Dennis C.
Lewis, Lynsey
Dobscha, Steven K.
TI The relationship between PTSD and chronic pain: Mediating role of coping
strategies and depression
SO PAIN
LA English
DT Article
DE Chronic pain; Chronic pain coping inventory; Coping strategies;
Mediation; Posttraumatic stress disorder; Quality of life
ID POSTTRAUMATIC-STRESS-DISORDER; COMORBID CHRONIC PAIN; MUTUAL
MAINTENANCE; FIT INDEXES; BACK-PAIN; VETERANS; SYMPTOMS; INVENTORY;
BELIEFS; MODELS
AB People with chronic pain and comorbid posttraumatic stress disorder (PTSD) report more severe pain and poorer quality of life than those with chronic pain alone. This study evaluated the extent to which associations between PTSD and chronic pain interference and severity are mediated by pain-related coping strategies and depressive symptoms. Veterans with chronic pain were divided into 2 groups, those with (n = 65) and those without (n = 136) concurrent PTSD. All participants completed measures of pain severity, interference, emotional functioning, and coping strategies. Those with current PTSD reported significantly greater pain severity and pain interference, had more symptoms of depression, and were more likely to meet diagnostic criteria for a current alcohol or substance use disorder (all p-values <.01). Participants with PTSD reported more use of several coping strategies, including guarding, resting, relaxation, exercise/stretching, and coping self-statements. Illness-focused pain coping (i.e., guarding, resting, and asking for assistance) and depressive symptoms jointly mediated the relationship between PTSD and both pain interference (total indirect effect = 0.194, p < .001) and pain severity (total indirect effect = 0.153, p = .004). Illness-focused pain coping also evidenced specific mediating effects, independent of depression. In summary, specific pain coping strategies and depressive symptoms partially mediated the relationship between PTSD and both pain interference and severity. Future research should examine whether changes in types of coping strategies after targeted treatments predict improvements in pain-related function for chronic pain patients with concurrent PTSD. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
C1 [Morasco, Benjamin J.; Lovejoy, Travis I.; Lu, Mary; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA.
[Morasco, Benjamin J.; Lu, Mary; Lewis, Lynsey; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Morasco, Benjamin J.; Lu, Mary; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Med & Psychiat, Portland, OR USA.
[Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM benjamin.morasco@va.gov
FU National Institute on Drug Abuse [K23DA023467]; Endo; Johnson Johnson;
Philips Respironics; National Institutes of Health; Eli Lilly; Empi;
Pfizer; SK Life Science
FX This study was supported in part by award K23DA023467 from the National
Institute on Drug Abuse to Dr. Morasco. The work was supported with
resources and the use of facilities at the Portland VA Medical Center.
During the past 12 months, Dr. Turk has received research support from
Endo, Johnson & Johnson, Philips Respironics, and the National
Institutes of Health, and consulting fees from Eli Lilly, Empi, Johnson
& Johnson, Pfizer, Philips Respironics, and SK Life Science. He is also
a Special Government Employee of the US Food and Drug Administration. No
other author reports having any potential conflict of interest with this
study. The authors appreciate the assistance of Susan Gritzner, Renee
Cavanagh, and Aysha Crain with data collection, and Jonathan Duckart,
MPS, for extracting data from the electronic medical record.
NR 55
TC 14
Z9 14
U1 3
U2 34
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD APR
PY 2013
VL 154
IS 4
BP 609
EP 616
DI 10.1016/j.pain.2013.01.001
PG 8
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 113HW
UT WOS:000316658200013
PM 23398939
ER
PT J
AU To, THM
Agar, M
Shelby-James, T
Abernethy, AP
Doogue, M
Rowett, D
Ko, D
Currow, DC
AF To, Timothy H. M.
Agar, Meera
Shelby-James, Tania
Abernethy, Amy P.
Doogue, Matthew
Rowett, Debra
Ko, Danielle
Currow, David C.
TI Off-label prescribing in palliative care - a cross-sectional national
survey of Palliative Medicine doctors
SO PALLIATIVE MEDICINE
LA English
DT Article
DE Off-label prescribing; palliative care; drug regulation; physician
knowledge; iatrogenic harm
ID ADVERSE DRUG-REACTIONS; RANDOMIZED CONTROLLED-TRIALS; TIME-LIMITED
TRIALS; PEDIATRIC WARDS; CANCER-PATIENTS; THE-LITERATURE; PRESCRIPTIONS;
MEDICATION; ONCOLOGY; LICENSE
AB Background: Regulatory bodies including the European Medicines Agency register medications (formulation, route of administration) for specific clinical indications. Once registered, prescription is at clinicians' discretion. Off-label use is beyond the registered use. While off-label prescribing may, at times, be appropriate, efficacy and toxicity data are often lacking.
Aim: The aim of this study was to document off-label use policies (including disclosure and consent) in Australian palliative care units and current practices by palliative care clinicians.
Design: A national, cross-sectional survey was conducted online following an invitation letter. The survey asked clinicians their most frequent off-label medication/indication dyads and unit policies. Dyads were classified into unregistered, off-label and on-label, and for the latter, whether medications were nationally subsidised.
Setting/participants: All Australian palliative medicine Fellows and advanced trainees.
Results: Overall, 105 clinicians responded (53% response rate). The majority did not have policies on off-label medications, and documented consent rarely. In all, 236 medication/indication dyads for 36 medications were noted: 45 dyads (19%) were for two unregistered medications, 118 dyads (50%) were for 26 off-label medications and 73 dyads (31%) were for 12 on-label medications.
Conclusions: Off-label prescribing with its clinical, legal and ethical implications is common yet poorly recognised by clinicians. A distinction needs to be made between where quality evidence exists but registration has not been updated by the pharmaceutical sponsor and the evidence has not been generated. Further research is required to quantify any iatrogenic harm from off-label prescribing in palliative care.
C1 [To, Timothy H. M.; Agar, Meera; Abernethy, Amy P.; Currow, David C.] Flinders Univ S Australia, Discipline Serv, Adelaide, SA 5001, Australia.
[To, Timothy H. M.; Agar, Meera; Abernethy, Amy P.; Currow, David C.] Flinders Univ S Australia, Palliat Serv, Adelaide, SA 5001, Australia.
[To, Timothy H. M.; Agar, Meera; Abernethy, Amy P.; Currow, David C.] Flinders Univ S Australia, Support Serv, Adelaide, SA 5001, Australia.
[To, Timothy H. M.] Southern Adelaide Palliat Serv, Adelaide, SA, Australia.
[To, Timothy H. M.] Repatriat Gen Hosp, Dept Rehabil & Aged Care, Adelaide, SA, Australia.
[Agar, Meera] Braeside Hosp, Prairiewood, NSW, Australia.
[Shelby-James, Tania] Flinders Univ S Australia, Flinders Prevent Promot & Primary Hlth Care, Adelaide, SA 5001, Australia.
[Abernethy, Amy P.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Doogue, Matthew] Flinders Med Ctr, Dept Clin Pharmacol, Adelaide, SA, Australia.
[Doogue, Matthew] Flinders Univ S Australia, Discipline Clin Pharmacol, Adelaide, SA 5001, Australia.
[Rowett, Debra] Repatriat Gen Hosp, Drug & Therapeut Informat Serv, Adelaide, SA, Australia.
[Ko, Danielle] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP To, THM (reprint author), Repatriat Gen Hosp, Dept Rehabil & Aged Care, Daw Pk, SA 5041, Australia.
EM timothy.to@health.sa.gov.au
OI To, Timothy/0000-0003-0025-6543; Doogue, Matt/0000-0002-2525-6307;
Currow, David/0000-0003-1988-1250
NR 67
TC 4
Z9 4
U1 0
U2 9
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-2163
J9 PALLIATIVE MED
JI Palliat. Med.
PD APR
PY 2013
VL 27
IS 4
BP 320
EP 328
DI 10.1177/0269216312464263
PG 9
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Medicine, General & Internal
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; General & Internal Medicine
GA 114PB
UT WOS:000316753200005
PM 23128901
ER
PT J
AU Shaikh, F
Nathan, PC
Hale, J
Uleryk, E
Frazier, L
AF Shaikh, Furqan
Nathan, Paul C.
Hale, Juliet
Uleryk, Elizabeth
Frazier, Lindsay
TI Is There a Role for Carboplatin in the Treatment of Malignant Germ Cell
Tumors? A Systematic Review of Adult and Pediatric Trials
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE chemotherapy; germ cell tumors; late effects
ID SINGLE-AGENT CARBOPLATIN; GOOD-RISK PATIENTS; TESTICULAR CANCER;
RANDOMIZED-TRIAL; COMBINATION CHEMOTHERAPY; CISPLATIN OTOTOXICITY;
METASTATIC SEMINOMA; PROGNOSTIC-FACTORS; DOSE CISPLATIN; ETOPOSIDE
AB Background. While cisplatin is considered superior to carboplatin for the treatment of malignant germ cell tumors (MGCTs) in adults, pediatric oncology collaborative groups still remain concerned about the late effects of cisplatin in children. Methods. We performed a literature search to identify randomized controlled trials (RCTs) that used carboplatin for MGCTs in adults. Since no RCTs were available in children, we identified cohort studies of pediatric MGCTs treated with carboplatin. We compared the adult and pediatric studies in terms of characteristics, doses of chemotherapy, and outcomes. Results. Of 2,131 publications retrieved, five RCTs in adults (1,340 patients) and four cohort studies in children (219 patients) met criteria for inclusion. All adult RCTs evaluated carboplatin versus cisplatin regimens in men with good-prognosis metastatic MGCTs. Carboplatin regimens had a higher risk of events (RR 2.51, P < 0.001) and of deaths (RR 2.21, P < 0.001) than cisplatin regimens. Across all five RCTs, 497/654 (76%) of adults who received carboplatin remained event-free. Compared to the adult trials, three pediatric studies used carboplatin at a higher dose, frequency, and number of cycles. Across these three studies, 158/179 (88%) of children remained event-free. Conclusions. Cisplatin is superior to carboplatin at the studied doses for the treatment of adult metastatic MGCTs. However, we observe that carboplatin is associated with good outcomes for children with MGCT when used at the higher doses. We hypothesize that a risk-adapted approach utilizing both platinum agents may achieve the optimal balance between cure and late effects. Pediatr Blood Cancer 2013;60:587-592. (C) 2012 Wiley Periodicals, Inc.
C1 [Shaikh, Furqan; Nathan, Paul C.] Hosp Sick Children, Div Paediat Haematol Oncol, Toronto, ON M5G 1X8, Canada.
[Hale, Juliet] Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[Uleryk, Elizabeth] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Frazier, Lindsay] Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA.
RP Shaikh, F (reprint author), Hosp Sick Children, Div Paediat Haematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM furqan.shaikh@sickkids.ca
OI Uleryk, Elizabeth/0000-0002-8989-5597
FU Pediatric Oncology Group of Ontario (POGO) Research Unit
FX Grant sponsor: Pediatric Oncology Group of Ontario (POGO) Research Unit.
NR 29
TC 4
Z9 4
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD APR
PY 2013
VL 60
IS 4
BP 587
EP 592
DI 10.1002/pbc.24288
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 108KI
UT WOS:000316291400012
PM 22976789
ER
PT J
AU Thibert, RL
Larson, AM
Hsieh, DT
Raby, AR
Thiele, EA
AF Thibert, Ronald L.
Larson, Anna M.
Hsieh, David T.
Raby, Annabel R.
Thiele, Elizabeth A.
TI Neurologic Manifestations of Angelman Syndrome
SO PEDIATRIC NEUROLOGY
LA English
DT Review
ID HAPPY PUPPET SYNDROME; EEG PATTERNS; MOLECULAR DIAGNOSIS;
CLINICAL-FEATURES; EPILEPSY; SLEEP; DELETION; INDIVIDUALS; CHILDREN;
BEHAVIOR
AB Angelman syndrome is a neurogenetic disorder characterized by the loss or reduction of the ubiquitin-protein ligase E3A enzyme. Angelman syndrome results from a deletion or mutation of the maternally inherited 15q11.2-13.1 region, paternal uniparental disomy of chromosome 15, or an imprinting error. Epilepsy is common and may present with multiple seizure types, including nonconvulsive status epilepticus. Seizures are often intractable and typically require broad-spectrum antiepileptic medications. Dietary therapy has also proved successful in Angelman syndrome. Electroencephalographic patterns include notched 8 and rhythmic theta activity and epileptiform discharges. Sleep disorders are also common, often characterized by abnormal sleep-wake cycles. Movement disorders are nearly universal in Angelman syndrome, most frequently presenting with ataxia and tremor. Neurocognitive impairment is always present to varying degrees, and expressive speech is typically severely affected. Individuals with Angelman syndrome often manifest psychiatric comorbidities including hyperactivity, anxiety, and challenging behaviors such as aggression and self-injury. We focus on a comprehensive whole-child approach to the diagnosis and long-term clinical care of individuals with Angelman syndrome. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Neurol, Angelman Syndrome Clin, Boston, MA 02114 USA.
RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA.
EM ethiele@partners.org
NR 92
TC 38
Z9 39
U1 4
U2 30
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD APR
PY 2013
VL 48
IS 4
BP 271
EP 279
DI 10.1016/j.pediatrneurol.2012.09.015
PG 9
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 114XZ
UT WOS:000316777600002
PM 23498559
ER
PT J
AU Nan, HM
Giovannucci, EL
Wu, KN
Selhub, J
Paul, L
Rosner, B
Fuchs, CS
Cho, E
AF Nan, Hongmei
Giovannucci, Edward L.
Wu, Kana
Selhub, Jacob
Paul, Ligi
Rosner, Bernard
Fuchs, Charles S.
Cho, Eunyoung
TI Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of
Colorectal Cancer in Women
SO PLOS ONE
LA English
DT Article
ID METHYLENETETRAHYDROFOLATE-REDUCTASE GENE; ONE-CARBON METABOLISM; FOLATE
STATUS; LIQUID-CHROMATOGRAPHY; COMMON MUTATION; BREAST-CANCER;
HYPOMETHYLATION; ADENOMA; CARCINOGENESIS; POLYMORPHISM
AB Background: Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia.
Methods: We evaluated the association between pre-diagnostic leukocyte genomic DNA methylation level and the risk of colorectal cancer in a nested case-control study of 358 colorectal cancer cases and 661 matched controls within the all-female cohort of the Nurses' Health Study (NHS). Among control subjects, we further examined major plasma components in the one-carbon metabolism pathway in relation to genomic DNA methylation level. Liquid chromatography/tandem mass spectrometry was used to examine leukocyte genomic DNA methylation level. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression.
Results: Overall genomic DNA methylation level was not associated with the risk of colorectal cancer (p for trend, 0.45). Compared with women in the lowest quintile of methylation, the multivariate OR of colorectal cancer risk was 1.32 (95% CI, 0.82-2.13) for those in the highest quintile. We did not find significant associations between major plasma components of one-carbon metabolism or risk factors for colorectal cancer and genomic DNA methylation level (all p for trend >0.05). Also, neither one-carbon metabolism-related plasma components nor well-known risk factors for colorectal cancer modified the association between genomic DNA methylation level and the risk of colorectal cancer (all p for interaction >0.05).
Conclusions: We found no evidence that hypomethylation of leukocyte genomic DNA increases risk of colorectal cancer among women. Additional studies are needed to investigate the association between pre-diagnostic genomic DNA methylation level and colorectal cancer risk among diverse populations.
C1 [Nan, Hongmei] Univ Maryland, Sch Med, Div Canc Epidemiol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Nan, Hongmei; Giovannucci, Edward L.; Rosner, Bernard; Fuchs, Charles S.; Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Nan, Hongmei; Giovannucci, Edward L.; Rosner, Bernard; Fuchs, Charles S.; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Selhub, Jacob; Paul, Ligi] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Cho, E (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
EM eunyoung.cho@channing.harvard.edu
FU United States National Institutes of Health [CA136950, CA55075]
FX This work was supported by research grants CA136950 and CA55075 from the
United States 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 42
TC 6
Z9 7
U1 0
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 APR 1
PY 2013
VL 8
IS 4
AR e59455
DI 10.1371/journal.pone.0059455
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117CY
UT WOS:000316930900017
PM 23560049
ER
PT J
AU Smucny, J
Rojas, DC
Eichman, LC
Tregellas, JR
AF Smucny, Jason
Rojas, Donald C.
Eichman, Lindsay C.
Tregellas, Jason R.
TI Neural Effects of Auditory Distraction on Visual Attention in
Schizophrenia
SO PLOS ONE
LA English
DT Article
ID FUSIFORM FACE AREA; DORSOLATERAL PREFRONTAL CORTEX; WORD FORM AREA;
BOTTOM-UP; HEMODYNAMIC-RESPONSE; NEURONAL MECHANISMS; NEGATIVE SYMPTOMS;
ODDBALL TASK; FMRI; MEMORY
AB Sensory flooding, particularly during auditory stimulation, is a common problem for patients with schizophrenia. The functional consequences of this impairment during cross-modal attention tasks, however, are unclear. The purpose of this study was to examine how auditory distraction differentially affects task-associated response during visual attention in patients and healthy controls. To that end, 21 outpatients with schizophrenia and 23 healthy comparison subjects performed a visual attention task in the presence or absence of distracting, environmentally relevant "urban'' noise while undergoing functional magnetic resonance imaging at 3T. The task had two conditions (difficult and easy); task-related neural activity was defined as difficult - easy. During task performance, a significant distraction (noise or silence) by group (patient or control) interaction was observed in the left dorsolateral prefrontal cortex, right hippocampus, left temporoparietal junction, and right fusiform gyrus, with patients showing relative hypoactivation during noise compared to controls. In patients, the ability to recruit the dorsolateral prefrontal cortex during the task in noise was negatively correlated with the effect of noise on reaction time. Clinically, the ability to recruit the fusiform gyrus during the task in noise was negatively correlated with SANS affective flattening score, and hippocampal recruitment during the task in noise was positively correlated with global functioning. In conclusion, schizophrenia may be associated with abnormalities in neural response during visual attention tasks in the presence of cross-modal noise distraction. These response differences may predict global functioning in the illness, and may serve as a biomarker for therapeutic development.
C1 [Smucny, Jason; Rojas, Donald C.; Tregellas, Jason R.] Univ Colorado, Neurosci Program, Aurora, CO 80045 USA.
[Smucny, Jason; Rojas, Donald C.; Eichman, Lindsay C.; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO USA.
[Rojas, Donald C.; Eichman, Lindsay C.; Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA.
RP Tregellas, JR (reprint author), Univ Colorado, Neurosci Program, Anschutz Med Campus, Aurora, CO 80045 USA.
EM Jason.Tregellas@ucdenver.edu
RI Tregellas, Jason/J-3637-2015;
OI Rojas, Don/0000-0001-6560-9616; Smucny, Jason/0000-0001-5656-7987
FU National Institute of Mental Health [MH-061412]; NIMH [MH-086383]; Brain
& Behavior Research Foundation; United States Department of Veterans
Affairs; Blowitz-Ridgeway Foundation
FX Funding came from National Institute of Mental Health Grant MH-061412
(http://www.nimh.nih.gov/index.shtml); NIMH Grant MH-086383; National
Alliance for Research on Schizophrenia and Depression, now Brain &
Behavior Research Foundation (No Grant Number) (bbrfoundation.org);
United States Department of Veterans Affairs (No Grant Number)
(www.va.gov); and Blowitz-Ridgeway Foundation (No Grant Number)
(http://www.blowitzridgeway.org/). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 66
TC 3
Z9 3
U1 3
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 APR 1
PY 2013
VL 8
IS 4
AR e60606
DI 10.1371/journal.pone.0060606
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117CY
UT WOS:000316930900071
PM 23560100
ER
PT J
AU Albert, RK
Connett, J
Bailey, WC
Casaburi, R
Cooper, JAD
Criner, GJ
Curtis, JL
Dransfield, MT
Han, MK
Lazarus, SC
Make, B
Marchetti, N
Martinez, FJ
Madinger, NE
Mcevoy, C
Niewoehner, DE
Porsasz, J
Price, CS
Reilly, J
Scanlon, PD
Sciurba, FC
Scharf, SM
Washko, GR
Woodruff, PG
Anthonisen, NR
AF Albert, R. K.
Connett, J.
Bailey, W. C.
Casaburi, R.
Cooper, J. A. D., Jr.
Criner, G. J.
Curtis, J. L.
Dransfield, M. T.
Han, M. K.
Lazarus, S. C.
Make, B.
Marchetti, N.
Martinez, F. J.
Madinger, N. E.
Mcevoy, C.
Niewoehner, D. E.
Porsasz, J.
Price, C. S.
Reilly, J.
Scanlon, P. D.
Sciurba, F. C.
Scharf, S. M.
Washko, G. R.
Woodruff, P. G.
Anthonisen, N. R.
CA COPD Clinical Res Network
TI LONG-TERM AZITHROMYCIN DECREASES COPD EXACERBATIONS
SO RESPIROLOGY
LA English
DT Meeting Abstract
C1 [Albert, R. K.; Price, C. S.] Denver Hlth, Med Serv, Denver, CO USA.
[Albert, R. K.; Price, C. S.] Univ Colorado Denver, Dept Med, Denver, CO USA.
[Connett, J.] Univ Minnesota, Div Biostat, Sch Publ Hlth, Minneapolis, MN 55455 USA.
[Bailey, W. C.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Dept Med, Birmingham, AL USA.
[Casaburi, R.; Porsasz, J.] Harbor UCLA Med Ctr, Dept Med, Div Resp & Crit Care Physiol & Med, Torrance, CA 90509 USA.
[Cooper, J. A. D., Jr.; Dransfield, M. T.] Birmingham VA Med Ctr, Pulm Sect, Birmingham, AL USA.
[Criner, G. J.; Marchetti, N.] Temple Univ, Div Pulm & Crit Care Med, Dept Med, Philadelphia, PA 19122 USA.
[Curtis, J. L.; Martinez, F. J.] Ann Arbor VA Med Ctr, Div Pulm & Crit Care Med, Ann Arbor, MI USA.
[Han, M. K.] Univ Michigan, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Lazarus, S. C.; Woodruff, P. G.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA.
[Lazarus, S. C.; Woodruff, P. G.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Make, B.] Natl Jewish Hlth, Div Pulm Med, Denver, CO USA.
[Madinger, N. E.] Univ Colorado Denver, Dept Med, Div Infect Dis, Denver, CO USA.
[Mcevoy, C.] HealthPartners Res Fdn, Pulm Crit Care & Sleep Dept, St Paul, MN USA.
[Niewoehner, D. E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Niewoehner, D. E.] Minneapolis Vet Affairs VA Med Ctr, Med Serv, Div Pulm Med, Minneapolis, MN USA.
[Reilly, J.; Washko, G. R.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Scanlon, P. D.] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA.
[Sciurba, F. C.] Univ Pittsburgh, Div Pulm & Crit Care Med, Dept Med, Pittsburgh, PA 15260 USA.
[Scharf, S. M.] Univ Maryland, Dept Med, Div Pulm & Crit Care, Baltimore, MD 21201 USA.
[Anthonisen, N. R.] Resp Hosp, Winnipeg, MB, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1323-7799
J9 RESPIROLOGY
JI Respirology
PD APR
PY 2013
VL 18
SU 1
SI SI
BP 5
EP 5
PG 1
WC Respiratory System
SC Respiratory System
GA 114RO
UT WOS:000316760200011
ER
PT J
AU Malhotra, A
Younes, M
Kuna, ST
Benca, R
Kushida, CA
Walsh, J
Hanlon, A
Staley, B
Pack, AI
Pien, GW
AF Malhotra, Atul
Younes, Magdy
Kuna, Samuel T.
Benca, Ruth
Kushida, Clete A.
Walsh, James
Hanlon, Alexandra
Staley, Bethany
Pack, Allan I.
Pien, Grace W.
TI Performance of an Automated Polysomnography Scoring System Versus
Computer-Assisted Manual Scoring
SO SLEEP
LA English
DT Article
DE apnea-hypopnea index; lung; polysomnography; reliability; scoring; sleep
ID SLEEP CLASSIFICATION; SIESTA DATABASE; SOMNOLYZER 24X7; VARIABILITY;
RELIABILITY; RECORDINGS; ADULTS; DISORDERS; AGREEMENT; INSOMNIA
AB Study Objectives: Manual scoring of polysomnograms (PSG) is labor intensive and has considerable variance between scorers. Automation of scoring could reduce cost and improve reproducibility. The purpose of this study was to compare a new automated scoring system (YST-Limited, Winnipeg, Canada) with computer-assisted manual scoring.
Design: Technical assessment.
Setting: Five academic medical centers.
Participants: N/A.
Interventions: N/A.
Measurements and Results: Seventy PSG files were selected at University of Pennsylvania (Penn) and distributed to five US academic sleep centers. Two blinded technologists from each center scored each file. Automatic scoring was performed at Penn by a YST Limited technician using a laptop containing the software. Variables examined were sleep stages, arousals, and apnea-hypopnea index (AHI) using three methods of identifying hypopneas. Automatic scores were not edited and were compared to the average scores of the 10 technologists. Intraclass correlation coefficient (ICC) was obtained for the 70 pairs and compared to across-sites ICCs for manually scored results. ICCs for automatic versus manual scoring were > 0.8 for total sleep time, stage N2, and nonrapid eye movement arousals and > 0.9 for AHI scored by primary and secondary American Academy of Sleep Medicine criteria. ICCs for other variables were not as high but were comparable to the across-site ICCs for manually scored results.
Conclusion: The automatic system yielded results that were similar to those obtained by experienced technologists. Very good ICCs were obtained for many primary PSG outcome measures. This automated scoring software, particularly if supplemented with manual editing, may increase laboratory efficiency and standardize PSG scoring results within and across sleep centers.
C1 [Malhotra, Atul] Harvard Univ, Dept Med, Boston, MA 02115 USA.
[Younes, Magdy] Univ Manitoba, Dept Med, Winnipeg, MB, Canada.
[Kuna, Samuel T.; Hanlon, Alexandra; Staley, Bethany; Pack, Allan I.; Pien, Grace W.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Kuna, Samuel T.; Hanlon, Alexandra; Staley, Bethany; Pack, Allan I.; Pien, Grace W.] Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA.
[Kuna, Samuel T.] Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA USA.
[Benca, Ruth] Univ Wisconsin, Dept Med, Madison, WI USA.
[Kushida, Clete A.] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA.
[Walsh, James] St Lukes Hosp, Sleep Med & Res Ctr, Chesterfield, MO USA.
RP Malhotra, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
EM amalhotra1@partners.org
FU NIH [R01 HL085695]; Academic Alliance for Sleep Research
(Philips-Respironics Foundation); Philips Respironics Foundation;
Philips Respironics; SHC; SGS; Apnex Medical; Pfizer; Apnicure; Merck;
Sanofi-Aventis; NovoNordisk; Vanda; Ventus; ResMed; Pacific Medico;
Cephalon; Ventus Medical; Jazz Pharmaceuticals; Apnex;
Philips-Respironics
FX Scorers at the University of Pennsylvania: Haideliza Soto-Calderon, Mary
Jones-Parker, RPSGT; scorers at Harvard University: Mary MacDonald,
RPSGT, Pam DeYoung, RPSGT; scorers at the University of Wisconsin at
Madison: Jennifer Noe, RPSGT, Rebecca Weise, RPSGT; scorers at Stanford
University: Martin Ukockis, RPSGT; scorers at St. Luke's Hospital:
Hilary Simon, RPSGT, Laura Rahubka, RPSGT. Eileen O'Leary, RPSGT
coordinated activity at Stanford University and assisted in data export
at the sites using Alice software. Sources of support: NIH R01 HL085695;
Academic Alliance for Sleep Research (Philips-Respironics Foundation);
This study was funded in part by the Philips Respironics Foundation. Dr.
Malhotra had previously received (prior to May 2012) consulting and/or
research income from Philips Respironics, SHC, SGS, Apnex Medical,
Pfizer and Apnicure. Dr. Kuna receives grant support from
Philips-Respironics. Dr. Benca has received consulting income from Merck
and Sanofi-Aventis. Dr. Walsh has received research support from Apnex,
NovoNordisk, Merck, Phillips-Respironics, Vanda, and Ventus. Dr. Younes
is the owner of YRT a research and development company. Dr. Kushida
receives research support from ResMed, Pacific Medico, Merck, Cephalon,
Ventus Medical, and Jazz Pharmaceuticals. He receives royalties from
Philips-Respironics. The other authors have indicated no financial
conflicts of interest.
NR 26
TC 20
Z9 20
U1 2
U2 14
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD APR 1
PY 2013
VL 36
IS 4
BP 573
EP 582
DI 10.5665/sleep.2548
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 117FN
UT WOS:000316939000017
PM 23565003
ER
PT J
AU Kuna, ST
Benca, R
Kushida, CA
Walsh, J
Younes, M
Staley, B
Hanlon, A
Pack, AI
Pien, GW
Malhotra, A
AF Kuna, Samuel T.
Benca, Ruth
Kushida, Clete A.
Walsh, James
Younes, Magdy
Staley, Bethany
Hanlon, Alexandra
Pack, Allan I.
Pien, Grace W.
Malhotra, Atul
TI Agreement in Computer-Assisted Manual Scoring of Polysomnograms across
Sleep Centers
SO SLEEP
LA English
DT Article
DE Apnea-hypopnea index; polysomnography; reliability; scoring
ID APNEA-HYPOPNEA INDEX; VARIABILITY; RELIABILITY; AROUSAL;
RECOMMENDATIONS; RECORDINGS; DISORDERS; IMPACT
AB Study Objectives: To determine intersite agreement in respiratory event scoring of polysomnograms (PSGs) using different hypopnea definitions.
Design: Technical assessment.
Setting: Five academic medical centers.
Participants: N/A.
Interventions: N/A.
Measurements and Results: Seventy good-quality PSGs performed in middle-aged women were manually scored by two experienced technologists at each of the five sleep centers using the particular laboratory's own software system. Studies were scored once by each scorer using American Academy of Sleep Medicine (AASM) standards for scoring sleep stages, arousals, and apneas. Hypopneas were then scored using three different AASM criteria: recommended, alternate, and research (Chicago). Means of each PSG variable for the scorers at each site were used to calculate an across-site intraclass correlation coefficient (ICC). Average AHI across the 10 scorers was 7.4 +/- 12.3 (standard deviation) events/h using recommended criteria (ICC 0.984; 95% confidence interval [CI] 0.977-0.990), 12.1 +/- 13.3 events/h using alternate criteria (ICC 0.947; 95% CI 0.889-0.972), and 15.1 +/- 13.9 events/h with Chicago criteria (ICC 0.800; 95% CI 0.768-0.828). ICC across sites was 0.870 (95% CI = 0.847-0.889) for total sleep time, 0.861 (95% CI 0.837-0.881) for number of obstructive apneas and 0.683 (95% CI 0.640-0.722) for number of central apneas. ICCs across sites for hypopneas were very good using recommended criteria (ICC 0.843; 95% CI 0.820-0.870) but decreased when alternate criteria (ICC 0.728; 95% CI 0.689-0.763) and Chicago criteria (ICC 0.535; 95% CI 0.485-0.583) were used.
Conclusion: Experienced scorers at different laboratories have very good agreement in hypopnea and AHI results when good-quality PSGs are scored using AASM-recommended criteria. Substantial degradation of reliability was observed for alternative definitions of hypopneas, particularly that proposed for research.
C1 [Kuna, Samuel T.; Staley, Bethany; Hanlon, Alexandra; Pack, Allan I.; Pien, Grace W.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Kuna, Samuel T.; Staley, Bethany; Hanlon, Alexandra; Pack, Allan I.; Pien, Grace W.] Univ Penn, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA.
[Kuna, Samuel T.] Philadelphia VA Med Ctr, Dept Med, Philadelphia, PA 19104 USA.
[Benca, Ruth] Univ Wisconsin, Dept Med, Madison, WI USA.
[Kushida, Clete A.] Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA.
[Walsh, James] St Lukes Hosp, Sleep Med & Res Ctr, Chesterfield, MO USA.
[Younes, Magdy] Univ Manitoba, Dept Med, Winnipeg, MB, Canada.
[Malhotra, Atul] Harvard Univ, Dept Med, Boston, MA 02115 USA.
RP Kuna, ST (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM skuna@mail.med.upenn.edu
FU NIH [R01 HL085695, 1PO1-1HL094307]; Academic Alliance for Sleep Research
(Philips-Respironics Foundation); Philips-Respironics; Merck;
Sanofi-Aventis; Philips Respironics; SHC; SGS; Apnex Medical; Pfizer;
Apnicure; ResMed; Pacific Medico; Cephalon; Ventus Medical; Jazz
Pharmaceuticals; Apnex; NovoNordisk; Vanda; Ventus
FX Scorers at the University of Pennsylvania: Haideliza Soto-Calderon, Mary
Jones-Parker, RPSGT; scorers at Harvard University: Mary MacDonald,
RPSGT, Pam DeYoung, RPSGT; scorers at the University of Wisconsin at
Madison: Jennifer Noe, RPSGT, Rebecca Weise, RPSGT; scorers at Stanford
University: Martin Ukockis, RPSGT, Julianne Blythe; scorers at St.
Luke's Hospital: Hilary Field, RPSGT, Laura Rahubka, RPSGT. Eileen
O'Leary, RPSGT coordinated activity at Stanford University and assisted
in data export at the sites using Alice software. Sources of support:
NIH R01 HL085695; NIH 1PO1-1HL094307; Academic Alliance for Sleep
Research (Philips-Respironics Foundation).; This was not an industry
supported study. Dr. Kuna receives grant support from
Philips-Respironics. Dr. Benca has received consulting income from Merck
and Sanofi-Aventis. Dr. Malhotra had previously received (prior to May
2012) consulting and/or research income from Philips Respironics, SHC,
SGS, Apnex Medical, Pfizer and Apnicure. Dr. Kushida receives research
support from ResMed, Pacific Medico, Merck, Cephalon, Ventus Medical,
and Jazz Pharmaceuticals. He receives royalties from
Philips-Respironics. Dr. Younes is the owner of YRT a research and
development company. Dr. Walsh has received research support from Apnex,
NovoNordisk, Merck, Phillips-Respironics, Vanda, and Ventus. The other
authors have indicated no financial conflicts of interest.
NR 25
TC 20
Z9 20
U1 1
U2 3
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD APR 1
PY 2013
VL 36
IS 4
BP 583
EP 589
DI 10.5665/sleep.2550
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 117FN
UT WOS:000316939000018
PM 23565004
ER
PT J
AU Passias, PG
Wang, SL
Zhao, D
Wang, SB
Kozanek, M
Wang, C
AF Passias, Peter G.
Wang, Shenglin
Zhao, Deng
Wang, Shaobai
Kozanek, Michal
Wang, Chao
TI The Reversibility of Swan Neck Deformity in Chronic Atlantoaxial
Dislocations
SO SPINE
LA English
DT Article
DE swan neck; cervical spine; alignment; atlantoaxial dislocation; kyphosis
ID LOWER CERVICAL-SPINE; RHEUMATOID-ARTHRITIS; OCCIPITOCERVICAL FUSION;
FOLLOW-UP; ALIGNMENT; ANGLE
AB Study Design. Prospective case series and radiographical analysis.
Objective. This study aimed to characterize the changes in subaxial alignment after surgical correction of occipitoaxial kyphosis, establish normal parameters, and report on clinical outcomes in a population of patients with chronic atlantoaxial dislocation patients presenting with swan neck deformities.
Summary of Background Data. Swan neck deformity of the cervical spine is a term used to describe the simultaneous development of both abnormal kyphosis and hyperlordosis malalignments. Currently, there are no published series that discuss their outcomes after treatment and, more specifically, the subsequent changes that occur in the subaxial spine after the correction of the primary deformity in cases of chronic hyperkyphosis at the occipitoaxial segment.
Methods. This was a prospective clinical and radiographical study in a population of patients with chronic atlantoaxial dislocation presenting with swan neck deformities. C0-C2 and C2-C7 angles were measured using plain radiographs pre- and postsurgery. The relationship between the alignment of the occipitoaxial joint and the subaxial cervical spine was evaluated. Japanese Orthopaedic Society scores were used to assess functional outcomes.
Results. C0-C2 improved from a mean of -14.4 degrees (SD, 9.5 degrees) preoperatively to a mean of 7.8 degrees (SD, 1.0 degrees) postoperatively (P = 0.02). C2-C7 changed from a mean of 43 degrees (SD, 2.8 degrees) to a mean of 18.6 degrees (SD, 11.2 degrees) postoperatively (P = 0.02). A significant correlation was detected between the changes that occurred in the upper and lower cervical alignments (R-2 = 0.133; P < 0.01). Clinically, the Japanese Orthopaedic Society preoperative scores improved significantly to postoperative (P < 0.01).
Conclusion. This study reports the novel auto-correction of subaxial abnormalities after treatment of the primary upper cervical deformity and delineates the relationship between these 2 occurrences, thus demonstrating the reversibility of such complex abnormalities. Furthermore, the clinical outcomes after surgical treatment of swan neck deformities secondary to atlantoaxial dislocation are favorable and associated with a low complication rate.
C1 [Passias, Peter G.] NYU, Hosp Joint Dis, Sch Med, Div Spinal Surg,Med Ctr, New York, NY 10003 USA.
[Wang, Shenglin; Zhao, Deng; Wang, Chao] Peking Univ, Dept Orthopaed, Hosp 3, Beijing 100191, Peoples R China.
[Wang, Shaobai; Kozanek, Michal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA USA.
RP Wang, C (reprint author), Peking Univ, Dept Orthopaed, Hosp 3, 49 North Garden St, Beijing 100191, Peoples R China.
EM wangchaoo@ynet.com
NR 19
TC 5
Z9 7
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD APR 1
PY 2013
VL 38
IS 7
BP E379
EP E385
DI 10.1097/BRS.0b013e31828625e4
PG 7
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 117FW
UT WOS:000316939900001
PM 23324935
ER
PT J
AU Janzen, DM
Cheng, DH
Schafenacker, AM
Paik, DY
Goldstein, AS
Witte, ON
Jaroszewicz, A
Pellegrini, M
Memarzadeh, S
AF Janzen, Deanna M.
Cheng, Donghui
Schafenacker, Amanda M.
Paik, Daniel Y.
Goldstein, Andrew S.
Witte, Owen N.
Jaroszewicz, Artur
Pellegrini, Matteo
Memarzadeh, Sanaz
TI Estrogen and progesterone together expand murine endometrial epithelial
progenitor cells
SO STEM CELLS
LA English
DT Article
DE Endometrial epithelial progenitors; Progesterone; Estrogen; Paracrine
signaling
ID LABEL-RETAINING CELLS; LARGE GENE LISTS; STEM-CELLS; PROSTATE-CANCER;
SELF-RENEWAL; POSTMENOPAUSAL WOMEN; UTERINE EPITHELIUM; MOUSE
ENDOMETRIUM; COLON-CARCINOMA; CD44 ISOFORMS
AB Synchronous with massive shifts in reproductive hormones, the uterus and its lining the endometrium expand to accommodate a growing fetus during pregnancy. In the absence of an embryo the endometrium, composed of epithelium and stroma, undergoes numerous hormonally regulated cycles of breakdown and regeneration. The hormonally mediated regenerative capacity of the endometrium suggests that signals that govern the growth of endometrial progenitors must be regulated by estrogen and progesterone. Here, we report an antigenic profile for isolation of mouse endometrial epithelial progenitors. These cells are EpCAM+CD44+ITGA6hiThy1PECAM1PTPRCTer119, comprise a minor subpopulation of total endometrial epithelia and possess a gene expression profile that is unique and different from other cells of the endometrium. The epithelial progenitors of the endometrium could regenerate in vivo, undergo multilineage differentiation and proliferate. We show that the number of endometrial epithelial progenitors is regulated by reproductive hormones. Coadministration of estrogen and progesterone dramatically expanded the endometrial epithelial progenitor cell pool. This effect was not observed when estrogen or progesterone was administered alone. Despite the remarkable sensitivity to hormonal signals, endometrial epithelial progenitors do not express estrogen or progesterone receptors. Therefore, their hormonal regulation must be mediated through paracrine signals resulting from binding of steroid hormones to the progenitor cell niche. Discovery of signaling defects in endometrial epithelial progenitors or their niche can lead to development of better therapies in diseases of the endometrium. STEM CELLS 2013;31:808822
C1 [Janzen, Deanna M.; Schafenacker, Amanda M.; Paik, Daniel Y.; Memarzadeh, Sanaz] Univ Calif Los Angeles, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Goldstein, Andrew S.; Witte, Owen N.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Goldstein, Andrew S.] Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Cheng, Donghui; Witte, Owen N.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90024 USA.
[Goldstein, Andrew S.; Witte, Owen N.; Pellegrini, Matteo; Memarzadeh, Sanaz] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90024 USA.
[Witte, Owen N.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA.
[Jaroszewicz, Artur; Pellegrini, Matteo] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90024 USA.
[Memarzadeh, Sanaz] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
RP Memarzadeh, S (reprint author), Univ Calif Los Angeles, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA 90024 USA.
EM smemarzadeh@mednet.ucla.edu
OI Goldstein, Andrew/0000-0003-0434-9149
FU VA CDA-2 Career Development Award; Mary Kay Foundation Award; PCF Young
Investigators Award; STOP Cancer Award; Broad Stem Cell Research Center,
Research Award; U54 CA 143,931 award; Kimmel Translational Scholar
Award; Joe and Ali Torre-Prostate Cancer Foundation Young Investigator
Award
FX SM is supported by a VA CDA-2 Career Development Award, a gift from the
Scholars in Translational Medicine Program, Mary Kay Foundation Award,
PCF Young Investigators Award, STOP Cancer Award, the Broad Stem Cell
Research Center, Research Award, the U54 CA 143,931 award and a Kimmel
Translational Scholar Award. ASG is supported by the Joe and Ali
Torre-Prostate Cancer Foundation Young Investigator Award. ONW is a
Howard Hughes Medical Institute investigator.
NR 84
TC 10
Z9 10
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD APR
PY 2013
VL 31
IS 4
BP 808
EP 822
DI 10.1002/stem.1337
PG 15
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 112WG
UT WOS:000316624300018
PM 23341289
ER
PT J
AU Rajamani, K
Kennedy, KF
Ruggiero, NJ
Rosenfield, K
Spertus, J
Chaturvedi, S
AF Rajamani, Kumar
Kennedy, Kevin F.
Ruggiero, Nicholas J.
Rosenfield, Kenneth
Spertus, John
Chaturvedi, Seemant
TI Outcomes of Carotid Endarterectomy in the Elderly Report From the
National Cardiovascular Data Registry
SO STROKE
LA English
DT Article; Proceedings Paper
CT International Stroke Conference
CY JAN 31-FEB 03, 2012
CL New Orleans, LA
DE Carotid Artery Revascularization and Endarterectomy registry; carotid
endarterectomy; National Cardiovascular Data Registry; elderly patients
ID MORTALITY; AGE
AB Background and Purpose-Benchmark trials of carotid endarterectomy often did not include elderly patients, and the results may not be easily extrapolated to the general population. Using the Carotid Artery Revascularization and Endarterectomy registry, we sought to determine real-world outcomes of carotid endarterectomy in the elderly.
Methods-This was a retrospective cohort study of patients aged >70 years. We compared outcomes stratified by age among symptomatic and asymptomatic patients.
Results-There were 4149 patients who underwent carotid endarterectomy; 1376 (33.1%) were symptomatic. Overall mortality rate was 0.5%. The primary outcome of in-hospital death, stroke, and myocardial infarction showed a significant trend and was highest in the age >85 years group (5.6%). Among symptomatic patients, mortality and the primary outcome were not statistically different between those aged >75 years and those aged 70 to 74 years. Among asymptomatic elderly patients, mortality rate was significantly higher in age group >75 years compared with <75 years (0.7% vs 0.0%); however, the combined outcome of stroke, death, and myocardial infarction was not statistically different.
Conclusions-Elderly patients >85 years of age were at increased risk for death or perioperative complications of stroke, death, and myocardial infarction compared with those who were relatively younger. More elderly patients underwent carotid endarterectomy for asymptomatic carotid stenosis and had higher mortality than the younger counterparts, underlining need for caution in subjecting them to the procedure. (Stroke. 2013;44:1172-1174.)
C1 [Rajamani, Kumar; Chaturvedi, Seemant] Wayne State Univ, Sch Med, Detroit, MI USA.
[Kennedy, Kevin F.; Spertus, John] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA.
[Ruggiero, Nicholas J.] Thomas Jefferson Univ, Jefferson Med Coll, Jefferson Heart Inst, Philadelphia, PA 19107 USA.
[Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Rajamani, K (reprint author), 8C UHC,4201 St Antoine, Detroit, MI 48201 USA.
EM krajaman@med.wayne.edu
FU American College of Cardiology Foundation's National Cardiovascular Data
Registry (NCDR); American College of Cardiology Foundation
FX The study was supported by American College of Cardiology Foundation's
National Cardiovascular Data Registry (NCDR). Views expressed are those
of the author(s) and do not necessarily represent the official views of
the NCDR or its associated professional societies. Dr Spertus has a
contract from American College of Cardiology Foundation to analyze the
Carotid Artery Revascularization and Endarterectomy registry. Dr
Chaturvedi is a consultant for Abbot Vascular and Thornhill Research. Dr
Ruggiero is consultant for St. Jude and Boston Scientific.
NR 7
TC 8
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD APR
PY 2013
VL 44
IS 4
BP 1172
EP 1174
DI 10.1161/STROKEAHA.111.000513
PG 3
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 113NE
UT WOS:000316673900052
PM 23422084
ER
PT J
AU Abbott, AL
Adelman, MA
Alexandrov, AV
Barber, PA
Barnett, HJM
Beard, J
Bell, P
Bjorck, M
Blacker, D
Bonati, LH
Brown, MM
Buckley, CJ
Cambria, RP
Castaldo, JE
Comerota, AJ
Connolly, ES
Dalman, RL
Davies, AH
Eckstein, HH
Faruqi, R
Feasby, TE
Fraedrich, G
Gloviczki, P
Hankey, GJ
Harbaugh, RE
Heldenberg, E
Hennerici, MG
Hill, MD
Kleinig, TJ
Mikhailidis, DP
Moore, WS
Naylor, R
Nicolaides, A
Paraskevas, KI
Pelz, DM
Prichard, JW
Purdie, G
Ricco, JB
Ringleb, PA
Riles, T
Rothwell, PM
Sandercock, P
Sillesen, H
Spence, JD
Spinelli, F
Sturm, J
Tan, A
Thapar, A
Veith, FJ
Wijeratne, T
Zhou, W
AF Abbott, Anne L.
Adelman, Mark A.
Alexandrov, Andrei V.
Barber, P. Alan
Barnett, Henry J. M.
Beard, Jonathan
Bell, Peter
Bjorck, Martin
Blacker, David
Bonati, Leo H.
Brown, Martin M.
Buckley, Clifford J.
Cambria, Richard P.
Castaldo, John E.
Comerota, Anthony J.
Connolly, E. Sander, Jr.
Dalman, Ronald L.
Davies, Alun H.
Eckstein, Hans-Henning
Faruqi, Rishad
Feasby, Thomas E.
Fraedrich, Gustav
Gloviczki, Peter
Hankey, Graeme J.
Harbaugh, Robert E.
Heldenberg, Eitan
Hennerici, Michael G.
Hill, Michael D.
Kleinig, Timothy J.
Mikhailidis, Dimitri P.
Moore, Wesley S.
Naylor, Ross
Nicolaides, Andrew
Paraskevas, Kosmas I.
Pelz, David M.
Prichard, James W.
Purdie, Grant
Ricco, Jean-Baptiste
Ringleb, Peter A.
Riles, Thomas
Rothwell, Peter M.
Sandercock, Peter
Sillesen, Henrik
Spence, J. David
Spinelli, Francesco
Sturm, Jonathon
Tan, Aaron
Thapar, Ankur
Veith, Frank J.
Wijeratne, Tissa
Zhou, Wei
TI Why Calls for More Routine Carotid Stenting Are Currently Inappropriate
An International, Multispecialty, Expert Review and Position Statement
SO STROKE
LA English
DT Article; Proceedings Paper
CT International Stroke Conference
CY JAN 31-FEB 03, 2012
CL New Orleans, LA
DE carotid angioplasty/stenting; carotid endarterectomy; carotid stenosis;
health policy; stroke prevention
ID ARTERY STENOSIS; UNITED-STATES; REVASCULARIZATION ENDARTERECTOMY;
COST-EFFECTIVENESS; MEDICAID SERVICES; CLINICAL-TRIALS; RISK; STROKE;
GUIDELINES; PROFESSIONALS
C1 [Abbott, Anne L.] Monash Univ, Alfred Ctr, Sch Publ Hlth & Prevent Med, Melbourne, Vic 3004, Australia.
[Abbott, Anne L.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Abbott, Anne L.] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia.
[Adelman, Mark A.] NYU, Langone Med Ctr, Div Vasc & Endovasc Surg, New York, NY USA.
[Alexandrov, Andrei V.] Univ Alabama Hosp & Clin, Comprehens Stroke Ctr, Birmingham, AL USA.
[Barber, P. Alan] Univ Auckland, Dept Med, Ctr Brain Res, Auckland, New Zealand.
[Barnett, Henry J. M.] Univ Western Ontario, Div Neurol, London, ON, Canada.
[Beard, Jonathan] No Gen Hosp, Sheffield Vasc Inst, Sheffield S5 7AU, S Yorkshire, England.
[Bell, Peter] Univ Leicester, Univ Leicester Hosp, Leicester, Leics, England.
[Bjorck, Martin] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
[Blacker, David] Sir Charles Gairdner Hosp, Dept Neurol, Perth, WA, Australia.
[Bonati, Leo H.] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland.
[Bonati, Leo H.] Univ Basel Hosp, Stroke Unit, CH-4031 Basel, Switzerland.
[Brown, Martin M.] Natl Hosp, UCL Inst Neurol, London WC1N 3BG, England.
[Buckley, Clifford J.] Cent Texas Vet Hlth Care Syst, Scott & White Hlth Care Syst, Texas A&M Hlth Sci Ctr, Coll Med, Temple, TX USA.
[Cambria, Richard P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA USA.
[Castaldo, John E.] Lehigh Valley Hlth Network, USF Coll Med, Div Neurol, Allentown, PA USA.
[Comerota, Anthony J.] Toledo Hosp, Jobst Vasc Inst, Toledo, OH USA.
[Connolly, E. Sander, Jr.] Columbia Univ, Dept Neurol Surg, New York, NY USA.
[Dalman, Ronald L.] Stanford Univ, Div Vasc Surg, Stanford, CA 94305 USA.
[Dalman, Ronald L.] Stanford Univ, Div Cardiovasc Hlth Qual & Outcomes, Stanford, CA 94305 USA.
[Davies, Alun H.] Charing Cross Hosp, Imperial Coll Sch Med, Dept Surg & Canc, Acad Sect Vasc Surg, London, England.
[Eckstein, Hans-Henning] Univ Munich, Klinikum Rechts Isar Tech, Vasc Ctr, Dept Vasc & Endovasc Surg, Munich, Germany.
[Faruqi, Rishad] Stanford Univ, Stanford, CA 94305 USA.
[Faruqi, Rishad] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Faruqi, Rishad] Kaiser Permanente Med Ctr, Dept Vasc & Endovasc Surg, Santa Clara, CA USA.
[Feasby, Thomas E.] Univ Calgary, Fac Med, Dept Clin Neurosci, Calgary, AB, Canada.
[Fraedrich, Gustav] Med Univ Innsbruck, Dept Vasc Surg, A-6020 Innsbruck, Austria.
[Gloviczki, Peter] Mayo Clin, Div Vasc & Endovasc Surg, Rochester, MN USA.
[Hankey, Graeme J.] Univ Western Australia, Royal Perth Hosp, Dept Neurol, Perth, WA 6009, Australia.
[Harbaugh, Robert E.] Penn State Univ, Penn State Inst Neurosci, Hershey, PA USA.
[Heldenberg, Eitan] Assaf Harofeh Med Ctr, Dept Vasc Surg, IL-70300 Zerifin, Israel.
[Heldenberg, Eitan] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Hennerici, Michael G.] UMM, Univ Med Mannheim, Neurol Univ Klin, Mannheim, Germany.
[Hennerici, Michael G.] Heidelberg Univ, Mannheim, Germany.
[Hill, Michael D.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB, Canada.
[Kleinig, Timothy J.] Royal Adelaide Hosp, Dept Neurol, Adelaide, SA 5000, Australia.
[Kleinig, Timothy J.] Lyell McEwin Hosp, Adelaide, SA, Australia.
[Kleinig, Timothy J.] Univ Adelaide, Dept Med, Adelaide, SA 5001, Australia.
[Mikhailidis, Dimitri P.] UCL, Sch Med, Dept Clin Biochem, Vasc Dis Prevent Clin, London W1N 8AA, England.
[Moore, Wesley S.] Univ Calif Los Angeles, Div Vasc Surg, Los Angeles, CA USA.
[Naylor, Ross] Univ Leicester, Leicester Royal Infirm, Div Cardiovasc Sci, Vasc Surg Grp, Leicester, Leics, England.
[Nicolaides, Andrew] Univ London Imperial Coll Sci Technol & Med, Dept Vasc Surg, Vasc Noninvas Diagnost Ctr, London, England.
[Paraskevas, Kosmas I.] Red Cross Hosp, Athens, Greece.
[Pelz, David M.; Spence, J. David] Univ Western Ontario, London, ON, Canada.
[Prichard, James W.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA.
[Purdie, Grant] Queen Elizabeth Hosp, Dept Neurol, Adelaide, SA, Australia.
[Ricco, Jean-Baptiste] Univ Poitiers, Vasc Surg Serv, Poitiers, France.
[Ringleb, Peter A.] Univ Heidelberg Hosp, Dept Neurol, Heidelberg, Germany.
[Riles, Thomas] NYU, Sch Med, Div Vasc Surg, New York, NY USA.
[Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
[Sandercock, Peter] Univ Edinburgh, Western Gen Hosp, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Sillesen, Henrik] Univ Copenhagen, Rigshosp, Dept Vasc Surg, DK-2100 Copenhagen, Denmark.
[Spence, J. David] Robarts Res Inst, Stroke Prevent & Atherosclerosis Res Ctr, London, ON N6A 5C1, Canada.
[Spinelli, Francesco] Univ Messina, Dept Cardiovasc & Thorac Sci, Messina, Italy.
[Sturm, Jonathon] Univ Newcastle, Gosford Hosp, Dept Neurol, Callaghan, NSW 2308, Australia.
[Sturm, Jonathon] Univ Newcastle, Wyong Hosp, Callaghan, NSW 2308, Australia.
Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Acad Sect Vasc Surg, London, England.
[Veith, Frank J.] Univ Hlth Sci, F Edward Hebert Sch Med, Case Western Reserve Univ,Div Vasc Surg, Lerner Sch Med,Cleveland Clin,NYU,Sch Med, New York, NY USA.
[Wijeratne, Tissa] Univ Melbourne, Western Clin Sch, Western Hosp, Dept Neurol, Melbourne, Vic, Australia.
[Zhou, Wei] Stanford Univ, Palo Alto VA Hlth Care Syst, Stanford, CA 94305 USA.
RP Abbott, AL (reprint author), Alfred Ctr, Sch Publ Hlth & Prevent Med, 99 Commercial Rd, Melbourne, Vic 3004, Australia.
EM Anne.L.Abbott@gmail.com
RI Abbott, Anne/G-6604-2013; Spence, J. David/K-6396-2013; Hankey, Graeme
/H-4968-2014; Bonati, Leo/G-4058-2012; Barber, Philip/C-7108-2016;
OI Barber, P Alan/0000-0003-2469-9023; Hill, Michael/0000-0002-6269-1543;
Adelman, Mark/0000-0001-9276-6131; Spence, J. David/0000-0001-7478-1098;
Hankey, Graeme /0000-0002-6044-7328; Bonati, Leo/0000-0003-1163-8133;
Spinelli, Francesco/0000-0001-6527-1993; Sandercock,
Peter/0000-0001-8484-0135; Alexandrov, Andrei V/0000-0001-8871-1023;
Eckstein, Hans-Henning/0000-0002-0743-1642; Ringleb,
Peter/0000-0002-5473-8671
FU Australian National Health and Medical Research Council Fellowship
[472700]; Victorian Government's OIS Program; Boehringer Ingelheim;
Carotid Revascularization Endarterectomy versus Stenting Trial (CREST);
Stroke Association; Merck; Novartis; Boehringer-Ingelheim; Canadian
Institutes of Health Research; Heart and Stroke Foundation of Canada
(Ontario); National Institutes of Health; Royal College of Surgeons of
England; National Institute of Health/National Institute of Neurological
Disorders and Stroke
FX Anne Abbott's time on this project was partially supported by an
Australian National Health and Medical Research Council Fellowship (ID:
472700) and supported in part by the Victorian Government's OIS
Program.; Henry Barnett was PI of the North American Symptomatic Carotid
Endarterectomy Trial (NASCET). Jonathan Beard is on the Steering
Committee of the International Carotid Stenting Study (ICSS). David
Blacker has received sponsorship to scientific meetings from Boehringer
Ingelheim. He has previously been a member of the advisory board for
NovoNorsdisk (regarding Factor VII) and receives funding for involvement
in the Prevention of Cerebrovascular and Cardiovascular Events of
Ischemic Origin With Terutroban in Patients With a History of Ischemic
Stroke or Transient Ischemic Attack (PERFORM) Study. Leo Bonati is a
member of the ICSS Study Group, a member of the Steering Committee of
the European Carotid Surgery Trial 2 (ECST-2) and the coordinating
member of the Steering Committee of the Carotid Stenting Trialists
Collaboration (CSTC). Prof Martin Brown is the Chief Investigator of the
Carotid and Vertebral Transluminal Angioplasty Study (CAVATAS), ICSS,
and the ECST-2. Richard Cambria is co-PI for a future transcervical
carotid stenting/flow reversal trial (ROADSTER). Anthony Comerota
received research funding for the Jobst Vascular Institute to
participate in the Carotid Revascularization Endarterectomy versus
Stenting Trial (CREST). Ronald Dalman previously served as site PI for
the Abbott Industries Protected Carotid Artery Stenting in Patients at
High Risk for Carotid Endarterectomy (PROTECT) trial for California and
is a co-holder of a provisional patent for a carotid distal protection
device. Alun Davies receives funding from the Stroke Association on the
evaluation of carotid plaque. Hans-Henning Eckstein is co-PI of the
Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus
Endarterectomy (SPACE-2) Study. He was a member of the Steering
Committee of the SPACE-1 Study. Gustav Fraedrich is member of the
steering committee of the Carotid Stenting Trialists Collaboration
(CSTC) and member of the steering committee of the SPACE-2-Study. He was
a member of the Writing Committee of the SPACE-1 Study. Graeme Hankey
was a member of the ECST Collaborative Group and the NASCET
Collaborators. Michael Hennerici founded the European Stroke Conference:
http://www.eurostroke.eu. He is a principal investigator, coordinator,
and board member for several international clinical trials including the
Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events Trial
(CAPRIE), Aspirin and Clopidogrel Compared With Clopidogrel Alone After
Recent Ischemic Stroke or Transient Ischemic Attack in High-Risk
Patients Trial (MATCH), Stroke Prevention by Aggressive Reduction in
Cholesterol Levels Trial (SPARCL), SPACE-1, and SPACE 2. Dimitri
Mikhailidis has given talks and attended conferences sponsored by Merck,
Sharp and Dohme, Genzyme, and Abbott Industries. Wesley Moore is a co-PI
for the CREST and member of the CREST Executive Committee. Peter A.
Ringleb is the Clinical coordinator of SPACE-1, a member of the steering
committee of SPACE-2 and a member of the guideline-committee of the
German Neurological Society, German Stroke Society, and European Stroke
Organization. Peter Rothwell is on the Data Monitoring Committee of the
SPACE-2 trial. He is Chair of the End point Adjudication Committee of
the Asymptomatic Carotid Artery Surgery Trial-2 (ACST-2). He is on the
Steering Committee of the ECST-2 and the General Anesthetic versus Local
Anesthetic (GALA) for Carotid Surgery Trial. Peter Sandercock is the
independent chair of the MRC/NIHR ACST-2 Trial. J.; David Spence has
received lecture fees or consulting fees from Merck, Novartis and
Boehringer-Ingelheim and sponsorship to scientific meetings from
Boehringer-Ingelheim. He obtains research funding from the Canadian
Institutes of Health Research, the Heart and Stroke Foundation of Canada
(Ontario), and the National Institutes of Health. Ankur Thapar receives
research funding from the Royal College of Surgeons of England. Wei Zhou
receives research funding from the National Institute of Health/National
Institute of Neurological Disorders and Stroke for evaluating outcomes
of carotid interventions. The other authors have no conflicts to report.
NR 46
TC 20
Z9 21
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD APR
PY 2013
VL 44
IS 4
BP 1186
EP 1190
DI 10.1161/STROKEAHA.111.000261
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 113NE
UT WOS:000316673900056
PM 23512977
ER
PT J
AU Goldberg, SB
Willers, H
Heist, RS
AF Goldberg, Sarah B.
Willers, Henning
Heist, Rebecca S.
TI Multidisciplinary Management of Small Cell Lung Cancer
SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Small cell lung cancer; Multidisciplinary management; Surgical
resection; Cranial irradiation
ID PHASE-III TRIAL; PROPHYLACTIC CRANIAL IRRADIATION; COUNCIL COMPARATIVE
TRIAL; THORACIC RADIOTHERAPY; SURGICAL RESECTION; RADIATION-THERAPY;
FOLLOW-UP; CHEMOTHERAPY; CARCINOMA; CISPLATIN
AB Multidisciplinary Management of Small Cell Lung Cancer Sarah B. Goldberg, Henning Willers, and Rebecca S. Heist The standard treatment of limited-stage small cell lung cancer (SCLC) is concurrent cisplatin and etoposide with thoracic radiation therapy, whereas treatment of extensive-stage disease is typically chemotherapy alone with a platinum compound plus etoposide. Surgical resection of early disease is generally reserved for patients with small, node-negative disease. Prophylactic cranial irradiation reduces the development of brain metastases and prolongs survival in patients with both limited-stage and extensive-stage disease who have responded to chemotherapy. Further understanding of the molecular underpinnings of SOLO is necessary to develop better treatment options and improve outcomes for patients.
C1 [Goldberg, Sarah B.] Yale Canc Ctr, Dept Hematol Oncol, New Haven, CT 06520 USA.
[Willers, Henning] Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Clark Ctr Radiat Oncol, Boston, MA 02114 USA.
[Heist, Rebecca S.] Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, Boston, MA 02114 USA.
RP Heist, RS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Hematol Oncol, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
EM rheist@partners.org
NR 52
TC 5
Z9 6
U1 1
U2 14
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1055-3207
EI 1558-5042
J9 SURG ONCOL CLIN N AM
JI Surg. Oncol. Clin. N. Am.
PD APR
PY 2013
VL 22
IS 2
BP 329
EP +
DI 10.1016/j.soc.2012.12.002
PG 16
WC Oncology; Surgery
SC Oncology; Surgery
GA 117SN
UT WOS:000316973500011
PM 23453338
ER
PT J
AU Ma, RS
Latif, R
Davies, TF
AF Ma, Risheng
Latif, Rauf
Davies, Terry F.
TI Thyroid Follicle Formation and Thyroglobulin Expression in Multipotent
Endodermal Stem Cells
SO THYROID
LA English
DT Article
ID SYNERGISTICALLY ACTIVATE; GENE-EXPRESSION; TRANSCRIPTION;
DIFFERENTIATION; MOUSE; PAX8; PRESERVATION; ORGANOIDS
AB Objective: The aim of this study was to assess the impact of transcriptional induction on thyroid follicular cell (TFC) differentiation from endodermally matured embryonic stem (ES) cells. The thyroid transcription factors-NKx2 homeobox 1 (NKx2-1, formerly called TTF-1) and Paired box gene 8 (Pax8)-are known to associate biochemically and synergistically in the activation of thyroid functional genes including the sodium/iodide symporter (NIS), thyrotropin (TSH) receptor (TSHR), thyroglobulin (Tg), and thyroid peroxidase (TPO) genes. In this study, we investigated the ability of ectopically expressed Pax8 and NKx2-1 to further the induction and differentiation of murine ES cells into potential TFCs.
Methods: ES cells were stably transfected with either the Pax8 gene, the NKx2-1 gene, or both genes to study the induction of NIS, TSHR, Tg, and TPO genes as assessed using both quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and protein expression. The derived cells were cultured with or without the presence of activin A to allow their differentiation into multipotent endodermal cells.
Results: The four thyroid-specific genes NIS, TSHR, Tg, and TPO were all significantly activated by expressing both transcription factors within the same ES cell. In contrast, significant but much lower transcriptional activity of the TSHR, Tg, and TPO genes was detected in cells expressing just NKx2-1, and only the NIS and TSHR genes responded to Pax8 alone. No Tg protein expression could be detected prior to their development into endodermal derivatives. However, after further differentiation of postembryoid body ES cells with activin A and TSH into endodermal cell lines, those cells with dual transfection of Pax8 and NKx2-1 demonstrated greatly enhanced expression of the NIS, TSHR, Tg, and TPO genes to such a degree that it was similar to that found in control thyroid cells. Furthermore, these same cells formed three-dimensional neofollicles in vitro and expressed Tg protein, but these phenomena were absent from lines expressing only Pax8 or NKx2-1.
Conclusion: These findings provide further evidence that co-expression of Pax8 and NKx2-1 in murine ES cells may induce the differentiation of thyroid-specific gene expression within endodermally differentiated ES cells and commit them to form three-dimensional neofollicular structures.
C1 [Ma, Risheng; Latif, Rauf; Davies, Terry F.] Icahn Sch Med Mt Sinai, Dept Med, Thyroid Res Unit, New York, NY USA.
[Ma, Risheng; Latif, Rauf; Davies, Terry F.] James J Peters VA Med Ctr, Dept Med, New York, NY USA.
RP Ma, RS (reprint author), VA Med Ctr, Room 2F-27,130 West Kingsbridge Rd, New York, NY 10468 USA.
EM risheng.ma@mssm.edu
OI latif, rauf/0000-0002-4226-3728
FU National Institutes of Health [DK080459, DK069713, DK052464]; VA Merit
Review Program
FX This work was supported in part by DK080459, DK069713, and DK052464 from
the National Institutes of Health and the VA Merit Review Program.
NR 14
TC 15
Z9 16
U1 1
U2 13
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD APR
PY 2013
VL 23
IS 4
BP 385
EP 391
DI 10.1089/thy.2012.0644
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 115FT
UT WOS:000316798700003
PM 23360087
ER
PT J
AU Anderson, RT
Linnehan, JE
Tongbram, V
Keating, K
Wirth, LJ
AF Anderson, Roger T.
Linnehan, John E.
Tongbram, Vanita
Keating, Karen
Wirth, Lori J.
TI Clinical, Safety, and Economic Evidence in Radioactive Iodine-Refractory
Differentiated Thyroid Cancer: A Systematic Literature Review
SO THYROID
LA English
DT Review
ID PHASE-II TRIAL; DISTANT METASTASES; CARCINOMA; SORAFENIB; THERAPY;
DOXORUBICIN; MANAGEMENT; PAPILLARY; TOXICITY; EFFICACY
AB Background: Thyroid cancer is the most common endocrine malignancy, with differentiated thyroid cancer (DTC) comprising similar to 93% of all thyroid cancers. While most cases of DTC are curable with the use of surgery and radioactive iodine (RAI) ablation of the remaining thyroid remnant, prognosis is dire and treatment options limited when DTC becomes RAI-refractory (RAI-R). Standard cytotoxic chemotherapy has limited efficacy, making enrollment in clinical trials of novel targeted therapies the preferred treatment approach. Thus, we conducted a comprehensive systematic review of the clinical trial scientific literature with a focus on efficacy, safety, and economics to identify all potential treatment options that have been or are currently being evaluated for the treatment of RAI-R DTC.
Methods: Embase.com (including Medline), Medline In-Process and other nonindexed citations, the Cochrane Libraries, ClinicalTrials.gov, and relevant recent conference proceedings were searched using predefined search criteria. Important inclusion criteria included English language, randomized controlled studies or interventional single-arm studies only, and studies of drug therapies only. Search results were screened utilizing the discretion of multiple researchers, and key data were abstracted.
Results: Forty-five unique trials (16 full-text, 4 conference abstracts, and 25 ClinicalTrials.gov entries) were included in the clinical review. No studies that met criteria for inclusion in the economic review were identified. Among 20 trials with results available, all were Phase II and only one was randomized. The most commonly studied drugs were tyrosine kinase inhibitors (TKIs); other drugs included celecoxib, doxorubicin with interferon alpha-2b, rosiglitazone, selumetinib (AZD6244), thalidomide, VEGF trap, and vorinostat. Overall, efficacy and safety profiles were specific to treatment regimen, with objective response rates (ORR) ranging from 0% on gefitinib, rosiglitazone, VEGF trap, and vorinostat to 50% on lenvatinib, a TKI.
Conclusions: Limited clinical research and no economic research has been conducted in RAI-R DTC. Certain treatments, notably TKIs, have shown promise in Phase II trials, and two Phase III randomized placebo-controlled trials are ongoing. New research on the economic and humanistic burden of RAI-R DTC must be paired with the clinical evidence currently in development to examine the existing burden and future promise in treating patients with RAI-R DTC.
C1 [Anderson, Roger T.] Penn State Univ, Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Linnehan, John E.] Oxford Outcomes, Dept Hlth Econ, Bethesda, MD USA.
[Tongbram, Vanita] Oxford Outcomes, Dept Hlth Econ, Morristown, NJ USA.
[Keating, Karen] Bayer Healthcare Pharmaceut, Dept Global Hlth Econ Outcomes Reimbursement & Ma, Montville, NJ USA.
[Wirth, Lori J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oncol, Boston, MA USA.
RP Linnehan, JE (reprint author), Oxford Outcomes, 7315 Wisconsin Ave,Suite 250W, Bethesda, MD 20814 USA.
EM john.linnehan@comcast.net
FU Bayer Healthcare Pharmaceuticals
FX This project was funded by Bayer Healthcare Pharmaceuticals. J.E.L. and
V.T. were paid consultants to Bayer Healthcare Pharmaceuticals for this
project. R.A. reports no compensation for the role of authorship of this
manuscript; he serves as a paid consultant to Bayer Pharma AG relating
to patient-reported outcomes assessments. L.J.W. reports no compensation
for the role of authorship of this manuscript; she serves as a paid
consultant to Bayer Pharma AG and Exelexis. K.K. is an employee of Bayer
Healthcare Pharmaceuticals.
NR 45
TC 23
Z9 25
U1 0
U2 12
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD APR
PY 2013
VL 23
IS 4
BP 392
EP 407
DI 10.1089/thy.2012.0520
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 115FT
UT WOS:000316798700004
PM 23294230
ER
PT J
AU Murphy, AM
Rabkin, SD
AF Murphy, Andrea M.
Rabkin, Samuel D.
TI Current status of gene therapy for brain tumors
SO TRANSLATIONAL RESEARCH
LA English
DT Review
ID MESENCHYMAL STEM-CELLS; HERPES-SIMPLEX-VIRUS; HIGH-GRADE GLIOMA;
LONG-TERM SURVIVAL; COMPETENT RETROVIRUS VECTORS; RECURRENT MALIGNANT
GLIOMAS; GUTLESS ADENOVIRUS VECTORS; HUMAN GLIOBLASTOMA CELLS;
MEASLES-VIRUS; ONCOLYTIC ADENOVIRUS
AB Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replication-competent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma. (Translational Research 2013;161:339-354)
C1 [Rabkin, Samuel D.] Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Brain Tumor Res Ctr, Boston, MA 02114 USA.
[Rabkin, Samuel D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Brain Tumor Res Ctr, 185 Cambridge St,CPZN-3800, Boston, MA 02114 USA.
EM rabkin@helix.mgh.harvard.edu
RI Waha, Andreas/J-2950-2014;
OI rabkin, samuel/0000-0003-2344-2795
FU National Institutes of Health (National Cancer Institute); National
Institutes of Health (National Institute of Neurologic Disorders and
Stroke); Department of Defense; American Brain Tumor Association
FX The authors thank past and current members of the laboratory for
contributing to our research, which has been supported by grants from
the National Institutes of Health (National Cancer Institute, National
Institute of Neurologic Disorders and Stroke), Department of Defense,
and the American Brain Tumor Association.
NR 181
TC 26
Z9 28
U1 3
U2 44
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1931-5244
J9 TRANSL RES
JI Transl. Res.
PD APR
PY 2013
VL 161
IS 4
BP 339
EP 354
DI 10.1016/j.trsl.2012.11.003
PG 16
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
Research & Experimental
SC Medical Laboratory Technology; General & Internal Medicine; Research &
Experimental Medicine
GA 115UM
UT WOS:000316837400013
PM 23246627
ER
PT J
AU Van Nieuwenhove, L
Buscher, P
Balharbi, F
Humbert, M
Guisez, Y
Lejon, V
AF Van Nieuwenhove, Liesbeth
Buescher, Philippe
Balharbi, Fatima
Humbert, Michael
Guisez, Yves
Lejon, Veerle
TI A LiTat 1.5 variant surface glycoprotein-derived peptide with diagnostic
potential for Trypanosoma brucei gambiense
SO TROPICAL MEDICINE & INTERNATIONAL HEALTH
LA English
DT Article
DE diagnosis; sensitivity; specificity; sleeping sickness; Trypanosoma
brucei gambiense; variant surface glycoprotein
AB Objective To evaluate the accuracy of a peptide, corresponding to the variant surface glycoprotein (VSG) LiTat 1.5 amino acid (AA) sequence 268281 and identified through alignment of monoclonal antibody selected mimotopes, for diagnosis of Trypanosoma brucei gambiense sleeping sickness. Methods A synthetic biotinylated peptide (peptide 1.5/268281), native VSG LiTat 1.3 and VSG LiTat 1.5 were tested in an indirect ELISA with 102 sera from patients with HAT and 102 endemic HAT-negative controls. Results The area under the curve (AUC) of peptide 1.5/268281 was 0.954 (95% confidence interval 0.9180.980), indicating diagnostic potential. The areas under the curve of VSG LiTat 1.3 and LiTat 1.5 were 1.000 (0.9821.000) and 0.997 (0.9731.000), respectively, and significantly higher than the AUC of peptide 1.5/268281. On a model of VSG LiTat 1.5, peptide 1.5/268281 was mapped near the top of the VSG. Conclusions A biotinylated peptide corresponding to AA 268281 of VSG LiTat 1.5 may replace the native VSG in serodiagnostic tests, but the diagnostic accuracy is lower than for the full-length native VSG LiTat 1.3 and VSG LiTat 1.5. Objectif Evaluer la precision diagnostique d'un peptide correspondant a une variante de la sequence des acides amines 268 a 281 de la glycoproteine de surface LiTat 1.5 et identifie grace a l'alignement des mimotopes selectionnes des anticorps monoclonaux, pour le diagnostic de la maladie du sommeil due a Trypanosoma brucei gambiense. Methodes Un peptide synthetique biotinyle (peptide 1.5/268-281) et les proteines de surface natives LiTat 1.3 et LiTat 1.5 ont ete testes dans une reaction ELISA indirecte sur 102 echantillons de serum provenant de patients atteints de THA et 102 controles negatifs de zone endemique. Resultats L'aire sous la courbe (AUC) du peptide 1.5/268-281 etait de 0.954 (IC95%: 0.918 a 0.980), ce qui indique un potentiel diagnostique. Les aires sous la courbe de LiTat 1.3 et LiTat 1.5 etaient de 1000 (0.982 a 1000) et 0.997 (0.973 a 1000), respectivement, et nettement superieures a l'AUC du peptide 1.5/268-281. Sur un modele de LiTat 1.5, le peptide 1.5/268-281 a ete cartographie pres du sommet de la glycoproteine de surface. Conclusions Un peptide biotinyle correspondant a la sequence des acides amines 268 a 281 de LiTat 1.5 pourrait remplacer la glycoproteine de surface native dans les tests de serodiagnostic, mais la precision du diagnostic est plus faible qu'avec l'entierete des glycoproteines de surfaces natives LiTat 1.3 et LiTat 1.5. Objetivo Evaluar la precision diagnostica de un peptido correspondiente a la secuencia de aminoacidos 268281 de la glicoproteina variante de superficie (VSG) LiTat 1.5, identificados mediante un alineamiento de una seleccion de mimotopes de anticuerpos monoclonales, para el diagnostico de la enfermedad del sueno por Trypanosoma brucei gambiense (HAT). Metodos Utilizando un ELISA indirecto, se probaron el peptido sintetico biotinilado (peptido 1.5/268-281), la VSG nativa LiTat 1.3 y la VSG LiTat 1.5, con 102 sueros de pacientes con HAT y 102 controles negativos endemicos. Resultados El area bajo la curva (ABC) del peptido 1.5/268-281 era de 0.954 (IC 95% 0.9180.980), indicando su potencial diagnostico. Las ABC de VSG LiTat 1.3 y LiTat 1.5 eran 1.000 (0.982-1.000) y 0.997 (0.9731.000) respectivamente, y significativamente mayor que el ABC del peptido 1.5/268-281. En un modelo del VSG LiTat 1.5, el peptido 1.5/268-281 se mapeo cerca de la parte superior del VSG. Conclusiones Un peptido biotinilado, que corresponde al AA 268281 del VSG LiTat 1.
5, podria reemplazar las pruebas serodiagnosticas basadas en la VSG nativa, pero la precision diagnostica es menor que para la VSG LiTat 1.3 nativa de tamano completo y la VSG LiTat 1.5.
C1 [Van Nieuwenhove, Liesbeth; Buescher, Philippe; Balharbi, Fatima; Lejon, Veerle] Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp, Belgium.
[Humbert, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Humbert, Michael] Harvard Univ, Sch Med, Boston, MA USA.
[Guisez, Yves] Univ Antwerp, Dept Biol, B-2020 Antwerp, Belgium.
RP Lejon, V (reprint author), Inst Trop Med, Natl Str 155, B-2000 Antwerp, Belgium.
EM vlejon@itg.be
RI Buscher, Philippe/B-9956-2012;
OI Buscher, Philippe/0000-0002-1926-7472; Lejon, Veerle/0000-0002-6795-0962
FU Belgian Directorate General for Development Cooperation; Research
Foundation of Flanders; FWO
FX We are grateful to Nicolas Bebronne and Annelies Ceusters for technical
assistance. The project was funded by the Belgian Directorate General
for Development Cooperation and the Research Foundation of Flanders.
Liesbeth Van Nieuwenhove was supported by a PhD scholarship of the FWO.
Development of the UCSF Chimera package from the Resource for
Biocomputing, Visualization, and Informatics at the University of
California, San Francisco, was supported by the NIH. The funders had no
role in study design, data collection and analysis, decision to publish
or preparation of the manuscript.
NR 0
TC 4
Z9 4
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1360-2276
J9 TROP MED INT HEALTH
JI Trop. Med. Int. Health
PD APR
PY 2013
VL 18
IS 4
BP 461
EP 465
DI 10.1111/tmi.12058
PG 5
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 112XF
UT WOS:000316627200011
PM 23289521
ER
PT J
AU Sealock, RJ
Kramer, JR
Verstovsek, G
Richardson, P
Rugge, M
Parente, P
Vela, M
El-Serag, HB
AF Sealock, R. J.
Kramer, J. R.
Verstovsek, G.
Richardson, P.
Rugge, M.
Parente, P.
Vela, M.
El-Serag, H. B.
TI The prevalence of oesophageal eosinophilia and eosinophilic
oesophagitis: a prospective study in unselected patients presenting to
endoscopy
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID CONSENSUS RECOMMENDATIONS; BARRETTS-ESOPHAGUS; ADULTS; POPULATION;
DYSPHAGIA; CHILDREN
AB Background Oesophageal eosinophilia (EE) is encountered in clinical practice as oesophageal biopsies are being obtained in patients with GI symptoms other than classical symptoms of eosinophilic oesophagitis (EoE). The prevalence, determinants and clinical relevance of EE identified irrespective of symptoms are unclear. Aim To determine the prevalence and risk factors of EE with or without EoE in a nonselected group of patients undergoing endoscopy and in primary care patients. Methods A cross-sectional study in a single VA centre in which we obtained at least one oesophageal biopsy from patients presenting to elective endoscopy, as well as a sample of patients eligible for screening colonoscopy recruited from primary care clinics. EE was defined by >15 eosinophils in a single HPF; and EoE was defined as definite, probable or none depending on the presence of EE, acid-suppressive therapy and oesophageal symptoms. Results EE was identified in 33 of 1357 patients (2.4%, 95% CI: 1.73.4); of whom 9 had definite EoE (0.66%, 95% CI: 0.231.10), 17 had probable EoE (1.25%), and the only 7 patients had EE without EoE. The prevalence of EE was 2.3% among patients undergoing elective endoscopy and 0.1% among patients eligible for screening colonoscopy. Seasonal allergies (adjusted OR: 2.78; 95% CI: 1.266.11) and oesophageal strictures (4.50; 0.9022.40) were associated with EE. Conclusions The prevalence of EE was 2.3% among unselected patients presenting to endoscopy most of whom have EoE. EE was present in 0.1% in primary care patients none of whom had EoE.
C1 [Sealock, R. J.; El-Serag, H. B.] Michael E DeBakey VA Med Ctr, Gastroenterol Sect, Houston, TX USA.
[Sealock, R. J.; Vela, M.; El-Serag, H. B.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA.
[Kramer, J. R.; Richardson, P.; El-Serag, H. B.] Michael E DeBakey VA Med Ctr, Houston VA Hlth Serv, Res & Dev Ctr Excellence, Houston, TX USA.
[Kramer, J. R.; Richardson, P.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Verstovsek, G.] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
[Rugge, M.] Univ Padua, Dept Med DIMED, Surg Pathol & Cytopathol Unit, Padua, Italy.
[Parente, P.] Casa Sollievo della Sofferenza, Dept Pathol, San Giovanni Rotondo, Italy.
RP El-Serag, HB (reprint author), VA Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hasheme@bcm.tmc.edu
RI Rugge, Massimo/K-7525-2016
FU National Institutes of Health (NIH) [NCI R01 116845]; Houston VA HSR&D
Center of Excellence [HFP90-020]; Texas Digestive Disease Center NIH
[DK58338]; NIDDK [K24-04-107]
FX This work is funded in part by National Institutes of Health (NIH) grant
NCI R01 116845, the Houston VA HSR&D Center of Excellence (HFP90-020),
and the Texas Digestive Disease Center NIH DK58338. Dr El-Serag is also
supported by NIDDK K24-04-107. The views expressed in this article are
those of the authors and do not necessarily represent the views of the
Department of Veterans Affairs, the US government, the NIH or Baylor
College of Medicine. The NIH had no role in the design and conduct of
the study; the collection, management, analysis and interpretation of
the data; or the preparation, review or approval of the manuscript.
NR 23
TC 9
Z9 9
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD APR
PY 2013
VL 37
IS 8
BP 825
EP 832
DI 10.1111/apt.12268
PG 8
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 108WC
UT WOS:000316325900008
PM 23441936
ER
PT J
AU Wang, JL
Wilbur, DC
AF Wang, Jessica L.
Wilbur, David C.
TI Negative Biopsy Specimens in the Setting of High A Priori Probability of
Disease Is It Time to Reconsider Quality Assurance Routines in a Time of
New Diagnostic Capabilities?
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Editorial Material
ID CERVICAL PATHOLOGY; AMERICAN SOCIETY; COLPOSCOPY; DYSPLASIA; LESIONS
C1 [Wang, Jessica L.; Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tames Homer Wright Lab Pathol, Boston, MA 02115 USA.
RP Wang, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tames Homer Wright Lab Pathol, Boston, MA 02115 USA.
NR 9
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD APR
PY 2013
VL 139
IS 4
BP 418
EP 420
DI 10.1309/AJCPU0UA5GYHXXIZ
PG 3
WC Pathology
SC Pathology
GA 109LF
UT WOS:000316369300002
PM 23525610
ER
PT J
AU Kim, SS
Okechukwu, CA
Buxton, OM
Dennerlein, JT
Boden, LI
Hashimoto, DM
Sorensen, G
AF Kim, Seung-Sup
Okechukwu, Cassandra A.
Buxton, Orfeu M.
Dennerlein, Jack T.
Boden, Leslie I.
Hashimoto, Dean M.
Sorensen, Glorian
TI Association between work-family conflict and musculoskeletal pain among
hospital patient care workers
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE workfamily conflict; musculoskeletal symptoms; low back pain; hospital
worker
ID NATIONAL COMORBIDITY SURVEY; LIFE CONFLICT; SICKNESS ABSENCE;
RISK-FACTORS; DEPRESSIVE SYMPTOMS; REGISTERED NURSES; MENTAL-HEALTH; JOB
DEMAND; QUESTIONNAIRE; SWITZERLAND
AB Background A growing body of evidence suggests that workfamily conflict is an important risk factor for workers' health and well-being. The goal of this study is to examine association between workfamily conflict and musculoskeletal pain among hospital patient care workers. Methods We analyzed a cross-sectional survey of 1,119 hospital patient care workers in 105 units in two urban, academic hospitals. Workfamily conflict was measured by 5-item WorkFamily Conflict Scale questionnaire. Multilevel logistic regression was applied to examine associations between workfamily conflict and self-reported musculoskeletal pain in the past 3 months, adjusting for covariates including work-related psychosocial factors and physical work factors. Results In fully adjusted models, high workfamily conflict was strongly associated with neck or shoulder pain (OR: 2.34, 95% CI: 1.643.34), arm pain (OR: 2.79, 95% CI: 1.644.75), lower extremity pain (OR: 2.20, 95% CI: 1.543.15) and any musculoskeletal pain (OR: 2.45, 95% CI: 1.563.85), and a number of body areas in pain (OR: 2.47, 95% CI: 1.823.36) in the past 3 months. The association with low back pain was attenuated and became non-significant after adjusting for covariates. Conclusions Given the consistent associations between workfamily conflict and self-reported musculoskeletal pains, the results suggest that workfamily conflict could be an important domain for health promotion and workplace policy development among hospital patient care workers. Am. J. Ind. Med. 56:488495, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Kim, Seung-Sup] Washington Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA.
[Okechukwu, Cassandra A.; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Buxton, Orfeu M.; Hashimoto, Dean M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Buxton, Orfeu M.; Hashimoto, Dean M.] Harvard Univ, Sch Med, Boston, MA USA.
[Dennerlein, Jack T.; Hashimoto, Dean M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Boden, Leslie I.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Hashimoto, Dean M.] Partners HealthCare Syst, Occupat Hlth Serv, Boston, MA USA.
[Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
RP Kim, SS (reprint author), Washington Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth & Hlth Serv, 2300 Eye St NW, Washington, DC 20037 USA.
EM sskim@gwu.edu
OI Boden, Leslie/0000-0002-9779-207X; Dennerlein, Jack/0000-0001-7703-643X
FU National Institute for Occupational Safety and Health [U19 OH008861];
National Heart, Lung and Blood Institute [R01HL107240]
FX Contract grant sponsor: National Institute for Occupational Safety and
Health; Contract grant number: U19 OH008861.; Contract grant sponsor:
National Heart, Lung and Blood Institute; Contract grant number:
R01HL107240.
NR 43
TC 12
Z9 12
U1 1
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
J9 AM J IND MED
JI Am. J. Ind. Med.
PD APR
PY 2013
VL 56
IS 4
BP 488
EP 495
DI 10.1002/ajim.22120
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 108UD
UT WOS:000316320800010
PM 23019044
ER
PT J
AU Ballard-Barbash, R
Siddiqi, SM
Berrigan, DA
Ross, SA
Nebeling, LC
Dowling, EC
AF Ballard-Barbash, Rachel
Siddiqi, Sameer M.
Berrigan, David A.
Ross, Sharon A.
Nebeling, Linda C.
Dowling, Emily C.
TI Trends in Research on Energy Balance Supported by the National Cancer
Institute
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID PHYSICAL-ACTIVITY; OBESITY RESEARCH; SURVIVORS; RECOMMENDATIONS;
INTERVENTIONS; METAANALYSIS; PREVENTION; OUTCOMES; BURDEN; HEALTH
AB Over the past decade, the body of research linking energy balance to the incidence, development, progression, and treatment of cancer has grown substantially. No prior NIH portfolio analyses have focused on energy balance within one institute. This portfolio analysis describes the growth of National Cancer Institute (NCI) grant research on energy balance-related conditions and behaviors from 2004 to 2010 following the release of an NCI research priority statement in 2003 on energy balance and cancer-related research. Energy balance grants from fiscal years (FY) 2004 to 2010 were identified using multiple search terms and analyzed between calendar years 2008 and 2010. Study characteristics related to cancer site, design, population, and energy balance area (physical activity, diet, and weight) were abstracted.
From FY2004 to FY2010, the NCI awarded 269 energy balance-relevant grants totaling $518 million. In FY2010, 4.2% of NCI's total research project grants budget was allocated to energy balance research, compared to 2.1% in FY2004. The NCI more than doubled support for investigator-initiated research project grants (R01) and increased support for cooperative agreement (U01, U54) and exploratory research (R21) grants. In the portfolio, research examining energy balance areas in combination accounted for 41.6%, and observational and interventional studies were equally represented (38.3% and 37.2%, respectively). Breast cancer was the most commonly studied cancer. Inclusion of minorities rose, and funding specific to cancer survivors more than doubled. From FY2004 to FY2010, NCI's investment in energy balance and related health behavior research showed growth in funding and diversity of mechanisms, topics, and disciplines growth that reflects new directions in this field. (Am J Prey Med 2013;44(4):416-423) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Ballard-Barbash, Rachel; Siddiqi, Sameer M.; Berrigan, David A.] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Nebeling, Linda C.] NCI, Behav Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Ross, Sharon A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Dowling, Emily C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
RP Ballard-Barbash, R (reprint author), NCI, Div Canc Control & Populat Sci, EPN 4005,6130 Executive Blvd MSC 7344, Bethesda, MD 20892 USA.
EM barbashr@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 28
TC 6
Z9 6
U1 0
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD APR
PY 2013
VL 44
IS 4
BP 416
EP 423
DI 10.1016/j.amepre.2012.11.033
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 111GM
UT WOS:000316509800014
PM 23498109
ER
PT J
AU Berris, T
Gupta, R
Rehani, MM
AF Berris, Theocharis
Gupta, Rajiv
Rehani, Madan M.
TI Radiation Dose From Cone-Beam CT in Neuroradiology Applications
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE cone-beam CT; neuroradiology; patient safety; radiation dose; radiation
safety; staff safety
ID IMAGE-GUIDED RADIOTHERAPY; COMPUTED-TOMOGRAPHY; PRINCIPLES; GUIDANCE;
QUALITY; SYSTEM; HEAD; NECK; RADIOLOGY; EXPOSURE
AB OBJECTIVE. In view of increasing concern about radiation dose, this article aims to provide a summary of radiation doses in neuroradiologic applications of cone-beam CT.
CONCLUSION. The conventional wisdom that cone-beam CT incurs a much lower radiation dose than MDCT may not be uniformly true, especially in intraoperative use if operators are tempted to overuse the 3D imaging capabilities. The emerging nature of cone-beam CT warrants extra caution to avoid overexposure of patients.
C1 [Berris, Theocharis; Rehani, Madan M.] IAEA, Radiat Protect Patients Unit, Vienna Int Ctr, A-1400 Vienna, Austria.
[Gupta, Rajiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA USA.
RP Rehani, MM (reprint author), IAEA, Radiat Protect Patients Unit, Vienna Int Ctr, POB 200, A-1400 Vienna, Austria.
EM madan.rehani@gmail.com
NR 36
TC 2
Z9 2
U1 5
U2 6
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD APR
PY 2013
VL 200
IS 4
BP 755
EP 761
DI 10.2214/AJR.12.10177
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 112VK
UT WOS:000316622100021
PM 23521443
ER
PT J
AU Covarrubias, DA
O'Connor, OJ
McDermott, S
Arellano, RS
AF Covarrubias, Diego Antonio
O'Connor, Owen J.
McDermott, Shaunagh
Arellano, Ronald S.
TI Radiologic Percutaneous Gastrostomy: Review of Potential Complications
and Approach to Managing the Unexpected Outcome
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE feeding tubes; management of procedure complications; percutaneous
gastrostomy
ID INTERVENTIONAL RADIOLOGY; NONVASCULAR INTERVENTIONS; MANAGEMENT;
GASTROJEJUNOSTOMY; GUIDELINES; GASTROPEXY; SOCIETY; ACCESS; TUBE
AB OBJECTIVE. Radiologic percutaneous gastrostomy tube placement is a widely accepted method of enteral access for patients requiring long-term nutritional support for a variety of conditions. Although the safety of this procedure is well documented, complications do occur. The purpose of this article is to review the major and minor complications associated with gastrostomy tube placement and to present appropriate and effective management strategies.
CONCLUSION. Familiarity with the potential complications, techniques for their prevention, and strategies for treatment will help practicing interventional radiologists successfully manage all possible outcomes.
C1 [Covarrubias, Diego Antonio] Kaiser Permanente West Los Angeles Med Ctr, Dept Intervent Radiol, Diagnost Imaging Serv, Los Angeles, CA 90034 USA.
[O'Connor, Owen J.] Cork Univ Hosp, Dept Radiol, Cork, Ireland.
[McDermott, Shaunagh; Arellano, Ronald S.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Div Abdominal Imaging & In, Boston, MA 02115 USA.
RP Covarrubias, DA (reprint author), Kaiser Permanente West Los Angeles Med Ctr, Dept Intervent Radiol, Diagnost Imaging Serv, 6041 Cadillac Ave, Los Angeles, CA 90034 USA.
EM diego.a.covarrubias@kp.org
NR 21
TC 13
Z9 13
U1 0
U2 2
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD APR
PY 2013
VL 200
IS 4
BP 921
EP 931
DI 10.2214/AJR.11.7804
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 112VK
UT WOS:000316622100049
PM 23521471
ER
PT J
AU Kraeft, JJ
Uppot, RN
Heffess, AM
AF Kraeft, Jessica J.
Uppot, Raul N.
Heffess, Alejandro M.
TI Imaging Findings in Eating Disorders
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE anorexia; bulimia; eating disorders; radiology
ID OF-THE-LITERATURE; ACUTE GASTRIC DILATATION; TRABECULAR
STRUCTURE-ANALYSIS; PANEL VOLUME CT; ANOREXIA-NERVOSA; PELVIC
ULTRASONOGRAPHY; SWALLOWED TOOTHBRUSH; RECTAL PROLAPSE; BULIMIA-NERVOSA;
ABDOMINAL-PAIN
AB OBJECTIVE. Eating disorders, such as anorexia nervosa and bulimia nervosa, are often undiagnosed but potentially treatable illnesses that, if not identified, can lead to morbidity and death. Often, because of embarrassment or social stigma, patients do not readily admit to these disorders when interviewed by caregivers. Imaging findings can suggest the presence of an eating disorder; understanding these findings allows the radiologist to contribute to the diagnosis of these insidious conditions and alert the referring caregiver. Current concepts in eating disorders and their multimodality imaging findings in several organ systems will be reviewed.
CONCLUSION. After reviewing this article, the radiologist will understand the imaging findings in eating disorders. This knowledge will empower the radiologist to raise the question of a patient's eating disorder, a condition that may be unsuspected by the referring caregiver and could otherwise remain undiagnosed.
C1 [Kraeft, Jessica J.; Heffess, Alejandro M.] Mt Auburn Hosp, Dept Radiol, Cambridge, MA 02138 USA.
[Uppot, Raul N.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
RP Kraeft, JJ (reprint author), Mt Auburn Hosp, Dept Radiol, 330 Mt Auburn St, Cambridge, MA 02138 USA.
EM jkraeft@mah.harvard.edu
NR 50
TC 3
Z9 3
U1 0
U2 17
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD APR
PY 2013
VL 200
IS 4
BP W328
EP W335
DI 10.2214/AJR.12.9641
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 112VK
UT WOS:000316622100001
PM 23521475
ER
PT J
AU Li, SP
Sheng, JH
Hu, JK
Yu, WH
Kishikawa, H
Hu, MFG
Shima, K
Wu, D
Xu, ZP
Xin, W
Sims, KB
Landers, JE
Brown, RH
Hu, GF
AF Li, Shuping
Sheng, Jinghao
Hu, Jamie K.
Yu, Wenhao
Kishikawa, Hiroko
Hu, Miaofen G.
Shima, Kaori
Wu, David
Xu, Zhengping
Xin, Winnie
Sims, Katherine B.
Landers, John E.
Brown, Robert H., Jr.
Hu, Guo-fu
TI Ribonuclease 4 protects neuron degeneration by promoting angiogenesis,
neurogenesis, and neuronal survival under stress
SO ANGIOGENESIS
LA English
DT Article
DE Ribonuclease 4; Angiogenin; Angiogenesis; Neurogenesis; Neuroprotection;
Amyotrophic lateral sclerosis (ALS)
ID AMYOTROPHIC-LATERAL-SCLEROSIS; EOSINOPHIL CATIONIC PROTEIN; EMBRYONAL
CARCINOMA-CELLS; TISSUE-SPECIFIC EXPRESSION; SITE-DIRECTED MUTAGENESIS;
TRANSFER-RNA; ENDOTHELIAL-CELLS; PANCREATIC RIBONUCLEASE; A SUPERFAMILY;
STEM-CELLS
AB Altered RNA processing is an underlying mechanism of amyotrophic lateral sclerosis (ALS). Missense mutations in a number of genes involved in RNA function and metabolisms are associated with ALS. Among these genes is angiogenin (ANG), the fifth member of the vertebrate-specific, secreted ribonuclease superfamily. ANG is an angiogenic ribonuclease, and both its angiogenic and ribonucleolytic activities are important for motor neuron health. Ribonuclease 4 (RNASE4), the fourth member of this superfamily, shares the same promoters with ANG and is co-expressed with ANG. However, the biological role of RNASE4 is unknown. To determine whether RNASE4 is involved in ALS pathogenesis, we sequenced the coding region of RNASE4 in ALS and control subjects and characterized the angiogenic, neurogenic, and neuroprotective activities of RNASE4 protein. We identified an allelic association of SNP rs3748338 with ALS and demonstrated that RNASE4 protein is able to induce angiogenesis in in vitro, ex vivo, and in vivo assays. RNASE4 also induces neural differentiation of P19 mouse embryonal carcinoma cells and mouse embryonic stem cells. Moreover, RNASE4 not only stimulates the formation of neurofilaments from mouse embryonic cortical neurons, but also protects hypothermia-induced degeneration. Importantly, systemic treatment with RNASE4 protein slowed weight loss and enhanced neuromuscular function of SOD1 (G93A) mice.
C1 [Li, Shuping; Sheng, Jinghao; Hu, Jamie K.; Yu, Wenhao; Kishikawa, Hiroko; Hu, Miaofen G.; Hu, Guo-fu] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA.
[Li, Shuping] Zhejiang Univ, Sch Med, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China.
[Sheng, Jinghao; Xu, Zhengping] Zhejiang Univ, Sch Med, Inst Environm Med, Hangzhou 310003, Zhejiang, Peoples R China.
[Shima, Kaori] Kagoshima Univ, Grad Sch Med & Dent Sci, Div Oral Pathol, Kagoshima 890, Japan.
[Wu, David] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Xin, Winnie; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Landers, John E.; Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
RP Hu, GF (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, 800 Washington St,Box 5069, Boston, MA 02111 USA.
EM guo-fu.hu@tufts.edu
FU National Institute of Health [R01 NS 065237]; NIH; ALS Therapy Alliance;
Harvard University Technology Development Accelerator Fund; National
Institute for Neurological Disease and Stroke; Angel Fund; ALS
Association
FX This work was supported by National Institute of Health grant R01 NS
065237 (to GFH). GFH receives fund from NIH, ALS Therapy Alliance, and
Harvard University Technology Development Accelerator Fund,
Massachusetts Alzheimer Disease Research Center, and Tufts University
CTSI program. RHB receives support from the National Institute for
Neurological Disease and Stroke, the Angel Fund, the ALS Association,
Project ALS, P2ALS. Pierre L. de Bourgknecht ALS Research Foundation,
the Al-Athel ALS Foundation, and the ALS Therapy Alliance. We thank
Robert Shapiro (Harvard Medical School) for helpful discussions on
biochemical characterization of RNASE4, Helene F. Rosenberg (NIH/NIAID)
for providing mouse Rnase4 expression plasmid, Jan Hofsteenge (Friedrich
Miescher Institute, Switzerland) for providing pig RNASE4 expression
plasmid.
NR 68
TC 9
Z9 12
U1 5
U2 16
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
J9 ANGIOGENESIS
JI Angiogenesis
PD APR
PY 2013
VL 16
IS 2
BP 387
EP 404
DI 10.1007/s10456-012-9322-9
PG 18
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 107FC
UT WOS:000316199200009
PM 23143660
ER
PT J
AU Jacoby, GA
Hooper, DC
AF Jacoby, George A.
Hooper, David C.
TI Phylogenetic Analysis of Chromosomally Determined Qnr and Related
Proteins
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID QUINOLONE-RESISTANCE DETERMINANT; PENTAPEPTIDE REPEAT PROTEINS;
STENOTROPHOMONAS-MALTOPHILIA; INTRINSIC RESISTANCE; TRANSFERABLE
PLASMID; VIBRIO-SPLENDIDUS; ESCHERICHIA-COLI; GENE; EXPRESSION; SMQNR
AB qnr genes were discovered on plasmids by their ability to reduce quinolone susceptibility, but homologs can be found in the genomes of at least 92 Gram-negative, Gram-positive, and strictly anaerobic bacterial species. The related pentapeptide repeat protein-encoding mfpA gene is present in the genome of at least 19 species of Mycobacterium and 10 other Actinobacteria species. The native function of these genes is not yet known.
C1 [Jacoby, George A.] Lahey Clin Fdn, Burlington, MA USA.
[Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Jacoby, GA (reprint author), Lahey Clin Fdn, Burlington, MA USA.
EM george.a.jacoby@lahey.org
FU National Institutes of Health, U.S. Public Health Service [R01 AI057576]
FX This work was supported by grant R01 AI057576 (to D.C.H. and G.A.J.)
from the National Institutes of Health, U.S. Public Health Service.
NR 46
TC 12
Z9 14
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD APR
PY 2013
VL 57
IS 4
BP 1930
EP 1934
DI 10.1128/AAC.02080-12
PG 5
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 106CN
UT WOS:000316119100052
PM 23318805
ER
PT J
AU Tanpowpong, P
Broder-Fingert, S
Katz, AJ
Camargo, CA
AF Tanpowpong, Pornthep
Broder-Fingert, Sarabeth
Katz, Aubrey J.
Camargo, Carlos A., Jr.
TI Characteristics of children with positive coeliac serology and normal
villous morphology: potential coeliac disease
SO APMIS
LA English
DT Article
DE Duodenum; biopsy; serology; gluten
ID SMALL-INTESTINAL MUCOSA; AT-RISK GROUPS; INTRAEPITHELIAL LYMPHOCYTOSIS;
GLUTEN; TRANSGLUTAMINASE; PREVALENCE; ANTIBODIES; DUODENOSIS; DIAGNOSIS;
SPECTRUM
AB Positive coeliac serology with normal villous morphology (NVM) indicates potential coeliac disease (CD). Few studies have compared characteristics of NVM vs villous atrophy in patients with positive serology. Our aim was to determine the independent clinical predictors of NVM in children with positive CD serology. We performed a structured medical record review of patients aged 119years who presented for an initial CD evaluation between 2000 and 2010 at a large teaching hospital. Data collection included demographics, medical history, prior history of gluten avoidance, CD-specific serology, oesophagogastroduodenoscopy and histopathology. Predictors of NVM (vs Marsh III) were determined using multivariable logistic regression. Among 320 patients with positive serology, we identified 62 patients (19%, 95% CI 1524) with NVM (i.e. potential CD). Younger children may have been more likely to exhibit NVM (p=0.06). Three significant predictors of NVM were prior gluten avoidance (OR 4.17, 95% CI 1.0217.13), positive tissue transglutaminase antibody but <100U/mL (OR 14.75, 95% CI 3.3365.30), and absence of gross duodenal abnormalities (OR 3.48, 95% CI 1.518.03). Among children with positive CD serology, prior gluten avoidance predicts NVM. Future studies are warranted on the impact of gluten intake and CD testing in children without prior established CD diagnosis.
C1 [Tanpowpong, Pornthep; Broder-Fingert, Sarabeth; Katz, Aubrey J.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp Children, Boston, MA 02115 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA.
EM ccamargo@partners.org
OI Broder-Fingert, Sarabeth/0000-0002-0932-4461
NR 25
TC 3
Z9 3
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0903-4641
J9 APMIS
JI APMIS
PD APR
PY 2013
VL 121
IS 4
BP 266
EP 271
DI 10.1111/j.1600-0463.2012.02966.x
PG 6
WC Immunology; Microbiology; Pathology
SC Immunology; Microbiology; Pathology
GA 114RZ
UT WOS:000316761400002
PM 23030455
ER
PT J
AU Therkelsen, KE
Pedley, A
Speliotes, EK
Massaro, JM
Murabito, J
Hoffmann, U
Fox, CS
AF Therkelsen, Kate E.
Pedley, Alison
Speliotes, Elizabeth K.
Massaro, Joseph M.
Murabito, Joanne
Hoffmann, Udo
Fox, Caroline S.
TI Intramuscular Fat and Associations With Metabolic Risk Factors in the
Framingham Heart Study
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE epidemiology; intramuscular fat; metabolism; obesity
ID INDUCED INSULIN-RESISTANCE; VISCERAL ADIPOSE-TISSUE; MUSCLE
LIPID-CONTENT; SKELETAL-MUSCLE; COMPUTED-TOMOGRAPHY;
CARDIOVASCULAR-DISEASE; HUMAN OBESITY; ACCUMULATION; CHOLESTEROL;
SENSITIVITY
AB Objective-Intramuscular fat accumulates between muscle fibers or within muscle cells. We investigated the association of intramuscular fat with other ectopic fat deposits and metabolic risk factors.
Approach and Results-Participants (n=2945; 50.2% women; mean age 50.8 years) from the Framingham Heart Study underwent multidetector computed tomography scanning of the abdomen. Regions of interest were placed on the left and right paraspinous muscle, and the muscle attenuation (MA) in Hounsfield units was averaged. We examined the association between MA and metabolic risk factors in multivariable models, and additionally adjusted for body mass index (BMI) and visceral adipose tissue (VAT) in separate models. MA was associated with dysglycemia, dyslipidemia, and hypertension in both sexes. In women, per standard deviation decrease in MA, there was a 1.34 (95% confidence interval, 1.10-1.64) increase in the odds of diabetes mellitus, a 1.40 (95% confidence interval, 1.22-1.61) increase in the odds of high triglycerides, and a 1.29 (95% confidence interval, 1.12-1.48) increase in the odds of hypertension. However, none of these associations persisted after adjustment for BMI or VAT. In men, we observed similar patterns for most risk factors. The exception was metabolic syndrome, which retained association in women even after adjustment for BMI and VAT, and low high density lipoprotein and high triglycerides in men, whose associations also persisted after adjustment for BMI and VAT.
Conclusions-MA was associated with metabolic risk factors, but most of these associations were lost after adjustment for BMI or VAT. However, a unique association remained for metabolic syndrome in women and lipids in men. (Arterioscler Thromb Vasc Biol. 2013;33:863-870.)
C1 [Therkelsen, Kate E.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Therkelsen, Kate E.; Pedley, Alison; Murabito, Joanne; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Speliotes, Elizabeth K.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Speliotes, Elizabeth K.] Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Murabito, Joanne] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA.
[Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
RP Fox, CS (reprint author), 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Murabito, Joanne/0000-0002-0192-7516; Massaro,
Joseph/0000-0002-2682-4812
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; [K23
DK080145-01]
FX The Framingham Heart Study of the National Heart, Lung, and Blood
Institute is supported by contract N01-HC-25195. Additionally, Dr
Speliotes is supported through K23 DK080145-01.
NR 35
TC 20
Z9 20
U1 0
U2 18
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 APR
PY 2013
VL 33
IS 4
BP 863
EP U541
DI 10.1161/ATVBAHA.112.301009
PG 19
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 105ZE
UT WOS:000316110400029
PM 23349188
ER
PT J
AU Evens, AM
Hong, FX
Gordon, LI
Fisher, RI
Bartlett, NL
Connors, JM
Gascoyne, RD
Wagner, H
Gospodarowicz, M
Cheson, BD
Stiff, PJ
Advani, R
Miller, TP
Hoppe, RT
Kahl, BS
Horning, SJ
AF Evens, Andrew M.
Hong, Fangxin
Gordon, Leo I.
Fisher, Richard I.
Bartlett, Nancy L.
Connors, Joseph M.
Gascoyne, Randy D.
Wagner, Henry
Gospodarowicz, Mary
Cheson, Bruce D.
Stiff, Patrick J.
Advani, Ranjana
Miller, Thomas P.
Hoppe, Richard T.
Kahl, Brad S.
Horning, Sandra J.
TI The efficacy and tolerability of adriamycin, bleomycin, vinblastine,
dacarbazine and Stanford V in older Hodgkin lymphoma patients: a
comprehensive analysis from the North American intergroup trial E2496
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE Hodgkin lymphoma; elderly; treatment-related toxicity; bleomycin lung
toxicity
ID EPSTEIN-BARR-VIRUS; LONG-TERM SURVIVAL; ELDERLY-PATIENTS; DISEASE
PATIENTS; POPULATION; CHEMOTHERAPY; TOXICITY; INTENSITY; PROGNOSIS;
OUTCOMES
AB There is a lack of contemporary prospective data examining the adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged60years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% vs. 0 center dot 3% for patients aged <60years (P<0 center dot 001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs. 74%, respectively, P=0 center dot 002; 5-year overall survival: 58% and 90%, respectively, P<0 center dot 0001), although time-to-progression (TTP) was not significantly different (5-year TTP: 68% vs. 78%, respectively, P=0 center dot 37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5years: 30% and 23%, respectively, P=0 center dot 30); however, the incidence of death without progression was significantly increased for older HL patients (22% vs. 9%, respectively, P<0 center dot 0001). Altogether, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events.
C1 [Evens, Andrew M.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
[Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Gordon, Leo I.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Fisher, Richard I.] Univ Rochester, Rochester, NY USA.
[Bartlett, Nancy L.] Washington Univ, St Louis, MO USA.
[Connors, Joseph M.; Gascoyne, Randy D.] BC Canc Agcy Ctr Lymphoid Canc, Vancouver, BC, Canada.
[Wagner, Henry] Penn State Canc Inst, Hershey, PA USA.
[Gospodarowicz, Mary] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Cheson, Bruce D.] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Stiff, Patrick J.] Loyola Univ, Chicago, IL 60611 USA.
[Advani, Ranjana; Hoppe, Richard T.] Univ Arizona, Tucson, AZ USA.
[Miller, Thomas P.] Stanford Univ, Palo Alto, CA 94304 USA.
[Kahl, Brad S.] Univ Wisconsin, Madison, WI USA.
[Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA.
RP Evens, AM (reprint author), Univ Massachusetts, Sch Med, Div Hematol Oncol, 55 Lake Ave North, Worcester, MA 01655 USA.
EM andrew.evens@umassmed.edu
OI Gordon, Leo/0000-0003-1666-7064
FU Public Health Service Grant from the National Cancer Institute, National
Institutes of Health and the Department of Health and Human Services
[CA21115, CA23318, CA66636, CA17145, CA77440, CA11083, CA32102, CA46441,
CA46282, CA38926, CA77202, CA21076, CA31946, CA13650]
FX E2496 was coordinated by the Eastern Cooperative Oncology Group (Robert
L. Comis, M.D., Chair) and supported in part by Public Health Service
Grants CA21115, CA23318, CA66636, CA17145, CA77440, CA11083, CA32102,
CA46441, CA46282, CA38926, CA77202, CA21076, CA31946, CA13650 and from
the National Cancer Institute, 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. This study was listed
on clinicaltrials.gov as NCT00003389.
NR 29
TC 29
Z9 30
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD APR
PY 2013
VL 161
IS 1
BP 76
EP 86
DI 10.1111/bjh.12222
PG 11
WC Hematology
SC Hematology
GA 108YW
UT WOS:000316333300009
PM 23356491
ER
PT J
AU Etchin, J
Sanda, T
Mansour, MR
Kentsis, A
Montero, J
Le, BT
Christie, AL
McCauley, D
Rodig, SJ
Kauffman, M
Shacham, S
Stone, R
Letai, A
Kung, AL
Look, AT
AF Etchin, Julia
Sanda, Takaomi
Mansour, Marc R.
Kentsis, Alex
Montero, Joan
Le, Bonnie T.
Christie, Amanda L.
McCauley, Dilara
Rodig, Scott J.
Kauffman, Michael
Shacham, Sharon
Stone, Richard
Letai, Anthony
Kung, Andrew L.
Look, A. Thomas
TI KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective
anti-leukaemic activity in preclinical models of T-cell acute
lymphoblastic leukaemia and acute myeloid leukaemia
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE Acute leukaemia; all; aml; new drugs for leukaemia; new drugs for
lymphoma
ID NUCLEOCYTOPLASMIC TRANSPORT; IN-VIVO; CANCER; EXPRESSION; SIGNALS;
RESTORATION; RESISTANCE; MUTATIONS; PROGNOSIS; PROTEINS
AB This study explored the anti-leukaemic efficacy of novel irreversible inhibitors of the major nuclear export receptor, chromosome region maintenance 1 (CRM1, also termed XPO1). We found that these novel CRM1 antagonists, termed SINE (Selective Inhibitors of Nuclear Export), induced rapid apoptosis at low nanomolar concentrations in a panel of 14 human T-cell acute lymphoblastic leukaemia (T-ALL) cell lines representing different molecular subtypes of the disease. To assess in vivo anti-leukaemia cell activity, we engrafted immunodeficient mice intravenously with the human T-ALL MOLT-4 cells, which harbour activating mutations of NOTCH1 and NRAS as well as loss of function of the CDKN2A, PTEN and TP53 tumour suppressors and express a high level of oncogenic transcription factor TAL1. Importantly, we examined the in vivo anti-leukaemic efficacy of the clinical SINE compound KPT-330 against T-ALL and acute myeloid leukaemia (AML) cells. These studies demonstrated striking in vivo activity of KPT-330 against T-ALL and AML cells, with little toxicity to normal murine haematopoietic cells. Taken together, our results show that SINE CRM1 antagonists represent promising first-in-class' drugs with a novel mechanism of action and wide therapeutic index, and imply that drugs of this class show promise for the targeted therapy of T-ALL and AML.
C1 [Etchin, Julia; Sanda, Takaomi; Mansour, Marc R.; Kentsis, Alex; Le, Bonnie T.; Christie, Amanda L.; Rodig, Scott J.; Kung, Andrew L.; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Etchin, Julia; Sanda, Takaomi; Mansour, Marc R.; Kentsis, Alex; Le, Bonnie T.; Christie, Amanda L.; Rodig, Scott J.; Kung, Andrew L.; Look, A. Thomas] Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp Boston, Boston, MA USA.
[Montero, Joan; Stone, Richard; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Montero, Joan; Stone, Richard; Letai, Anthony] Harvard Univ, Sch Med, Boston, MA USA.
[McCauley, Dilara; Kauffman, Michael; Shacham, Sharon] Karyopharm Therapeut, Natick, MA USA.
RP Look, AT (reprint author), Dana Farber Canc Inst, Mayer Bldg,Rm 630,450 Brookline Ave, Boston, MA 02215 USA.
EM thomas_look@dfci.harvard.edu
OI Kentsis, Alex/0000-0002-8063-9191; Kung, Andrew/0000-0002-9091-488X
FU William Lawrence and Hughes Blanche Foundation; Karyopharm Therapeutics
Incorporated; Alex's Lemonade Stand; Leukemia and Lymphoma Society;
National Cancer Institute [1K99CA157951]; Children's Leukemia Research
Association; Japan Society for the Promotion of Science; Kay Kendall
Leukaemia Fund, UK; [NIH-K08CA160660]
FX The research was supported by William Lawrence and Hughes Blanche
Foundation (J.E. and T. S.), Karyopharm Therapeutics Incorporated,
Alex's Lemonade Stand (J.E.), the Leukemia and Lymphoma Society
Translational grant (A. T. L.), National Cancer Institute (1K99CA157951;
T. S.), the Children's Leukemia Research Association (T.S.) and the
Japan Society for the Promotion of Science (T.S.), the Kay Kendall
Leukaemia Fund, UK (M.R.M.), and NIH-K08CA160660 (A.K.).
NR 42
TC 72
Z9 72
U1 2
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD APR
PY 2013
VL 161
IS 1
BP 117
EP 127
DI 10.1111/bjh.12231
PG 11
WC Hematology
SC Hematology
GA 108YW
UT WOS:000316333300013
PM 23373539
ER
PT J
AU Englander, M
Chen, TC
Paschalis, EI
Miller, JW
Kim, IK
AF Englander, Miriam
Chen, Teresa C.
Paschalis, Eleftherios I.
Miller, Joan W.
Kim, Ivana K.
TI Intravitreal injections at the Massachusetts Eye and Ear Infirmary:
analysis of treatment indications and postinjection endophthalmitis
rates
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID TRIAMCINOLONE ACETONIDE INJECTION; GROWTH-FACTOR THERAPY; MACULAR
DEGENERATION; NONINFECTIOUS ENDOPHTHALMITIS; RANIBIZUMAB; SAFETY;
ANTIBIOTICS; AGENTS; TRIAL; RISK
AB Aim To report the incidence rate of acute postoperative endophthalmitis secondary to therapeutic intravitreal injections.
Methods A retrospective review of all consecutive eyes after intravitreal injections was performed at the Massachusetts Eye and Ear Infirmary, Boston, from 1 January 2007 to 31 December 2011.
Results During the 5-year study interval, 10 208 intravitreal injections were performed. The overall incidence rate of endophthalmitis was 0.029% per injection (3 of 10 208 injections). In the three cases, in our series, the endophthalmitis occurred at an average of seven injections, which lies within the SD of the mean number of injections received by each eye in this study, suggesting approximately equal probability of infection for each eye after receiving multiple, sequential injections. Bacterial cultures and Gram stain revealed coagulase-negative Staphylococcus species (n=1), moderate bacteria with negative culture (n=1) and moderate Staphylococcus epidermidis (n=1). All cases were successfully treated using either intravitreal antibiotics and steroids or pars plana vitrectomy. Best-corrected visual acuity reduction was not clinically significant at the last visit (>7 months for all cases).
Conclusions Acute endophthalmitis is a rare potential complication after intravitreal injection. Further studies are required to elucidate the best prophylactic and aseptic techniques to prevent this rare complication.
C1 [Englander, Miriam; Chen, Teresa C.; Paschalis, Eleftherios I.; Miller, Joan W.; Kim, Ivana K.] Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA.
RP Englander, M (reprint author), Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA.
EM englander.miri@gmail.com
OI Paschalis, Eleftherios/0000-0002-4544-4452
NR 25
TC 14
Z9 15
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD APR
PY 2013
VL 97
IS 4
BP 460
EP 465
DI 10.1136/bjophthalmol-2012-302435
PG 6
WC Ophthalmology
SC Ophthalmology
GA 107ZM
UT WOS:000316259900018
PM 23390167
ER
PT J
AU Suhler, EB
Lowder, CY
Goldstein, DA
Giles, T
Lauer, AK
Kurz, PA
Pasadhika, S
Lee, ST
de Saint Sardos, A
Butler, NJ
Tessler, HH
Smith, JR
Rosenbaum, JT
AF Suhler, Eric B.
Lowder, Careen Y.
Goldstein, Debra A.
Giles, Tracy
Lauer, Andreas K.
Kurz, Paul A.
Pasadhika, Sirichai
Lee, Shelly T.
de Saint Sardos, Alexandre
Butler, Nicholas J.
Tessler, Howard H.
Smith, Justine R.
Rosenbaum, James T.
TI Adalimumab therapy for refractory uveitis: results of a multicentre,
open-label, prospective trial
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; ANTERIOR UVEITIS; INFLIXIMAB THERAPY; PREVALENCE;
CHILDHOOD; EFFICACY; DISEASES
AB Objective Tumour necrosis factor (TNF) blockers have been demonstrated to be effective in the treatment of systemic and ocular inflammatory diseases. We conducted a prospective, multicentre, open-label Phase II clinical trial to assess the effectiveness and safety of adalimumab, a fully human anti-TNF monoclonal antibody, in treating refractory uveitis.
Methods Subjects with non-infectious uveitis refractory to corticosteroids and at least one other immunosuppressive medication were enrolled. Treatment outcome was ascertained by a composite endpoint comprised of visual acuity, intraocular inflammation, ability to taper immunosuppressives, and posterior segment imaging. Clinical response was defined by improvement in at least one parameter, worsening in none, and well controlled intraocular inflammation. Week 10 responders were permitted to continue receiving adalimumab for the study duration of 50 weeks.
Results Twenty-one of 31 patients (68%) were characterised as clinical responders at 10 weeks, of whom 12 patients (39%) exhibited durable response after 50 weeks. The most common reason for study termination was primary or secondary inefficacy. No patients experienced treatment-limiting toxicity clearly related to study therapy.
Conclusions Adalimumab was safe and effective in 68% of refractory uveitis patients 10 weeks after study enrolment, and maintained in 39% after 1 year. Ongoing study is required to determine the place of adalimumab and other TNF blockers in the treatment of uveitis.
C1 [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Suhler, Eric B.; Giles, Tracy; Lauer, Andreas K.; Kurz, Paul A.; Pasadhika, Sirichai; Lee, Shelly T.; de Saint Sardos, Alexandre; Butler, Nicholas J.; Smith, Justine R.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97239 USA.
[Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
[Lowder, Careen Y.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
[Goldstein, Debra A.; Tessler, Howard H.] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA.
[Tessler, Howard H.] Northwestern Univ, Dept Ophthalmol, Chicago, IL 60611 USA.
[Smith, Justine R.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Depatment Cell Biol, Portland, OR 97239 USA.
[Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA.
[Rosenbaum, James T.] Devers Eye Inst, Portland, OR USA.
RP Suhler, EB (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97239 USA.
EM suhlere@ohsu.edu
FU Abbott (Chicago, IL) [HUM05-029]; Department of Veterans' Affairs;
Research to Prevent Blindness; University of Illinois-Chicago; Rosenfeld
Family Trust; William and Mary Bauman Foundation; William C Kuzell
Foundation; Abbott; Bristol-Myers-Squibb; EyeGate; Genentech; LuxBio;
Novartis
FX This work was supported by Abbott (Chicago, IL) protocol number
HUM05-029. Research support was provided by the Department of Veterans'
Affairs (EBS), Research to Prevent Blindness (unrestricted grant to
Casey Eye Institute and University of Illinois-Chicago, Senior Scholar
Award to JTR), the Rosenfeld Family Trust (JTR), the William and Mary
Bauman Foundation, and the William C Kuzell Foundation. Dr Suhler has
served as a paid consultant to LuxBio. Dr Rosenbaum has served as a paid
consultant to Amgen, LuxBio, Xoma, Centocor, Genentech, Pfizer and
Abbott. Dr Suhler, Dr Rosenbaum and Ms Giles have received research
support from Abbott, Bristol-Myers-Squibb, EyeGate, Genentech, LuxBio
and Novartis. Dr Goldstein has served as a paid consultant to Bausch and
Lomb, Allergan, GSK, Santen, LuxBio, and serves on an IDMC for Abbott.
Dr Lowder serves on an advisory board for Allergan. Authorship is based
on (1) substantial contributions to conception and design, acquisition
of data, or analysis and interpretation of data; (2) drafting the
article or revising it critically for important intellectual content;
and (3) final approval of the version to be published.
NR 30
TC 28
Z9 29
U1 0
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD APR
PY 2013
VL 97
IS 4
BP 481
EP 486
DI 10.1136/bjophthalmol-2012-302292
PG 6
WC Ophthalmology
SC Ophthalmology
GA 107ZM
UT WOS:000316259900022
PM 23376607
ER
PT J
AU Nagler, EM
Viswanath, K
Ebbeling, CB
Stoddard, AM
Sorensen, G
AF Nagler, Eve M.
Viswanath, K.
Ebbeling, Cara B.
Stoddard, Anne M.
Sorensen, Glorian
TI Correlates of fruit and vegetable consumption among construction
laborers and motor freight workers
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Fruit and vegetable consumption; Blue-collar workers; Work-related
health factors; Intervention development; Cancer prevention
ID CANCER PREVENTION; PHYSICAL-ACTIVITY; TRUCK DRIVERS; UNITED-STATES; FOOD
CHOICES; SOCIAL-CONTEXT; LORRY DRIVERS; HEART-DISEASE; TOBACCO USE; RISK
AB The aim of this study was to compare and contrast correlates of fruit and vegetable consumption in two blue-collar populations: construction laborers and motor freight workers.
Cross-sectional data were collected from two groups of male workers: (1) construction laborers (n = 1,013; response rate = 44 %) randomly selected from a national sample, as part of a diet and smoking cessation study; and (2) motor freight workers (n = 542; response rate = 78 %) employed in eight trucking terminals, as part of a tobacco cessation and weight management study. Data were analyzed using linear regression modeling methods.
For both groups, higher income and believing it was important to eat right because of work were positively associated with fruit and vegetable consumption; conversely, being white was associated with lower intake. Construction laborers who reported eating junk food due to workplace stress and fatigue had lower fruit and vegetable intake. For motor freight workers, perceiving fast food to be the only choice at work and lack of time to eat right were associated with lower consumption.
Comparing occupational groups illustrates how work experiences may be related to fruit and vegetable consumption in different ways as well as facilitates the development of interventions that can be used across groups.
C1 [Nagler, Eve M.; Viswanath, K.; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Viswanath, K.; Sorensen, Glorian] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02115 USA.
[Ebbeling, Cara B.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Stoddard, Anne M.] New England Res Inst, Watertown, MA 02472 USA.
RP Nagler, EM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 450 Brookline Ave,LW722, Boston, MA 02115 USA.
EM eve_nagler@dfci.harvard.edu
FU Centers for Disease Control and Prevention [5 R01 DP000099-03]; National
Institutes of Health [2 R25 CA057713-06, R01 CA 84387-04, 5 K05
CA108663-05]
FX The authors wish to thank the members of the Laborers' International
Union, the Laborers' Health and Safety Fund of North America, the
International Brotherhood of Teamsters, and the Motor Freight Carriers
Association for their support of and contributions to this study. The
authors also wish to thank the numerous investigators and staff members
who contributed to this study, including Elizabeth Barbeau, Josh Gagne,
Elizabeth Harden, Kerry Kokkinogenis, Ruth Lederman, Lesley Pereira,
Laura Shulman, and Lorraine Wallace. This work was supported by the
Centers for Disease Control and Prevention [grant number 5 R01
DP000099-03 to G. S.], and National Institutes of Health [grant number 2
R25 CA057713-06 to G. S., R01 CA 84387-04 to G. S. and 5 K05 CA108663-05
to G.S.].
NR 53
TC 6
Z9 6
U1 1
U2 14
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD APR
PY 2013
VL 24
IS 4
BP 637
EP 647
DI 10.1007/s10552-012-9998-6
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 109FX
UT WOS:000316352900003
PM 22729935
ER
PT J
AU Patterson, RE
Colditz, GA
Hu, FB
Schmitz, KH
Ahima, RS
Brownson, RC
Carson, KR
Chavarro, JE
Chodosh, LA
Gehlert, S
Gill, J
Glanz, K
Haire-Joshu, D
Herbst, KL
Hoehner, CM
Hovmand, PS
Irwin, ML
Jacobs, LA
James, AS
Jones, LW
Kerr, J
Kibel, AS
King, IB
Ligibel, JA
Meyerhardt, JA
Natarajan, L
Neuhouser, ML
Olefsky, JM
Proctor, EK
Redline, S
Rock, CL
Rosner, B
Sarwer, DB
Schwartz, JS
Sears, DD
Sesso, HD
Stampfer, MJ
Subramanian, SV
Taveras, EM
Tchou, J
Thompson, B
Troxel, AB
Wessling-Resnick, M
Wolin, KY
Thornquist, MD
AF Patterson, Ruth E.
Colditz, Graham A.
Hu, Frank B.
Schmitz, Kathryn H.
Ahima, Rexford S.
Brownson, Ross C.
Carson, Kenneth R.
Chavarro, Jorge E.
Chodosh, Lewis A.
Gehlert, Sarah
Gill, Jeff
Glanz, Karen
Haire-Joshu, Debra
Herbst, Karen Louise
Hoehner, Christine M.
Hovmand, Peter S.
Irwin, Melinda L.
Jacobs, Linda A.
James, Aimee S.
Jones, Lee W.
Kerr, Jacqueline
Kibel, Adam S.
King, Irena B.
Ligibel, Jennifer A.
Meyerhardt, Jeffrey A.
Natarajan, Loki
Neuhouser, Marian L.
Olefsky, Jerrold M.
Proctor, Enola K.
Redline, Susan
Rock, Cheryl L.
Rosner, Bernard
Sarwer, David B.
Schwartz, J. Sanford
Sears, Dorothy D.
Sesso, Howard D.
Stampfer, Meir J.
Subramanian, S. V.
Taveras, Elsie M.
Tchou, Julia
Thompson, Beti
Troxel, Andrea B.
Wessling-Resnick, Marianne
Wolin, Kathleen Y.
Thornquist, Mark D.
TI The 2011-2016 Transdisciplinary Research on Energetics and Cancer (TREC)
Initiative: Rationale and Design
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Energetics; Obesity; Diet; Physical activity; Cancer; Transdisciplinary
ID PHYSICAL-ACTIVITY; EPIDEMIOLOGIC EVIDENCE; TEAM SCIENCE;
CONTROLLED-TRIAL; CLINICAL-TRIAL; EXERCISE; OBESITY; WOMEN; RISK; BREAST
AB Recognition of the complex, multidimensional relationship between excess adiposity and cancer control outcomes has motivated the scientific community to seek new research models and paradigms.
The National Cancer Institute developed an innovative concept to establish a center grant mechanism in nutrition, energetics, and physical activity, referred to as the Transdisciplinary Research on Energetics and Cancer (TREC) Initiative. This paper gives an overview of the 2011-2016 TREC Collaborative Network and the 15 research projects being conducted at the centers.
Four academic institutions were awarded TREC center grants in 2011: Harvard University, University of California San Diego, University of Pennsylvania, and Washington University in St. Louis. The Fred Hutchinson Cancer Research Center is the Coordination Center. The TREC research portfolio includes three animal studies, three cohort studies, four randomized clinical trials, one cross-sectional study, and two modeling studies. Disciplines represented by TREC investigators include basic science, endocrinology, epidemiology, biostatistics, behavior, medicine, nutrition, physical activity, genetics, engineering, health economics, and computer science. Approximately 41,000 participants will be involved in these studies, including children, healthy adults, and breast and prostate cancer survivors. Outcomes include biomarkers of cancer risk, changes in weight and physical activity, persistent adverse treatment effects (e.g., lymphedema, urinary and sexual function), and breast and prostate cancer mortality.
The NIH Science of Team Science group will evaluate the value added by this collaborative science. However, the most important outcome will be whether this transdisciplinary initiative improves the health of Americans at risk of cancer as well as cancer survivors.
C1 [Patterson, Ruth E.; Herbst, Karen Louise; Kerr, Jacqueline; Natarajan, Loki; Olefsky, Jerrold M.; Rock, Cheryl L.; Sears, Dorothy D.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Colditz, Graham A.; Brownson, Ross C.; Carson, Kenneth R.; Gehlert, Sarah; Gill, Jeff; Haire-Joshu, Debra; Hoehner, Christine M.; Hovmand, Peter S.; James, Aimee S.; Proctor, Enola K.; Wolin, Kathleen Y.] Washington Univ, St Louis, MO USA.
[Hu, Frank B.; Chavarro, Jorge E.; Kibel, Adam S.; Stampfer, Meir J.; Subramanian, S. V.; Wessling-Resnick, Marianne] Harvard Univ, Boston, MA 02115 USA.
[Schmitz, Kathryn H.; Ahima, Rexford S.; Chodosh, Lewis A.; Glanz, Karen; Jacobs, Linda A.; Sarwer, David B.; Schwartz, J. Sanford; Tchou, Julia; Troxel, Andrea B.] Univ Penn, Philadelphia, PA 19104 USA.
[Irwin, Melinda L.] Yale Univ, New Haven, CT USA.
[Jones, Lee W.] Duke Canc Inst, Durham, NC USA.
[King, Irena B.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Ligibel, Jennifer A.; Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Boston, MA USA.
[Neuhouser, Marian L.; Thompson, Beti; Thornquist, Mark D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Redline, Susan; Sesso, Howard D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rosner, Bernard] Channing Labs, Boston, MA USA.
[Taveras, Elsie M.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
RP Thornquist, MD (reprint author), Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
EM mthornqu@fhcrc.org
RI Colditz, Graham/A-3963-2009;
OI Colditz, Graham/0000-0002-7307-0291; James, Aimee/0000-0002-1411-9307;
Troxel, Andrea/0000-0002-1393-3075
FU National Cancer Institute Centers for Transdisciplinary Research on
Energetics and Cancer (TREC) [U01 CA116850, U54 CA155626, U54 CA155435,
U54 CA155850, U54 CA155496]; NCI as part of the TREC Initiative
FX This work was supported by the National Cancer Institute Centers for
Transdisciplinary Research on Energetics and Cancer (TREC) (U01
CA116850, U54 CA155626, U54 CA155435, U54 CA155850, U54 CA155496). All
authors were funded by the NCI as part of the TREC Initiative. The
opinions or assertions contained herein are the private ones of the
authors and are not considered as official or reflecting the views of
the National Institutes of Health. Thanks are expressed to all the
co-principal investigators, investigators, and co-investigators who are
contributing to the study, and also to key staff at each site: TREC
Coordination Center: Carolyn C. Ehret and Gina Widell. Harvard
University: Vanessa Boulanger, Nancy Campbell, Amy Lane, Laura Shockro,
Miranda West, and Devin Wigler. University of California, San Diego:
Lisa A. Cadmus-Bertram, Lesley G. Ellies, Shirley W. Flatt, Suneeta
Godbole, Simon J. Marshall, Jessica L. Oratowski Coleman, Bilge Pakiz,
Brinda K. Rana, and Nicholas J. Webster. University of Pennsylvania:
Renata Alford, Justin Brown, Laura DiGiovanni, Rebecca Dilks, Deborah
Dole, Margaret Evangelista, Anagha Kumar, Venetia Lambert, Monica
Laudermilk, and Zi Zhang. Washington University in St. Louis: Victoria
Anwuri, Casey Fagin, Robert Grubb III, Jennifer Haslag-Minoff, Timothy
Hower, Christine Marx, Qiang Wang, and Jessica Wu. Finally, the TREC
Initiative is thankful to all the study participants whose involvement
is critical to curing cancer!
NR 39
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U1 2
U2 28
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD APR
PY 2013
VL 24
IS 4
BP 695
EP 704
DI 10.1007/s10552-013-0150-z
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 109FX
UT WOS:000316352900008
PM 23378138
ER
PT J
AU Je, Y
Lee, JE
Ma, J
Zhang, XH
Cho, E
Rosner, B
Selhub, J
Fuchs, CS
Meyerhardt, J
Giovannucci, E
AF Je, Youjin
Lee, Jung Eun
Ma, Jing
Zhang, Xuehong
Cho, Eunyoung
Rosner, Bernard
Selhub, Jacob
Fuchs, Charles S.
Meyerhardt, Jeffrey
Giovannucci, Edward
TI Prediagnostic plasma vitamin B6 (pyridoxal 5 '-phosphate) and survival
in patients with colorectal cancer
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Vitamin B6; Pyridoxal 5 ' phosphate (PLP); Colorectal cancer; Mortality;
Survival; Prospective study
ID NATIONAL DEATH INDEX; THYMIDYLATE SYNTHASE; COLON TUMORIGENESIS;
CELL-PROLIFERATION; REGRESSION-MODELS; NURSES HEALTH; RISK; FOLATE;
INHIBITION; ASSAY
AB Higher plasma pyridoxal 5'-phosphate (PLP) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma PLP on survival of patients with colorectal cancer is unknown. We prospectively examined whether prediagnostic plasma PLP levels are associated with mortality among colorectal cancer patients.
We included 472 incident cases of colorectal cancer identified in the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physicians' Health Study from 1984 to 2002. The patients provided blood samples two or more years before cancer diagnosis. Stratified Cox proportional hazards models were used to calculate hazard ratios (HR) with 95 % confidence intervals (CI) adjusted for other risk factors for cancer survival.
Higher plasma PLP levels were not associated with a significant reduction in colorectal cancer-specific (169 deaths) or overall mortality (259 deaths). Compared with patients who had less than 45 pmol/ml of plasma PLP (median: 33.6 pmol/ml), those who had 110 pmol/ml or higher levels (median: 158.8 pmol/ml) had multivariable HRs of 0.85 (95 % CI 0.50-1.45, p trend = 0.37) and 0.87 (95 % CI 0.56-1.35, p trend = 0.24) for colorectal cancer-specific and overall mortality. Higher plasma PLP levels, however, seemed to be associated with better survival among patients who had lower circulating 25-hydroxyvitamin D-3 levels (< 26.5 ng/ml) (p interaction a parts per thousand currency sign.005).
Higher prediagnostic plasma PLP levels were not associated with an improvement on colorectal cancer survival overall. Further research is needed to clarify the influence of vitamin B6 on colorectal cancer progression and survival.
C1 [Je, Youjin] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea.
[Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea.
[Ma, Jing; Zhang, Xuehong; Cho, Eunyoung; Rosner, Bernard; Fuchs, Charles S.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Selhub, Jacob] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA.
[Fuchs, Charles S.; Meyerhardt, Jeffrey] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA.
RP Giovannucci, E (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM edward.giovannucci@channing.harvard.edu
OI Lee, Jung Eun/0000-0003-1141-878X
FU American Institute of Cancer Research; NIH [CA87969, CA55075]
FX We are indebted to the participants and staffs in the Nurses' Health
Study, Health Professionals Follow-up Study, and Physicians' Health
Study for their dedication and commitment. This work was supported by a
grant from American Institute of Cancer Research and the NIH grants
CA87969 and CA55075.
NR 45
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD APR
PY 2013
VL 24
IS 4
BP 719
EP 729
DI 10.1007/s10552-013-0152-x
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 109FX
UT WOS:000316352900010
PM 23340905
ER
PT J
AU Sorensen, G
Allen, JD
Adamkiewicz, G
Yang, M
Tamers, SL
Stoddard, AM
AF Sorensen, Glorian
Allen, Jennifer D.
Adamkiewicz, Gary
Yang, May
Tamers, Sara L.
Stoddard, Anne M.
TI Intention to quit smoking and concerns about household environmental
risks: findings from the Health in Common Study in low-income housing
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Smoking; Tobacco use; Household hazards; Environmental toxins; Low
income
ID INNER-CITY CHILDREN; TRANSTHEORETICAL MODEL; SOCIOECONOMIC-STATUS;
CANCER PREVENTION; PUBLIC-HEALTH; UNITED-STATES; DISPARITIES;
PERCEPTION; ADULTS; VULNERABILITY
AB To assess the association between intention to quit smoking and perceptions of household environmental risks among racially/ethnically diverse residents of low-income housing.
Baseline data were collected from 2007 to 2009 for the Health in Common Study, which assessed social and physical determinants of cancer risk-related behaviors among residents of 20 low-income housing developments in the Greater Boston metropolitan area. Participants were surveyed about their tobacco use and concerns about household exposures. Household environmental inspections were also conducted to identify conditions associated with increased risk of exposure to indoor environmental agents, including pesticides, mold, and cleaning products.
Intention to quit smoking was associated with a greater degree of concern about exposures in the home, yet not with the actual presence of household hazards, as identified by home inspections and survey findings.
An ecological approach targeting multiple levels of influence may help to highlight the importance of both quitting tobacco and reducing potential household environmental exposures as part of comprehensive efforts to promote individual and household health.
C1 [Sorensen, Glorian; Allen, Jennifer D.; Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Sorensen, Glorian; Tamers, Sara L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA.
[Adamkiewicz, Gary] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Yang, May; Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA.
RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
EM glorian_sorensen@dfci.harvard.edu
RI Allen, Jennifer/M-2113-2015
FU National Cancer Institute [R01 CA111310-01A1, K05 CA108663-05]
FX This research was supported by the National Cancer Institute, (grant
numbers R01 CA111310-01A1; K05 CA108663-05). The authors would like to
thank the 20 low-income housing sites that participated in this
research, and the assistance from the Cambridge, Somerville, and Chelsea
Public Housing Authorities. The authors also acknowledge the
administrative and field staff at the Harvard School of Public Health
and Dana-Farber Cancer Institute, and the study participants for their
contributions to this project. They also thank Marty Alvarez-Reeves,
Linnea Benson-Whelan, Caitlin Caspi, Amy Harley, Ruth Lederman, Samuel
Lipson, Carol Lowenstein, Reginald Tucker-Seeley, Brianna Wadler and
Lorraine Wallace for their contributions to the overall study design and
implementation. The authors declare they have no competing financial
interests.
NR 43
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Z9 5
U1 2
U2 19
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD APR
PY 2013
VL 24
IS 4
BP 805
EP 811
DI 10.1007/s10552-013-0149-5
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 109FX
UT WOS:000316352900019
PM 23334887
ER
PT J
AU Torii, M
Hackett, TA
Rakic, P
Levitt, P
Polley, DB
AF Torii, Masaaki
Hackett, Troy A.
Rakic, Pasko
Levitt, Pat
Polley, Daniel B.
TI EphA Signaling Impacts Development of Topographic Connectivity in
Auditory Corticofugal Systems
SO CEREBRAL CORTEX
LA English
DT Article
DE axon guidance; corticofugal; Eph; feedback; top-down
ID MEDIAL GENICULATE-BODY; VESICULAR GLUTAMATE TRANSPORTERS;
STIMULUS-SPECIFIC ADAPTATION; BRAIN-STEM; EPHRIN-AS; IMMUNOCYTOCHEMICAL
LOCALIZATION; CORTICOTHALAMIC CONNECTIONS; STRUCTURED ACTIVITY;
FUNCTIONAL MAPS; GENE-EXPRESSION
AB Auditory stimulus representations are dynamically maintained by ascending and descending projections linking the auditory cortex (Actx), medial geniculate body (MGB), and inferior colliculus. Although the extent and topographic specificity of descending auditory corticofugal projections can equal or surpass that of ascending corticopetal projections, little is known about the molecular mechanisms that guide their development. Here, we used in utero gene electroporation to examine the role of EphA receptor signaling in the development of corticothalamic (CT) and corticocollicular connections. Early in postnatal development, CT axons were restricted to a deep dorsal zone (DDZ) within the MGB that expressed low levels of the ephrin-A ligand. By hearing onset, CT axons had innervated surrounding regions of MGB in control-electroporated mice but remained fixed within the DDZ in mice overexpressing EphA7. In vivo neurophysiological recordings demonstrated a corresponding reduction in spontaneous firing rate, but no changes in sound-evoked responsiveness within MGB regions deprived of CT innervation. Structural and functional CT disruption occurred without gross alterations in thalamocortical connectivity. These data demonstrate a potential role for EphA/ephrin-A signaling in the initial guidance of corticofugal axons and suggest that "genetic rewiring" may represent a useful functional tool to alter cortical feedback without silencing Actx.
C1 [Torii, Masaaki; Rakic, Pasko] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
[Torii, Masaaki; Rakic, Pasko] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA.
[Torii, Masaaki; Levitt, Pat] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
[Torii, Masaaki; Levitt, Pat] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA.
[Hackett, Troy A.] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Sch Med, Dept Hearing & Speech Sci, Nashville, TN 37232 USA.
[Polley, Daniel B.] Harvard Univ, Sch Med, Eaton Peabody Lab, Massachusetts Eye & Ear Infirm,Dept Otol & Laryng, Boston, MA 02114 USA.
RP Torii, M (reprint author), Yale Univ, Sch Med, Dept Neurobiol, Kavli Inst Neurosci, 333 Cedar St SHM C316, New Haven, CT 06510 USA.
EM masaaki.torii@yale.edu
FU National Institutes of Health [DC009488, DC009836, DC04318, NS014841,
DA022785]; NARSAD; Kavli Institute for Neuroscience at Yale
FX National Institutes of Health (grant DC009488 and DC009836 to D. B. P.,
DC04318 to T. A. H., NS014841 to P. R., and DA022785 to P. L.); NARSAD
Young Investigator Award (to M. T.); and Kavli Institute for
Neuroscience at Yale (to M.T. and P.R.).
NR 75
TC 11
Z9 11
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD APR
PY 2013
VL 23
IS 4
BP 775
EP 785
DI 10.1093/cercor/bhs066
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 108EY
UT WOS:000316275800003
PM 22490549
ER
PT J
AU Napadow, V
Sheehan, JD
Kim, J
LaCount, LT
Park, K
Kaptchuk, TJ
Rosen, BR
Kuo, B
AF Napadow, Vitaly
Sheehan, James D.
Kim, Jieun
LaCount, Lauren T.
Park, Kyungmo
Kaptchuk, Ted J.
Rosen, Bruce R.
Kuo, Braden
TI The Brain Circuitry Underlying the Temporal Evolution of Nausea in
Humans
SO CEREBRAL CORTEX
LA English
DT Article
DE brain-gut interactions; interoception; motion sickness; neuroimaging
ID MOTION SICKNESS; INTEROCEPTIVE AWARENESS; CORTEX; STIMULATION;
EXPRESSION; PATHWAYS; SALIENCE; SYSTEM; MODEL; FMRI
AB Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus-associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom.
C1 [Napadow, Vitaly; Kim, Jieun; LaCount, Lauren T.; Rosen, Bruce R.] Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Napadow, Vitaly; Kim, Jieun; LaCount, Lauren T.; Rosen, Bruce R.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Sheehan, James D.; Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA.
[Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea.
[Kaptchuk, Ted J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Napadow, V (reprint author), Martinos Ctr Biomed Imaging, 149 13th St 2301, Charlestown, MA 02129 USA.
EM vitaly@nmr.mgh.harvard.edu
FU National Institutes of Health [K01-AT002166, R01-AT004714, P01-AT002048,
F05-AT003770, K23-DK069614, K24-AT004095]; National Center for Research
Resources [P41RR14075, CRC 1 UL1 RR025758]; Mental Illness and
Neuroscience Discovery (MIND) Institute; International Foundation of
Functional Gastrointestinal Disorders; Information Technology
Advancement, Korea [IITA-2008-(C1090-0801-0002)]
FX This work was supported by the National Institutes of Health (grant
numbers K01-AT002166 and R01-AT004714 to V.N., P01-AT002048 to B. R. R.,
F05-AT003770 to K. P., K23-DK069614 to B. K., K24-AT004095 to T. K.);
the National Center for Research Resources (P41RR14075; CRC 1 UL1
RR025758, Harvard Clinical and Translational Science Center); Mental
Illness and Neuroscience Discovery (MIND) Institute; the International
Foundation of Functional Gastrointestinal Disorders; and Information
Technology Advancement, Korea (grant number IITA-2008-(C1090-0801-0002)
to K. P.). The content is solely the responsibility of the authors and
does not necessarily represent the official views of our sponsors.
NR 53
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U1 3
U2 22
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD APR
PY 2013
VL 23
IS 4
BP 806
EP 813
DI 10.1093/cercor/bhs073
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 108EY
UT WOS:000316275800006
PM 22473843
ER
PT J
AU Rosen, GD
Azoulay, NG
Griffin, EG
Newbury, A
Koganti, L
Fujisaki, N
Takahashi, E
Grant, PE
Truong, DT
Fitch, RH
Lu, L
Williams, RW
AF Rosen, G. D.
Azoulay, N. G.
Griffin, E. G.
Newbury, A.
Koganti, L.
Fujisaki, N.
Takahashi, E.
Grant, P. E.
Truong, D. T.
Fitch, R. H.
Lu, L.
Williams, R. W.
TI Bilateral Subcortical Heterotopia with Partial Callosal Agenesis in a
Mouse Mutant
SO CEREBRAL CORTEX
LA English
DT Article
DE diffusion spectrum imaging; neuronal migration; rapid auditory
discrimination; recombinant inbred; stereology
ID NEURONAL MIGRATION DISORDERS; INDUCED CEREBROCORTICAL MICROGYRIA;
AUDITORY PROCESSING DEFICITS; X-LINKED MALFORMATIONS; CEREBRAL-CORTEX;
NODULAR HETEROTOPIA; CORPUS-CALLOSUM; CORTICAL MALFORMATION; BAND
HETEROTOPIA; AUTOIMMUNE MICE
AB Cognition and behavior depend on the precise placement and interconnection of complex ensembles of neurons in cerebral cortex. Mutations that disrupt migration of immature neurons from the ventricular zone to the cortical plate have provided major insight into mechanisms of brain development and disease. We have discovered a new and highly penetrant spontaneous mutation that leads to large nodular bilateral subcortical heterotopias with partial callosal agenesis. The mutant phenotype was first detected in a colony of fully inbred BXD29 mice already known to harbor a mutation in Tlr4. Neurons confined to the heterotopias are mainly born in midgestation to late gestation and would normally have migrated into layers 2-4 of overlying neocortex. Callosal cross-sectional area and fiber number are reduced up to 50% compared with coisogenic wildtype BXD29 substrain controls. Mutants have a pronounced and highly selective defect in rapid auditory processing. The segregation pattern of the mutant phenotype is most consistent with a two-locus autosomal recessive model, and selective genotyping definitively rules out the Tlr4 mutation as a cause. The discovery of a novel mutation with strong pleiotropic anatomical and behavioral effects provides an important new resource for dissecting molecular mechanisms and functional consequences of errors of neuronal migration.
C1 [Rosen, G. D.; Azoulay, N. G.; Griffin, E. G.; Newbury, A.; Koganti, L.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Fujisaki, N.; Takahashi, E.; Grant, P. E.] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
[Fujisaki, N.; Takahashi, E.; Grant, P. E.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Takahashi, E.; Grant, P. E.] Harvard Univ, Div Newborn Med, Childrens Hosp Boston, Dept Med,Med Sch, Boston, MA 02115 USA.
[Takahashi, E.; Grant, P. E.] Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston, MA 02115 USA.
[Grant, P. E.] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Grant, P. E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Truong, D. T.; Fitch, R. H.] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA.
[Lu, L.; Williams, R. W.] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Ctr Integrat & Translat Genom, Memphis, TN 38163 USA.
RP Rosen, GD (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, E CLS 643,330 Brookline Ave, Boston, MA 02215 USA.
EM grosen@bidmc.harvard.edu
OI Azoulay, Norman/0000-0003-1453-4882; Rosen, Glenn/0000-0001-8281-5446;
Williams, Robert/0000-0001-8924-4447
FU National Institute on Drug Abuse; National Institute of Mental Health
[P20 DA021131]; National Institute of Neurological Diseases and Stroke
[R01 NS052397-01A2]; National Eye Institute [R01EY021200]; National
Center for Research Resources [1S10RR023401, 1S10RR019307,
1S10RR023043]; National Institutes of Health
FX The National Institute on Drug Abuse and the National Institute of
Mental Health (grant number P20 DA021131); the National Institute of
Neurological Diseases and Stroke (grant number R01 NS052397-01A2); the
National Eye Institute (grant number R01EY021200), and Shared
Instrumentation Grants from the National Center for Research Resources
(grant numbers 1S10RR023401, 1S10RR019307, and 1S10RR023043), which are
all at the National Institutes of Health.
NR 74
TC 10
Z9 11
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD APR
PY 2013
VL 23
IS 4
BP 859
EP 872
DI 10.1093/cercor/bhs080
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 108EY
UT WOS:000316275800011
PM 22455839
ER
PT J
AU de Villiers, TJ
Gass, MLS
Haines, CJ
Hall, JE
Lobo, RA
Pierroz, DD
Rees, M
AF de Villiers, T. J.
Gass, M. L. S.
Haines, C. J.
Hall, J. E.
Lobo, R. A.
Pierroz, D. D.
Rees, M.
TI Global Consensus Statement on Menopausal Hormone Therapy
SO CLIMACTERIC
LA English
DT Editorial Material
AB The following Consensus Statement is endorsed by The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society.
C1 [de Villiers, T. J.] Univ Stellenbosch, MediClin Panorama, Cape Town, South Africa.
[de Villiers, T. J.] Univ Stellenbosch, Dept Obstet & Gynecol, Cape Town, South Africa.
[Gass, M. L. S.] Case Western Reserve Univ, Sch Med, Dept Surg, Cleveland Clin,Lerner Coll Med, Cleveland, OH 44106 USA.
[Haines, C. J.] Chinese Univ Hong Kong, Dept Obstet & Gynecol, Prince Wales Hosp, Shatin, Hong Kong, Peoples R China.
[Hall, J. E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hall, J. E.] Harvard Univ, Sch Med, Boston, MA USA.
[Lobo, R. A.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Pierroz, D. D.] Univ Geneva, CH-1211 Geneva 4, Switzerland.
[Rees, M.] Univ Oxford, Oxford OX1 2JD, England.
RP de Villiers, TJ (reprint author), MediClin Panorama, ZA-7500 Parow, South Africa.
OI Hall, Janet/0000-0003-4644-3061
NR 0
TC 79
Z9 89
U1 0
U2 11
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1369-7137
J9 CLIMACTERIC
JI Climacteric
PD APR
PY 2013
VL 16
IS 2
BP 203
EP 204
DI 10.3109/13697137.2013.771520
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 107BY
UT WOS:000316190900002
PM 23488524
ER
PT J
AU Goldstein, AM
Hofstra, RMW
Burns, AJ
AF Goldstein, A. M.
Hofstra, R. M. W.
Burns, A. J.
TI Building a brain in the gut: development of the enteric nervous system
SO CLINICAL GENETICS
LA English
DT Review
DE enteric nervous system; Hirschsprung disease; enteric neuropathies;
neural crest cells; RET
ID NEURAL CREST CELLS; ENDOTHELIN-B RECEPTOR;
WAARDENBURG-HIRSCHSPRUNG-DISEASE; MICE LACKING GDNF; SMAD INTERACTING
PROTEIN-1; GENOME-WIDE ASSOCIATION; HOMEOBOX GENE PHOX2B; RET
PROTOONCOGENE; TYROSINE KINASE; IN-VITRO
AB The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is an essential component of the gut neuromusculature and controls many aspects of gut function, including coordinated muscular peristalsis. The ENS is entirely derived from neural crest cells (NCC) which undergo a number of key processes, including extensive migration into and along the gut, proliferation, and differentiation into enteric neurons and glia, during embryogenesis and fetal life. These mechanisms are under the molecular control of numerous signaling pathways, transcription factors, neurotrophic factors and extracellular matrix components. Failure in these processes and consequent abnormal ENS development can result in so-called enteric neuropathies, arguably the best characterized of which is the congenital disorder Hirschsprung disease (HSCR), or aganglionic megacolon. This review focuses on the molecular and genetic factors regulating ENS development from NCC, the clinical genetics of HSCR and its associated syndromes, and recent advances aimed at improving our understanding and treatment of enteric neuropathies.
C1 [Goldstein, A. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA.
[Hofstra, R. M. W.; Burns, A. J.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Burns, A. J.] UCL Inst Child Hlth, Neural Dev Unit, London WC1N 1EH, England.
[Burns, A. J.] UCL Inst Child Hlth, Gastroenterol Unit, London WC1N 1EH, England.
RP Burns, AJ (reprint author), UCL Inst Child Hlth, Neural Dev Unit, 30 Guilford St, London WC1N 1EH, England.
EM alan.burns@ucl.ac.uk
RI Burns, Alan/C-4988-2008;
OI Hofstra, Robert/0000-0001-7498-3829
FU NIH [R01DK080914]
FX A. M. G. is supported by NIH R01DK080914.
NR 114
TC 44
Z9 47
U1 3
U2 58
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD APR
PY 2013
VL 83
IS 4
BP 307
EP 316
DI 10.1111/cge.12054
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 107OD
UT WOS:000316226600002
PM 23167617
ER
PT J
AU Mitsuma, SF
Mansour, MK
Dekker, JP
Kim, J
Rahman, MZ
Tweed-Kent, A
Schuetz, P
AF Mitsuma, S. F.
Mansour, M. K.
Dekker, J. P.
Kim, J.
Rahman, M. Z.
Tweed-Kent, A.
Schuetz, P.
TI Promising New Assays and Technologies for the Diagnosis and Management
of Infectious Diseases
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
DE procalcitonin; gene expression profiling; mass spectrometry; MALDI-TOF
MS; sepsis
ID DESORPTION IONIZATION-TIME; FLIGHT MASS-SPECTROMETRY;
STAPHYLOCOCCUS-AUREUS; DIRECT IDENTIFICATION; ANTIBIOTIC-THERAPY; DNA
APTAMERS; HUMAN SEPSIS; RNA APTAMER; PROCALCITONIN; BACTERIA
AB In the first decade of the 21st century, we have seen the completion of the human genome project and marked progress in the human microbiome project. The vast amount of data generated from these efforts combined with advances in molecular and biomedical technologies have led to the development of a multitude of assays and technologies that may be useful in the diagnosis and management of infectious diseases. Here, we identify several new assays and technologies that have recently come into clinical use or have potential for clinical use in the near future. The scope of this review is broad and includes topics such as the serum marker procalcitonin, gene expression profiling, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and nucleic acid aptamers. Principles that underlie each assay or technology, their clinical applications, and potential strengths and limitations are addressed.
C1 [Mitsuma, S. F.; Mansour, M. K.; Rahman, M. Z.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Dekker, J. P.; Kim, J.] Massachusetts Gen Hosp, Dept Clin Pathol, Boston, MA 02114 USA.
[Tweed-Kent, A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Schuetz, P.] Univ Basel, Kantonsspital Aarau, Dept Internal Med, CH-4003 Basel, Switzerland.
RP Schuetz, P (reprint author), Kantonsspital, Med Univ Dept, Tellstr, CH-5001 Aarau, Switzerland.
EM schuetzph@gmail.com
FU NIAID NIH [T32-AI007061-35]; BRAHMS; bioMerieux
FX M. K. M. is supported by NIAID NIH T32-AI007061-35.; P. S. has received
support from BRAHMS and bioMerieux: to attend meetings and has fulfilled
speaking engagements. All other authors report no potential conflicts.
NR 49
TC 23
Z9 24
U1 4
U2 82
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 APR 1
PY 2013
VL 56
IS 7
BP 996
EP 1002
DI 10.1093/cid/cis1014
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 106TG
UT WOS:000316167000015
PM 23223587
ER
PT J
AU Chen, WT
Yuan, RY
Chiang, SC
Sheu, JJ
Yu, JM
Tseng, IJ
Yang, SK
Chang, HH
Hu, CJ
AF Chen, Wei-Ta
Yuan, Rey-Yue
Chiang, Shu-Chiung
Sheu, Jau-Jiuan
Yu, Jia-Ming
Tseng, Ing-Jy
Yang, Szu-Kuan
Chang, Hsiu-Hui
Hu, Chaur-Jong
TI OnabotulinumtoxinA Improves Tactile and Mechanical Pain Perception in
Painful Diabetic Polyneuropathy
SO CLINICAL JOURNAL OF PAIN
LA English
DT Article
DE onabotulinumtoxinA (BoNT/A); diabetes mellitus; neuropathic pain; pain
threshold; tactile threshold; quantitative sensory testing (QST)
ID TOXIN TYPE-A; LONGITUDINAL DATA-ANALYSIS; NEUROPATHIC PAIN;
BOTULINUM-TOXIN; PERIPHERAL NEUROPATHY; THRESHOLDS; FIBERS
AB Objectives: Diabetic neuropathic pain may be relieved by onabotulinumtoxinA (BoNT/A). However, whether BoNT/A changes sensory perception in neuropathic patients remains unknown. This study used a double-blind crossover design to explore the possible effect of BoNT/A on sensory perception.
Methods: Eighteen patients with painful diabetic polyneuropathy underwent 2 consecutive 12-week periods of treatment either in the sequence of saline (control) and then BoNT/A (SB cohort, n=9) or BoNT/A followed by saline (BS cohort, n=9). Sensory perception was assessed according to the tactile threshold [TT, logarithmized force (g) of von Frey filaments] and mechanical pain threshold [PT, logarithmized weight (g) of weighted syringes], both being averages from 4 individual measurements of bilateral medial and lateral feet obtained at baseline (before injections) and at weeks 1, 4, 8, and 12 after treatment.
Results: In either the SB or the BS cohort, there was a decrease in the TT and the PT after treatment with BoNT/A but not with saline. In the analysis merging both cohorts (n=18), BoNT/A resulted in a significant decrease in TT and PT at weeks 1, 4, 8, and 12 (all Ps<0.05 vs. saline). The longitudinal effect of BoNT/A on TT and PT remained significant when baseline values, treatment sequences, and periods were controlled using generalized estimating equations.
Discussion: BoNT/A may improve tactile and mechanical pain perception in painful diabetic polyneuropathy. The beneficial effects of BoNT/A deserves further study to elucidate the exact mechanism and potential for preventing insensate injuries.
C1 [Chen, Wei-Ta] Natl Yang Ming Univ, Neurol Inst, Taipei 112, Taiwan.
[Chiang, Shu-Chiung] Natl Yang Ming Univ, Taichung Vet Gen Hosp, Informat Management Off, Taipei 112, Taiwan.
[Chen, Wei-Ta] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
[Chen, Wei-Ta; Yuan, Rey-Yue; Sheu, Jau-Jiuan; Yu, Jia-Ming; Hu, Chaur-Jong] Taipei Med Univ & Hosp, Dept Neurol, Taipei, Taiwan.
[Tseng, Ing-Jy] Taipei Med Univ & Hosp, Coll Nursing, Taipei, Taiwan.
[Chang, Hsiu-Hui] Chungyu Inst Technol, Dept Int Trade, Keelung, Taiwan.
[Yang, Szu-Kuan] Chang Bing Show Chwan Mem Hosp, Dept Neurol, Changhua, Taiwan.
[Hu, Chaur-Jong] Taipei Med Univ, Shuang Ho Hosp, Dept Neurol, New Taipei City 235, Taiwan.
[Chen, Wei-Ta] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Hu, CJ (reprint author), Taipei Med Univ, Shuang Ho Hosp, Dept Neurol, 291 Jhongjheng Rd, New Taipei City 235, Taiwan.
EM chaurjongh@tmu.edu.tw
FU National Science Council (Taiwan) [NSC-95-2314-B-075-121, NSC
96-2314-B-075 -073 -MY3, NSC 97-2314-B-038-010-MY2]; Taipei Veterans
General Hospital [V99C1-124]; Taipei Medical University [94TMU-WFH-217]
FX Supported by the National Science Council (Taiwan; NSC-95-2314-B-075-121
and NSC 96-2314-B-075 -073 -MY3 to W-T. C., NSC 97-2314-B-038-010-MY2 to
C-J. H.), Taipei Veterans General Hospital (V99C1-124 to W-T. C.),
Taipei Medical University (94TMU-WFH-217 to C-J. H.). Allergan Asia Ltd.
(Taipei, Taiwan) provided BOTOX (onabotulinumtoxinA). The authors
declare no conflict of interest.
NR 31
TC 7
Z9 7
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0749-8047
J9 CLIN J PAIN
JI Clin. J. Pain
PD APR
PY 2013
VL 29
IS 4
BP 305
EP 310
DI 10.1097/AJP.0b013e318255c132
PG 6
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 104ML
UT WOS:000315997400004
PM 23462284
ER
PT J
AU Mendoza, PR
Jakobiec, FA
Yoon, MK
AF Mendoza, Pia R.
Jakobiec, Frederick A.
Yoon, Michael K.
TI Keratinous Cyst of the Palpebral Conjunctiva: New Observations
SO CORNEA
LA English
DT Article
DE palpebral conjunctiva; eyelid; keratin; cyst
ID HYPERPLASIA
AB Purpose: To describe an acquired keratinizing cyst of the palpebral conjunctiva.
Methods: Observational case report with clinical and histopathologic correlations.
Results: A 41-year-old man presented with diffuse mild left upper eyelid swelling, eye pain, and redness in the absence of a nodule. Eversion of the eyelid revealed a whitish-gray, well-demarcated, superficial 4 x 4 mm lesion on the medial portion of the palpebral surface accompanied by a large epithelial erosion in the superior aspect of the cornea. The lesion was excised completely, sparing the tarsus. The site of excision healed completely after 1 week with no recurrence during 6 months of follow-up. Histopathologically, the lesion consisted of a round, eosinophilic, compact, acellular mass of keratin. The cyst's epithelial covering was a mixture of mostly flattened but occasionally polygonal basaloid epithelial cells, sometimes with foci of parakeratosis and pigmentation. There was no apparent keratohyalin granular layer (trichilemmal rather than epidermoid keratinization).
Conclusions: The pathogenesis of this peculiar lesion is hypothesized to involve a pseudogland of Henle that developed trichilemmal keratinization. It represents another easily overlooked cause of corneal epithelial erosion.
C1 [Mendoza, Pia R.; Jakobiec, Frederick A.] Harvard Univ, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA.
[Mendoza, Pia R.; Jakobiec, Frederick A.; Yoon, Michael K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Jakobiec, FA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 321,243 Charles St, Boston, MA 02114 USA.
EM fred_jakobiec@meei.harvard.edu
NR 12
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3740
J9 CORNEA
JI Cornea
PD APR
PY 2013
VL 32
IS 4
BP 513
EP 516
DI 10.1097/ICO.0b013e31827932f3
PG 4
WC Ophthalmology
SC Ophthalmology
GA 104NC
UT WOS:000315999500036
PM 23238396
ER
PT J
AU Eisenstat, SA
Ulman, K
Siegel, AL
Carlson, K
AF Eisenstat, Stephanie A.
Ulman, Kathleen
Siegel, Allison L.
Carlson, Karen
TI Diabetes Group Visits: Integrated Medical Care and Behavioral Support to
Improve Diabetes Care and Outcomes from a Primary Care Perspective
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Diabetes; Group visits; Shared medical appointments; Self-management;
Behavioral change; Medical care; Behavioral support
ID QUALITY-OF-LIFE; SELF-MANAGEMENT EDUCATION; HEALTH MAINTENANCE
ORGANIZATION; INSURED PATIENT POPULATION; CONTROLLED CLINICAL-TRIAL;
RANDOMIZED-TRIAL; OLDER-ADULTS; DEPRESSIVE SYMPTOMS; COMORBID
DEPRESSION; GROUP-PSYCHOTHERAPY
AB Of the many innovations in health care delivery proposed in the context of health reform for those with chronic diseases such as diabetes, the group visit model is relatively easy to implement and is effective for improving health outcomes and patient and provider satisfaction, with a neutral to positive effect on health care costs. This article describes the evolution of group visits for those with diabetes, the theory underlying group visits for patients with chronic medical conditions, and the existing evidence for the effectiveness of this model. It also addresses implementation of groups in practice, with an emphasis on the practical aspects of program implementation, integration of behavioral expertise into medical groups, individualization in various practice settings, and reimbursement issues.
C1 [Eisenstat, Stephanie A.; Ulman, Kathleen; Carlson, Karen] Harvard Univ, Sch Med, Boston, MA USA.
[Siegel, Allison L.] John D Stoeckle Ctr Primary Care Innovat, Boston, MA 02114 USA.
RP Eisenstat, SA (reprint author), Massachusetts Gen Hosp, Shared Med Care Program, Womens Hlth Associates, 55 Fruit St, Boston, MA 02114 USA.
EM saeisenstat@partners.org; kulman@partners.org; Asiegel1@partners.org;
kcarlson@partners.org
NR 128
TC 8
Z9 8
U1 6
U2 23
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD APR
PY 2013
VL 13
IS 2
BP 177
EP 187
DI 10.1007/s11892-012-0349-5
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 105KZ
UT WOS:000316069500003
PM 23207990
ER
PT J
AU Lorincz, IS
Lawson, BCT
Long, JA
AF Lorincz, Ilona S.
Lawson, Brittany C. T.
Long, Judith A.
TI Provider and Patient Directed Financial Incentives to Improve Care and
Outcomes for Patients with Diabetes
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Diabetes mellitus; Reimbursement; Incentives; Pay for performance;
Economics; Behavioral
ID PAY-FOR-PERFORMANCE; WEIGHT-LOSS; BARIATRIC SURGERY; RANDOMIZED-TRIAL;
MEDICAL THERAPY; UNITED-KINGDOM; QUALITY; MANAGEMENT; IMPACT; ENGLAND
AB Incentive programs directed at both providers and patients have become increasingly widespread. Pay-for-performance (P4P) where providers receive financial incentives to carry out specific care or improve clinical outcomes has been widely implemented. The existing literature indicates they probably spur initial gains which then level off or partially revert if incentives are withdrawn. The literature also indicates that process measures are easier to influence through P4P programs but that intermediate outcomes such as glucose, blood pressure, and cholesterol control are harder to influence, and the long-term impact of P4P programs on health is largely unknown. Programs directed at patients show greater promise as a means to influence patient behavior and intermediate outcomes such as weight loss; however, the evidence for long-term effects are lacking. In combination, both patient and provider incentives are potentially powerful tools but whether they are cost-effective has yet to be determined.
C1 [Lorincz, Ilona S.] Univ Penn, Perelman Sch Med, Dept Med, Div Endocrine, Philadelphia, PA 19104 USA.
[Lawson, Brittany C. T.; Long, Judith A.] Univ Penn, Perelman Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Long, Judith A.] Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Long, Judith A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
RP Long, JA (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Div Gen Internal Med, 1021 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM Ilona.Lorincz@uphs.upenn.edu; blaws@mail.med.upenn.edu;
jalong@mail.med.upenn.edu
FU NIDDK
FX I.S. Lorincz: none; B.C.T. Lawson: none; J.A. Long: has received grant
support from NIDDK.
NR 45
TC 3
Z9 3
U1 1
U2 15
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD APR
PY 2013
VL 13
IS 2
BP 188
EP 195
DI 10.1007/s11892-012-0353-9
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 105KZ
UT WOS:000316069500004
PM 23225214
ER
PT J
AU Lacroix, M
Kina, E
Hivert, MF
AF Lacroix, Marilyn
Kina, Eralda
Hivert, Marie-France
TI Maternal/Fetal Determinants of Insulin Resistance in Women During
Pregnancy and in Offspring Over Life
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Insulin resistance; Pregnancy; Early origin; Maternal metabolism; Fetal
determinants; Programming; Epigenetics; Offspring
ID GESTATIONAL DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; BETA-CELL
FUNCTION; BODY-MASS INDEX; GLUCOSE-TOLERANCE; INDIAN CHILDREN;
SKELETAL-MUSCLE; METABOLIC SYNDROME; DNA METHYLATION; NORMAL-WEIGHT
AB Insulin resistance is a component of the pathophysiology of both type 2 diabetes and gestational diabetes mellitus (GDM), but is also characteristic of normal glycemic physiology during pregnancy. In recent years, many studies have tried to understand determinants of insulin resistance in normal pregnancy and GDM, revealing that the placenta is capable of secreting many cytokines and hormones, classically considered as adipokines. More specifically, it appears that leptin and TNF alpha could be implicated in gestational insulin resistance and GDM pathophysiology. In addition, the maternal metabolic milieu was also identified as a key determinant of later insulin resistance in offspring, a phenomenon often described as 'fetal programming'. This article reviews the established risk factors and the more novel suspected biomarkers involved in maternal insulin resistance during pregnancy as well as the maternal and early life determinants of insulin resistance in offspring later in their life. We are also highlighting recent reports of the potential mechanisms involved in 'programming' of insulin resistance such as epigenetic modulation.
C1 [Lacroix, Marilyn; Kina, Eralda; Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada.
[Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
RP Hivert, MF (reprint author), Univ Sherbrooke, Dept Med, 3001,12E Ave Nord, Sherbrooke, PQ J1K 2R1, Canada.
EM marie-france.hivert@usherbrooke.ca
NR 64
TC 14
Z9 16
U1 0
U2 27
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD APR
PY 2013
VL 13
IS 2
BP 238
EP 244
DI 10.1007/s11892-012-0360-x
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 105KZ
UT WOS:000316069500010
PM 23307191
ER
PT J
AU Braun, JM
Sathyanarayana, S
Hauser, R
AF Braun, Joseph M.
Sathyanarayana, Sheela
Hauser, Russ
TI Phthalate exposure and children's health
SO CURRENT OPINION IN PEDIATRICS
LA English
DT Review
DE children; endocrine disruption; epidemiology; phthalates
ID IN-UTERO EXPOSURE; BODY TOPICAL APPLICATION; PERSONAL CARE PRODUCTS;
SCHOOL-AGE-CHILDREN; NEW-YORK-CITY; URINARY CONCENTRATIONS; PRENATAL
EXPOSURE; BISPHENOL-A; DIETHYLHEXYL PHTHALATE; DI(2-ETHYLHEXYL)PHTHALATE
DEHP
AB Purpose of review
Phthalates are multifunctional chemicals used in personal care products, medications, and plastics. We reviewed the epidemiological literature examining the relationship between early life phthalate exposure and pediatric health outcomes.
Recent findings
Five studies from Asia, Europe, and the United States suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-butyl phthalate (DBP), and di-ethyl phthalate (DEP) exposures are associated with alterations in infant/toddler physical development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure.
Summary
Several epidemiological studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. Although anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes.
C1 [Braun, Joseph M.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[Sathyanarayana, Sheela] Univ Washington, Dept Pediat, Seattle Childrens Res Inst, Seattle, WA 98195 USA.
[Hauser, Russ] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Fertil Ctr, Dept Obstet & Gynecol,Div Reprod Endocrinol & Inf, Boston, MA USA.
[Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Braun, JM (reprint author), Brown Univ, Dept Epidemiol, Box G-S121-2, Providence, RI 02912 USA.
EM joseph_braun_1@brown.edu
RI Braun, Joseph/H-8649-2014
FU NIEHS [K99 ES020346, R01 ES021357, R01 ES009718]
FX J.M.B. was supported by NIEHS grants K99 ES020346 and R01 ES021357. R.
H. is supported by NIEHS grant R01 ES009718.
NR 75
TC 70
Z9 73
U1 8
U2 113
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8703
J9 CURR OPIN PEDIATR
JI CURR. OPIN. PEDIATR.
PD APR
PY 2013
VL 25
IS 2
BP 247
EP 254
DI 10.1097/MOP.0b013e32835e1eb6
PG 8
WC Pediatrics
SC Pediatrics
GA 105YV
UT WOS:000316109500015
PM 23429708
ER
PT J
AU Preer, G
Sorrentino, D
Ryznar, E
Newton, AW
AF Preer, Genevieve
Sorrentino, Deborah
Ryznar, Elizabeth
Newton, Alice W.
TI Child maltreatment: promising approaches and new directions
SO CURRENT OPINION IN PEDIATRICS
LA English
DT Review
DE abusive head trauma; child abuse; child maltreatment; child sexual
abuse; neglect; shaken baby syndrome
ID ABUSIVE HEAD TRAUMA; UNITED-STATES; SEXUAL-ABUSE; PREVENTION; RISK;
INJURIES; HOME; PRESENTATIONS; PREVALENCE; DISORDERS
AB Purpose of review
This review summarizes the key articles in the field of child maltreatment, addressing abusive head trauma, physical abuse, sexual abuse, and global issues surrounding maltreatment. This topic is salient for both general pediatricians as well as specialists.
Recent findings
Many articles this year focus on the importance of making an accurate diagnosis when considering child maltreatment, whether in the form of physical or sexual abuse. There is also a focus on understanding the epidemiology of abuse, as some data show a decrease in numbers, which is felt by many in the field to be a misleading impression.
Summary
An appreciation of the scope of Child Abuse Pediatrics requires an understanding of physical abuse, sexual abuse, and neglect. The authors summarize notable advances in our understanding of these key areas in a review of the year's best literature.
C1 [Preer, Genevieve] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA.
[Preer, Genevieve] Boston Med Ctr, Dept Pediat, Div Family & Child Advocacy, Boston, MA USA.
[Sorrentino, Deborah; Newton, Alice W.] Childrens Hosp, Child Protect Program, Boston, MA 02115 USA.
[Ryznar, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA.
[Newton, Alice W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Newton, Alice W.] Massachusetts Gen Hosp, Child Protect Program, Boston, MA 02114 USA.
RP Newton, AW (reprint author), Childrens Hosp, Child Protect Program, 300 Longwood Ave, Boston, MA 02115 USA.
EM Alice.Newton@childrens.harvard.edu
OI Preer, Genevieve/0000-0001-8264-3541; Ryznar,
Elizabeth/0000-0002-2922-7677
NR 37
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U1 1
U2 26
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8703
J9 CURR OPIN PEDIATR
JI CURR. OPIN. PEDIATR.
PD APR
PY 2013
VL 25
IS 2
BP 268
EP 274
DI 10.1097/MOP.0b013e32835eb347
PG 7
WC Pediatrics
SC Pediatrics
GA 105YV
UT WOS:000316109500018
PM 23429709
ER
PT J
AU Hansen, HM
Stasko, KD
AF Hansen, H. M.
Stasko, K. D.
TI BRIDGING THE GAP: PROVIDING A WEB-BASED FORUM FOR EDUCATION AND
COMMUNICATION IN A CHALLENGING WORKPLACE ENVIRONMENT
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Hansen, H. M.; Stasko, K. D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
J9 CYTOTHERAPY
JI Cytotherapy
PD APR
PY 2013
VL 15
IS 4
SU S
MA 82
BP S26
EP S26
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 111QL
UT WOS:000316535700081
ER
PT J
AU Liney, DJ
AF Liney, D. J.
TI COLLECTING HIGH QUALITY CORD BLOOD UNITS: THE CONTRAST BETWEEN MD AND
DEDICATED COLLECTION SPECIALIST COLLECTIONS
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Liney, D. J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
J9 CYTOTHERAPY
JI Cytotherapy
PD APR
PY 2013
VL 15
IS 4
SU S
MA 97
BP S30
EP S30
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 111QL
UT WOS:000316535700096
ER
PT J
AU Sturtevant, OJ
Jacobsen, ED
Lehman, LE
Ritz, J
O'Rourke, S
Kelley, MA
Liney, D
Urbina, M
AF Sturtevant, O. J.
Jacobsen, E. D.
Lehman, L. E.
Ritz, J.
O'Rourke, S.
Kelley, M. A.
Liney, D.
Urbina, M.
TI AN ON-GOING QUALITY IMPROVEMENT PROJECT TO LOWER THE RATE OF BACTERIAL
CONTAMINATION IN HIPC -MARROW PRODUCTS
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Sturtevant, O. J.; Jacobsen, E. D.; Ritz, J.; O'Rourke, S.; Kelley, M. A.; Liney, D.; Urbina, M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lehman, L. E.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
J9 CYTOTHERAPY
JI Cytotherapy
PD APR
PY 2013
VL 15
IS 4
SU S
MA 95
BP S29
EP S29
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 111QL
UT WOS:000316535700094
ER
PT J
AU Wolpert, HA
Atakov-Castillo, A
Smith, SA
Steil, GM
AF Wolpert, Howard A.
Atakov-Castillo, Astrid
Smith, Stephanie A.
Steil, Garry M.
TI Dietary Fat Acutely Increases Glucose Concentrations and Insulin
Requirements in Patients With Type 1 Diabetes Implications for
carbohydrate-based bolus dose calculation and intensive diabetes
management
SO DIABETES CARE
LA English
DT Article
ID ARTIFICIAL PANCREAS; SENSITIVITY; HUMANS; RESISTANCE; ACIDS; MEAL;
COMPLICATIONS; HYPERGLYCEMIA; SECRETION; DELIVERY
AB OBJECTIVE-Current guidelines for intensive treatment of type 1 diabetes base the mealtime insulin bolus calculation exclusively on carbohydrate counting. There is strong evidence that free fatty acids impair insulin sensitivity. We hypothesized that patients with type 1 diabetes would require more insulin coverage for higher-fat meals than lower-fat meals with identical carbohydrate content.
RESEARCH DESIGN AND METHODS-We used a crossover design comparing two 18-h periods of closed-loop glucose control after high-fat (HF) dinner compared with low-fat (LF) dinner. Each dinner had identical carbohydrate and protein content, but different fat content (60 vs. 10 g).
RESULTS-Seven patients with type 1 diabetes (age, 55 +/- 12 years; A1C 7.2 +/- 0.8%) successfully completed the protocol. HF dinner required more insulin than LF dinner (12.6 +/- 1.9 units vs. 9.0 +/- 1.3 units; P = 0.01) and, despite the additional insulin, caused more hyperglycemia (area under the curve >120 mg/dL = 16,967 +/- 2,778 vs. 8,350 +/- 1,907 mg/dL.min; P < 0001). Carbohydrate-to-insulin ratio for HF dinner was significantly lower (9 +/- 2 vs. 13 +/- 3 g/unit; P = 0.01). There were marked interindividual differences in the effect of dietary fat on insulin requirements (percent increase significantly correlated with daily insulin requirement; R-2 = 0.64; P = 0.03).
CONCLUSIONS-This evidence that dietary fat increases glucose levels and insulin requirements highlights the limitations of the current carbohydrate-based approach to bolus dose calculation. These findings point to the need for alternative insulin dosing algorithms for higher-fat meals and suggest that dietary fat intake is an important nutritional consideration for glycemic control in individuals with type 1 diabetes. Diabetes Care 36:810-816, 2013
C1 [Wolpert, Howard A.; Atakov-Castillo, Astrid; Smith, Stephanie A.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Wolpert, Howard A.; Steil, Garry M.] Harvard Univ, Sch Med, Boston, MA USA.
[Steil, Garry M.] Childrens Hosp, Boston, MA 02115 USA.
RP Wolpert, HA (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.
EM howard.wolpert@joslin.harvard.edu
FU Scripps Foundation; Juvenile Diabetes Research Foundation [1-2011-581,
UL1 RR025758]; Harvard Clinical and Translational Science Center;
National Center for Research Resources
FX This project was supported by the Scripps Foundation, Juvenile Diabetes
Research Foundation grants 1-2011-581 and UL1 RR025758, the Harvard
Clinical and Translational Science Center, and the National Center for
Research Resources. Abbott Diabetes Care and Animas Corporation provided
devices for this study. No other potential conflicts of interest
relevant to this article were reported.
NR 34
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PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2013
VL 36
IS 4
BP 810
EP 816
DI 10.2337/dc12-0092
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 110RG
UT WOS:000316462400023
PM 23193216
ER
PT J
AU Gonzalez, JS
Schneider, HE
Wexler, DJ
Psaros, C
Delahanty, LM
Cagliero, E
Safren, SA
AF Gonzalez, Jeffrey S.
Schneider, Havah E.
Wexler, Deborah J.
Psaros, Christina
Delahanty, Linda M.
Cagliero, Enrico
Safren, Steven A.
TI Validity of Medication Adherence Self-Reports in Adults With Type 2
Diabetes
SO DIABETES CARE
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; DSM-IV; DEPRESSION;
NONADHERENCE; METAANALYSIS; MORTALITY; THERAPY; RECALL; SCALE;
ASSOCIATION
AB OBJECTIVE-To assess the validity of self-report measures of diabetes medication adherence and evaluate the effect of depression on the validity of these reports.
RESEARCH DESIGN AND METHODS-Adults with type 2 diabetes, treated with oral medications, completed a set of medication adherence self-reports that varied response scales and time frames, were administered structured clinical interviews for depression, and provided blood samples for HbA(1c) as part of a screening for an intervention study. A subsample of participants with HbA(1c) >= 7.0% and clinically significant depression received Medication Event Monitoring System (MEMS) bottle caps to record adherence. Analyses examined relationships between adherence measures and HbA(1c) and, in the subsample, MEMS. Moderated linear regression evaluated whether depression severity modified relationships with HbA(1c).
RESULTS-Participant (n = 170, 57% men, 81% white, mean HbA(1c) 8.3% [SD, 1.7]) adherence self-reports were significantly (r = -0.18 to -0.28; P < 0.03) associated with lower HbA(1c). In the subsample (n = 88), all self-reports were significantly (r = 0.35 to 0.55; P <= 0.001) associated with MEMS-measured adherence. Depression significantly moderated the relationship between three of six self-reports and HbA(1c); at high levels of depression, associations with HbA(1c) became nonsignificant.
CONCLUSIONS-Results support the validity of easily administered self-reports for diabetes medication adherence. One-month, percentage-based ratings of adherence had the strongest associations with MEMS and HbA(1c); those requiring the report of missed doses had weaker associations. One-week self-ratings and measures that require respondents to record the number of missed doses appear to be vulnerable to bias from depression severity. Diabetes Care 36: 831-837, 2013
C1 [Gonzalez, Jeffrey S.; Schneider, Havah E.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY 10033 USA.
[Gonzalez, Jeffrey S.] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA.
[Wexler, Deborah J.; Delahanty, Linda M.; Cagliero, Enrico] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet,Dept Med, Boston, MA USA.
[Psaros, Christina; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Gonzalez, JS (reprint author), Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY 10033 USA.
EM jeffrey.gonzalez@einstein.yu.edu
FU National Institute of Mental Health (NIMH) [R01-MH-078571]; LifeScan,
Inc.; Harvard Catalyst/Harvard Clinical and Translational Science Center
by National Institutes of Health (NIH) [1 UL1-RR-025758-03]; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[DK-020541, DK-080228-05]
FX This project was supported by National Institute of Mental Health (NIMH)
Grant R01-MH-078571; Principal Investigator: S. A. S. Additional support
came from the Investigator-Initiated Study Program of LifeScan, Inc., in
the form of donated glucometers and glucose test strips, and the Harvard
Catalyst/Harvard Clinical and Translational Science Center by National
Institutes of Health (NIH) Grant 1 UL1-RR-025758-03, for a portion of
nurse and dietician study visits. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH/NIMH, LifeScan, or the Harvard Catalyst.
J.S.G. was partially supported by Grant DK-020541 from the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). D. W.
was supported by NIDDK Grant DK-080228-05.
NR 36
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U2 15
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2013
VL 36
IS 4
BP 831
EP 837
DI 10.2337/dc12-0410
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 110RG
UT WOS:000316462400026
PM 23204245
ER
PT J
AU Pisprasert, V
Ingram, KH
Lopez-Davila, MF
Munoz, AJ
Garvey, WT
AF Pisprasert, Veeradej
Ingram, Katherine H.
Lopez-Davila, Maria F.
Munoz, A. Julian
Garvey, W. Timothy
TI Limitations in the Use of Indices Using Glucose and Insulin Levels to
Predict Insulin Sensitivity Impact of race and gender and superiority of
the indices derived from oral glucose tolerance test in African
Americans
SO DIABETES CARE
LA English
DT Article
ID BETA-CELL FUNCTION; HOMEOSTASIS MODEL ASSESSMENT; NON-HISPANIC WHITES;
CLAMP TECHNIQUE; RESISTANCE ATHEROSCLEROSIS; CHECK INDEX; IN-VIVO;
SECRETION; BLACK; CLEARANCE
AB OBJECTIVE-To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs).
RESEARCH DESIGN AND METHODS-Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SI(is)OGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression.
RESULTS-GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SIisOGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381-0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SI(is)OGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall.
CONCLUSIONS-Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SI(is)OGTT are reliable in studies that include AA males. Diabetes Care 36:845-853, 2013
C1 [Pisprasert, Veeradej; Lopez-Davila, Maria F.; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Ingram, Katherine H.] Kennesaw State Univ, Dept Exercise Sci & Sport Management, Kennesaw, GA USA.
[Munoz, A. Julian] Univ S Carolina, Sch Med, Div Endocrinol, Columbia, SC USA.
[Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Pisprasert, V (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
EM veeradej@uab.edu
FU National Institutes of Health [DK-083562, DK-038764]; Merit Review
program of the U.S. Department of Veterans Affairs; UAB Diabetes
Research and Training Center [P60-DK079626]
FX This work was supported from grants from the National Institutes of
Health (DK-083562 and DK-038764 to W.T.G.) and by the Merit Review
program of the U.S. Department of Veterans Affairs (W.T.G.).; The
authors are grateful to Dr. Barbara Gower (Department of Nutrition
Sciences, University of Alabama at Birmingham) and Dr. Mark Beasley
(Department of Biostatistics, University of Alabama at Birmingham) for
insightful discussions regarding these data. The authors thank the
support of the research core facilities of the UAB Diabetes Research and
Training Center (P60-DK079626) and their research volunteers.
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PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2013
VL 36
IS 4
BP 845
EP 853
DI 10.2337/dc12-0840
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 110RG
UT WOS:000316462400028
PM 23223406
ER
PT J
AU Foo, JP
Aronis, KN
Chamberland, JP
Paruthi, J
Moon, HS
Mantzoros, CS
AF Foo, Joo-Pin
Aronis, Konstantinos N.
Chamberland, John P.
Paruthi, Jason
Moon, Hyun-Seuk
Mantzoros, Christos S.
TI Fibroblast Growth Factor 21 Levels in Young Healthy Females Display Day
and Night Variations and Are Increased in Response to Short-Term Energy
Deprivation Through a Leptin-Independent Pathway
SO DIABETES CARE
LA English
DT Article
ID METHIONYL HUMAN LEPTIN; FREE FATTY-ACIDS; ANOREXIA-NERVOSA; PPAR-ALPHA;
HYPOTHALAMIC AMENORRHEA; INSULIN SENSITIVITY; METABOLIC REGULATOR;
CIRCADIAN-RHYTHM; FGF21; OBESITY
AB OBJECTIVE-Fibroblast growth factor (FGF)-21 is an endocrine factor with potent metabolic effects. Its day-night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated. We aim to elucidate day-night pattern of FGF-21 levels and its relationship to FFA, to assess whether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes.
RESEARCH DESIGN AND METHODS-Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8: 00 A. M. on day 4 until 8: 00 A. M. on day 5.
RESULTS-FGF-21 exhibited day-night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day-night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states.
CONCLUSIONS-A day-night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close cross-correlations with FFA in both fed state and energy deprivation, needs to be studied further. Diabetes Care 36:935-942, 2013
C1 [Foo, Joo-Pin; Aronis, Konstantinos N.; Chamberland, John P.; Paruthi, Jason; Moon, Hyun-Seuk; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA.
[Aronis, Konstantinos N.; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Endocrinol Sect, Boston VA Healthcare Syst, Sch Med, Boston, MA 02115 USA.
RP Mantzoros, CS (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA.
EM cmantzor@bidmc.harvard.edu
RI Aronis, Konstantinos/F-3586-2012; Moon, Hyun-Seuk/G-8576-2015;
OI Aronis, Konstantinos/0000-0001-7189-8434; Moon,
Hyun-Seuk/0000-0002-5216-2090; Chamberland, John/0000-0002-7862-1371
FU National Institute of Diabetes and Digestive and Kidney Diseases [58785,
79929, 81913]; Clinical Science Research and Development Service of the
VA Office of Research and Development [1I01CX000422-01A1]; National
Institutes of Health National Center for Research Resources grant
[M01-RR-01032]
FX This study was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases grants 58785, 79929, and 81913. The
project described was also supported by Award Number 1I01CX000422-01A1
from the Clinical Science Research and Development Service of the VA
Office of Research and Development. Funding was also received from the
National Institutes of Health National Center for Research Resources
grant M01-RR-01032 (Harvard Clinical and Translational Science Center).
Amylin Pharmaceuticals, Inc. supplied metreleptin for this study but had
no role in the study design, conduct of the study, collection,
management, analysis, and interpretation of the data, or the
preparation, review, or approval of the manuscript. No other potential
conflicts of interest relevant to this article were reported.
NR 39
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U1 0
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2013
VL 36
IS 4
BP 935
EP 942
DI 10.2337/dc12-0497
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 110RG
UT WOS:000316462400041
PM 23193213
ER
PT J
AU Cummings, DE
Cohen, RV
AF Cummings, David E.
Cohen, Ricardo V.
TI Response to Comment on: Cohen et al. Effects of Gastric Bypass Surgery
in Patients With Type 2 Diabetes and Only Mild Obesity. Diabetes Care
2012;35:1420-1428
SO DIABETES CARE
LA English
DT Letter
ID BARIATRIC SURGERY; MEDICAL THERAPY
C1 [Cummings, David E.] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA.
[Cummings, David E.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Cohen, Ricardo V.] Oswaldo Cruz Hosp, Ctr Excellence Bariatr & Metab Surg, Sao Paulo, Brazil.
[Cohen, Ricardo V.] Marcia Maria Braido Hosp, Sao Paulo, Brazil.
RP Cummings, DE (reprint author), Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA.
EM davidec@u.washington.edu
NR 6
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U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD APR
PY 2013
VL 36
IS 4
BP E59
EP E59
DI 10.2337/dc12-2243
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 110RG
UT WOS:000316462400012
PM 23520383
ER
PT J
AU Nowak, N
Skupien, J
Cyganek, K
Matejko, B
Malecki, MT
AF Nowak, N.
Skupien, J.
Cyganek, K.
Matejko, B.
Malecki, M. T.
TI 1,5-Anhydroglucitol as a marker of maternal glycaemic control and
predictor of neonatal birthweight in pregnancies complicated by type 1
diabetes mellitus
SO DIABETOLOGIA
LA English
DT Article
DE 1,5-Anhydroglucitol; Birthweight; Haemoglobin A(1c); HbA(1c); Pregnancy;
Type 1 diabetes mellitus
ID GLUCOSE-LEVELS; WOMEN; MACROSOMIA
AB Most pregnant women with type 1 diabetes mellitus achieve HbA(1c) targets; however, macrosomia remains prevalent and better pregnancy glycaemic markers are therefore needed. 1,5-Anhydroglucitol (1,5-AG) is a short-term marker of glycaemia, reflecting a period of 1 to 2 weeks. Its excretion rate depends on the renal glucose threshold and thus it is unclear whether it may be used in pregnant type 1 diabetes women. We evaluated 1,5-AG as a glycaemic marker and birthweight predictor in pregnant women with type 1 diabetes, and compared its performance with HbA(1c).
1,5-AG and HbA(1c) were measured in 82 pregnant women with type 1 diabetes. In addition, 58 continuous glucose monitoring system (CGMS) records were available. Macrosomia was defined as birthweight > 90th centile. The data were analysed with Pearson's correlations, and linear and logistic regression models. Receiver operating characteristic (ROC) analysis was used to evaluate third trimester 1,5-AG as a predictor of macrosomia.
Unlike HbA(1c), 1,5-AG strongly correlated with CGMS indices: the AUC above 7.8 mmol/l (r = -0.66; p < 0.001), average maximum glucose (r = -0.58; p < 0.001) and mean glucose (r = -0.54; p < 0.001). In the third trimester, 1,5-AG was the strongest predictor of macrosomia, with ROC AUC 0.81 (95% CI 0.70, 0.89). In contrast, HbA(1c) in the third trimester had a ROC AUC of 0.69 (95% CI 0.58, 0.81). The best discrimination was achieved when both markers were used jointly, yielding a ROC AUC of 0.84 (95% CI 0.76, 0.93).
In pregnant women with type 1 diabetes, 1,5-AG is a better glycaemic marker than HbA(1c), as assessed by CGMS. A decreased third trimester 1,5-AG level, either singly or with HbA(1c), is a strong predictor of macrosomia.
C1 [Nowak, N.; Skupien, J.; Matejko, B.; Malecki, M. T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland.
[Skupien, J.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA.
[Cyganek, K.; Malecki, M. T.] Univ Hosp, Dept Metab Dis, Krakow, Poland.
RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland.
EM maciej.malecki@uj.edu.pl
FU Polish Ministry of Science [N N407 414436]
FX This work was supported by the Polish Ministry of Science Grant No. N
N407 414436
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PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD APR
PY 2013
VL 56
IS 4
BP 709
EP 713
DI 10.1007/s00125-013-2830-3
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 105MX
UT WOS:000316076300004
PM 23377619
ER
PT J
AU Goldfine, AB
Conlin, PR
Halperin, F
Koska, J
Permana, P
Schwenke, D
Shoelson, SE
Reaven, PD
AF Goldfine, A. B.
Conlin, P. R.
Halperin, F.
Koska, J.
Permana, P.
Schwenke, D.
Shoelson, S. E.
Reaven, P. D.
TI A randomised trial of salsalate for insulin resistance and
cardiovascular risk factors in persons with abnormal glucose tolerance
SO DIABETOLOGIA
LA English
DT Article
DE Adipose tissue; Cardiovascular risk factors; Endothelial function;
Impaired glucose tolerance; Inflammation; Insulin resistance;
Salicylates
ID SODIUM-SALICYLATE; DIABETES-MELLITUS; IKK-BETA; ACETYLSALICYLIC-ACID;
KAPPA-B; ASPIRIN; INFLAMMATION; HEALTHY; IDENTIFICATION; INDIVIDUALS
AB Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance.
We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment.
Seventy-one individuals were randomised to placebo (n = 36) or salsalate (n = 35). Glucose disposal did not change in either group (salsalate 1% [95% CI -39%, 56%]; placebo 6% [95% CI -20%, 61%], p = 0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p = 0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p = 0.01) and adiponectin increased by 53% (p = 0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor kappa B (NF-kappa B) activity declined in the salsalate group compared with placebo (-16% vs 42%, p = 0.005), but was not correlated with metabolic improvements. The frequency of tinnitus was low but tended to be higher with salsalate therapy (n = 4 vs n = 2).
In summary, salsalate therapy was well tolerated, lowered fasting glucose, increased adiponectin and reduced adipose tissue NF-kappa B activity. These changes were not related to changes in peripheral insulin sensitivity, suggesting additional mechanisms for metabolic improvement.
ClinicalTrials.gov NCT00330733
Office of Research and Development, Medical Research Service, Department of Veterans Affairs and NIH K24 DK63214.
C1 [Goldfine, A. B.; Halperin, F.; Shoelson, S. E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA.
[Conlin, P. R.] Brigham & Womens Hosp, Boston VA Hlth Care Syst, Dept Med, Boston, MA 02115 USA.
[Koska, J.; Permana, P.; Schwenke, D.] Phoenix VA Hlth Care Syst, Res Dept, Phoenix, AZ USA.
[Reaven, P. D.] Phoenix VA Hlth Care Syst, Dept Med, Phoenix, AZ USA.
[Reaven, P. D.] Univ Arizona, Dept Med, Phoenix, AZ USA.
RP Reaven, PD (reprint author), Phoenix VA Hlth Care Syst, Dept Med, Phoenix, AZ USA.
EM Peter.Reaven@va.gov
FU Office of Research and Development, Medical Research Service, Department
of Veterans Affairs; NIH [K24 DK63214]
FX This material is based upon work supported by the Office of Research and
Development, Medical Research Service, Department of Veterans Affairs
and NIH K24 DK63214. The contents do not represent the views of the
Department of Veterans Affairs or the US Government.
NR 42
TC 40
Z9 42
U1 1
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD APR
PY 2013
VL 56
IS 4
BP 714
EP 723
DI 10.1007/s00125-012-2819-3
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 105MX
UT WOS:000316076300005
PM 23370525
ER
PT J
AU Rountree, AM
Reed, BJ
Cummings, BP
Jung, SR
Stanhope, KL
Graham, JL
Griffen, SC
Hull, RL
Havel, PJ
Sweet, IR
AF Rountree, A. M.
Reed, B. J.
Cummings, B. P.
Jung, S. -R.
Stanhope, K. L.
Graham, J. L.
Griffen, S. C.
Hull, R. L.
Havel, P. J.
Sweet, I. R.
TI Loss of coupling between calcium influx, energy consumption and insulin
secretion associated with development of hyperglycaemia in the UCD-T2DM
rat model of type 2 diabetes
SO DIABETOLOGIA
LA English
DT Article
DE Calcium; Hyperglycaemia; Insulin secretion; Islets; Oxygen consumption
ID PANCREATIC BETA-CELLS; PYRUVATE-CARBOXYLASE; ENDOPLASMIC-RETICULUM;
OXYGEN-CONSUMPTION; B-CELLS; GLUCOSE; ISLETS; CHANNELS; RELEASE;
MITOCHONDRIA
AB Previous studies on isolated islets have demonstrated tight coupling between calcium (Ca2+) influx and oxygen consumption rate (OCR) that is correlated with insulin secretion rate (ISR). To explain these observations, we have proposed a mechanism whereby the activation of a highly energetic process (Ca2+/metabolic coupling process [CMCP]) by Ca2+ mediates the stimulation of ISR. The aim of the study was to test whether impairment of the CMCP could play a role in the development of type 2 diabetes.
Glucose- and Ca2+-mediated changes in OCR and ISR in isolated islets were compared with the time course of changes of plasma insulin concentrations observed during the progression to hyperglycaemia in a rat model of type-2 diabetes (the University of California at Davis type 2 diabetes mellitus [UCD-T2DM] rat). Islets were isolated from UCD-T2DM rats before, 1 week, and 3 weeks after the onset of hyperglycaemia.
Glucose stimulation of cytosolic Ca2+ and OCR was similar for islets harvested before and 1 week after the onset of hyperglycaemia. In contrast, a loss of decrement in islet OCR and ISR in response to Ca2+ channel blockade coincided with decreased fasting plasma insulin concentrations observed in rats 3 weeks after the onset of hyperglycaemia.
These results suggest that phenotypic impairment of diabetic islets in the UCD-T2DM rat is downstream of Ca2+ influx and involves unregulated stimulation of the CMCP. The continuously elevated levels of CMCP induced by chronic hyperglycaemia in these islets may mediate the loss of islet function.
C1 [Rountree, A. M.; Reed, B. J.; Jung, S. -R.; Sweet, I. R.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98109 USA.
[Cummings, B. P.; Stanhope, K. L.; Graham, J. L.; Havel, P. J.] Univ Calif Davis, Dept Mol Biosci, Sch Vet Med, Davis, CA 95616 USA.
[Cummings, B. P.; Stanhope, K. L.; Graham, J. L.; Havel, P. J.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA.
[Griffen, S. C.] Bristol Myers Squibb Co, Princeton, NJ USA.
[Hull, R. L.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA.
[Hull, R. L.] Univ Washington, Seattle, WA 98109 USA.
RP Sweet, IR (reprint author), Univ Washington, Diabet & Obes Ctr Excellence, 850 Republican St, Seattle, WA 98109 USA.
EM isweet@u.washington.edu
OI Hull, Rebecca/0000-0001-9690-4087
FU Merck Investigator Initiated Sponsored Program [33171]; National
Institutes of Health [DK17047, DK063986, R01 HL075675, R01 HL091333,
AT002599, AT002993, AT003645]; Washington State Life Sciences Discovery
Fund; American Diabetes Association
FX This research was funded by grants from Merck Investigator Initiated
Sponsored Program (No. 33171), the National Institutes of Health
(DK17047 and DK063986) and the Washington State Life Sciences Discovery
Fund. P. J. Havel's laboratory also receives, or received, support
during the time the experiments were conducted from NIH grants R01
HL075675, R01 HL091333, AT002599, AT002993, AT003645 and the American
Diabetes Association.
NR 35
TC 5
Z9 5
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD APR
PY 2013
VL 56
IS 4
BP 803
EP 813
DI 10.1007/s00125-012-2808-6
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 105MX
UT WOS:000316076300014
PM 23404441
ER
PT J
AU Tyler, JA
Fox, JP
Desai, MM
Perry, WB
Glasgow, SC
AF Tyler, Joshua A.
Fox, Justin P.
Desai, Mayur M.
Perry, W. Brian
Glasgow, Sean C.
TI Outcomes and Costs Associated With Robotic Colectomy in the Minimally
Invasive Era
SO DISEASES OF THE COLON & RECTUM
LA English
DT Article
DE Robotic surgery; Colectomy; Laparoscopic colectomy; Colon cancer
ID SHORT-TERM OUTCOMES; MRC CLASICC TRIAL; COLON-CANCER; RANDOMIZED-TRIAL;
ASSISTED SURGERY
AB BACKGROUND: Robotic-assisted surgery has become increasingly common; however, it is unclear if its use for colectomy improves in-hospital outcomes compared with the laparoscopic approach.
OBJECTIVE: The aim of the study is to compare in-hospital outcomes and costs between patients undergoing robotic or laparoscopic colectomy.
DESIGN: This study is a retrospective review of the 2008 to 2009 Nationwide Inpatient Sample.
SETTINGS, PATIENTS, INTERVENTIONS: All adult patients who underwent an elective robotic or laparoscopic colectomy in hospitals performing both procedures (N = 2583 representing an estimated 12,732 procedures) were included.
MAIN OUTCOME MEASURES: Outcomes included intraoperative and postoperative complications, length of stay, and direct costs of care. Regression models were used to compare these outcomes between procedural approaches while controlling for baseline differences in patient characteristics.
RESULTS: Overall, 6.1% of patients underwent a robotic procedure. Factors associated with robotic-assisted colectomy included younger age, benign diagnoses, and treatment at a lower-volume center. Patients undergoing robotic and laparoscopic procedures experienced similar rates of intraoperative (3.0% vs 3.3%; adjusted OR = 0.88 (0.35-2.22)) and postoperative (21.7% vs 21.6%; adjusted OR = 0.84 (0.54-1.30)) complications, as well as risk-adjusted average lengths of stay (5.4 vs 5.5 days, p = 0.66). However, robotic-assisted colectomy resulted in significantly higher costs of care ($19,231 vs $ 15,807, p < 0.001). Although the overall postoperative morbidity rate was similar between groups, the individual complications experienced by each group were different.
LIMITATIONS: A limitation of this study is the potential miscoding of robotic cases in administrative data.
CONCLUSIONS: Robotic-assisted colectomy significantly increases the costs of care without providing clear reductions in overall morbidity or length of stay. As the use of robotic technology in colon surgery continues to evolve, critical appraisal of the benefits offered in comparison with the resources consumed is required.
C1 [Tyler, Joshua A.; Glasgow, Sean C.] San Antonio Mil Med Ctr, Dept Surg, San Antonio, TX USA.
[Fox, Justin P.; Desai, Mayur M.] Yale Univ, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, New Haven, CT USA.
[Desai, Mayur M.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Perry, W. Brian] South Texas Vet Hlth Care Syst, Dept Gen Surg, San Antonio, TX USA.
RP Tyler, JA (reprint author), San Antonio Mil Med Ctr, Dept Gen Surg, 3851 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA.
EM Joshua.Tyler.1@us.af.mil
FU Robert Wood Johnson Foundation
FX Drs Fox and Desai are involved with the Clinical Scholars Program, which
is supported by the Robert Wood Johnson Foundation.
NR 25
TC 27
Z9 28
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0012-3706
J9 DIS COLON RECTUM
JI Dis. Colon Rectum
PD APR
PY 2013
VL 56
IS 4
BP 458
EP 466
DI 10.1097/DCR.0b013e31827085ec
PG 9
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 106ZB
UT WOS:000316183200467
PM 23478613
ER
PT J
AU Wicksell, RK
Kemani, M
Jensen, K
Kosek, E
Kadetoff, D
Sorjonen, K
Ingvar, M
Olsson, GL
AF Wicksell, R. K.
Kemani, M.
Jensen, K.
Kosek, E.
Kadetoff, D.
Sorjonen, K.
Ingvar, M.
Olsson, G. L.
TI Acceptance and commitment therapy for fibromyalgia: A randomized
controlled trial
SO EUROPEAN JOURNAL OF PAIN
LA English
DT Article
ID COGNITIVE-BEHAVIORAL THERAPY; MAJOR DEPRESSIVE DISORDER; PAIN DISABILITY
INDEX; HEALTH SURVEY SF-36; VALUES-BASED ACTION; LOW-BACK-PAIN;
PSYCHOLOGICAL INTERVENTIONS; IMPACT QUESTIONNAIRE; MUSCULOSKELETAL PAIN;
GENERAL-POPULATION
AB Background Fibromyalgia (FM) is characterized by widespread pain and co-morbid symptoms such as fatigue and depression. For FM, medical treatments alone appear insufficient. Recent meta-analyses point to the utility of cognitive behaviour therapy (CBT), but effects are moderate. Within the continuous development of CBT, the empirical support for acceptance and commitment therapy (ACT) has increased rapidly. ACT focuses on improving functioning by increasing the patient's ability to act in accordance with personal values also in the presence of pain and distress (i.e., psychological flexibility). However, no study has yet explored the utility of ACT in FM. Objectives To evaluate the efficacy of ACT for FM and the role of psychological inflexibility as a mediator of improvement. Methods In this randomized controlled trial, ACT was evaluated in comparison to a waiting list control condition. Forty women diagnosed with FM participated in the study. Assessments were made pre- and post-treatment and at 3 months of follow-up. The ACT intervention consisted of 12 weekly group sessions. Results Significant differences in favour of ACT were seen in pain-related functioning, FM impact, mental health-related quality of life, self-efficacy, depression, anxiety and psychological inflexibility. Changes in psychological inflexibility during the course of treatment were found to mediate pre- to follow-up improvements in outcome variables. Conclusions The results correspond with previous studies on ACT for chronic pain and suggest the utility of ACT for FM as well as the role of psychological inflexibility as a mediator of improvement.
C1 [Wicksell, R. K.; Kemani, M.; Olsson, G. L.] Karolinska Univ Hosp, Behav Med Pain Treatment Serv, Stockholm, Sweden.
[Wicksell, R. K.; Kemani, M.; Kosek, E.; Kadetoff, D.; Sorjonen, K.; Ingvar, M.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Olsson, G. L.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
[Jensen, K.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Jensen, K.] Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
[Kosek, E.; Kadetoff, D.; Ingvar, M.] Karolinska Inst, Osher Ctr Integrat Med, Stockholm, Sweden.
RP Wicksell, RK (reprint author), Karolinska Univ Hosp, Behav Med Pain Treatment Serv, Stockholm, Sweden.
EM rikard.wicksell@karolinska.se
OI Jensen, Karin/0000-0003-2521-3160; Ingvar, Martin/0000-0002-9041-5714
FU Swedish Research Council [K2009-53X-21070-01-3]; Stockholm County
Council; Swedish Rheumatism Association
FX One author (E. K.) received support from the Swedish Research Council,
Project No. K2009-53X-21070-01-3, the Stockholm County Council, and the
Swedish Rheumatism Association.
NR 65
TC 36
Z9 37
U1 15
U2 81
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1090-3801
EI 1532-2149
J9 EUR J PAIN
JI Eur. J. Pain
PD APR
PY 2013
VL 17
IS 4
BP 599
EP 611
DI 10.1002/j.1532-2149.2012.00224.x
PG 13
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 108HT
UT WOS:000316284100015
PM 23090719
ER
PT J
AU Su, DA
Shukla, AK
Chen, BW
Kim, JS
Nakayasu, E
Qu, Y
Aryal, U
Weitz, K
Clauss, TRW
Monroe, ME
Camp, DG
Bigelow, DJ
Smith, RD
Kulkarni, RN
Qian, WJ
AF Su, Dian
Shukla, Anil K.
Chen, Baowei
Kim, Jong-Seo
Nakayasu, Ernesto
Qu, Yi
Aryal, Uma
Weitz, Karl
Clauss, Therese R. W.
Monroe, Matthew E.
Camp, David G., II
Bigelow, Diana J.
Smith, Richard D.
Kulkarni, Rohit N.
Qian, Wei-Jun
TI Quantitative site-specific reactivity profiling of S-nitrosylation in
mouse skeletal muscle using cysteinyl peptide enrichment coupled with
mass spectrometry
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE S-nitrosylation; Redox regulation; Chemical enrichment; Mouse muscle;
Proteomics; LC-MS/MS; Free radicals
ID BIOTIN-SWITCH ASSAY; COMPLEX PROTEIN MIXTURES; RETICULUM CA-ATPASE;
LARGE GENE LISTS; NITRIC-OXIDE; POSTTRANSLATIONAL MODIFICATION;
NITROSATED PROTEINS; SIGNAL-TRANSDUCTION; RYANODINE RECEPTOR;
INSULIN-RECEPTOR
AB S-nitrosylation, the formation of S-nitrosothiol (SNO), is an important reversible thiol oxidation event that has been increasingly recognized for its role in cell signaling. Although many proteins susceptible to S-nitrosylation have been reported, site-specific identification of physiologically relevant SNO modifications remains an analytical challenge because of the low abundance and labile nature of this modification. Herein we present further improvement and optimization of the recently reported resin-assisted cysteinyl peptide enrichment protocol for SNO identification and its application to mouse skeletal muscle to identify specific cysteine sites sensitive to S-nitrosylation by a quantitative reactivity profiling strategy. Our results indicate that the protein- and peptide-level enrichment protocols provide comparable specificity and coverage of SNO-peptide identifications. S-nitrosylation reactivity profiling was performed by quantitatively comparing the site-specific SNO modification levels in samples treated with S-nitrosoglutathione, an NO donor, at two different concentrations (i.e., 10 and 100 mu M). The reactivity profiling experiments led to the identification of 488 SNO-modified sites from 197 proteins with specificity of similar to 95% at the unique peptide level, i.e., similar to 95% of enriched peptides contain cysteine residues as the originally SNO-modified sites. Among these sites, 281 from 145 proteins were considered more sensitive to S-nitrosylation based on the ratios of observed SNO levels between the two treatments. These SNO-sensitive sites are more likely to be physiologically relevant. Many of the SNO-sensitive proteins are localized in mitochondria, contractile fiber, and actin cytoskeleton, suggesting the susceptibility of these subcellular compartments to redox regulation. Moreover, these observed SNO-sensitive proteins are primarily involved in metabolic pathways, including the tricarboxylic acid cycle, glycolysis/gluconeogenesis, glutathione metabolism, and fatty acid metabolism, suggesting the importance of redox regulation in muscle metabolism and insulin action. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Su, Dian; Shukla, Anil K.; Chen, Baowei; Kim, Jong-Seo; Nakayasu, Ernesto; Qu, Yi; Aryal, Uma; Weitz, Karl; Clauss, Therese R. W.; Monroe, Matthew E.; Camp, David G., II; Bigelow, Diana J.; Smith, Richard D.; Qian, Wei-Jun] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA.
[Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Qian, WJ (reprint author), Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA.
EM Weijun.qian@pnnl.gov
RI Smith, Richard/J-3664-2012
OI Smith, Richard/0000-0002-2381-2349
FU NIH [DP2OD006668, R01 DK074795, P41 RR018522, P41 GM103493]; DOE
[DE-AC05-76RLO-1830]
FX Portions of this work were supported by the NIH Director's New Innovator
Award Program DP2OD006668, a DOE Early Career Research Award, and NIH
Grants R01 DK074795, P41 RR018522, and P41 GM103493. Experimental work
was performed in the Environmental Molecular Science Laboratory, a
DOE/BER national scientific user facility at PNNL in Richland,
Washington. PNNL is operated by Battelle for the DOE under Contract
DE-AC05-76RLO-1830.
NR 79
TC 20
Z9 20
U1 0
U2 36
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 APR
PY 2013
VL 57
BP 68
EP 78
DI 10.1016/j.freeradbiomed.2012.12.010
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 105AC
UT WOS:000316037000008
PM 23277143
ER
PT J
AU Rosenberg, DE
Huang, DL
Simonovich, SD
Belza, B
AF Rosenberg, Dori E.
Huang, Deborah L.
Simonovich, Shannon D.
Belza, Basia
TI Outdoor Built Environment Barriers and Facilitators to Activity among
Midlife and Older Adults with Mobility Disabilities
SO GERONTOLOGIST
LA English
DT Article
DE Ambulation; Neighborhood; Physical function; Walkability; Physical
activity; Disability
ID PHYSICAL-ACTIVITY; NEIGHBORHOOD ENVIRONMENT; QUALITATIVE RESEARCH;
METROPOLITAN-AREAS; PEOPLE; HEALTH; WALKABILITY; VALIDATION; FRAMEWORK;
ACCESS
AB Purpose: To gain better understanding of how the built environment impacts neighborhood-based physical activity among midlife and older adults with mobility disabilities. Design and methods: We conducted in-depth interviews with 35 adults over age 50, which used an assistive device and lived in King County, Washington, U.S. In addition, participants wore Global Positioning Systems (GPS) devices for 3 days prior to the interview. The GPS maps were used as prompts during the interviews. Open coding of the 35 interviews using latent content analysis resulted in key themes and subthemes that achieved consensus between coders. Two investigators independently coded the text of each interview. Results: Participants were on average of 67 years of age (range: 5086) and predominantly used canes (57%), walkers (57%), or wheelchairs (46%). Key themes pertained to curb ramp availability and condition, sidewalk availability and condition, hills, aesthetics, lighting, ramp availability, weather, presence and features of crosswalks, availability of resting places and shelter on streets, paved or smooth walking paths, safety, and traffic on roads. Implications: A variety of built environment barriers and facilitators to neighborhood-based activity exist for midlife and older adults with mobility disabilities. Preparing our neighborhood environments for an aging population that uses assistive devices will be important to foster independence and health.
C1 [Rosenberg, Dori E.] Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Huang, Deborah L.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S 182, Seattle, WA USA.
[Simonovich, Shannon D.; Belza, Basia] Univ Washington, Sch Nursing, Seattle, WA 98195 USA.
[Belza, Basia] Univ Washington, Hlth Promot Res Ctr, Seattle, WA 98195 USA.
RP Rosenberg, DE (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA.
EM rosenberg.d@ghc.org
FU NCCDPHP CDC HHS [U48-DP001911]
NR 38
TC 39
Z9 39
U1 6
U2 70
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD APR
PY 2013
VL 53
IS 2
BP 268
EP 279
DI 10.1093/geront/gns119
PG 12
WC Gerontology
SC Geriatrics & Gerontology
GA 106MR
UT WOS:000316148600009
PM 23010096
ER
PT J
AU Pischke, CR
Galarce, EM
Nagler, E
Aghi, M
Sorensen, G
Gupta, PC
Pednekar, MS
Sinha, DN
Viswanath, K
AF Pischke, Claudia R.
Galarce, Ezequiel M.
Nagler, Eve
Aghi, Mira
Sorensen, Glorian
Gupta, Prakash C.
Pednekar, Mangesh S.
Sinha, Dhirendra N.
Viswanath, K.
TI Message formats and their influence on perceived risks of tobacco use: a
pilot formative research project in India
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID FEAR APPEALS; HEALTH; SMOKING; PSYCHOLOGY; BEHAVIORS
AB In India, tobacco kills 900 000 people every year though the burden of tobacco is faced disproportionately in poorer states such as Bihar. Teachers may be a particularly influential group in setting norms around tobacco use in the Indian context. However, tobacco use among teachers remains high and perceptions of tobacco-related health risks are unexplored. To qualitatively explore perceptions about tobacco use among teachers in Bihar and to examine how risk information may be communicated through a variety of message formats, 12 messages on tobacco health risks varying in formats were tested in focus groups with teachers from Bihar. Participants stated that teachers were already aware of tobacco-related health risks. To further increase awareness of these risks, the inclusion of evidence-based facts in messages was recommended. Communicating risk information using negative emotions had a great appeal to teachers and was deemed most effective for increasing risk perception. Messages using narratives of teachers' personal accounts of quitting tobacco were deemed effective for increasing knowledge about the benefits of quitting. To conclude, messages using evidence-based information, possibly with negative emotions, testimonials with role models and those messages emphasizing self-efficacy in the format of narratives appear to appeal to teachers in Bihar.
C1 [Pischke, Claudia R.] BIPS Inst Epidemiol & Prevent Res, D-28359 Bremen, Germany.
[Galarce, Ezequiel M.; Nagler, Eve; Sorensen, Glorian; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Ctr Community Based Res, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Aghi, Mira; Gupta, Prakash C.; Pednekar, Mangesh S.] Healis Sekhsaria Inst Publ Hlth, Bombay 400614, Maharashtra, India.
[Sinha, Dhirendra N.] Sch Prevent Oncol, Patna 800001, Bihar, India.
RP Pischke, CR (reprint author), BIPS Inst Epidemiol & Prevent Res, Achterstr 30, D-28359 Bremen, Germany.
EM pischke@bips.uni-bremen.de
FU NCI NIH HHS [2R25 CA057713-06, 5K05 CA108663-05, 5R01CA120958-02, K05
CA108663]
NR 24
TC 3
Z9 3
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1153
J9 HEALTH EDUC RES
JI Health Educ. Res.
PD APR
PY 2013
VL 28
IS 2
BP 326
EP 338
DI 10.1093/her/cys112
PG 13
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA 108DY
UT WOS:000316273100012
PM 23221589
ER
PT J
AU McCauley, MP
Blake, KD
Meissner, HI
Viswanath, K
AF McCauley, M. P.
Blake, K. D.
Meissner, H. I.
Viswanath, K.
TI The social group influences of US health journalists and their impact on
the newsmaking process
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID NATIONAL-SURVEY; MEDIA COVERAGE; CANCER CONTROL; NEWS MEDIA;
DISPARITIES; WOMEN; REPORTERS; SCIENCE; CARE; OPPORTUNITIES
AB The news media play a vital role in disseminating health information, yet little is known about the social characteristics of health journalists or the impact they have on the newsmaking process. This study examines how the social group influences of US health journalists impact two important aspects of news production-'media agenda-setting' and 'framing'. Using data from a national survey of health and medical science journalists, the authors conducted multivariable logistic regression analyses to study the links between the gender, age and race/ethnicity of respondents, and the ways in which they utilized news sources, other resources, news priorities and story angles. Female respondents were more likely than males to say that educating people to make informed decisions and disseminating new, accurate information are important priorities. Female and minority journalists were more likely than white males to use a variety of sources, and to say it is important to develop the health and scientific literacy of audiences and influence public health behaviors. The gender and race/ethnicity of journalists play an important role in the production of health news. Health educators can foster improved coverage by learning more about the life experiences of health journalists and developing better working relationships with them.
C1 [McCauley, M. P.; Viswanath, K.] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02215 USA.
[McCauley, M. P.; Viswanath, K.] Dana Farber Canc Inst, McGraw Patterson Ctr Populat Sci, Boston, MA 02215 USA.
[Blake, K. D.] NCI, Hlth Commun & Informat Res Branch, NIH, Bethesda, MD 20892 USA.
[Meissner, H. I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
RP McCauley, MP (reprint author), Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02215 USA.
EM michael_mccauley@dfci.harvard.edu
RI McCauley, Michael/C-3642-2014
OI McCauley, Michael/0000-0003-3851-1765
FU NCI NIH HHS [R25 CA057713]
NR 70
TC 7
Z9 7
U1 4
U2 26
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1153
J9 HEALTH EDUC RES
JI Health Educ. Res.
PD APR
PY 2013
VL 28
IS 2
BP 339
EP 351
DI 10.1093/her/cys086
PG 13
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA 108DY
UT WOS:000316273100013
PM 22907539
ER
PT J
AU Navathe, AS
Silber, JH
Small, DS
Rosen, AK
Romano, PS
Even-Shoshan, O
Wang, YL
Zhu, JS
Halenar, MJ
Volpp, KG
AF Navathe, Amol S.
Silber, Jeffrey H.
Small, Dylan S.
Rosen, Amy K.
Romano, Patrick S.
Even-Shoshan, Orit
Wang, Yanli
Zhu, Jingsan
Halenar, Michael J.
Volpp, Kevin G.
TI Teaching Hospital Financial Status and Patient Outcomes Following ACGME
Duty Hour Reform
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Resident duty hour reform; quality of care; hospital financial health;
patient outcomes; health policy
ID QUALITY-OF-CARE; RESIDENTS WORK HOURS; ADMINISTRATIVE DATA; MEDICARE
BENEFICIARIES; COMORBIDITY MEASURES; COST IMPLICATIONS; SAFETY;
MORTALITY; STAY; REIMBURSEMENT
AB Objective To examine whether hospital financial health was associated with differential changes in outcomes after implementation of 2003 ACGME duty hour regulations. Data Sources/Study Setting Observational study of 3,614,174 Medicare patients admitted to 869 teaching hospitals from July 1, 2000 to June 30, 2005. Study Design Interrupted time series analysis using logistic regression to adjust for patient comorbidities, secular trends, and hospital site. Outcomes included 30-day mortality, AHRQ Patient Safety Indicators (PSIs), failure-to-rescue (FTR) rates, and prolonged length of stay (PLOS). Principal Findings All eight analyses measuring the impact of duty hour reform on mortality by hospital financial health quartile, in postreform year 1 (Post 1) or year 2 (Post 2) versus the prereform period, were insignificant: Post 1 OR range 1.001.02 and Post 2 OR range 0.991.02. For PSIs, all six tests showed clinically insignificant effect sizes. The FTR rate analysis demonstrated nonsignificance in both postreform years (OR 1.00 for both). The PLOS outcomes varied significantly only for the combined surgical sample in Post 2, but this effect was very small, OR 1.03 (95% CI 1.02, 1.04). Conclusions The impact of 2003 ACGME duty hour reform on patient outcomes did not differ by hospital financial health. This finding is somewhat reassuring, given additional financial pressure on teaching hospitals from 2011 duty hour regulations.
C1 [Navathe, Amol S.; Silber, Jeffrey H.; Small, Dylan S.; Even-Shoshan, Orit; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Navathe, Amol S.; Zhu, Jingsan; Halenar, Michael J.; Volpp, Kevin G.] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA.
[Navathe, Amol S.; Silber, Jeffrey H.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management & Econ, Philadelphia, PA 19104 USA.
[Navathe, Amol S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Silber, Jeffrey H.; Even-Shoshan, Orit; Wang, Yanli] Childrens Hosp Philadelphia, Ctr Outcomes Res, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.] Univ Penn, Dept Pediat, Sch Med, Philadelphia, PA 19104 USA.
[Silber, Jeffrey H.] Univ Penn, Dept Anesthesiol & Crit Care, Sch Med, Philadelphia, PA 19104 USA.
[Small, Dylan S.] Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA.
[Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Rosen, Amy K.] Vet Adm Hosp, Ctr Org Leadership & Management Res, Boston, MA USA.
[Romano, Patrick S.] Univ Calif Davis, Div Gen Med, Sch Med, Sacramento, CA 95817 USA.
[Romano, Patrick S.] Univ Calif Davis, Ctr Healthcare Policy & Res, Sch Med, Sacramento, CA 95817 USA.
[Halenar, Michael J.; Volpp, Kevin G.] Vet Adm Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Navathe, AS (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk,Room 202, Philadelphia, PA 19104 USA.
EM amol@wharton.upenn.edu
RI Romano, Patrick/N-4225-2014
OI Romano, Patrick/0000-0001-6749-3979
FU National Heart, Lung, and Blood Institute (NHLBI) [R01 HL082637]
FX This study was supported by grant R01 HL082637 from the National Heart,
Lung, and Blood Institute (NHLBI), "Impact of Resident Work Hour Rules
on Errors and Quality."
NR 48
TC 4
Z9 4
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
J9 HEALTH SERV RES
JI Health Serv. Res.
PD APR
PY 2013
VL 48
IS 2
BP 476
EP 498
DI 10.1111/j.1475-6773.2012.01453.x
PN 1
PG 23
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 106CW
UT WOS:000316120200008
PM 22862427
ER
PT J
AU Ghaffarzadegan, N
Epstein, AJ
Martin, EG
AF Ghaffarzadegan, Navid
Epstein, Andrew J.
Martin, Erika G.
TI Practice Variation, Bias, and Experiential Learning in Cesarean
Delivery: A Data-Based System Dynamics Approach
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Cesarean delivery; practice variation; experiential learning;
simulation; system dynamics
ID IDENTIFY INDICATIONS; DECISION-MAKING; HEALTH; MODEL; FEEDBACK;
OUTCOMES; AGREEMENT; PHYSICIAN; SELECTION; SERVICES
AB Objectives To simulate physician-driven dynamics of delivery mode decisions (scheduled cesarean delivery [CD] vs. vaginal delivery [VD] vs. unplanned CD after labor), and to evaluate a behavioral theory of how experiential learning leads to emerging bias toward more CD and practice variation across obstetricians. Data Sources/Study Setting Hospital discharge data on deliveries performed by 300 randomly selected obstetricians in Florida who finished obstetrics residency and started practice after 1991. Study Design We develop a system dynamics simulation model of obstetricians' delivery mode decision based on the literature of experiential learning. We calibrate the model and investigate the extent to which the model replicates the data. Principal Findings Our learning-based simulation model replicates the empirical data, showing that physicians are more likely to schedule CD as they practice longer. Variation in CD rates is related to the way that physicians learn from outcomes of past decisions and accumulate experience. Conclusions The repetitive nature of medical decision making, learning from past practice, and accumulating experience can account for increases in CD decisions and practice variation across physicians. Policies aimed at improving medical decision making should account for providers' feedback-based learning mechanisms.
C1 [Ghaffarzadegan, Navid] MIT, Engn Syst Div, Cambridge, MA 02139 USA.
[Epstein, Andrew J.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Martin, Erika G.] SUNY Albany, Rockefeller Coll Publ Affairs & Policy, Albany, NY 12222 USA.
[Martin, Erika G.] SUNY Albany, Nelson A Rockefeller Inst Govt, Albany, NY 12222 USA.
RP Ghaffarzadegan, N (reprint author), MIT, Engn Syst Div, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM navidg@mit.edu
NR 52
TC 6
Z9 6
U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
J9 HEALTH SERV RES
JI Health Serv. Res.
PD APR
PY 2013
VL 48
IS 2
BP 713
EP 734
DI 10.1111/1475-6773.12040
PN 2
PG 22
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 106CZ
UT WOS:000316120600004
PM 23398502
ER
PT J
AU Lindrooth, RC
Konetzka, RT
Navathe, AS
Zhu, JS
Chen, W
Volpp, K
AF Lindrooth, Richard C.
Konetzka, R. Tamara
Navathe, Amol S.
Zhu, Jingsan
Chen, Wei
Volpp, Kevin
TI The Impact of Profitability of Hospital Admissions on Mortality
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Hospital quality; medicare reimbursement; hospital finances
ID ACUTE MYOCARDIAL-INFARCTION; PROSPECTIVE PAYMENT; HEALTH-CARE; QUALITY
INFORMATION; COMPETITION; REIMBURSEMENT; MEDICARE; OUTCOMES; INCENTIVES;
NONPROFIT
AB Background Fiscal constraints faced by Medicare are leading to policies designed to reduce expenditures. Evidence of the effect of reduced reimbursement on the mortality of Medicare patients discharged from all major hospital service lines is limited. Methods We modeled risk-adjusted 30-day mortality of patients discharged from 21 hospital service lines as a function of service line profitability, service line time trends, and hospital service line and year-fixed effects. We simulated the effect of alternative revenue-neutral reimbursement policies on mortality. Our sample included all Medicare discharges from PPS-eligible hospitals (1997, 2001, and 2005). Results The results reveal a statistically significant inverse relationship between changes in profitability and mortality. A $0.19 average reduction in profit per $1.00 of costs led to a 0.0100.020 percentage-point increase in mortality rates (p<.001). Mortality in newly unprofitable service lines is significantly more sensitive to reduced payment generosity than in service lines that remain profitable. Policy simulations that target service line inequities in payment generosity result in lower mortality rates, roughly 70013,000 fewer deaths nationally. Conclusions The policy simulations raise questions about the trade-offs implicit in universal reductions in reimbursement. The effect of reduced payment generosity on mortality could be mitigated by targeting highly profitable services only for lower reimbursement.
C1 [Lindrooth, Richard C.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO 80045 USA.
[Konetzka, R. Tamara] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Navathe, Amol S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Zhu, Jingsan; Chen, Wei] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Volpp, Kevin] Univ Penn, Perelman Sch Med, Leonard Davis Inst, Philadelphia VA Med Ctr,Ctr Hlth Incent & Behav E, Philadelphia, PA 19104 USA.
[Volpp, Kevin] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
RP Lindrooth, RC (reprint author), Univ Colorado, Colorado Sch Publ Hlth, Anschutz Med Campus,13001 E 17th Pl,Campus Box B1, Aurora, CO 80045 USA.
EM richard.lindrooth@ucdenver.edu
OI Lindrooth, Richard/0000-0001-9538-9749
FU Robert Wood Johnson Foundation's Health Care Financing and Organization
Initiative; Agency for Healthcare Research and Quality
FX Joint Acknowledgment/Disclosure Statement: We thank Robert Wood Johnson
Foundation's Health Care Financing and Organization Initiative and the
Agency for Healthcare Research and Quality for funding this research. We
also thank Jeff Stensland for helpful comments on a previous draft of
this manuscript.
NR 34
TC 7
Z9 7
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
J9 HEALTH SERV RES
JI Health Serv. Res.
PD APR
PY 2013
VL 48
IS 2
BP 792
EP 809
DI 10.1111/1475-6773.12026
PN 2
PG 18
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 106CZ
UT WOS:000316120600008
PM 23346946
ER
PT J
AU Focks, JJ
Brouwer, MA
van Oijen, MGH
Lanas, A
Bhatt, DL
Verheugt, FWA
AF Focks, Jeroen Jaspers
Brouwer, Marc A.
van Oijen, Martijn G. H.
Lanas, Angel
Bhatt, Deepak L.
Verheugt, Freek W. A.
TI Concomitant use of clopidogrel and proton pump inhibitors: impact on
platelet function and clinical outcome- a systematic review
SO HEART
LA English
DT Review
ID PERCUTANEOUS CORONARY INTERVENTION; DUAL-ANTIPLATELET THERAPY; ACUTE
MYOCARDIAL-INFARCTION; EXPERT CONSENSUS DOCUMENTS; FOUNDATION
TASK-FORCE; STENT IMPLANTATION; CARDIOVASCULAR OUTCOMES;
GASTROINTESTINAL RISKS; HEALTHY-SUBJECTS; CONTROLLED-TRIAL
AB Background Clopidogrel as an adjunct to aspirin has improved outcomes after acute coronary syndromes, but laboratory studies suggest a reduced antiplatelet effect when proton pump inhibitors (PPIs) are co-administered. Despite corroborating data from retrospective studies, new clinical data fuel the controversy on this issue.
Purpose Systematic review of the impact of the addition of PPIs to clopidogrel on platelet function and cardiovascular outcome.
Data sources PubMed, Web-of-Science, Cochrane Database and reference lists of related articles.
Study selection Published articles on controlled studies addressing the addition of PPIs to clopidogrel. Platelet function studies describe patients as well as healthy volunteers. Clinical studies concern patients using clopidogrel for acute coronary syndromes or because of stent implantation for stable coronary disease.
Data extraction Two investigators independently reviewed the identified articles for eligibility, and one author extracted the data.
Data synthesis In 70% (7/10) of the laboratory studies examining healthy volunteers on clopidogrel, addition of PPIs resulted in a significant reduction in platelet inhibition. For patients, this was observed in 11/18 (61%) studies. The 33 clinical studies showed significant heterogeneity in observed outcomes, with risk ratios for major adverse cardiovascular events varying from 0.64 to 4.58 in the case of PPI use, which was randomly allocated in only two studies. Consequently, imbalances between prognosticators at baseline and PPI prescription bias markedly contributed to the variability in results.
Conclusions Despite indications of reduced antiplatelet activity ex vivo in the case of PPI administration in clopidogrel users, data on the clinical consequences are controversial. With the accumulating evidence from better designed, prospective clinical studies, an adverse effect of PPI use on clinical outcome in patients on clopidogrel cannot be substantiated. This review challenges the validity of conclusions based on quantitative analyses of predominantly non-randomised data.
C1 [Focks, Jeroen Jaspers; Brouwer, Marc A.; Verheugt, Freek W. A.] Radboud Univ Nijmegen, Med Ctr, Dept Cardiol, NL-6500 HB Nijmegen, Netherlands.
[van Oijen, Martijn G. H.] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[van Oijen, Martijn G. H.] Univ Calif Los Angeles, Dept Gastroenterol & Hepatol, Los Angeles, CA USA.
[Lanas, Angel] Univ Zaragoza, CIBERehd, Hosp Clin, Dept Gastroenterol, Zaragoza, Spain.
[Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Cardiol, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Focks, JJ (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Cardiol 670, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM j.jaspersfocks@gmail.com
RI Brouwer, Marc/B-1158-2014; Verheugt, F.W.A./H-8105-2014
FU AstraZeneca; Nycomed; Pfizer; Amarin; Bristol-Myers Squibb; Eisai;
Ethicon; Medtronic; Sanofi Aventis; Medicines Company; Bayer AG; Roche;
Eli Lilly; Boehringer Ingelheim
FX MGHvO has served as a consultant for and has received unrestricted grant
support from AstraZeneca, Nycomed and Pfizer; AL has served as a
consultant for AstraZeneca, Pfizer and Bayer AG; DLB discloses the
following relationships - Advisory Board: Medscape Cardiology; Board of
Directors: Boston VA Research Institute, Society of Chest Pain Centers;
Chair: American Heart Association Get With The Guidelines Science
Subcommittee; Honoraria: American College of Cardiology (Editor,
Clinical Trials, Cardiosource), Duke Clinical Research Institute
(clinical trial steering committees), Slack Publications (Chief Medical
Editor, Cardiology Today Intervention), WebMD (CME steering committees);
Other: Senior Associate Editor, Journal of Invasive Cardiology; Research
Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon,
Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research:
FlowCo, PLx Pharma, Takeda, and Chair of the COGENT study. FWAV has
received educational and research grants from Bayer AG, Roche, Eli Lilly
and Boehringer Ingelheim and has received honoraria for consultancies
from Daiichi Sankyo, Eli Lilly, Merck, The Medicines Company and Bayer
AG.
NR 78
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Z9 44
U1 2
U2 20
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD APR
PY 2013
VL 99
IS 8
BP 520
EP 527
DI 10.1136/heartjnl-2012-302371
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 108SX
UT WOS:000316317500004
PM 22851683
ER
PT J
AU Smith, KR
Dahl, HHM
Canafoglia, L
Andermann, E
Damiano, J
Morbin, M
Bruni, AC
Giaccone, G
Cossette, P
Saftig, P
Grotzinger, J
Schwake, M
Andermann, F
Staropoli, JF
Sims, KB
Mole, SE
Franceschetti, S
Alexander, NA
Cooper, JD
Chapman, HA
Carpenter, S
Berkovic, SF
Bahlo, M
AF Smith, Katherine R.
Dahl, Hans-Henrik M.
Canafoglia, Laura
Andermann, Eva
Damiano, John
Morbin, Michela
Bruni, Amalia C.
Giaccone, Giorgio
Cossette, Patrick
Saftig, Paul
Groetzinger, Joachim
Schwake, Michael
Andermann, Frederick
Staropoli, John F.
Sims, Katherine B.
Mole, Sara E.
Franceschetti, Silvana
Alexander, Noreen A.
Cooper, Jonathan D.
Chapman, Harold A.
Carpenter, Stirling
Berkovic, Samuel F.
Bahlo, Melanie
TI Cathepsin F mutations cause Type B Kufs disease, an adult-onset neuronal
ceroid lipofuscinosis
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID SEQUENCING DATA; VARIANTS; GENE
AB Kufs disease, an adult-onset neuronal ceroid lipofuscinosis, is challenging to diagnose and genetically heterogeneous. Mutations in CLN6 were recently identified in recessive Kufs disease presenting as progressive myoclonus epilepsy (Type A), whereas the molecular basis of cases presenting with dementia and motor features (Type B) is unknown. We performed genome-wide linkage mapping of two families with recessive Type B Kufs disease and identified a single region on chromosome 11 to which both families showed linkage. Exome sequencing of five samples from the two families identified homozygous and compound heterozygous missense mutations in CTSF within this linkage region. We subsequently sequenced CTSF in 22 unrelated individuals with suspected recessive Kufs disease, and identified an additional patient with compound heterozygous mutations. CTSF encodes cathepsin F, a lysosomal cysteine protease, dysfunction of which is a highly plausible candidate mechanism for a storage disorder like ceroid lipofuscinosis. In silico modeling suggested the missense mutations would alter protein structure and function. Moreover, re-examination of a previously published mouse knockout of Ctsf shows that it recapitulates the light and electron-microscopic pathological features of Kufs disease. Although CTSF mutations account for a minority of cases of type B Kufs, CTSF screening should be considered in cases with early-onset dementia and may avoid the need for invasive biopsies.
C1 [Smith, Katherine R.; Bahlo, Melanie] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Melbourne, Vic 3052, Australia.
[Smith, Katherine R.] Univ Melbourne, Fac Med Biol, Melbourne, Vic 3010, Australia.
[Bahlo, Melanie] Univ Melbourne, Dept Math & Stat, Melbourne, Vic 3010, Australia.
[Dahl, Hans-Henrik M.; Damiano, John; Berkovic, Samuel F.] Univ Melbourne, Dept Med, Epilepsy Res Ctr, Melbourne, Vic 3081, Australia.
[Canafoglia, Laura; Franceschetti, Silvana] IRCCS Fdn, C Besta Neurol Inst, Unit Neurophysiopathol, I-20133 Milan, Italy.
[Morbin, Michela; Giaccone, Giorgio] IRCCS Fdn, C Besta Neurol Inst, I-20133 Milan, Italy.
[Andermann, Eva; Andermann, Frederick] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
[Andermann, Eva] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2B4, Canada.
[Andermann, Eva] McGill Univ, Neurogenet Unit, Montreal, PQ H3A 2B4, Canada.
[Andermann, Frederick] McGill Univ, Epilepsy Serv, Montreal, PQ H3A 2B4, Canada.
[Andermann, Frederick] McGill Univ, Seizure Clin, Montreal, PQ H3A 2B4, Canada.
[Andermann, Frederick] McGill Univ, Montreal Neurol Hosp & Inst, Dept Pediat, Montreal, PQ H3A 2B4, Canada.
[Bruni, Amalia C.] Azienda Sanit Prov, Lamezia Terme, Reg Neurogenet Ctr, I-88100 Catanzaro, Italy.
[Cossette, Patrick] Univ Montreal, CHUM Hop Notre Dame, Dept Med, Montreal, PQ H3C 3T5, Canada.
[Saftig, Paul; Groetzinger, Joachim; Schwake, Michael] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany.
[Staropoli, John F.; Sims, Katherine B.] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Ctr Human Genet Res, Boston, MA 02114 USA.
[Mole, Sara E.] UCL, UCL Inst Child Hlth, Mol Med Unit, MRC Lab Mol Cell Biol, London WC1E 6BT, England.
[Mole, Sara E.] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
[Alexander, Noreen A.; Cooper, Jonathan D.] Kings Coll London, Inst Psychiat, Kings Hlth Partners Ctr Neurodegenerat Res, Dept Neurosci,Ctr Cellular Basis Behav, London SE5 8AF, England.
[Chapman, Harold A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Chapman, Harold A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Carpenter, Stirling] Hosp Sao Joao, Serv Anat Patol, P-4200319 Oporto, Portugal.
RP Berkovic, SF (reprint author), Univ Melbourne, Dept Med, Epilepsy Res Ctr, Melbourne, Vic 3081, Australia.
EM s.berkovic@unimelb.edu.au; bahlo@wehi.edu.au
RI Saftig, Paul/A-7966-2010; Cooper, Jonathan/C-8117-2009; Canafoglia,
Laura/K-4787-2016;
OI Cooper, Jonathan/0000-0003-1339-4750; Canafoglia,
Laura/0000-0002-5385-761X; Morbin, Michela/0000-0001-8034-3123;
Berkovic, Samuel/0000-0003-4580-841X; Mole, Sara/0000-0003-4385-4957
FU Australian Government National Health and Medical Research Council
[490037, 628952, 466671]; Australian Research Council [FT100100764];
Victorian State Government; Deutsche Forschungsgemeinschaft [SFB877];
National Institutes of Health [NS41930]; Pratt Foundation; Batten
Disease Support and Research Association; Natalie Fund
FX This work was supported by the Australian Government National Health and
Medical Research Council (490037 to M.B., 628952 and 466671 to S.F.B.,
the Independent Research Institute Infrastructure Support Scheme to M.B.
and K.R.S.); The Australian Research Council (FT100100764 to M.B.); the
Victorian State Government (Operational Infrastructure Program to M.B.
and K.R.S.); the Deutsche Forschungsgemeinschaft (SFB877 to P.S., J.G.
and M.S.); the National Institutes of Health (NS41930 to J.D.C.); the
Pratt Foundation (to K.R.S.), The Batten Disease Support and Research
Association (to S.E.M., J.D.C., J.M.S. and K.B.S.) and the Natalie Fund
(to J.D.C.).
NR 19
TC 34
Z9 37
U1 0
U2 9
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 APR 1
PY 2013
VL 22
IS 7
BP 1417
EP 1423
DI 10.1093/hmg/dds558
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 108MH
UT WOS:000316297000013
PM 23297359
ER
PT J
AU Forman, JP
Scott, JB
Ng, K
Drake, BF
Suarez, EG
Hayden, DL
Bennett, GG
Chandler, PD
Hollis, BW
Emmons, KM
Giovannucci, EL
Fuchs, CS
Chan, AT
AF Forman, John P.
Scott, Jamil B.
Ng, Kimmie
Drake, Bettina F.
Suarez, Elizabeth Gonzalez
Hayden, Douglas L.
Bennett, Gary G.
Chandler, Paulette D.
Hollis, Bruce W.
Emmons, Karen M.
Giovannucci, Edward L.
Fuchs, Charles S.
Chan, Andrew T.
TI Effect of Vitamin D Supplementation on Blood Pressure in Blacks
SO HYPERTENSION
LA English
DT Article
DE black; blood pressure; hypertension; randomized controlled trial;
vitamin D
ID CARDIOVASCULAR RISK-FACTORS; RENIN-ANGIOTENSIN SYSTEM;
PLACEBO-CONTROLLED TRIAL; PLASMA 25-HYDROXYVITAMIN D; DOUBLE-BLIND;
CHOLECALCIFEROL SUPPLEMENTATION; INCIDENT HYPERTENSION; DIETARY
REQUIREMENT; RANDOMIZED-TRIAL; RENAL PERFUSION
AB Blacks have significantly higher rates of hypertension than whites, and lower circulating levels of 25-hydroxyvitamin D. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on blood pressure in blacks. During 2 winters from 2008 to 2010, 283 blacks (median age, 51 years) were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 international units of cholecalciferol per day. At baseline, 3 months, and 6 months, systolic and diastolic pressure and 25-hydroxyvitamin D were measured. The 3-month follow-up was completed in 250 (88%) participants. The difference in systolic pressure between baseline and 3 months was +1.7 mm Hg for those receiving placebo, -0.66 mm Hg for 1000 U/d, -3.4 mm Hg for 2000 U/d, and -4.0 mm Hg for 4000 U/d of cholecalciferol (-1.4 mm Hg for each additional 1000 U/d of cholecalciferol; P=0.04). For each 1-ng/mL increase in plasma 25-hydroxyvitamin D, there was a significant 0.2-mm Hg reduction in systolic pressure (P=0.02). There was no effect of cholecalciferol supplementation on diastolic pressure (P=0.37). Within an unselected population of blacks, 3 months of oral vitamin D3 supplementation significantly, yet modestly, lowered systolic pressure. Future trials of vitamin D supplementation on blood pressure are needed to confirm these promising results, particularly among blacks, a population for whom vitamin D deficiency may play a more specific mechanistic role in the pathogenesis of hypertension. (Hypertension. 2013;61:779-785.). Online Data Supplement
C1 [Forman, John P.] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA.
[Chandler, Paulette D.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Scott, Jamil B.; Emmons, Karen M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Ng, Kimmie; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Scott, Jamil B.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA.
[Drake, Bettina F.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Hayden, Douglas L.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Dept Med, Boston, MA 02114 USA.
[Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
[Hollis, Bruce W.] Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA.
RP Forman, JP (reprint author), Brigham & Womens Hosp, Div Renal, 41 Ave Louis Pasteur,Suite 120, Boston, MA 02115 USA.
EM jforman@partners.org
OI Drake, Bettina/0000-0001-9340-5848
FU National Heart, Lung, and Blood Institute [5R01HL105440]; National
Cancer Institute [P50CA127003, K07CA148894, K22CA126992, 5K05CA124415];
Department of Defense Prostate Cancer Research Program [PC081669];
American Society of Clinical Oncology Career Development Award;
Pharmavite LLC (Mission Hill, CA)
FX This trial was funded by the National Heart, Lung, and Blood Institute
(5R01HL105440 [Dr Forman]), the National Cancer Institute (P50CA127003;
K07CA148894 [Dr Ng]; K22CA126992; 5K05CA124415 [Dr Emmons]), the
Department of Defense Prostate Cancer Research Program (PC081669 [Dr
Drake]), the American Society of Clinical Oncology Career Development
Award (Dr Ng), and Pharmavite LLC (Mission Hill, CA). These funding
sources had no role in the conception or conduct of the study, took no
part in the data collection or analysis, and had no role in the
drafting, review, or approval of the article.
NR 51
TC 79
Z9 82
U1 4
U2 27
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD APR
PY 2013
VL 61
IS 4
BP 779
EP 785
DI 10.1161/HYPERTENSIONAHA.111.00659
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 106AC
UT WOS:000316112800019
PM 23487599
ER
PT J
AU Kostis, WJ
Cabrera, J
Hooper, WC
Whelton, PK
Espeland, MA
Cosgrove, NM
Cheng, JQ
Deng, YZ
De Staerck, C
Pyle, M
Maruthur, N
Reyes, I
Anderson, CAM
Liu, J
Kostis, JB
AF Kostis, William J.
Cabrera, Javier
Hooper, W. Craig
Whelton, Paul K.
Espeland, Mark A.
Cosgrove, Nora M.
Cheng, Jerry Q.
Deng, Yingzi
De Staerck, Christine
Pyle, Meredith
Maruthur, Nisa
Reyes, Ingrid
Anderson, Cheryl A. M.
Liu, Jie
Kostis, John B.
TI Relationships Between Selected Gene Polymorphisms and Blood Pressure
Sensitivity to Weight Loss in Elderly Persons With Hypertension
SO HYPERTENSION
LA English
DT Article
DE blood pressure; genetics; obesity; sodium
ID SALT SENSITIVITY; NONPHARMACOLOGIC INTERVENTIONS; SODIUM REDUCTION;
DIETARY-SODIUM; OLDER PERSONS; TRIAL; ASSOCIATION; PREVENTION;
CONTRIBUTE; DISEASE
AB Salt sensitivity, the heterogeneity in the response of blood pressure (BP) to alterations in sodium intake, has been studied extensively, whereas weight sensitivity, the heterogeneity in BP response to weight change, has received scant attention. We examined the relationship of 21 gene polymorphisms previously found to be associated with hypertension, diabetes mellitus, or obesity, with weight sensitivity in the Trial of Nonpharmacologic Interventions in the Elderly, where participants with hypertension were randomized to receive intensive dietary intervention of sodium reduction, weight loss, both, or attention control, whereas pharmacological therapy was kept constant. After correcting for multiplicity, we identified significant associations of 3 polymorphisms with weight sensitivity of systolic BP (rs4646994, rs2820037, and rs1800629) and 3 polymorphisms for diastolic BP (rs4646994, rs2820037, and rs5744292). A recursive partitioning algorithm selected the combination of rs4646994, rs1800629, rs1982073, and rs1800896 as the set associated with the highest weight sensitivity. Polymorphisms related to hypertension, obesity, and diabetes mellitus are associated with weight sensitivity of BP. (Hypertension. 2013;61:857-863.) circle Online Data Supplement
C1 [Kostis, William J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Cabrera, Javier; Reyes, Ingrid; Liu, Jie] Rutgers State Univ, Dept Stat, Piscataway, NJ USA.
[Cabrera, Javier; Cosgrove, Nora M.; Cheng, Jerry Q.; Deng, Yingzi; Kostis, John B.] UMDNJ Robert Wood Johnson Med Sch, Cardiovasc Inst, New Brunswick, NJ USA.
[Hooper, W. Craig; De Staerck, Christine; Pyle, Meredith] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Whelton, Paul K.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Espeland, Mark A.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Maruthur, Nisa] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA.
[Maruthur, Nisa; Anderson, Cheryl A. M.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
RP Kostis, WJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 800, Boston, MA 02114 USA.
EM wkostis@partners.org
FU National Institute on Aging; National Heart, Lung, and Blood Institute;
Robert Wood Johnson Foundation
FX This study was supported, in part, by the National Institute on Aging,
the National Heart, Lung, and Blood Institute, and the Robert Wood
Johnson Foundation.
NR 34
TC 6
Z9 6
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD APR
PY 2013
VL 61
IS 4
BP 857
EP +
DI 10.1161/HYPERTENSIONAHA.111.00712
PG 23
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 106AC
UT WOS:000316112800030
PM 23438931
ER
PT J
AU Ma, JQ
Chen, W
Zhang, LJ
Tucker, B
Zhu, GC
Sasaki, H
Hao, L
Wang, L
Ci, HL
Jiang, HB
Stashenko, P
Li, YP
AF Ma, Junqing
Chen, Wei
Zhang, Lijie
Tucker, Byron
Zhu, Guochun
Sasaki, Hajime
Hao, Liang
Wang, Lin
Ci, Hongliang
Jiang, Hongbing
Stashenko, Philip
Li, Yi-Ping
TI RNA Interference-Mediated Silencing of Atp6i Prevents Both Periapical
Bone Erosion and Inflammation in the Mouse Model of Endodontic Disease
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PERIODONTAL-LIGAMENT CELLS; MICRO-COMPUTED TOMOGRAPHY; T-CELL; IN-VITRO;
OSTEOCLAST DIFFERENTIATION; APICAL PERIODONTITIS; PARKINSONS-DISEASE;
ROOT RESORPTION; B-LYMPHOCYTE; DENTAL-PULP
AB Dental caries is one of the most prevalent infectious diseases in the United States, affecting approximately 80% of children and the majority of adults. Dental caries may lead to endodontic disease, where the bacterial infection progresses to the root canal system of the tooth, leading to periapical inflammation, bone erosion, severe pain, and tooth loss. Periapical inflammation may also exacerbate inflammation in other parts of the body. Although conventional clinical therapies for this disease are successful in approximately 80% of cases, there is still an urgent need for increased efficacy of treatment. In this study, we applied a novel gene-therapeutic approach using recombinant adeno-associated virus (AAV)-mediated Atp6i RNA interference (RNAi) knockdown of Atp6i/TIRC7 gene expression to simultaneously target periapical bone resorption and periapical inflammation. We found that Atp6i inhibition impaired osteoclast function in vitro and in vivo and decreased the number of T cells in the periapical lesion. Notably, AAV-mediated Atp6i/TIRC7 knockdown gene therapy reduced bacterial infection-stimulated bone resorption by 80% in the mouse model of endodontic disease. Importantly, Atp6i(+/-) mice with haploinsufficiency of Atp6i exhibited protection similar to that in mice with bacterial infection-stimulated bone erosion and periapical inflammation, which confirms the potential therapeutic effect of AAV-small hairpin RNA (shRNA)-Atp6i/TIRC7. Our results demonstrate that AAV-mediated Atp6i/TIRC7 knockdown in periapical tissues can inhibit endodontic disease development, bone resorption, and inflammation, indicating for the first time that this potential gene therapy may significantly improve the health of those who suffer from endodontic disease.
C1 [Ma, Junqing; Chen, Wei; Tucker, Byron; Zhu, Guochun; Hao, Liang; Ci, Hongliang; Jiang, Hongbing; Li, Yi-Ping] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Ma, Junqing; Wang, Lin; Jiang, Hongbing] Nanjing Med Univ, Inst Stomatol, Nanjing, Jiangsu, Peoples R China.
[Zhang, Lijie; Sasaki, Hajime; Stashenko, Philip] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA.
[Tucker, Byron] Harvard Univ, Dept Restorat Dent Endodont, Sch Dent Med, Owings Mills, MD USA.
RP Li, YP (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
EM wechen@uab.edu; ypli@uab.edu
FU NIH [RC1-DE-020533, R01-AR-055307]
FX This work was supported by NIH grants RC1-DE-020533 (Y.P.L.) and
R01-AR-055307 (Y.P.L.).
NR 46
TC 11
Z9 12
U1 0
U2 20
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2013
VL 81
IS 4
BP 1021
EP 1030
DI 10.1128/IAI.00756-12
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 108RM
UT WOS:000316313700001
PM 23166162
ER
PT J
AU Biswas, A
Kobayashi, KS
AF Biswas, Amlan
Kobayashi, Koichi S.
TI Regulation of intestinal microbiota by the NLR protein family
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Review
DE Crohns disease; inflammasome; NLRP6; NOD2; microbiome
ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; ILEAL CROHNS-DISEASE; TOLL-LIKE
RECEPTORS; EPITHELIAL-CELLS; PANETH CELLS; DENDRITIC CELLS; INNATE
IMMUNITY; NOD2; EXPRESSION
AB Regulation of intestinal microbiota by NLR proteins.The human intestine harbors a diverse microbial community consisting of a large number of bacteria and other micro-organisms that have co-evolved with the host intestinal immune system. During this process, microbiota and the host immune system shape one another by various mechanisms to achieve a successful symbiotic relationship. An increasing amount of evidence suggests that dysbiosisuthe breakdown of such harmonized colonizationumay result in infectious and inflammatory disorders, and recent advances in our studies indicate that receptors such as Toll-like receptors and NLR (nucleotide-binding oligomerization domain-like receptor; or nucleotide-binding domain- and leucine-rich repeat-containing receptor) proteins that detect micro-organisms and their products play a critical role in maintaining intestinal homeostasis. In this review, we summarize the role of NLR proteins in the regulation of intestinal microbiota. NLR proteins belong to a diverse family of cytoplasmic microbial sensors, mutations of which are involved in various disorders, including inflammatory bowel diseases. Understanding of the different roles of NLR family proteins in the intestine is, therefore, an important step towards the development of therapeutics against digestive diseases.
C1 [Biswas, Amlan; Kobayashi, Koichi S.] Texas A&M Hlth Sci Ctr, Dept Microbial & Mol Pathogenesis, College Stn, TX 77843 USA.
[Biswas, Amlan; Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Biswas, Amlan; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02215 USA.
RP Kobayashi, KS (reprint author), Texas A&M Hlth Sci Ctr, Coll Med, Dept Microbial & Mol Pathogenesis, 415A Reynolds Med Bldg, College Stn, TX 77843 USA.
EM kobayashi@medicine.tamhsc.edu
FU National Institutes of Health [R01DK074738]; Broad Medical Research
Program of the Eli and Edythe L. Broad Foundations [IBD-0328]; Cancer
Research Institute; Claudia Adams Barr Award; Crohn's and Colitis
Foundation of America
FX National Institutes of Health (R01DK074738 to K.S.K.); the Broad Medical
Research Program of the Eli and Edythe L. Broad Foundations (IBD-0328 to
K.S.K.). K.S.K. is a recipient of the Investigator Award from the Cancer
Research Institute and the Claudia Adams Barr Award. A.B. is a recipient
of fellowship from the Crohn's and Colitis Foundation of America.
NR 73
TC 12
Z9 12
U1 0
U2 32
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
J9 INT IMMUNOL
JI Int. Immunol.
PD APR
PY 2013
VL 25
IS 4
BP 207
EP 214
DI 10.1093/intimm/dxs116
PG 8
WC Immunology
SC Immunology
GA 108KQ
UT WOS:000316292200001
PM 23325116
ER
PT J
AU Mondolfi, AEP
Duffey, GB
Horton, LE
Tirado, M
Jaimes, OR
Perez-Alvarez, A
Zerpa, O
AF Paniz Mondolfi, Alberto E.
Duffey, Gabrielle Baker
Horton, Lucy E.
Tirado, Mariantonieta
Reyes Jaimes, Oscar
Perez-Alvarez, Alexandra
Zerpa, Olga
TI Intermediate/borderline disseminated cutaneous leishmaniasis
SO INTERNATIONAL JOURNAL OF DERMATOLOGY
LA English
DT Article
ID NEW-WORLD; MUCOCUTANEOUS LEISHMANIASIS; RISK-FACTORS; SPECTRUM;
CLASSIFICATION; CHEMOTHERAPY; AMAZONENSIS; VENEZUELA; TRAVELERS;
FEATURES
AB Leishmaniasis is a diverse group of vector-borne diseases caused by a subset of predominantly intracellular protozoal species of the genus Leishmania. Cutaneous disease may be subdivided into localized, intermediate, and diffuse forms. Intermediate cutaneous leishmaniasis is distributed widely in Latin America and is characterized by cutaneous lesions, which may be accompanied by mucosal disease and demonstrate a tendency toward chronicity and relapse as well as resistance to standard treatment regimens. Leishmania parasites of the subgenus Viannia have been identified as the major etiologic agent of this subset of infections. The present review provides a brief perspective on leishmaniasis followed by a review of classification, transmission, clinical presentation, and evolution of disease, immunology, and current treatment approaches for the intermediate/borderline disseminated subset of cutaneous leishmaniasis.
C1 [Paniz Mondolfi, Alberto E.; Horton, Lucy E.] Tufts Med Ctr, Dept Dermatol, Boston, MA USA.
[Paniz Mondolfi, Alberto E.; Horton, Lucy E.] Miraca Life Sci, Boston, MA USA.
[Paniz Mondolfi, Alberto E.; Perez-Alvarez, Alexandra] UCV IVSS, Lab Bioquim, Inst Biomed, Caracas, Venezuela.
[Duffey, Gabrielle Baker] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Tirado, Mariantonieta] Baptist Hlth Syst, Dept Pathol, Birmingham, AL USA.
[Reyes Jaimes, Oscar] UCV MSDS, Dept Dermatopatol, Inst Biomed, Caracas, Venezuela.
[Zerpa, Olga] UCV MSDS, Secc Leishmaniasis, Inst Biomed, Caracas, Venezuela.
RP Mondolfi, AEP (reprint author), Tufts Med Ctr, Dept Dermatol, Boston, MA USA.
EM albertopaniz@yahoo.com
NR 53
TC 9
Z9 9
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0011-9059
EI 1365-4632
J9 INT J DERMATOL
JI Int. J. Dermatol.
PD APR
PY 2013
VL 52
IS 4
BP 446
EP 455
DI 10.1111/j.1365-4632.2012.05709.x
PG 10
WC Dermatology
SC Dermatology
GA 108WS
UT WOS:000316327500010
ER
PT J
AU Esfahani, SA
Close, C
Yousefzadeh, DK
AF Esfahani, Shadi Abdar
Close, Clare
Yousefzadeh, David K.
TI Side-to-side and interpolar renal duplications: the nonpolar variety
SO INTERNATIONAL UROLOGY AND NEPHROLOGY
LA English
DT Article
DE Duplication; Kidney; Nonpolar; Variation; Intravenous pyelogram
ID URETERAL QUADRUPLICATION; KIDNEY; TRIPLICATION; CHILDREN; GIRLS
AB The Weigert-Meyer rule predicts the draining pattern of duplex ureters in bipolar renal duplications. This paper introduces two cases of nonpolar renal duplication. A 3-month-old and a 15-year-old female with history of urinary tract infection were evaluated with intravenous pyelograms (IVP) and eleven different parameters were analyzed. The infant's IVP showed an unobstructed side-to-side right renal duplication with normal-sized nondisplaced lateral moiety and a complete set of calyces, without drooping lily sign. The nonobstructed moiety projected medial and mildly inferior to the lateral moiety which had normal height and axis. The ureters joined each other in lower abdomen. Severe platyspondyly was noted due to hyperalimentation-induced metabolic bone disease. The second case had an unobstructed interpolar extra moiety between the upper and the lower poles with an otherwise unobstructed, normally sized single-system kidney, without drooping lily sign. The paradigm shift from classic anatomic to contemporary cell biological theory validates the nonpolar renal duplication concept, with side-to-side and interpolar arrangements of the moieties, in defiance of Weigert-Meyer rule.
C1 [Esfahani, Shadi Abdar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
[Close, Clare] Close Pediat Urol Ctr, Henderson, NV USA.
[Yousefzadeh, David K.] Univ Chicago, Dept Pediat, Comers Children Hosp, Chicago, IL 60076 USA.
[Yousefzadeh, David K.] Univ Chicago, Dept Radiol, Comers Children Hosp, Chicago, IL 60076 USA.
RP Yousefzadeh, DK (reprint author), Univ Chicago, Dept Pediat, Comers Children Hosp, 8900 Little Elm Bend Skokie, Chicago, IL 60076 USA.
EM dyousefz@yahoo.com
NR 25
TC 0
Z9 0
U1 1
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-1623
J9 INT UROL NEPHROL
JI Int. Urol. Nephrol.
PD APR
PY 2013
VL 45
IS 2
BP 333
EP 338
DI 10.1007/s11255-013-0383-5
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 108YZ
UT WOS:000316333600006
PM 23381502
ER
PT J
AU Schwartz, GK
Carvajal, RD
Midgley, R
Rodig, SJ
Stockman, PK
Ataman, O
Wilson, D
Das, S
Shapiro, GI
AF Schwartz, Gary K.
Carvajal, Richard D.
Midgley, Rachel
Rodig, Scott J.
Stockman, Paul K.
Ataman, Ozlem
Wilson, David
Das, Shampa
Shapiro, Geoffrey I.
TI Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B
kinase, in patients with advanced solid tumors
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Barasertib; AZD1152; Aurora B kinase; Solid tumors; Phase I;
Pharmacokinetics
ID ACUTE MYELOID-LEUKEMIA; CELL LUNG-CARCINOMA; TARGETS; CANCER;
PHARMACOKINETICS; OVEREXPRESSION; EFFICACY; FREQUENT; GROWTH; SAFETY
AB The purpose of this study was to determine the maximum-tolerated dose (MTD), pharmacokinetics and safety profile for two different dosing regimens of barasertib, a selective inhibitor of Aurora B Kinase. In this Phase I trial, patients with advanced solid malignancies were treated with escalating doses of barasertib, administered as either a 48-h continuous infusion or as two 2-h infusions on consecutive days, both every 14 days of a 28-day cycle. Thirty-five patients were treated. The MTDs were 150 mg as a 48-h continuous infusion and 220 mg administered as two 2-h infusions (110 mg/day, days 1, 2, 15 and 16), with neutropenia the dose-limiting toxicity (DLT) of each schedule. Common Terminology Criteria of Adverse Events (CTCAE) grade a parts per thousand yenaEuro parts per thousand 3 neutropenia (with or without fever) occurred in 34 % of patients overall. Other adverse events, many of hematologic or gastrointestinal etiology, were of mild or moderate intensity. No objective tumor responses were observed, although stable disease was observed in 23 % of patients. Systemic exposure to barasertib-hQPA, the more active moiety to which barasertib is converted, was observed by 1 and 6 h into the 2-h and continuous infusion, respectively, and exhibited linear pharmacokinetics. In summary, barasertib was generally well tolerated, with neutropenia the most frequent and dose-limiting toxicity, irrespective of schedule. Future development of barasertib will depend on better definition of its therapeutic index.
C1 [Schwartz, Gary K.; Carvajal, Richard D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Midgley, Rachel] Univ Oxford, Dept Oncol, Oxford, England.
[Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Stockman, Paul K.; Ataman, Ozlem; Wilson, David; Das, Shampa] AstraZeneca, Macclesfield, Cheshire, England.
[Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Boston, MA 02215 USA.
RP Schwartz, GK (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
EM schwartzg@mskcc.org; geoffrey_shapiro@dfci.harvard.edu
FU AstraZeneca
FX We thank Merran Macpherson of AstraZeneca UK Ltd. Clinical Pharmacology
Science, for assistance with interpretation of pharmacokinetic
assessments. We also thank the study teams at Memorial Sloan-Kettering
Cancer Center and the Dana-Farber Cancer Institute, including Andrew
Wolanski NP, Tracy Bell RN and Sarah Scofield. Editorial assistance was
provided by Dr. Zoe van Helmond from Mudskipper Bioscience, funded by
AstraZeneca.
NR 30
TC 26
Z9 27
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2013
VL 31
IS 2
BP 370
EP 380
DI 10.1007/s10637-012-9825-7
PG 11
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 105OQ
UT WOS:000316081900013
PM 22661287
ER
PT J
AU Ott, PA
Carvajal, RD
Pandit-Taskar, N
Jungbluth, AA
Hoffman, EW
Wu, BW
Bomalaski, JS
Venhaus, R
Pan, LD
Old, LJ
Pavlick, AC
Wolchok, JD
AF Ott, Patrick A.
Carvajal, Richard D.
Pandit-Taskar, Neeta
Jungbluth, Achim A.
Hoffman, Eric W.
Wu, Bor-Wen
Bomalaski, John S.
Venhaus, Ralph
Pan, Linda
Old, Lloyd J.
Pavlick, Anna C.
Wolchok, Jedd D.
TI Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in
patients with advanced melanoma
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Melanoma; Metastatic; Auxotrophy; Arginine deiminase; Argininosuccinate
synthetase
ID METASTATIC MELANOMA; ARGININOSUCCINATE SYNTHETASE;
HEPATOCELLULAR-CARCINOMA; MALIGNANT-MELANOMA; PLUS DACARBAZINE; IN-VIVO;
DEPRIVATION; CANCER; INHIBITION; THERAPY
AB Background Arginine deiminase (ADI) is an enzyme that degrades arginine, an amino acid that is important for growth and development of normal and neoplastic cells. Melanoma cells are auxotrophic for arginine, because they lack argininosuccinatesynthetase (ASS), a key enzyme required for the synthesis of arginine. Patients and methods Patients with advanced melanoma were treated with 40, 80 or 160 IU/m(2) ADI-PEG 20 i.m. weekly. Primary endpoints were toxicity and tumor response, secondary endpoints included metabolic response by (18)FDG-PET, pharmacodynamic (PD) effects upon circulating arginine levels, and argininosuccinate synthetase tumor expression by immunohistochemistry. Results 31 previously treated patients were enrolled. The main toxicities were grade 1 and 2 adverse events including injection site pain, rash, and fatigue. No objective responses were seen. Nine patients achieved stable disease (SD), with 2 of these durable for > 6 months. Four of the 9 patients with SD had uveal melanoma. PD analysis showed complete plasma arginine depletion in 30/31 patients by day 8. Mean plasma levels of ADI-PEG 20 correlated inversely with ADI-PEG 20 antibody levels. Immunohistochemical ASS expression analysis in tumor tissue was negative in 24 patients, whereas 5 patients had < 5 % cells positive. Conclusions ADI-PEG 20 is well tolerated in advanced melanoma patients and leads to consistent, but transient, arginine depletion. Although no RECIST responses were observed, the encouraging rate of SD in uveal melanoma patients indicates that it may be worthwhile to evaluate ADI-PEG 20 in this melanoma subgroup.
C1 [Ott, Patrick A.; Pavlick, Anna C.] NYU, Sch Med, Dept Med Oncol, New York, NY USA.
[Carvajal, Richard D.; Pandit-Taskar, Neeta; Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Jungbluth, Achim A.; Hoffman, Eric W.; Venhaus, Ralph; Pan, Linda; Old, Lloyd J.; Wolchok, Jedd D.] Branch Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York, NY USA.
[Wu, Bor-Wen; Bomalaski, John S.] Polaris Pharmaceut, San Diego, CA USA.
[Ott, Patrick A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA.
RP Ott, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
EM Patrick_Ott@dfci.harvard.edu
FU NCI NIH HHS [P30 CA008748]
NR 33
TC 39
Z9 41
U1 0
U2 14
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD APR
PY 2013
VL 31
IS 2
BP 425
EP 434
DI 10.1007/s10637-012-9862-2
PG 10
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 105OQ
UT WOS:000316081900019
PM 22864522
ER
PT J
AU Williams, DL
Goldstein, G
Minshew, NJ
AF Williams, Diane L.
Goldstein, Gerald
Minshew, Nancy J.
TI The Modality Shift Experiment in Adults and Children with High
Functioning Autism
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism; Attentional shifting; Speed of processing; Perceptual
development
ID DIAGNOSTIC OBSERVATION SCHEDULE; SPECTRUM DISORDER; COGNITIVE-STYLE;
YOUNG-CHILDREN; ATTENTION; DISENGAGEMENT; DYSFUNCTION; INTERVIEW;
DEFICITS
AB This study used the modality shift experiment, a relatively simple reaction time measure to visual and auditory stimuli, to examine attentional shifting within and across modalities in 33 children and 42 adults with high-functioning autism as compared to matched numbers of age- and ability-matched typical controls. An exaggerated "modality shift effect" relative to the TD children occurred for the children with autism in conditions involving the reaction time when shifting from sound to light but not from light to sound. No exaggerated MSE was found for the adults with autism; rather, their responses were characterized by a generalized slowness relative to the adults with TD. These results suggest a lag in maturational development in autism in basic information processing mechanisms.
C1 [Williams, Diane L.] Duquesne Univ, Dept Speech Language Pathol, Pittsburgh, PA 15219 USA.
[Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA.
[Goldstein, Gerald] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15206 USA.
[Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15206 USA.
[Minshew, Nancy J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15206 USA.
RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151R, Pittsburgh, PA 15206 USA.
EM williamsd2139@duq.edu; ggold@nb.net
RI Williams, Diane/B-4128-2017
FU NICHD NIH HHS [P50 HD055748, P01 HD035469, HD35469, HD055748, U19
HD035469]; NIDCD NIH HHS [K23DC006691, K23 DC006691]; NINDS NIH HHS [R01
NS033355]
NR 52
TC 7
Z9 7
U1 2
U2 12
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD APR
PY 2013
VL 43
IS 4
BP 794
EP 806
DI 10.1007/s10803-012-1618-5
PG 13
WC Psychology, Developmental
SC Psychology
GA 109KG
UT WOS:000316365400005
PM 22865151
ER
PT J
AU Cidav, Z
Lawer, L
Marcus, SC
Mandell, DS
AF Cidav, Zuleyha
Lawer, Lindsay
Marcus, Steven C.
Mandell, David S.
TI Age-Related Variation in Health Service Use and Associated Expenditures
Among Children with Autism
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism; Economics; Cost; Expenditures; Utilization; Medicaid; Age
variation
ID PSYCHOTROPIC MEDICATION USE; SPECTRUM DISORDERS;
PSYCHIATRIC-HOSPITALIZATION; CARE EXPENDITURES; ELIGIBLE CHILDREN;
ENROLLED CHILDREN; ADULTS; DIAGNOSIS; COSTS; INDIVIDUALS
AB This study examined differences by age in service use and associated expenditures during 2005 for Medicaid-enrolled children with autism spectrum disorders. Aging was associated with significantly higher use and costs for restrictive, institution-based care and lower use and costs for community-based therapeutic services. Total expenditures increased by 5 % with each year of age; by 23 % between 3-5 and 6-11 year olds, 23 % between 6-11 and 12-16, and 14 % between 12-16 and 17-20 year olds. Use of and expenditures for long-term care, psychiatric medications, case management, medication management, day treatment/partial hospitalization, and respite services increased with age; use of and expenditures for occupational/physical therapy, speech therapy, mental health services, diagnostic/assessment services, and family therapy declined.
C1 [Cidav, Zuleyha; Lawer, Lindsay; Mandell, David S.] Univ Penn, Childrens Hosp Philadelphia, Ctr Mental Hlth Policy & Serv Res, Ctr Autism Res,Perelman Sch Med, Philadelphia, PA 19104 USA.
[Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
RP Cidav, Z (reprint author), Univ Penn, Childrens Hosp Philadelphia, Ctr Mental Hlth Policy & Serv Res, Ctr Autism Res,Perelman Sch Med, Philadelphia, PA 19104 USA.
EM zcidav@upenn.edu
RI Mandell, David/H-2730-2012
OI Mandell, David/0000-0001-8240-820X
FU NIMH NIH HHS [R01 MH077000]
NR 39
TC 20
Z9 20
U1 2
U2 31
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD APR
PY 2013
VL 43
IS 4
BP 924
EP 931
DI 10.1007/s10803-012-1637-2
PG 8
WC Psychology, Developmental
SC Psychology
GA 109KG
UT WOS:000316365400017
PM 22941343
ER
PT J
AU Schmidt, K
Zimmerman, A
Bauman, M
Ferrone, C
Venter, J
Spybrook, J
Henry, C
AF Schmidt, Karmen
Zimmerman, Andrew
Bauman, Margaret
Ferrone, Christine
Venter, Jacob
Spybrook, Jessaca
Henry, Charles
TI Brief Report: Asperger's Syndrome and Sibling Birth Order
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Asperger's syndrome; Pervasive developmental disorders; Birth order;
Epidemiology
ID AUTISM SPECTRUM DISORDERS; RISK-FACTORS; FETAL-BRAIN; OBSTETRIC
COMPLICATIONS; AUTOIMMUNE-DISEASES; PERINATAL FACTORS; PREGNANCY;
CHILDREN; AGE; ANTIBODIES
AB Prior investigations suggest that birth order position may be associated with the risk for developing a pervasive developmental disorder. This retrospective chart review examined the birth order status of 29 psychiatrically-referred patients with Asperger's Syndrome (AS). Eighty-six percent of the subjects were first born. The finding was statistically significant when compared to an expected random distribution of AS subjects chi(2) (1, N = 29) = 9.18, p < 0.01. The reasons for such an association are unclear though birth stoppage, obstetric complications, and immunological mechanisms may play a role.
C1 [Schmidt, Karmen; Zimmerman, Andrew; Bauman, Margaret; Ferrone, Christine] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Venter, Jacob; Henry, Charles] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Spybrook, Jessaca] Western Michigan Univ, Evaluat Measurement & Res Dept, Kalamazoo, MI 49008 USA.
[Henry, Charles] Lurie Ctr, Lexington, MA 02421 USA.
RP Henry, C (reprint author), Lurie Ctr, 1 Maguire Rd, Lexington, MA 02421 USA.
EM charles_henry@hms.harvard.edu
NR 55
TC 2
Z9 2
U1 1
U2 16
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
EI 1573-3432
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD APR
PY 2013
VL 43
IS 4
BP 973
EP 977
DI 10.1007/s10803-012-1620-y
PG 5
WC Psychology, Developmental
SC Psychology
GA 109KG
UT WOS:000316365400021
PM 22872214
ER
PT J
AU Ai, AL
Hall, D
Pargament, K
Tice, TN
AF Ai, Amy L.
Hall, Daniel
Pargament, Kenneth
Tice, Terrence N.
TI Posttraumatic growth in patients who survived cardiac surgery: the
predictive and mediating roles of faith-based factors
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Posttraumatic growth; Cardiovascular diseases and surgery; Religion;
faith; and spiritual support; Social support; Optimism and hope
ID PERCEIVED SOCIAL SUPPORT; CORONARY-HEART-DISEASE; BREAST-CANCER
PATIENTS; ARTERY-BYPASS SURGERY; QUALITY-OF-LIFE; PSYCHOLOGICAL
ADJUSTMENT; RELIGIOUS INVOLVEMENT; DEPRESSIVE SYMPTOMS; COPING
STRATEGIES; GRAFT-SURGERY
AB Despite the growing knowledge of posttraumatic growth, only a few studies have examined personal growth in the context of cardiac health. Similarly, longitudinal research is lacking on the implications of religion/spirituality for patients with advanced cardiac diseases. This paper aims to explore the effect of preoperative religious coping on long-term postoperative personal growth and potential mediation in this effect. Analyses capitalized on a preoperative survey and medical indices from the Society of Thoracic Surgeons' National Database of patients undergoing cardiac surgery. Participants in the current follow-up study completed a mailed survey 30 months after surgery. Hierarchical regression analysis was performed to evaluate the extent to which preoperative use of religious coping predicted growth at follow-up, after controlling for key demographics, medical indices, mental health, and protective factors. Predictors of posttraumatic growth at follow-up were positive religious coping and a living status without a partner. Medical indices, optimistic expectations, social support, and other religious factors were unrelated to posttraumatic growth. Including religious factors diminished effects of gender, age, and race. Including perceived spiritual support completely eliminated the role of positive religious coping, indicating mediation. Preoperative positive religious coping may have a long-term effect on postoperative personal growth, explainable by higher spiritual connections as a part of significance-making. These results suggest that spirituality may play a favorable role in cardiac patients' posttraumatic growth after surviving a life-altering operation. The elimination of demographic effects may help explain previously mixed findings concerning the association between these factors and personal growth.
C1 [Ai, Amy L.] Florida State Univ, Tallahassee, FL 32306 USA.
[Hall, Daniel] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Pargament, Kenneth] Bowling Green State Univ, Bowling Green, OH 43403 USA.
[Tice, Terrence N.] Iliff Univ Theol, Denver, CO USA.
RP Ai, AL (reprint author), Florida State Univ, FL 2313,Univ Ctr Bldg C, Tallahassee, FL 32306 USA.
EM amyai8@gmail.com
RI Hall, Daniel/H-4843-2013;
OI Hall, Daniel/0000-0001-6382-0522
FU NCCIH NIH HHS [P50 AT00011]; PHS HHS [1 RO3 AGO 15686-01]
NR 70
TC 5
Z9 6
U1 3
U2 20
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0160-7715
J9 J BEHAV MED
JI J. Behav. Med.
PD APR
PY 2013
VL 36
IS 2
BP 186
EP 198
DI 10.1007/s10865-012-9412-6
PG 13
WC Psychology, Clinical
SC Psychology
GA 109RG
UT WOS:000316385600008
PM 22460360
ER
PT J
AU Oral, E
Neils, AL
Rowell, SL
Lozynsky, AJ
Muratoglu, OK
AF Oral, Ebru
Neils, Andrew L.
Rowell, Shannon L.
Lozynsky, Andrew J.
Muratoglu, Orhun K.
TI Increasing irradiation temperature maximizes vitamin E grafting and wear
resistance of ultrahigh molecular weight polyethylene
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
LA English
DT Article
DE wear; vitamin E; joint implants; crosslinking; grafting; oxidation
ID CROSS-LINKED POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; ALPHA-TOCOPHEROL;
MECHANICAL-PROPERTIES; FOLLOW-UP; UHMWPE; RADIATION; COMPONENTS;
OXIDATION; IMPLANTS
AB Vitamin E stabilization of radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) for total joint implants can be done by blending of UHMWPE resin powder with vitamin E, followed by consolidation and irradiation of the blend. It is well known that vitamin E prevents crosslinking in UHMWPE during ionizing radiation. We hypothesized that there would also be a significant amount of grafting of vitamin E onto UHMWPE during irradiation. Spectroscopic analysis of radiation crosslinked vitamin E-blended UHMWPE before and after extraction with boiling hexane showed vitamin E grafting in up to 30% of the blended vitamin E. Grafting increased with irradiation temperature. We also discovered that increasing irradiation temperature resulted in better preservation of active vitamin E in the polymer and increased crosslinking efficiency of UHMWPE. As a result, warm-irradiated vitamin E-blended UHMWPEs had significantly less wear than those irradiated at ambient temperature. It may be desirable to graft vitamin E on UHMWPE to decrease the possibility of elution and increase long-term stability. Warm irradiation of vitamin E blends may present an advantage in increasing vitamin E potency, as well as decreasing the wear of UHMWPE, which is crucial in decreasing the incidence of periprosthetic osteolysis in total joint replacement patients. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 436440, 2013.
C1 [Oral, Ebru; Rowell, Shannon L.; Lozynsky, Andrew J.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Oral, Ebru; Neils, Andrew L.; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA.
RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
EM eoral@partners.org
NR 29
TC 15
Z9 16
U1 0
U2 33
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4973
J9 J BIOMED MATER RES B
JI J. Biomed. Mater. Res. Part B
PD APR
PY 2013
VL 101B
IS 3
BP 436
EP 440
DI 10.1002/jbm.b.32807
PG 5
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 112DY
UT WOS:000316573600007
PM 23115033
ER
PT J
AU Fan, XD
Liu, E
Freudenreich, O
Copeland, P
Hayden, D
Ghebremichael, M
Cohen, B
Ongur, D
Goff, DC
Henderson, DC
AF Fan, Xiaoduo
Liu, Emily
Freudenreich, Oliver
Copeland, Paul
Hayden, Douglas
Ghebremichael, Musie
Cohen, Bruce
Ongur, Dost
Goff, Donald C.
Henderson, David C.
TI No Effect of Adjunctive, Repeated-Dose Intranasal Insulin Treatment on
Psychopathology and Cognition in Patients With Schizophrenia
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE intranasal; insulin; schizophrenia; psychopathology; cognition
ID CENTRAL-NERVOUS-SYSTEM; PIK3C3 PROMOTER VARIANT; CAENORHABDITIS-ELEGANS;
RAT HIPPOCAMPUS; PHENCYCLIDINE; LOCALIZATION; DELIVERY; THERAPY;
INHIBITION; MODULATION
AB Objective: This study examined the effect of adjunctive intranasal insulin therapy on psychopathology and cognition in patients with schizophrenia.
Methods: Each subject had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or schizo-affective disorder and been on stable antipsychotics for at least 1 month. In an 8-week randomized, double-blind, placebo-controlled study, subjects received either intranasal insulin (40 IU 4 times per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale and the Scale for Assessment of Negative Symptoms. A neuropsychological battery was used to assess cognitive performance. The assessment for psychopathology and cognition was conducted at baseline, week 4, and week 8.
Results: A total of 45 subjects were enrolled in the study (21 in the insulin group and 24 in the placebo group). The mixed model analysis showed that there were no significant differences between the 2 groups at week 8 on various psychopathology and cognitive measures (P > 0.1).
Conclusions: Adjunctive therapy with intranasal insulin did not seem to be beneficial in improving schizophrenia symptoms or cognition in the present study. The implications for future studies were discussed.
C1 [Fan, Xiaoduo] UMass Mem Med Ctr, Psychot Disorders Program, Worcester, MA USA.
[Fan, Xiaoduo] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Liu, Emily] Partners Community Healthcare Inc, Haverhill, MA USA.
[Freudenreich, Oliver; Goff, Donald C.; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA.
[Freudenreich, Oliver; Copeland, Paul; Ghebremichael, Musie; Cohen, Bruce; Ongur, Dost; Goff, Donald C.; Henderson, David C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Copeland, Paul] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hayden, Douglas] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Ghebremichael, Musie] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA.
[Cohen, Bruce; Ongur, Dost] McLean Hosp, Belmont, MA 02178 USA.
RP Fan, XD (reprint author), Suite 100,365 Plantat St, Worcester, MA 01605 USA.
EM xiaoduo.fan@umassmed.edu
FU National Institutes of Health [5K23MH082098]; NARSAD Young Investigator
Award; National Institutes of Health, National Center for Research
Resources General Clinical Research Centers Program (MGH Clinical
research Center) [M01-RR-01066, UL1 RR025758-01]; Eli Lilly and Company;
AstraZeneca; Bristol-Myer Squibb; Janssen; Eli Lilly; Cephalon; Pfizer;
Bristol-Myers Squibb; Indevus Pharmaceuticals; H. Lundbeck;
Schering-Plough; Takeda; Biovail; Sovay; Hoffman-La Roche; Cypress;
Dainippon Sumitomo; Abbott Laboratories; Genentech; Novartis; PamLab;
GlaxoSmithKline; Endo Pharmaceuticals; Solvay; Covance; Alkermis
FX This study was supported by Grant 5K23MH082098 from the National
Institutes of Health (Dr Fan), the NARSAD Young Investigator Award (Dr
Fan), Grant M01-RR-01066 and Grant UL1 RR025758-01 from the National
Institutes of Health, National Center for Research Resources General
Clinical Research Centers Program (MGH Clinical research Center), and an
investigator initiated trial grant from Eli Lilly and Company (Dr Fan).;
Dr Fan has received research support or honoraria from Eli Lilly,
AstraZeneca, Bristol-Myer Squibb, Janssen, and Pfizer. Dr Freudenreich
has received research support or honoraria from AstraZeneca,
Bristol-Myer Squibb, Janssen, Eli Lilly, Cephalon, and Pfizer. Dr Goff
has received research support or honoraria from Bristol-Myers Squibb,
Indevus Pharmaceuticals, H. Lundbeck, Schering-Plough, Eli Lilly,
Takeda, Biovail, Sovay, Hoffman-La Roche, Cypress, Dainippon Sumitomo,
Abbott Laboratories, Genentech, Pfizer, Janssen, Novartis, PamLab, and
GlaxoSmithKline, and Endo Pharmaceuticals. He served on a DSMB for
Otsuka. Dr Henderson has received research support or honoraria from
Takeda, Janssen, Solvay, Novartis, Covance, Alkermis, and Pfizer. Dr
Copeland serves as a consultant for Sanofi. Drs Liu, Ghebremichael,
Cohen, and Ongur and Mr Hayden report no competing interests.
NR 39
TC 3
Z9 3
U1 0
U2 1
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 APR
PY 2013
VL 33
IS 2
BP 226
EP 230
DI 10.1097/JCP.0b013e31828701d0
PG 5
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 108NX
UT WOS:000316303700014
PM 23422397
ER
PT J
AU Meszaros, ZS
Abdul-Malak, Y
Dimmock, JA
Wang, DL
Ajagbe, TO
Batki, SL
AF Meszaros, Zsuzsa Szombathyne
Abdul-Malak, Ynesse
Dimmock, Jacqueline A.
Wang, Dongliang
Ajagbe, Tolani O.
Batki, Steven L.
TI Varenicline Treatment of Concurrent Alcohol and Nicotine Dependence in
Schizophrenia A Randomized, Placebo-Controlled Pilot Trial
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE varenicline; schizophrenia; alcohol; nicotine; smoking
ID CONSENSUS COGNITIVE BATTERY; USE DISORDERS; SCHIZOAFFECTIVE DISORDER;
SUBSTANCE USE; SMOKING; SCALE; STANDARDIZATION; INTERVENTIONS;
OUTPATIENTS; PREVALENCE
AB Alcohol and nicotine dependence are common in schizophrenia. Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers. The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia. Outpatients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week, double-blind, randomized, placebo-controlled trial. Alcohol use and smoking were assessed using self-report (Timeline Follow-Back) and biological measures. Adverse events were recorded. Changes in the number of standard drinks per week and cigarettes per week were compared in the 2 groups. Because of safety concerns or loss to follow-up, of 55 patients enrolled, only 10 started study medication, 5 each on varenicline and placebo. Gastrointestinal adverse effects, such as severe abdominal pain, limited study completion to only 4 subjects. Number of standard alcoholic drinks consumed per week decreased by [mean (SD)] 16.6 (20.1) in the varenicline group and by 2.4 (27.4) in the placebo group. Mean (SD) number of cigarettes smoked per week decreased by 66 (65) its the varenicline group and by 47 (77) in the placebo group. Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability (gastrointestinal adverse effects) limiting retention. There was no increased number of serious neuropsychiatric adverse events in the varenicline group. Based on this small sample, concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline.
C1 [Meszaros, Zsuzsa Szombathyne; Abdul-Malak, Ynesse; Dimmock, Jacqueline A.; Ajagbe, Tolani O.; Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Wang, Dongliang] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY 13210 USA.
[Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Meszaros, ZS (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St,IHP 3302, Syracuse, NY 13210 USA.
EM meszaroz@upstate.edu
FU Brain & Behavior Research Foundation (NARSAD) Young Investigator Award;
NIH/NIAAA [R01 AA013655]; Alkermes, Inc.
FX This research was supported by the Brain & Behavior Research Foundation
(NARSAD) 2008 Young Investigator Award to Dr Szombathyne Meszaros. Dr
Batki has received research funding from NIH/NIAAA (R01 AA013655) and
Alkermes, Inc. The authors alone are responsible for the content and
writing of the paper.
NR 41
TC 11
Z9 11
U1 3
U2 13
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 APR
PY 2013
VL 33
IS 2
BP 243
EP 247
DI 10.1097/JCP.0b013e3182870551
PG 5
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 108NX
UT WOS:000316303700018
PM 23422399
ER
PT J
AU True, G
Butler, AE
Lamparska, BG
Lempa, ML
Shea, JA
Asch, DA
Werner, RM
AF True, Gala
Butler, Anneliese E.
Lamparska, Bozena G.
Lempa, Michele L.
Shea, Judy A.
Asch, David A.
Werner, Rachel M.
TI Open Access in the Patient-Centered Medical Home: Lessons from the
Veterans Health Administration
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE patient-centered access; primary care; continuity of care; veterans
health; qualitative evaluation
ID PRIMARY-CARE; READINESS
AB The Veterans Health Administration (VHA) has undertaken a 5-year initiative to transform to a patient-centered medical home model. An early focus of implementation was on creating open access, defined as continuity and capacity in primary care.
We describe the impact of readiness for implementation on efforts of pilot teams to make changes to improve access and identify successful strategies used by early adopters to overcome barriers to change.
A qualitative, formative evaluation of the first 18 months of implementation in one Veterans Integrated Service Network (VISN) spread across six states.
Members of local implementation teams including administrators, primary care providers, and staff from primary care clinics located at 10 medical centers and 45 outpatient clinics.
We conducted site visits during the first 6 months of implementation, observations at Learning Collaboratives, semi-structured interviews, and review of internal organizational documents. All data collection took place between April 2010 and December 2011.
Early adopters employed various strategies to enhance access, with a focus on decreasing demand for face-to-face care, increasing supply of different types of primary care encounters, and improving clinic efficiencies. Our interviews with key contacts revealed three important areas where readiness for implementation (or lack thereof) had an impact on interventions to improve access: leadership engagement, staffing resources, and access to information and knowledge.
Key factors related to readiness for implementation had an impact on which interventions pilot teams could put into place, as well as the viability and sustainability of access gains. Wide variations in interventions to improve access occurring across sites situated within one organization have important implications for efforts to measure the impact of enhanced access on patient outcomes, costs, and other systems-level indicators of the Medical Home.
C1 [True, Gala; Butler, Anneliese E.; Lamparska, Bozena G.; Lempa, Michele L.; Shea, Judy A.; Asch, David A.; Werner, Rachel M.] Philadelphia Vet Affairs Med Ctr, CEPACT, Philadelphia, PA 19104 USA.
[True, Gala; Shea, Judy A.; Asch, David A.; Werner, Rachel M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP True, G (reprint author), Philadelphia Vet Affairs Med Ctr, CEPACT, Bldg 4100,Univ & Woodland Aves, Philadelphia, PA 19104 USA.
EM Jennifer.True2@va.gov
OI Asch, David/0000-0002-7970-286X
FU Office of Primary Care, Veterans Health Administration, Department of
Veterans Affairs
FX The authors wish to thank the staff of the Center for Evaluation of
Patient Aligned Care Teams (CEPACT), members of the CEPACT Advisory
Board and the VISN 4 PACT Steering Committee, the VISN 4 Offices, and
staff at VISN 4 Medical Facilities. We are also grateful for the
insightful comments and suggestions from the three anonymous reviewers.
Funding for the VISN 4 Center for Evaluation of PACT is through the
Office of Primary Care, Veterans Health Administration, Department of
Veterans Affairs. The views expressed in this paper do not necessarily
represent the official views of the Department of Veterans Affairs.
NR 20
TC 18
Z9 18
U1 4
U2 38
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2013
VL 28
IS 4
BP 539
EP 545
DI 10.1007/s11606-012-2279-y
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 109VV
UT WOS:000316398400010
PM 23192447
ER
PT J
AU Schleifer, JW
Centor, RM
Heudebert, GR
Estrada, CA
Morris, JL
AF Schleifer, J. William
Centor, Robert M.
Heudebert, Gustavo R.
Estrada, Carlos A.
Morris, Jason L.
TI NSTEMI or Not: A 59-Year-Old Man with Chest Pain and Troponin Elevation
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
ID AORTIC DISSECTION; FREQUENCY
AB A 59-year-old African-American man with a history of hypertension, hyperlipidemia, and cerebrovascular disease presented to the emergency department complaining of chest pain. He stated that the pain began suddenly while he was seated at home several hours prior to presentation. He described the pain as throbbing, 9 out of 10 in intensity, substernal, and associated with nausea, diaphoresis, and dyspnea. He stated that the pain radiated to his left leg but not to his arm or jaw. The pain resolved spontaneously after an hour, but then recurred 3 hours later. He had never experienced pain like this before. He initially delayed coming to the hospital, expecting the chest pain to subside spontaneously again; but finally his family brought him in when he became disoriented and confused.
C1 [Schleifer, J. William; Heudebert, Gustavo R.; Morris, Jason L.] Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, Birmingham, AL 35294 USA.
[Centor, Robert M.; Heudebert, Gustavo R.; Estrada, Carlos A.; Morris, Jason L.] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA.
[Centor, Robert M.] Univ Alabama Birmingham, Huntsville, AL USA.
[Centor, Robert M.; Heudebert, Gustavo R.; Estrada, Carlos A.; Morris, Jason L.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA.
[Morris, Jason L.] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
RP Morris, JL (reprint author), Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, BDB 345,1720 2nd Ave South, Birmingham, AL 35294 USA.
EM jlmorris@uab.edu
OI Schleifer, John/0000-0002-2074-108X
NR 14
TC 2
Z9 2
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2013
VL 28
IS 4
BP 583
EP 590
DI 10.1007/s11606-012-2236-9
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 109VV
UT WOS:000316398400019
PM 23054926
ER
PT J
AU Fink, EC
Fisher, DE
AF Fink, Emma C.
Fisher, David E.
TI BRAF and MC1R in Melanoma: Different in Head and Neck Tumors?
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID MUTANT MELANOMA; MUTATIONS; VARIANTS; RISK
AB In this issue, Hacker et al. (2013) report the largest study to date on the association between MC1R variants and BRAF mutant melanoma. Although they did not observe a significant overall correlation, there was a significant negative association between BRAF and MC1R mutations for head/heck melanomas. This suggests a fundamental difference in pathogenesis between head/neck and truncal melanomas, which could contribute to their divergent prognoses. Journal of Investigative Dermatology (2013) 133,878-880. doi:10.1038/jid.2012.475
C1 [Fink, Emma C.; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA.
EM dfisher3@partners.org
OI , /0000-0002-6589-8558
FU NIGMS NIH HHS [T32 GM007753]
NR 12
TC 0
Z9 0
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD APR
PY 2013
VL 133
IS 4
BP 878
EP 880
DI 10.1038/jid.2012.475
PG 3
WC Dermatology
SC Dermatology
GA 106OI
UT WOS:000316154000006
PM 23486431
ER
PT J
AU Markova, A
Weinstock, MA
AF Markova, Alina
Weinstock, Martin A.
TI Risk of Skin Cancer Associated with the Use of UV Nail Lamp
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
C1 [Markova, Alina] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
[Markova, Alina; Weinstock, Martin A.] Brown Univ, Dept Dermatol, Alpert Med Sch, Providence, RI 02912 USA.
[Markova, Alina; Weinstock, Martin A.] Vet Affairs Med Ctr, Dermatoepidemiol Unit 111D, Providence, RI USA.
RP Markova, A (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
EM alina.markova.md@gmail.com
NR 5
TC 4
Z9 4
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD APR
PY 2013
VL 133
IS 4
BP 1097
EP 1099
DI 10.1038/jid.2012.440
PG 3
WC Dermatology
SC Dermatology
GA 106OI
UT WOS:000316154000032
PM 23223132
ER
PT J
AU Puntervoll, HE
Yang, XHR
Vetti, HH
Bachmann, IM
Avril, MF
Benfodda, M
Catricala, C
Dalle, S
Duval-Modeste, AB
Ghiorzo, P
Grammatico, P
Harland, M
Hayward, NK
Hu, HH
Jouary, T
Martin-Denavit, T
Ozola, A
Palmer, JM
Pastorino, L
Pjanova, D
Soufir, N
Steine, SJ
Stratigos, AJ
Thomas, L
Tinat, J
Tsao, H
Veinalde, R
Tucker, MA
Bressac-de Paillerets, BBD
Newton-Bishop, JA
Goldstein, AM
Akslen, LA
Molven, A
AF Puntervoll, Hanne Eknes
Yang, Xiaohong R.
Vetti, Hildegunn Hoberg
Bachmann, Ingeborg M.
Avril, Marie Francoise
Benfodda, Meriem
Catricala, Caterina
Dalle, Stephane
Duval-Modeste, Anne B.
Ghiorzo, Paola
Grammatico, Paola
Harland, Mark
Hayward, Nicholas K.
Hu, Hui-Han
Jouary, Thomas
Martin-Denavit, Tanguy
Ozola, Aija
Palmer, Jane M.
Pastorino, Lorenza
Pjanova, Dace
Soufir, Nadem
Steine, Solrun J.
Stratigos, Alexander J.
Thomas, Luc
Tinat, Julie
Tsao, Hensin
Veinalde, Ruta
Tucker, Margaret A.
Bressac-de Paillerets, Brigitte
Newton-Bishop, Julia A.
Goldstein, Alisa M.
Akslen, Lars A.
Molven, Anders
TI Melanoma prone families with CDK4 germline mutation: phenotypic profile
and associations with MC1R variants
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID 1 RECEPTOR MC1R; CDKN2A MUTATIONS; CUTANEOUS MELANOMA; RED HAIR;
MALIGNANT-MELANOMA; PANCREATIC-CANCER; DYSPLASTIC NEVI; INCREASED RISK;
ATYPICAL NEVI; GENE VARIANTS
AB Background CDKN2A and CDK4 are high risk susceptibility genes for cutaneous malignant melanoma. Melanoma families with CDKN2A germline mutations have been extensively characterised, whereas CDK4 families are rare and lack a systematic investigation of their phenotype.
Methods All known families with CDK4 germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL). Phenotypic data related to primary melanoma and pigmentation characteristics were collected. The CDK4 exon 2 and the complete coding region of the MC1R gene were sequenced.
Results Eleven families carried the CDK4 R24H mutation whereas six families had the R24C mutation. The total number of subjects with verified melanoma was 103, with a median age at first melanoma diagnosis of 39 years. Forty-three (41.7%) subjects had developed multiple primary melanomas (MPM). A CDK4 mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects. CDK4 positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than CDK4 negative family members (p<0.001). MPM subjects had a higher frequency of MC1R red hair colour variants compared with subjects with one tumour (p=0.010).
Conclusion Our study shows that families with CDK4 germline mutations cannot be distinguished phenotypically from CDKN2A melanoma families, which are characterised by early onset of disease, increased occurrence of clinically atypical nevi, and development of MPM. In a clinical setting, the CDK4 gene should therefore always be examined when a melanoma family tests negative for CDKN2A mutation.
C1 [Puntervoll, Hanne Eknes; Bachmann, Ingeborg M.; Steine, Solrun J.; Akslen, Lars A.; Molven, Anders] Univ Bergen, Sect Pathol, Gade Inst, N-5021 Bergen, Norway.
[Yang, Xiaohong R.; Tucker, Margaret A.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Vetti, Hildegunn Hoberg] Haukeland Hosp, Ctr Med Genet & Mol Med, Western Norway Familial Canc Ctr, N-5021 Bergen, Norway.
[Bachmann, Ingeborg M.] Haukeland Hosp, Dept Dermatol, N-5021 Bergen, Norway.
[Avril, Marie Francoise] Univ Paris 05, Hop Cochin Tarnier, AP HP, Paris, France.
[Benfodda, Meriem; Hu, Hui-Han; Soufir, Nadem] Univ Paris 07, St Louis Hosp, AP HP, Dept Genet,Bichat Hosp, Paris, France.
[Benfodda, Meriem; Hu, Hui-Han; Soufir, Nadem] Univ Paris 07, INSERM, St Louis Hosp, Cutaneous Res Ctr,U976, Paris, France.
[Catricala, Caterina] IRCCS, San Gallicano Dermatol Inst, Dept Dermatol Oncol, Rome, Italy.
[Dalle, Stephane; Martin-Denavit, Tanguy; Thomas, Luc] Univ Lyon 1, Hosp Civils Lyon, Ctr Hosp Lyon Sud, Unit Dermatol, F-69365 Lyon, France.
[Duval-Modeste, Anne B.] Rouen Univ Hosp, Dept Dermatol, Rouen, France.
[Ghiorzo, Paola; Pastorino, Lorenza] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Ghiorzo, Paola; Pastorino, Lorenza] San Martino IST Res Hosp, Lab Genet Rare Hereditary Canc, Genoa, Italy.
[Grammatico, Paola] Univ Roma La Sapienza, Dept Mol Med, S Camillo Forlanini Hosp, Rome, Italy.
[Harland, Mark; Newton-Bishop, Julia A.] St James Univ Hosp, Leeds Canc Res UK Ctr, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England.
[Hayward, Nicholas K.; Palmer, Jane M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Jouary, Thomas] Serv Dermatol, Unite Cancerol Cutanee, Bordeaux, France.
[Ozola, Aija; Pjanova, Dace; Veinalde, Ruta] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Stratigos, Alexander J.] Univ Athens, Sch Med, Andreas Sygros Hosp, Dept Dermatol,Dermatooncol Unit, GR-11527 Athens, Greece.
[Tinat, Julie] Rouen Univ Hosp, Dept Genet, Rouen, France.
[Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Serv Genet, Dept Biopathol, Villejuif, France.
[Bressac-de Paillerets, Brigitte] Fdn Jean Dausset, INSERM, U946, Paris, France.
[Akslen, Lars A.] Univ Bergen, Ctr Canc Biomarkers, Gade Inst, N-5021 Bergen, Norway.
[Akslen, Lars A.; Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway.
RP Molven, A (reprint author), Univ Bergen, Haukeland Univ Hosp, Gade Inst, Sect Pathol, N-5021 Bergen, Norway.
EM anders.molven@gades.uib.no
RI Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; Akslen,
Lars /C-1202-2017;
OI hayward, nicholas/0000-0003-4760-1033; Akslen, Lars
/0000-0003-2710-9543; Newton Bishop, Julia/0000-0001-9147-6802;
Veinalde, Ruta/0000-0001-9190-5574
FU European Commission [LSHC-CT-2006-018702]; Cancer Research UK
[C588/A4994, C588/A10589, C8216/A6129]; US National Institutes of Health
(NIH) [CA83115]; University of Bergen; INSERM Research Fellowship; INCA;
Norwegian Cancer Society [71512-PR-2006-0356]; Intramural Research
Program of the NIH, National Cancer Institute, Division of Cancer
Epidemiology and Genetics; Leeds Cancer Research UK Centre
[C37059/A11941]; Latvian Council of Science [10.0010.8]; National Health
and Medical Research Council of Australia; Italian Ministry of Health;
PRIN; Sapienza University of Rome; Institut National du Cancer PHRC [AOM
07, 195, N107004]; Lyon 1 University; Hospices Civils de Lyon; Ligue
Contre le Cancer du Rhone; NIH [K24 CA149202]
FX The GenoMEL study was funded by the European Commission under the 6th
Framework Programme (contract no. LSHC-CT-2006-018702), by Cancer
Research UK Programme Awards (C588/A4994 and C588/A10589), by a Cancer
Research UK Project grant (C8216/A6129), and by a grant from the US
National Institutes of Health (NIH; CA83115). This research was also
supported by a PhD fellowship from the University of Bergen to HEP, an
INSERM Research Fellowship for hospital based scientists and an INCA
coordinator or grant to BB-de P, and grants from the following sources:
Norwegian Cancer Society (71512-PR-2006-0356); Intramural Research
Program of the NIH, National Cancer Institute, Division of Cancer
Epidemiology and Genetics; Leeds Cancer Research UK Centre
(C37059/A11941); Latvian Council of Science (No. 10.0010.8); National
Health and Medical Research Council of Australia; Italian Ministry of
Health; PRIN 2008; Sapienza University of Rome; Institut National du
Cancer PHRC 2007 (AOM 07, 195, N107004); Lyon 1 University; Hospices
Civils de Lyon; Ligue Contre le Cancer du Rhone; and NIH (K24 CA149202).
NR 41
TC 38
Z9 39
U1 3
U2 15
PU BMJ 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 APR
PY 2013
VL 50
IS 4
BP 264
EP U82
DI 10.1136/jmedgenet-2012-101455
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 106AW
UT WOS:000316114800008
PM 23384855
ER
PT J
AU Blumenthal, C
Curran, J
Benzel, EC
Potter, R
Magge, SN
Harrington, JF
Coumans, JV
Ghogawala, Z
AF Blumenthal, Claire
Curran, Jill
Benzel, Edward C.
Potter, Rachel
Magge, Subu N.
Harrington, J. Frederick, Jr.
Coumans, Jean-Valery
Ghogawala, Zoher
TI Radiographic predictors of delayed instability following decompression
without fusion for degenerative Grade I lumbar spondylolisthesis
Clinical article
SO JOURNAL OF NEUROSURGERY-SPINE
LA English
DT Article
DE degenerative lumbar spondylolisthesis; reoperation; radiographic
predictor; outcome; laminectomy
ID UNITED-STATES TRENDS; SPINAL STENOSIS; COST-EFFECTIVENESS; SURGERY;
LAMINECTOMY; INSTRUMENTATION; REOPERATION; COMPLICATIONS; ARTHRODESIS;
OPERATIONS
AB Object. It is not known whether adding fusion to lumbar decompression is necessary for all patients undergoing surgery for degenerative lumbar spondylolisthesis with symptomatic stenosis. Determining specific radiographic traits that might predict delayed instability following decompression surgery might guide clinical decision making regarding the utility of up-front fusion in patients with degenerative Grade I spondylolisthesis.
Methods. Patients with Grade I degenerative lumbar spondylolisthesis (3-14 mm) with symptomatic stenosis were prospectively enrolled from a single site between May 2002 and September 2009 and treated with decompressive laminectomy without fusion. Patients with mechanical back pain or with gross motion (>3 mm) on flexion-extension lumbar radiographs were excluded. The baseline radiographic variables measured included amount of slippage, disc height, facet angle, motion at spondylolisthesis (flexion-extension), and sagittal rotation angle. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, Student t-test, and ANOVA.
Results. Forty patients were enrolled and treated with laminectomy without fusion, and all patients had complete radiographic data sets that were available for analysis. Reoperation was performed in 15 (37.5%) of 40 patients, with a mean follow-up duration of 3.6 years. Reoperation was performed for pain caused by instability at the index level in all 15 cases. Using multivariate stepwise logistic regression with a threshold p value of 0.35, motion at spondylolisthesis, disc height, and facet angle were predictors of reoperation following surgery. Facet angle > 50 degrees was associated with a 39% rate of reoperation, disc height > 6.5 mm was associated with a 45% rate of reoperation, and motion at spondylolisthesis > 1.25 mm was associated with a 54% rate of reoperation. Patients with all 3 risk factors for instability had a 75% rate of reoperation, whereas patients with no risk factors for instability had a 0% rate of reoperation (p = 0.14).
Conclusions. Patients with motion at spondylolisthesis > 1.25 mm, disc height > 6.5 mm, and facet angle > 50 degrees are more likely to experience instability following decompression surgery for Grade I lumbar spondylolisthesis. Identification of key risk factors for instability might improve patient selection for decompression without fusion surgery. Clinical trial registration no.: NCT00109213 (http://thejns.org/doi/abs/10.3171/2013.1.SPINE12537)
C1 [Blumenthal, Claire] Harvard Univ, Cambridge, MA 02138 USA.
[Magge, Subu N.; Ghogawala, Zoher] Lahey Clin Med Ctr, Dept Neurosurg, Burlington, MA 01805 USA.
[Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Blumenthal, Claire; Curran, Jill; Potter, Rachel; Ghogawala, Zoher] Greenwich Hosp, Wallace Clin Trials Ctr, Greenwich, CT USA.
[Benzel, Edward C.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA.
[Harrington, J. Frederick, Jr.] Univ New Mexico, Dept Neurosurg, Albuquerque, NM 87131 USA.
RP Ghogawala, Z (reprint author), Lahey Clin Med Ctr, Dept Neurosurg, 41 Mall Rd, Burlington, MA 01805 USA.
EM zoher.ghogawala@lahey.org
FU Greenwich Lumbar Stenosis SLIP Study Fund [GH384]; Jean and David
Wallace Foundation [GH382]
FX Funding was received from the Greenwich Lumbar Stenosis SLIP Study Fund
(Grant No. GH384) and the Jean and David Wallace Foundation (Grant No.
GH382). The authors report no conflict of interest concerning the
materials or methods used in this study or the findings specified in
this paper.
NR 29
TC 21
Z9 23
U1 2
U2 5
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1547-5654
J9 J NEUROSURG-SPINE
JI J. Neurosurg.-Spine
PD APR
PY 2013
VL 18
IS 4
BP 340
EP 346
DI 10.3171/2013.1.SPINE12537
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 114BU
UT WOS:000316715800006
PM 23373567
ER
PT J
AU Becerra, L
Upadhyay, J
Chang, PC
Bishop, J
Anderson, J
Baumgartner, R
Schwarz, AJ
Coimbra, A
Wallin, D
Nutile, L
George, E
Maier, G
Sunkaraneni, S
Iyengar, S
Evelhoch, JL
Bleakman, D
Hargreaves, R
Borsook, D
AF Becerra, Lino
Upadhyay, Jaymin
Chang, Pei-Ching
Bishop, James
Anderson, Julie
Baumgartner, Richard
Schwarz, Adam J.
Coimbra, Alexandre
Wallin, Diana
Nutile, Lauren
George, Edward
Maier, Gary
Sunkaraneni, Soujanya
Iyengar, Smriti
Evelhoch, Jeffrey L.
Bleakman, David
Hargreaves, Richard
Borsook, David
TI Parallel Buprenorphine phMRI Responses in Conscious Rodents and Healthy
Human Subjects
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID PHARMACOLOGICAL MRI; DRUG DISCOVERY; HUMAN BRAIN; TRANSLATIONAL
MEDICINE; OPIOID RECEPTORS; ALZHEIMERS-DISEASE; THERMAL STIMULI; PAIN
MANAGEMENT; RHESUS-MONKEYS; DEFAULT MODE
AB Pharmacological magnetic resonance imaging (phMRI) is one method by which a drug's pharmacodynamic effects in the brain can be assessed. Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined. In the current investigation, we aimed to build on recent clinical work in which the functional response to 0.1 and 0.2 mg/70 kg i.v. buprenorphine (partial mu-opioid receptor agonist) was measured in healthy humans. Here, we measured the phMRI response to 0.04 and 0.1 mg/kg i.v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species. PhMRI of 0.04 and 0.1 mg/kg i.v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum. Similar dose-dependent phMRI activation was observed in the human phMRI studies. These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia. This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development.
C1 [Becerra, Lino; Upadhyay, Jaymin; Chang, Pei-Ching; Bishop, James; Anderson, Julie; Baumgartner, Richard; Schwarz, Adam J.; Coimbra, Alexandre; Wallin, Diana; Nutile, Lauren; George, Edward; Maier, Gary; Sunkaraneni, Soujanya; Iyengar, Smriti; Evelhoch, Jeffrey L.; Bleakman, David; Hargreaves, Richard; Borsook, David] Childrens Hosp Boston, PAIN Grp, Imaging Consortium Drug Dev, Waltham, MA USA.
[Becerra, Lino; Upadhyay, Jaymin; Chang, Pei-Ching; Bishop, James; Anderson, Julie; Wallin, Diana; Nutile, Lauren; George, Edward] Childrens Hosp Boston, PAIN Grp, Waltham, MA USA.
[Becerra, Lino] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Baumgartner, Richard; Coimbra, Alexandre; Evelhoch, Jeffrey L.; Hargreaves, Richard] Merck & Co Inc, Merck Res Labs, West Point, PA USA.
[Schwarz, Adam J.; Iyengar, Smriti] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Maier, Gary; Sunkaraneni, Soujanya] Sunovion Inc, Marlborough, MA USA.
RP Becerra, L (reprint author), Harvard Univ, Sch Med, Children Hosp Boston, 9 Hope Ave, Waltham, MA 02453 USA.
EM Lino.Becerra@childrens.harvard.edu
OI Wallin, Diana/0000-0003-4244-0314
FU Imaging Consortium for Drug Development
FX This work was supported by the Imaging Consortium for Drug Development
(to D.B. and L.B.).
NR 79
TC 12
Z9 12
U1 1
U2 23
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD APR
PY 2013
VL 345
IS 1
BP 41
EP 51
DI 10.1124/jpet.112.201145
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 109KT
UT WOS:000316367000006
PM 23370795
ER
PT J
AU Shen, KZ
Johnson, SW
AF Shen, Ke-Zhong
Johnson, Steven W.
TI Group I mGluRs Evoke K-ATP Current by Intracellular Ca2+ Mobilization in
Rat Subthalamus Neurons
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID METABOTROPIC GLUTAMATE RECEPTORS; SENSITIVE POTASSIUM CHANNELS;
DOPAMINERGIC MIDBRAIN NEURONS; PARKINSONS-DISEASE; NITRIC-OXIDE;
SUBSTANTIA-NIGRA; GLOBUS-PALLIDUS; BASAL GANGLIA; NUCLEUS; ACTIVATION
AB We reported previously that Ca2+ influx through N-methly-D-aspartate- gated channels evokes ATP-sensitive K+ (K-ATP) currents in rat subthalamic nucleus (STN) neurons. By using whole-cell patch clamp recordings in brain slices, we investigated the ability of (RS)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR) agonist, to evoke K-ATP currents. DHPG (20 mu M) evoked outward current at -70 mV and was associated with a positive slope conductance of 2.7 nS. The sulfonylurea agent tolbutamide (100 mu M) converted the positive slope to negative slope conductance, indicating mediation by K-ATP channels (ATP-sensitive K+ channels). Currents evoked by DHPG were significantly reduced by a combination of mGluR1 and mGluR5 negative allosteric modulators. DHPG-evoked outward current was blocked by cyclopiazonic acid and thapsigargin and mimicked by caffeine, suggesting mediation by release of intracellular Ca2+. DHPG outward current was also blocked by ryanodine and 2-aminoethoxydiphenylborane, suggesting mediation by ryanodine-and inositol 1,4,5-triphosphate-sensitive Ca2+ release. The nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester and inhibitors of protein kinase G activity also suppressed DHPG-induced outward current. Voltage recordings showed that tolbutamide prolonged depolarizing plateau potentials and increased the spontaneous firing rate of STN neurons recorded in the presence of DHPG. These results show that group I mGluR stimulation generates K-ATP current by a nitric oxide-and protein kinase G-dependent process that is mediated by release of Ca2+ from intracellular stores. Because burst firing is linked to symptoms of Parkinson's disease, we suggest that K-ATP channels might provide a physiologically important inhibitory influence on STN neuronal activity.
C1 [Shen, Ke-Zhong; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Johnson, Steven W.] Portland VA Med Ctr, Portland, OR 97207 USA.
RP Johnson, SW (reprint author), Portland VA Med Ctr, RD 61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA.
EM johnsost@ohsu.edu
FU National Institutes of Health National Institute of Neurological
Disorders and Stroke [NS38715]; Portland Veterans Affairs Parkinson's
Disease Research, Education, and Clinical Center
FX This work was supported by the National Institutes of Health National
Institute of Neurological Disorders and Stroke [Grant NS38715]; and by
the Portland Veterans Affairs Parkinson's Disease Research, Education,
and Clinical Center.
NR 54
TC 3
Z9 3
U1 1
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD APR
PY 2013
VL 345
IS 1
BP 139
EP 150
DI 10.1124/jpet.112.201566
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 109KT
UT WOS:000316367000016
PM 23335392
ER
PT J
AU Koyama, A
O'Brien, J
Weuve, J
Blacker, D
Metti, AL
Yaffe, K
AF Koyama, Alain
O'Brien, Jacqueline
Weuve, Jennifer
Blacker, Deborah
Metti, Andrea L.
Yaffe, Kristine
TI The Role of Peripheral Inflammatory Markers in Dementia and Alzheimer's
Disease: A Meta-Analysis
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Dementia; Alzheimer; Cognitive decline; Inflammation; c-reactive
protein; Interleukin-6
ID C-REACTIVE PROTEIN; MILD COGNITIVE IMPAIRMENT; CARDIOVASCULAR-DISEASE;
CONTROLLED-TRIAL; CLINICAL-TRIALS; FOLLOW-UP; RISK; HEALTH;
INTERLEUKIN-6; PROGRESSION
AB Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimers disease (AD).
The researchers conducted a literature search of observational studies indexed in the PubMed and PsycInfo databases. Selected studies included those with at least one peripheral inflammatory biomarker and its association with risk of all-cause dementia or AD. Random effects models were used to generate pooled hazard ratios (HRs) comparing the top versus bottom quantile of inflammatory marker level. Heterogeneity was assessed using the I-2 statistic.
Seven studies were identified, combining for a total 5,717 participants, 746 cases of all-cause dementia and 565 cases of AD. An increased level of C-reactive protein was associated with a 45% increased risk of all-cause dementia (HR: 1.45; 95% CI: 1.10, 1.91). Similarly, a higher level of interleukin-6 was associated with a 32% increased risk (HR: 1.32; 95% CI: 1.06, 1.64) of all-cause dementia. For AD alone, the association with C-reactive protein was less pronounced (HR: 1.21; 95% CI: 1.03, 1.42) and interleukin-6 was not associated with risk of AD (HR: 1.06; 95% CI: 0.83, 1.35). No significant heterogeneity was found in any of the meta-analyses (I-2 = 0%40%, p .16).
An increased peripheral level of inflammatory markers is associated with a modest increase in risk of all-cause dementia. Evidence for an association with risk of AD alone is limited.
C1 [Koyama, Alain] Northern Calif Inst Res & Educ, San Francisco, CA USA.
[Koyama, Alain; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[O'Brien, Jacqueline; Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Weuve, Jennifer] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Dept Internal Med, Chicago, IL 60612 USA.
[Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Metti, Andrea L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
RP Koyama, A (reprint author), San Francisco VA Med Ctr, 4150 Clement St,VAMC 116H, San Francisco, CA 94121 USA.
EM alain.koyama@va.gov
FU National Institute of Aging [K24 AG 031155, R01 AG 026720]; Alzheimer's
Association [IIRG-08-88872]
FX This work was supported by the National Institute of Aging (K24 AG
031155, R01 AG 026720) and the Alzheimer's Association (IIRG-08-88872).
NR 35
TC 49
Z9 49
U1 1
U2 29
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD APR
PY 2013
VL 68
IS 4
BP 433
EP 440
DI 10.1093/gerona/gls187
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 108DX
UT WOS:000316273000013
PM 22982688
ER
PT J
AU Wang, L
Porter, B
Maynard, C
Evans, G
Bryson, C
Sun, HL
Gupta, I
Lowy, E
McDonell, M
Frisbee, K
Nielson, C
Kirkland, F
Fihn, SD
AF Wang, Li
Porter, Brian
Maynard, Charles
Evans, Ginger
Bryson, Christopher
Sun, Haili
Gupta, Indra
Lowy, Elliott
McDonell, Mary
Frisbee, Kathleen
Nielson, Christopher
Kirkland, Fred
Fihn, Stephan D.
TI Predicting Risk of Hospitalization or Death Among Patients Receiving
Primary Care in the Veterans Health Administration
SO MEDICAL CARE
LA English
DT Article
DE primary care; statistical models; hospitalization; death
ID READMISSION; MODEL; REGRESSION
AB Background: Statistical models that identify patients at elevated risk of death or hospitalization have focused on population subsets, such as those with a specific clinical condition or hospitalized patients. Most models have limitations for clinical use. Our objective was to develop models that identified high-risk primary care patients.
Methods: Using the Primary Care Management Module in the Veterans Health Administration (VHA)'s Corporate Data Warehouse, we identified all patients who were enrolled and assigned to a VHA primary care provider on October 1, 2010. The outcome variable was the occurrence of hospitalization or death during the subsequent 90 days and 1 year. We extracted predictors from 6 categories: sociodemographics, medical conditions, vital signs, prior year use of health services, medications, and laboratory tests and then constructed multinomial logistic regression models to predict outcomes for over 4.6 million patients.
Results: In the predicted 95th risk percentiles, observed 90-day event rates were 19.6%, 6.2%, and 22.6%, respectively, for hospitalization, death, and either hospitalization or death, compared with population averages of 2.7%, 0.7%, and 3.4%, respectively; 1-year event rates were 42.3%, 19.4%, and 51.3%, respectively, compared with population averages of 8.2%, 2.6%, and 10.8%, respectively. The C-statistics for 90-day outcomes were 0.83, 0.86, and 0.81, respectively, for hospitalization, death, and either hospitalization or death and were 0.81, 0.85, and 0.79, respectively, for 1-year outcomes.
Conclusions: Prediction models using electronic clinical data accurately identified patients with elevated risk for hospitalization or death. This information can enhance the coordination of care for patients with complex clinical conditions.
C1 [Wang, Li; Maynard, Charles; Evans, Ginger; Bryson, Christopher; Sun, Haili; Gupta, Indra; Lowy, Elliott] VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA.
[Porter, Brian; Evans, Ginger; Bryson, Christopher; Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA USA.
[Maynard, Charles] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[McDonell, Mary; Frisbee, Kathleen; Nielson, Christopher; Kirkland, Fred; Fihn, Stephan D.] VHA Off Informat & Analyt Analyt & Business Intel, Washington, DC USA.
RP Maynard, C (reprint author), VA Puget Sound Hlth Care Syst, HSR&D 1100 Olive Way Suite 1400, Seattle, WA 98101 USA.
EM cmaynard@u.washington.edu
RI Maynard, Charles/N-3906-2015
OI Maynard, Charles/0000-0002-1644-7814
NR 19
TC 32
Z9 32
U1 0
U2 9
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 APR
PY 2013
VL 51
IS 4
BP 368
EP 373
DI 10.1097/MLR.0b013e31827da95a
PG 6
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 107HS
UT WOS:000316207100013
PM 23269113
ER
PT J
AU Herzig, MCS
Hildreth, K
Huamani, J
Perez, M
Goins, BA
McMahan, CA
Reddick, RL
Walter, CA
AF Herzig, Maryanne C. S.
Hildreth, Kim
Huamani, Jessica
Perez, Marissa
Goins, Beth A.
McMahan, C. Alex
Reddick, Robert L.
Walter, Christi A.
TI Human O-6-methylguanine-DNA methyltransferase containing C145A does not
prevent hepatocellular carcinoma in C3HeB/FeJ transgenic mice
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE liver cancer; DNA repair; mouse model; computed tomography; imaging
ID HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; DNA-REPAIR PROTEIN; HUMAN
LIVER-CANCER; MOUSE MODELS; ESCHERICHIA-COLI; TUMORS;
DIMETHYLNITROSAMINE; EXPRESSION; MUTATIONS; APOPTOSIS
AB The prevalence of hepatocellular carcinoma (HCC) was diminished from 60% to 18% at 15 months of age in C3HeB/FeJ male transgenic mice expressing hMGMT in our previous studies. To directly test if the methyltransferase activity is required for diminished tumor prevalence, two separate lines of transgenic mice bearing an enzymatically inactive form of hMGMT were used. In these lines, cysteine 145 was substituted with alanine (C145A). Expression of the hMGMT C145A transgene in liver was demonstrated by Northern blots and Western blots. Immunohistochemistry revealed predominantly nuclear localization of the hMGMT C145A protein. hMGMT C145A transgenic mice were crossed with lacI transgenic mice to assess mutant frequencies in the presence of the mutant protein. Mutant frequencies were similar among livers of lacIxhMGMT C145A bi-transgenic mice and lacIxwild-type (WT) mice. DNA sequence analysis of recovered lacI mutants revealed similar mutation spectra for hMGMT C145A and WT mice. The prevalence of HCC was also similar for the two tested lines of hMGMT C145A mice, 45% and 48% prevalence with median tumor sizes of 11 and 8mm, and WT mice, 40% prevalence and median tumor size of 10mm. These results provide evidence that residue C145 in hMGMT is required to reduce the prevalence of HCC in C3HeB/FeJ mice transgenic for hMGMT. (c) 2011 Wiley Periodicals, Inc.
C1 [Herzig, Maryanne C. S.; Hildreth, Kim; Perez, Marissa; Walter, Christi A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Huamani, Jessica] Childrens Healthcare Atlanta, Dept Radiol, Atlanta, GA USA.
[Goins, Beth A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[McMahan, C. Alex; Reddick, Robert L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Walter, Christi A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Walter, Christi A.] Barshop Inst Longev & Aging Studies, San Antonio, TX USA.
[Walter, Christi A.] Canc Therapy & Res Inst, San Antonio, TX USA.
RP Walter, CA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
FU VA Merit Award
FX This study was supported by a VA Merit Award (to C.A.W.). The generous
gift of the hMGMT C145A cDNA from Dr Anthony Pegg is gratefully
acknowledged. We would like to thank Dr. LuZhe Sun and Dr. Thomas J.
Slaga for their helpful comments in reviewing this article. We thank Dr.
Anu Soundararajan and Dr. Max Amurao for their technical assistance
during microCT image acquisition. We also thank Ms. Rebecca Garcia for
excellent technical assistance.
NR 71
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD APR
PY 2013
VL 52
IS 4
BP 275
EP 285
DI 10.1002/mc.21855
PG 11
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 112CQ
UT WOS:000316570000004
PM 22213062
ER
PT J
AU Jung, MK
Kim, KY
Lee, NY
Kang, YS
Hwang, YJ
Kim, Y
Sung, JJ
McKee, A
Kowall, N
Lee, J
Ryu, H
AF Jung, Min-Kyung
Kim, Ki Yoon
Lee, Na-Young
Kang, Young-Sook
Hwang, Yu Jin
Kim, Yunha
Sung, Jung-Joon
McKee, Ann
Kowall, Neil
Lee, Junghee
Ryu, Hoon
TI Expression of Taurine Transporter (TauT) is Modulated by Heat Shock
Factor 1 (HSF1) in Motor Neurons of ALS
SO MOLECULAR NEUROBIOLOGY
LA English
DT Review
DE Taurine transporter; Heat shock factor 1; Transcription; Taurine uptake;
Amyotrophic lateral sclerosis
ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU,ZN SUPEROXIDE-DISMUTASE; SPINAL-CORD;
AMINO-ACIDS; LINKED SOD1; BIOSYNTHETIC-ENZYMES; GENE-EXPRESSION;
NITRIC-OXIDE; CELL MODEL; BRAIN
AB Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive paralysis caused by the degeneration of motor neurons throughout the central nervous system. Mutations of the free radical scavenging enzyme Cu/Zn superoxide dismutase 1 (SOD1) are a cause of familial ALS. In the present study, we demonstrated an age-dependent increase in taurine transporter (TauT) immunoreactivity in spinal cord motor neurons of ALS transgenic mice (mutant SOD1 (G93A)) and a similar increase in TauT in spinal motor neurons of patients with ALS. Chromatin immunoprecipitation analysis verified that heat shock factor 1 (HSF1) preferentially occupies the HSF1 binding element in the promoter of TauT under oxidative stress conditions. Knockdown of HSF1 by small interfering RNA reduced the transcriptional activity of TauT. Using [H-3] taurine, we confirmed that an elevated expression of TauT directly contributes to increased taurine uptake in ALS motor neurons. In addition, we showed that taurine plays an antioxidant role and may prevent motor neuron loss due to oxidative stress in ALS. Our findings suggest that HSF1-induced TauT expression partially protects motor neurons by compensating for constitutive oxidative stress, which is thought to be a key mechanism contributing to the pathogenesis of ALS. Taken together, our results suggest that TauT is a novel pathological marker for stressed motor neurons in ALS and that modulation of TauT and taurine may slow neuronal degeneration in ALS.
C1 [Jung, Min-Kyung; Kim, Ki Yoon; Hwang, Yu Jin; Kim, Yunha; Ryu, Hoon] Seoul Natl Univ, Coll Med, WCU Neurocyt Grp, Dept Biomed Sci, Seoul 110799, South Korea.
[Lee, Na-Young; Kang, Young-Sook] Sookmyung Womens Univ, Coll Pharm, Res Ctr Cell Fate Control, Seoul 140742, South Korea.
[Sung, Jung-Joon] Seoul Natl Univ Hosp, Dept Neurol, Seoul 110799, South Korea.
[McKee, Ann; Kowall, Neil; Lee, Junghee; Ryu, Hoon] Boston VA Healthcare Syst, Boston, MA 02130 USA.
[McKee, Ann; Kowall, Neil; Lee, Junghee; Ryu, Hoon] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA.
[McKee, Ann; Kowall, Neil; Lee, Junghee; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
RP Lee, J (reprint author), Boston VA Healthcare Syst, Bldg 1A,Room 105,150 South Huntington Ave, Boston, MA 02130 USA.
EM junghee@bu.edu; hoonryu@bu.edu
RI Kowall, Neil/G-6364-2012
OI Kowall, Neil/0000-0002-6624-0213
FU Rare Disease Research Center Grant from Korea Ministry of Health and
Welfare; SRC Grant [2010-0029-403]; WCU Neurocytomics Program Grant
[800-20080848]; National Research Foundation of Korea (NRF)
[2011-0030701]; Korean government (MEST); VA Merit Award
FX This study was supported by the Rare Disease Research Center Grant from
Korea Ministry of Health and Welfare (HR), SRC Grant (2010-0029-403)
(HR) and WCU Neurocytomics Program Grant (800-20080848) (HR). This study
was also supported by the National Research Foundation of Korea (NRF)
grant (no. 2011-0030701) (YSK) funded by the Korean government (MEST)
and VA Merit Award (JL and NK).
NR 38
TC 4
Z9 5
U1 2
U2 15
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD APR
PY 2013
VL 47
IS 2
BP 699
EP 710
DI 10.1007/s12035-012-8371-9
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 106DC
UT WOS:000316120900021
PM 23180277
ER
PT J
AU Ho, NF
Hooker, JM
Sahay, A
Holt, DJ
Roffman, JL
AF Ho, N. F.
Hooker, J. M.
Sahay, A.
Holt, D. J.
Roffman, J. L.
TI In vivo imaging of adult human hippocampal neurogenesis: progress,
pitfalls and promise
SO MOLECULAR PSYCHIATRY
LA English
DT Review
DE Adult human hippocampal neurogenesis; in vivo neuroimaging
ID POSTTRAUMATIC-STRESS-DISORDER; NEURAL PROGENITOR CELLS; DENTATE GRANULE
CELLS; VOXEL-BASED MORPHOMETRY; TERM LITHIUM TREATMENT; MEDIAL
TEMPORAL-LOBE; RAT HIPPOCAMPUS; ELECTROCONVULSIVE SEIZURES; HUMAN BRAIN;
ENRICHED ENVIRONMENT
AB New neurons are produced within the hippocampus of the mammalian brain throughout life. Evidence from animal studies has suggested that the function of these adult-born neurons is linked to cognition and emotion. Until we are able to detect and measure levels of adult neurogenesis in living human brains-a formidable challenge for now-we cannot establish its functional importance in human health, disease and new treatment development. Current non-invasive neuroimaging modalities can provide live snapshots of the brain's structure, chemistry, activity and connectivity. This review explores whether existing macroscopic imaging methods can be used to understand the microscopic dynamics of adult hippocampal neurogenesis in living individuals. We discuss recent studies that have found correlations between neuroimaging measures of human hippocampal biology and levels of pro- or anti-neurogenic stimuli, weigh whether these correlations reflect changes in adult neurogenesis, detail the conceptual and technical limitations of these studies and elaborate on what will be needed to validate in vivo neuroimaging measures of adult neurogenesis for future investigations. Molecular Psychiatry (2013) 18, 404-416; doi:10.1038/mp.2013.8; published online 26 February 2013
C1 [Ho, N. F.; Holt, D. J.; Roffman, J. L.] Massachusetts Gen Hosp, Dept Psychiat, Schizophrenia Program, Boston, MA 02114 USA.
[Ho, N. F.; Holt, D. J.; Roffman, J. L.] Massachusetts Gen Hosp, Psychiat Neurosci Res Program, Charlestown, MA USA.
[Hooker, J. M.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Sahay, A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Sahay, A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Sahay, A.] Harvard Stem Cell Inst, Boston, MA USA.
[Ho, N. F.; Hooker, J. M.; Sahay, A.; Holt, D. J.; Roffman, J. L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ho, NF (reprint author), Schizophrenia Res Program, 149 13th St,Suite 2611, Charlestown, MA 02129 USA.
EM newfei@nmr.mgh.harvard.edu
OI Hooker, Jacob/0000-0002-9394-7708
FU Howard Hughes Medical Institute Early Career Physician-Scientist Award;
US National Institute of Mental Health grant [4R00MH086615-03]; Ellison
Medical Foundation New Scholar in Aging; Whitehall Foundation
FX This work was supported by the Howard Hughes Medical Institute Early
Career Physician-Scientist Award (JLR), US National Institute of Mental
Health grant 4R00MH086615-03 (AS) and the Ellison Medical Foundation New
Scholar in Aging and the Whitehall Foundation (AS).
NR 167
TC 29
Z9 30
U1 4
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD APR
PY 2013
VL 18
IS 4
BP 404
EP 416
DI 10.1038/mp.2013.8
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 112CE
UT WOS:000316568600007
PM 23439487
ER
PT J
AU Sullivan, PF
Daly, MJ
Ripke, S
Lewis, CM
Lin, DY
Wray, NR
Neale, B
Levinson, DF
Breen, G
Byrne, EM
Wray, NR
Levinson, DF
Rietschel, M
Hoogendijk, W
Ripke, S
Sullivan, PF
Hamilton, SP
Levinson, DF
Lewis, CM
Ripke, S
Weissman, MM
Wray, NR
Breuer, R
Cichon, S
Degenhardt, F
Frank, J
Gross, M
Herms, S
Hoefels, S
Maier, W
Mattheisen, M
Noethen, MM
Rietschel, M
Schulze, TG
Steffens, M
Treutlein, J
Boomsma, DI
De Geus, EJ
Hoogendijk, W
Hottenga, JJ
Jung-Ying, T
Lin, DY
Middeldorp, CM
Nolen, WA
Penninx, BP
Smit, JH
Sullivan, PF
van Grootheest, G
Willemsen, G
Zitman, FG
Coryell, WH
Knowles, JA
Lawson, WB
Levinson, DF
Potash, JB
Scheftner, WA
Shi, JX
Weissman, MM
Holsboer, F
Muglia, P
Tozzi, F
Blackwood, DHR
Boomsma, DI
De Geus, EJ
Hottenga, JJ
MacIntyre, DJ
McIntosh, A
McLean, A
Middeldorp, CM
Nolen, WA
Penninx, BP
Ripke, S
Smit, JH
Sullivan, PF
van Grootheest, G
Willemsen, G
Zitman, FG
van den Oord, EJCG
Holsboer, F
Lucae, S
Binder, E
Muller-Myhsok, B
Ripke, S
Czamara, D
Kohli, MA
Ising, M
Uhr, M
Bettecken, T
Barnes, MR
Breen, G
Craig, IW
Farmer, AE
Lewis, CM
McGuffin, P
Muglia, P
Byrne, E
Gordon, SD
Heath, AC
Henders, AK
Hickie, IB
Madden, PAF
Martin, NG
Montgomery, GM
Nyholt, DR
Pergadia, ML
Wray, NR
Hamilton, SP
McGrath, PJ
Shyn, SI
Slager, SL
Oskarsson, H
Sigurdsson, E
Stefansson, H
Stefansson, K
Steinberg, S
Thorgeirsson, T
Levinson, DF
Potash, JB
Shi, JX
Weissman, MM
Guipponi, M
Lewis, G
O'Donovan, M
Tansey, KE
Uher, R
Coryell, WH
Knowles, JA
Lawson, WB
Levinson, DF
Potash, JB
Scheftner, WA
Shi, JX
Weissman, MM
Castro, VM
Churchill, SE
Fava, M
Gainer, VS
Gallagher, PJ
Goryachev, S
Iosifescu, DV
Kohane, IS
Murphy, SN
Perlis, RH
Smoller, JW
Weilburg, JB
Kutalik, Z
Preisig, M
Grabe, HJ
Nauck, M
Schulz, A
Teumer, A
Volzke, H
Landen, M
Lichtenstein, P
Magnusson, P
Pedersen, N
Viktorin, A
AF Sullivan, Patrick F.
Daly, Mark J.
Ripke, Stephan
Lewis, Cathryn M.
Lin, Dan-Yu
Wray, Naomi R.
Neale, Benjamin
Levinson, Douglas F.
Breen, Gerome
Byrne, Enda M.
Wray, Naomi R.
Levinson, Douglas F.
Rietschel, Marcella
Hoogendijk, Witte
Ripke, Stephan
Sullivan, Patrick F.
Hamilton, Steven P.
Levinson, Douglas F.
Lewis, Cathryn M.
Ripke, Stephan
Weissman, Myrna M.
Wray, Naomi R.
Breuer, Rene
Cichon, Sven
Degenhardt, Franziska
Frank, Josef
Gross, Magdalena
Herms, Stefan
Hoefels, Susanne
Maier, Wolfgang
Mattheisen, Manuel
Noeethen, Markus M.
Rietschel, Marcella
Schulze, Thomas G.
Steffens, Michael
Treutlein, Jens
Boomsma, Dorret I.
De Geus, Eco J.
Hoogendijk, Witte
Hottenga, Jouke Jan
Jung-Ying, Tzeng
Lin, Dan-Yu
Middeldorp, Christel M.
Nolen, Willem A.
Penninx, Brenda P.
Smit, Johannes H.
Sullivan, Patrick F.
van Grootheest, Gerard
Willemsen, Gonneke
Zitman, Frans G.
Coryell, William H.
Knowles, James A.
Lawson, William B.
Levinson, Douglas F.
Potash, James B.
Scheftner, William A.
Shi, Jianxin
Weissman, Myrna M.
Holsboer, Florian
Muglia, Pierandrea
Tozzi, Federica
Blackwood, Douglas H. R.
Boomsma, Dorret I.
De Geus, Eco J.
Hottenga, Jouke Jan
MacIntyre, Donald J.
McIntosh, Andrew
McLean, Alan
Middeldorp, Christel M.
Nolen, Willem A.
Penninx, Brenda P.
Ripke, Stephan
Smit, Johannes H.
Sullivan, Patrick F.
van Grootheest, Gerard
Willemsen, Gonneke
Zitman, Frans G.
van den Oord, Edwin J. C. G.
Holsboer, Florian
Lucae, Susanne
Binder, Elisabeth
Mueller-Myhsok, Bertram
Ripke, Stephan
Czamara, Darina
Kohli, Martin A.
Ising, Marcus
Uhr, Manfred
Bettecken, Thomas
Barnes, Michael R.
Breen, Gerome
Craig, Ian W.
Farmer, Anne E.
Lewis, Cathryn M.
McGuffin, Peter
Muglia, Pierandrea
Byrne, Enda
Gordon, Scott D.
Heath, Andrew C.
Henders, Anjali K.
Hickie, Ian B.
Madden, Pamela A. F.
Martin, Nicholas G.
Montgomery, Grant M.
Nyholt, Dale R.
Pergadia, Michele L.
Wray, Naomi R.
Hamilton, Steven P.
McGrath, Patrick J.
Shyn, Stanley I.
Slager, Susan L.
Oskarsson, Hoegni
Sigurdsson, Engilbert
Stefansson, Hreinn
Stefansson, Kari
Steinberg, Stacy
Thorgeirsson, Thorgeir
Levinson, Douglas F.
Potash, James B.
Shi, Jianxin
Weissman, Myrna M.
Guipponi, Michel
Lewis, Glyn
O'Donovan, Michael
Tansey, Katherine E.
Uher, Rudolf
Coryell, William H.
Knowles, James A.
Lawson, William B.
Levinson, Douglas F.
Potash, James B.
Scheftner, William A.
Shi, Jianxin
Weissman, Myrna M.
Castro, Victor M.
Churchill, Susanne E.
Fava, Maurizio
Gainer, Vivian S.
Gallagher, Patience J.
Goryachev, Sergey
Iosifescu, Dan V.
Kohane, Isaac S.
Murphy, Shawn N.
Perlis, Roy H.
Smoller, Jordan W.
Weilburg, Jeffrey B.
Kutalik, Zoltan
Preisig, Martin
Grabe, Hans J.
Nauck, Matthias
Schulz, Andrea
Teumer, Alexander
Voelzke, Henry
Landen, Mikael
Lichtenstein, Paul
Magnusson, Patrik
Pedersen, Nancy
Viktorin, Alexander
CA Psychiat GWAS Consortium
TI A mega-analysis of genome-wide association studies for major depressive
disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE genetics; genome-wide association study; major depressive disorder;
mega-analysis; meta-analysis
ID CARDIOVASCULAR RISK-FACTORS; NATIONAL COMORBIDITY SURVEY; SEROTONIN
TRANSPORTER GENE; BIPOLAR DISORDER; SUSCEPTIBILITY LOCI;
PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; MOOD DISORDERS; TWIN REGISTRY;
HUMAN HEIGHT
AB Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5x10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9x10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status. Molecular Psychiatry (2013) 18, 497-511; doi:10.1038/mp.2012.21; published online 3 April 2012
C1 [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Daly, Mark J.; Ripke, Stephan] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Wray, Naomi R.] Univ Queensland, Queensland Inst Med Res, Brisbane, Qld 4072, Australia.
[Lewis, Cathryn M.; Breen, Gerome; Craig, Ian W.; Farmer, Anne E.; McGuffin, Peter; Tansey, Katherine E.; Uher, Rudolf] Kings Coll London, Inst Psychiat, London, England.
[Hamilton, Steven P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Weissman, Myrna M.; McGrath, Patrick J.] Columbia Univ, New York, NY 10027 USA.
[Blackwood, Douglas H. R.; MacIntyre, Donald J.; McIntosh, Andrew; McLean, Alan] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke Jan; Middeldorp, Christel M.; Willemsen, Gonneke] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Cichon, Sven; Degenhardt, Franziska; Gross, Magdalena; Herms, Stefan; Hoefels, Susanne; Maier, Wolfgang; Mattheisen, Manuel; Noeethen, Markus M.; Steffens, Michael] Univ Bonn, Bonn, Germany.
[Heath, Andrew C.; Madden, Pamela A. F.; Pergadia, Michele L.] Washington Univ, St Louis, MO USA.
[Byrne, Enda M.; Gordon, Scott D.; Henders, Anjali K.; Martin, Nicholas G.; Montgomery, Grant M.; Nyholt, Dale R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Penninx, Brenda P.; Smit, Johannes H.; van Grootheest, Gerard] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Coryell, William H.; Potash, James B.] Univ Iowa, Iowa City, IA 52242 USA.
[Rietschel, Marcella; Breuer, Rene; Frank, Josef; Treutlein, Jens] Heidelberg Univ, Cent Inst Mental Hlth, Heidelberg, Germany.
[Sullivan, Patrick F.; Lin, Dan-Yu] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Shi, Jianxin] NCI, Bethesda, MD 20892 USA.
[Grabe, Hans J.; Nauck, Matthias; Schulz, Andrea; Teumer, Alexander; Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.
[Lichtenstein, Paul; Magnusson, Patrik; Pedersen, Nancy; Viktorin, Alexander] Karolinska Inst, S-10401 Stockholm, Sweden.
[Fava, Maurizio; Gallagher, Patience J.; Iosifescu, Dan V.; Murphy, Shawn N.; Smoller, Jordan W.; Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kutalik, Zoltan] Univ Lausanne, CH-1015 Lausanne, Switzerland.
[O'Donovan, Michael] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales.
[Guipponi, Michel] Univ Geneva, CH-1211 Geneva 4, Switzerland.
[Hickie, Ian B.] Univ Sydney, Sydney, NSW 2006, Australia.
Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
[Jung-Ying, Tzeng] N Carolina State Univ, Raleigh, NC 27695 USA.
[Knowles, James A.] Univ So Calif, Los Angeles, CA 90089 USA.
[Kohane, Isaac S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
Queen Mary Univ London, London, England.
[Lawson, William B.] Howard Univ, Washington, DC USA.
[Lewis, Glyn] Univ Bristol, Bristol BS8 1TH, Avon, England.
Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
[Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
[Scheftner, William A.] Rush Univ, Med Ctr, Chicago, IL USA.
[Shyn, Stanley I.] Univ Washington, Seattle, WA 98195 USA.
[Slager, Susan L.] Mayo Clin, Rochester, MN 55905 USA.
[van den Oord, Edwin J. C. G.] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Zitman, Frans G.] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Levinson, Douglas F.] Stanford Univ, Stanford, CA 94305 USA.
RP Sullivan, PF (reprint author), Univ N Carolina, Dept Genet, CB 7264, Chapel Hill, NC 27599 USA.
EM pfsulliv@med.unc.edu
RI Lewis, Glyn/E-9944-2012; Breen, Gerome/A-5540-2010; Wray,
Naomi/C-8639-2015; Mattheisen, Manuel/B-4949-2012; Magnusson,
Patrik/C-4458-2017; Schulze, Thomas/H-2157-2013; Nolen,
Willem/E-9006-2014; Lewis, Cathryn/A-5225-2010; Tansey,
Katherine/B-1033-2013; McGrath, Patrick/I-6410-2013; McGuffin,
Peter/A-1565-2012; McIntosh, Andrew/B-9379-2008; Uher,
Rudolf/A-5477-2008; Colaus, PsyColaus/K-6607-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; van Grootheest,
Gerard/C-6942-2014; Sigurdsson, Engilbert/D-2486-2014
OI Landen, Mikael/0000-0002-4496-6451; lichtenstein,
paul/0000-0003-3037-5287; Viktorin, Alexander/0000-0003-2141-2816;
Stefansson, Hreinn/0000-0002-9331-6666; Nothen,
Markus/0000-0002-8770-2464; Middeldorp, Christel/0000-0002-6218-0428;
Thorgeirsson, Thorgeir/0000-0002-5149-7040; de Geus,
Eco/0000-0001-6022-2666; Lewis, Glyn/0000-0001-5205-8245; Breen,
Gerome/0000-0003-2053-1792; Wray, Naomi/0000-0001-7421-3357; Mattheisen,
Manuel/0000-0002-8442-493X; MacIntyre, Donald J/0000-0001-6963-1335;
Hamilton, Steven/0000-0001-8106-6260; Craig, Ian/0000-0002-4063-1005;
Lewis, Cathryn/0000-0002-8249-8476; Tansey,
Katherine/0000-0002-9663-3376; McGrath, Patrick/0000-0001-7217-7321;
McGuffin, Peter/0000-0002-9888-2907; McIntosh,
Andrew/0000-0002-0198-4588; Uher, Rudolf/0000-0002-2998-0546; Cichon,
Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; van
Grootheest, Gerard/0000-0003-4350-6661; Sigurdsson,
Engilbert/0000-0001-9404-7982
FU NIMH [MH085520, MH080403, MH061686, MH059542, MH075131, MH059552,
MH059541, MH060912, MH086026, MH081802, MH072802, N01MH90003]; German
Federal Ministry of Education and Research; National Genome Research
Network 2 (NGFN-2); National Genome Research Network plus (NGFNplus);
Integrated Genome Research Network (IG) MooDS [01GS08144, 01GS08147];
European Union [LSHM-CT-2006-037761, PIAP-GA-2008-218251,
HEALTH-F2-2009-223423]; Medical Research Council (UK); Mental Health
Research Network; Innovative Medicines Initiative [115008]; National
Alliance for Research on Schizophrenia and Depression; i2b2 Center
(Informatics for Integrating Biology and the Bedside); NIH
[U54LM008748]; BMBF Program Molecular Diagnostics: Validation of
Biomarkers for Diagnosis and Outcome in Major Depression [01ES0811];
Netherlands Organization for Scientific Research (MagW/ZonMW)
[904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 912-100-20,
56-464-14192, 10-000-1002]; Center for Medical Systems Biology (NWO
Genomics); Biobanking and Biomolecular Resources Research
Infrastructure; VU University's Institutes for Health and Care Research
and Neuroscience Campus Amsterdam; NBIC/BioAssist/RK [2008.024];
European Science Foundation [EU/QLRT-2001-01254]; European Community;
ENGAGE [HEALTH-F4-2007-201413]; European Science Council (ERC) [230374];
Genetic Association Information Network (GAIN) of the Foundation for the
US National Institutes of Health; GAIN; Netherlands Organization for
Scientific Research (NOW-VENI grant) [916-76-125]; Swiss National
Science Foundation [3200B0-105993, 3200B0-118'308, 33CSC0-122661];
GlaxoSmithKline (Psychiatry Center of Excellence for Drug Discovery and
Genetics Division, Drug Discovery - Verona, RD); Australian National
Health; Medical Research Council [241944, 339462, 389927, 389875,
389891, 389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498,
613602, 613608, 613674, 619667]; Australian Research Council [FT0991360,
FT0991022]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; US National
Institutes of Health [AA07535, AA10248, AA13320, AA13321, AA13326,
AA14041, MH66206, DA12854, DA019951, U01 DK066134]; Center for Inherited
Disease Research (Baltimore, MD, USA); UK Medical Research Council;
GlaxoSmithKline [G0701420]; National Institute for Health Research
(NIHR) Specialist Biomedical Research Centre for Mental Health at the
South London; Maudsley NHS Foundation Trust; Institute of Psychiatry,
King's College London; UK Medical Research Council [G0000647]; European
Commission [LSHB-CT-2003-503428]; Federal Ministry of Education and
Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural
Affairs; Social Ministry of the Federal State of Mecklenburg-West
Pomerania; Federal Ministry of Education and Research; Siemens
Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West
Pomerania; German Research Foundation [DFG: GR 1912/5-1]; Swedish
Ministry for Higher Education; Swedish Research Council [M-2005-1112];
GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254]; Swedish Foundation
for Strategic Research; Wellcome Trust [076113, 085475]; [U54
RR020278]; [RC2MH089916]
FX We thank the thousands of people with MDD who donated time and effort to
make this research possible. The PGC was funded by NIMH Grants MH085520
(lead PI PFS) and MH080403. We thank our colleagues in the PGC Bipolar
Disorder Working Group who allowed pre-publication access to their GWAS
mega-analysis results for the MDD-BIP cross-disorder analyses. The
Bonn/Mannheim (BoMa) GWAS was supported by the German Federal Ministry
of Education and Research, within the context of the National Genome
Research Network 2 (NGFN-2), the National Genome Research Network plus
(NGFNplus) and the Integrated Genome Research Network (IG) MooDS (Grant
01GS08144 to S Cichon and MM Noethen, and Grant 01GS08147 to M
Rietschel). The work at deCODE was funded by European Union Grants
LSHM-CT-2006-037761 (Project SGENE), PIAP-GA-2008-218251 (Project
PsychGene) and HEALTH-F2-2009-223423 (Project PsychCNVs). GenPod was
funded by the Medical Research Council (UK) and supported by the Mental
Health Research Network. Genotyping of the GenPod sample was funded by
the Innovative Medicines Initiative Joint Undertaking under Grant
Agreement number 115008 (NEWMEDS). The GenRED GWAS project was supported
by NIMH R01 Grants MH061686 (DF Levinson), MH059542 (WH Coryell),
MH075131 (WB Lawson), MH059552 (JB Potash), MH059541 (WA Scheftner) and
MH060912 (MM Weissman). We acknowledge the contributions of Dr George S
Zubenko and Dr Wendy N Zubenko, Department of Psychiatry, University of
Pittsburgh School of Medicine, to the GenRED I project. The NIMH Cell
Repository at Rutgers University and the NIMH Center for Collaborative
Genetic Studies on Mental Disorders made essential contributions to this
project. Genotyping was carried out by the Broad Institute Center for
Genotyping and Analysis with support from Grant U54 RR020278 (which
partially subsidized the genotyping of the GenRED cases). Collection and
quality control analyses of the control data set were supported by
grants from NIMH and the National Alliance for Research on Schizophrenia
and Depression. We are grateful to Knowledge Networks (Menlo Park, CA,
USA) for assistance in collecting the control data set. We express our
profound appreciation to the families who participated in this project,
and to the many clinicians who facilitated the referral of participants
to the study. The Depression Genes and Networks ARRA grant was funded by
RC2MH089916. Funding for the Harvard i2b2 sample was provided by a
subcontract to RH Perlis and JW Smoller as part of the i2b2 Center
(Informatics for Integrating Biology and the Bedside), an NIH-funded
National Center for Biomedical Computing based at Partners HealthCare
System (U54LM008748, PI: IS Kohane), and by an NIMH Grant to RH Perlis
(MH086026). Max Planck Institute of Psychiatry MARS study was supported
by the BMBF Program Molecular Diagnostics: Validation of Biomarkers for
Diagnosis and Outcome in Major Depression (01ES0811). Genotyping was
supported by the Bavarian Ministry of Commerce, and the Federal Ministry
of Education and Research (BMBF) in the framework of the National Genome
Research Network (NGFN2 and NGFN-Plus, FKZ 01GS0481 and 01GS08145). The
Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands
Twin Register (NTR) contributed to GAIN-MDD and to MDD2000.; Funding was
from: the Netherlands Organization for Scientific Research (MagW/ZonMW
Grants 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717,
912-100-20; Spinozapremie 56-464-14192; Geestkracht program Grant
10-000-1002); the Center for Medical Systems Biology (NWO Genomics),
Biobanking and Biomolecular Resources Research Infrastructure, VU
University's Institutes for Health and Care Research and Neuroscience
Campus Amsterdam, NBIC/BioAssist/RK (2008.024); the European Science
Foundation (EU/QLRT-2001-01254); the European Community's Seventh
Framework Program (FP7/2007-2013); ENGAGE (HEALTH-F4-2007-201413); and
the European Science Council (ERC, 230374). Genotyping was funded in
part by the Genetic Association Information Network (GAIN) of the
Foundation for the US National Institutes of Health, and analysis was
supported by grants from GAIN and the NIMH (MH081802). CM Middeldorp was
supported by the Netherlands Organization for Scientific Research
(NOW-VENI grant 916-76-125). The PsyCoLaus study was supported by grants
from the Swiss National Science Foundation (#3200B0-105993,
#3200B0-118'308, 33CSC0-122661) and from GlaxoSmithKline (Psychiatry
Center of Excellence for Drug Discovery and Genetics Division, Drug
Discovery - Verona, R&D). We express our gratitude to the Lausanne
inhabitants who volunteered to participate in the PsyCoLaus study. We
also thank V Mooser, G Weaber and P Vollenweider who initiated the
CoLaus project. Funding for the QIMR samples was provided by the
Australian National Health and Medical Research Council (241944, 339462,
389927, 389875, 389891, 389892, 389938, 442915, 442981, 496675, 496739,
552485, 552498, 613602, 613608, 613674, 619667), the Australian Research
Council (FT0991360, FT0991022), the FP-5 GenomEUtwin Project
(QLG2-CT-2002-01254) and the US National Institutes of Health (AA07535,
AA10248, AA13320, AA13321, AA13326, AA14041, MH66206, DA12854,
DA019951), and the Center for Inherited Disease Research (Baltimore, MD,
USA). We thank the twins and their families registered at the Australian
Twin Registry for their participation in the many studies that have
contributed to this research. RADIANT was funded by: a joint grant from
the UK Medical Research Council and GlaxoSmithKline (G0701420); the
National Institute for Health Research (NIHR) Specialist Biomedical
Research Centre for Mental Health at the South London and Maudsley NHS
Foundation Trust and the Institute of Psychiatry, King's College London;
and the UK Medical Research Council (G0000647). The GENDEP study was
funded by a European Commission Framework 6 grant, EC Contract Ref.:
LSHB-CT-2003-503428. 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 (Grants no. 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 (Grant
no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen,
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. SHIP-LEGEND is funded by the
German Research Foundation (DFG: GR 1912/5-1). Genotyping of
STARstarD was supported by an NIMH Grant to SP Hamilton
(MH072802).; STARstarD was funded by the National Institute
of Mental Health (contract N01MH90003) to the University of Texas
Southwestern Medical Center at Dallas (AJ Rush, principal investigator).
The TwinGene study was supported by the Swedish Ministry for Higher
Education, the Swedish Research Council (M-2005-1112), GenomEUtwin
(EU/QLRT-2001-01254; QLG2-CT-2002-01254), the Swedish Foundation for
Strategic Research and the US National Institutes of Health (U01
DK066134). This study makes use of data generated by the Wellcome Trust
Case-Control Consortium. A full list of the investigators who
contributed to the generation of the data is available from
http://www.wtccc.org.uk. Funding for the project was provided by the
Wellcome Trust under awards 076113 and 085475.
NR 87
TC 105
Z9 106
U1 12
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD APR
PY 2013
VL 18
IS 4
BP 497
EP 511
DI 10.1038/mp.2012.21
PG 15
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 112CE
UT WOS:000316568600016
ER
PT J
AU Ferguson, M
Bianchi, MT
Sutter, R
Rosenthal, ES
Cash, SS
Kaplan, PW
Westover, MB
AF Ferguson, Matthew
Bianchi, Matt T.
Sutter, Raoul
Rosenthal, Eric S.
Cash, Sydney S.
Kaplan, Peter W.
Westover, M. Brandon
TI Calculating the Risk Benefit Equation for Aggressive Treatment of
Non-convulsive Status Epilepticus
SO NEUROCRITICAL CARE
LA English
DT Article
DE Non-convulsive status epilepticus; Risk benefit analysis; NCSE; Decision
analysis
ID REFRACTORY STATUS EPILEPTICUS; INTENSIVE-CARE-UNIT; CONVULSIVE STATUS
EPILEPTICUS; TRAUMATIC BRAIN-INJURY; QUALITY-OF-LIFE;
RESPIRATORY-DISTRESS-SYNDROME; INTRACEREBRAL HEMORRHAGE; ABSENCE STATUS;
ELECTROGRAPHIC SEIZURES; HOSPITAL MORTALITY
AB To address the question: does non-convulsive status epilepticus warrant the same aggressive treatment as convulsive status epilepticus?
We used a decision model to evaluate the risks and benefits of treating non-convulsive status epilepticus with intravenous anesthetics and ICU-level aggressive care. We investigated how the decision to use aggressive versus non-aggressive management for non-convulsive status epilepticus impacts expected patient outcome for four etiologies: absence epilepsy, discontinued antiepileptic drugs, intraparenchymal hemorrhage, and hypoxic ischemic encephalopathy. Each etiology was defined by distinct values for five key parameters: baseline mortality rate of the inciting etiology; efficacy of non-aggressive treatment in gaining control of seizures; the relative contribution of seizures to overall mortality; the degree of excess disability expected in the case of delayed seizure control; and the mortality risk of aggressive treatment.
Non-aggressive treatment was favored for etiologies with low morbidity and mortality such as absence epilepsy and discontinued antiepileptic drugs. The risk of aggressive treatment was only warranted in etiologies where there was significant risk of seizure-induced neurologic damage. In the case of post-anoxic status epilepticus, expected outcomes were poor regardless of the treatment chosen. The favored strategy in each case was determined by strong interactions of all five model parameters.
Determination of the optimal management approach to non-convulsive status epilepticus is complex and is ultimately determined by the inciting etiology.
C1 [Ferguson, Matthew; Bianchi, Matt T.; Rosenthal, Eric S.; Cash, Sydney S.; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sutter, Raoul] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Div Neurosci Crit Care, Baltimore, MD 21205 USA.
[Sutter, Raoul; Kaplan, Peter W.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA.
[Westover, M. Brandon] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Westover, MB (reprint author), Massachusetts Gen Hosp, Wang 7 Neurol,55 Fruit St, Boston, MA 02114 USA.
EM gferguson1212@gmail.com; mtbianchi@partners.org; rsutter3@jhmi.edu;
erosenthal@partners.org; pkaplan@jhmi.edu; mb.westover@gmail.com
OI Sutter, Raoul/0000-0002-6575-356X; Rosenthal, Eric/0000-0003-3900-356X
FU NIH/NINDS [NS062092]; American Brain Foundation; National Center for
Research Resources: Harvard Clinical and Translational Science Center;
Center for Integration of Medicine and Innovative Technology (CIMIT);
NIH/NIBIB [5U54EB007954-04]; Department of Defense [W81XWH-08-2-0154];
Andrew David Heitman Neuroendovascular Research Foundation
FX MBW receives research support from the NIH/NINDS (NS062092) and American
Brain Foundation. MTB receives research support from the National Center
for Research Resources: Harvard Clinical and Translational Science
Center and the Center for Integration of Medicine and Innovative
Technology (CIMIT). ESR receives research support from the Center for
Integration of Medicine and Innovative Technology (CIMIT), the NIH/NIBIB
(5U54EB007954-04), the Department of Defense (W81XWH-08-2-0154), and the
Andrew David Heitman Neuroendovascular Research Foundation.
NR 78
TC 12
Z9 12
U1 0
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1541-6933
J9 NEUROCRIT CARE
JI Neurocrit. Care
PD APR
PY 2013
VL 18
IS 2
BP 216
EP 227
DI 10.1007/s12028-012-9785-y
PG 12
WC Critical Care Medicine; Clinical Neurology
SC General & Internal Medicine; Neurosciences & Neurology
GA 105PR
UT WOS:000316084700009
PM 23065689
ER
PT J
AU Battey, TWK
Falcone, GJ
Sheth, KN
Goldstein, JN
Rosand, J
AF Battey, Thomas W. K.
Falcone, Guido J.
Sheth, Kevin N.
Goldstein, Joshua N.
Rosand, Jonathan
TI Authors' Reply: Confounding by Indication in Retrospective Studies of
Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality
SO NEUROCRITICAL CARE
LA English
DT Letter
ID VOLUME
C1 [Battey, Thomas W. K.; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA.
[Battey, Thomas W. K.; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA.
[Battey, Thomas W. K.; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Sheth, Kevin N.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA.
EM jrosand@partners.org
RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016
OI Falcone, Guido/0000-0002-6407-0302
NR 4
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1541-6933
J9 NEUROCRIT CARE
JI Neurocrit. Care
PD APR
PY 2013
VL 18
IS 2
BP 287
EP 288
DI 10.1007/s12028-013-9820-7
PG 2
WC Critical Care Medicine; Clinical Neurology
SC General & Internal Medicine; Neurosciences & Neurology
GA 105PR
UT WOS:000316084700020
PM 23408339
ER
PT J
AU Huang, SN
Farrar, CT
Dai, GP
Kwon, SJ
Bogdanov, AA
Rosen, BR
Kim, YR
AF Huang, Shuning
Farrar, Christian T.
Dai, Guangping
Kwon, Seon Joo
Bogdanov, Alexei A., Jr.
Rosen, Bruce R.
Kim, Young R.
TI Dynamic monitoring of blood-brain barrier integrity using water exchange
index (WEI) during mannitol and CO2 challenges in mouse brain
SO NMR IN BIOMEDICINE
LA English
DT Article
DE blood-brain barrier; water exchange; cerebral blood volume; mannitol;
CO2; mouse
ID NUCLEAR-MAGNETIC-RESONANCE; MIDDLE CEREBRAL-ARTERY;
QUANTITATIVE-EVALUATION; CONTRAST AGENT; IN-VIVO; VOLUME; PERMEABILITY;
ISCHEMIA; RATS; MRI
AB The integrity of the bloodbrain barrier (BBB) is critical to normal brain function. Traditional techniques for the assessment of BBB disruption rely heavily on the spatiotemporal analysis of extravasating contrast agents. However, such methods based on the leakage of relatively large molecules are not suitable for the detection of subtle BBB impairment or for the performance of repeated measurements in a short time frame. Quantification of the water exchange rate constant (WER) across the BBB using strictly intravascular contrast agents could provide a much more sensitive method for the quantification of the BBB integrity. To estimate WER, we have recently devised a powerful new method using a water exchange index (WEI) biomarker and demonstrated BBB disruption in an acute stroke model. Here, we confirm that WEI is sensitive to even very subtle changes in the integrity of the BBB caused by: (i) systemic hypercapnia and (ii) low doses of a hyperosmolar solution. In addition, we have examined the sensitivity and accuracy of WEI as a biomarker of WER using computer simulation. In particular, the dependence of the WEIWER relation on changes in vascular blood volume, T1 relaxation of cellular magnetization and transcytolemmal water exchange was explored. Simulated WEI was found to vary linearly with WER for typically encountered exchange rate constants (14Hz), regardless of the blood volume. However, for very high WER (>5Hz), WEI became progressively more insensitive to increasing WER. The incorporation of transcytolemmal water exchange, using a three-compartment tissue model, helped to extend the linear WEI regime to slightly higher WER, but had no significant effect for most physiologically important WERs (WER<4Hz). Variation in cellular T1 had no effect on WEI. Using both theoretical and experimental approaches, our study validates the utility of the WEI biomarker for the monitoring of BBB integrity. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Huang, Shuning; Rosen, Bruce R.] MIT, HST, Cambridge, MA 02139 USA.
[Huang, Shuning; Farrar, Christian T.; Dai, Guangping; Kwon, Seon Joo; Rosen, Bruce R.; Kim, Young R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Bogdanov, Alexei A., Jr.] Univ Massachusetts, Sch Med, Worcester, MA USA.
RP Kim, YR (reprint author), Harvard Univ, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Sch Med, Massachusetts Gen Hosp East, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM spmn@nmr.mgh.harvard.edu
FU National Institutes of Health (NIH) [5R01EB002066-17]; American Heart
Association SDG [0835451N]; NIH [S10RR025563]
FX This work was supported by National Institutes of Health (NIH) grant
5R01EB002066-17, the American Heart Association SDG #0835451N and NIH
grant S10RR025563.
NR 39
TC 2
Z9 2
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD APR
PY 2013
VL 26
IS 4
BP 376
EP 385
DI 10.1002/nbm.2871
PG 10
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 107IK
UT WOS:000316209200003
PM 23055278
ER
PT J
AU Wu, WE
Tal, A
Kirov, II
Rusinek, H
Charytonowicz, D
Babb, JS
Ratai, EM
Gonzalez, RG
Gonen, O
AF Wu, William E.
Tal, Assaf
Kirov, Ivan I.
Rusinek, Henry
Charytonowicz, Daniel
Babb, James S.
Ratai, Eva-Maria
Gonzalez, R. Gilberto
Gonen, Oded
TI Global gray and white matter metabolic changes after simian
immunodeficiency virus infection in CD8-depleted rhesus macaques: proton
MRS imaging at 3 T
SO NMR IN BIOMEDICINE
LA English
DT Article
DE animal disease models; brain; HIV-1; Macaca mulatta; MRS; simian
immunodeficiency virus
ID MAGNETIC-RESONANCE-SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; ACTIVE
ANTIRETROVIRAL THERAPY; SIV INFECTION; RELAXATION-TIMES; NEURONAL
INJURY; HIV-INFECTION; BRAIN-INJURY; DEMENTIA; MODEL
AB To test the hypotheses that global decreased neuro-axonal integrity reflected by decreased N-acetylaspartate (NAA) and increased glial activation reflected by an elevation in its marker, the myo-inositol (mI), present in a CD8-depleted rhesus macaque model of HIV-associated neurocognitive disorders. To this end, we performed quantitative MRI and 16x16x4 multivoxel proton MRS imaging (TE/TR=33/1400ms) in five macaques pre- and 46weeks post-simian immunodeficiency virus infection. Absolute NAA, creatine, choline (Cho), and mI concentrations, gray and white matter (GM and WM) and cerebrospinal fluid fractions were obtained. Global GM and WM concentrations were estimated from 224 voxels (at 0.125cm3 spatial resolution over similar to 35% of the brain) using linear regression. Pre- to post-infection global WM NAA declined 8%: 6.6 +/- 0.4 to 6.0 +/- 0.5mM (p=0.05); GM Cho declined 20%: 1.3 +/- 0.2 to 1.0 +/- 0.1mM (p<0.003); global mI increased 11%: 5.7 +/- 0.4 to 6.5 +/- 0.5mM (p<0.03). Global GM and WM brain volume fraction changes were statistically insignificant. These metabolic changes are consistent with global WM (axonal) injury and glial activation, and suggest a possible GM host immune response. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Wu, William E.; Tal, Assaf; Kirov, Ivan I.; Rusinek, Henry; Charytonowicz, Daniel; Babb, James S.; Gonen, Oded] NYU, Dept Radiol, Sch Med, New York, NY 10016 USA.
[Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp East, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Ratai, Eva-Maria; Gonzalez, R. Gilberto] Massachusetts Gen Hosp East, Neuroradiol Div, Charlestown, MA 02129 USA.
RP Gonen, O (reprint author), NYU, Dept Radiol, Sch Med, 660 1st Ave,4th Floor, New York, NY 10016 USA.
EM oded.gonen@med.nyu.edu
OI Wu, William/0000-0003-0990-4164; Kirov, Ivan/0000-0001-5641-8578; Gonen,
Oded/0000-0002-3148-2028
FU NIH [EB01015, NS050520, NS050041, NS051129, NS059331, NS040237];
National Center for Research Resources [P41RR14075]; Human Frontiers
Science Project's Cross-Disciplinary Fellowship
FX We thank Drs Andrew A. Maudsley and Brian J. Soher for their
SITools-FITT software and Dr Joanne Morris and Ms Shannon Luboyeski for
animal veterinary care. The study was supported by NIH Grants EB01015,
NS050520, NS050041, NS051129, NS059331, NS040237 and NS059331. The
Athinoula A. Martinos Center for Biomedical Imaging is supported by
National Center for Research Resources grant number P41RR14075. Assaf
Tal acknowledges support from the Human Frontiers Science Project's
Cross-Disciplinary Fellowship.
NR 56
TC 5
Z9 5
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD APR
PY 2013
VL 26
IS 4
BP 480
EP 488
DI 10.1002/nbm.2889
PG 9
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 107IK
UT WOS:000316209200015
PM 23418159
ER
PT J
AU Gupta, R
Khosroshahi, A
Shinagare, S
Fernandez, C
Ferrone, C
Lauwers, GY
Stone, JH
Deshpande, V
AF Gupta, Rajib
Khosroshahi, Arezou
Shinagare, Shweta
Fernandez, Carlos
Ferrone, Cristina
Lauwers, Gregory Y.
Stone, John H.
Deshpande, Vikram
TI Does Autoimmune Pancreatitis Increase the Risk of Pancreatic Carcinoma?
A Retrospective Analysis of Pancreatic Resections
SO PANCREAS
LA English
DT Article
DE autoimmune pancreatitis; chronic pancreatitis; IgG4-related disease;
pancreatic carcinoma
ID INTRAEPITHELIAL NEOPLASIA; SCLEROSING PANCREATITIS; DUCTAL
ADENOCARCINOMA; CANCER; DISEASE; CLASSIFICATION; INACTIVATION;
METAANALYSIS; LESIONS
AB Objectives: To estimate the risk of malignancy in autoimmune pancreatitis (AIP).
Methods: We examined resected pancreata to compare the prevalence of pancreatic intraepithelial neoplasia (PanIN) in 28 cases of AIP and 30 cases of chronic pancreatitis not otherwise specified (CP-NOS). We also reviewed a cohort of 84 AIP cases.
Results: The mean age of the AIP cohort (57 years) was significantly higher than that of the cohort of CP-NOS (47 years) (P = 0.01). Twenty-three cases (82%) of AIP showed PanIN, and 7 cases (25%) showed grade 2 PanIN. Grade 3 PanIN was identified in one case of AIP. There was no statistically significant difference in the number of cases with high-grade PanIN lesions between the cases of type 1 as opposed to type 2 AIP. In comparison to CP-NOS, a comparable percentage of patients with AIP had PanIN (82% of AIP cases vs 63% of CP-NOS cases) (P = NS) and PanIN 2 (25% AIP vs 20% CP-NOS) (P = NS). Of the 84 AIP cases at our institution (mean follow-up, 49 months), 2 cases of pancreatic carcinoma were identified 6 and 10 years after the diagnoses of AIP.
Conclusions: These findings raise concern that AIP is associated with an elevated risk of malignancy and should prompt additional studies.
C1 [Gupta, Rajib; Shinagare, Shweta; Lauwers, Gregory Y.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Khosroshahi, Arezou; Stone, John H.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol, Boston, MA 02114 USA.
[Fernandez, Carlos; Ferrone, Cristina] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Deshpande, V (reprint author), Massachusetts Gen Hosp Warren 2, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM vdeshpande@partners.org
NR 24
TC 23
Z9 25
U1 0
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD APR
PY 2013
VL 42
IS 3
BP 506
EP 510
DI 10.1097/MPA.0b013e31826bef91
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 107FZ
UT WOS:000316201700018
PM 23271394
ER
PT J
AU Lim, D
Oliva, E
AF Lim, D.
Oliva, E.
TI Precursors and pathogenesis of ovarian carcinoma
SO PATHOLOGY
LA English
DT Article
DE Origin; ovarian cancer; pathogenesis; precursors
ID GRADE SEROUS CARCINOMA; TUBAL INTRAEPITHELIAL CARCINOMA; CLEAR-CELL
CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION;
MOLECULAR-GENETIC-ANALYSIS; MALIGNANT POTENTIAL TUMORS; MUCINOUS
BORDERLINE TUMORS; COMMON EPITHELIAL TUMORS; K-RAS PROTOONCOGENE;
FALLOPIAN-TUBE
AB The ultimate goal of defining cancer specific precursors is to facilitate early detection and intervention before the development of invasive malignancy. Unlike other malignancies involving the female genital tract such as cervical or endometrial carcinomas, precursor lesions of ovarian carcinomas have not been well characterised, resulting in a failure to develop effective screening programs. Recent clinicopathological and molecular studies have provided new insight into the origin and pathogenesis of ovarian carcinomas. It has been shown that ovarian cancer is comprised of different tumour types differing not only in morphology, but also in pathogenesis, molecular alterations and clinical progression. A dualistic model of ovarian carcinogenesis has been proposed. Type I tumours which include low grade serous, low grade endometrioid, clear cell, mucinous carcinomas and Brenner tumours, are generally indolent and tend to be genetically stable, although clear cell carcinoma would probably belong to an intermediate category. They demonstrate a step-wise progression from a benign precursor such as a benign to borderline tumour or endometriosis and are characterised by genetic aberrations targeting specific cell signalling pathways. Type II tumours comprise high grade serous, high grade endometrioid, and undifferentiated carcinomas as well as malignant mixed mesodermal tumours. They are clinically aggressive and exhibit high genetic instability with frequent p53 mutations. Mounting evidence suggests that many high grade serous carcinomas originate from the epithelium of the distal fallopian tube, and that serous tubal intraepithelial carcinoma (STIC) represents the putative precursor of these neoplasms. Low grade serous carcinomas arise via transformation of benign and borderline serous tumours, thought to be derived from inclusion cysts originating from the ovarian surface or tubal epithelium. Recently it has been suggested that papillary tubal hyperplasia may be a putative precursor lesion for serous borderline tumours. Both endometrioid and clear cell carcinomas develop from endometriosis, via alterations affecting different genetic pathways. The origin of mucinous and transitional cell neoplasms is not well characterised, although new data suggest a possible origin from transitional cell nests present at the tubal-mesothelial junction. Likewise, the pathogenesis of carcinosarcomas is also not well established because of their rarity but there is accumulating evidence that the carcinomatous component determines the course of the disease and gives rise to the malignant mesenchymal component. This review discusses recent developments in the pathogenesis of ovarian carcinoma, with particular emphasis on the putative precursor lesions that give rise to the major histological subtypes. Recognition of these lesions is not only important in improving the understanding of ovarian carcinogenesis, but it will also influence our approach to prevent, detect and treat these tumours.
C1 [Lim, D.] Natl Univ Hlth Syst, Dept Pathol, Singapore, Singapore.
[Oliva, E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA.
EM eoliva@partners.org
NR 186
TC 37
Z9 38
U1 2
U2 30
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0031-3025
EI 1465-3931
J9 PATHOLOGY
JI Pathology
PD APR
PY 2013
VL 45
IS 3
BP 229
EP 242
DI 10.1097/PAT.0b013e32835f2264
PG 14
WC Pathology
SC Pathology
GA 107TT
UT WOS:000316244400004
PM 23478230
ER
PT J
AU Liu, TT
Glover, GH
Mueller, BA
Greve, DN
Brown, GG
AF Liu, Thomas T.
Glover, Gary H.
Mueller, Bryon A.
Greve, Douglas N.
Brown, Gregory G.
TI An Introduction to Normalization and Calibration Methods in Functional
MRI
SO PSYCHOMETRIKA
LA English
DT Article
DE functional MRI; arterial spin labeling; cerebral blood flow;
quantitative fMRI; calibrated fMRI; hypercapnia
ID CEREBRAL-BLOOD-FLOW; BOLD HEMODYNAMIC-RESPONSES; OXYGEN-METABOLISM
CHANGES; RAT SOMATOSENSORY CORTEX; MEMORY-ENCODING TASK; NEURAL
ACTIVITY; OXIDATIVE-METABOLISM; NEURONAL-ACTIVITY; FMRI RESPONSE;
HYPERCAPNIC NORMALIZATION
AB In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.
C1 [Liu, Thomas T.] Univ Calif San Diego, Ctr Funct MRI, La Jolla, CA 92093 USA.
[Glover, Gary H.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
[Mueller, Bryon A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
[Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Brown, Gregory G.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Brown, Gregory G.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
RP Liu, TT (reprint author), Univ Calif San Diego, Ctr Funct MRI, 9500 Gilman Dr,MC 0677, La Jolla, CA 92093 USA.
EM ttliu@ucsd.edu
FU NIH National Center for Research Resources for the FBIRN consortium
[U24-RR021992]; [P41-RR009784]; [R01NS051661]; [R01MH084796]
FX We acknowledge funding support by the NIH National Center for Research
Resources for the FBIRN consortium (Grant U24-RR021992) as well as
individual grants to coinvestigators: P41-RR009784 (GHG), R01NS051661,
and R01MH084796 (TTL).
NR 82
TC 4
Z9 4
U1 2
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3123
J9 PSYCHOMETRIKA
JI Psychometrika
PD APR
PY 2013
VL 78
IS 2
BP 308
EP 321
DI 10.1007/s11336-012-9309-x
PG 14
WC Mathematics, Interdisciplinary Applications; Social Sciences,
Mathematical Methods; Psychology, Mathematical
SC Mathematics; Mathematical Methods In Social Sciences; Psychology
GA 109CV
UT WOS:000316344000007
PM 25107618
ER
PT J
AU Nambiar, AM
AF Nambiar, Anoop M.
TI Procalcitonin in acute exacerbations of interstitial pneumonia: Another
tool in the toolbox?
SO RESPIROLOGY
LA English
DT Editorial Material
DE acute respiratory distress syndrome; interstitial; lung disease;
pneumonia; pulmonary fibrosis
ID IDIOPATHIC PULMONARY-FIBROSIS; DIAGNOSIS
C1 Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Med, Audie L Murphy Div,Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA.
RP Nambiar, AM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, Dept Med, Audie L Murphy Div,Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA.
NR 13
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1323-7799
J9 RESPIROLOGY
JI Respirology
PD APR
PY 2013
VL 18
IS 3
BP 389
EP 390
DI 10.1111/resp.12055
PG 2
WC Respiratory System
SC Respiratory System
GA 112ZV
UT WOS:000316636000001
PM 23336530
ER
PT J
AU Porcel, JM
Leung, CC
Restrepo, MI
Takahashi, K
Lee, P
AF Porcel, Jose M.
Leung, Chi Chiu
Restrepo, Marcos I.
Takahashi, Kazuhisa
Lee, Pyng
TI Year in review 2012: Lung cancer, respiratory infections, tuberculosis,
pleural diseases, bronchoscopic intervention and imaging
SO RESPIROLOGY
LA English
DT Review
DE bronchoscopic intervention and imaging; lung cancer; pleural disease;
respiratory infection; tuberculosis
ID COMMUNITY-ACQUIRED PNEUMONIA; DRUG-RESISTANT TUBERCULOSIS; OBSTRUCTIVE
PULMONARY-DISEASE; EPITHELIAL-MESENCHYMAL TRANSITIONS; C-REACTIVE
PROTEIN; ENDOBRONCHIAL ULTRASOUND; PARAPNEUMONIC EFFUSIONS; CONSENSUS
GUIDELINES; PREDICTING MORTALITY; THORACIC-SOCIETY
C1 [Porcel, Jose M.] Arnau de Vilanova Univ Hosp, Dept Internal Med, Pleural Dis Unit, Biomed Res Inst Lleida, Lleida 25198, Spain.
[Leung, Chi Chiu] Dept Hlth, TB & Chest Serv, Hong Kong, Hong Kong, Peoples R China.
[Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA.
[Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implement Ctr, San Antonio, TX USA.
[Takahashi, Kazuhisa] Juntendo Univ, Grad Sch Med, Dept Resp Med, Tokyo, Japan.
[Lee, Pyng] Natl Univ Singapore Hosp, Dept Med, Singapore 117548, Singapore.
RP Porcel, JM (reprint author), Arnau de Vilanova Univ Hosp, Dept Internal Med, Avda Alcalde Rovira Roure 80, Lleida 25198, Spain.
EM jporcelp@yahoo.es
RI Restrepo, Marcos/H-4442-2014
FU National Heart, Lung, and Blood Institute [K23HL096054]
FX M.I.R.'s time is partially protected by Award Number K23HL096054 from
the National Heart, Lung, and Blood Institute. The content of M.I.R.'s
contribution on respiratory infections is solely the responsibility of
the author and does not necessarily represent the official views of the
National Heart, Lung, And Blood Institute, the National Institutes of
Health or the Department of Veterans Affairs.
NR 82
TC 2
Z9 2
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1323-7799
EI 1440-1843
J9 RESPIROLOGY
JI Respirology
PD APR
PY 2013
VL 18
IS 3
BP 573
EP 583
DI 10.1111/resp.12048
PG 11
WC Respiratory System
SC Respiratory System
GA 112ZV
UT WOS:000316636000028
PM 23317457
ER
PT J
AU Brada, M
Bortfeld, T
AF Brada, Michael
Bortfeld, Thomas
TI Proton Therapy: The Present and the Future
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Editorial Material
C1 [Brada, Michael] Univ Coll London Hosp NHS Fdn Trust, Leaders Oncol Care, London, England.
[Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA USA.
RP Brada, M (reprint author), Univ Coll London Hosp NHS Fdn Trust, Leaders Oncol Care, London, England.
NR 0
TC 7
Z9 7
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 1053-4296
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD APR
PY 2013
VL 23
IS 2
BP 75
EP 76
DI 10.1016/j.semradonc.2012.11.001
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 111NF
UT WOS:000316527300001
PM 23473683
ER
PT J
AU Paganetti, H
van Luijk, P
AF Paganetti, Harald
van Luijk, Peter
TI Biological Considerations When Comparing Proton Therapy. With Photon
Therapy
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID CELL LUNG-CANCER; EARLY DNA-DAMAGE; INTENSITY-MODULATED PHOTON; VOLUME
HISTOGRAM ANALYSIS; CULTURED MAMMALIAN-CELLS; NEUTRON DOSE-EQUIVALENT;
PAROTID-GLAND FUNCTION; BIOL-PHYS 2006/65/1-7; CERVICAL-SPINAL CORD;
INDUCED 2ND CANCERS
AB Owing to the limited availability of data on the outcome of proton therapy, treatments are generally optimized based on broadly available data on photon-based treatments. However, the microscopic pattern of energy deposition of protons differs from that of photons, leading to a different biological effect. Consequently, proton therapy needs a correction factor (relative biological effectiveness) to relate proton doses to photon doses, and currently, a generic value is used. Moreover, the macroscopic distribution of dose in proton therapy differs compared with photon treatments. Although this may offer new opportunities to reduce dose to normal tissues, it raises the question whether data obtained from photon-based treatments offer sufficient information on dose-volume effects to optimally use unique features of protons. In addition, there are potential differences in late effects due to low doses of secondary radiation outside the volume irradiated by the primary beam. This article discusses the controversies associated with these 3 issues when comparing proton and photon therapy. Semin Radiat Oncol 23:77-87 (C) 2013 Elsevier Inc. All rights reserved.
C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA.
[van Luijk, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Radiat Oncol, Groningen, Netherlands.
[van Luijk, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands.
RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM hpaganetti@partners.org
RI van Luijk, Peter/A-6877-2013
OI van Luijk, Peter/0000-0001-7959-1234
NR 119
TC 20
Z9 20
U1 1
U2 14
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1053-4296
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD APR
PY 2013
VL 23
IS 2
BP 77
EP 87
DI 10.1016/j.semradonc.2012.11.002
PG 11
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 111NF
UT WOS:000316527300002
PM 23473684
ER
PT J
AU Mouw, KW
Trofimov, A
Zietman, AL
Efstathiou, JA
AF Mouw, Kent W.
Trofimov, Alexei
Zietman, Anthony L.
Efstathiou, Jason A.
TI Clinical Controversies: Proton Therapy for Prostate Cancer
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID INTENSITY-MODULATED RADIOTHERAPY; CONFORMAL RADIATION-THERAPY; INDUCED
DOSE REDUCTION; BEAM TREATMENT; TARGET VOLUME; PHASE-II; MOVEMENT;
TRIAL; TOXICITIES; OUTCOMES
AB Proton therapy has been used in the treatment of prostate cancer for several decades, and interest surrounding its use continues to grow. Proton-based treatment techniques have evolved significantly over this period, and several centers now routinely use technologies such as pencil-beam scanning. However, whether the theoretical dosimetric advantages of the proton beam translate into clinically meaningful improvements for prostate cancer patients is unknown, and outcomes from single-arm experiences using whole courses of proton beam therapy in the treatment of early-stage prostate cancer have shown mixed results when compared with contemporary intensity-modulated radiotherapy. A randomized trial comparing proton beam therapy with intensity-modulated radiotherapy in early-stage disease has been launched and will be important in defining the role for proton therapy in this setting. We review the available evidence and present the current state of proton beam therapy for prostate cancer. Semin Radiat Oncol 23:109-114 (C) 2013 Elsevier Inc. All rights reserved.
C1 [Mouw, Kent W.] Harvard Radiat Oncol Program, Boston, MA USA.
[Trofimov, Alexei; Zietman, Anthony L.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Mouw, KW (reprint author), Harvard Radiat Oncol Program, Boston, MA USA.
EM kmouw@lroc.harvard.edu
FU NCI NIH HHS [C06 CA059267]
NR 36
TC 7
Z9 7
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1053-4296
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD APR
PY 2013
VL 23
IS 2
BP 109
EP 114
DI 10.1016/j.semradonc.2012.11.009
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 111NF
UT WOS:000316527300005
PM 23473687
ER
PT J
AU Flanz, J
Bortfeld, T
AF Flanz, Jacob
Bortfeld, Thomas
TI Evolution of Technology to Optimize the Delivery of Proton Therapy: The
Third Generation
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; COMPUTED-TOMOGRAPHY; RADIATION-THERAPY;
PROSTATE-CANCER; BEAM DELIVERY; PROMPT GAMMA; RANGE; VERIFICATION;
RADIOTHERAPY; SIMULATIONS
AB The evolution of proton therapy technology will lead to a new generation of systems that allow for greater accuracy and precision of the dose delivery and will be more compact. We envision that over the next 10-15 years, the quality of deliverable proton dose distributions in the patient will be pushed nearly toward the physical limit of proton therapy. Those future proton therapy systems will fit into treatment rooms of similar size as today's conventional radiation treatment rooms. At the same time, due to technological advancements, the cost of proton therapy will come down to the cost of advanced photon therapy. We discuss some of the technologies that will put these speculative improvements within reach. Semin Radiat Oncol 23:142-148 (C) 2013 Elsevier Inc. All rights reserved.
C1 [Flanz, Jacob] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Flanz, Jacob] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Flanz, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM jflanz@partners.org
NR 34
TC 8
Z9 8
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1053-4296
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD APR
PY 2013
VL 23
IS 2
BP 142
EP 148
DI 10.1016/j.semradonc.2012.11.006
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 111NF
UT WOS:000316527300010
PM 23473692
ER
PT J
AU Anaya, HD
Butler, JN
Solomon, JL
Knapp, H
Hoang, T
Kan, V
Rodriguez-Barradas, MC
Hare, KA
Kertz, B
Bokhour, B
AF Anaya, Henry D.
Butler, Jaimi N.
Solomon, Jeffrey L.
Knapp, Herschel
Hoang, Tuyen
Kan, Virginia
Rodriguez-Barradas, Maria C.
Hare, Katherine A.
Kertz, Barbara
Bokhour, Barbara
TI Implementation of Nurse-Initiated Rapid HIV Testing at High-Prevalence
Primary Care Sites Within the US Veterans Affairs Health Care System
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID UNITED-STATES; IMMUNIZATION; DISEASE; RISK
AB Nurse-initiated HIV rapid testing (NRT) increases testing/receipt of results compared with traditional testing. We implemented NRT in primary care clinics at 2 Veterans Affairs hospitals.
At site 1, 2364 tests were conducted; 5 HIV positives were identified. At site 2, 2522 tests were conducted; 9 HIV positives were identified. Success varied across demographic/clinical strata.
C1 [Anaya, Henry D.; Butler, Jaimi N.; Knapp, Herschel; Hoang, Tuyen] VA Greater Los Angeles Healthcare Syst, Vet Affairs VA Qual Enhancement Res Initiat HIV &, Los Angeles, CA USA.
[Anaya, Henry D.; Butler, Jaimi N.; Knapp, Herschel; Hoang, Tuyen] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, VA Greater Los Angeles Hlth Serv Res & Dev Ctr Ex, Los Angeles, CA USA.
[Anaya, Henry D.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA.
[Anaya, Henry D.] VA Chicago Healthcare Syst, VA Ctr Management Complex Chron Condit, Chicago, IL USA.
[Anaya, Henry D.] VA Chicago Healthcare Syst, Qual Enhancement Res Initiat Spinal Cord Injury S, Chicago, IL USA.
[Solomon, Jeffrey L.; Bokhour, Barbara] VA New England Healthcare Syst, Bedford, MA USA.
[Kan, Virginia; Hare, Katherine A.] VA Med Ctr, Washington, DC USA.
[Kan, Virginia] George Washington Univ, Infect Dis Sect, Washington, DC USA.
[Rodriguez-Barradas, Maria C.; Kertz, Barbara] Michael E DeBakey VA Med Ctr, Infect Dis Sect, Houston, TX USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
RP Anaya, HD (reprint author), 11301Wilshire Blvd 111G, Los Angeles, CA 90073 USA.
EM henry.anaya@va.gov
OI Bokhour, Barbara/0000-0001-8238-0745
FU VA Quality Enhancement Research Initiative (QUERI) [SDP07-318];
Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development Service; Veterans Health
Administration
FX This research was funded by VA Quality Enhancement Research Initiative
(QUERI) grant SDP07-318 awarded to the first author and supported by the
Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development Service. The authors thank the primary
care clinics and all the nurses who participated in these testing
efforts; their participation, dedication, support, and patience were
invaluable. The views and opinions expressed in this article are those
of the authors and do not necessarily represent the views of the US
Department of Veterans Affairs. The Veterans Health Administration
supported this study but had no input in the design or reporting, or
decision to submit this manuscript for publication. This study was
reviewed and sanctioned by a US Department of Veterans Affairs
institutional review board process.
NR 18
TC 6
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD APR
PY 2013
VL 40
IS 4
BP 341
EP 345
DI 10.1097/OLQ.0b013e31828417a5
PG 5
WC Infectious Diseases
SC Infectious Diseases
GA 107CQ
UT WOS:000316192700018
PM 23486502
ER
PT J
AU Mehtsun, WT
Ibrahim, AM
Diener-West, M
Pronovost, PJ
Makary, MA
AF Mehtsun, Winta T.
Ibrahim, Andrew M.
Diener-West, Marie
Pronovost, Peter J.
Makary, Martin A.
TI Surgical never events in the United States
SO SURGERY
LA English
DT Article
ID WRONG-SITE SURGERY; QUALITY-OF-CARE; ADVERSE EVENTS; PATIENT SAFETY;
PREVENTION; PERFORMANCE; MANAGEMENT; CHECKLIST; PATTERNS
AB Background. Surgical never events are being used increasingly as quality metrics in health care in the United States. However, little is known about their costs to the health care system, the outcomes of patients, or the characteristics of the providers involved. We designed a study to describe the number and magnitude of paid malpractice claims for surgical never events, as well as associated patient and provider characteristics.
Methods. We used the National Practitioner Data Bank, a federal repository of medical malpractice claims, to identify malpractice settlements and judgments of surgical never events, including retained foreign bodies, wrong-site, wrongpatient, and wrong-procedure surgery. Payment amounts, patient outcomes, and provider characteristics were evaluated.
Results. We identified a total of 9,744 paid malpractice settlement and judgments for surgical never events occurring between 1990 and 2010. Malpractice payments for surgical never events totaled $1.3 billion. Mortality occurred in 6.6% of patients, permanent injury in 32.9%, and temporary injury in 59.2%. Based on literature rates of surgical adverse events resulting in paid malpractice claims, we estimated that 4,082 surgical never event claims occur each year in the United States. Increased payments were associated with severe patient outcomes and claims involving a physician with multiple malpractice reports. Of physicians named in a surgical never event claim, 12.4% were later named in at least 1 future surgical never event claim.
Conclusion. Surgical never events are costly to the health care system and are associated with serious harm to patients. Patient and provider characteristics may help to guide prevention strategies. (Surgery 2013;153:465-72.)
C1 [Mehtsun, Winta T.; Ibrahim, Andrew M.; Pronovost, Peter J.; Makary, Martin A.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA.
[Pronovost, Peter J.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol Crit Care Med, Baltimore, MD 21287 USA.
[Mehtsun, Winta T.; Pronovost, Peter J.; Makary, Martin A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
[Mehtsun, Winta T.; Diener-West, Marie] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Mehtsun, Winta T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Ibrahim, Andrew M.] Univ Hosp Case Med Ctr, Dept Surg, Cleveland, OH USA.
RP Makary, MA (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Osler 624,600 N Wolfe St, Baltimore, MD 21287 USA.
EM mmakary1@jhmi.edu
NR 40
TC 27
Z9 27
U1 0
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD APR
PY 2013
VL 153
IS 4
BP 465
EP 472
DI 10.1016/j.surg.2012.10.005
PG 8
WC Surgery
SC Surgery
GA 113FD
UT WOS:000316651000006
PM 23257079
ER
PT J
AU Nguyen, B
Tao, M
Yu, P
Mauro, C
Seidman, MA
Wang, YYE
Mitchell, J
Ozaki, CK
AF Binh Nguyen
Tao, Ming
Yu, Peng
Mauro, Christine
Seidman, Michael A.
Wang, Yaoyu E.
Mitchell, James
Ozaki, C. Keith
TI Preoperative diet impacts the adipose tissue response to surgical trauma
SO SURGERY
LA English
DT Article
ID ISCHEMIA-REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; INFLAMMATION;
FAT; OBESITY; MICE; RESTRICTION; PHENOTYPE; DISEASE; HUMANS
AB Background. Short-term changes in preoperative nutrition can have profound effects on surgery-related outcomes such as ischemia/reperfusion injury in preclinical models. Dietary interventions that lend protection against stress in animal models (eg, fasting, dietary restriction [DR]) impact adipose tissue quality/ quantity. Adipose tissue holds high surgical relevance because of its anatomic location and large tissue volume, and it is ubiquitously traumatized during surgery. Yet the response of adipose tissue to trauma under clinically relevant circumstances including dietary status remains poorly defined. We hypothesized that preoperative diet alters the adipose tissue response to surgical trauma.
Methods. A novel mouse model of adipose tissue surgical trauma was employed. Dietary conditions (dietinduced obesity [DIM preoperative DR) were modulated before application of surgical adipose tissue trauma in the context of clinically common scenarios. (different ages, simulated bacterial wound contamination). Local/distant adipose tissue phenotypic responses were measured as represented by gene expression of inflammatory, tissue remodeling/growth, and metabolic markers.
Results. Surgical trauma had a profound effect on adipose tissue phenotype at the site of trauma. Milder but significant distal effects on non-traumatized adipose tissue were also observed. DIO exacerbated the inflammatory aspects of this response, and preoperative DR tended to reverse these changes. Age and lipopolysaccharide (LPS)-simulated bacterial contamination also impacted the adipose tissue response to trauma, with young adult animals and LPS treatment exacerbating the proinflammatory response.
Conclusion. Surgical trauma dramatically impacts both local and distal adipose tissue biology. Shortterm preoperative DR may offer a strategy to attenuate this response. (Surgery 2013;153:584-93.)
C1 [Binh Nguyen; Tao, Ming; Yu, Peng; Mauro, Christine; Ozaki, C. Keith] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Seidman, Michael A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol & Lab Med, Boston, MA 02115 USA.
[Wang, Yaoyu E.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA.
[Mitchell, James] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
RP Ozaki, CK (reprint author), 75 Francis St, Boston, MA 02115 USA.
EM CKOzaki@partners.org
FU National Heart, Lung, and.Blood Institute [T32HL007734]; American Heart
Association [12GRNT9510001]; Carl and Ruth Shapiro Family Foundation;
CCCB; Dana-Farber Strategic Plan Initiative
FX Supported by the National Heart, Lung, and.Blood Institute
(T32HL007734), American Heart Association (12GRNT9510001), and the Carl
and Ruth Shapiro Family Foundation. YEW is supported through the CCCB
and the Dana-Farber Strategic Plan Initiative.
NR 42
TC 5
Z9 6
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD APR
PY 2013
VL 153
IS 4
BP 584
EP 593
DI 10.1016/j.surg.2012.11.901
PG 10
WC Surgery
SC Surgery
GA 113FD
UT WOS:000316651000020
PM 23274098
ER
PT J
AU Kadauke, S
Picarelli, A
Di Tola, M
Parikh, RK
Naylor, P
Zhou, WL
Bowman, J
Bullock, D
Tobi, M
AF Kadauke, S.
Picarelli, A.
Di Tola, M.
Parikh, R. K.
Naylor, P.
Zhou, W. -L.
Bowman, J.
Bullock, D.
Tobi, M.
TI Letter: Adnab-9 as a potential non-invasive biomarker for prediction of
malignancy in coeliac disease
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Letter
ID MONOCLONAL-ANTIBODY ADNAB-9; SMALL-INTESTINE; MARKER; CANCER
C1 [Kadauke, S.] Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA 19104 USA.
[Picarelli, A.; Di Tola, M.] Univ Roma La Sapienza, Dept Internal Med & Med Special, Rome, Italy.
[Parikh, R. K.; Naylor, P.; Zhou, W. -L.; Bowman, J.; Bullock, D.; Tobi, M.] Wayne State Univ, Sch Med, John D Dingell VAMC Dept Med, Detroit, MI USA.
[Tobi, M.] Philadelphia Vet Affairs Med Ctr, Div Gastroenterol, Gastroenterol Sect, Philadelphia, PA USA.
[Tobi, M.] Perelman Sch Med, Philadelphia, PA USA.
RP Kadauke, S (reprint author), Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA 19104 USA.
EM martin.tobi@va.gov
OI Picarelli, Antonio/0000-0002-6104-8193
NR 8
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD APR
PY 2013
VL 37
IS 7
BP 761
EP 762
DI 10.1111/apt.12231
PG 2
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 100ZC
UT WOS:000315743300023
PM 23458541
ER
PT J
AU Konstantinidis, IT
Warshaw, AL
Allen, JN
Blaszkowsky, LS
Fernandez-del Castillo, C
Deshpande, V
Hong, TS
Kwak, EL
Lauwers, GY
Ryan, DP
Wargo, JA
Lillemoe, KD
Ferrone, CR
AF Konstantinidis, Ioannis T.
Warshaw, Andrew L.
Allen, Jill N.
Blaszkowsky, Lawrence S.
Fernandez-del Castillo, Carlos
Deshpande, Vikram
Hong, Theodore S.
Kwak, Eunice L.
Lauwers, Gregory Y.
Ryan, David P.
Wargo, Jennifer A.
Lillemoe, Keith D.
Ferrone, Cristina R.
TI Pancreatic Ductal Adenocarcinoma Is There a Survival Difference for R1
Resections Versus Locally Advanced Unresectable Tumors? What Is a "True"
R0 Resection?
SO ANNALS OF SURGERY
LA English
DT Article
DE locally advanced; pancreatic adenocarcinoma; R1 resections; 1-mm margin
ID QUALITY-OF-LIFE; COMPARING STANDARD PANCREATICODUODENECTOMY; MINIMAL
POSTOPERATIVE COMPLICATIONS; SINGLE-INSTITUTION EXPERIENCE; RANDOMIZED
CONTROLLED TRIAL; LONG-TERM SURVIVAL; EXTENDED LYMPHADENECTOMY;
SURGICAL-TREATMENT; PERIAMPULLARY ADENOCARCINOMA; SURGEONS CONTRIBUTION
AB Objective: Patients who undergo an R0 resection of their pancreatic ductal adenocarcinoma (PDAC) have an improved survival compared with patients who undergo an R1 resection. It is unclear whether an R1 resection confers a survival benefit over locally advanced (LA) unresectable tumors. Our aim was to compare the survival of patients undergoing an R1 resection with those having LA tumors and to explore the prognostic significance of a 1-mm surgical margin.
Methods: Clinicopathologic data from a pancreatic cancer database between January 1993 and July 2008 were reviewed. Locally advanced tumors had no evidence of metastatic disease at exploration.
Results: A total of 1705 patients were evaluated for PDAC in the Department of Surgery. Of the 1084 (64%) patients who were surgically explored, 530 (49%) were considered unresectable (286 locally unresectable, 244 with distant metastasis). One hundred fifty-seven (28%) of the resected PDACs had an R1 resection. Patients undergoing an R1 resection had a slightly longer survival compared with those who had locally advanced unresectable cancers (14 vs 11 months; P < 0.001). Patients with R0 resections had a favorable survival compared with those with R1 resections (23 vs 14 months; P < 0.001), but survival after resections with 1-mm margin or less (R0-close) were similar to R1 resections: both groups had a significantly shorter median survival than patients with amargin of greater than 1mm (R0-wide) (16 vs 14 vs 35 months, respectively; P < 0.001).
Conclusions: Patients undergoing an R1 resection still have an improved survival compared with patients with locally advanced unresectable pancreatic adenocarcinoma. R0 resections have an improved survival compared with R1 resections, but this survival benefit is lost when the tumor is within 1 mm of the resection margin.
C1 [Konstantinidis, Ioannis T.; Warshaw, Andrew L.; Fernandez-del Castillo, Carlos; Wargo, Jennifer A.; Lillemoe, Keith D.; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Allen, Jill N.; Blaszkowsky, Lawrence S.; Kwak, Eunice L.; Ryan, David P.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA.
[Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Deshpande, Vikram; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Ferrone, CR (reprint author), Wang Ambulatory Care Ctr 460,15 Parkman St, Boston, MA 02114 USA.
EM cferrone@partners.org
NR 41
TC 102
Z9 105
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD APR
PY 2013
VL 257
IS 4
BP 731
EP 736
DI 10.1097/SLA.0b013e318263da2f
PG 6
WC Surgery
SC Surgery
GA 104JY
UT WOS:000315990100030
PM 22968073
ER
PT J
AU Ross, SA
Allen, DN
Goldstein, G
AF Ross, Sylvia An
Allen, Daniel N.
Goldstein, Gerald
TI Factor Structure of the Halstead-Reitan Neuropsychological Battery: A
Review and Integration
SO APPLIED NEUROPSYCHOLOGY-ADULT
LA English
DT Article
DE factor analysis; Halstead-Reitan Neuropsychological Battery;
neuropsychological assessment
ID BRAIN-DAMAGE; WAIS-R; TESTS; PERFORMANCE; DYSFUNCTION; ATTENTION;
VALIDITY; MATRIX; SKILLS
AB The Halstead-Reitan Neuropsychological Battery (HRNB) was the first factor-analyzed neuropsychological battery. It was based on a series of tests studied in Ward Halstead's laboratory at the University of Chicago, was accomplished in collaboration with a group of eminent statisticians, and was published in 1947. Four factors were extracted based on Halstead's tests called central integrative field, abstraction, power, and directional and constituted what was described as biological intelligence. Since this original analysis, Reitan's additions to the battery, and the proposal of Reitan and Wolfson's model of neuropsychological functioning, this factor-analytic research continued. This article reviews factor-analytic research concluding that Halstead's analysis has held up reasonably well and there is support for the Reitan and Wolfson model. However, Reitan's revisions of the battery added tests that form a distinct language factor and the sensory-perceptual tests that generally form a separate factor. Other tests and scoring methods used in individual studies modified the core battery and produced somewhat differing solutions. The complexity of the tests prevents the HRNB from being a factorially pure battery, and simple structure is rarely, if ever, reached. Current versions of the HRNB appear to evaluate both biological and psychometric intelligence, which appear to load on separate factors.
C1 [Ross, Sylvia An; Allen, Daniel N.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA.
[Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Allen, DN (reprint author), Univ Nevada, Dept Psychol, 4505 Maryland Pkwy, Las Vegas, NV 89154 USA.
EM daniel.allen@unlv.edu
FU Mental Illness Research, Education, and Clinical Center (MIRECC), VA
Pittsburgh Healthcare System; Medical Research Service, Department of
Veterans Affairs
FX Indebtedness is expressed to the Mental Illness Research, Education, and
Clinical Center (MIRECC), VA Pittsburgh Healthcare System, and the
Medical Research Service, Department of Veterans Affairs for support of
this research.
NR 49
TC 0
Z9 0
U1 1
U2 5
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND
SN 0908-4282
J9 APPL NEUROPSYCH-ADUL
JI Appl. Neuropsychol.-Adult
PD APR 1
PY 2013
VL 20
IS 2
BP 120
EP 135
DI 10.1080/09084282.2012.690798
PG 16
WC Clinical Neurology; Psychology
SC Neurosciences & Neurology; Psychology
GA 100EA
UT WOS:000315677400006
PM 23397998
ER
PT J
AU Bredella, MA
Fazeli, PK
Lecka-Czernik, B
Rosen, CJ
Klibanski, A
AF Bredella, Miriam A.
Fazeli, Pouneh K.
Lecka-Czernik, Beata
Rosen, Clifford J.
Klibanski, Anne
TI IGFBP-2 is a negative predictor of cold-induced brown fat and bone young
non-obese women
SO BONE
LA English
DT Article
DE Brown adipose tissue (BAT); IGFBP-2; Bone mineral density (BMD);
Anorexia nervosa (AN)
ID GROWTH FACTOR-I; FACTOR-BINDING PROTEIN-2; ADIPOSE-TISSUE; MINERAL
DENSITY; ANOREXIA-NERVOSA; INSULIN; DIFFERENTIATION; PROGRAM; NECDIN;
IGF-1
AB Recent studies have shown a positive correlation between brown adipose tissue (BAT) and bone mineral density (BMD). However, mechanisms underlying this relationship are unknown. Insulin-like growth factor 1 (IGF-1) is an important regulator of stem cell differentiation promoting bone formation. IGF binding protein 2 (IGFBP-2) binds IGF-1 in the circulation and has been reported to inhibit bone formation in humans. IGF-1 is also a crucial regulator of brown adipocyte differentiation. We hypothesized that IGFBP-2 is a negative and IGF-1 a positive regulator of BAT-mediated osteoblastogenesis. We therefore investigated a cohort of 15 women (mean age 27.7 +/- 5.7 years): 5 with anorexia nervosa (AN) in whom IGF-1 levels were low due to starvation, 5 recovered AN (AN-R), and 5 women of normal weight. All subjects underwent assessment of cold-activated BAT by PET/CT, BMD of the spine, hip, femoral neck, and total body by DXA, thigh muscle area by MRI, IGF-1 and IGFBP-2. There was a positive correlation between BAT and BMD and an inverse association between IGFBP-2 and both BAT and BMD. There was no association between IGF-1 and BAT. We show for the first time that IGFBP-2 is a negative predictor of cold-induced BAT and BMD in young non-obese women, suggesting that IGFBP-2 may serve as a regulator of BAT-mediated osteoblastogenesis. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Bredella, Miriam A.; Fazeli, Pouneh K.; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Fazeli, Pouneh K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Lecka-Czernik, Beata] Univ Toledo, Dept Orthoped Surg, Ctr Diabet & Endocrine Res, Coll Med, Toledo, OH 43606 USA.
[Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA.
RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA.
EM mbredella@partners.org
FU National Institutes of Health [R24 DK084970, UL1 RR025758]
FX This work was supported by National Institutes of Health Grants R24
DK084970 and UL1 RR025758.
NR 23
TC 9
Z9 11
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD APR
PY 2013
VL 53
IS 2
BP 336
EP 339
DI 10.1016/j.bone.2012.12.046
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 101GR
UT WOS:000315763700003
PM 23291564
ER
PT J
AU Pozzi, S
Fulciniti, M
Yan, H
Vallet, S
Eda, H
Patel, K
Santo, L
Cirstea, D
Hideshima, T
Schirtzinge, L
Kuhstoss, S
Anderson, KC
Munshi, N
Scadden, D
Kronenberg, HM
Raje, N
AF Pozzi, Samantha
Fulciniti, Mariateresa
Yan, Hua
Vallet, Sonia
Eda, Homare
Patel, Kishan
Santo, Loredana
Cirstea, Diana
Hideshima, Teru
Schirtzinge, Linda
Kuhstoss, Stuart
Anderson, Kenneth C.
Munshi, Nikhil
Scadden, David
Kronenberg, Henry M.
Raje, Noopur
TI In vivo and in vitro effects of a novel anti-Dkk1 neutralizing antibody
in multiple myeloma
SO BONE
LA English
DT Article
DE Dkk1; wnt; Multiple myeloma; Osteoclast; Osteoblast
ID STEM-CELL TRANSPLANTATION; BONE-DISEASE; SERUM CONCENTRATIONS;
OSTEOCLAST DIFFERENTIATION; DICKKOPF-1; DKK1; OSTEOBLASTS; INHIBITOR;
SUPPRESSION; EXPRESSION
AB Over-expression of the protein Dickkopf-1 (Dkk1) has been associated with multiple myeloma bone disease. Previous reports with the use of anti-Dkk1 neutralizing Ab directed strategies have demonstrated a pro-anabolic effect with associated anti-myeloma activity in 2 in vivo mouse models. However new insights on the role of the wnt pathway in osteoclasts (OC) are emerging and the potential effect of a neutralizing Ab to Dkk1 in osteoclastogenesis remains to be elucidated. In order to better define the effect of an anti-Dkkl neutralizing Ab on osteoclastogenesis and myeloma, we studied a novel anti-Dkk1 monoclonal Ab in our pre-clinical models. In vivo data confirmed the pro-anabolic and anti-MM effect. In vitro data in part confirmed the in vivo observation, suggesting an indirect anti-MM effect secondary to inhibition of osteoclastogenesis and thus the interaction between MM and bone microenvironment. However, when studies on osteoclastogenesis were extended to samples derived from MM patients, we observed a variable response to anti-Dkk1 treatment without correlation to expression of surface receptors for Dkk1 in OCs suggesting potential heterogeneity in the efficacy of such a strategy. In conclusion, Dkk1 is a promising target for the treatment of both MM and bone disease, and ongoing clinical studies will help elucidate its efficacy. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Pozzi, Samantha; Yan, Hua; Vallet, Sonia; Eda, Homare; Patel, Kishan; Santo, Loredana; Cirstea, Diana; Scadden, David; Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Pozzi, Samantha; Fulciniti, Mariateresa; Yan, Hua; Vallet, Sonia; Eda, Homare; Patel, Kishan; Santo, Loredana; Cirstea, Diana; Hideshima, Teru; Anderson, Kenneth C.; Munshi, Nikhil; Scadden, David; Raje, Noopur] Harvard Univ, Sch Med, Boston, MA USA.
[Pozzi, Samantha; Fulciniti, Mariateresa; Vallet, Sonia; Santo, Loredana; Cirstea, Diana; Hideshima, Teru; Anderson, Kenneth C.; Munshi, Nikhil; Raje, Noopur] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Schirtzinge, Linda; Kuhstoss, Stuart] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
RP Raje, N (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, MGH Canc Ctr, POB 216,55 Fruit St, Boston, MA 02114 USA.
EM nraje@partners.org
RI Pozzi, Samantha/A-7617-2012
OI Pozzi, Samantha/0000-0001-7917-1774
FU Claflin Distinguished Scholar Award; Brian Dune International Myeloma
Foundation
FX SZ is the recipient of the Brian Dune International Myeloma Foundation
junior fellow award. NR is a LLS Clinical Scholar and recipient of the
Claflin Distinguished Scholar Award.
NR 33
TC 24
Z9 26
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD APR
PY 2013
VL 53
IS 2
BP 487
EP 496
DI 10.1016/j.bone.2013.01.012
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 101GR
UT WOS:000315763700020
PM 23333523
ER
PT J
AU Goy, DP
Gorosito, E
Coletta, DJ
Costa, HS
Mortarino, P
Pedemonte, NA
Toledo, J
Abranson, D
Zingoni, N
Mansur, HS
Jamin, A
Pereira, MM
Battaglino, R
Feldman, S
AF Goy, D. P.
Gorosito, E.
Coletta, D. J.
Costa, H. S.
Mortarino, P.
Acosta Pedemonte, N.
Toledo, J.
Abranson, D.
Zingoni, N.
Mansur, H. S.
Jamin, A.
Pereira, M. M.
Battaglino, R.
Feldman, S.
TI Hybrid matrix grafts to favor tissue regeneration in rabbit femur bone
lesions
SO BONE
LA English
DT Meeting Abstract
CT 29th Annual Meeting of the
Argentine-Association-of-Osteology-and-Mineral-Metabolism
CY AUG 23-25, 2012
CL Buenos Aires, ARGENTINA
SP Argentine Assoc Osteol & Mineral Metab
C1 [Goy, D. P.; Gorosito, E.; Coletta, D. J.; Mortarino, P.; Acosta Pedemonte, N.; Toledo, J.; Abranson, D.; Zingoni, N.; Mansur, H. S.; Jamin, A.; Feldman, S.] Univ Nac Rosario, Fac Cs Med, Lab Biol Osteoarticular Ing Tisular & Terapias Em, Rosario, Santa Fe, Argentina.
[Costa, H. S.; Pereira, M. M.] Univ Fed Minas Gerais, Dep Eng Met & Mat, Belo Horizonte, MG, Brazil.
[Battaglino, R.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD APR
PY 2013
VL 53
IS 2
BP 602
EP 602
DI 10.1016/j.bone.2012.12.031
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 101GR
UT WOS:000315763700047
ER
PT J
AU Doornberg, JN
Guitton, TG
Ring, D
AF Doornberg, Job N.
Guitton, Thierry G.
Ring, David
CA Sci Variation Grp
TI Diagnosis of Elbow Fracture Patterns on Radiographs: Interobserver
Reliability and Diagnostic Accuracy
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID ANTEROMEDIAL FACET; INSTABILITY; DISLOCATION; AGREEMENT
AB Studies of traumatic elbow instability suggest that recognition of a pattern in the combination and character of the fractures and joint displacements helps predict soft tissue injury and guide the treatment of traumatic elbow instability, but there is no evidence that patterns can be identified reliably.
We therefore determined (1) the interobserver reliability of identifying specific patterns of traumatic elbow instability on radiographs for subgroups of orthopaedic surgeons; and (2) the diagnostic accuracy of radiographic diagnosis.
Seventy-three orthopaedic surgeons evaluated 53 sets of radiographs and diagnosed one of five common patterns of traumatic elbow instability by using a web-based survey. The interobserver reliability was analyzed using Cohen's multirater kappa. Intraoperative diagnosis was the reference for fracture pattern in calculations of the sensitivity, specificity, accuracy, and positive predictive and negative predictive values of radiographic diagnosis.
The overall interobserver reliability for patterns of traumatic elbow instability on radiographs was kappa = 0.41. Treatment of greater than five such injuries a year was associated with greater interobserver agreement, but years in practice were not. Diagnostic accuracy ranged from 76% to 93% and was lowest for the terrible triad pattern of injury.
Specific patterns of traumatic elbow instability can be diagnosed with moderate interobserver reliability and reasonable accuracy on radiographs.
Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
C1 [Doornberg, Job N.; Guitton, Thierry G.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
[Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02163 USA.
RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02163 USA.
EM dring@partners.org
RI Page, Richard/K-6327-2015;
OI Page, Richard/0000-0002-2225-7144; Guitton, Thierry/0000-0002-2599-1985;
Frihagen, Frede/0000-0002-4811-669X
FU Wright Medical (DR) (Arlington, TN, USA); Biomet (DR) (Warsaw, IN, USA);
Skeletal Dynamics (DR)(Miami, FL, USA); Biomet (DR)(Warsaw, IN, USA)
FX One of the authors certifies that he (DR) has or may receive payments or
benefits, during the study period, an amount of less than $10,000 from
Wright Medical (DR) (Arlington, TN, USA) and Biomet (DR) (Warsaw, IN,
USA). The institution of one or more of the authors (DR) has received
funding from Skeletal Dynamics (DR)(Miami, FL, USA) and Biomet
(DR)(Warsaw, IN, USA).
NR 18
TC 12
Z9 12
U1 0
U2 5
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 APR
PY 2013
VL 471
IS 4
BP 1373
EP 1378
DI 10.1007/s11999-012-2742-4
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 097YW
UT WOS:000315510400047
PM 23247817
ER
PT J
AU Li, CW
Shi, L
Yan, Y
Gordon, BR
Gordon, WM
Wang, DY
AF Li, Chunwei
Shi, Li
Yan, Yan
Gordon, Bruce R.
Gordon, William M.
Wang, De-Yun
TI Gene Expression Signatures: A New Approach to Understanding the
Pathophysiology of Chronic Rhinosinusitis
SO CURRENT ALLERGY AND ASTHMA REPORTS
LA English
DT Review
DE Chronic rhinosinusitis (CRS); Pathophysiology; Inflammation; Remodeling;
Environmental factors; Nasal epithelium; Host defense mechanisms; Gene
expression signatures; Regulatory T cells (T-reg); Glucocorticosteroids;
Nasal polyps
ID EPITHELIAL-CELL EXPRESSION; CD4(+)CD25(+) T-CELLS; NASAL POLYPS;
MESSENGER-RNA; AIRWAY INFLAMMATION; PROSTAGLANDIN D-2; IMMUNE
REGULATION; UP-REGULATION; STEM-CELLS; C-JUN
AB Chronic rhinosinusitis (CRS) is a complex inflammatory disease with variable disease manifestation. Though external risk factors are associated with development and/or persistence of CRS, the host mucosal response is also important, as nasal epithelium acts as a physical and immune barrier. Under inflammatory stress, the nasal epithelium can undergo injury, followed by a rapid remodeling response ranging from epithelial hyperplasia, to goblet-cell metaplasia, to denudation, loss of cilia, fibrosis, and basement membrane thickening. Identification of gene expression signatures and molecular pathways in CRS pathogenesis have now begun to contribute significantly to a better understanding of the genetic and molecular alterations underlying CRS development and progression. Genetic studies are especially illuminating when multiple gene variants synergize within a permissive environmental context, and are expected to guide development of more effective therapeutic targets for CRS treatment.
C1 [Li, Chunwei; Yan, Yan; Wang, De-Yun] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Otolaryngol, Singapore 119228, Singapore.
[Shi, Li] Shandong Univ, Qilu Hosp, Dept Otolaryngol, Jinan 250012, Shandong, Peoples R China.
[Gordon, Bruce R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Gordon, Bruce R.] Cape Cod Hosp, Div Otolaryngol, Hyannis, MA USA.
[Gordon, William M.] Univ Calif Irvine, Dept Med & Biol Chem, Irvine, CA USA.
RP Wang, DY (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Otolaryngol, 1E Kent Ridge Rd, Singapore 119228, Singapore.
EM shili126@sina.com; entwdy@nus.edu.sg
FU National Medical Research Council (NMRC) [IRG10may086]; Singapore
Immunology Network (SIgN) of Singapore [SIgN 10-028]; National Nature
Science Foundation of China [81170897]
FX This work was supported by grants from the National Medical Research
Council (NMRC, IRG10may086), from Singapore Immunology Network (SIgN,
SIgN 10-028) of Singapore, and from the National Nature Science
Foundation of China (no. 81170897).
NR 74
TC 8
Z9 8
U1 0
U2 6
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1529-7322
J9 CURR ALLERGY ASTHM R
JI Curr. Allergy Asthma Rep.
PD APR
PY 2013
VL 13
IS 2
BP 209
EP 217
DI 10.1007/s11882-012-0328-6
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA 100XI
UT WOS:000315738100009
PM 23225138
ER
PT J
AU Battle, CL
Greer, JA
Ortiz-Hernandez, S
Todd, DM
AF Battle, Cynthia L.
Greer, Joseph A.
Ortiz-Hernandez, Samia
Todd, David M.
TI Developing and Implementing a Bereavement Support Program for College
Students
SO DEATH STUDIES
LA English
DT Article
AB The death of a loved one can be particularly difficult for college students, as significant losses are not anticipated during this time. Bereavement experiences are, however, not uncommon among college students, and campus environments can be isolating and nonconducive to recovery. To date, few interventions have been developed to meet bereaved college students' needs. The authors describe the rationale, development, and structure of a campus-based bereavement support program in New England, which provided a series of 17 support groups serving 105 students. They present feedback data from a subset of participants and discuss issues to consider in providing similar on-campus services.
C1 [Battle, Cynthia L.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Butler Hosp,Psychosocial Res Program, Providence, RI 02912 USA.
[Greer, Joseph A.] Harvard Univ, Sch Med, Ctr Psychiat Oncol & Behav Sci, Massachusetts Gen Hosp,Canc Ctr, Boston, MA USA.
[Ortiz-Hernandez, Samia] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Todd, David M.] Univ Massachusetts Amherst, Dept Psychol, Amherst, MA USA.
RP Battle, CL (reprint author), Butler Hosp Psychosocial Res, Dept Psychiat, 345 Blackstone Blvd, Providence, RI 02906 USA.
EM cbattle@butler.org
NR 27
TC 0
Z9 0
U1 1
U2 7
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0748-1187
J9 DEATH STUD
JI Death Stud.
PD APR 1
PY 2013
VL 37
IS 4
BP 362
EP 382
DI 10.1080/07481187.2011.634087
PG 21
WC Psychology, Multidisciplinary; Social Issues; Social Sciences,
Biomedical
SC Psychology; Social Issues; Biomedical Social Sciences
GA 100HM
UT WOS:000315689000004
PM 24520892
ER
PT J
AU Parmelee, PA
Harralson, TL
McPherron, JA
Schumacher, HR
AF Parmelee, Patricia A.
Harralson, Tina L.
McPherron, Jesse A.
Schumacher, H. Ralph
TI The structure of affective symptomatology in older adults with
osteoarthritis
SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE affective symptoms; comorbidity; depression; anxiety; osteoarthritis
ID GENERALIZED ANXIETY DISORDER; PRIMARY-CARE PATIENTS; SELF-RATED HEALTH;
SOMATIC SYMPTOMS; ELDERLY-PATIENTS; STATUS QUESTIONNAIRE; PHYSICAL
SYMPTOMS; MIXED ANXIETY; DEPRESSION; PAIN
AB Objective To examine the structure of symptoms of affective disorder among older adults with a chronic health problem (osteoarthritis) and to explore cross-sectional and longitudinal associations of obtained affective symptom clusters with key health outcomes (pain, functional disability, perceived health). Methods One-year longitudinal study of older adults with diagnosed osteoarthritis of the knee. Symptoms of DSM depression and anxiety were assessed in a research diagnostic interview by using a DSM-IV symptom checklist; self-reports captured demographic characteristics, objective health, pain, disability, and perceived health. Confirmatory factor analysis tested comparability of affective symptom structure in this sample to findings of previous research; ordinary least squares regression examined cross-sectional and longitudinal associations of affective symptoms with health outcomes, controlling for demographics and objective health. Results The current sample displayed an affective symptom structure comparable with that observed in previous research, with symptoms clustering into depressed mood (DM), somatic symptoms (SS), and psychic anxiety (PA) factors. DM was cross-sectionally associated with pain and disability and marginally with perceived health; SS predicted current pain and perceived health. Only DM predicted 1year change in disability and perceived health (but not pain). Conclusions This research confirms the role of SS of distress in fueling disability and perceived ill health among older adults who are chronically ill. However, it is DM that drives changes in perceived health and functional ability. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Parmelee, Patricia A.; McPherron, Jesse A.] Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL 35487 USA.
[Parmelee, Patricia A.; McPherron, Jesse A.] Univ Alabama, Dept Psychol, Tuscaloosa, AL USA.
[Harralson, Tina L.] Polaris Hlth Care, Philadelphia, PA USA.
[Schumacher, H. Ralph] Vet Affairs Med Ctr, Philadelphia, PA USA.
[Schumacher, H. Ralph] Univ Penn, Sch Med, Dept Rheumatol, Philadelphia, PA 19104 USA.
RP Parmelee, PA (reprint author), Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL 35487 USA.
EM pparmelee@ua.edu
FU National Institute of Mental Health [1-R01-MH51800]
FX This research was supported by the National Institute of Mental Health
grant 1-R01-MH51800 to the first author for research conducted at the
Philadelphia Geriatric Center and the University of Pennsylvania. We
thank Lori Smith for project management, James Hollander, Meredith
Olderman, and Beth Chmar for collecting the data, Hui Wu and Yunqi Zhang
for data management, and Elaine Benoff and Susan Gallagher for
administrative support.
NR 55
TC 4
Z9 7
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-6230
J9 INT J GERIATR PSYCH
JI Int. J. Geriatr. Psychiatr.
PD APR
PY 2013
VL 28
IS 4
BP 393
EP 401
DI 10.1002/gps.3837
PG 9
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 103ZR
UT WOS:000315958800009
PM 22653754
ER
PT J
AU Maust, DT
Mavandadi, S
Benson, A
Streim, JE
DiFilippo, S
Snedden, T
Weber, AL
Oslin, DW
AF Maust, Donovan T.
Mavandadi, Shahrzad
Benson, Amy
Streim, Joel E.
DiFilippo, Suzanne
Snedden, Thomas
Weber, Anita L.
Oslin, David W.
TI Telephone-based care management for older adults initiated on
psychotropic medication
SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE care management; telepsychiatry; psychotropics; depression
ID LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH; RISK;
BENZODIAZEPINE; VALIDATION; DISABILITY; SEVERITY; SYMPTOMS; VALIDITY
AB Objective This study aimed to explore the longitudinal, 6-month symptom course of older adults newly started on an antidepressant or anxiolytic by non-psychiatrist physicians and enrolled in a care management program. Method This is a naturalistic cohort study of older adults (age 65years) receiving pharmacotherapy and telephone-based care management. Participants are non-institutionalized adults participating in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly who completed telephone-based clinical assessments including demographic data, self-report on history of psychiatric treatment and adherence, and standardized symptom scales. Results A total of 162 participants with an average age of 77.2years (SD 6.8) were followed and, for analysis, split into two groups by PHQ-9 score: 75 (46.3%) scoring 04 (minimally symptomatic group, MSG) and 87 (53.7%) scoring 5 (symptomatic group, SG). Over 6months, the SG improved with PHQ-9 scores beginning on average at 10.0 (SD 4.6) and falling to 5.4 (SD 4.2) (F(1, 86)=29.53, p<0.0001). The MSG had no significant change in depressive symptoms. Emotional health as measured by SF-12 Mental Composite Score mirrored the PHQ-9 change and lack thereof in the SG and MSG, respectively. No clinical or demographic features were associated with symptom improvement in the SG although they were more likely to report medication adherence (66.7% vs. 44.0%, 2(1)=8.4, p=0.0037) compared with the MSG. Conclusions Participation of symptomatic older adults initiated on psychotropic medication in a telephone-based care management program was associated with improvement in depressive symptoms and overall emotional well-being, notable findings given participants' advanced age, state-wide distribution, and history of limited utilization of mental health care. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Maust, Donovan T.; Mavandadi, Shahrzad; Benson, Amy; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Mavandadi, Shahrzad; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Philadelphia, PA USA.
[Snedden, Thomas] Penn Dept Aging, PACE Program, Harrisburg, PA USA.
[Weber, Anita L.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Maust, DT (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM Donovan.Maust@uphs.upenn.edu
FU PACE Program, Pennsylvania Department of Aging, Harrisburg, PA, USA;
NIMH [R25-MH060490]
FX This study has been supported by the PACE Program, Pennsylvania
Department of Aging, Harrisburg, PA, USA. D. T. M. was supported by the
NIMH-funded Clinical Research Scholars Program (R25-MH060490) of the
Department of Psychiatry, University of Pennsylvania.
NR 39
TC 5
Z9 5
U1 5
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-6230
EI 1099-1166
J9 INT J GERIATR PSYCH
JI Int. J. Geriatr. Psychiatr.
PD APR
PY 2013
VL 28
IS 4
BP 410
EP 416
DI 10.1002/gps.3839
PG 7
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 103ZR
UT WOS:000315958800011
PM 22678956
ER
PT J
AU Tipper, C
Sodroski, J
AF Tipper, Christopher
Sodroski, Joseph
TI Enhanced Autointegration in Hyperstable Simian Immunodeficiency Virus
Capsid Mutants Blocked after Reverse Transcription
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TYPE-1 PREINTEGRATION COMPLEXES; INTEGRATION IN-VIVO; CYCLOPHILIN-A;
HIV-1 REPLICATION; NUCLEAR IMPORT; RESTRICTION FACTORS; NONDIVIDING
CELLS; VIRAL REPLICATION; INFECTION; PROTEIN
AB After entering a host cell, retroviruses such as simian immunodeficiency virus (SIV) uncoat, disassembling the viral capsid. Rates of uncoating that are too high and too low can be detrimental to the efficiency of infection. Rapid uncoating typically leads to blocks in reverse transcription, but the basis for replication defects associated with slow uncoating is less clear. Here we characterize the phenotypes of two SIVmac239 mutants with changes, A87E and A87D, in the helix 4/5 loop of the capsid protein. These mutant viruses exhibited normal capsid morphology but were significantly attenuated for infectivity. The infectivity of wild-type and mutant SIVmac239 was not decreased by aphidicolin-induced growth arrest of the target cells. In the cytosol of infected cells, the A87E and A87D capsids remained in particulate form longer than the wild-type SIVmac239 capsid, suggesting that the mutants uncoat more slowly than the wild-type capsid. Both mutants exhibited much higher levels of autointegrated DNA forms than wild-type SIVmac239. Thus, some changes in the helix 4/5 loop of the SIVmac239 capsid protein result in capsid hyperstability and an increase in autointegration.
C1 [Tipper, Christopher; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Sodroski, Joseph] Massachusetts Gen Hosp, Ragon Inst, Massachusetts Inst Technol & Harvard, Boston, MA 02114 USA.
RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA.
EM joseph_sodroski@dfci.harvard.edu
FU National Institutes of Health [AI063987]; National Institutes of Health
(Center for AIDS Research) [AI06354]; International AIDS Vaccine
Initiative
FX We thank the National Institutes of Health (award AI063987 and Center
for AIDS Research award AI06354), the International AIDS Vaccine
Initiative, and the late William F. McCarty-Cooper.
NR 55
TC 4
Z9 4
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2013
VL 87
IS 7
BP 3628
EP 3639
DI 10.1128/JVI.03239-12
PG 12
WC Virology
SC Virology
GA 103ZC
UT WOS:000315957100002
PM 23345510
ER
PT J
AU Wang, X
Helfer, CM
Pancholi, N
Bradner, JE
You, JX
AF Wang, Xin
Helfer, Christine M.
Pancholi, Neha
Bradner, James E.
You, Jianxin
TI Recruitment of Brd4 to the Human Papillomavirus Type 16 DNA Replication
Complex Is Essential for Replication of Viral DNA
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; POLYMERASE ALPHA-PRIMASE; INVASIVE
CERVICAL-CANCER; E1 PROTEIN; E2 PROTEIN; TRANSCRIPTIONAL ACTIVATION;
BOVINE PAPILLOMAVIRUS; S-PHASE; E2-DEPENDENT TRANSCRIPTION; ACETYLATED
CHROMATIN
AB Replication of the human papillomavirus (HPV) DNA genome relies on viral factors E1 and E2 and the cellular replication machinery. Bromodomain-containing protein 4 (Brd4) interacts with viral E2 protein to mediate papillomavirus (PV) genome maintenance and viral transcription. However, the functional role of Brd4 in the HPV life cycle remains to be clearly defined. In this study, we provide the first look into the E2-Brd4 interaction in the presence of other important viral factors, such as the HPV16 E1 protein and the viral genome. We show that Brd4 is recruited to actively replicating HPV16 origin foci together with HPV16 E1, E2, and a number of the cellular replication factors: replication protein A70 (RPA70), replication factor C1 (RFC1), and DNA polymerase delta. Mutagenesis disrupting the E2-Brd4 interaction abolishes the formation of the HPV16 replication complex and impairs HPV16 DNA replication in cells. Brd4 was further demonstrated to be necessary for HPV16 viral DNA replication using a cell-free replication system in which depletion of Brd4 by small interfering RNA (siRNA) silencing leads to impaired HPV16 viral DNA replication and recombinant Brd4 protein is able to rescue viral DNA replication. In addition, releasing endogenous Brd4 from cellular chromatin by using the bromodomain inhibitor JQ1(+) enhances HPV16 DNA replication, demonstrating that the role of Brd4 in HPV DNA replication could be uncoupled from its function in chromatin-associated transcriptional regulation and cell cycle control. Our study reveals a new role for Brd4 in HPV genome replication, providing novel insights into understanding the life cycle of this oncogenic DNA virus.
C1 [Wang, Xin; Helfer, Christine M.; Pancholi, Neha; You, Jianxin] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP You, JX (reprint author), Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM jianyou@mail.med.upenn.edu
FU HIV-Associated Malignancies Pilot Project Award (National Cancer
Institute); National Institutes of Health (NIH) [R01CA148768,
R01CA142723]
FX This work was supported by the HIV-Associated Malignancies Pilot Project
Award (National Cancer Institute) and by National Institutes of Health
(NIH) grants R01CA148768 and R01CA142723.
NR 56
TC 30
Z9 31
U1 1
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2013
VL 87
IS 7
BP 3871
EP 3884
DI 10.1128/JVI.03068-12
PG 14
WC Virology
SC Virology
GA 103ZC
UT WOS:000315957100024
PM 23365439
ER
PT J
AU Medjahed, H
Pacheco, B
Desormeaux, A
Sodroski, J
Finzi, A
AF Medjahed, Halima
Pacheco, Beatriz
Desormeaux, Anik
Sodroski, Joseph
Finzi, Andres
TI The HIV-1 gp120 Major Variable Regions Modulate Cold Inactivation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ENVELOPE GLYCOPROTEIN; GP41; ANTIBODIES; COFACTOR; RECEPTOR
AB HIV-1 entry involves the viral envelope glycoproteins (Env gps) and receptors on the target cell. Receptor binding channels the intrinsic high potential energy of Env into the force required to fuse the membranes of virus and target cell. For some HIV-1 strains, prolonged incubation on ice decreases Env potential energy and results in functional inactivation. By characterizing chimeras between two primary clade C HIV-1 strains that differ in sensitivities to cold, soluble CD4, and neutralizing antibodies, we found that these properties were largely determined by discrete elements within the gp120 variable regions V1V2 and V3.
C1 [Medjahed, Halima; Desormeaux, Anik; Finzi, Andres] Univ Montreal, Ctr Rech CHUM, Montreal, PQ, Canada.
[Medjahed, Halima; Finzi, Andres] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada.
[Finzi, Andres] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada.
[Pacheco, Beatriz; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA USA.
[Pacheco, Beatriz; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Aids, Boston, MA USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Sodroski, Joseph] Ragon Inst Massachusetts Gen Hosp, Massachusetts Inst Technol & Harvard, Charlestown, MA USA.
RP Finzi, A (reprint author), Univ Montreal, Ctr Rech CHUM, Montreal, PQ, Canada.
EM andres.finzi@umontreal.ca
FU Canada Foundation for Innovation [29866]; CIHR [257792]; FRQS [24639];
FRSQ Chercheur Boursier Junior 1 fellowship [24639]; National Institutes
of Health [AI24755, AI67854]; International AIDS Vaccine Initiative
FX This work was supported by Canada Foundation for Innovation Program
Leader grant 29866, by CIHR operating grant 257792, and by FRQS
Establishment of Young Scientist grant 24639 to A. F. A. F. is the
recipient of an FRSQ Chercheur Boursier Junior 1 fellowship (no. 24639).
This work was also supported by grants from the National Institutes of
Health (AI24755 and AI67854), the International AIDS Vaccine Initiative,
and a gift from the late William F. McCarty-Cooper.
NR 18
TC 10
Z9 10
U1 0
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR
PY 2013
VL 87
IS 7
BP 4103
EP 4111
DI 10.1128/JVI.03124-12
PG 9
WC Virology
SC Virology
GA 103ZC
UT WOS:000315957100047
PM 23345516
ER
PT J
AU Luke, JJ
Rubinstein, LV
Smith, GL
Ivy, SP
Harris, PJ
AF Luke, Jason J.
Rubinstein, Lawrence V.
Smith, Gary L.
Ivy, S. Percy
Harris, Pamela J.
TI Similar efficacy for phase I trials in comparison with DTIC for advanced
malignant melanoma: an analysis of melanoma outcomes in CTEP-sponsored
phase I trials 1995-2011
SO MELANOMA RESEARCH
LA English
DT Article
DE chemotherapy; CTEP; dacarbazine; melanoma; phase I
ID METASTATIC MELANOMA; CLINICAL-TRIALS; ONCOLOGY TRIALS; SOLID TUMORS;
CANCER; DACARBAZINE; SURVIVAL; THERAPY; ETHICS; TEMOZOLOMIDE
AB After ipilimumab, vemurafenib, and interleukin-2, standard of care chemotherapy for melanoma remains dacarbazine (response rate similar to 9%). Despite this, many physicians hesitate to refer patients to phase I protocols given a perceived lack of clinical benefit and potential for harm. To better understand the validity of these perceptions, the experience of all patients with melanoma treated on phase I trials sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) from 1995 to 2011 were analyzed and compared with the pooled results of six contemporary phase III trials of dacarbazine. A total of 937 patients with melanoma were treated in 148 CTEP phase I trials. The majority were men with a median of two prior therapies (46% receiving prior dacarbazine). Response and clinical benefit rates in these trials were not clinically different from those of dacarbazine (phase I: 6.3 and 26.8% vs. dacarbazine: 8.8 and 27.9%) although grades 3 and 4 toxicity was significantly higher (54 vs. 28%). Efficacy and toxicity were generally consistent within phase I subgroups (targeted agents, immunotherapies, or chemotherapeutics) though targeted therapy was associated with a lower response rate, immunotherapy higher incidence of grade 4 toxicity. Thus, the perception of limited efficacy of phase I trials for patients with melanoma was disproven, whereas the perception of toxicity was observed. However, this difference in toxicity may have been largely because of the nature of phase I vs. phase III trials (i.e. more heavily pretreated) and because of the phase I trials often being multiagent as opposed to dacarbazine alone. Melanoma Res 23:152-158 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Luke, Jason J.] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA.
[Rubinstein, Lawrence V.; Smith, Gary L.; Ivy, S. Percy; Harris, Pamela J.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Luke, JJ (reprint author), Dana Farber Canc Inst, Melanoma Dis Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
EM jason_luke@dfci.harvard.edu
NR 29
TC 2
Z9 2
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0960-8931
J9 MELANOMA RES
JI Melanoma Res.
PD APR
PY 2013
VL 23
IS 2
BP 152
EP 158
DI 10.1097/CMR.0b013e32835f73b2
PG 7
WC Oncology; Dermatology; Medicine, Research & Experimental
SC Oncology; Dermatology; Research & Experimental Medicine
GA 101YM
UT WOS:000315810300009
PM 23411478
ER
PT J
AU Caplan, D
Waters, G
AF Caplan, David
Waters, Gloria
TI Memory mechanisms supporting syntactic comprehension
SO PSYCHONOMIC BULLETIN & REVIEW
LA English
DT Review
DE Language/memory interactions; Language comprehension
ID SHORT-TERM-MEMORY; GARDEN PATH SENTENCES; VERB-PHRASE ELLIPSIS;
WORKING-MEMORY; EYE-MOVEMENTS; SERIAL ORDER; PARKINSONS-DISEASE;
ALZHEIMERS-DISEASE; PHONOLOGICAL SIMILARITY; INDIVIDUAL-DIFFERENCES
AB Efforts to characterize the memory system that supports sentence comprehension have historically drawn extensively on short-term memory as a source of mechanisms that might apply to sentences. The focus of these efforts has changed significantly in the past decade. As a result of changes in models of short-term working memory (ST-WM) and developments in models of sentence comprehension, the effort to relate entire components of an ST-WM system, such as those in the model developed by Baddeley (Nature Reviews Neuroscience 4: 829-839, 2003) to sentence comprehension has largely been replaced by an effort to relate more specific mechanisms found in modern models of ST-WM to memory processes that support one aspect of sentence comprehension-the assignment of syntactic structure (parsing) and its use in determining sentence meaning (interpretation) during sentence comprehension. In this article, we present the historical background to recent studies of the memory mechanisms that support parsing and interpretation and review recent research into this relation. We argue that the results of this research do not converge on a set of mechanisms derived from ST-WM that apply to parsing and interpretation. We argue that the memory mechanisms supporting parsing and interpretation have features that characterize another memory system that has been postulated to account for skilled performance-long-term working memory. We propose a model of the relation of different aspects of parsing and interpretation to ST-WM and long-term working memory.
C1 [Caplan, David] Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA.
[Waters, Gloria] Boston Univ, Dept Speech & Hearing Sci, Sargent Coll, Boston, MA 02215 USA.
RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, 175 Cambridge St,Suite 340, Boston, MA 02114 USA.
EM dcaplan@partners.org
FU NIDCD NIH HHS [DC00942, DC011032, R01 DC000942, R01 DC011032]
NR 170
TC 24
Z9 25
U1 6
U2 38
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1069-9384
EI 1531-5320
J9 PSYCHON B REV
JI Psychon. Bull. Rev.
PD APR
PY 2013
VL 20
IS 2
BP 243
EP 268
DI 10.3758/s13423-012-0369-9
PG 26
WC Psychology, Mathematical; Psychology, Experimental
SC Psychology
GA 104PO
UT WOS:000316006900004
PM 23319178
ER
PT J
AU Lou, E
Peters, KB
Sumrall, AL
Desjardins, A
Reardon, DA
Lipp, ES
Herndon, JE
Coan, A
Bailey, L
Turner, S
Friedman, HS
Vredenburgh, JJ
AF Lou, Emil
Peters, Katherine B.
Sumrall, Ashley L.
Desjardins, Annick
Reardon, David A.
Lipp, Eric S.
Herndon, James E., II
Coan, April
Bailey, Leighann
Turner, Scott
Friedman, Henry S.
Vredenburgh, James J.
TI Phase II trial of upfront bevacizumab and temozolomide for unresectable
or multifocal glioblastoma
SO CANCER MEDICINE
LA English
DT Article
DE Bevacizumab; glioblastoma; neoadjuvant therapy; temozolomide;
unresectable; upfront
AB Patients with unresectable glioblastomas have a poor prognosis, with median survival of 6-10 months. We conducted a phase II trial of upfront 5-day temozolomide (TMZ) and bevacizumab (BV) in patients with newly diagnosed unresectable or multifocal glioblastoma. Patients received up to four cycles of TMZ at 200 mg/m(2) on days 1-5, and BV at 10 mg/kg on days 1 and 15 of a 28-day cycle. Brain magnetic resonance imaging (MRI) was performed monthly. Therapy was continued as long as there was no tumor progression, grade 4 non-hematologic toxicity, or recurrent grade 4 hematologic toxicity after dose reduction. The primary end point was best tumor response as measured on MRI. Forty-one patients were accrued over 12 months; 39 had a full set of MRI scans available for evaluation. Assessment for best radiographic responses was as follows: partial responses in 24.4%, stable disease in 68.3%, and progressive disease in 2.4%. Treatment-related toxicities included seven grade 4 toxicities and one grade 5 toxicity (myocardial infarction). From this study, it was concluded that an upfront regimen of TMZ and BV for unresectable glioblastoma was well tolerated and provided a significant level of disease stabilization. Therapeutic toxicities were consistent with those seen in the adjuvant setting using these agents. The upfront approach to treatment of glioblastoma in the unresectable population warrants further investigation in randomized controlled phase III trials.
C1 [Lou, Emil; Lipp, Eric S.; Turner, Scott] Duke Univ, Med Ctr, Dept Surg, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA.
[Peters, Katherine B.; Sumrall, Ashley L.; Desjardins, Annick; Bailey, Leighann; Vredenburgh, James J.] Duke Univ, Med Ctr, Dept Med, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA.
[Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA.
[Herndon, James E., II; Coan, April] Duke Univ, Med Ctr, Dept Biostat, Ctr Canc, Durham, NC USA.
[Friedman, Henry S.] Duke Univ, Med Ctr, Dept Surg & Pediat, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC USA.
RP Lou, E (reprint author), Div Hematol Oncol & Transplantat, Mayo Mail Code 480,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM emil-lou@umn.edu
OI Sykes, April/0000-0002-7667-8155
FU National Institutes of Health [5 P50 NS20023, 5 P50 CA108786]; Genentech
Pharmaceuticals
FX This work was supported by National Institutes of Health Grants 5 P50
NS20023 and 5 P50 CA108786; and a grant from Genentech Pharmaceuticals.
NR 37
TC 22
Z9 25
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD APR
PY 2013
VL 2
IS 2
BP 185
EP 195
DI 10.1002/cam4.58
PG 11
WC Oncology
SC Oncology
GA V36KI
UT WOS:000209210600007
PM 23634286
ER
PT J
AU Katz, DL
Grant, DL
McGuire, TJ
McQuigg, S
Voci, K
Volpp, K
AF Katz, David L.
Grant, Deborah Lewison
McGuire, Todd J.
McQuigg, Scott
Voci, Karen
Volpp, Kevin
TI Working on the Health of Families: Where Children Fit in Worksite Health
Promotion Efforts
SO CHILDHOOD OBESITY
LA English
DT Editorial Material
ID GLOBAL CAPACITY
C1 [Katz, David L.] Yale Univ, Prevent Res Ctr, Griffin Hosp, Derby, CT 06418 USA.
[Grant, Deborah Lewison] FoodFight, New York, NY USA.
[McGuire, Todd J.] IncentaHLTH LLC, Denver, CO USA.
[McQuigg, Scott] HealthTeacher Inc, Nashville, TN USA.
[Voci, Karen] Harvard Pilgrim Hlth Care Fdn, Harvard Pilgrim Hlth Care, Wellesley, MA USA.
[Volpp, Kevin] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Volpp, Kevin] Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA USA.
[Volpp, Kevin] Penn CMU Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA USA.
[Volpp, Kevin] UPHS Ctr Innovat Hlth Care Financing, Philadelphia, PA USA.
[Volpp, Kevin] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Volpp, Kevin] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
RP Katz, DL (reprint author), Yale Univ, Prevent Res Ctr, Griffin Hosp, 2nd Floor 130 Div St, Derby, CT 06418 USA.
EM david.katz@yale.edu
OI Katz, David/0000-0001-6845-6192
NR 6
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-2168
EI 2153-2176
J9 CHILD OBES
JI Child Obes.
PD APR
PY 2013
VL 9
IS 2
BP 95
EP 103
DI 10.1089/chi.2013.9202
PG 9
WC Pediatrics
SC Pediatrics
GA AI4PB
UT WOS:000336846200003
PM 23517280
ER
PT J
AU Bartley, J
Garrett, J
Grant, CC
Camargo, CA
AF Bartley, Jim
Garrett, Jeff
Grant, Cameron C.
Camargo, Carlos A., Jr.
TI Could Vitamin D Have a Potential Anti-Inflammatory and Anti-Infective
Role in Bronchiectasis?
SO CURRENT INFECTIOUS DISEASE REPORTS
LA English
DT Article
DE Bronchiectasis; Inflammation; Obstructive lung disease; Pathophysiology;
Pathology; Vitamin D; Innate immunity; Adaptive immunity; Antimicrobial
peptides; Chronic rhinosinusitis; Microbiotia
ID CYSTIC FIBROSIS BRONCHIECTASIS; RANDOMIZED CONTROLLED-TRIAL; REGULATORY
T-CELLS; OBSTRUCTIVE PULMONARY-DISEASE; PLACEBO-CONTROLLED TRIAL;
QUALITY-OF-LIFE; D SUPPLEMENTATION; 1,25-DIHYDROXYVITAMIN D-3; PEPTIDE
LL-37; MYCOBACTERIUM-TUBERCULOSIS
AB Bronchiectasis is a chronic infective and inflammatory respiratory disease that causes significant morbidity and mortality. Patients with non-cystic-fibrosis bronchiectasis are frequently vitamin D deficient, and vitamin D levels correlate with disease severity. Infection-specific actions of vitamin D include the enhancement of innate immunity and the moderation of inflammation caused by the adaptive immune response. Potentially, vitamin D could influence the processes that lead to bronchiectasis and the frequency and severity of acute exacerbations. Randomized trials of vitamin D supplementation have shown effects that are likely to be protective against the development of bronchiectasis. Several issues need to be clarified before the development of clinical trials to investigate the role of vitamin D in bronchiectasis. These include an optimal vitamin D supplementation dose and appropriate and sensitive outcome measures that include assessment of exacerbation frequency and severity, lung function, and health-related quality of life.
C1 [Bartley, Jim] Univ Auckland, Dept Surg, Auckland 1023, New Zealand.
[Garrett, Jeff] Univ Auckland, Dept Med, Auckland 1023, New Zealand.
[Grant, Cameron C.] Univ Auckland, Dept Paediat, Auckland 1023, New Zealand.
[Grant, Cameron C.] Univ Auckland, Ctr Longitudinal Res He Ara Ki Mua, Auckland 1023, New Zealand.
[Grant, Cameron C.] Auckland City Hosp, Starship Childrens Hosp, Auckland Dist Hlth Board, Auckland 1023, New Zealand.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Bartley, J (reprint author), Univ Auckland, Dept Surg, 10 Owens Rd, Auckland 1023, New Zealand.
EM jbartley@ihug.co.nz; jegarrett@middlemore.co.nz;
cc.grant@auckland.ac.nz; ccamargo@partners.org
OI Grant, Cameron/0000-0002-4032-7230
FU Health Research Council of New Zealand grant
FX Dr. Bartley, Dr. Garrett, and Professor Camargo Jr. have received a
Health Research Council of New Zealand grant with which they are
investigating the role of Vitamin D supplementation in adult
bronchiectasis.
NR 102
TC 4
Z9 4
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3847
EI 1534-3146
J9 CURR INFECT DIS REP
JI Curr. Infect. Dis. Rep.
PD APR
PY 2013
VL 15
IS 2
BP 148
EP 157
DI 10.1007/s11908-013-0321-9
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA AK2YP
UT WOS:000338286800009
PM 23371406
ER
PT J
AU Mitin, T
Shipley, WU
Efstathiou, JA
Heney, NM
Kaufman, DS
Lee, RJ
Zietman, AL
AF Mitin, Timur
Shipley, William U.
Efstathiou, Jason A.
Heney, Niall M.
Kaufman, Donald S.
Lee, Richard J.
Zietman, Anthony L.
TI Trimodality Therapy for Bladder Conservation in Treatment of Invasive
Bladder Cancer
SO CURRENT UROLOGY REPORTS
LA English
DT Article
DE Bladder cancer; Radiation therapy; Trimodality therapy; Bladder
preservation; Muscle invasive; Cystectomy
ID SELECTIVE ORGAN PRESERVATION; TRANSITIONAL-CELL CARCINOMA; RADICAL
CYSTECTOMY; UROTHELIAL CARCINOMA; RADIATION-THERAPY; ONCOLOGY-GROUP;
NEOADJUVANT CHEMOTHERAPY; TRANSURETHRAL SURGERY; ADJUVANT CHEMOTHERAPY;
SPARING TREATMENT
AB During the past 25 years, prospective clinical trials have established that bladder preservation therapy for select patients with muscle-invasive bladder cancer is a safe and effective alternative to an immediate cystectomy. Cisplatin-based chemoradiation is the most well-studied and accepted component of trimodality therapy; however, other systemic agents have recently been shown effective in combination with radiation therapy, increasing the range of options to allow for better personalization of care. In this review, the most recent advances in the field of bladder-preserving trimodality therapy are presented, and future directions for improving the outcomes are outlined.
C1 [Mitin, Timur; Shipley, William U.; Efstathiou, Jason A.; Zietman, Anthony L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
[Heney, Niall M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA.
[Kaufman, Donald S.; Lee, Richard J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol & Oncol, Boston, MA 02114 USA.
RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
EM wshipley@partners.org
NR 34
TC 8
Z9 8
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1527-2737
J9 CURR UROL REP
JI Curr. Urol. Rep.
PD APR
PY 2013
VL 14
IS 2
BP 109
EP 115
DI 10.1007/s11934-012-0301-x
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AI1FC
UT WOS:000336594700008
PM 23341373
ER
PT J
AU Rehman, MQ
Beal, D
Liang, YM
Noronha, A
Winter, H
Farraye, FA
Ganley-Leal, L
AF Rehman, Mian Qasim
Beal, Dominic
Liang, YanMei
Noronha, Ansu
Winter, Harland
Farraye, Francis A.
Ganley-Leal, Lisa
TI B Cells Secrete Eotaxin-1 in Human Inflammatory Bowel Disease
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE eosinophil; B cell; eotaxin-1; inflammatory bowel disease
ID ESCHERICHIA-COLI LIPOPOLYSACCHARIDE; PERIPHERAL-BLOOD EOSINOPHILS;
CHEMOKINE RECEPTOR CCR3; ULCERATIVE-COLITIS; CROHNS-DISEASE;
GASTROINTESTINAL EOSINOPHILS; INCREASED EXPRESSION; CYTOKINE PRODUCTION;
EPITHELIAL-CELLS; IN-VITRO
AB Background: Our previous studies have demonstrated that B cells in human inflammatory bowel disease (IBD) are highly activated and produce copious amounts of chemokines. Here, we showed that B cells produce eotaxin-1, a selective chemokine for acute eosinophilia. Increased levels of activated eosinophils have been found in the intestinal mucosa in patients with IBD, but their role(s) and the regulation of their migration patterns remain poorly defined.
Methods: To determine how B-cell secretion of eotaxin-1 influences eosinophil activation and migration, we performed immunoepidemiological approaches coupled with in vitro studies. B cells and eosinophils from patients with Crohn's disease and ulcerative colitis were isolated, and responses to Toll-like receptor ligands (TLR) were measured and assessed for the relationship with clinical disease.
Results: Eotaxin-1 from recirculating B cells, and TLR ligands, regulated eosinophil homing mechanisms in IBD. B cells stimulated with hypo-acylated lipopolysaccharide (LPS) produced copious amounts of eotaxin-1, which influenced eosinophil activation profiles in the bloodstream. We also found that hexa-acylated LPS, such Escherichia coli LPS, directly activated TLR2-expressing and TLR4-expressing eosinophils from patients with IBD to express a different repertoire of mucosal homing receptors, namely CCR9 and CCR10. Whereas B-cell production of eotaxin-1 was correlated with reduced disease activity, eosinophil activation by hexa-acylated LPS was associated with increased disease activity.
Conclusions: These results suggest that systemic TLR ligands influence eosinophil migration patterns, both directly and indirectly, through B cells. Our report uncovers unexpected mechanisms of cross talk between certain immune cells that shed new light on IBD immunology.
C1 [Rehman, Mian Qasim; Liang, YanMei; Ganley-Leal, Lisa] Boston Univ, Sch Med, Infect Dis Sect, Dept Med,Boston Med Ctr, Boston, MA 02118 USA.
[Beal, Dominic] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA.
[Noronha, Ansu; Farraye, Francis A.] Boston Med Ctr, Gastroenterol Sect, Boston, MA USA.
[Winter, Harland] MassGen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA USA.
RP Ganley-Leal, L (reprint author), Boston Univ, Sch Med, Infect Dis Sect, Dept Med,Boston Med Ctr, 650 Albany St,Room 630, Boston, MA 02118 USA.
EM lisaganley@comcast.net
OI Farraye, Francis/0000-0001-6371-2441
FU Broad Medical Research Program of the Broad Foundation, a Department of
Medicine CTSI Pilot Award [1ULIRR025771]; Evans Medical Foundation Blood
Microbiome ARC
FX This study was supported by the Broad Medical Research Program of the
Broad Foundation, a Department of Medicine CTSI Pilot Award
1ULIRR025771, and the Evans Medical Foundation Blood Microbiome ARC.
NR 61
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD APR
PY 2013
VL 19
IS 5
BP 922
EP 933
DI 10.1097/MIB.0b013e3182802950
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH4GA
UT WOS:000336084200017
PM 23511032
ER
PT J
AU Herfarth, HH
Katz, JA
Hanauer, SB
Sandborn, WJ
Loftus, EV
Sands, BE
Galanko, JA
Walkup, D
Isaacs, KL
Martin, CF
Sandler, RS
Sartor, RB
AF Herfarth, Hans H.
Katz, Jeffry A.
Hanauer, Stephen B.
Sandborn, William J.
Loftus, Edward V., Jr.
Sands, Bruce E.
Galanko, Joseph A.
Walkup, Dolly
Isaacs, Kim L.
Martin, Christopher F.
Sandler, Robert S.
Sartor, Ryan B.
TI Ciprofloxacin for the Prevention of Postoperative Recurrence in Patients
with Crohn's Disease: A Randomized, Double-blind, Placebo-controlled
Pilot Study
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE Crohn's disease/surgery; ciprofloxacin; quinolone; anti-infective
agents/adverse effects; inflammatory bowel diseases
ID INFLAMMATORY-BOWEL-DISEASE; CONTROLLED-TRIAL; ENDOSCOPIC RECURRENCE;
ULCERATIVE-COLITIS; ILEAL RESECTION; FOLLOW-UP; SURGERY; PROPHYLAXIS;
THERAPY; RISK
AB Background: The commensal bacterial flora plays a critical role in the postoperative recurrence of Crohn's disease (CD). We conducted a randomized, double-blind, placebo-controlled 6-month pilot trial of ciprofloxacin for the prevention of endoscopic recurrence in patients with CD who underwent surgery.
Methods: Thirty-three patients with CD, who had undergone surgery with ileocolonic anastomosis within the previous 2 weeks, were randomized to treatment with ciprofloxacin (500 mg twice daily) or placebo tablets for 6 months. Endpoints were endoscopic recurrence at 6 months and safety and tolerability of long-term ciprofloxacin therapy.
Results: Thirty-three patients were randomized; 14 patients discontinued the study early. Significant endoscopic recurrence was observed in 3 of 9 patients (33%) in the ciprofloxacin group and 5 of 10 patients (50%) in the placebo group at 6 months after surgery (P < 0.578). The intention-to-treat analysis demonstrated endoscopic recurrence in 11 of 17 patients (65%) in the ciprofloxacin group and 11 of 16 patients (69%) in the placebo group at month 6 (P < 0.805). Thirty-six adverse events occurred in 19 of 33 patients (58%). Possible drug-associated adverse events occurred significantly more often in the ciprofloxacin group (P < 0.043), leading to study drug discontinuation in 24% (4 of 17) and 6% of patients (1 of 16) in the ciprofloxacin and placebo groups, respectively (P < 0.166).
Conclusions: In this pilot study, ciprofloxacin was not more effective than placebo for the prevention of postoperative recurrence in patients with CD. Long-term ciprofloxacin therapy is limited by drug-associated side effects. Future studies in postoperative prevention of CD should evaluate antibiotic approaches with a more favorable safety profile.
C1 [Herfarth, Hans H.; Galanko, Joseph A.; Walkup, Dolly; Isaacs, Kim L.; Martin, Christopher F.; Sandler, Robert S.; Sartor, Ryan B.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA.
[Katz, Jeffry A.] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr, Div Gastroenterol & Liver Dis, Cleveland, OH USA.
[Hanauer, Stephen B.] Univ Chicago, Sect Gastroenterol & Nutr, Chicago, IL 60637 USA.
[Sandborn, William J.; Loftus, Edward V., Jr.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Sandborn, William J.] Univ Calif San Diego, Div Gastroenterol, La Jolla, CA 92093 USA.
[Sands, Bruce E.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA.
[Sands, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA.
[Sands, Bruce E.] Mt Sinai Sch Med, Dept Med, Henry D Janowitz Div Gastroenterol, New York, NY USA.
RP Herfarth, HH (reprint author), Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Bioinformat Bldg,CB 7080, Chapel Hill, NC 27599 USA.
EM hherf@med.unc.edu
RI Loftus, Edward/E-8304-2011
FU Crohn's and Colitis Foundation of America (CCFA); National Institute of
Diabetes & Digestive & Kidney Diseases [1R21DK080408-01, P30 DK034987]
FX Supported by a Senior Research Award of the Crohn's and Colitis
Foundation of America (CCFA) and by grants of the National Institute of
Diabetes & Digestive & Kidney Diseases (1R21DK080408-01; P30 DK034987).
NR 35
TC 14
Z9 14
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD APR
PY 2013
VL 19
IS 5
BP 1073
EP 1079
DI 10.1097/01.MIB.0000428910.36091.10
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH4GA
UT WOS:000336084200035
PM 23511031
ER
PT J
AU Gheorghiade, M
Vaduganathan, M
Shah, SJ
AF Gheorghiade, Mihai
Vaduganathan, Muthiah
Shah, Sanjiv J.
TI Evaluative Framework for Phase II Studies in Patients With Heart Failure
and Preserved Ejection Fraction
SO JACC-HEART FAILURE
LA English
DT Editorial Material
DE diastolic dysfunction; heart failure with preserved ejection fraction;
late sodium current inhibition
C1 [Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA.
[Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
[Shah, Sanjiv J.] Northwestern Univ, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Gheorghiade, M (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 645 North Michigan Ave,Suite 1006, Chicago, IL 60611 USA.
EM m-gheorghiade@northwestern.edu
NR 12
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD APR
PY 2013
VL 1
IS 2
BP 123
EP 126
DI 10.1016/j.jchf.2013.01.001
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA V41GT
UT WOS:000209535400005
PM 24621837
ER
PT J
AU Hill, RR
Vorderstrasse, A
Turner, B
Pereira, K
Thompson, J
AF Hill, Rebecca Russo
Vorderstrasse, Allison
Turner, Barbara
Pereira, Katherine
Thompson, Julie
TI Screening for Depression in Patients with Diabetes: Addressing the
Challenge
SO JNP-JOURNAL FOR NURSE PRACTITIONERS
LA English
DT Article
DE depression screening; diabetes mellitus; patient health questionnaire-9;
primary care
AB This quality improvement project instituted a routine depression screening using the Patient Health Questionnaire-9 for patients in a primary care practice with the goal of earlier identification and treatment of depression. A total of 115 patients were screened. A retrospective chart review revealed a statistically significant difference in the incidence and new diagnoses of depression among those with diabetes. The use of this screening was devoid of significant barriers to implementation. Although several new cases of depression were diagnosed, many patients refused treatment of any kind, necessitating future research in the area of patient barriers to depression management.
C1 [Hill, Rebecca Russo] Duke Univ, Durham, NC 27706 USA.
[Hill, Rebecca Russo] MCPHS Univ, Sch Nursing, Boston, MA USA.
[Hill, Rebecca Russo] Massachusetts Gen Hosp, Emergency Med, Boston, MA 02114 USA.
[Vorderstrasse, Allison; Pereira, Katherine; Thompson, Julie] Duke Univ, Sch Nursing, Durham, NC USA.
[Turner, Barbara] Duke Univ, Sch Nursing, Nursing Practice Program, Durham, NC USA.
RP Hill, RR (reprint author), Duke Univ, Durham, NC 27706 USA.
EM Rebecca.Hill1@mcphs.edu
NR 13
TC 2
Z9 2
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1555-4155
EI 1878-058X
J9 JNP-J NURSE PRACT
JI JNP-J. Nurse Pract.
PD APR
PY 2013
VL 9
IS 4
BP 208
EP 213
DI 10.1016/j.nurpra.2013.01.009
PG 6
WC Nursing
SC Nursing
GA V39HV
UT WOS:000209403000009
ER
PT J
AU Tonetti, MS
Van Dyke, TE
AF Tonetti, Maurizio S.
Van Dyke, Thomas E.
CA Joint EFP AAP Workshop
TI Periodontitis and atherosclerotic cardiovascular disease: consensus
report of the Joint EFP/AAP Workshop on Periodontitis and Systemic
Diseases (Reprinted from Journal of Clinical Periodontology, vol 40, pg
S24-S29, 2013)
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Reprint
DE atherosclerosis; bacteremia; cardiovascular diseases; clinical trials;
C-reactive protein; epidemiology; inflammation; myocardial infarction;
periodontal diseases; periodontitis; stroke
ID OF-CARDIOLOGY; INTERVENTIONS; PROGRESSION; GUIDELINES; MANAGEMENT;
HEALTH
AB Background: This consensus report is concerned with the association between periodontitis and atherosclerotic cardiovascular disease (ACVD). Periodontitis is a chronic multifactorial inflammatory disease caused by microorganisms and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss; as such, it is a major public health issue.
Aims: This report examined biological plausibility, epidemiology and early results from intervention trials.
Plausibility: Periodontitis leads to entry of bacteria in the blood stream. The bacteria activate the host inflammatory response by multiple mechanisms. The host immune response favors atheroma formation, maturation and exacerbation.
Epidemiology: In longitudinal studies assessing incident cardiovascular events, statistically significant excess risk for ACVD was reported in individuals with periodontitis. This was independent of established cardiovascular risk factors. The amount of the adjusted excess risk varies by type of cardiovascular outcome and across populations by age and gender. Given the high prevalence of periodontitis, even low to moderate excess risk is important from a public health perspective.
Intervention: There is moderate evidence that periodontal treatment: (i) reduces systemic inflammation as evidenced by reduction in C-reactive protein (CRP) and improvement of both clinical and surrogate measures of endothelial function; but (ii) there is no effect on lipid profiles - supporting specificity. Limited evidence shows improvements in coagulation, biomarkers of endothelial cell activation, arterial blood pressure and subclinical atherosclerosis after periodontal therapy. The available evidence is consistent and speaks for a contributory role of periodontitis to ACVD. There are no periodontal intervention studies on primary ACVD prevention and there is only one feasibility study on secondary ACVD prevention.
Conclusions: It was concluded that: (i) there is consistent and strong epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; and (ii) while in vitro, animal and clinical studies do support the interaction and biological mechanism, intervention trials to date are not adequate to draw further conclusions. Well-designed intervention trials on the impact of periodontal treatment on prevention of ACVD hard clinical outcomes are needed.
C1 [Tonetti, Maurizio S.] European Res Grp Periodontol, I-16149 Genoa, Italy.
[Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA USA.
RP Tonetti, MS (reprint author), European Res Grp Periodontol, WTC Tower Genoa, Via De Marini 1, I-16149 Genoa, Italy.
EM maurizio.tonetti@ergoperio.eu
FU Colgate-Palmolive; American Academy of Periodontology
FX The workshop was funded by an unrestricted educational grant from
Colgate-Palmolive to the European Federation of Periodontology and the
American Academy of Periodontology.
NR 15
TC 14
Z9 14
U1 1
U2 4
PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
EI 1943-3670
J9 J PERIODONTOL
JI J. Periodont.
PD APR
PY 2013
VL 84
IS 4
SU S
SI SI
BP S24
EP S29
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA V40CD
UT WOS:000209455800004
ER
PT J
AU Van Dyke, TE
van Winkelhoff, AJ
AF Van Dyke, Thomas E.
van Winkelhoff, Arie Jan
TI Infection and inflammatory mechanisms (Reprinted from Journal of
Clinical Periodontology, vol 40, pg S1-S7, 2013)
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Reprint
DE cardiovascular disease; infection; inflammation; pathogenesis;
periodontitis; systemic diseases
ID HUMAN PERIODONTAL-LIGAMENT; CORONARY-HEART-DISEASE;
TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; ATHEROSCLEROTIC
CARDIOVASCULAR-DISEASE; ANTIINFLAMMATORY LIPID MEDIATORS; EDITORS
CONSENSUS PERIODONTITIS; JOURNAL-OF-CARDIOLOGY;
ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS
AB This introductory article examines the potential mechanisms that may play a role in the associations between periodontitis and the systemic conditions being considered in the EFP/AAP Workshop in Segovia, Spain. Three basic mechanisms have been postulated to play a role in these interactions; metastatic infections, inflammation and inflammatory injury, and adaptive immunity. The potential role of each alone and together is considered in in vitro and animal studies and in human studies when available. This is not a systematic or critical review, but rather an overview of the field to set the stage for the critical reviews in each of the working groups.
C1 [Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA 02142 USA.
[van Winkelhoff, Arie Jan] Univ Groningen, Dept Dent & Oral Hyg, Groningen, Netherlands.
RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Appl Oral Sci, Clin & Translat Res Chair, 245 First St, Cambridge, MA 02142 USA.
EM tvandyke@forsyth.org
OI Van Dyke, Thomas/0000-0003-0568-124X
FU Colgate-Palmolive; American Academy of Periodontology
FX The workshop was funded by an unrestricted educational grant from
Colgate-Palmolive to the European Federation of Periodontology and the
American Academy of Periodontology.
NR 94
TC 10
Z9 10
U1 1
U2 1
PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
EI 1943-3670
J9 J PERIODONTOL
JI J. Periodont.
PD APR
PY 2013
VL 84
IS 4
SU S
SI SI
BP S1
EP S7
DI 10.1902/jop.2013.1340018
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA V40CD
UT WOS:000209455800001
PM 23631571
ER
PT J
AU Halford, C
Gau, V
Churchill, BM
Haake, DA
AF Halford, Colin
Gau, Vincent
Churchill, Bernard M.
Haake, David A.
TI Bacterial Detection & Identification Using Electrochemical Sensors
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Bioengineering; Issue 74; Microbiology; Genetics; Molecular Biology;
Cellular Biology; Biochemistry; Biomedical Engineering; Medicine;
Immunology; Bacteria; Electrochemical sensor; ribosomal RNA; rRNA; 16S
RNA; DNA; probe; assay
AB Electrochemical sensors are widely used for rapid and accurate measurement of blood glucose and can be adapted for detection of a wide variety of analytes. Electrochemical sensors operate by transducing a biological recognition event into a useful electrical signal. Signal transduction occurs by coupling the activity of a redox enzyme to an amperometric electrode. Sensor specificity is either an inherent characteristic of the enzyme, glucose oxidase in the case of a glucose sensor, or a product of linkage between the enzyme and an antibody or probe.
Here, we describe an electrochemical sensor assay method to directly detect and identify bacteria. In every case, the probes described here are DNA oligonucleotides. This method is based on sandwich hybridization of capture and detector probes with target ribosomal RNA (rRNA). The capture probe is anchored to the sensor surface, while the detector probe is linked to horseradish peroxidase (HRP). When a substrate such as 3,3', 5,5'-tetramethylbenzidine (TMB) is added to an electrode with capture-target-detector complexes bound to its surface, the substrate is oxidized by HRP and reduced by the working electrode. This redox cycle results in shuttling of electrons by the substrate from the electrode to HRP, producing current flow in the electrode.
C1 [Halford, Colin] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
[Halford, Colin; Churchill, Bernard M.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
[Gau, Vincent] GeneFluidics, Duarte, CA USA.
[Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA.
[Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
RP Haake, DA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
EM dhaake@ucla.edu
FU National Institute of Allergy and Infectious Diseases [AI075565]; Wendy
and Ken Ruby Fund for Excellence in Pediatric Urology Research
FX This study was supported by Cooperative Agreement Award AI075565 (to
D.A.H.) from the National Institute of Allergy and Infectious Diseases
and by the Wendy and Ken Ruby Fund for Excellence in Pediatric Urology
Research. B.M.C. is the Judith and Robert Winston Chair in Pediatric
Urology.
NR 12
TC 0
Z9 0
U1 2
U2 14
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 APR
PY 2013
IS 74
AR UNSP e4282
DI 10.3791/4282
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36QY
UT WOS:000209227100006
PM 23644406
ER
PT J
AU Timpone, V
Schneider, BE
Sherman, PM
AF Timpone, Vincent
Schneider, Brett E.
Sherman, Paul M.
TI Screening CT Angiography for Detection of Blunt Carotid and Vertebral
Artery Injury in the Setting of Combat-Related Trauma
SO MILITARY MEDICINE
LA English
DT Article
ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; CEREBROVASCULAR INJURIES; DIAGNOSIS;
THERAPY
AB Blunt carotid and vertebral artery injury (BCVI) is a relatively rare injury reported in the civilian sector and is associated with high morbidity and mortality. The purpose of our study was to use an optimized computed tomography angiography protocol in the deployed setting to determine the prevalence of BCVI in a consecutive patient population having experienced recent wartime-related traumatic injuries. From July 2008 to September 2009, a total of 307 consecutive trauma patients were included in this study. At least 233 (76%) patients were known to have experienced blast-related traumatic injuries. 135 (44%) patients had injuries to the head, face, or neck. 4 patients (1.3%) sustained BCVI. There was no statistically significant difference between the prevalence of BCVI in the deployed setting and the civilian sector. We speculate that in our study population, the relatively decreased prevalence of cervical spinal fractures (3.3%) observed may counter the theoretical increased risk of vascular injury from blast trauma, ultimately producing a similar prevalence of overall BCVI compared to civilian study populations. Based on our observations, we cannot advocate for or against more liberalized screening of BCVI in the deployed setting, and military physicians may elect to continue screening for these injuries with currently established and accepted practice guidelines developed in civilian trauma populations.
C1 [Timpone, Vincent] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA.
[Schneider, Brett E.] David Grant USAF Med Ctr, Dept Radiol, Div Neuroradiol, Travis Afb, CA 94535 USA.
[Sherman, Paul M.] Wilford Hall USAF Med Ctr, Dept Radiol, Div Neuroradiol, Lackland AFB, TX 78236 USA.
RP Timpone, V (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02114 USA.
NR 20
TC 1
Z9 1
U1 0
U2 1
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD APR
PY 2013
VL 178
IS 4
BP 416
EP 420
DI 10.7205/MILMED-D-12-00108
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA AN7TY
UT WOS:000340805100013
PM 23707827
ER
PT J
AU La Fountaine, MF
Wecht, JM
Bauman, WA
AF La Fountaine, M. F.
Wecht, J. M.
Bauman, W. A.
TI Acute nitric oxide synthase inhibition and cardiac conduction in persons
with spinal cord injury: a short report
SO PHARMAZIE
LA English
DT Article
ID AUTONOMIC NERVOUS-SYSTEM; HEART-RATE-VARIABILITY; BLOOD-PRESSURE;
INCREASED SUSCEPTIBILITY; VENTRICULAR-ARRHYTHMIAS;
SARCOPLASMIC-RETICULUM; EXCHANGER EXPRESSION; PARAPLEGIC RATS; RATE
RESPONSE; TETRAPLEGIA
AB N-G-nitro L-arginine methyl ester (L-NAME) is a potent and non-specific inhibitor of nitric oxide synthase (NOS). NOS inhibition with L-NAME has been shown to adversely prolong electrocardiogram (ECG) intervals in an animal model, an observation which has yet to be evaluated in humans. We determined the effects of several weight-based L-NAME doses on ECG intervals in persons with tetraplegia and a neurologically-intact control group. This two-part investigation determined the effects of different weight-based doses of L-NAME in the supine (Study 1) and orthostatic position (Study 2). Subjects completed an open-label trial with intravenous administration of L-NAME at specific doses [i.e., 0, 1, 2 or 4 mg.kg(-1)] in the supine position. The SCI group completed an orthostatic challenge with or without L-NAME [i.e., 0, 1 or 2 mg.kg(-1)] and controls completed only a single visit [0 mg-kg(-1)]. Digital ECGs were obtained at baseline (BL), after infusion (60 minutes) and 1 hour post-infusion (120 minutes) in Study 1, and at BL, 60 minutes and at two, 10 minute post-infusion time points after head up tilt (Post-Tilt 1 and 2) in Study 2. Heart rate, PQ, QT, and heart rate corrected QT (QTC) intervals were determined. The groups were matched for demographics. Seven subjects with tetraplegia and 6 controls participated in Study 1; 7 subjects with tetraplegia and 7 controls participated in Study 2. No statistical differences were noted between or within groups at baseline on each study visit for the ECG variables. L-NAME, regardless of dose, did not significantly change any ECG interval. NOS inhibition with L-NAME, at the weight-based doses tested do not induce hypertensive crises and, did not adversely affect any ECG interval in persons with SCI or neurologically intact control subjects during supine rest or orthostatic provocation.
C1 [La Fountaine, M. F.; Wecht, J. M.; Bauman, W. A.] James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, Bronx, NY 10468 USA.
[La Fountaine, M. F.; Wecht, J. M.; Bauman, W. A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA.
[La Fountaine, M. F.; Bauman, W. A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[La Fountaine, M. F.] Seton Hall Univ, Sch Hlth & Med Sci, Dept Phys Therapy, S Orange, NJ 07079 USA.
[Wecht, J. M.; Bauman, W. A.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA.
RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, VA RR&D Natl Ctr Excellence Med Consequences Spin, Room 7A-13 M,130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM michael.lafountaine@va.gov
FU Veteran Affairs Rehabilitation Research and Development Service [B9212C,
B3600R, B3346 V]; James J. Peters VA Medical Center
FX This research was supported by the Veteran Affairs Rehabilitation
Research and Development Service (#B9212C, #B3600R, and #B3346 V) and
the James J. Peters VA Medical Center.
NR 35
TC 2
Z9 2
U1 0
U2 1
PU GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH
PI ESCHBORN
PA PHARMAZEUTISCCARL MANNICH STR 26, D-65760 ESCHBORN, GERMANY
SN 0031-7144
J9 PHARMAZIE
JI Pharmazie
PD APR
PY 2013
VL 68
IS 4
BP 245
EP 250
DI 10.1691/ph.2013.2794
PG 6
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA AE8NZ
UT WOS:000334259900003
PM 23700789
ER
PT J
AU Maselli, DJ
Adams, SG
Peters, JI
Levine, SM
AF Maselli, Diego J.
Adams, Sandra G.
Peters, Jay I.
Levine, Stephanie M.
TI Management of asthma during pregnancy
SO THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE
LA English
DT Review
DE asthma; management of asthma; pregnancy
ID RANDOMIZED CONTROLLED-TRIAL; PROTON-PUMP INHIBITORS; SEVERE
ALLERGIC-ASTHMA; DOUBLE-BLIND-TRIAL; PERINATAL OUTCOMES;
CONGENITAL-MALFORMATIONS; INHALED BECLOMETHASONE; NEDOCROMIL SODIUM;
MATERNAL ASTHMA; MODERATE ASTHMA
AB Asthma is an inflammatory lung condition that is the most common chronic disease affecting pregnancy. The changes in pulmonary physiology during pregnancy include increased minute ventilation, decreased functional residual capacity, increased mucus production, and airway mucosa hyperemia and edema. Pregnancy is also associated with a physiological suppression of the immune system. Many studies have described the heterogeneous immune system response in women with asthma during pregnancy, which partly explains why asthma has been shown to worsen, improve, or remain stable in equal proportions of women during pregnancy. Asthma may be associated with poor maternal and fetal outcomes. However, better maternal and fetal outcomes are observed with better asthma control. Asthma controller medications are generally thought to be safe during pregnancy, but limited data are available for some of the medicines. Newer medications like omalizumab open avenues for the treatment of asthma, but also pose a challenge, as there is limited experience with their use. Therefore, a multidisciplinary approach, including obstetricians, asthma specialists, and pediatricians should collaborate with the patient to carefully weigh the risks and benefits to determine an optimal management plan for each individual patient. The aim of this review article is to summarize the most recent literature about the immunological changes that occur during pregnancy, physiological and clinical implications of asthma on pregnancy, and asthma management and medication use in pregnant women.
C1 [Maselli, Diego J.; Adams, Sandra G.; Peters, Jay I.; Levine, Stephanie M.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis & Crit Care, San Antonio, TX 78229 USA.
[Adams, Sandra G.; Peters, Jay I.; Levine, Stephanie M.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Maselli, DJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis & Crit Care, 7400 Merton Minter MC 111E, San Antonio, TX 78229 USA.
EM masellicacer@uthscsa.edu
NR 82
TC 10
Z9 10
U1 0
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1753-4658
EI 1753-4666
J9 THER ADV RESPIR DIS
JI Ther. Adv. Respir. Dis.
PD APR
PY 2013
VL 7
IS 2
BP 87
EP 100
DI 10.1177/1753465812464287
PG 14
WC Respiratory System
SC Respiratory System
GA AH3KU
UT WOS:000336023000003
PM 23129568
ER
PT J
AU Milos, G
Kuenzli, C
Soelch, CM
Schumacher, S
Moergeli, H
Mueller-Pfeiffer, C
AF Milos, Gabriella
Kuenzli, Cornelia
Soelch, Chantal Martin
Schumacher, Sonja
Moergeli, Hanspeter
Mueller-Pfeiffer, Christoph
TI How much should I eat? Estimation of meal portions in anorexia nervosa
SO APPETITE
LA English
DT Article
DE Anorexia nervosa; Portion size; Intent-to-eat; Food amount; Eating
behavior
ID BULIMIA-NERVOSA; SIZE; FOOD; BEHAVIOR; SAMPLE
AB Pathological concern regarding one's weight and weight gain is a crucial feature of anorexia nervosa. Consequently, anorexia nervosa patients often claim that they are uncertain regarding the amount of food they should eat. The present study investigated whether individuals with anorexia nervosa show an altered estimation of meal portion sizes and whether this estimation is modulated by an intent-to-eat instruction (where patients are asked to imagine having to eat the presented meal), meal type and meal portion size. Twenty-four women with anorexia nervosa and 27 healthy women estimated, using a visual analogue scale, the size of six different portions of three different meals, with and without intent-to-eat instructions. Subjects with anorexia nervosa estimated the size of small and medium meal portions (but not large meal servings) as being significantly larger, compared to estimates of healthy controls. The overestimation of small meal portions by anorexia nervosa subjects was significantly greater in the intent-to-eat, compared to general, condition. These findings suggest that disturbed perceptions associated with anorexia nervosa not only include interoceptive awareness (i.e., body weight and shape), but also extend to external disorder-related objects such as meal portion size. Specific therapeutic interventions, such as training regarding meal portion evaluation, could address these difficulties. (C) 2013 Published by Elsevier Ltd.
C1 [Milos, Gabriella; Kuenzli, Cornelia; Schumacher, Sonja; Moergeli, Hanspeter; Mueller-Pfeiffer, Christoph] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland.
[Soelch, Chantal Martin] Univ Fribourg, Dept Psychol, CH-1700 Fribourg, Switzerland.
[Mueller-Pfeiffer, Christoph] Psychiat Serv Cty St Gallen North, Ctr Educ & Res COEUR, Wil, Switzerland.
[Mueller-Pfeiffer, Christoph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.
RP Milos, G (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland.
EM gabriella.milos@usz.ch
NR 30
TC 4
Z9 4
U1 1
U2 39
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-6663
J9 APPETITE
JI Appetite
PD APR 1
PY 2013
VL 63
BP 42
EP 47
DI 10.1016/j.appet.2012.12.016
PG 6
WC Behavioral Sciences; Nutrition & Dietetics
SC Behavioral Sciences; Nutrition & Dietetics
GA 095WV
UT WOS:000315366600007
PM 23276722
ER
PT J
AU Horton, LC
Frosch, MP
Vangel, MG
Weigel-DiFranco, C
Berson, EL
Schmahmann, JD
AF Horton, Laura C.
Frosch, Matthew P.
Vangel, Mark G.
Weigel-DiFranco, Carol
Berson, Eliot L.
Schmahmann, Jeremy D.
TI Spinocerebellar Ataxia Type 7: Clinical Course, Phenotype-Genotype
Correlations, and Neuropathology
SO CEREBELLUM
LA English
DT Article
DE Trinucleotide repeat expansion; Cerebellum; Ataxia; Pathology;
Electroretinography
ID DOMINANT CEREBELLAR-ATAXIA; RESTLESS LEGS SYNDROME;
RETINITIS-PIGMENTOSA; SUBTHALAMIC STIMULATION; MACULAR DYSTROPHY; CAG
REPEATS; SCA7; DEGENERATION; DISORDER; FEATURES
AB Spinocerebellar ataxia type 7 is a neurodegenerative polyglutamine disease characterized by ataxia and retinal degeneration. The longitudinal course is unknown, and relationships between repeat expansion, clinical manifestations, and neuropathology remain uncertain. We followed 16 affected individuals of a 61-member kindred over 27 years with electroretinograms, neurological examinations including the Brief Ataxia Rating Scale, neuroimaging in five, and autopsy in four cases. We identified four stages of the illness: Stage 0, gene-positive but phenotypically silent; Stage 1, no symptoms, but hyperreflexia and/or abnormal electroretinograms; Stage 2, symptoms and signs progress modestly; and Stage 3, rapid clinical progression. CAG repeat length correlated inversely with age of onset of visual or motor signs (r = -0.74, p = 0.002). Stage 3 rate of progression did not differ between cases (p = 0.18). Electroretinograms correlated with Brief Ataxia Rating Scale score and were a biomarker of disease onset and progression. All symptomatic patients developed gait ataxia, extremity dysmetria, dysarthria, dysrhythmia, and oculomotor abnormalities. Funduscopy revealed pale optic discs and pigmentary disturbances. Visual acuity declined to blindness in those with longer CAG expansions. Hyperreflexia was present from Stage 1 onwards. Restless legs syndrome and sensory impairment were common. Neuropathological hallmarks were neuronal loss in cerebellar cortex, deep cerebellar nuclei, inferior olive, and anterior horns of the spinal cord, and axonal loss in spinocerebellar tracts, dorsal nerve roots, and posterior columns. Retinal pathology included photoreceptor degeneration and disruption of retinal pigment epithelium. Spinocerebellar ataxia type 7 evolves through four clinical stages; neuropathological findings underlie the clinical presentation; electroretinograms are a potential biomarker of disease progression.
C1 [Horton, Laura C.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Lab Neuroanat & Cerebellar Neurobiol, Ataxia Unit,Cognit & Behav Neurol Unit, Boston, MA 02114 USA.
[Horton, Laura C.; Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, Pathol Serv, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
[Vangel, Mark G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Weigel-DiFranco, Carol; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Dept Ophthalmol,Med Sch, Boston, MA 02114 USA.
RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Lab Neuroanat & Cerebellar Neurobiol, Ataxia Unit,Cognit & Behav Neurol Unit, Suite 340,Charles River Plaza South,175 Cambridge, Boston, MA 02114 USA.
EM jschmahmann@partners.org
OI Horton, Laura/0000-0002-7098-3650
FU NIA NIH HHS [P50 AG005134]; NIMH NIH HHS [R01 MH067980]
NR 34
TC 20
Z9 20
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1473-4222
J9 CEREBELLUM
JI Cerebellum
PD APR
PY 2013
VL 12
IS 2
BP 176
EP 193
DI 10.1007/s12311-012-0412-4
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA 099RJ
UT WOS:000315638600007
PM 22915085
ER
PT J
AU Halperin, F
Goldfine, AB
AF Halperin, Florencia
Goldfine, Allison B.
TI Metabolic surgery for type 2 diabetes: efficacy and risks
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Review
DE bariatric surgery; glycemic control; type 2 diabetes
ID GASTRIC-BYPASS-SURGERY; MORBIDLY OBESE SUBJECTS; GLUCAGON-LIKE
PEPTIDE-1; BETA-CELL FUNCTION; INDUCED WEIGHT-LOSS; BARIATRIC SURGERY;
SLEEVE GASTRECTOMY; INSULIN SENSITIVITY; GUT HORMONE; HYPERINSULINEMIC
HYPOGLYCEMIA
AB Purpose of review
Bariatric surgery has emerged as a highly effective treatment for obesity and is increasingly recognized to have benefits for glycemic management in patients with pre-existing type 2 diabetes mellitus (T2DM), and for diabetes prevention. This article will review the efficacy and mechanisms of metabolic surgery for the treatment of T2DM.
Recent findings
Recent small randomized studies with 1-2 years of follow-up begin to provide level 1 data of the effects of surgical procedures compared to medical management on glycemic control. Physiology studies using sophisticated metabolic techniques to evaluate insulin secretion, action, and entero-endocrine changes in patients preoperatively and postoperatively have shed light on the mechanisms that lead to changes in glycemia observed after bariatric surgery.
Summary
Understanding the efficacy and physiologic effects of bariatric surgery on metabolism will help guide patient management in the context of a growing epidemic of obesity and T2DM, and may also ultimately enable us to develop less invasive but equally effective therapeutic strategies for weight loss and metabolic control.
C1 [Halperin, Florencia; Goldfine, Allison B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Halperin, Florencia; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Halperin, Florencia; Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA.
RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
EM allison.goldfine@joslin.harvard.edu
FU National Institutes of Health (NIH) [5RC1DK086918-02, 1R56DK095451-01];
KL2/MeRIT program of Harvard Catalyst/The Harvard Clinical and
Translational Science Center [UL1 RR 025758]; Harvard University
FX The authors wish to acknowledge that this work was supported by the
National Institutes of Health (NIH) grants 5RC1DK086918-02 and
1R56DK095451-01 (A.B.G.), as well as the KL2/MeRIT program of Harvard
Catalyst/The Harvard Clinical and Translational Science Center (Award
#UL1 RR 025758 and financial contributions from Harvard University and
its affiliated academic healthcare centers) (F.H.).
NR 96
TC 8
Z9 9
U1 1
U2 30
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 APR
PY 2013
VL 20
IS 2
BP 98
EP 105
DI 10.1097/MED.0b013e32835edbb0
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 097ND
UT WOS:000315479900003
PM 23403742
ER
PT J
AU Restrepo, MI
Faverio, P
Anzueto, A
AF Restrepo, Marcos I.
Faverio, Paola
Anzueto, Antonio
TI Long-term prognosis in community-acquired pneumonia
SO CURRENT OPINION IN INFECTIOUS DISEASES
LA English
DT Review
DE biomarkers; community-acquired pneumonia; outcome
ID RESPIRATORY-DISTRESS-SYNDROME; PRACTICE POPULATION COHORT; GERMAN
COMPETENCE NETWORK; ACUTE CORONARY SYNDROMES; OLD MANS FRIEND;
FOLLOW-UP; INFLAMMATORY MARKERS; SEVERITY ASSESSMENT; ELDERLY-PATIENTS;
ACUTE INFECTION
AB Purpose of review
Pneumonia is considered the leading infectious diseases cause of death and the seventh leading cause of death overall in the US. There is significant interest in understanding the relationship between community-acquired pneumonia (CAP) and mortality.
Recent findings
Most clinical studies examining patients with CAP have used an arbitrary in-hospital or 30-day mortality as a short-term mortality clinical end point. However, long-term mortality (arbitrary >3 months) factors, incidence, prediction, and implications on patient care are important issues that require further evaluation in patients with CAP. This review focuses on the most recent literature assessing the importance and the frequency of long-term associated outcomes in patients with CAP, the risk factors, and possible implications for future strategies. Multiple risk factors that include age, sex, comorbid conditions, type of pneumonia, and severity of illness are associated with higher long-term mortality. In addition, several biomarkers were demonstrated to be independently associated with long-term mortality.
Summary
Despite advances in the understanding of long-term mortality among CAP patients, there is still a high unacceptable long-term mortality. Public health programs should address this important gap, considering the high level of complexity factors in patients with CAP.
C1 [Restrepo, Marcos I.; Faverio, Paola; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.; Anzueto, Antonio] S Texas Vet Healthcare Syst, Audie L Murphy Div, San Antonio, TX USA.
[Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA.
[Faverio, Paola] Univ Milano Bicocca, Monza, Italy.
[Faverio, Paola] San Gerardo Hosp, Dept Resp Med, Monza, Italy.
RP Restrepo, MI (reprint author), 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA.
EM restrepom@uthscsa.edu
RI Restrepo, Marcos/H-4442-2014
FU National Heart, Lung, and Blood Institute [K23HL096054]
FX Dr Restrepo time is partially protected by Award Number K23HL096054 from
the National Heart, Lung, and Blood Institute. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Heart, Lung, And Blood Institute or the
National Institutes of Health. The funding agencies had no role in the
preparation, review, or approval of the manuscript. The views expressed
in this article are those of the author and do not necessarily represent
the views of the Department of Veterans Affairs.
NR 85
TC 29
Z9 30
U1 0
U2 11
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 APR
PY 2013
VL 26
IS 2
BP 151
EP 158
DI 10.1097/QCO.0b013e32835ebc6d
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 097IY
UT WOS:000315468400008
PM 23426328
ER
PT J
AU Moon, HS
Liu, XW
Nagel, JM
Chamberland, JP
Diakopoulos, KN
Brinkoetter, MT
Hatziapostolou, M
Wu, Y
Robson, SC
Iliopoulos, D
Mantzoros, CS
AF Moon, Hyun-Seuk
Liu, Xiaowen
Nagel, Jutta M.
Chamberland, John P.
Diakopoulos, Kalliope N.
Brinkoetter, Mary T.
Hatziapostolou, Maria
Wu, Yan
Robson, Simon C.
Iliopoulos, Dimitrios
Mantzoros, Christos S.
TI Salutary effects of adiponectin on colon cancer: in vivo and in vitro
studies in mice
SO GUT
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR-D; COLORECTAL-CANCER;
CELL-PROLIFERATION; CIRCULATING ADIPONECTIN; MAMMARY CARCINOMAS;
SIGNALING PATHWAY; OBESITY; RISK; MECHANISMS
AB Background Obesity and a high-fat diet are associated with the risk and progression of colon cancer. Low adiponectin levels may play an important role in the development of colon and other obesity-related malignancies. No previous studies have directly investigated the mechanistic effects of adiponectin on colon cancer in the settings of obesity, a high-fat diet and/or adiponectin deficiency.
Objective To investigate the effects of adiponectin on the growth of colorectal cancer in adiponectin-deficient or wild-type-C57BL/6 mice fed a low-fat or high-fat diet.
Results Mice fed a high-fat-diet gained more weight and had larger tumours than mice fed a low-fat-diet. Adiponectin administration suppressed implanted tumour growth, causing larger central necrotic areas. Adiponectin treatment also suppressed angiogenesis assessed by CD31 staining and VEGFb and VEGFd mRNA expression in tumours obtained from mice fed a high-fat-diet and from adiponectin-deficient mice. Adiponectin treatment decreased serum insulin levels in mice on a high-fat-diet and increased serum-interleukin (IL)-12 levels in adiponectin-deficient mice. In vitro, it was found that adiponectin directly controls malignant potential (cell proliferation, adhesion, invasion and colony formation) and regulates metabolic (AMPK/S6), inflammatory (STAT3/VEGF) and cell cycle (p21/p27/p53/cyclins) signalling pathways in both mouse MCA38 and human HT29, HCT116 and LoVo colon cancer cell lines in a LKB1-dependent way.
Conclusion These new mechanistic and pathophysiology studies provide evidence for an important role of adiponectin in colon cancer. The data indicate that adiponectin or analogues might be useful agents in the management or chemoprevention of colon cancer.
C1 [Moon, Hyun-Seuk; Liu, Xiaowen; Nagel, Jutta M.; Chamberland, John P.; Diakopoulos, Kalliope N.; Brinkoetter, Mary T.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02130 USA.
[Hatziapostolou, Maria; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Hatziapostolou, Maria; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02130 USA.
[Wu, Yan; Robson, Simon C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Gastroenterol & Transplantat Inst, Boston, MA 02130 USA.
[Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA 02130 USA.
RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, JP9B52A,150 S Huntington Ave, Boston, MA 02130 USA.
EM cmantzor@bidmc.harvard.edu
RI Moon, Hyun-Seuk/G-8576-2015; Hatziapostolou, Maria/N-1820-2015;
OI Moon, Hyun-Seuk/0000-0002-5216-2090; Hatziapostolou,
Maria/0000-0003-2493-7028; Chamberland, John/0000-0002-7862-1371;
Diakopoulos, Kalliope/0000-0002-9236-0489
FU joint California Walnut Commission; AICR grant; National Institute of
Diabetes and Digestive and Kidney Diseases [DK79929-02, DK058785-08,
DK081913-02]; NIH [HL076540, HL094400]; Beth Israel Deaconess Medical
Center; VA Merit award [10684957]
FX This study was supported by a joint California Walnut Commission and
AICR grant. The Mantzoros Laboratory is supported by DK79929-02,
DK058785-08 and DK081913-02 grants from the National Institute of
Diabetes and Digestive and Kidney Diseases. The Robson laboratory
acknowledges support from NIH via HL076540 and HL094400. The Mantzoros
Laboratory is also supported by a discretionary grant from Beth Israel
Deaconess Medical Center and a VA Merit award (grant 10684957).
NR 45
TC 36
Z9 39
U1 0
U2 21
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD APR
PY 2013
VL 62
IS 4
BP 561
EP 570
DI 10.1136/gutjnl-2012-302092
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 099CB
UT WOS:000315595800012
PM 22735569
ER
PT J
AU Babson, KA
Boden, MT
Harris, AH
Stickle, TR
Bonn-Miller, MO
AF Babson, Kimberly A.
Boden, Matthew Tyler
Harris, Alex H.
Stickle, Timothy R.
Bonn-Miller, Marcel O.
TI Poor sleep quality as a risk factor for lapse following a cannabis quit
attempt
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Sleep; Marijuana; Cannabis; Lapse
ID MARIJUANA DEPENDENCE; ANXIETY SENSITIVITY; SEEKING TREATMENT; COPING
MOTIVES; WITHDRAWAL; ALCOHOL; USERS; PREVALENCE; SYMPTOMS; NICOTINE
AB Treatments for cannabis dependence are associated with high rates of lapse/relapse, underscoring the importance of identifying malleable risk factors that are associated with quit failure. Whereas research has demonstrated that poor sleep quality following cannabis discontinuation is related to subsequent use, there has yet to be an examination of whether poor sleep quality prior to a quit attempt results in a similar pattern of lapse. The present study addressed this gap by examining the role of pre-quit sleep quality on early lapse to cannabis use following a self-guided quit attempt, among 55 cannabis dependent military veterans. Results indicated that participants who experienced poor pre-quit sleep quality had greater risk for lapse within the first 2 days (out of 7) following their quit attempt. Findings are discussed in terms of improving treatments for individuals who report poor sleep quality prior to a cannabis quit attempt. Published by Elsevier Inc.
C1 [Babson, Kimberly A.] Stanford Univ, Ctr Hlth Care Evaluat, Vet Affairs Palo Alto Hlth Care Syst, Menlo Pk, CA 94025 USA.
[Babson, Kimberly A.] Stanford Univ, Dept Psychiat & Behav Sci, Menlo Pk, CA 94025 USA.
[Boden, Matthew Tyler; Harris, Alex H.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA.
[Stickle, Timothy R.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA.
[Bonn-Miller, Marcel O.] Philadelphia Vet Affairs Med Ctr, Ctr Excellence Substance Abuse Treatment & Educ, Philadelphia, PA 19104 USA.
[Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA.
[Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA.
RP Babson, KA (reprint author), 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA.
EM Kimberly.Babson@va.gov
OI Babson, Kimberly/0000-0002-9233-8230
NR 46
TC 9
Z9 9
U1 0
U2 16
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 APR
PY 2013
VL 44
IS 4
BP 438
EP 443
DI 10.1016/j.jsat.2012.08.224
PG 6
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 096TD
UT WOS:000315426300011
PM 23098380
ER
PT J
AU Arakaki, R
Kroshinsky, D
AF Arakaki, Ryan
Kroshinsky, Daniela
TI Analyzing inpatient dermatology consultations for pediatric patients
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Arakaki, Ryan] Harvard Univ, Sch Med, Boston, MA USA.
[Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB171
EP AB171
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600677
ER
PT J
AU Arakaki, R
Kroshinsky, D
AF Arakaki, Ryan
Kroshinsky, Daniela
TI Treatment of cutaneous dystrophic calcification with intralesional
sodium thiosulfate
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Arakaki, Ryan] Harvard Univ, Sch Med, Boston, MA USA.
[Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB73
EP AB73
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600289
ER
PT J
AU Coley, M
Kroshinsky, D
AF Coley, Marcelyn
Kroshinsky, Daniela
TI Neuro-Sweet syndrome responds to hydroxychloroquine
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Coley, Marcelyn] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Kroshinsky, Daniela] Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB55
EP AB55
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600220
ER
PT J
AU Hartman, R
Kroshinsky, D
Tsiaras, W
AF Hartman, Rebecca
Kroshinsky, Daniela
Tsiaras, William
TI Voriconazole-induced photosensitivity concerning for Stevens-Johnson
syndrome
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Hartman, Rebecca] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kroshinsky, Daniela; Tsiaras, William] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB187
EP AB187
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600743
ER
PT J
AU Hartman, R
Kroshinsky, D
Tsiaras, W
AF Hartman, Rebecca
Kroshinsky, Daniela
Tsiaras, William
TI Adult-onset Still disease in a geriatric patient: Updates and pearls in
diagnosis
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Hartman, Rebecca] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kroshinsky, Daniela; Tsiaras, William] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB8
EP AB8
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600031
ER
PT J
AU Higgins, HW
Kroumpouzos, G
Jenkins, SJ
Horn, T
AF Higgins, H. William, II
Kroumpouzos, George
Jenkins, States Jennifer
Horn, Thomas
TI Pregnancy-associated hyperkeratosis of the nipple: A study of 25 cases
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Higgins, H. William, II; Kroumpouzos, George] Brown Univ, Providence, RI 02912 USA.
[Jenkins, States Jennifer] Miraca Life Sci Tufts Med Ctr, Newton, MA USA.
[Horn, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB58
EP AB58
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600232
ER
PT J
AU Javorsky, E
Kimball, AB
AF Javorsky, Emilia
Kimball, Alexa Boer
TI Hidradenitis suppurativa: Patient experiences with bariatric surgery
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Javorsky, Emilia] Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA.
[Kimball, Alexa Boer] Harvard Univ, Sch Med, Massachuetts Gen Hosp, Dept Dermatol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB89
EP AB89
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600354
ER
PT J
AU Kauvar, A
Gilchrest, BA
Yu, B
Ross, EV
Anderson, RR
Langer, RS
Kilmer, S
AF Kauvar, Arielle
Gilchrest, Barbara A.
Yu, Betty
Ross, E. Victor
Anderson, Richard Rox
Langer, Robert S.
Kilmer, Suzanne
TI A pilot study of a novel noninvasive topical under-eye contouring
technology
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 71st Annual Meeting of the American-Academy-of-Dermatology (AAD)
CY MAR 01-05, 2013
CL Miami Beach, FL
SP Amer Acad Dermatol (AAD)
C1 [Kauvar, Arielle] New York Laser & Skin Care, New York, NY USA.
[Gilchrest, Barbara A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Yu, Betty] Living Proof, Cambridge, MA USA.
[Ross, E. Victor] Scripps Clin Carmel Valley, San Diego, CA USA.
[Anderson, Richard Rox] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Langer, Robert S.] MIT, Boston, MA USA.
[Kilmer, Suzanne] Laser & Skin Surg Ctr Northern Calif, Sacramento, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD APR
PY 2013
VL 68
IS 4
SU 1
BP AB20
EP AB20
PG 1
WC Dermatology
SC Dermatology
GA 096NZ
UT WOS:000315412600081
ER
PT J
AU King, SDW
Fitchett, G
Berry, DL
AF King, Stephen D. W.
Fitchett, George
Berry, Donna L.
TI Screening for religious/spiritual struggle in blood and marrow
transplant patients
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Cancer; Oncology; Screening; Religious/spiritual struggle; Chaplain
ID QUALITY-OF-LIFE; ADVANCED CANCER-PATIENTS; LONG-TERM ADJUSTMENT; ILL
ELDERLY-PATIENTS; BREAST-CANCER; RELIGIOUS STRUGGLE; SPIRITUAL CONCERNS;
HEALTH; CARE; PREDICTORS
AB A growing body of research documents the harmful effects of religious/spiritual (R/S) struggle (e.g., feeling abandoned or punished by God) among patients with a wide variety of diagnoses. Documented effects include poorer quality of life, greater emotional distress, poorer recovery, and increased disability. This study reports the use of a screening protocol that identified patients who may have been experiencing R/S struggle. We also examined the prevalence and correlates of possible R/S struggle, its association with quality of life, pain, and depressive symptoms and compared the results from the screening protocol with social workers' assessments.
One hundred seventy-eight blood and marrow transplant patients completed the Electronic Self-Report Assessment-Cancer (ESRA-C) which included the Rush Religious Struggle Screening Protocol and other measures of quality of life, pain, and depressive symptoms prior to transplant therapy. All participants were assessed by a social worker, 90 % within 2 weeks of the ESRA-C assessment.
Using the Rush Protocol, 18 % of the patients were identified as potentially experiencing R/S struggle. R/S struggle was not reported in any social work assessments. In a multivariable model, potential R/S struggle was more likely in patients who were more recently diagnosed, male, and Asian/Pacific Islanders. There were no significant associations between potential R/S struggle and quality of life, pain, or depressive symptoms.
Early identification of patients with R/S struggle will facilitate their referral for further assessment and appropriate intervention. Further research is needed to identify the best methods of screening patients for R/S struggle.
C1 [King, Stephen D. W.] Seattle Canc Care Alliance, Seattle, WA 98109 USA.
[Fitchett, George] Rush Univ, Med Ctr, Dept Relig Hlth & Human Values, Chicago, IL 60612 USA.
[Berry, Donna L.] Harvard Univ, Sch Med, Boston, MA USA.
[Berry, Donna L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP King, SDW (reprint author), Seattle Canc Care Alliance, POB 19023,G-1035, Seattle, WA 98109 USA.
EM sking@seattlecca.org
FU National Institute of Nursing Research [R01 NR008726]
FX The ESRA-C trial was funded by the National Institute of Nursing
Research, R01 NR008726), PI Donna Berry. We also express appreciation to
Geila Rajaee who assisted with coding the social work assessments.
NR 54
TC 11
Z9 11
U1 4
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD APR
PY 2013
VL 21
IS 4
BP 993
EP 1001
DI 10.1007/s00520-012-1618-1
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 096ZV
UT WOS:000315444600012
PM 23052922
ER
PT J
AU Lee, EQ
Norden, AD
Drappatz, J
Wen, PY
AF Lee, Eudocia Q.
Norden, Andrew D.
Drappatz, Jan
Wen, Patrick Y.
TI Application of Targeted Therapy to Malignant Gliomas and Response to
Treatment
SO CURRENT SIGNAL TRANSDUCTION THERAPY
LA English
DT Article
DE Targeted therapy; malignant glioma; angiogenesis; clinical trials;
multi-targeted therapy
ID PHASE-II TRIAL; GROWTH-FACTOR-RECEPTOR; RECURRENT
GLIOBLASTOMA-MULTIFORME; HIGH-GRADE GLIOMAS; BEVACIZUMAB PLUS
IRINOTECAN; NEWLY-DIAGNOSED GLIOBLASTOMA; PROGRESSION-FREE SURVIVAL;
BRAIN-TUMOR CONSORTIUM; SCATTER FACTOR EXPRESSION; CANCER STEM-CELLS
AB The prognosis for malignant gliomas remains poor despite multimodality therapy. An increased understanding of the molecular pathogenesis involved in glioma development and growth has resulted in development of agents that specifically target these molecular processes and pathways. Except for inhibitors of the vascular endothelial growth factor pathway, results from most single agent trials have been modest at best. Tailoring therapy to the individual patients is an attractive strategy although most studies have failed to determine predictive biomarkers. Numerous novel agents, multi-targeted agents, and combination therapies are now in clinical trials for malignant glioma.
C1 [Lee, Eudocia Q.; Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Ctr Neurooncol,Dana Farber Brigham & Womens Canc, Boston, MA 02115 USA.
[Lee, Eudocia Q.; Norden, Andrew D.; Wen, Patrick Y.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Drappatz, Jan] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA.
EM pwen@partners.org
FU Genentech; Schering; Novartis; Astra Zeneca; Exelixis; Boehringer
Ingelheim; Melinda M. Wanatick Brain Tumor Research Fund; Par Fore The
Cure Brain Tumor Research Fund
FX Patrick Wen receives research support Genentech, Schering, Novartis,
Astra Zeneca, Exelixis, Boehringer Ingelheim, and Amgen as acts as a
consultant for Angiochem and Nexgenix.; We gratefully acknowledge the
support of the Melinda M. Wanatick and Par Fore The Cure Brain Tumor
Research Funds.
NR 136
TC 0
Z9 0
U1 0
U2 10
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1574-3624
EI 2212-389X
J9 CURR SIGNAL TRANSD T
JI Curr. Signal Transduct. Ther.
PD APR
PY 2013
VL 8
IS 1
BP 14
EP 24
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 093NK
UT WOS:000315198400004
ER
PT J
AU Sonpavde, G
Pond, GR
Fougeray, R
Choueiri, TK
Qu, AQ
Vaughn, DJ
Niegisch, G
Albers, P
James, ND
Wong, YN
Ko, YJ
Sridhar, SS
Galsky, MD
Petrylak, DP
Vaishampayan, UN
Khan, A
Vogelzang, NJ
Beer, TM
Stadler, WM
O'Donnell, PH
Sternberg, CN
Rosenberg, JE
Bellmunt, J
AF Sonpavde, Guru
Pond, Gregory R.
Fougeray, Ronan
Choueiri, Toni K.
Qu, Angela Q.
Vaughn, David J.
Niegisch, Guenter
Albers, Peter
James, Nicholas D.
Wong, Yu-Ning
Ko, Yoo-Joung
Sridhar, Srikala S.
Galsky, Matthew D.
Petrylak, Daniel P.
Vaishampayan, Ulka N.
Khan, Awais
Vogelzang, Nicholas J.
Beer, Tomasz M.
Stadler, Walter M.
O'Donnell, Peter H.
Sternberg, Cora N.
Rosenberg, Jonathan E.
Bellmunt, Joaquim
TI Time from Prior Chemotherapy Enhances Prognostic Risk Grouping in the
Second-line Setting of Advanced Urothelial Carcinoma: A Retrospective
Analysis of Pooled, Prospective Phase 2 Trials
SO EUROPEAN UROLOGY
LA English
DT Article
DE Urothelial carcinoma; Second line; Prognosis; Time from prior
chemotherapy; Hemoglobin; Liver metastasis; Performance status
ID TRANSITIONAL-CELL CARCINOMA; PLATINUM-CONTAINING REGIMEN; III TRIAL;
CANCER; PACLITAXEL; VINFLUNINE; TRACT; GEMCITABINE; THERAPY; PLUS
AB Background: Outcomes for patients in the second-line setting of advanced urothelial carcinoma (UC) are dismal. The recognized prognostic factors in this context are Eastern Cooperative Oncology Group (ECOG) performance status (PS) >0, hemoglobin level (Hb) <10 g/dl, and liver metastasis (LM).
Objectives: The purpose of this retrospective study of prospective trials was to investigate the prognostic value of time from prior chemotherapy (TFPC) independent of known prognostic factors.
Design, setting, and participants: Data from patients from seven prospective trials with available baseline TFPC, Hb, PS, and LM values were used for retrospective analysis (n = 570). External validation was conducted in a second-line phase 3 trial comparing best supportive care (BSC) versus vinflunine plus BSC (n = 352).
Outcome measurements and statistical analysis: Cox proportional hazards regression was used to evaluate the association of factors, with overall survival (OS) and progression-free survival (PFS) being the respective primary and secondary outcome measures.
Results and limitations: ECOG-PS >0, LM, Hb <10 g/dl, and shorter TFPC were significant prognostic factors for OS and PFS on multivariable analysis. Patients with zero, one, two, and three to four factors demonstrated median OS of 12.2, 6.7, 5.1, and 3.0 mo, respectively (concordance statistic = 0.638). Setting of prior chemotherapy (metastatic disease vs perioperative) and prior platinum agent (cisplatin or carboplatin) were not prognostic factors. External validation demonstrated a significant association of TFPC with PFS on univariable and most multivariable analyses, and with OS on univariable analyses. Limitations of retrospective analyses are applicable.
Conclusions: Shorter TFPC enhances prognostic classification independent of ECOG-PS >0, Hb <10 g/dl, and LM in the setting of second-line therapy for advanced UC. These data may facilitate drug development and interpretation of trials. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
C1 [Sonpavde, Guru; Khan, Awais] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA.
[Pond, Gregory R.] McMaster Univ, Hamilton, ON, Canada.
[Pond, Gregory R.] Ontario Clin Oncol Grp, Hamilton, ON, Canada.
[Fougeray, Ronan] Inst Rech Pierre Fabre, Boulogne, France.
[Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Choueiri, Toni K.; Qu, Angela Q.] Harvard Univ, Sch Med, Boston, MA USA.
[Vaughn, David J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Niegisch, Guenter; Albers, Peter] Univ Dusseldorf, D-40225 Dusseldorf, Germany.
[James, Nicholas D.] Univ Birmingham, Birmingham, W Midlands, England.
[Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Ko, Yoo-Joung] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Sridhar, Srikala S.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Galsky, Matthew D.] Mt Sinai Sch Med, Tisch Canc Ctr Inst, New York, NY USA.
[Petrylak, Daniel P.] Yale Canc Ctr, New Haven, CT USA.
[Vaishampayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA.
[Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Stadler, Walter M.; O'Donnell, Peter H.] Univ Chicago, Chicago, IL 60637 USA.
[Sternberg, Cora N.] San Camillo Hosp, Rome, Italy.
[Sternberg, Cora N.] Forlanini Hosp, Rome, Italy.
[Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Bellmunt, Joaquim] Univ Hosp Mar IMIM, Barcelona, Spain.
RP Bellmunt, J (reprint author), Hosp Mar, Paseig Maritim 25-29, Barcelona, Spain.
EM joaquim.bellmunt@gmail.com
OI Niegisch, Gunter/0000-0001-6929-8691; Rosenberg,
Jonathan/0000-0003-2637-4249
FU Boehringer-Ingelheim; AstraZeneca; Pierre-Fabre; BMS; Celgene; GSK; Eli
Lilly
FX Joaquim Bellmunt certifies that all conflicts of interest, including
specific financial interests and relationships and affiliations relevant
to the subject matter or materials discussed in the manuscript (eg,
employment/affiliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents
filed, received, or pending), are the following: G. Sonpavde, N.J.
Vogelzang, W. M. Stadler, P. H. O'Donnell, and D.J. Vaughn have received
research support from Boehringer-Ingelheim. R Fougeray is an employee of
Pierre-Fabre. T. K. Choueiri, A. Q. Qu, J.E. Rosenberg, and G. Sonpavde
have received research support from AstraZeneca. N.D. James, D.J.
Vaughn, and J.M. Bellmunt have received research support from
Pierre-Fabre. N.D. James also has received speaker fees from
Pierre-Fabre. Y.N. Wong has received research support from BMS. Y. Ko,
S. Sridhar, and G. Sonpavde have received research support from Celgene.
U.N. Vaishampayan and W. M. Stadler have received research support from
GSK, and G. Sonpavde has received speaker fees from GSK. M. D. Galsky
has received research support from Eli Lilly. G. Niegisch and P. Albers
have received research support from Eli Lilly and BMS.
NR 21
TC 43
Z9 43
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2013
VL 63
IS 4
BP 717
EP 723
DI 10.1016/j.eururo.2012.11.042
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 093LC
UT WOS:000315192400032
PM 23206856
ER
PT J
AU Taneja, AK
Bierry, G
Simeone, FJ
Chang, CY
Bredella, MA
Torriani, M
AF Taneja, Atul K.
Bierry, Guillaume
Simeone, F. Joseph
Chang, Connie Y.
Bredella, Miriam A.
Torriani, Martin
TI Diagnostic yield of CT-guided sampling in suspected sternoclavicular
joint infection
SO SKELETAL RADIOLOGY
LA English
DT Article
DE Sternoclavicular joint; Biopsy; Infectious arthritis; CT-guided
ID SEPTIC ARTHRITIS; COMPUTED-TOMOGRAPHY; BONE-BIOPSY; OSTEOMYELITIS;
CULTURES; STERNUM
AB To determine the prevalence of infection diagnosed by percutaneous computed tomography (CT)-guided sternoclavicular (SC) sampling in cases of suspected joint infection.
A retrospective search was performed in reports of SC joint CT-guided biopsies in adults from July 1992 to July 2012. We reviewed medical records, radiology, microbiology, laboratory, and surgical reports. A positive result was defined as demonstration of a pathogenic organism, either by microscopy or growth in culture, confirming the diagnosis of SC joint infection. A negative result was defined as the absence of such findings. Patients in whom sampling was unsuccessful or not subjected to microbiology were excluded. In addition, CT images were reviewed by the consensus of two musculoskeletal radiologists.
A total of 41 patients (mean age 57.1 years) underwent CT-guided SC joint sampling, 27 of whom underwent microbiology studies. Sampling was performed using core biopsy alone in 19 %, fine needle aspiration alone in 44 %, and aspiration combined with core biopsy in 37 %. Positive results were found in 52 % (14/27) of patients. Related diseases and predisposing conditions for infection were found in 79 % of positive patients. Negative results were found in 48 % (13/27) of patients. There were no procedure-related complications. The dominant CT findings were soft tissue swelling (negative group), and effusion and/or capsular hypertrophy/distension (positive group).
CT-guided sampling is a safe procedure with positive microbiological cultures in slightly more than half of cases.
C1 [Taneja, Atul K.; Bierry, Guillaume; Simeone, F. Joseph; Chang, Connie Y.; Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Taneja, Atul K.; Bierry, Guillaume; Simeone, F. Joseph; Chang, Connie Y.; Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Torriani, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St,YAW 6048, Boston, MA 02114 USA.
EM torriani.martin@mgh.harvard.edu
RI Taneja, Atul/N-3133-2014
OI Taneja, Atul/0000-0002-4655-2033
NR 25
TC 2
Z9 2
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2348
J9 SKELETAL RADIOL
JI Skeletal Radiol.
PD APR
PY 2013
VL 42
IS 4
BP 479
EP 485
DI 10.1007/s00256-012-1535-x
PG 7
WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
GA 090KN
UT WOS:000314978100004
PM 23179735
ER
PT J
AU Makris, N
Swaab, DF
van der Kouwe, A
Abbs, B
Boriel, D
Handa, RJ
Tobet, S
Goldstein, JM
AF Makris, Nikos
Swaab, Dick F.
van der Kouwe, Andre
Abbs, Brandon
Boriel, Denise
Handa, Robert J.
Tobet, Stuart
Goldstein, Jill M.
TI Volumetric parcellation methodology of the human hypothalamus in
neuroimaging: Normative data and sex differences
SO NEUROIMAGE
LA English
DT Article
DE Structural MRI; Volumetry; Hypothalamus; Hypothalamic nuclei; Tuberal
region; Sex differences
ID CORTICOTROPIN-RELEASING HORMONE; ADULT HUMAN BRAIN; PARAVENTRICULAR
NUCLEUS; AROUSAL CIRCUITRY; CEREBRAL-CORTEX; IN-VIVO; MRI; NEURONS;
SYSTEM; SCHIZOPHRENIA
AB There is increasing evidence regarding the importance of the hypothalamus for understanding sex differences in relation to neurological, psychiatric, endocrine and sleep disorders. Although different in histology, physiology, connections and function, multiple hypothalamic nuclei subserve non-voluntary functions and are nodal points for the purpose of maintaining homeostasis of the organism. Thus, given the critical importance of hypothalamic nuclei and their key multiple roles in regulating basic functions, it is important to develop the ability to conduct in vivo human studies of anatomic structure, volume, connectivity, and function of hypothalamic regions represented at the level of its nuclei. The goals of the present study were to develop a novel method of semi-automated volumetric parcellation for the human hypothalamus that could be used to investigate clinical conditions using MRI and to demonstrate its applicability. The proposed new method subdivides the hypothalamus into five parcels based on visible anatomic landmarks associated with specific nuclear groupings and was confirmed using two ex vivo hypothalami that were imaged in a 7 T (7 T) scanner and processed histologically. Imaging results were compared with histology from the same brain. Further, the method was applied to 44 healthy adults (26 men: 18 women, comparable on age, handedness, ethnicity, SES) to derive normative volumes and assess sex differences in hypothalamic regions using 1.5 T MRI. Men compared to women had a significantly larger total hypothalamus, relative to cerebrum size, similar for both hemispheres, a difference that was primarily driven by the tuberal region, with the sex effect size being largest in the superior tuberal region and, to a lesser extent, inferior tuberal region. Given the critical role of hypothalamic nuclei in multiple chronic diseases and the importance of sex differences, we argue that the use of the novel methodology presented here will allow for critical investigations of these disorders and further delineation of potential treatments, particularly sex-specific approaches to gene and drug discoveries that involve hypothalamic nuclei. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Makris, Nikos; Goldstein, Jill M.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA.
[Makris, Nikos] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Makris, Nikos; Boriel, Denise] MGH Ctr Morphometr Anal, Charlestown, MA 02129 USA.
[Makris, Nikos; van der Kouwe, Andre; Abbs, Brandon; Boriel, Denise; Goldstein, Jill M.] MGH & MIT Athinoula Martinos Biomed Imaging Ctr, Charlestown, MA 02129 USA.
[Swaab, Dick F.] Netherlands Inst Neurosci, Dept Neuropsychiat Disorders, NL-1105 BA Amsterdam, Netherlands.
[van der Kouwe, Andre] MGH, Dept Radiol, Charlestown, MA 02129 USA.
[Abbs, Brandon; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02120 USA.
[Abbs, Brandon; Goldstein, Jill M.] BWH, Dept Med, Div Womens Hlth, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA.
[Abbs, Brandon; Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Abbs, Brandon; Goldstein, Jill M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Handa, Robert J.] Univ Arizona, Coll Med, Dept Basic Med Sci, Phoenix, AZ 85004 USA.
[Tobet, Stuart] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA.
RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1 Brigham Circle,1620 Tremont St,3rd Flr, Boston, MA 02120 USA.
EM nikos@cma.mgh.harvard.edu; d.f.swaab@nin.knaw.nl;
andre@nmr.mgh.harvard.edu; babbs@partners.org; dlb@cma.mgh.harvard.edu;
rhanda@arizona.edu; Stuart.Tobet@colostate.edu;
jill_goldstein@hms.harvard.edu
RI Kruisbrink, Jenneke/D-8060-2013;
OI Tobet, Stuart/0000-0002-1615-7331
FU ORWH-NIMH [R21MH084041]; ORWH-NIMH SCOR [P50MH082679]; NIDA
[R01DA027804]
FX This study was primarily supported by ORWH-NIMH R21MH084041 (Makris, PI)
and ORWH-NIMH SCOR P50MH082679, (Goldstein, Tobet, Handa, PI). Some of
the methodological work related to addiction was in part supported by
NIDA R01DA027804 (Makris, PI). The authors also thank Larry Seidman,
Ph.D. [NIMH R01 MH63951 (Seidman, PI) and NIMH R01 MH56956 (Goldstein,
PI)] for contributing to original collection of the healthy control
subjects used in these analyses, Bruce Rosen, MD, PhD for his
administrative support in the use of the 7 T magnet at MGH, and Jonathan
Kaiser, M.S. for help in image construction.
NR 53
TC 13
Z9 15
U1 2
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD APR 1
PY 2013
VL 69
BP 1
EP 10
DI 10.1016/j.neuroimage.2012.12.008
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 085PX
UT WOS:000314627800001
PM 23247186
ER
PT J
AU McNab, JA
Polimeni, JR
Wang, RP
Augustinack, JC
Fujimoto, K
Stevens, A
Janssens, T
Farivar, R
Folkerth, RD
Vanduffel, W
Wald, LL
AF McNab, Jennifer A.
Polimeni, Jonathan R.
Wang, Ruopeng
Augustinack, Jean C.
Fujimoto, Kyoko
Stevens, Allison
Janssens, Thomas
Farivar, Reza
Folkerth, Rebecca D.
Vanduffel, Wim
Wald, Lawrence L.
TI Surface based analysis of diffusion orientation for identifying
architectonic domains in the in vivo human cortex
SO NEUROIMAGE
LA English
DT Article
DE Cerebral cortex; Diffusion tensor imaging; Laminar analysis; Human;
Brain
ID ANISOTROPIC WATER DIFFUSION; MAGNETIC-RESONANCE IMAGES; HUMAN
CEREBRAL-CORTEX; HUMAN BRAIN; CORTICAL THICKNESS; MRI; ORGANIZATION;
SEGMENTATION; REGISTRATION; CONNECTIONS
AB Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in gray matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical gray matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1 mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1. (c) 2012 Elsevier Inc. All rights reserved.
C1 [McNab, Jennifer A.] Stanford Univ, RM Lucas Ctr Imaging, Stanford, CA 94305 USA.
[McNab, Jennifer A.; Polimeni, Jonathan R.; Wang, Ruopeng; Augustinack, Jean C.; Fujimoto, Kyoko; Stevens, Allison; Janssens, Thomas; Farivar, Reza; Vanduffel, Wim; Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Imaging, Boston, MA USA.
[Vanduffel, Wim] KU Leuven Med Sch, Lab Neuro & Psychophysiol, Louvain, Belgium.
[Farivar, Reza] McGill Univ, Dept Opthalmol, McGill Vis Res Unit, Montreal, PQ, Canada.
[Folkerth, Rebecca D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Folkerth, Rebecca D.] Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp Boston, Boston, MA 02115 USA.
RP McNab, JA (reprint author), Stanford Univ, Dept Radiol, RM Lucas Ctr Imaging, 1201 Welch Rd,Room P270, Stanford, CA 94305 USA.
EM mcnabj@stanford.edu
RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009;
OI Polimeni, Jonathan/0000-0002-1348-1179; Fujimoto,
Kyoko/0000-0002-0087-1397
FU Canadian Institute for Health Research (Fellowship); NIH [U01MH093765,
P41RR014075/R01EB006847, S10RR019307]
FX Many thanks to Drs. George Dai and Karl Helmer for their assistance in
scanning on the 4.7 T scanner. Thanks to Michelle Roy, Sita Kakunoori
and Louis Vinke for their help with sample preparation. Many thanks for
informative discussions with Drs. Bruce Rosen, Julien Cohen-Adad, Thomas
Witzel, Thomas Benner, Himanshu Bhat, Keith Heberlein, Thorsten Feiweier
and Brian Edlow. Thanks to Annelies Gerits and Helen Deng for help with
animal imaging experiments. Thanks to Marian Slaney for her assistance
in the neuropathology lab. This work was funded by the Canadian
Institute for Health Research (Fellowship) and NIH: U01MH093765,
P41RR014075/R01EB006847, and S10RR019307.
NR 64
TC 29
Z9 29
U1 1
U2 19
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD APR 1
PY 2013
VL 69
BP 87
EP 100
DI 10.1016/j.neuroimage.2012.11.065
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 085PX
UT WOS:000314627800010
PM 23247190
ER
PT J
AU Wang, Q
Wu, PC
Dong, DZ
Ivanova, I
Chu, E
Zeliadt, S
Vesselle, H
Wu, DY
AF Wang, Qin
Wu, Peter C.
Dong, David Z.
Ivanova, Iana
Chu, Elizabeth
Zeliadt, Steven
Vesselle, Hubert
Wu, Daniel Y.
TI Polyploidy road to therapy-induced cellular senescence and escape
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE polyploidy; cellular senescence; Cdc2; Cdk1; cancer therapeutics
ID ADRIAMYCIN-INDUCED SENESCENCE; BREAST-TUMOR CELLS; MITOTIC CATASTROPHE;
CANCER CELLS; GIANT-CELLS; DNA-DAMAGE; ACTIVATION; KINASE; APOPTOSIS;
DIVISION
AB Therapy-induced cellular senescence (TCS), characterized by prolonged cell cycle arrest, is an in vivo response of human cancers to chemotherapy and radiation. Unfortunately, TCS is reversible for a subset of senescent cells, leading to cellular reproliferation and ultimately tumor progression. This invariable consequence of TCS recapitulates the clinical treatment experience of patients with advanced cancer. We report the findings of a clinicopathological study in patients with locally advanced non-small cell lung cancer demonstrating that marker of in vivo TCS following neoadjuvant therapy prognosticate adverse clinical outcome. In our efforts to elucidate key molecular pathways underlying TCS and cell cycle escape, we have previously shown that the deregulation of mitotic kinase Cdk1 and its downstream effectors are important mediators of survival and cell cycle reentry. We now report that aberrant expression of Cdk1 interferes with apoptosis and promotes the formation of polyploid senescent cells during TCS. These polyploid senescent cells represent important transition states through which escape preferentially occurs. The Cdk1 pathway is in part modulated differentially by p21 and p27 two members of the KIP cyclin-dependent kinase inhibitor family during TCS. Altogether, these studies underscore the importance of TCS in cancer therapeutics.
C1 [Wang, Qin; Wu, Peter C.; Ivanova, Iana; Chu, Elizabeth; Wu, Daniel Y.] VA Puget Sound Hlth Care Syst, Seattle Inst Biomed & Clin Res, Seattle, WA 98108 USA.
[Wu, Peter C.] VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA 98108 USA.
[Wu, Peter C.] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Dong, David Z.] VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA 98108 USA.
[Zeliadt, Steven] VA Puget Sound Hlth Care Syst, Dept Hlth Serv, Seattle, WA 98108 USA.
[Vesselle, Hubert] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Wu, Daniel Y.] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA.
[Wu, Daniel Y.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Wang, Q (reprint author), VA Puget Sound Hlth Care Syst, Seattle Inst Biomed & Clin Res, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM proteins@hotmail.com
FU National Cancer Institute [R01-CA113892-01]; Veteran Affairs Office of
Research and Development Medical Research Service; Veteran Affairs
Office of Research & Development Medical Research Service (Biomedical
Laboratory R&D Career Development Award-2)
FX Grant sponsor: National Cancer Institute; Grant number: R01-CA113892-01;
Grant sponsor: Veteran Affairs Office of Research and Development
Medical Research Service; This material is based upon work supported by
the National Cancer Institute (R01-CA113892-01, D. Wu) and Veteran
Affairs Office of Research & Development Medical Research Service
(Biomedical Laboratory R&D Career Development Award-2, P. Wu). The
authors thank Dr. Liu Yang for his critical reading of our manuscript
and his insightful suggestions. They also thank Dr. Chris Guthrie for
assisting to obtain the time lapse images.
NR 49
TC 21
Z9 21
U1 0
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD APR 1
PY 2013
VL 132
IS 7
BP 1505
EP 1515
DI 10.1002/ijc.27810
PG 11
WC Oncology
SC Oncology
GA 079NN
UT WOS:000314177500003
PM 22945332
ER
PT J
AU Cuk, K
Zucknick, M
Heil, J
Madhavan, D
Schott, S
Turchinovich, A
Arlt, D
Rath, M
Sohn, C
Benner, A
Junkermann, H
Schneeweiss, A
Burwinkel, B
AF Cuk, Katarina
Zucknick, Manuela
Heil, Joerg
Madhavan, Dharanija
Schott, Sarah
Turchinovich, Andrey
Arlt, Dorit
Rath, Michelle
Sohn, Christof
Benner, Axel
Junkermann, Hans
Schneeweiss, Andreas
Burwinkel, Barbara
TI Circulating microRNAs in plasma as early detection markers for breast
cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE microRNA; circulating microRNA; breast cancer; early detection;
molecular marker
ID BLOOD-BASED MARKERS; SERUM; BIOMARKERS; MECHANISM; CARCINOMA; LEUKEMIA;
PCR
AB In recent years, circulating miRNAs have attracted a great deal of attention as promising novel markers for various diseases. Here, we investigated their potential to serve as minimally invasive, early detection markers for breast cancer in blood plasma. We profiled miRNAs extracted from the plasma of early stage breast cancer patients (taken at the time-point of diagnosis) and healthy control individuals using TaqMan low-density arrays (TLDA). Selected candidates identified in the initial screen were further validated in an extended study cohort of 207 individuals including 127 sporadic breast cancer cases and 80 healthy controls via RT-qPCR. Four miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) were shown to be significantly upregulated in the plasma of breast cancer patients. ROC curve analysis showed that the combination of only three miRNAs (miR-148b, miR-409-3p and miR-801) had an equal discriminatory power between breast cancer cases and healthy controls as all four miRNAs together (AUC = 0.69). In conclusion, the identified miRNAs might be of potential use in the development of a multimarker blood-based test to complement and improve early detection of breast cancer. Such a multimarker blood test might for instance provide a prescreening tool, especially for younger women, to facilitate decisions about which individuals to recommend for further diagnostic tests.
C1 [Cuk, Katarina; Zucknick, Manuela; Benner, Axel] German Canc Res Ctr, Div Biostat, Heidelberg, BW, Germany.
[Heil, Joerg; Schott, Sarah; Sohn, Christof; Junkermann, Hans; Schneeweiss, Andreas] Univ Womens Clin, Dept Gynecol & Obstet, Heidelberg, BW, Germany.
[Arlt, Dorit] Univ Med Ctr Freiburg, CCI, Freiburg, BW, Germany.
[Arlt, Dorit] Univ Freiburg, D-79106 Freiburg, BW, Germany.
[Rath, Michelle] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Schneeweiss, Andreas; Burwinkel, Barbara] Natl Ctr Tumor Dis NCT, Heidelberg, BW, Germany.
RP Cuk, K (reprint author), German Canc Res Ctr, Div Biostat, Heidelberg, BW, Germany.
EM k.cuk@dkfz.de
RI turchinovich, andrey/B-2700-2014;
OI Heil, Joerg/0000-0002-4684-9099
FU Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research
Center (DKFZ)
FX Grant sponsors: Dietmar-Hopp Foundation, Helmholtz Society and German
Cancer Research Center (DKFZ)
NR 45
TC 91
Z9 99
U1 3
U2 77
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD APR 1
PY 2013
VL 132
IS 7
BP 1602
EP 1612
DI 10.1002/ijc.27799
PG 11
WC Oncology
SC Oncology
GA 079NN
UT WOS:000314177500013
PM 22927033
ER
PT J
AU Cacciola, JS
Alterman, AI
DePhilippis, D
Drapkin, ML
Valadez, C
Fala, NC
Oslin, D
Mckay, JR
AF Cacciola, John S.
Alterman, Arthur I.
DePhilippis, Dominick
Drapkin, Michelle L.
Valadez, Charles, Jr.
Fala, Natalie C.
Oslin, David
Mckay, James R.
TI Development and initial evaluation of the Brief Addiction Monitor (BAM)
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Addiction; Substance abuse; Reliability; Validity; Assessment
ID SUBSTANCE-ABUSE TREATMENT; RECOVERY MANAGEMENT CHECKUPS; USE DISORDERS;
FOLLOW-UP; TREATMENT RETENTION; ARBITRARY METRICS; SEVERITY INDEX;
ALCOHOL-USE; RELIABILITY; VALIDITY
AB This project developed and tested a 17-item monitoring instrument covering important substance use related behaviors to support measurement-based care and outcomes assessment. The study consisted of two phases, an instrument development phase and an initial study to examine its psychometric properties. Participants were 175 patients entering VA outpatient substance abuse treatment. The findings revealed that this Brief Addiction Monitor (BAM) exhibited acceptable characteristics. Exploratory factor analysis yielded three summary factors; recovery protection, physical and psychological problems, and substance use and risk. The root mean square error of approximation estimate was acceptable and the factors had alpha values exceeding or approaching 0.70. All three factors were sensitive to change and had excellent test-retest reliability. Predictive validity was demonstrated for two factors; recovery protection, and substance use and risk. At the item level, there was little indication of inappropriate response patterns. Change over time was significant for most items, and test-retest reliability was acceptable for nearly all items. Additional research is warranted to further establish the BAM's reliability, validity and usefulness. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Cacciola, John S.] Treatment Res Inst, Philadelphia, PA 19106 USA.
[Cacciola, John S.; Alterman, Arthur I.; DePhilippis, Dominick; Drapkin, Michelle L.; Oslin, David; Mckay, James R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[DePhilippis, Dominick; Drapkin, Michelle L.; Oslin, David; Mckay, James R.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
[Valadez, Charles, Jr.] La Salle Univ, Philadelphia, PA 19141 USA.
[Fala, Natalie C.] Florida Inst Technol, Melbourne, FL 32901 USA.
RP Cacciola, JS (reprint author), Treatment Res Inst, 600 Publ Ledger Bldg,150 S Independence Mall W, Philadelphia, PA 19106 USA.
EM jcacciola@tresearch.org
FU NIDA NIH HHS [R01 DA021154, K24 DA029062, R01 DA21154]; PHS HHS [NIDA
K24DA029062]
NR 55
TC 24
Z9 24
U1 2
U2 24
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 APR
PY 2013
VL 44
IS 3
BP 256
EP 263
DI 10.1016/j.jsat.2012.07.013
PG 8
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 077EQ
UT WOS:000314011100002
PM 22898042
ER
PT J
AU Ataer-Cansizoglu, E
Bas, E
Kalpathy-Cramer, J
Sharp, GC
Erdogmus, D
AF Ataer-Cansizoglu, Esra
Bas, Erhan
Kalpathy-Cramer, Jayashree
Sharp, Greg C.
Erdogmus, Deniz
TI Contour-based shape representation using principal curves
SO PATTERN RECOGNITION
LA English
DT Article
DE Shape representation and analysis; Curve/contour matching
ID DIGITAL PLANAR CURVES; POLYGONAL-APPROXIMATION; DOMINANT POINTS;
SEGMENTATION; ALGORITHM
AB Extraction and representation of contours are challenging problems and are crucial for many image processing applications. In this study, given a membership function that returns the score of a point belonging to a contour, we propose a method for contour representation based on the principal curve (PC) of this function. The proposed method provides a piecewise linear representation of the contour with fewer points while preserving shape. Varied experiments are conducted, including lung boundary representation in CT images and shape representation in handwritten images. The results show that the technique provides accurate shape representation. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Ataer-Cansizoglu, Esra; Erdogmus, Deniz] Northeastern Univ, Cognit Syst Lab, Boston, MA 02115 USA.
[Bas, Erhan] GE Global Res, Niskayuna, NY USA.
[Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
RP Ataer-Cansizoglu, E (reprint author), Northeastern Univ, Cognit Syst Lab, Boston, MA 02115 USA.
EM ataer@ece.neu.edu
OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618
FU NSF [BCS-1027724, IIS1118061, IIS-1149570]; NIH [8P41GM103545-14]
FX We thank Murat Akcakaya and Sarah Brown for assistance with editing the
manuscript. This work was partially supported by NSF under grants
BCS-1027724, IIS1118061, IIS-1149570, and by NIH under grant
8P41GM103545-14.
NR 37
TC 4
Z9 4
U1 3
U2 29
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0031-3203
EI 1873-5142
J9 PATTERN RECOGN
JI Pattern Recognit.
PD APR
PY 2013
VL 46
IS 4
BP 1140
EP 1150
DI 10.1016/j.patcog.2012.10.014
PG 11
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA 075BI
UT WOS:000313858400004
ER
PT J
AU Leshner, AF
Tom, SR
Kern, RS
AF Leshner, Anna F.
Tom, Shelley R.
Kern, Robert S.
TI Errorless learning and social problem solving ability in schizophrenia:
An examination of the compensatory effects of training
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Cognitive rehabilitation; Errorless learning; Compensatory; Memory;
Severe mental illness
ID OF-THE-LITERATURE; COGNITIVE REHABILITATION; NEUROCOGNITIVE DEFICITS;
RETROGRADE-AMNESIA; ALZHEIMERS-DISEASE; MEMORY; INDIVIDUALS;
PERFORMANCE; METAANALYSIS; REMEDIATION
AB Compensatory approaches to cognitive rehabilitation in schizophrenia aim to improve functioning by bypassing or compensating for impaired areas of cognition. At present, there is little empirical evidence that these approaches actually compensate for neurocognitive impairments in improving community functioning. This study examined the effects of errorless learning (EL), a compensatory cognitive rehabilitation approach, on social problem solving ability in schizophrenia. The study included 60 outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder. Participants received a baseline battery to assess explicit and implicit memory functioning. Participants were stratified according to gender and level of memory functioning and then randomized to EL or symptom management training. Training was conducted over two days lasting a total of 6 h for each group. Assessment of social problem-solving ability, using the Assessment of Interpersonal Problem Solving Skills (AIPSS), was conducted after completion of training and at a 3-month follow-up without further intervention. Results from hierarchical multiple regression and analysis of covariance each supported the compensatory effects of training. These findings indicate that EL facilitates learning of new skills across varying levels of memory impairment. Future efforts may aim to explore the specific neurocognitive mechanisms involved in EL Published by Elsevier Ireland Ltd.
C1 [Leshner, Anna F.; Tom, Shelley R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Kern, Robert S.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Kern, Robert S.] VISN 22 Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA.
RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Ctr MIRECC 210, Bldg 210,Room 116,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM rkern@ucla.edu
FU Stanley Medical Research Institute; NIMH [R01 MH082939]; VA Merit Award
FX This project was supported in part by Stanley Medical Research
Institute, the NIMH Grant R01 MH082939, and a VA Merit Award received by
R. Kern (Principal Investigator).
NR 46
TC 6
Z9 6
U1 2
U2 26
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 MAR 30
PY 2013
VL 206
IS 1
BP 1
EP 7
DI 10.1016/j.psychres.2012.10.007
PG 7
WC Psychiatry
SC Psychiatry
GA 124DB
UT WOS:000317442900001
PM 23158835
ER
PT J
AU Pilkonis, PA
Choi, SW
Salsman, JM
Butt, Z
Moore, TL
Lawrence, SM
Zill, N
Cyranowski, JM
Kelly, MAR
Knox, SS
Cella, D
AF Pilkonis, Paul A.
Choi, Seung W.
Salsman, John M.
Butt, Zeeshan
Moore, Tara L.
Lawrence, Suzanne M.
Zill, Nicholas
Cyranowski, Jill M.
Kelly, Morgen A. R.
Knox, Sarah S.
Cella, David
TI Assessment of self-reported negative affect in the NIH Toolbox
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Sadness; Fear; Anger; Item response theory; Measurement
ID ITEM RESPONSE THEORY; QUALITY-OF-LIFE; DEPRESSIVE SYMPTOMS; TRIPARTITE
MODEL; EMOTIONAL DISORDERS; CHILDRENS REPORTS; ANXIETY; MOTHERS; SCALES;
PARENT
AB We report on the selection of self-report measures for inclusion in the NIH Toolbox that are suitable for assessing the full range of negative affect including sadness, fear, and anger. The Toolbox is intended to serve as a "core battery" of assessment tools for cognition, sensation, motor function, and emotional health that will help to overcome the lack of consistency in measures used across epidemiological, observational, and intervention studies. A secondary goal of the NIH Toolbox is the identification of measures that are flexible, efficient, and precise, an agenda best fulfilled by the use of item banks calibrated with models from item response theory (IRT) and suitable for adaptive testing. Results from a sample of 1763 respondents supported use of the adult and pediatric item banks for emotional distress from the Patient-Reported Outcomes Measurement Information System (PROMIS) as a starting point for capturing the full range of negative affect in healthy individuals. Content coverage for the adult Toolbox was also enhanced by the development of a scale for somatic arousal using items from the Mood and Anxiety Symptom Questionnaire (MASQ) and scales for hostility and physical aggression using items from the Buss-Perry Aggression Questionnaire (BPAQ). (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Pilkonis, Paul A.; Moore, Tara L.; Lawrence, Suzanne M.; Cyranowski, Jill M.; Kelly, Morgen A. R.] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Choi, Seung W.; Salsman, John M.; Butt, Zeeshan; Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Salsman, John M.; Butt, Zeeshan; Cella, David] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Butt, Zeeshan] Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA.
[Butt, Zeeshan; Cella, David] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA.
[Zill, Nicholas] Westat Corp, Rockville, MD USA.
[Kelly, Morgen A. R.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Knox, Sarah S.] W Virginia Univ, Sch Med, Dept Community Med, Morgantown, WV 26506 USA.
RP Pilkonis, PA (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM pilkonispa@upmc.edu
FU Federal funds from the Blueprint for Neuroscience Research; Office of
Behavioral and Social Sciences Research, National Institutes of Health
[HHS-N-260-2006-00007-C]
FX This project is funded in whole or in part with Federal funds from the
Blueprint for Neuroscience Research and the Office of Behavioral and
Social Sciences Research, National Institutes of Health, under Contract
no. HHS-N-260-2006-00007-C.
NR 67
TC 5
Z9 5
U1 6
U2 19
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 MAR 30
PY 2013
VL 206
IS 1
BP 88
EP 97
DI 10.1016/j.psychres.2012.09.034
PG 10
WC Psychiatry
SC Psychiatry
GA 124DB
UT WOS:000317442900015
PM 23083918
ER
PT J
AU Roussos, P
McClure, MM
Hazlett, EA
New, AS
Siever, LJ
Bitsios, P
Giakoumaki, SG
AF Roussos, Panos
McClure, Margaret M.
Hazlett, Erin A.
New, Antonia S.
Siever, Larry J.
Bitsios, Panos
Giakoumaki, Stella G.
TI CACNA1C as a risk factor for schizotypal personality disorder and
schizotypy in healthy individuals
SO PSYCHIATRY RESEARCH
LA English
DT Letter
ID BIPOLAR DISORDER; ASSOCIATION ANALYSIS; SCHIZOPHRENIA; ANK3
C1 [Roussos, Panos; McClure, Margaret M.; Hazlett, Erin A.; New, Antonia S.; Siever, Larry J.] Mt Sinai Sch Med, Dept Psychiat, Bronx, NY 10468 USA.
[Roussos, Panos; McClure, Margaret M.; Hazlett, Erin A.; New, Antonia S.; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN 3, Bronx, NY USA.
[Roussos, Panos; Bitsios, Panos; Giakoumaki, Stella G.] Univ Crete, Fac Med, Dept Psychiat & Behav Sci, Iraklion, Crete, Greece.
RP Roussos, P (reprint author), Mt Sinai Sch Med, Dept Psychiat, Room 4F-21,130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM panagiotis.roussos@mssm.edu
RI Roussos, Panos/J-7090-2013
OI Roussos, Panos/0000-0002-4640-6239
FU NIMH NIH HHS [R01 MH056140]
NR 10
TC 16
Z9 16
U1 0
U2 10
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 MAR 30
PY 2013
VL 206
IS 1
BP 122
EP 123
DI 10.1016/j.psychres.2012.08.039
PG 2
WC Psychiatry
SC Psychiatry
GA 124DB
UT WOS:000317442900021
PM 22985546
ER
PT J
AU Foland-Ross, LC
Thompson, PM
Sugar, CA
Narr, KL
Penfold, C
Vasquez, RE
Townsend, J
Fischer, J
Saharan, P
Bearden, CE
Altshuler, LL
AF Foland-Ross, Lara C.
Thompson, Paul M.
Sugar, Catherine A.
Narr, Katherine L.
Penfold, Conor
Vasquez, Roxanne E.
Townsend, Jennifer
Fischer, Jeffrey
Saharan, Priya
Bearden, Carrie E.
Altshuler, Lori L.
TI Three-dimensional mapping of hippocampal and amygdalar structure in
euthymic adults with bipolar disorder not treated with lithium
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Mood disorder; Magnetic resonance imaging; Hippocampus; Amygdala;
Lithium; Bipolar disorder
ID FACIAL EMOTION RECOGNITION; TEMPORAL-LOBE STRUCTURES; RATING-SCALE;
WHITE-MATTER; YOUNG-ADULTS; MRI; VOLUME; SCHIZOPHRENIA; BRAIN; MANIA
AB Structural neuroimaging studies of the amygdala and hippocampus in bipolar disorder have been largely inconsistent. This may be due in part to differences in the proportion of subjects taking lithium or experiencing an acute mood state, as both factors have recently been shown to influence gray matter structure. To avoid these problems, we evaluated euthymic subjects not currently taking lithium. Thirty-two subjects with bipolar type I disorder and 32 healthy subjects were scanned using magnetic resonance imaging. Subcortical regions were manually traced, and converted to three-dimensional meshes to evaluate the main effect of bipolar illness on radial distance. Statistical analyses found no evidence for a main effect of bipolar illness in either region, although exploratory analyses found a significant age by diagnosis interaction in the right amygdala, as well as positive associations between radial distance of the left amygdala and both prior hospitalizations for mania and current medication status. These findings suggest that, when not treated with lithium or in an acute mood state, patients with bipolar disorder exhibit no structural abnormalities of the amygdala or hippocampus. Future studies, nevertheless, that further elucidate the impact of age, course of illness, and medication on amygdala structure in bipolar disorder are warranted. Published by Elsevier Ireland Ltd.
C1 [Foland-Ross, Lara C.; Thompson, Paul M.; Saharan, Priya] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA.
[Sugar, Catherine A.; Narr, Katherine L.; Penfold, Conor; Vasquez, Roxanne E.; Townsend, Jennifer; Fischer, Jeffrey; Bearden, Carrie E.; Altshuler, Lori L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA.
[Altshuler, Lori L.] West Los Angeles Healthcare Ctr, Dept Psychiat, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Altshuler, LL (reprint author), UCLA Mood Disorders Res Program, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA.
EM laltshuler@mednet.ucla.edu
FU National Institute of Mental Health [MH078556, MH075944, MH01848];
National Association for Research on Schizophrenia and Affective
Disorders (NARSAD); Brain Mapping Medical Research Organization; Brain
Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson
Foundation; William M. and Linda R. Dietel Philanthropic Fund at the
Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer
Jones-Simon Foundation; Capital Group Companies Charitable Foundation;
Robson Family; Northstar Fund; National Center for Research Resources
(NCRR), a component of the National Institutes of Health (NIH) [RR12169,
RR13642, RR00865]
FX This work was supported by Grants from the National Institute of Mental
Health (MH078556 to LCFR, and MH075944 and MH01848 to LLA). Additional
support for algorithm development was provided by the NIA, NIBIB, and
the National Center for Research Resources (AG016570, EB01651, RR019771
to PT). For their generous support, the authors also thank the National
Association for Research on Schizophrenia and Affective Disorders
(NARSAD), Brain Mapping Medical Research Organization, Brain Mapping
Support Foundation, Pierson-Lovelace Foundation, The Ahmanson
Foundation, William M. and Linda R. Dietel Philanthropic Fund at the
Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer
Jones-Simon Foundation, Capital Group Companies Charitable Foundation,
Robson Family and Northstar Fund. The project was also supported by
Grants RR12169, RR13642 and RR00865 from the National Center for
Research Resources (NCRR), a component of the National Institutes of
Health (NIH).
NR 54
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U1 0
U2 5
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 MAR 30
PY 2013
VL 211
IS 3
BP 195
EP 201
DI 10.1016/j.pscychresns.2012.08.002
PG 7
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 123HN
UT WOS:000317379100002
PM 23149020
ER
PT J
AU Hoogenboom, WS
Perlis, RH
Smoller, JW
Zeng-Treitler, Q
Gainer, VS
Murphy, SN
Churchill, SE
Kohane, IS
Shenton, ME
Iosifescu, DV
AF Hoogenboom, Wouter S.
Perlis, Roy H.
Smoller, Jordan W.
Zeng-Treitler, Qing
Gainer, Vivian S.
Murphy, Shawn N.
Churchill, Susanne E.
Kohane, Isaac S.
Shenton, Martha E.
Iosifescu, Dan V.
TI Feasibility of studying brain morphology in major depressive disorder
with structural magnetic resonance imaging and clinical data from the
electronic medical record: A pilot study
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Major depressive disorder (MDD); Refractory depression; Structural MRI;
Hippocampus; Legacy data; Natural language processing
ID TREATMENT-RESISTANT DEPRESSION; HUMAN CEREBRAL-CORTEX; OF-THE-ART;
HIPPOCAMPAL VOLUME; DISCOVERY RESEARCH; SEGMENTATION; MRI;
ABNORMALITIES; SCHIZOPHRENIA; METAANALYSIS
AB For certain research questions related to long-term outcomes or to rare disorders, designing prospective studies is impractical or prohibitively expensive. Such studies could instead utilize clinical and magnetic resonance imaging data (MRI) collected as part of routine clinical care, stored in the electronic medical record (EMR). Using major depressive disorder (MDD) as a disease model, we examined the feasibility of studying brain morphology and associations with remission using clinical and MRI data exclusively drawn from the EMR. Advanced automated tools were used to select MDD patients and controls from the EMR who had brain MRI data, but no diagnosed brain pathology. MDD patients were further assessed for remission status by review of clinical charts. Twenty MDD patients (eight full-remitters, six partial-remitters, and six non-remitters), and 15 healthy control subjects met all study criteria for advanced morphometric analyses. Compared to controls, MDD patients had significantly smaller right rostral-anterior cingulate volume, and level of non-remission was associated with smaller left hippocampus and left rostral-middle frontal gyrus volume. The use of EMR data for psychiatric research may provide a timely and cost-effective approach with the potential to generate large study samples reflective of the real population with the illness studied. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Hoogenboom, Wouter S.; Perlis, Roy H.; Iosifescu, Dan V.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA.
[Hoogenboom, Wouter S.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Dept Psychiat,Med Sch, Boston, MA 02215 USA.
[Perlis, Roy H.] Massachusetts Gen Hosp, Lab Psychiat Pharmacogen, Ctr Human Genet Res, Boston, MA 02114 USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA.
[Zeng-Treitler, Qing] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84112 USA.
[Zeng-Treitler, Qing] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT 84148 USA.
[Gainer, Vivian S.; Murphy, Shawn N.] Partners HealthCare Syst Inc, Informat Syst, Charlestown, MA 02129 USA.
[Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA.
[Churchill, Susanne E.; Kohane, Isaac S.] Brigham & Womens Hosp, Natl Ctr Biomed Comp 2B2, Boston, MA 02215 USA.
[Shenton, Martha E.] VA Boston Healthcare Syst, Clin Neurosci Div, Lab Neurosci, Dept Psychiat,Brockton Div, Brockton, MA 02301 USA.
[Iosifescu, Dan V.] Mt Sinai Sch Med, Mood & Anxiety Disorders Program, New York, NY 10029 USA.
RP Hoogenboom, WS (reprint author), Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Dept Psychiat,Med Sch, 1249 Boylston St, Boston, MA 02215 USA.
EM hoogenboomw@gmail.com
FU Driving Biological Project by the i2b2 grant (National Institutes of
Health) [NIH U54-LM008748]; National Institutes of Health Career
Development Award [K23 MH067111]; National Institutes of Health [R01 MH
50740]; Department of Veterans Affairs (VA) (VA Merit Award); Department
of Veterans Affairs (VA) (VA Schizophrenia Research Center Grant);
National Institute of Mental Health [MH086026]
FX This work is funded as a Driving Biological Project (PI: Dr. Iosifescu)
by the i2b2 grant (National Institutes of Health, NIH U54-LM008748; PI:
Dr. Kohane). Dr. Iosifescu is supported by the National Institutes of
Health Career Development Award K23 MH067111. Dr. Shenton is supported
by grants from the National Institutes of Health (R01 MH 50740), and the
Department of Veterans Affairs (VA) (VA Merit Award and VA Schizophrenia
Research Center Grant). Dr. Perlis is supported by a grant from the
National Institute of Mental Health (MH086026). The authors thank Victor
Castro, B.S., for his assistance in collecting data from the Research
Patient Data Registry; Sergey Goryachev, M.S., for his assistance with
natural language processing; Kenneth Nesbitt, for providing access to
magnetic resonance imaging data from Massachusetts General Hospital; Dr.
Bouix and Dr. Kubicki, for their advice in the development of the
imaging study; and special thanks to all research assistants at the
psychiatry neuroimaging laboratory for their kind help at the time of
this study.
NR 52
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U1 0
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD MAR 30
PY 2013
VL 211
IS 3
BP 202
EP 213
DI 10.1016/j.pscychresns.2012.07.007
PG 12
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 123HN
UT WOS:000317379100003
PM 23149041
ER
PT J
AU Xiang, SH
Pacheco, B
Bowder, D
Yuan, W
Sodroski, J
AF Xiang, Shi-hua
Pacheco, Beatriz
Bowder, Dane
Yuan, Wen
Sodroski, Joseph
TI Characterization of a dual-tropic Human immunodeficiency virus (HIV-1)
strain derived from the prototypical X4 isolate HXBc2
SO VIROLOGY
LA English
DT Article
DE HIV-1; Envelope glycoproteins; Entry; Tropism; Gp120; V3 loop; CCR5;
CXCR4; Chemokine receptor; Trimer
ID 2ND EXTRACELLULAR LOOP; ENVELOPE GLYCOPROTEIN TRIMERS; T-CELL-LINE; V3
LOOP; CORECEPTOR USAGE; CHEMOKINE RECEPTORS; MONOCLONAL-ANTIBODY;
SYNCYTIUM FORMATION; MACROPHAGE TROPISM; MEMBRANE-FUSION
AB Human immunodeficiency virus type 1 (HIV-1) coreceptor usage and tropism can be modulated by the V3 loop sequence of the gp120 exterior envelope glycoprotein. For coreceptors, R5 viruses use CCR5, X4 viruses use CXCR4, and dual-tropic (R5X4) viruses use either CCR5 or CXCR4. To understand the requirements for dual tropism, we derived and analyzed a dual-tropic variant of an X4 virus. Changes in the V3 base, which allow gp120 to interact with the tyrosine-sulfated CCR5 N-terminus, and deletion of residues 310/311 in the V3 tip were necessary for efficient CCR5 binding and utilization. Thus, both sets of V3 changes allowed CCR5 utilization with retention of the ability to use CXCR4. We also found that the stable association of gp120 with the trimeric envelope glycoprotein complex in R5X4 viruses, as in X4 viruses, is less sensitive to V3 loop changes than gp120-trimer association in R5 viruses. Published by Elsevier Inc.
C1 [Xiang, Shi-hua; Pacheco, Beatriz; Yuan, Wen; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Xiang, Shi-hua; Pacheco, Beatriz; Yuan, Wen; Sodroski, Joseph] Harvard Univ, Sch Med, Div Aids, Dept Microbiol & Immunobiol, Boston, MA 02215 USA.
[Xiang, Shi-hua; Bowder, Dane] Univ Nebraska, Nebraska Ctr Virol, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Sodroski, Joseph] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA.
[Sodroski, Joseph] Harvard Univ, Cambridge, MA 02138 USA.
RP Xiang, SH (reprint author), Univ Nebraska, Nebraska Ctr Virol, Sch Vet Med & Biomed Sci, Morrison Ctr 337,4240 Fair St, Lincoln, NE 68583 USA.
EM sxiang2@unl.edu
FU National Institutes of Health [AI24755, AI67854]; International AIDS
Vaccine Initiative; Bill and Melinda Gates Foundation
FX We thank Yvette McLaughlin and Elizabeth Carpelan for manuscript
preparation. We thank Dr. James Robinson for the 412d and E51 monoclonal
antibodies. This work was supported by grants from the National
Institutes of Health (AI24755 and AI67854), by the International AIDS
Vaccine Initiative, by the Bill and Melinda Gates Foundation, and by the
late William F. McCarty-Cooper.
NR 60
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U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 30
PY 2013
VL 438
IS 1
BP 5
EP 13
DI 10.1016/j.virol.2013.01.002
PG 9
WC Virology
SC Virology
GA 104ZW
UT WOS:000316036400002
PM 23369572
ER
PT J
AU Pezzolesi, MG
Jeong, J
Smiles, AM
Skupien, J
Mychaleckyj, JC
Rich, SS
Warram, JH
Krolewski, AS
AF Pezzolesi, Marcus G.
Jeong, Jackson
Smiles, Adam M.
Skupien, Jan
Mychaleckyj, Josyf C.
Rich, Stephen S.
Warram, James H.
Krolewski, Andrzej S.
TI Family-Based Association Analysis Confirms the Role of the Chromosome
9q21.32 Locus in the Susceptibility of Diabetic Nephropathy
SO PLOS ONE
LA English
DT Article
ID URINARY ALBUMIN EXCRETION; STAGE RENAL-DISEASE; KIDNEY-DISEASE; GENE;
VARIANTS; TYPE-1; HERITABILITY; SCAN; PVT1
AB A genome-wide association scan of type 1 diabetic patients from the GoKinD collections previously identified four novel diabetic nephropathy susceptibility loci that have subsequently been shown to be associated with diabetic nephropathy in unrelated patients with type 2 diabetes. To expand these findings, we examined whether single nucleotide polymorphisms (SNPs) at these susceptibility loci were associated with diabetic nephropathy in patients from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection. Six SNPs across the four loci identified in the GoKinD collections and 7 haplotype tagging SNPs, were genotyped in 66 extended families of European ancestry. Pedigrees from this collection contained an average of 18.5 members, including 2 to 14 members with type 2 diabetes. Among diabetic family members, the 9q21.32 locus approached statistical significance with advanced diabetic nephropathy (P=0.037 [adjusted P=0.222]). When we expanded our definition of diabetic nephropathy to include individuals with high microalbuminuria, the strength of this association improved significantly (P=1.42x10(-3) [adjusted P=0.009]). This same locus also trended toward statistical significance with variation in urinary albumin excretion in family members with type 2 diabetes (P=0.032 [adjusted P=0.192]) and in analyses expanded to include all relatives (P=0.019 [adjusted P=0.114]). These data increase support that SNPs identified in the GoKinD collections on chromosome 9q21.32 are true diabetic nephropathy susceptibility loci.
C1 [Pezzolesi, Marcus G.; Jeong, Jackson; Smiles, Adam M.; Skupien, Jan; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Pezzolesi, Marcus G.; Skupien, Jan; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Mychaleckyj, Josyf C.; Rich, Stephen S.] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
RP Pezzolesi, MG (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM marcus.pezzolesi@joslin.harvard.edu
FU National Institutes of Health (NIH) [DK090125, DK096628, DK58549,
DK77532, DK36836]; Juvenile Diabetes Research Foundation (JDRF)
[3-2009-397]
FX The authors acknowledge grant support from the National Institutes of
Health (NIH) (DK090125 and DK096628 to M.G.P., DK58549 and DK77532 to
A.S.K., and DK36836 to the Genetics Core of the Diabetes and
Endocrinology Research Center at the Joslin Diabetes Center). The
authors also acknowledge support from the Juvenile Diabetes Research
Foundation (JDRF) (3-2009-397 to J.S.). 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 2
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 MAR 29
PY 2013
VL 8
IS 3
AR e60301
DI 10.1371/journal.pone.0060301
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 121SG
UT WOS:000317263900067
PM 23555951
ER
PT J
AU Lobo, GP
Amengual, J
Baus, D
Shivdasani, RA
Taylor, D
von Lintig, J
AF Lobo, Glenn P.
Amengual, Jaume
Baus, Diane
Shivdasani, Ramesh A.
Taylor, Derek
von Lintig, Johannes
TI Genetics and Diet Regulate Vitamin A Production via the Homeobox
Transcription Factor ISX
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BETA-CAROTENE 15,15'-MONOOXYGENASE; RETINOIC ACID; CELLULAR UPTAKE;
DOUBLE-TRACER; SR-BI; METABOLISM; EXPRESSION; CONVERSION; TRANSPORT;
EMBRYOGENESIS
AB Low dietary intake of beta-carotene is associated with chronic disease and vitamin A deficiency. beta-Carotene is converted to vitamin A in the intestine by the enzyme beta-carotene-15,15'-monoxygenase (BCMO1) to support vision, reproduction, immune function, and cell differentiation. Considerable variability for this key step in vitamin A metabolism, as reported in the human population, could be related to genetics and individual vitamin A status, but it is unclear how these factors influence beta-carotene metabolism and vitamin A homeostasis. Here we show that the intestine-specific transcription factor ISX binds to the Bcmo1 promoter. Moreover, upon induction by the beta-carotene derivative retinoic acid, this ISX binding decreased expression of a luciferase reporter gene in human colonic CaCo-2 cells indicating that ISX acts as a transcriptional repressor of BCMO1 expression. Mice deficient for this transcription factor displayed increased intestinal BCMO1 expression and produced significantly higher amounts of vitamin A from supplemental beta-carotene. The ISX binding site in the human BCMO1 promoter contains a common single nucleotide polymorphism that is associated with decreased conversion rates and increased fasting blood levels of beta-carotene. Thus, our study establishes ISX as a critical regulator of vitamin A production and provides a mechanistic explanation for how both genetics and diet can affect this process.
C1 [Lobo, Glenn P.; Amengual, Jaume; Baus, Diane; Taylor, Derek; von Lintig, Johannes] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA.
[Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP von Lintig, J (reprint author), Case Western Reserve Univ, Sch Med, Dept Pharmacol W341, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM johannes.vonlintig@case.edu
FU National Institutes of Health [EY019641, EY020551]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants EY019641 and EY020551.
NR 34
TC 21
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U1 1
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 MAR 29
PY 2013
VL 288
IS 13
BP 9017
EP 9027
DI 10.1074/jbc.M112.444240
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 116DG
UT WOS:000316862200021
PM 23393141
ER
PT J
AU Suva, ML
Riggi, N
Bernstein, BE
AF Suva, Mario L.
Riggi, Nicolo
Bernstein, Bradley E.
TI Epigenetic Reprogramming in Cancer
SO SCIENCE
LA English
DT Review
ID B-CELL LYMPHOMAS; STEM-CELLS; SOMATIC MUTATIONS; GENOMIC ANALYSIS;
PROSTATE-CANCER; SELF-RENEWAL; HISTONE H3; C-MYC; GENE; PLURIPOTENCY
AB The demonstration of induced pluripotency and direct lineage conversion has led to remarkable insights regarding the roles of transcription factors and chromatin regulators in mediating cell state transitions. Beyond its considerable implications for regenerative medicine, this body of work is highly relevant to multiple stages of oncogenesis, from the initial cellular transformation to the hierarchical organization of established malignancies. Here, we review conceptual parallels between the respective biological phenomena, highlighting important interrelationships among transcription factors, chromatin regulators, and preexisting epigenetic states. The shared mechanisms provide insights into oncogenic transformation, tumor heterogeneity, and cancer stem cell models.
C1 [Suva, Mario L.; Riggi, Nicolo; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Suva, Mario L.; Riggi, Nicolo; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Suva, Mario L.; Riggi, Nicolo; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
[Suva, Mario L.; Riggi, Nicolo; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Suva, Mario L.; Riggi, Nicolo; Bernstein, Bradley E.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
RP Bernstein, BE (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
EM bernstein.bradley@mgh.harvard.edu
FU Howard Hughes Medical Institute; National Human Genome Research
Institute; NIH Common Fund; National Heart, Lung, and Blood Institute;
Harvard Stem Cell Institute; Burroughs Wellcome Fund; Medic Foundation;
Nuovo Soldati Foundation; Swiss National Science Foundation; Oncosuisse
FX We thank E. Rheinbay, R. Ryan, M. Rivera, I. Bernstein, and A. Meissner
for critical comments, and L. Gaffney for figure design. This work was
supported by the Howard Hughes Medical Institute, the National Human
Genome Research Institute, the NIH Common Fund, the National Heart,
Lung, and Blood Institute, the Harvard Stem Cell Institute, the
Burroughs Wellcome Fund, the Medic Foundation, the Nuovo Soldati
Foundation, the Swiss National Science Foundation, and Oncosuisse.
NR 64
TC 233
Z9 238
U1 16
U2 157
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 MAR 29
PY 2013
VL 339
IS 6127
BP 1567
EP 1570
DI 10.1126/science.1230184
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 114HL
UT WOS:000316731600039
PM 23539597
ER
PT J
AU Losman, JA
Looper, RE
Koivunen, P
Lee, S
Schneider, RK
McMahon, C
Cowley, GS
Root, DE
Ebert, BL
Kaelin, WG
AF Losman, Julie-Aurore
Looper, Ryan E.
Koivunen, Peppi
Lee, Sungwoo
Schneider, Rebekka K.
McMahon, Christine
Cowley, Glenn S.
Root, David E.
Ebert, Benjamin L.
Kaelin, William G., Jr.
TI (R)-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its
Effects Are Reversible
SO SCIENCE
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ISOCITRATE DEHYDROGENASE 1; ONCOMETABOLITE
2-HYDROXYGLUTARATE; 2 MUTATIONS; IN-VIVO; DIFFERENTIATION; HYPOXIA;
CELLS; TET2; TRANSFORMATION
AB Mutations in IDH1 and IDH2, the genes coding for isocitrate dehydrogenases 1 and 2, are common in several human cancers, including leukemias, and result in overproduction of the (R)-enantiomer of 2-hydroxyglutarate [(R)-2HG]. Elucidation of the role of IDH mutations and (R)-2HG in leukemogenesis has been hampered by a lack of appropriate cell-based models. Here, we show that a canonical IDH1 mutant, IDH1 R132H, promotes cytokine independence and blocks differentiation in hematopoietic cells. These effects can be recapitulated by (R)-2HG, but not (S)-2HG, despite the fact that (S)-2HG more potently inhibits enzymes, such as the 5'-methylcytosine hydroxylase TET2, that have previously been linked to the pathogenesis of IDH mutant tumors. We provide evidence that this paradox relates to the ability of (S)-2HG, but not (R)-2HG, to inhibit the EglN prolyl hydroxylases. Additionally, we show that transformation by (R)-2HG is reversible.
C1 [Losman, Julie-Aurore; Lee, Sungwoo; McMahon, Christine; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Losman, Julie-Aurore; Schneider, Rebekka K.; Ebert, Benjamin L.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02215 USA.
[Looper, Ryan E.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
[Koivunen, Peppi] Univ Oulu, Oulu Ctr Cell Matrix Res, Dept Med Biochem & Mol Biol, Bioctr Oulu, FIN-90014 Oulu, Finland.
[Cowley, Glenn S.; Root, David E.; Ebert, Benjamin L.] Broad Inst MIT & Harvard, Cambridge, MA 02143 USA.
[Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM william_kaelin@dfci.harvard.edu
OI Looper, Ryan/0000-0003-1626-1363
FU NIH; HHMI
FX We thank K. Yen, M. Su, and Agios Pharmaceuticals for the IDH1 inhibitor
and for sharing unpublished data; R. Bejar and A. Mullally for their
valuable input; A. Lane and D. Sykes for assistance with the SCF
ER-Hoxb8 cells; M. Paktinat and R. Mathieu for assistance with flow
cytometry; and members of the Kaelin and Ebert lab for technical help
and valuable discussion. This work was supported by the NIH (W. G. K.
and J.-A.L.) and HHMI (W. G. K.). W. G. K. is a HHMI Investigator and a
paid Scientific Advisor for Agios, a biotechnology company developing
IDH inhibitors. W. G. K. is also a paid consultant for and owns equity
in Fibrogen, Inc., a biotechnology company developing EglN inhibitors.
NR 28
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Z9 217
U1 4
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 MAR 29
PY 2013
VL 339
IS 6127
BP 1621
EP 1625
DI 10.1126/science.1231677
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 114HL
UT WOS:000316731600053
PM 23393090
ER
PT J
AU Gotlib, J
Pardanani, A
Akin, C
Reiter, A
George, T
Hermine, O
Kluin-Nelemans, H
Hartmann, K
Sperr, WR
Brockow, K
Schwartz, LB
Orfao, A
DeAngelo, DJ
Arock, M
Sotlar, K
Horny, HP
Metcalfe, DD
Escribano, L
Verstovsek, S
Tefferi, A
Valent, P
AF Gotlib, Jason
Pardanani, Animesh
Akin, Cem
Reiter, Andreas
George, Tracy
Hermine, Olivier
Kluin-Nelemans, Hanneke
Hartmann, Karin
Sperr, Wolfgang R.
Brockow, Knut
Schwartz, Lawrence B.
Orfao, Alberto
DeAngelo, Daniel J.
Arock, Michel
Sotlar, Karl
Horny, Hans-Peter
Metcalfe, Dean D.
Escribano, Luis
Verstovsek, Srdan
Tefferi, Ayalew
Valent, Peter
TI International Working Group-Myeloproliferative Neoplasms Research and
Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM)
consensus response criteria in advanced systemic mastocytosis
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; MAST-CELL LEUKEMIA;
OF-THE-LITERATURE; PHASE-II TRIAL; C-KIT MUTATION; INTERFERON-ALPHA;
IMATINIB MESYLATE; SPANISH NETWORK; CLADRIBINE
AB Systemic mastocytosis (SM) is characterized by accumulation of neoplastic mast cells and is classified into indolent and aggressive forms. The latter include aggressive SM (ASM), mast cell leukemia (MCL), and SM associated with a myeloid neoplasm wherein 1 or both disease compartments exhibit advanced features. These variants, henceforth collectively referred to as advanced SM for the purposes of this report, are typically characterized by organ damage and shortened survival duration. In contrast to indolent SM, in which symptoms are usually managed by noncytotoxic antimediator therapy, cytoreduction is usually necessary for disease control in advanced SM. Unfortunately, current drug treatment of these patients rarely results in complete clinical and histopathologic remissions or improved survival time. Previously defined response criteria were adapted to the heterogeneous presentations of advanced SM and the limited effects of available drugs. However, recent advances in understanding the molecular pathogenesis of SM and the corresponding prospect in targeted therapy make it a priority to modify these criteria. Our current study is the product of an international group of experts and summarizes the challenges in accomplishing this task and forwards a new proposal for response criteria, which builds on prior proposals and should facilitate response evaluation in clinical trials.
C1 [Gotlib, Jason; George, Tracy] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Pardanani, Animesh; Tefferi, Ayalew] Mayo Clin, Rochester, MN USA.
[Akin, Cem] Harvard Univ, Sch Med, Boston, MA USA.
[Akin, Cem] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Reiter, Andreas] Univ Med Mannheim, Med Klin 3, Mannheim, Germany.
[Hermine, Olivier] Paris Descartes Univ, CNRS, Unite Mixte Rech 8147, Paris, France.
[Hermine, Olivier] Paris Descartes Univ, Necker Hosp, Paris, France.
[Kluin-Nelemans, Hanneke] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Hartmann, Karin] Univ Cologne, D-50931 Cologne, Germany.
[Sperr, Wolfgang R.; Valent, Peter] Med Univ Vienna, Vienna, Austria.
[Brockow, Knut] Biederstein Tech Univ, Munich, Germany.
[Schwartz, Lawrence B.] Virginia Commonwealth Univ, Richmond, VA USA.
[Orfao, Alberto; Escribano, Luis] Univ Salamanca, E-37008 Salamanca, Spain.
[DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Arock, Michel] Grp Hosp Pitie Salpetriere, Cent Hematol Lab, F-75634 Paris, France.
[Arock, Michel] Ecole Normale Super, LBPA, CNRS UMR 8113, F-75231 Paris, France.
[Sotlar, Karl; Horny, Hans-Peter] Univ Munich, Munich, Germany.
[Metcalfe, Dean D.] NIAID, NIH, Bethesda, MD 20892 USA.
[Verstovsek, Srdan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Gotlib, J (reprint author), Stanford Canc Inst, 875 Blake Wilbur Dr,Room 2324, Stanford, CA 94305 USA.
EM jason.gotlib@stanford.edu
RI Hartmann, Karin/N-4865-2015;
OI Hartmann, Karin/0000-0002-4595-8226; Akin, Cem/0000-0001-6301-4520
FU Charles and Ann Johnson Foundation; Division of Intramural Research,
NIAID, National Institutes of Health; Ministerio de Sanidad y Asuntos
Sociales [FIS PS09/00032]; Austrian Science Fund (FWF) SFB-project
[F4704-B20]
FX This work was supported in part by the Charles and Ann Johnson
Foundation (J.G.), the Division of Intramural Research, NIAID, National
Institutes of Health (D. D. M), a grant by the Ministerio de Sanidad y
Asuntos Sociales (FIS PS09/00032) (L. E.), and by the Austrian Science
Fund (FWF) SFB-project F4704-B20.
NR 58
TC 35
Z9 35
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 28
PY 2013
VL 121
IS 13
BP 2393
EP 2401
DI 10.1182/blood-2012-09-458521
PG 9
WC Hematology
SC Hematology
GA 182RT
UT WOS:000321762400009
PM 23325841
ER
PT J
AU Harris, JM
Esain, V
Frechette, GM
Harris, LJ
Cox, AG
Cortes, M
Garnaas, MK
Carroll, KJ
Cutting, CC
Khan, T
Elks, PM
Renshaw, SA
Dickinson, BC
Chang, CJ
Murphy, MP
Paw, BH
Vander Heiden, MG
Goessling, W
North, TE
AF Harris, James M.
Esain, Virginie
Frechette, Gregory M.
Harris, Lauren J.
Cox, Andrew G.
Cortes, Mauricio
Garnaas, Maija K.
Carroll, Kelli J.
Cutting, Claire C.
Khan, Tahsin
Elks, Philip M.
Renshaw, Stephen A.
Dickinson, Bryan C.
Chang, Christopher J.
Murphy, Michael P.
Paw, Barry H.
Vander Heiden, Matthew G.
Goessling, Wolfram
North, Trista E.
TI Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC
induction in vivo
SO BLOOD
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; INDUCIBLE FACTOR-I; AORTIC ENDOTHELIUM;
CHILDHOOD LEUKEMIA; ENERGY-METABOLISM; BIRTH-WEIGHT; MOUSE EMBRYO;
HIF-ALPHA; HYPOXIA; ZEBRAFISH
AB Many pathways regulating blood formation have been elucidated, yet how each coordinates with embryonic biophysiology to modulate the spatiotemporal production of hematopoietic stem cells (HSCs) is currently unresolved. Here, we report that glucose metabolism impacts the onset and magnitude of HSC induction in vivo. In zebrafish, transient elevations in physiological glucose levels elicited dose-dependent effects on HSC development, including enhanced runx1 expression and hematopoietic cluster formation in the aorta-gonad-mesonephros region; embryonic-to-adult transplantation studies confirmed glucose increased functional HSCs. Glucose uptake was required to mediate the enhancement in HSC development; likewise, metabolic inhibitors diminished nascent HSC production and reversed glucose-mediated effects on HSCs. Increased glucose metabolism preferentially impacted hematopoietic and vascular targets, as determined by gene expression analysis, through mitochondrial-derived reactive oxygen species (ROS)-mediated stimulation of hypoxia-inducible factor 1 alpha (hif1 alpha). Epistasis assays demonstrated that hif1 alpha regulates HSC formation in vivo and mediates the dose-dependent effects of glucose metabolism on the timing and magnitude of HSC production. We propose that this fundamental metabolic-sensing mechanism enables the embryo to respond to changes in environmental energy input and adjust hematopoietic output to maintain embryonic growth and ensure viability.
C1 [Harris, James M.; Esain, Virginie; Frechette, Gregory M.; Harris, Lauren J.; Cortes, Mauricio; Carroll, Kelli J.; North, Trista E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Cox, Andrew G.; Garnaas, Maija K.; Cutting, Claire C.; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.
[Cox, Andrew G.; Garnaas, Maija K.; Cutting, Claire C.; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA.
[Khan, Tahsin; Vander Heiden, Matthew G.] MIT, Koch Inst, Cambridge, MA 02139 USA.
[Elks, Philip M.; Renshaw, Stephen A.] Ctr Dev & Biomed Genet, MRC, Sheffield, S Yorkshire, England.
[Dickinson, Bryan C.; Chang, Christopher J.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Dickinson, Bryan C.; Chang, Christopher J.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
[Murphy, Michael P.] MRC Mitochondrial Biol Unit, Cambridge, England.
[Paw, Barry H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA.
[Paw, Barry H.; Vander Heiden, Matthew G.; Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Goessling, Wolfram; North, Trista E.] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Goessling, W (reprint author), Brigham & Womens Hosp, Div Genet, NRB458,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM wgoessling@partners.org; tnorth@bidmc.harvard.edu
RI Renshaw, Stephen/E-6192-2010;
OI Renshaw, Stephen/0000-0003-1790-1641; Elks, Philip/0000-0003-1683-0749;
Goessling, Wolfram/0000-0001-9972-1569
FU Harvard Stem Cell Institute Blood Program; National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[5K01DK080226, 1R01DK090311]
FX This work was supported by the Harvard Stem Cell Institute Blood Program
(T.E.N.) and the National Institutes of Health National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) 5K01DK080226 (T.E.N.)
and 1R01DK090311 (W.G.).
NR 50
TC 28
Z9 30
U1 0
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 28
PY 2013
VL 121
IS 13
BP 2483
EP 2493
DI 10.1182/blood-2012-12-471201
PG 11
WC Hematology
SC Hematology
GA 182RT
UT WOS:000321762400018
PM 23341543
ER
PT J
AU Stefater, JA
Rao, S
Bezold, K
Aplin, AC
Nicosia, RF
Pollard, JW
Ferrara, N
Lang, RA
AF Stefater, James A., III
Rao, Sujata
Bezold, Katie
Aplin, Alfred C.
Nicosia, Roberto F.
Pollard, Jeffrey W.
Ferrara, Napoleone
Lang, Richard A.
TI Macrophage Wnt-Calcineurin-Flt1 signaling regulates mouse wound
angiogenesis and repair
SO BLOOD
LA English
DT Article
ID IMMUNOSUPPRESSED MICE; INFLAMMATORY CELLS; TGF-BETA; VEGF; RECEPTOR;
CALCINEURIN; PROTEIN; INHIBITION; LETHALITY; SECRETION
AB The treatment of festering wounds is one of the most important aspects of medical care. Macrophages are important components of wound repair, both in fending off infection and in coordinating tissue repair. Here we show that macrophages use a Wnt-Calcineurin-Flt1 signaling pathway to suppress wound vasculature and delay repair. Conditional mutants deficient in both Wntless/GPR177, the secretory transporter of Wnt ligands, and CNB1, the essential component of the nuclear factor of activated T cells dephosporylation complex, displayed enhanced angiogenesis and accelerated repair. Furthermore, in myeloid-like cells, we show that noncanonical Wnt activates Flt1, a naturally occurring inhibitor of vascular endothelial growth factor-A-mediated angiogenesis, but only when calcineurin function is intact. Then, as expected, conditional deletion of Flt1 in macrophages resulted in enhanced wound angiogenesis and repair. These results are consistent with the published link between enhanced angiogenesis and enhanced repair, and establish novel therapeutic approaches for treatment of wounds.
C1 [Stefater, James A., III; Rao, Sujata; Bezold, Katie; Lang, Richard A.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, Visual Syst Grp, Cincinnati, OH 45229 USA.
[Stefater, James A., III; Rao, Sujata; Bezold, Katie; Lang, Richard A.] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
[Stefater, James A., III; Rao, Sujata; Bezold, Katie; Lang, Richard A.] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH USA.
[Aplin, Alfred C.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Aplin, Alfred C.; Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Pathol & Lab Med, Seattle, WA USA.
[Pollard, Jeffrey W.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA.
[Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA.
RP Lang, RA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM richard.lang@cchmc.org
FU National Institutes of Health [R01CA131270, T32GM063483-08S1]
FX This work was supported by grants from the National Institutes of Health
(R01CA131270) (J.P. and R. A. L) and (T32GM063483-08S1) (J.A.S).
NR 40
TC 19
Z9 19
U1 1
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 28
PY 2013
VL 121
IS 13
BP 2574
EP 2578
DI 10.1182/blood-2012-06-434621
PG 5
WC Hematology
SC Hematology
GA 182RT
UT WOS:000321762400029
PM 23303818
ER
PT J
AU Hong, FX
Bosco, JLF
Bush, N
Berry, DL
AF Hong, Fanxing
Bosco, Jaclyn L. F.
Bush, Nigel
Berry, Donna L.
TI Patient self-appraisal of change and minimal clinically important
difference on the European organization for the research and treatment
of cancer quality of life questionnaire core 30 before and during cancer
therapy
SO BMC CANCER
LA English
DT Article
DE Cancer treatment; Health related quality of life; Quality of life
questionnaire-core; Subject significance questionnaire; Minimal
clinically important differences
ID EORTC QLQ-C30; SCORES
AB Background: Clinical interpretation of health related quality of life (HRQOL) scores is challenging. The purpose of this analysis was to interpret score changes and identify minimal clinically important differences (MCID) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) before (T1) and during (T2) cancer treatment.
Methods: Patients (N = 627) in stem cell transplant (SCT) and medical (MED) or radiation (RAD) oncology at two comprehensive cancer centers, enrolled in the Electronic Self-Report Assessment-Cancer study and completed the QLQ-C30 at T1 and T2. Perceived changes in five QOL domains, physical (PF), emotional (EF), social (SF), cognitive functioning (CF) and global quality of life (QOL), were reported using the Subject Significance Questionnaire (SSQ) at T2. Anchored on SSQ ratings indicating "improvement", "the same", or "deterioration", means and effect sizes were calculated for QLQ-C30 score changes. MCID was calculated as the mean difference in QLQ-C30 score changes reflecting one category change on SSQ rating, using a two-piece linear regression model.
Results: A majority of SCT patients (54%) perceived deteriorating global HRQOL versus improvement (17%), while approximately equal proportions of MED/RAD patients perceived improvement (25%) and deterioration (26%). Global QOL decreased 14.2 (SCT) and 2.0 (MED/RAD) units, respectively, among patients reporting "the same" in the SSQ. The MCID ranged 5.7-11.4 (SCT) and 7.2-11.8 (MED/RAD) units among patients reporting deteriorated HRQOL; ranged 2.7-3.4 units among MED/RAD patients reporting improvement. Excepting for the global QOL (MCID = 6.9), no meaningful MCID was identified among SCT patients reporting improvement.
Conclusions: Cancer treatment has greater impact on HRQOL among SCT patients than MED/RAD patients. The MCID for QLQ-C30 score change differed across domains, and differed for perceived improvement and deterioration, suggesting different standards for self-evaluating changes in HRQOL during cancer treatment. Specifically, clinical attention can be focused on patients who report at least a 6 point decrease, and for patients who report at least a 3 point increase on QLQ-C30 domains.
C1 [Hong, Fanxing] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Bosco, Jaclyn L. F.; Berry, Donna L.] Harvard Univ, Sch Med, Phyllis F Cantor Ctr, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA.
[Bush, Nigel] Natl Ctr Telehlth & Technol, Joint Base Lewis McChord, Tacoma, WA USA.
RP Hong, FX (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
EM fxhong@jimmy.harvard.edu
FU National Institute of Nursing Research [NR008726]
FX The study was supported by the National Institute of Nursing Research
grant NR008726. The authors acknowledge Barbara Halpenny for
constructive discussions, the time and effort of all study participants,
the dedication of the research staff, the generous support from the
clinicians and administrators at the study sites for the original ESRA-C
study.
NR 23
TC 4
Z9 5
U1 2
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD MAR 28
PY 2013
VL 13
AR 165
DI 10.1186/1471-2407-13-165
PG 8
WC Oncology
SC Oncology
GA 136YA
UT WOS:000318398500001
PM 23537330
ER
PT J
AU Garraway, LA
Lander, ES
AF Garraway, Levi A.
Lander, Eric S.
TI Lessons from the Cancer Genome
SO CELL
LA English
DT Review
ID ACUTE MYELOID-LEUKEMIA; ISLAND METHYLATOR PHENOTYPE; CHROMATIN
REMODELING GENES; LINEAGE-SURVIVAL ONCOGENE; SQUAMOUS-CELL CARCINOMA;
CHRONIC LYMPHOCYTIC-LEUKEMIA; RECURRENT SOMATIC MUTATIONS; CLINICAL
TUMOR SAMPLES; LONG-RANGE INTERACTION; 21 BREAST CANCERS
AB Systematic studies of the cancer genome have exploded in recent years. These studies have revealed scores of new cancer genes, including many in processes not previously known to be causal targets in cancer. The genes affect cell signaling, chromatin, and epigenomic regulation; RNA splicing; protein homeostasis; metabolism; and lineage maturation. Still, cancer genomics is in its infancy. Much work remains to complete the mutational catalog in primary tumors and across the natural history of cancer, to connect recurrent genomic alterations to altered pathways and acquired cellular vulnerabilities, and to use this information to guide the development and application of therapies.
C1 [Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA.
[Garraway, Levi A.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Garraway, Levi A.; Lander, Eric S.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Lander, ES (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM lander@broadinstitute.org
FU U.S. National Human Genome Research Institute; U.S. National Cancer
Institute; Slim Initiative for Genomic Medicine; Broad Institute;
Department of Defense; Starr Cancer Consortium; Prostate Cancer
Foundation; Melanoma Research Alliance; Adelson Medical Research
Foundation
FX We thank Todd Golub, Matthew Meyerson, and Michael Stratton for
reviewing the manuscript and for valuable comments. We thank Gad Getz,
Charles Roberts, and Matthew Freedman for helpful discussions. The
design of figures was aided by materials from ScienceSlides
(http://www.visiscience.com). L.A.G. and E.S.L. are supported by the
U.S. National Human Genome Research Institute, the U.S. National Cancer
Institute, the Slim Initiative for Genomic Medicine, and the Broad
Institute. L.A.G. also receives support from the Department of Defense,
the Starr Cancer Consortium, the Prostate Cancer Foundation, the
Melanoma Research Alliance, and the Adelson Medical Research Foundation.
L.A.G. and E.S.L. are consultants and equity holders in Foundation
Medicine, Inc.
NR 191
TC 357
Z9 368
U1 21
U2 218
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 28
PY 2013
VL 153
IS 1
BP 17
EP 37
DI 10.1016/j.cell.2013.03.002
PG 21
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 116AI
UT WOS:000316853700004
PM 23540688
ER
PT J
AU Kaelin, WG
McKnight, SL
AF Kaelin, William G., Jr.
McKnight, Steven L.
TI Influence of Metabolism on Epigenetics and Disease
SO CELL
LA English
DT Review
ID HISTONE LYSINE DEMETHYLASES; OFFSPRING DNA METHYLATION; ACETYL-COA
SYNTHETASE; COMBINED FOLIC-ACID; OXIDATIVE STRESS; GENE-EXPRESSION;
CELL-CYCLE; ONCOMETABOLITE 2-HYDROXYGLUTARATE; MYELOID MALIGNANCIES;
S-ADENOSYLMETHIONINE
AB Chemical modifications of histones and DNA, such as histone methylation, histone acetylation, and DNA methylation, play critical roles in epigenetic gene regulation. Many of the enzymes that add or remove such chemical modifications are known, or might be suspected, to be sensitive to changes in intracellular metabolism. This knowledge provides a conceptual foundation for understanding how mutations in the metabolic enzymes SDH, FH, and IDH can result in cancer and, more broadly, for how alterations in metabolism and nutrition might contribute to disease. Here, we review literature pertinent to hypothetical connections between metabolic and epigenetic states in eukaryotic cells.
C1 [Kaelin, William G., Jr.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Kaelin, William G., Jr.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA.
[Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[McKnight, Steven L.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM william_kaelin@dfci.harvard.edu; steven.mcknight@utsouthwestern.edu
FU Howard Hughes Medical Institute; NCI NIH HHS [R01 CA068490, R01
CA076120]
NR 127
TC 222
Z9 225
U1 32
U2 219
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 28
PY 2013
VL 153
IS 1
BP 56
EP 69
DI 10.1016/j.cell.2013.03.004
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 116AI
UT WOS:000316853700006
PM 23540690
ER
PT J
AU Huang, SC
Do, J
Mahalanabis, M
Fan, A
Zhao, L
Jepeal, L
Singh, SK
Klapperich, CM
AF Huang, Shichu
Do, Jaephil
Mahalanabis, Madhumita
Fan, Andy
Zhao, Lei
Jepeal, Lisa
Singh, Satish K.
Klapperich, Catherine M.
TI Low Cost Extraction and Isothermal Amplification of DNA for Infectious
Diarrhea Diagnosis
SO PLOS ONE
LA English
DT Article
ID IMMUNOCHROMATOGRAPHIC STRIP TEST; DISPOSABLE DETECTION DEVICE; REAL-TIME
PCR; ON-A-CHIP; CLOSTRIDIUM-DIFFICILE; GLOBAL HEALTH; IDENTIFICATION;
MICROFLUIDICS; TECHNOLOGIES; SYSTEMS
AB In order to counter the common perception that molecular diagnostics are too complicated to work in low resource settings, we have performed a difficult sample preparation and DNA amplification protocol using instrumentation designed to be operated without wall or battery power. In this work we have combined a nearly electricity-free nucleic acid extraction process with an electricity-free isothermal amplification assay to detect the presence of Clostridium difficile (C. difficile) DNA in the stool of infected patients. We used helicase-dependent isothermal amplification (HDA) to amplify the DNA in a low-cost, thermoplastic reaction chip heated with a pair of commercially available toe warmers, while using a simple Styrofoam insulator. DNA was extracted from known positive and negative stool samples. The DNA extraction protocol utilized an air pressure driven solid phase extraction device run using a standard bicycle pump. The simple heater setup required no electricity or battery and was capable of maintaining the temperature at 65 degrees C +/- 62 degrees C for 55 min, suitable for repeatable HDA amplification. Experiments were performed to explore the adaptability of the system for use in a range of ambient conditions. When compared to a traditional centrifuge extraction protocol and a laboratory thermocycler, this disposable, no power platform achieved approximately the same lower limit of detection (1.25 x 10(-2) pg of C. difficile DNA) while requiring much less raw material and a fraction of the lab infrastructure and cost. This proof of concept study could greatly impact the accessibility of molecular assays for applications in global health.
C1 [Huang, Shichu; Do, Jaephil; Mahalanabis, Madhumita; Fan, Andy; Klapperich, Catherine M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Zhao, Lei] Boston Univ, Dept Biol, Boston, MA 02215 USA.
[Jepeal, Lisa; Singh, Satish K.] Boston Univ, Dept Gastroenterol, Boston, MA 02215 USA.
[Singh, Satish K.] VA Boston Hlth Care Syst, Dept Med, Boston, MA USA.
[Klapperich, Catherine M.] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA.
RP Klapperich, CM (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
EM catherin@bu.edu
OI Klapperich, Catherine /0000-0001-6103-849X; Singh,
Satish/0000-0002-7664-3155
FU NIH [R21 AI71261]
FX This work was funded by NIH Grant R21 AI71261 to CMK and SS. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 48
TC 22
Z9 23
U1 3
U2 59
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 MAR 28
PY 2013
VL 8
IS 3
AR e60059
DI 10.1371/journal.pone.0060059
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 121RP
UT WOS:000317262200075
PM 23555883
ER
PT J
AU Epstein, AJ
Srinivas, SK
Nicholson, S
Herrin, J
Asch, DA
AF Epstein, Andrew J.
Srinivas, Sindhu K.
Nicholson, Sean
Herrin, Jeph
Asch, David A.
TI Association between physicians' experience after training and maternal
obstetrical outcomes: cohort study
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Article
ID LEARNING-CURVE; MORTALITY; SURGEONS; CARE
AB Objective To assess the association between obstetricians' years of experience after training and the maternal complications of their patients during their first 40 years of post-residency practice.
Design Retrospective cohort analysis.
Setting Obstetrical discharges from acute care hospitals in Florida and New York between academic years 1992 and 2009.
Population 6 704 311 deliveries performed by 5175 obstetricians.
Main outcome measure Three composite measures of maternal complication rates per physician year from vaginal and cesarean births separately and combined, adjusted for secular trends.
Results Obstetricians' maternal complication rates declined during the first three decades after completion of residency. The improvement was largest in the first decade and diminished thereafter. For all deliveries, the change was -0.21 (95% confidence interval -0.23 to -0.19) percentage points per year in the first decade, -0.11 (-0.13 to -0.09) percentage points per year in the second decade, and -0.05 (-0.08 to -0.01) percentage points in the third decade (P<0.001 for second to first decade comparison; P=0.001 for third to second decade comparison). The patterns were comparable for cesarean deliveries and vaginal deliveries and across several sensitivity checks.
Conclusions Among obstetricians practicing in Florida and New York, those with more years of experience had fewer maternal complications. This association persisted over the first three decades of practice but diminished in magnitude.
C1 [Epstein, Andrew J.; Asch, David A.] Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA.
[Epstein, Andrew J.; Asch, David A.] Univ Penn, Div Gen Internal Med, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Epstein, Andrew J.; Srinivas, Sindhu K.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Srinivas, Sindhu K.] Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Nicholson, Sean] Cornell Univ, Dept Policy Anal & Management, Coll Human Ecol, Ithaca, NY 14853 USA.
[Herrin, Jeph] Yale Univ, Sect Cardiovasc Med, Dept Med, Sch Med, New Haven, CT 06510 USA.
[Herrin, Jeph] Hlth Res & Educ Trust, Chicago, IL 60606 USA.
RP Epstein, AJ (reprint author), Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs, Ctr Hlth Equity Res & Promot, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM eandrew@mail.med.upenn.edu
OI Asch, David/0000-0002-7970-286X
NR 17
TC 2
Z9 2
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD MAR 28
PY 2013
VL 346
AR f1596
DI 10.1136/bmj.f1596
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 117XI
UT WOS:000316986200003
PM 23538919
ER
PT J
AU Hanada, T
Weitzer, S
Mair, B
Bernreuther, C
Wainger, BJ
Ichida, J
Hanada, R
Orthofer, M
Cronin, SJ
Komnenovic, V
Minis, A
Sato, F
Mimata, H
Yoshimura, A
Tamir, I
Rainer, J
Kofler, R
Yaron, A
Eggan, KC
Woolf, CJ
Glatzel, M
Herbst, R
Martinez, J
Penninger, JM
AF Hanada, Toshikatsu
Weitzer, Stefan
Mair, Barbara
Bernreuther, Christian
Wainger, Brian J.
Ichida, Justin
Hanada, Reiko
Orthofer, Michael
Cronin, Shane J.
Komnenovic, Vukoslav
Minis, Adi
Sato, Fuminori
Mimata, Hiromitsu
Yoshimura, Akihiko
Tamir, Ido
Rainer, Johannes
Kofler, Reinhard
Yaron, Avraham
Eggan, Kevin C.
Woolf, Clifford J.
Glatzel, Markus
Herbst, Ruth
Martinez, Javier
Penninger, Josef M.
TI CLP1 links tRNA metabolism to progressive motor-neuron loss
SO NATURE
LA English
DT Article
ID 3-END FORMATION; PHOSPHORYLATION; ENDONUCLEASE; STRESS; ENZYME; MOUSE;
HCLP1; SITE; IA
AB CLP1 was the first mammalian RNA kinase to be identified. However, determining its in vivo function has been elusive. Here we generated kinase-dead Clp1 (Clp1(K/K)) mice that show a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. Transgenic rescue experiments show that CLP1 functions in motor neurons. Mechanistically, loss of CLP1 activity results in accumulation of a novel set of small RNA fragments, derived from aberrant processing of tyrosine pre-transfer RNA. These tRNA fragments sensitize cells to oxidative-stress-induced p53 (also known as TRP53) activation and p53-dependent cell death. Genetic inactivation of p53 rescues Clp1(K/K) mice from the motor neuron loss, muscle denervation and respiratory failure. Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53.
C1 [Hanada, Toshikatsu; Weitzer, Stefan; Mair, Barbara; Hanada, Reiko; Orthofer, Michael; Komnenovic, Vukoslav; Martinez, Javier; Penninger, Josef M.] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
[Bernreuther, Christian; Glatzel, Markus] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, D-20246 Hamburg, Germany.
[Wainger, Brian J.; Cronin, Shane J.; Woolf, Clifford J.] Boston Childrens Hosp, Program Neurobiol, Boston, MA 02115 USA.
[Wainger, Brian J.; Cronin, Shane J.; Woolf, Clifford J.] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
[Wainger, Brian J.] Massachusetts Gen Hosp, Department Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Ichida, Justin; Eggan, Kevin C.] Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Minis, Adi; Yaron, Avraham] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
[Sato, Fuminori; Mimata, Hiromitsu] Oita Univ, Dept Urol, Fac Med, Oita 8795593, Japan.
[Yoshimura, Akihiko] Keio Univ, Dept Microbiol & Immunol, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan.
[Tamir, Ido] Campus Sci Support Facil GmbH, A-1030 Vienna, Austria.
[Rainer, Johannes; Kofler, Reinhard] Med Univ Innsbruck, Div Mol Pathophysiol, Bioctr, A-6020 Innsbruck, Austria.
[Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Herbst, Ruth] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria.
RP Martinez, J (reprint author), Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
EM javier.martinez@imba.oeaw.ac.at; josef.penninger@imba.oeaw.ac.at
RI Penninger, Josef/I-6860-2013; Glatzel, Markus/G-3356-2011; Yoshimura,
Akihiko/K-5515-2013;
OI Penninger, Josef/0000-0002-8194-3777; Glatzel,
Markus/0000-0002-7720-8817; Mair, Barbara/0000-0001-6982-2529
FU Institute of Molecular Biotechnology of the Austrian Academy of Sciences
(IMBA); Austrian Ministry of Sciences; Austrian Academy of Sciences;
AustroMouse network of Genome Research in Austria (GEN-AU); Apoptosis
systems biology applied to cancer and AIDS (ApoSys); European Research
Council Advanced Grant from the European Union; IMBA; GEN-AU
(AustroMouse); Japan Society for the Promotion of Science; Astellas
Foundation; National Institutes of Health (NIH) [K99NS077435-01A1];
German Research Foundation (DFG) [FG885, GRK 1459];
Landesexzellenzinitiative Hamburg (Neurodapt); Austrian Science Fund
[P19223, P21667]; NIH [NS038253]
FX We thank A. Meixner, M. Foong, T. Nakashima, H. C. Theussl, J. R.
Wojciechowski, A. Bichl, the mouse pathology unit of the
Universitatsklinikum Hamburg-Eppendorf, and G. P. Resch for discussions
and technical support. We also thank T. Buerckstuemmer for providing the
pRV-NTAP vector. J. M. P. is supported by grants from the Institute of
Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), the
Austrian Ministry of Sciences, the Austrian Academy of Sciences,
AustroMouse network of Genome Research in Austria (GEN-AU), Apoptosis
systems biology applied to cancer and AIDS (ApoSys) and a European
Research Council Advanced Grant from the European Union. J. M., S. W.
and B. M. are supported by IMBA and GEN-AU (AustroMouse). T. H. is
supported by the Japan Society for the Promotion of Science and the
Astellas Foundation. J. K. I. was supported by National Institutes of
Health (NIH) grant K99NS077435-01A1. M. G. is supported by grants from
the German Research Foundation (DFG) (FG885 and GRK 1459), the
Landesexzellenzinitiative Hamburg (Neurodapt). R. H. was supported by
the Austrian Science Fund (P19223, P21667). C. J. W. is supported by the
NIH (NS038253).
NR 27
TC 54
Z9 59
U1 3
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 474
EP 480
DI 10.1038/nature11923
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800038
PM 23474986
ER
PT J
AU Stone, JH
Murali, MR
AF Stone, John H.
Murali, Mandakolathur R.
TI Case 10-2013: A 30-Year-Old Man with Fever, Myalgias, Arthritis, and
Rash
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; MIDLINE DESTRUCTIVE LESIONS;
RHEUMATIC MANIFESTATIONS; INFECTIVE ENDOCARDITIS; COCAINE; HEROIN;
LEVAMISOLE; VASCULITIS; PURPURA; EARS
C1 [Stone, John H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
FU Roche; Genentech
FX Dr. Stone reports receiving consulting fees from Roche and Genentech,
grant support through his institution from Roche and Genentech, and
travel support from Genentech, Biogen-IDEC, and Genzyme. No other
potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full
text of this article at NEJM.org.
NR 21
TC 2
Z9 2
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 28
PY 2013
VL 368
IS 13
BP 1239
EP 1245
DI 10.1056/NEJMcpc1210260
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 116FU
UT WOS:000316869000014
PM 23514249
ER
PT J
AU Ecker, JL
MacGillivray, TE
Fitzsimons, MG
AF Ecker, Jeffrey L.
MacGillivray, Thomas E.
Fitzsimons, Michael G.
TI Case 40-2012: A Woman with Cardiorespiratory Arrest after a Cesarean
Section REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Ecker, Jeffrey L.; MacGillivray, Thomas E.; Fitzsimons, Michael G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Ecker, JL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 28
PY 2013
VL 368
IS 13
BP 1261
EP 1261
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 116FU
UT WOS:000316869000028
PM 23534575
ER
PT J
AU Palumbo, T
Faucz, FR
Azevedo, M
Xekouki, P
Iliopoulos, D
Stratakis, CA
AF Palumbo, T.
Faucz, F. R.
Azevedo, M.
Xekouki, P.
Iliopoulos, D.
Stratakis, C. A.
TI Functional screen analysis reveals miR-26b and miR-128 as central
regulators of pituitary somatomammotrophic tumor growth through
activation of the PTEN-AKT pathway
SO ONCOGENE
LA English
DT Article
DE microRNAs; growth-hormone producing adenomas; Carney complex;
acromegaly; pituitary hyperplasia; protein kinase A
ID MCCUNE-ALBRIGHT-SYNDROME; CELL SELF-RENEWAL; CARNEY COMPLEX; MICRORNA
GENES; BREAST-CANCER; BMI-1; EXPRESSION; ADENOMAS; PROLIFERATION;
MUTATIONS
AB MicroRNAs (miRNAs) have been involved in the pathogenesis of different types of cancer; however, their function in pituitary tumorigenesis remains poorly understood. Cyclic-AMP-dependent protein kinase-defective pituitaries occasionally form aggressive growth-hormone (GH)-producing pituitary tumors in the background of hyperplasia caused by haploinsufficiency of the protein kinase's main regulatory subunit, PRKAR1A. The molecular basis for this development remains unknown. We have identified a 17-miRNA signature of pituitary tumors formed in the background of hyperplasia (caused in half of the cases by PRKAR1A-mutations). We selected two miRNAs on the basis of their functional screen analysis: inhibition of miR-26b expression and upregulation of miR-128 suppressed the colony formation ability and invasiveness of pituitary tumor cells. Furthermore, we identified that miR-26b and miR-128 affected pituitary tumor cell behavior through regulation of their direct targets, PTEN and BMI1, respectively. In addition, we found that miR-128 through BMI1 direct binding on the PTEN promoter affected PTEN expression levels and AKT activity in the pituitary tumor cells. Our in vivo data revealed that inhibition of miR-26b and overexpression of miR-128 could suppress pituitary GH3 tumor growth in xenografts. Taken together, we have identified a miRNA signature for GH-producing pituitary tumors and found that miR-26b and miR-128 regulate the activity of the PTEN-AKT pathway in these tumors. This is the first suggestion of the possible involvement of miRNAs regulating the PTEN-AKT pathway in GH-producing pituitary tumor formation in the context of hyperplasia or due to germline PRKAR1A defects. MiR-26b suppression and miR-128 upregulation could have therapeutic potential in GH-producing pituitary tumor patients. Oncogene (2013) 32, 1651-1659; doi: 10.1038/onc.2012.190; published online 21 May 2012
C1 [Palumbo, T.; Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Palumbo, T.; Iliopoulos, D.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Faucz, F. R.; Azevedo, M.; Xekouki, P.; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Bethesda, MD USA.
[Faucz, F. R.] Pontificia Univ Catolica Parana, Grp Adv Mol Invest, Grad Program Hlth Sci, Ctr Biol & Sci, Curitiba, Parana, Brazil.
RP Iliopoulos, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
EM Dimitrios_iliopoulos@dfci.harvard.edu; stratakc@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008920-02]
NR 49
TC 45
Z9 52
U1 4
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 28
PY 2013
VL 32
IS 13
BP 1651
EP 1659
DI 10.1038/onc.2012.190
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 116AY
UT WOS:000316855800005
PM 22614013
ER
PT J
AU Liu, Z
Zanata, SM
Kim, J
Peterson, MA
Di Vizio, D
Chirieac, LR
Pyne, S
Agostini, M
Freeman, MR
Loda, M
AF Liu, Z.
Zanata, S. M.
Kim, J.
Peterson, M. A.
Di Vizio, D.
Chirieac, L. R.
Pyne, S.
Agostini, M.
Freeman, M. R.
Loda, M.
TI The ubiquitin-specific protease USP2a prevents endocytosis-mediated EGFR
degradation
SO ONCOGENE
LA English
DT Article
DE USP2a; DUB; EGFR; endocytosis
ID EPIDERMAL-GROWTH-FACTOR; DEUBIQUITINATING ENZYME USP2A; RECEPTOR
TYROSINE KINASES; CLATHRIN-COATED PITS; DOWN-REGULATION;
PROSTATE-CANCER; MEMBRANE-PROTEIN; PLASMA-MEMBRANE; LUNG-CANCER;
CELL-GROWTH
AB Ubiquitination of epidermal growth factor receptor (EGFR) is required for downregulation of the receptor by endocytosis. Impairment of this pathway results in constitutively active EGFR, which is associated with carcinogenesis, particularly in lung cancer. We previously demonstrated that the deubiquitinating enzyme ubiquitin-specific protease 2a (USP2a) has oncogenic properties. Here, we show a new role for USP2a as a regulator of EGFR endocytosis. USP2a localizes to early endosomes and associates with EGFR, stabilizing the receptor, which retains active downstream signaling. HeLa cells transiently expressing catalytically active, but not mutant (MUT), USP2a show increased plasma membrane-localized EGFR, as well as decreased internalized and ubiquitinated EGFR. Conversely, USP2a silencing reverses this phenotype. Importantly, USP2a prevents the degradation of MUT in addition to wild-type EGFR. Finally, we observed that USP2a and EGFR proteins are coordinately overexpressed in non-small cell lung cancers. Taken together, our data indicate that USP2a antagonizes EGFR endocytosis and thus amplifies signaling activity from the receptor. Our findings suggest that regulation of deubiquitination could be exploited therapeutically in cancers overexpressing EGFR. Oncogene (2013) 32, 1660-1669; doi:10.1038/onc.2012.188; published online 18 June 2012
C1 [Liu, Z.; Zanata, S. M.; Peterson, M. A.; Chirieac, L. R.; Pyne, S.; Agostini, M.; Loda, M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Liu, Z.; Zanata, S. M.; Peterson, M. A.; Chirieac, L. R.; Pyne, S.; Agostini, M.; Loda, M.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA.
[Liu, Z.; Loda, M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Zanata, S. M.] Univ Fed Parana, Dept Basic Pathol, BR-80060000 Curitiba, Parana, Brazil.
[Zanata, S. M.] Univ Fed Parana, Dept Cell Biol, BR-80060000 Curitiba, Parana, Brazil.
[Kim, J.; Di Vizio, D.; Freeman, M. R.] Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA.
[Kim, J.; Di Vizio, D.; Freeman, M. R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Freeman, M. R.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Loda, M.] Kings Coll London, Div Canc Studies, London WC2R 2LS, England.
RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, DA1536,450 Brookline Ave, Boston, MA 02215 USA.
EM Massimo_loda@dfci.harvard.edu
RI Agostini, Michelle/I-1275-2012
FU National Cancer Institute [RO1CA131945, PO1CA89021, P50 CA90381];
Prostate Cancer Foundation; CAPES, Brazil [3665/10-0]
FX We thank Tomas Kirchhausen for AMSH constructs, Mihee Ji and Erik
McCauley for technical assistance, Jane Hayward for help with
preparation of the figures, Giulio Draetta and Richard J Flavin for
critical reading of the manuscript. This work was supported by the
National Cancer Institute (RO1CA131945, PO1CA89021, P50 CA90381 and the
Prostate Cancer Foundation). SMZ was supported by CAPES (no. 3665/10-0),
Brazil.
NR 61
TC 15
Z9 16
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 28
PY 2013
VL 32
IS 13
BP 1660
EP 1669
DI 10.1038/onc.2012.188
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 116AY
UT WOS:000316855800006
PM 22710717
ER
PT J
AU Utzschneider, KM
Bayer-Carter, JL
Arbuckle, MD
Tidwell, JM
Richards, TL
Craft, S
AF Utzschneider, Kristina M.
Bayer-Carter, Jennifer L.
Arbuckle, Matthew D.
Tidwell, Jaime M.
Richards, Todd L.
Craft, Suzanne
TI Beneficial effect of a weight-stable, low-fat/low-saturated
fat/low-glycaemic index diet to reduce liver fat in older subjects
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Non-alcoholic fatty liver; Dietary fat; Glycaemic index; Saturated fat
ID MAGNETIC-RESONANCE-SPECTROSCOPY; HIGH-CARBOHYDRATE DIET; HEPATIC
STEATOSIS; NONALCOHOLIC STEATOHEPATITIS; INSULIN SENSITIVITY; ACID
SYNTHESIS; GLUCOSE; DISEASE; OBESE; RESISTANCE
AB Non-alcoholic fatty liver disease is associated with insulin resistance and dyslipidaemia and can progress to steatohepatitis and cirrhosis. We sought to determine whether dietary fat and saturated fat content alter liver fat in the absence of weight change in an older population. Liver fat was quantified by magnetic resonance spectroscopy before and after 4 weeks on an isoenergetic low-fat/low-saturated fat/low-glycaemic index (LGI) (LSAT: 23% fat/7% saturated fat/GI < 55) or a high-fat/high-saturated fat/high-GI (HSAT: 43% fat/24% saturated fat/GI > 70) diet in older subjects. In the present study, twenty subjects (seven males/thirteen females; age 69.3 (SEM 1.6) years, BMI 26.9 (SEM 0.8) kg/m(2)) were randomised to the LSAT diet and fifteen subjects (six males/nine females; age 68.6 (SEM 1.8) years, BMI 28.1 (SEM 0.9) kg/m(2)) to the HSAT diet. Weight remained stable. Liver fat decreased significantly on the LSAT diet (median 2.2 (interquartile range (IQR) 3.1) to 1.7 (IQR 1.8) %, P = 0.002) but did not change on the HSAT diet (median 1.2 (IQR 4.1) to 1.6 (IQR 3.9) %). The LSAT diet lowered fasting glucose and total cholesterol, HDL-cholesterol and LDL-cholesterol and raised TAG (P<0.05), while the HSAT diet had no effect on glucose or HDL-cholesterol but increased total cholesterol and LDL-cholesterol (P<0.05). Fasting insulin and homeostasis model of insulin resistance did not change significantly on either diet, but the Matsuda index of insulin sensitivity improved on the LSAT diet (P<0.05). Assignment to the LSAT v. HSAT diet was a predictor of changes in lipid parameters but not liver fat. We conclude that diet composition may be an important factor in the accumulation of liver fat, with a low-fat/low-saturated fat/LGI diet being beneficial.
C1 [Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA.
[Utzschneider, Kristina M.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
[Bayer-Carter, Jennifer L.; Arbuckle, Matthew D.; Tidwell, Jaime M.; Craft, Suzanne] VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA.
[Bayer-Carter, Jennifer L.; Craft, Suzanne] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Richards, Todd L.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
RP Utzschneider, KM (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 South Columbian Way, Seattle, WA 98108 USA.
EM kutzschn@u.washington.edu
FU VA Office of Research and Development Medical Research Service [R37
AG-10880, UL1RR025014, P30 DK017047]; University of Washington
Diagnostic Imaging Science Center
FX We are grateful to the study participants for their contribution and
time. This study was supported in part by the VA Office of Research and
Development Medical Research Service, grant no. R37 AG-10880,
UL1RR025014, P30 DK017047 and the University of Washington Diagnostic
Imaging Science Center. The funding agencies had no role in the design,
implementation, analysis or interpretation of the data. The authors'
responsibilities were as follows: K. M. U. designed the MRS sub-study,
analysed the data and wrote the manuscript; J. L. B.-C. designed the
diet interventions; M. D. A. and J. M. T. coordinated the study and data
entry; T. L. R. designed the MRS protocol and interpreted the scans; S.
C. designed the parent study and assisted with the data analysis. All
authors read and approved the final manuscript. None of the authors had
a conflict of interest to disclose.
NR 53
TC 20
Z9 20
U1 1
U2 11
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD MAR 28
PY 2013
VL 109
IS 6
BP 1096
EP 1104
DI 10.1017/S0007114512002966
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 107GE
UT WOS:000316202300015
PM 22849970
ER
PT J
AU Kettl, P
AF Kettl, Paul
TI The NRA Let Me Down
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 Philadelphia VA Med Ctr, Philadelphia, PA USA.
RP Kettl, P (reprint author), Philadelphia VA Med Ctr, Philadelphia, PA USA.
EM paul.kettl@va.gov
NR 2
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 MAR 27
PY 2013
VL 309
IS 12
BP 1239
EP 1240
DI 10.1001/jama.2013.1302
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 112WO
UT WOS:000316625200023
PM 23532239
ER
PT J
AU Redfield, MM
Chen, HH
Borlaug, BA
Semigran, MJ
Lee, KL
Lewis, G
LeWinter, MM
Rouleau, JL
Bull, DA
Mann, DL
Deswal, A
Stevenson, LW
Givertz, MM
Ofili, EO
O'Connor, CM
Felker, GM
Goldsmith, SR
Bart, BA
McNulty, SE
Ibarra, JC
Lin, G
Oh, JK
Patel, MR
Kim, RJ
Tracy, RP
Velazquez, EJ
Anstrom, KJ
Hernandez, AF
Mascette, AM
Braunwald, E
AF Redfield, Margaret M.
Chen, Horng H.
Borlaug, Barry A.
Semigran, Marc J.
Lee, Kerry L.
Lewis, Gregory
LeWinter, Martin M.
Rouleau, Jean L.
Bull, David A.
Mann, Douglas L.
Deswal, Anita
Stevenson, Lynne W.
Givertz, Michael M.
Ofili, Elizabeth O.
O'Connor, Christopher M.
Felker, G. Michael
Goldsmith, Steven R.
Bart, Bradley A.
McNulty, Steven E.
Ibarra, Jenny C.
Lin, Grace
Oh, Jae K.
Patel, Manesh R.
Kim, Raymond J.
Tracy, Russell P.
Velazquez, Eric J.
Anstrom, Kevin J.
Hernandez, Adrian F.
Mascette, Alice M.
Braunwald, Eugene
CA RELAX Trial
TI Effect of Phosphodiesterase-5 Inhibition on Exercise Capacity and
Clinical Status in Heart Failure With Preserved Ejection Fraction A
Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PULMONARY-HYPERTENSION; RIGHT VENTRICLE; OXYGEN-UPTAKE; SILDENAFIL;
DYSFUNCTION; PREVENTS; 1-YEAR; RATS; HEMODYNAMICS; ASSOCIATION
AB Importance Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF).
Objective To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF.
Design Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 stable outpatients with HF, ejection fraction >= 50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012.
Interventions Sildenafil (n=113) or placebo (n=103) administered orally at 20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks. Main Outcome Measures Primary end point was change in peak oxygen consumption after 24 weeks of therapy. Secondary end points included change in 6-minute walk distance and a hierarchical composite clinical status score (range, 1-n, a higher value indicates better status; expected value with no treatment effect, 95) based on time to death, time to cardiovascular or cardiorenal hospitalization, and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks.
Results Median age was 69 years, and 48% of patients were women. At baseline, median peak oxygen consumption (11.7 mL/kg/min) and 6-minute walk distance (308 m) were reduced. The median E/e' (16), left atrial volume index (44 mL/m(2)), and pulmonary artery systolic pressure (41 mm Hg) were consistent with chronically elevated left ventricular filling pressures. At 24 weeks, median (IQR) changes in peak oxygen consumption (mL/kg/min) in patients who received placebo (-0.20 [IQR, -0.70 to 1.00]) or sildenafil (-0.20 [IQR, -1.70 to 1.11]) were not significantly different (P=.90) in analyses in which patients with missing week-24 data were excluded, and in sensitivity analysis based on intention to treat with multiple imputation for missing values (mean between-group difference, 0.01 mL/kg/min, [95% CI, -0.60 to 0.61]). The mean clinical status rank score was not significantly different at 24 weeks between placebo (95.8) and sildenafil (94.2) (P=.85). Changes in 6-minute walk distance at 24 weeks in patients who received placebo (15.0 m [IQR, -26.0 to 45.0]) or sildenafil (5.0 m [IQR, -37.0 to 55.0]; P=.92) were also not significantly different. Adverse events occurred in 78 placebo patients (76%) and 90 sildenafil patients (80%). Serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%).
Conclusion and Relevance Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status.
Trial Registration clinicaltrials.gov Identifier: NCT00763867 JAMA. 2013; 309(12): 1268-1277 Published online March 11, 2013. doi: 10.1001/jama.2013.2024 www.jama.com
C1 [Redfield, Margaret M.; Chen, Horng H.; Borlaug, Barry A.; Lin, Grace; Oh, Jae K.] Mayo Clin, Dept Med, Rochester, MN 55905 USA.
[Semigran, Marc J.; Lewis, Gregory] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Lee, Kerry L.; Anstrom, Kevin J.] Duke Clin Res Inst, Dept Biostat & Bioinformat, Durham, NC USA.
[Velazquez, Eric J.; Hernandez, Adrian F.] Duke Clin Res Inst, Dept Med, Durham, NC USA.
[McNulty, Steven E.] Duke Clin Res Inst, Dept Stat, Durham, NC USA.
[Ibarra, Jenny C.] Duke Clin Res Inst, Dept Project Management, Durham, NC USA.
[LeWinter, Martin M.] Univ Vermont, Dept Med, Burlington, VT 05405 USA.
[Tracy, Russell P.] Univ Vermont, Dept Pathol & Biochem, Burlington, VT 05405 USA.
[Rouleau, Jean L.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Rouleau, Jean L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Bull, David A.] Univ Utah, Dept Surg, Salt Lake City, UT USA.
[Mann, Douglas L.] Barnes Jewish Hosp, Dept Med, St Louis, MO 63110 USA.
[Deswal, Anita] Michael E DeBakey VA Med Ctr, Dept Med, Houston, TX USA.
[Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA.
[Stevenson, Lynne W.; Givertz, Michael M.; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Ofili, Elizabeth O.] Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA.
[O'Connor, Christopher M.; Felker, G. Michael; Patel, Manesh R.; Kim, Raymond J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Kim, Raymond J.] Duke Univ, Med Ctr, Duke Cardiovasc Magnet Resonance Ctr, Durham, NC USA.
Duke Heart Ctr, Durham, NC USA.
[Goldsmith, Steven R.; Bart, Bradley A.] Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA.
[Mascette, Alice M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Redfield, MM (reprint author), Mayo Clin, Div Cardiovasc Dis, 200 1st St SW,Guggenheim 9, Rochester, MN 55905 USA.
EM redfield.margaret@mayo.edu
RI Hernandez, Adrian F./A-7818-2016;
OI Hernandez, Adrian F./0000-0003-3387-9616; Mann, Douglas
/0000-0002-2516-0145
FU National Institutes of Health (NIH); Medscape; Medscape, Amgen;
GlaxoSmithKline; Atcor Medical and Gilead; National Heart, Lung, and
Blood Institute; National Institute on Minority Health and Health
Disparities; Roche Diagnostics; Amgen; Novartis; Ikaria; Acetlion
Pharma; Heartware; ResMed; Pozen; GE Healthcare; Johnson Johnson;
Gilead; Critical Diagnostics; BG Medicine; Otsuka; Astellas; Novella;
Novella, Cytokinetics; Capricor; Singulex; Bristol-Myers Squibb; Amylin;
National Heart, Lung, and Blood Institute [U10HL084904, U10HL084861,
U10HL084875, U10HL084877, U10HL084889, U10HL084890, U10HL084891,
U10HL084899, U10HL084907, U10HL084931]; National Center for Advancing
Translational Sciences [UL1TR000454]; National Institute on Minority
Health and Health Disparities [8 U54 MD007588]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Redfield reported receiving
financial support from the National Institutes of Health (NIH) and
royalties from Annexon. Dr Chen reported receiving funding for patents
that his institution has licensed to Nile Therapeutics and Annexon with
other patents pending at the US Patent and Trademark Office. He also
reported that he has royalties with Nile Therapeutics, Annexon, and Up
To Date. Dr Borlaug reported receiving consulting fees from Medscape,
Amgen, and GlaxoSmithKline and receiving financial support from Atcor
Medical and Gilead. Dr Semigran reported receiving financial support
from the NIH for participation in the Heart Failure Network and from
Bayer. Dr Lee reported receiving financial support from the NIH for
participation in the Heart Failure Network. Dr LeWinter reported
receiving financial support from the NIH for participation in the Heart
Failure Network. Dr Bull reported receiving financial support from the
NIH for participation in the Heart Failure Network. Dr Deswal reported
receiving financial support from the NIH for participation in the Heart
Failure Network. Dr Stevenson reported receiving financial support from
the NIH for participation in the Heart Failure Network. Dr Givertz
reported receiving financial support from the NIH for participation in
the Heart Failure Network. Dr Ofili reported receiving financial support
from the NIH, receiving consulting fees from Merck, Novartis, and Arbor
Pharmaceuticals and lecture fees from Arbor Pharmaceuticals. She is
currently employed by the Morehouse School of Medicine and has grants
pending from the National Heart, Lung, and Blood Institute and National
Institute on Minority Health and Health Disparities. DrO'Connor reported
receiving consulting fees from Roche Diagnostics, Amgen, Novartis,
Ikaria, Acetlion Pharma, Heartware, ResMed, Pozen, GE Healthcare,
Johnson & Johnson, Gilead, Critical Diagnostics, BG Medicine, Otsuka,
Astellas, Novella, Cytokinetics, and Capricor; holding stock options
with Neurotronik/Interventional Autonomics Corporation; editing American
College of Cardiology; and coowning Cardiology Consulting Associates. Dr
Felker reported receiving financial support from the NIH; consulting
fees from Novartis, Amgen, Trevena, Roche Diagnostics, Merck, Singulex,
and BG Medicine; and funding from Amgen, Otsuka, and Roche Diagnostics.
Dr Bart reported receiving financial support from the NIH for
participation in the Heart Failure Network. Ms Ibarra reported receiving
financial support from the NIH for participation in the Heart Failure
Network. Dr Oh received financial support from the NIH for the Echo Core
Lab. Dr Patel has received consulting fees from Genzyme, Baxter, Jensen,
and Bayer, and his financial institution receives financial support from
AstraZeneca, Johnson & Johnson, and Maquet. Dr Kim reported receiving
financial support from the NIH as the Heart Failure Network Data
Coordinating Center and MRI Core Lab, and funding for a patent with
Northwestern University. His institution has received a grant from
Siemens. Dr Tracy reported receiving financial support from the NIH for
participation in the Heart Failure Network, and consulting fees
fromMerck, Tibotec-Johnson & Johnson, and Abbott. He has also given
expert testimony about biomarkers in blood clotting and is the owner of
Haematologic Technologies. Dr Velazquez reported receiving financial
support from the NIH for participation in the Heart Failure Network.; Dr
Anstrom reported receiving financial support from the NIH for
participation in the Heart Failure Network. Dr Hernandez reported
receiving financial support from the NIH for participation in the Heart
Failure Network and consulting fees from AstraZeneca, Corthera, Janseen,
and Bristol-Myers Squibb. His institution has received funding from
Amylin, Johnson & Johnson, and Bristol-Myers Squibb. Dr Braunwald
reported receiving consulting fees from Merck, Daiichi Sankyo, Genzyme,
Amorcyte, Medicines Co, MC Communications, Ikaria, CardioRentis,
sanofiaventis; funding (or pending funding) from AstraZeneca, Johnson &
Johnson, Merck, sanofi-aventis, Daiichi Sankyo, GlaxoSmithKline,
Bristol-Myers Squibb, Beckman Coulter, Roche Diagnostics, and Pfizer;
compensation for lectures for Eli Lilly, Merck, CVRx (no compensation),
CV Therapeutics (now Gilead), Daiichi Sankyo, MC Communications,
Manarini International, Medscape, and Bayer; and payment for
devel-opment of educational presentations from MC Communications. No
other disclosures were reported.; This work was supported by grants
U10HL084904 (for the data coordinating center), and U10HL084861,
U10HL084875, U10HL084877, U10HL084889, U10HL084890, U10HL084891,
U10HL084899, U10HL084907, and U10HL084931 (for the clinical centers)
from the National Heart, Lung, and Blood Institute. This work is also
supported by grant UL1TR000454 from the National Center for Advancing
Translational Sciences and grant 8 U54 MD007588 from the National
Institute on Minority Health and Health Disparities. Pfizer provided
study drug (sildenafil and matched placebo).
NR 31
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U1 5
U2 36
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 27
PY 2013
VL 309
IS 12
BP 1268
EP 1277
DI 10.1001/jama.2013.2024
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 112WO
UT WOS:000316625200027
PM 23478662
ER
PT J
AU Maison, SF
Usubuchi, H
Liberman, MC
AF Maison, Stephane F.
Usubuchi, Hajime
Liberman, M. Charles
TI Efferent Feedback Minimizes Cochlear Neuropathy from Moderate Noise
Exposure
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CROSSED OLIVOCOCHLEAR BUNDLE; AUDITORY-NERVE FIBERS;
ELECTRICAL-STIMULATION; MAMMALIAN COCHLEA; ACOUSTIC INJURY; CELL
SYNAPSES; BRAIN-STEM; CAT; RESPONSES; MOUSE
AB Although protective effects of the cochlea's efferent feedback pathways have been well documented, prior work has focused on hair cell damage and cochlear threshold elevation and, correspondingly, on the high sound pressure levels (>100 dB SPL) necessary to produce them. Here we explore the noise-induced loss of cochlear neurons that occurs with lower-intensity exposures and in the absence of permanent threshold shifts. Using confocal microscopy to count synapses between hair cells and cochlear nerve fibers, and using measurement of auditory brainstem responses and otoacoustic emissions to assess cochlear presynaptic and postsynaptic function, we compare the damage from a weeklong exposure to moderate-level noise (84 dB SPL) in mice with varying degrees of cochlear de-efferentation induced by surgical lesion to the olivocochlear pathway. Such exposure causes minimal acute threshold shifts and no chronic shifts in mice with normal efferent feedback. In de-efferented animals, there was up to 40% loss of cochlear nerve synapses and a corresponding decline in the amplitude of the auditory brainstem response. Quantitative analysis of the de-efferentation in inner versus outer hair cell areas suggested that outer hair cell efferents are the most important in minimizing this neuropathy, presumably by virtue of their sound-evoked feedback reduction of cochlear amplification. The moderate nature of this acoustic overexposure suggests that cochlear neurons are at risk even in everyday acoustic environments, so the need for cochlear protection is plausible as a driving force in the design of this feedback pathway.
C1 [Maison, Stephane F.; Usubuchi, Hajime; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Maison, Stephane F.; Usubuchi, Hajime; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Maison, Stephane F.; Liberman, M. Charles] Harvard Program Speech & Hearing Biosci & Technol, Boston, MA 02114 USA.
RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM stephane_maison@meei.harvard.edu
FU National Institute on Deafness and Other Communication Disorders [R01 DC
0188, P30 DC 05209]
FX This work was supported by the National Institute on Deafness and Other
Communication Disorders (Grants R01 DC 0188 and P30 DC 05209). We thank
Leslie Liberman for flawless technical support in the preparation and
immunostaining of cochlear whole mounts.
NR 50
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U1 0
U2 14
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 MAR 27
PY 2013
VL 33
IS 13
BP 5542
EP 5552
DI 10.1523/JNEUROSCI.5027-12.2013
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 117JD
UT WOS:000316948600012
PM 23536069
ER
PT J
AU Foerde, K
Race, E
Verfaellie, M
Shohamy, D
AF Foerde, Karin
Race, Elizabeth
Verfaellie, Mieke
Shohamy, Daphna
TI A Role for the Medial Temporal Lobe in Feedback-Driven Learning:
Evidence from Amnesia
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FREE-OPERANT ACQUISITION; MULTIPLE MEMORY-SYSTEMS; SHORT-TERM-MEMORY;
DELAYED REINFORCEMENT; DOPAMINE NEURONS; HUMAN BRAIN; WORKING-MEMORY;
PARKINSONS-DISEASE; RELATIONAL MEMORY; REWARD
AB The ability to learn from feedback is a key component of adaptive behavior. This type of learning is traditionally thought to depend on neural substrates in the striatum and not on the medial temporal lobe (MTL). Here we show that in humans the MTL becomes necessary for feedback-based learning when feedback is delayed. Specifically, amnesic patients with MTL damage were impaired at probabilistic learning of cue-outcome associations when response-contingent feedback was delayed by a few seconds, but not when feedback was immediate. By contrast, patients with striatal dysfunction due to Parkinson's disease demonstrated the opposite pattern: impaired learning when trial-by-trial feedback was immediate but not when feedback was delayed, indicating that the striatum is necessary for learning only when feedback is immediate. Together, these results reveal that multiple complementary learning processes support what appears to be identical behavior in healthy individuals and point to an important role for the MTL in feedback-driven learning.
C1 [Foerde, Karin; Shohamy, Daphna] Columbia Univ, Dept Psychol, New York, NY 10027 USA.
[Race, Elizabeth; Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02118 USA.
[Race, Elizabeth; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Foerde, K (reprint author), Schermerhorn Hall 312,1190 Amsterdam Ave,MC 5501, New York, NY 10027 USA.
EM kf2265@columbia.edu; ds2619@columbia.edu
OI Verfaellie, Mieke/0000-0001-5535-4584; Foerde, Karin/0000-0002-5804-9312
FU NIH [NIDA 1R03DA026957, NINDS NRSA 5F32NS063632, F32NS073212]; NSF
Career Development Award; Clinical Science Research and Development
Service of the Department of Veterans Affairs
FX This work was supported by the NIH (NIDA 1R03DA026957 to D. S., NINDS
NRSA 5F32NS063632 to K. F., and F32NS073212 to E. R.), an NSF Career
Development Award to D. S., and the Clinical Science Research and
Development Service of the Department of Veterans Affairs. We are
grateful to Dr. Lucien Cote for recruitment of participants with
Parkinson's disease and to Erin Kendall Braun for assistance with data
collection.
NR 67
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U1 1
U2 16
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 27
PY 2013
VL 33
IS 13
BP 5698
EP 5704
DI 10.1523/JNEUROSCI.5217-12.2013
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 117JD
UT WOS:000316948600026
PM 23536083
ER
PT J
AU Loving, GS
Mukherjee, S
Caravan, P
AF Loving, Galen S.
Mukherjee, Shreya
Caravan, Peter
TI Redox-Activated Manganese-Based MR Contrast Agent
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID MAGNETIC-RESONANCE; THIOL/DISULFIDE REDOX; TUMOR HYPOXIA; COMPLEXES;
CELL; STATE; METABOLISM; BINDING; THIOLS; CANCER
AB Here we report a simple Mn coordination complex with utility as a redox-sensitive MR probe. The HBET ligand stabilizes both the Mn2+ and Mn3+ oxidation states. In the presence of glutathione (GSH), low relaxivity Mn-III-HBET is converted to high relaxivity Mn-II-HBET with a 3-fold increase in relaxivity, and concomitant increase in MR signal. Alternately, hydrogen peroxide can convert Mn-II-HBET to Mn-III-HBET with a reduction in MR signal.
C1 [Loving, Galen S.; Mukherjee, Shreya; Caravan, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Caravan, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA.
EM caravan@nmr.mgh.harvard.edu
FU National Cancer Institute [CA161221, CA009502]; National Center for
Research Resources [RR14075]
FX Dr. Anna Moore is gratefully acknowledged for providing access to a
spectrophotometer. This work was supported by grants from the National
Cancer Institute (CA161221 to PC and a T32 post-doctoral fellowship to
GSL, CA009502) and instrumentation funded by the National Center for
Research Resources (RR14075).
NR 34
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Z9 45
U1 4
U2 81
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD MAR 27
PY 2013
VL 135
IS 12
BP 4620
EP 4623
DI 10.1021/ja312610j
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 118NK
UT WOS:000317032000012
PM 23510406
ER
PT J
AU Liou, AP
Paziuk, M
Luevano, JM
Machineni, S
Turnbaugh, PJ
Kaplan, LM
AF Liou, Alice P.
Paziuk, Melissa
Luevano, Jesus-Mario, Jr.
Machineni, Sriram
Turnbaugh, Peter J.
Kaplan, Lee M.
TI Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host
Weight and Adiposity
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID DIET-INDUCED OBESITY; CHAIN FATTY-ACIDS; PROTEIN-COUPLED RECEPTOR;
ENERGY-EXPENDITURE; GASTROINTESTINAL-TRACT; SURGERY; MECHANISMS; MOUSE;
MICE; DIVERSITY
AB Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.
C1 [Liou, Alice P.; Paziuk, Melissa; Machineni, Sriram; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA.
[Liou, Alice P.; Paziuk, Melissa; Machineni, Sriram; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Luevano, Jesus-Mario, Jr.; Turnbaugh, Peter J.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
RP Turnbaugh, PJ (reprint author), Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
EM pturnbaugh@fas.harvard.edu; LMKaplan@partners.org
RI Biguzzi, Felipe/E-4724-2015;
OI Turnbaugh, Peter/0000-0002-0888-2875
FU NIH [DK088661, P50 GM068763, F32 DK095561, P30DK034854]; Ethicon
Surgical Care
FX NIH DK088661 (L. M. K.), NIH P50 GM068763 (P.J.T.), F32 DK095561 (A. P.
L.), P30DK034854 (Harvard Digestive Diseases Center), and Ethicon
Surgical Care (L.M.K.).
NR 56
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U1 7
U2 73
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 27
PY 2013
VL 5
IS 178
AR 178ra41
DI 10.1126/scitranslmed.3005687
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 115EL
UT WOS:000316795300005
PM 23536013
ER
PT J
AU Luiz, CR
Machado, CM
Canto, CLM
Christ, SCC
Pestana, JOM
Kotton, CN
Camargo, LFA
AF Luiz, Claudia R.
Machado, Clarisse M.
Canto, Cynthia L. M.
Christ, Silvia C. C.
Pestana, Jose O. M.
Kotton, Camille N.
Camargo, Luis F. A.
TI Monitoring for HHV-6 Infection After Renal Transplantation: Evaluation
of Risk Factors for Sustained Viral Replication
SO TRANSPLANTATION
LA English
DT Article
DE Human herpesvirus 6 (HHV-6); Renal transplantation; PCR; Active viral
infection; Sustained viral replication
ID HUMAN-HERPESVIRUS 6; STEM-CELL TRANSPLANTATION; HUMAN-HERPESVIRUS-6 DNA;
LIVER-TRANSPLANTATION; RECIPIENTS; PCR; ENCEPHALITIS; BLOOD;
PATHOGENESIS; DISEASE
AB Background. Human herpesvirus-6 (HHV-6) is known to reactivate after renal transplantation and has been associated with several clinical manifestations. Risk factors for sustained viral replication, however, remain unclear.
Methods. Thirty consecutive kidney transplant patients were prospectively followed for HHV-6 replication between February 2007 and February 2008. Plasma samples for DNA detection were collected from the donor and the recipient before transplantation and from the recipient weekly for the first 2 months after transplantation and then every 2 weeks for 2 additional months. HHV-6 active infection was defined as detection of viral DNA in plasma, by polymerase chain reaction, in at least two consecutive samples over an interval of at least 1 week.
Results. Active viral infection was detected in 25% of the recipients before transplantation and 27% (8 of 30) of the patients after transplantation. The mean time to onset of viral replication was 28.1 days after transplantation and 7 of 8 (87.5%) were asymptomatic. Risk factors associated with active HHV-6 infection were receiving an organ from a living donor (P=0.028), recipients with IgM antibodies detected before transplantation (P=0.005), and pretransplantation recipient HHV-6 viral load more than 10,000 copies/mL plasma (P=0.034).
Conclusions. Active HHV-6 infection occurs early after renal transplantation and is mostly asymptomatic. Donor or recipient infection may occur at the time of transplantation and are related to higher rates of posttransplantation infections.
C1 [Luiz, Claudia R.; Camargo, Luis F. A.] Univ Fed Sao Paulo UNIFESP, Dept Infect Dis, BR-05685090 Sao Paulo, Brazil.
[Machado, Clarisse M.; Canto, Cynthia L. M.] Univ Sao Paulo, Inst Med Trop Sao Paulo, Virol Lab, Sao Paulo, Brazil.
[Christ, Silvia C. C.] Univ Fed Sao Paulo, Dept Infect Dis, Sao Paulo, Brazil.
[Pestana, Jose O. M.] Univ Fed Sao Paulo UNIFESP, Dept Med, Div Nephrol, BR-05685090 Sao Paulo, Brazil.
[Kotton, Camille N.] Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Serv, Boston, MA 02114 USA.
RP Camargo, LFA (reprint author), Univ Fed Sao Paulo UNIFESP, Dept Infect Dis, Rua Barao Santa Eulalia 170 Ap 21, BR-05685090 Sao Paulo, Brazil.
EM Luis_camargo@einstein.br
FU FAPESP
FX This work was supported by a grant from FAPESP.
NR 31
TC 2
Z9 2
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD MAR 27
PY 2013
VL 95
IS 6
BP 842
EP 846
DI 10.1097/TP.0b013e3182807ab7
PG 5
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 109CO
UT WOS:000316343000017
PM 23354300
ER
PT J
AU Wilson, LB
Rojas, DC
Shatti, S
Tregellas, JR
AF Wilson, Lisa B.
Rojas, Donald C.
Shatti, Shireen
Tregellas, Jason R.
TI Greater neuronal responses during automatic semantic processing in
schizophrenia
SO NEUROREPORT
LA English
DT Article
DE functional magnetic resonance imaging; fusiform gyrus; schizophrenia;
semantic priming; superior temporal gyrus
ID MRC PSYCHOLINGUISTIC DATABASE; ACTIVATION; BRAIN
AB A core feature of schizophrenia is a disturbance of associative processes. To date, no functional MRI studies have investigated semantic priming in schizophrenia under experimental conditions that measure automatic, as opposed to strategic, processing. The present study's focus was to investigate hemodynamic responses during indirect semantic priming at a short stimulus onset asynchrony (i.e. 350 ms), conditions which are considered to be a particularly sensitive measure of automatic spreading activation during semantic processing and of the associative disturbances in schizophrenia. Seventeen individuals with DSM-IV, schizophrenia and 15 comparison participants underwent functional scanning while performing a lexical decision task on directly related, indirectly related, unrelated, and word/nonword pairs. A random-effects region of interest analysis within a priori temporal and frontal regions was performed. Whereas comparison individuals exhibited hemodynamic suppression in response to priming, individuals with schizophrenia exhibited hemodynamic enhancement. Relative to the comparison group, these enhancements were observed in the left fusiform and superior temporal gyri for indirectly related word pairs relative to unrelated pairs. Greater priming-related responses within temporal regions may reflect increased and prolonged automatic spreading activation during semantic processing in schizophrenia. NeuroReport 24:212-216 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Wilson, Lisa B.; Rojas, Donald C.; Shatti, Shireen; Tregellas, Jason R.] Univ Colorado Denver, Dept Psychiat, Aurora, CO 80045 USA.
[Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO USA.
RP Wilson, LB (reprint author), Univ Colorado Denver, Dept Psychiat, 13001 East 17th Pl, Aurora, CO 80045 USA.
EM lisa.wilson@ucdenver.edu
RI Tregellas, Jason/J-3637-2015;
OI Rojas, Don/0000-0001-6560-9616
FU National Institute of Mental Health (NIMH) [MH60214]; National Institute
of Child Health and Human Development (NICHHD) [HD041697]; Brain and
Behavior Research Foundation; Blowitz-Ridgeway Foundation
FX Funding for this study was provided by the National Institute of Mental
Health (NIMH) Grant MH60214, the National Institute of Child Health and
Human Development (NICHHD) Grant HD041697 the Brain and Behavior
Research Foundation and the Blowitz-Ridgeway Foundation.
NR 24
TC 4
Z9 4
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD MAR 27
PY 2013
VL 24
IS 5
BP 212
EP 216
DI 10.1097/WNR.0b013e32835eb688
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 103VD
UT WOS:000315946700002
PM 23399997
ER
PT J
AU Cornes, BK
Brody, J
Morrison, AC
Siscovick, D
Meigs, JB
AF Cornes, Belinda K.
Brody, Jennifer
Morrison, Alanna C.
Siscovick, David
Meigs, James B.
CA CHARGE-S Diabet WG
TI Rare Variants in and Near IRS1 are Associated with Fasting Insulin in
CHARGE-S Cohorts
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Diabetes mellitus; Genetics; Insulin
C1 [Cornes, Belinda K.; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Brody, Jennifer; Siscovick, David] Univ Washington, Seattle, WA 98195 USA.
[Morrison, Alanna C.] Univ Texas Hlth Sci Cntr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P054
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100195
ER
PT J
AU Lopez, L
Porneala, B
deLemos, JA
Ayers, CR
Albert, MA
AF Lopez, Lenny
Porneala, Bianca
deLemos, James A.
Ayers, Colby R.
Albert, Michelle A.
TI Perceived Discrimination and Subclinical Atherosclerosis in the Dallas
Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Atherosclerosis; Racial/ethnic disparities; Coronary artery disease
C1 [Lopez, Lenny; Porneala, Bianca] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[deLemos, James A.; Ayers, Colby R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Albert, Michelle A.] Howard Univ, Washington, DC 20059 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P237
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100357
ER
PT J
AU Lopez, L
Marceau, L
Piccolo, R
Liu, G
Vassy, J
Grant, R
Meigs, JB
McKinlay, J
AF Lopez, Lenny
Marceau, Lisa
Piccolo, Rebecca
Liu, Gretchen
Vassy, Jason
Grant, Richard
Meigs, James B.
McKinlay, John
TI Impact of Acculturation and Health Literacy on Prevalent Fasting
Glycemia Among Latinos: Results From the Boston Area Community Health
(BACH) Survey
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Diabetes mellitus; Racial/ethnic disparities
C1 [Lopez, Lenny; Vassy, Jason; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Marceau, Lisa; Piccolo, Rebecca; Liu, Gretchen; McKinlay, John] New England Rsch Inst, Watertown, MA USA.
[Grant, Richard] Kaiser Permanente, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P236
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100356
ER
PT J
AU McMahon, GM
O'Seaghdha, CM
Hwang, SJ
Meigs, JB
Fox, CS
AF McMahon, Gearoid M.
O'Seaghdha, Conall M.
Hwang, Shih-Jen
Meigs, James B.
Fox, Caroline S.
TI The Association of the CUBN Polymorphism rs1801239 and the Association
of Albuminuria and Cardiovascular Disease in the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Cardiovascular disease; Risk factors; Renal function
C1 [McMahon, Gearoid M.; O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[McMahon, Gearoid M.; O'Seaghdha, Conall M.; Hwang, Shih-Jen; Fox, Caroline S.] Cntr Populat Studies, Framingham, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P309
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100428
ER
PT J
AU Miedema, MD
Petrone, A
Pankow, J
Hunt, SC
Kraja, AT
Arnett, DK
Gaziano, JM
Djousse, L
AF Miedema, Michael D.
Petrone, Andrew
Pankow, James
Hunt, Steven C.
Kraja, Aldi T.
Arnett, Donna K.
Gaziano, J. Michael
Djousse, Luc
TI Adult Height and Coronary Artery Calcium in the NHLBI Family Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Subclinical atherosclerosis
C1 [Miedema, Michael D.; Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Boston, MA USA.
[Petrone, Andrew] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Pankow, James] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Hunt, Steven C.] Univ Utah, Salt Lake City, UT USA.
[Kraja, Aldi T.] Washington Univ, Div Stat Genom, St Louis, MO USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P386
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100504
ER
PT J
AU Rodriguez, F
Meigs, JB
Porneala, B
Lopez, L
AF Rodriguez, Fatima
Meigs, James B.
Porneala, Bianca
Lopez, Lenny
TI The Impact of Acculturation on Hyperglycemia and Cardio-Metabolic Risk
Factors among Hispanic Adults: Results from the National and Nutrition
Examination Survey 1999-2008
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Diabetes mellitus; Obesity
C1 [Rodriguez, Fatima; Meigs, James B.; Porneala, Bianca; Lopez, Lenny] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P232
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100352
ER
PT J
AU Rosenquist, KJ
Massaro, JM
Krieger, BE
Murabito, JM
Hoffmann, U
Fox, CS
AF Rosenquist, Klara J.
Massaro, Joseph M.
Krieger, Bernard E.
Murabito, Joanne M.
Hoffmann, Udo
Fox, Caroline S.
TI Fat Quality Estimated by Computed Tomography and Associations with
Incident Cardiovascular Disease and All Cause Mortality
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Obesity; Outcomes
C1 [Rosenquist, Klara J.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Rosenquist, Klara J.] Harvard Univ, Sch Med, Boston, MA USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Krieger, Bernard E.; Murabito, Joanne M.] Boston Med Cntr, Gen Internal Med Sect, Boston, MA USA.
[Krieger, Bernard E.; Murabito, Joanne M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Div Intra Mural Rsch, Framingham, MA USA.
[Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP63
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100111
ER
PT J
AU Suchindran, S
Regan, S
Meigs, JB
Grinspoon, SK
Triant, VA
AF Suchindran, Sujit
Regan, Susan
Meigs, James B.
Grinspoon, Steven K.
Triant, Virginia A.
TI Aspirin Use and Myocardial Infarction in HIV versus Non-HIV Patients
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Aspirin; Myocardial infarction; Viruses
C1 [Suchindran, Sujit; Regan, Susan; Meigs, James B.; Grinspoon, Steven K.; Triant, Virginia A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA 030
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100028
ER
PT J
AU Thorndike, AN
Riis, J
Sonnenberg, L
Levy, DE
AF Thorndike, Anne N.
Riis, Jason
Sonnenberg, Lillian
Levy, Douglas E.
TI Long-term Effectiveness of a Color-coded Food Labeling Intervention in
Promoting Healthy Choices
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Nutrition; Public health; Obesity
C1 [Thorndike, Anne N.; Sonnenberg, Lillian; Levy, Douglas E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Riis, Jason] Harvard Univ, Sch Business, Boston, MA 02163 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA 060
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100052
ER
PT J
AU Tsao, CW
Pencina, K
Massaro, JM
Levy, D
Vasan, RS
Hoffmann, U
O'Donnell, CJ
Mitchell, GF
AF Tsao, Connie W.
Pencina, Karol
Massaro, Joseph M.
Levy, Daniel
Vasan, Ramachandran S.
Hoffmann, Udo
O'Donnell, Christopher J.
Mitchell, Gary F.
TI Relations of Subclinical Measures of Arterial Stiffness and Pulsatility
with Arterial Calcification in Men and Women
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Aortic diseases; Calcification; Subclinical atherosclerosis
C1 [Tsao, Connie W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tsao, Connie W.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Boston, MA USA.
[Tsao, Connie W.] Beth Israel Deaconess Med Ctr, Framingham, MA USA.
[Tsao, Connie W.; Levy, Daniel; Vasan, Ramachandran S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Pencina, Karol; Massaro, Joseph M.; Vasan, Ramachandran S.] Boston Univ, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Framingham, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc F, Norwood, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P381
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100499
ER
PT J
AU Vassy, JL
Porneala, B
Florez, JC
Dupuis, J
Meigs, JB
AF Vassy, Jason L.
Porneala, Bianca
Florez, Jose C.
Dupuis, Josee
Meigs, James B.
TI Type 2 Diabetes Prediction with 17-, 40-, and 62-variant Genotype Risk
Scores: The Framingham Offspring Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Diabetes mellitus; Genomics; Risk factors
C1 [Vassy, Jason L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Porneala, Bianca; Florez, Jose C.; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP58
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100106
ER
PT J
AU Weinberg, I
Gona, P
O'Donnell, CJ
Jaff, MR
Murabito, J
AF Weinberg, Ido
Gona, Philimon
O'Donnell, Christopher J.
Jaff, Michael R.
Murabito, Joanne
TI Inter-arm Blood Pressure Difference and Cardiovascular Disease Risk in
the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Subclinical atherosclerosis; Cardiovascular disease; Risk factors
C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gona, Philimon] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Boston, MA USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Murabito, Joanne] Framingham Heart Dis Epidemiol Study, Boston, MA USA.
[Murabito, Joanne] Boston Univ, Sch Med, Boston, MA 02118 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA P075
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100216
ER
PT J
AU Xanthakis, V
Larson, M
Vasan, RS
Wollert, KC
Januzzi, JL
Wang, TJ
AF Xanthakis, Vanessa
Larson, Martin
Vasan, Ramachandran S.
Wollert, Kai C.
Januzzi, James L.
Wang, Thomas J.
TI Screening for Left Ventricular Dysfunction and Hypertrophy with Novel
Biomarkers of Cardiovascular Stress
SO CIRCULATION
LA English
DT Meeting Abstract
CT Scientific Sessions of the American-Heart-Association on Epidemiology
and Prevention/Physical Activity, Nutrition and Metabolism
CY MAR 19-22, 2013
CL New Orleans, LA
SP Amer Heart Assoc
DE Cardiac markers; Cardiovascular disease prevention; Heart failure
C1 [Xanthakis, Vanessa; Larson, Martin; Vasan, Ramachandran S.] Boston Univ, Boston, MA 02215 USA.
[Wollert, Kai C.] Hans Borst Cntr Heart & Stem Cell Rsch, Hannover, Germany.
[Januzzi, James L.; Wang, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 26
PY 2013
VL 127
IS 12
SU S
MA MP05
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 302HW
UT WOS:000330596100057
ER
PT J
AU Kurra, V
Krajewski, KM
Jagannathan, J
Giardino, A
Berlin, S
Ramaiya, N
AF Kurra, Vikram
Krajewski, Katherine M.
Jagannathan, Jyothi
Giardino, Angela
Berlin, Suzanne
Ramaiya, Nikhil
TI Typical and atypical metastatic sites of recurrent endometrial carcinoma
SO CANCER IMAGING
LA English
DT Review
DE Recurrent endometrial carcinoma; oncologic imaging; computed tomography;
magnetic resonance imaging; positron emission tomography
ID PROGNOSTIC-FACTORS; CANCER; PET/CT
AB The purpose of this article is to illustrate the imaging findings of typical and atypical metastatic sites of recurrent endometrial carcinoma. Typical sites include local pelvic recurrence, pelvic and para-aortic nodes, peritoneum, and lungs. Atypical sites include extra-abdominal lymph nodes, liver, adrenals, brain, bones and soft tissue. It is important for radiologists to recognize the typical and atypical sites of metastases in patients with recurrent endometrial carcinoma to facilitate earlier diagnosis and treatment.
C1 [Kurra, Vikram; Krajewski, Katherine M.; Jagannathan, Jyothi; Giardino, Angela; Berlin, Suzanne; Ramaiya, Nikhil] Brigham & Womens Hosp, Dept Imaging, Boston, MA 02115 USA.
[Krajewski, Katherine M.; Jagannathan, Jyothi; Giardino, Angela; Berlin, Suzanne; Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.
RP Kurra, V (reprint author), Brigham & Womens Hosp, Dept Imaging, 75 Francis St, Boston, MA 02115 USA.
EM vkurra@partners.org
NR 14
TC 5
Z9 5
U1 1
U2 3
PU E-MED
PI LONDON
PA PO BOX 29761, LONDON, NW3 7ZS, ENGLAND
SN 1470-7330
J9 CANCER IMAGING
JI Cancer Imaging
PD MAR 26
PY 2013
VL 13
IS 1
BP 113
EP 122
DI 10.1102/1470-7330.2013.0011
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 173CY
UT WOS:000321056900001
PM 23545091
ER
PT J
AU Desmet, CJ
Gallenne, T
Prieur, A
Reyal, F
Visser, NL
Wittner, BS
Smit, MA
Geiger, TR
Laoukili, J
Iskit, S
Rodenko, B
Zwart, W
Evers, B
Horlings, H
Ajouaou, A
Zevenhoven, J
Van Vliet, M
Ramaswamy, S
Wessels, LFA
Peeper, DS
AF Desmet, Christophe J.
Gallenne, Tristan
Prieur, Alexandre
Reyal, Fabien
Visser, Nils L.
Wittner, Ben S.
Smit, Marjon A.
Geiger, Thomas R.
Laoukili, Jamila
Iskit, Sedef
Rodenko, Boris
Zwart, Wilbert
Evers, Bastiaan
Horlings, Hugo
Ajouaou, Abderrahrim
Zevenhoven, John
Van Vliet, Martin
Ramaswamy, Sridhar
Wessels, Lodewyk F. A.
Peeper, Daniel S.
TI Identification of a pharmacologically tractable Fra-1/ADORA2B axis
promoting breast cancer metastasis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE epithelial-mesenchymal transition; invasion
ID EPITHELIAL-MESENCHYMAL TRANSITION; NEUROTROPHIC RECEPTOR TRKB;
GENE-EXPRESSION PROFILES; ANOIKIS RESISTANCE; TRANSCRIPTION FACTORS;
FRA-1 EXPRESSION; THYROID-CELLS; TUMOR-GROWTH; IN-VITRO; TRANSFORMATION
AB Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular processes to clinical outcome, we aimed to identify transcriptional nodes regulating cancer cell metastasis. Using rodent xenograft models that we previously developed, we identified the transcription factor Fos-related antigen-1 (Fra-1) as a key coordinator of metastasis. Because Fra-1 often is overexpressed in human metastatic breast cancers and has been shown to control their invasive potential in vitro, we aimed to assess the implication and prognostic significance of the Fra-1-dependent genetic program in breast cancer metastasis and to identify potential Fra-1-dependent therapeutic targets. In several in vivo assays in mice, we demonstrate that stable RNAi depletion of Fra-1 from human breast cancer cells strongly suppresses their ability to metastasize. These results support a clinically important role for Fra-1 and the genetic program it controls. We show that a Fra-1-dependent gene-expression signature accurately predicts recurrence of breast cancer. Furthermore, a synthetic lethal drug screen revealed that antagonists of the adenosine receptor A(2B) (ADORA2B) are preferentially toxic to breast tumor cells expressing Fra-1. Both RNAi silencing and pharmacologic blockade of ADORA2B inhibited filopodia formation and invasive activity of breast cancer cells and correspondingly reduced tumor outgrowth in the lungs. These data show that Fra-1 activity is causally involved in and is a prognostic indicator of breast cancer metastasis. They suggest that Fra-1 activity predicts responsiveness to inhibition of pharmacologically tractable targets, such as ADORA2B, which may be used for clinical interference of metastatic breast cancer.
C1 [Desmet, Christophe J.; Gallenne, Tristan; Prieur, Alexandre; Visser, Nils L.; Smit, Marjon A.; Geiger, Thomas R.; Laoukili, Jamila; Iskit, Sedef; Zevenhoven, John; Peeper, Daniel S.] Netherlands Canc Inst, Dept Mol Oncol, NL-1066 CX Amsterdam, Netherlands.
[Reyal, Fabien; Horlings, Hugo; Ajouaou, Abderrahrim] Netherlands Canc Inst, Dept Pathol, NL-1066 CX Amsterdam, Netherlands.
[Rodenko, Boris; Van Vliet, Martin] Netherlands Canc Inst, Dept Cell Biol 2, NL-1066 CX Amsterdam, Netherlands.
[Zwart, Wilbert] Netherlands Canc Inst, Dept Mol Pathol, NL-1066 CX Amsterdam, Netherlands.
[Evers, Bastiaan; Van Vliet, Martin; Wessels, Lodewyk F. A.] Netherlands Canc Inst, Dept Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands.
[Wittner, Ben S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Ramaswamy, Sridhar] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Wessels, Lodewyk F. A.] Delft Univ Technol, Fac Elect Engn Math & Comp Sci, NL-2628 CD Delft, Netherlands.
RP Peeper, DS (reprint author), Netherlands Canc Inst, Dept Mol Oncol, NL-1066 CX Amsterdam, Netherlands.
EM d.peeper@nki.nl
RI Rodenko, Boris /E-5492-2010
OI Rodenko, Boris /0000-0001-5223-4296
FU Netherlands Organization for Scientific research; Association for Cancer
Research; French Medical Academy; Dutch Cancer Society; European Union;
A Sister's Hope
FX We thank E. Mesman for histochemical analysis; W. Mooi, R. Sneepers,
J.-Y. Song, M. van der Valk, and T. Westphal for help with animal
pathology, pathological analysis, and experiments; K. Flach for help
with ChIP experiments; S. Greven, H. Grimminck, L. Rijswijk, T.
Schrauwers, and M. Voetel for technical assistance with animal
experiments; M. Heimerikx, M. Nieuwland, J. de Ronde, D. Sie, and R.
Kerkhoven for performing the microarray analyses and for helpful
discussions; M. Lopez Yarda for help with statistical analyses; A.
Gerard, S. Mertens, J. Collard, and W. Mooi for various reagents and for
helpful discussions; S. Douma and A. Rosado for technical assistance; A.
Berns, R. Bernards, W. Meuleman, L. van 't Veer, and J. Wesseling for
valuable comments and critical reading of the manuscript; and the
members of our laboratory and division for helpful suggestions and
discussions. A.P. was funded by the Netherlands Organization for
Scientific research. F.R. is funded by the Association for Cancer
Research and the French Medical Academy. H.H. and A.A. were funded by
the Dutch Cancer Society. C.J.D., T.G., and D.S.P. were funded by the
Dutch Cancer Society and by grants from the European Union Sixth
Framework Programme. T.G., N.L.V., and D.S.P. also received support from
A Sister's Hope.
NR 48
TC 54
Z9 54
U1 1
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 26
PY 2013
VL 110
IS 13
BP 5139
EP 5144
DI 10.1073/pnas.1222085110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131XN
UT WOS:000318031900062
PM 23483055
ER
PT J
AU Robinson, EB
Lichtenstein, P
Anckarsater, H
Happe, F
Ronald, A
AF Robinson, Elise B.
Lichtenstein, Paul
Anckarsater, Henrik
Happe, Francesca
Ronald, Angelica
TI Examining and interpreting the female protective effect against autistic
behavior
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE epidemiology; genetics; family studies
ID RARE DE-NOVO; GENERAL-POPULATION; SPECTRUM DISORDERS; SEX-DIFFERENCES;
TELEPHONE INTERVIEW; A-TAC; TRAITS; TWIN; GIRLS; RISK
AB Male preponderance in autistic behavioral impairment has been explained in terms of a hypothetical protective effect of female sex, yet little research has tested this hypothesis empirically. If females are protected, they should require greater etiologic load to manifest the same degree of impairment as males. The objective of this analysis was to examine whether greater familial etiologic load was associated with quantitative autistic impairments in females compared with males. Subjects included 3,842 dizygotic twin pairs from the Twins Early Development Study (TEDS) and 6,040 dizygotic twin pairs from the Child and Adolescent Twin Study of Sweden (CATSS). In both samples, we compared sibling autistic traits between female and male probands, who were identified as children scoring in the top 90th and 95th percentiles of the population autistic trait distributions. In both TEDS and CATSS, siblings of female probands above the 90th percentile had significantly more autistic impairments than the siblings of male probands above the 90th percentile. The siblings of female probands above the 90th percentile also had greater categorical recurrence risk in both TEDS and CATSS. Results were similar in probands above the 95th percentile. This finding, replicated across two nationally-representative samples, suggests that female sex protects girls from autistic impairments and that girls may require greater familial etiologic load to manifest the phenotype. It provides empirical support for the hypothesis of a female protective effect against autistic behavior and can be used to inform and interpret future gene finding efforts in autism spectrum disorders.
C1 [Robinson, Elise B.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Robinson, Elise B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Anckarsater, Henrik] Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-40530 Gothenburg, Sweden.
[Happe, Francesca; Ronald, Angelica] Kings Coll London, Inst Psychiat, Med Res Council Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.
[Ronald, Angelica] Univ London, Ctr Brain & Cognit Dev, Dept Psychol Sci, London WC1E 7HX, England.
RP Robinson, EB (reprint author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
EM erobinson@atgu.mgh.harvard.edu
RI Ronald, Angelica/C-7812-2009;
OI Ronald, Angelica/0000-0002-9576-2176; Robinson,
Elise/0000-0003-2314-2792; lichtenstein, paul/0000-0003-3037-5287;
Happe, Francesca/0000-0001-9226-4000
FU Medical Research Council [G0500079]; Swedish Council for Working Life
and Social Research; Swedish Research Council; Training Program in
Psychiatric Genetics and Translational Research Grant at the Harvard
School of Public Health [T32MH017119]
FX We thank the participants of the Twins Early Development Study (TEDS)
and Child and Adolescent Twin Study of Sweden for making this research
possible as well as Prof. Robert Plomin for use of the TEDS data. TEDS
is funded by Medical Research Council Grant G0500079. CATSS is supported
in part by the Swedish Council for Working Life and Social Research and
the Swedish Research Council. E.B.R. was supported by the Training
Program in Psychiatric Genetics and Translational Research Grant
T32MH017119 at the Harvard School of Public Health.
NR 43
TC 81
Z9 83
U1 3
U2 30
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 26
PY 2013
VL 110
IS 13
BP 5258
EP 5262
DI 10.1073/pnas.1211070110
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131XN
UT WOS:000318031900082
PM 23431162
ER
PT J
AU Brizendine, KD
Baddley, JW
Pappas, PG
AF Brizendine, Kyle D.
Baddley, John W.
Pappas, Peter G.
TI Predictors of Mortality and Differences in Clinical Features among
Patients with Cryptococcosis According to Immune Status
SO PLOS ONE
LA English
DT Article
ID ORGAN TRANSPLANT RECIPIENTS; VIRUS-NEGATIVE PATIENTS; AMPHOTERICIN-B;
PULMONARY CRYPTOCOCCOSIS; NEOFORMANS INFECTION; RANDOMIZED-TRIAL;
MENINGITIS; FLUCYTOSINE; FLUCONAZOLE; DISEASE
AB Introduction: Cryptococcosis is an invasive fungal infection causing substantial morbidity and mortality. Prognostic factors are largely derived from trials conducted prior to the modern era of antifungal and potent combination antiretroviral therapies, immunosuppression, and transplantation. Data describing the clinical features and predictors of mortality in a modern cohort are needed.
Methods: We conducted a retrospective cohort study of patients at our institution diagnosed with cryptococcosis from 1996 through 2010. Data included demographics, clinical features, diagnostics, treatment, and outcomes.
Results: We identified 302 individuals: 108 (36%) human immunodeficiency virus (HIV)-positive, 84 (28%) organ transplant recipients (OTRs), and 110 (36%) non-HIV, non-transplant (NHNT) patients including 39 with no identifiable immunodeficiency. Mean age was 49 years, 203 (67%) were male and 170 (56%) were white. All-cause mortality at 90 days was 21%. In multivariable logistic regression analyses, cryptococcemia (OR 5.09, 95% CI 2.54-10.22) and baseline opening pressure >25 cmH(2)O (OR 2.93, 95% CI 1.25-6.88) were associated with increased odds of mortality; HIV-positive patients (OR 0.46, 95% CI 0.19-1.16) and OTRs (OR 0.46, 95% CI 0.21-1.05) had lower odds of death compared to NHNT patients.
Conclusions: Predictors of mortality from cryptococcosis in the modern period include cryptococcemia, high intracranial pressure, and NHNT status while drug(s) used for induction and historical prognostic factors including organ failure syndromes and hematologic malignancy were not associated with mortality.
C1 [Brizendine, Kyle D.] Cleveland Clin, Dept Infect Dis, Cleveland, OH 44106 USA.
[Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Baddley, John W.; Pappas, Peter G.] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
RP Brizendine, KD (reprint author), Cleveland Clin, Dept Infect Dis, Cleveland, OH 44106 USA.
EM brizenk@ccf.org; pappas@uab.edu
FU National Institutes of Health [T32AI520699]
FX KDB acknowledges National Institutes of Health mentored training grant,
T32AI520699. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 31
TC 35
Z9 36
U1 0
U2 2
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 MAR 26
PY 2013
VL 8
IS 3
AR e60431
DI 10.1371/journal.pone.0060431
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 123VE
UT WOS:000317418500134
PM 23555970
ER
PT J
AU Sotnikov, I
Veremeyko, T
Starossom, SC
Barteneva, N
Weiner, HL
Ponomarev, ED
AF Sotnikov, Ilya
Veremeyko, Tatyana
Starossom, Sarah C.
Barteneva, Natalia
Weiner, Howard L.
Ponomarev, Eugene D.
TI Platelets Recognize Brain-Specific Glycolipid Structures, Respond to
Neurovascular Damage and Promote Neuroinflammation
SO PLOS ONE
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MICROVASCULAR
ENDOTHELIAL-CELLS; SIALIC-ACID; MULTIPLE-SCLEROSIS; ALZHEIMER-DISEASE;
PERTUSSIS TOXIN; ISCHEMIC-STROKE; SPINAL-CORD; GANGLIOSIDES; BLOOD
AB Platelets respond to vascular damage and contribute to inflammation, but their role in the neurodegenerative diseases is unknown. We found that the systemic administration of brain lipid rafts induced a massive platelet activation and degranulation resulting in a life-threatening anaphylactic-like response in mice. Platelets were engaged by the sialated glycosphingolipids (gangliosides) integrated in the rigid structures of astroglial and neuronal lipid rafts. The brain-abundant gangliosides GT1b and GQ1b were specifically recognized by the platelets and this recognition involved multiple receptors with P-selectin (CD62P) playing the central role. During the neuroinflammation, platelets accumulated in the central nervous system parenchyma, acquired an activated phenotype and secreted proinflammatory factors, thereby triggering immune response cascades. This study determines a new role of platelets which directly recognize a neuronal damage and communicate with the cells of the immune system in the pathogenesis of neurodegenerative diseases.
C1 [Sotnikov, Ilya; Veremeyko, Tatyana; Starossom, Sarah C.; Weiner, Howard L.; Ponomarev, Eugene D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
[Sotnikov, Ilya] Emory Univ, Sch Med, Div Neonatal Perinatal Med, Atlanta, GA USA.
[Barteneva, Natalia] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA.
[Ponomarev, Eugene D.] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
RP Weiner, HL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
EM hweiner@rics.bwh.harvard.edu; eponomarev@cuhk.edu.hk
OI Starossom, Sarah/0000-0001-7935-9910
FU [R01 NS071039-01A1]
FX The work was supported in part by R01 NS071039-01A1 grant. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript. No additional external
funding received for this study.
NR 86
TC 12
Z9 12
U1 1
U2 12
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 MAR 26
PY 2013
VL 8
IS 3
AR e58979
DI 10.1371/journal.pone.0058979
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 123VE
UT WOS:000317418500019
PM 23555611
ER
PT J
AU Atkinson, C
Floerchinger, B
Qiao, F
Casey, S
Williamson, T
Moseley, E
Stoica, S
Goddard, M
Ge, XP
Tullius, SG
Tomlinson, S
AF Atkinson, Carl
Floerchinger, Bernhard
Qiao, Fei
Casey, Sarah
Williamson, Tucker
Moseley, Ellen
Stoica, Serban
Goddard, Martin
Ge, Xupeng
Tullius, Stefan G.
Tomlinson, Stephen
TI Donor Brain Death Exacerbates Complement-Dependent Ischemia/Reperfusion
Injury in Transplanted Hearts
SO CIRCULATION
LA English
DT Article
DE inflammation; ischemia; reperfusion injury; transplantation
ID ISCHEMIA-REPERFUSION INJURY; P-SELECTIN LIGAND; LIVER-REGENERATION;
ACTIVATION; RAT; C3A; ALLOGRAFT; C5A; MEDIATORS; KIDNEY
AB Background-Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia/reperfusion injury after transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on posttransplantation cardiac ischemia/reperfusion injury. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of BD donor hearts and addressed the clinical relevance of these studies by analyzing human heart biopsies from BD and domino (living) donors.
Methods and Results-Hearts from living or BD donor C57BL/6 mice were transplanted into C57BL/6 or BALB/c recipients. Recipient mice were treated with the complement inhibitor CR2-Crry or vehicle control (n=6). Isografts were analyzed 48 hours after transplantation for injury, inflammation, and complement deposition, and allografts were monitored for graft survival. Human cardiac biopsies were analyzed for complement deposition and inflammatory cell infiltration. In the murine model, donor BD exacerbated ischemia/reperfusion injury and graft rejection, as demonstrated by increased myocardial injury, serum cardiac troponin, cellular infiltration, complement deposition, inflammatory chemokine and cytokine levels, and by decreased graft survival. CR2-Crry treatment of recipients significantly reduced all measured outcomes in grafts from both BD and living donors compared with controls. Analysis of human samples documented the relevance of our experimental findings and revealed exacerbated complement deposition and inflammation in grafts from BD donors compared with grafts from living donors.
Conclusions-BD exacerbates posttransplantation cardiac ischemia/reperfusion injury in mice and humans and decreases survival of mouse allografts. Furthermore, targeted complement inhibition in recipient mice ameliorates BD-exacerbated ischemia/reperfusion injury. (Circulation. 2013; 127: 1290-1299.)
C1 [Atkinson, Carl; Qiao, Fei; Casey, Sarah; Williamson, Tucker; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Floerchinger, Bernhard; Tullius, Stefan G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Transplant Surg, Boston, MA 02115 USA.
[Floerchinger, Bernhard; Tullius, Stefan G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplant Surg Res Lab, Boston, MA 02115 USA.
[Floerchinger, Bernhard] Univ Med Ctr Regensburg, Dept Cardiothorac Surg, Regensburg, Germany.
[Moseley, Ellen; Stoica, Serban; Goddard, Martin] Papworth Hosp NHS Trust, Dept Pathol, Cambridge, England.
[Stoica, Serban] Bristol Childrens Hosp, Bristol, Avon, England.
[Stoica, Serban] Inst Heart, Bristol, Avon, England.
[Ge, Xupeng] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
EM stullius@partners.org; tomlinss@musc.edu
FU National Institutes of Health [RO1 HL 86562, HL082485]; US Department of
Veterans Affairs [1BX001218]; American Heart Association [SDG AHA
065100]; Fundacion Carlos Slim de la Salud; Deutsche
Forschungsgemeinschaft [DFG/FL 703/1-1]; University of Regensburg; South
Carolina Clinical & Translational Research Institute, Medical University
of South Carolina's CTSA, National Institutes of Health/National Center
for Advancing Translational Sciences [UL1TR000062]
FX This study was supported by grants from the National Institutes of
Health (RO1 HL 86562 and HL082485 to Dr Tomlinson), the US Department of
Veterans Affairs (1BX001218 to Dr Tomlinson), the American Heart
Association (SDG AHA 065100 to Dr Atkinson), the Fundacion Carlos Slim
de la Salud (to Dr Tullius), Deutsche Forschungsgemeinschaft (DFG/FL
703/1-1) and the University of Regensburg (to Dr Floerchinger), and
South Carolina Clinical & Translational Research Institute, Medical
University of South Carolina's CTSA, National Institutes of
Health/National Center for Advancing Translational Sciences grant
UL1TR000062.
NR 36
TC 17
Z9 18
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 MAR 26
PY 2013
VL 127
IS 12
BP 1290
EP +
DI 10.1161/CIRCULATIONAHA.112.000784
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 113NQ
UT WOS:000316675100021
PM 23443736
ER
PT J
AU Grutzner, C
Wibral, M
Sun, LM
Rivolta, D
Singer, W
Maurer, K
Uhlhaas, PJ
AF Gruetzner, Christine
Wibral, Michael
Sun, Limin
Rivolta, Davide
Singer, Wolf
Maurer, Konrad
Uhlhaas, Peter J.
TI Deficits in high- (> 60 Hz) gamma-band oscillations during visual
processing in schizophrenia
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE MEG; gamma; schizophrenia; perceptual organization; synchrony
ID WORKING-MEMORY; PERCEPTUAL ORGANIZATION; NEURAL ACTIVITY; EEG
RECORDINGS; CORTEX; SYNCHRONIZATION; FREQUENCY; STIMULATION;
ABNORMALITIES; INTERNEURONS
AB Current theories of the pathophysiology of schizophrenia have focused on abnormal temporal coordination of neural activity. Oscillations in the gamma-band range (>25 Hz) are of particular interest as they establish synchronization with great precision in local cortical networks. However, the contribution of high gamma (>60 Hz) oscillations toward the pathophysiology is less established. To address this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated patients with chronic schizophrenia and 16 controls during the perception of Mooney faces. MEG data were analysed in the 25150 Hz frequency range. Patients showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces while responses to inverted stimuli were intact. Impaired processing of Mooney faces in schizophrenia patients was accompanied by a pronounced reduction in spectral power between 60120 Hz (effect size: d = 1.26) which was correlated with disorganized symptoms (r = -0.72). Our findings demonstrate that deficits in high gamma-band oscillations as measured by MEG are a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting an important aspect of the pathophysiology of the disorder.
C1 [Gruetzner, Christine; Sun, Limin; Rivolta, Davide; Singer, Wolf; Uhlhaas, Peter J.] Max Planck Inst Brain Res, Dept Neurophysiol, Frankfurt, Germany.
[Wibral, Michael] Goethe Univ Frankfurt, Brain Imaging Ctr, MEG Unit, D-60054 Frankfurt, Germany.
[Sun, Limin] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA.
[Rivolta, Davide; Singer, Wolf; Uhlhaas, Peter J.] Max Planck Gesell, Ernst Strungmann Inst Neurosci Cooperat, Frankfurt, Germany.
[Singer, Wolf] Goethe Univ Frankfurt, Frankfurt Inst Adv Studies, D-60054 Frankfurt, Germany.
[Maurer, Konrad] Goethe Univ Frankfurt, Dept Psychiat, D-60054 Frankfurt, Germany.
[Uhlhaas, Peter J.] Univ Glasgow, Inst Neurosci & Psychol, Glasgow G12 8QB, Lanark, Scotland.
RP Uhlhaas, PJ (reprint author), Univ Glasgow, Inst Neurosci & Psychol, Hillead Str 58, Glasgow G12 8QB, Lanark, Scotland.
EM peter.uhlhaas@glasgow.ac.uk
RI Singer, Wolf/D-6874-2012;
OI Wibral, Michael/0000-0001-8010-5862
FU Max Planck Society; BMBF [01GWS055]; LOWE grant Neuronale Koordination
Forschungsschwerpunkt Frankfurt (NeFF)
FX This work was supported by the Max Planck Society (Peter J. Uhlhaas) and
through the BMBF (Grant: 01GWS055) (Peter J. Uhlhaas, Wolf Singer).
Davide Rivolta is supported by the LOWE grant Neuronale Koordination
Forschungsschwerpunkt Frankfurt (NeFF).
NR 64
TC 32
Z9 32
U1 4
U2 30
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD MAR 26
PY 2013
VL 7
AR 88
DI 10.3389/fnhum.2013.00088
PG 11
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 114FJ
UT WOS:000316726200001
PM 23532620
ER
PT J
AU Shunk, RL
AF Shunk, Rebecca Lesto
TI Professionalism A Piercing Dilemma
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Shunk, Rebecca Lesto] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shunk, Rebecca Lesto] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Shunk, RL (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA.
EM rebecca.shunk@va.gov
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 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 25
PY 2013
VL 173
IS 6
BP 406
EP 406
DI 10.1001/jamainternmed.2013.2744
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 154NA
UT WOS:000319681400001
PM 23420355
ER
PT J
AU Singh, H
Giardina, TD
Meyer, AND
Forjuoh, SN
Reis, MD
Thomas, EJ
AF Singh, Hardeep
Giardina, Traber Davis
Meyer, Ashley N. D.
Forjuoh, Samuel N.
Reis, Michael D.
Thomas, Eric J.
TI Types and Origins of Diagnostic Errors in Primary Care Settings
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID ADVERSE EVENTS; MALPRACTICE CLAIMS; CANCER-DIAGNOSIS; MISSED
OPPORTUNITIES; MULTISITE SURVEY; GENERAL-PRACTICE; MEDICAL ERRORS;
INTERVENTIONS; PHYSICIANS; HARM
AB Importance: Diagnostic errors are an understudied aspect of ambulatory patient safety.
Objectives: To determine the types of diseases missed and the diagnostic processes involved in cases of confirmed diagnostic errors in primary care settings and to determine whether record reviews could shed light on potential contributory factors to inform future interventions.
Design: We reviewed medical records of diagnostic errors detected at 2 sites through electronic health record-based triggers. Triggers were based on patterns of patients' unexpected return visits after an initial primary care index visit.
Setting: A large urban Veterans Affairs facility and a large integrated private health care system.
Participants: Our study focused on 190 unique instances of diagnostic errors detected in primary care visits between October 1, 2006, and September 30, 2007.
Main Outcome Measures: Through medical record reviews, we collected data on presenting symptoms at the index visit, types of diagnoses missed, process breakdowns, potential contributory factors, and potential for harm from errors.
Results: In 190 cases, a total of 68 unique diagnoses were missed. Most missed diagnoses were common conditions in primary care, with pneumonia (6.7%), decompensated congestive heart failure (5.7%), acute renal failure (5.3%), cancer (primary) (5.3%), and urinary tract infection or pyelonephritis (4.8%) being most common. Process breakdowns most frequently involved the patient-practitioner clinical encounter (78.9%) but were also related to referrals (19.5%), patient-related factors (16.3%), follow-up and tracking of diagnostic information (14.7%), and performance and interpretation of diagnostic tests (13.7%). A total of 43.7% of cases involved more than one of these processes. Patient-practitioner encounter breakdowns were primarily related to problems with history-taking (56.3%), examination (47.4%), and/or ordering diagnostic tests for further workup (57.4%). Most errors were associated with potential for moderate to severe harm.
Conclusions and Relevance: Diagnostic errors identified in our study involved a large variety of common diseases and had significant potential for harm. Most errors were related to process breakdowns in the patient-practitioner clinical encounter. Preventive interventions should target common contributory factors across diagnoses, especially those that involve data gathering and synthesis in the patient-practitioner encounter.
C1 [Singh, Hardeep; Giardina, Traber Davis; Meyer, Ashley N. D.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA.
[Singh, Hardeep; Giardina, Traber Davis; Meyer, Ashley N. D.] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX USA.
[Forjuoh, Samuel N.; Reis, Michael D.] Texas A&M Hlth Sci Ctr, Coll Medi, Dept Family & Community Med, Temple, TX USA.
[Thomas, Eric J.] Univ Texas Houston, Mem Hermann Ctr Health care Qual & Safety, Houston, TX USA.
[Thomas, Eric J.] Univ Texas Houston, Div Gen Med, Dept Med, Sch Med, Houston, TX USA.
RP Singh, H (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA Hlth Serv Res & Dev Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hrdeeps@bcm.edu
OI Davis Giardina, Traber/0000-0002-9184-6524; Meyer,
Ashley/0000-0001-7993-8584
FU National Institutes of Health K23 Career Development Award
[K23CA125585]; Agency for Health Care Research and Quality Health
Services Research Demonstration and Dissemination grant [R18HS17244-02];
Houston VA HSR&D Center of Excellence [HFP90-020]; VA Office of Academic
Affiliations Fellowship Program
FX The study was supported by National Institutes of Health K23 Career
Development Award K23CA125585 to Dr Singh, by Agency for Health Care
Research and Quality Health Services Research Demonstration and
Dissemination grant R18HS17244-02 to Dr Thomas, and in part by Houston
VA HSR&D Center of Excellence grant HFP90-020 and the VA Office of
Academic Affiliations Fellowship Program to Dr Meyer.
NR 38
TC 69
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U1 2
U2 18
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 25
PY 2013
VL 173
IS 6
BP 418
EP 425
DI 10.1001/jamainternmed.2013.2777
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 154NA
UT WOS:000319681400004
PM 23440149
ER
PT J
AU Beach, MC
Fitzgerald, A
Saha, S
AF Beach, Mary Catherine
Fitzgerald, April
Saha, Somnath
TI White Coat Hype: Branding Physicians With Professional Attire
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID APPEARANCE
C1 [Beach, Mary Catherine; Fitzgerald, April] Johns Hopkins Univ Hosp, Div Gen Internal Med, Baltimore, MD 21287 USA.
[Saha, Somnath] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Sect Gen Internal Med, Portland, OR 97201 USA.
RP Beach, MC (reprint author), Johns Hopkins Univ Hosp, Div Gen Internal Med, 2024 Monument St,Room 2-511, Baltimore, MD 21287 USA.
EM mcbeach@jhmi.edu
NR 10
TC 3
Z9 3
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 25
PY 2013
VL 173
IS 6
BP 467
EP 468
DI 10.1001/jamainternmed.2013.3766
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 154NA
UT WOS:000319681400017
PM 23420503
ER
PT J
AU Prigerson, HG
Zhang, BH
Nilsson, ME
AF Prigerson, Holly G.
Zhang, Baohui
Nilsson, Matthew E.
TI End-of-Life Care: Where Does the Standard Oncology Care Fail Our
Patients and What Do We, as Oncologists, Need to Do Differently? Reply
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
C1 [Prigerson, Holly G.; Zhang, Baohui; Nilsson, Matthew E.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA.
[Prigerson, Holly G.] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA.
[Prigerson, Holly G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, 1134 Dana Bldg,450 Brookline Ave, Boston, MA 02115 USA.
EM Holly_Prigerson@dfci.harvard.edu
NR 0
TC 1
Z9 1
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 25
PY 2013
VL 173
IS 6
BP 475
EP 475
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 154NA
UT WOS:000319681400023
PM 23529553
ER
PT J
AU Gao, Y
Geng, LY
Orson, F
Kinsey, B
Kosten, TR
Shen, XY
Brimijoin, S
AF Gao, Yang
Geng, Liyi
Orson, Frank
Kinsey, Berma
Kosten, Thomas R.
Shen, Xiaoyun
Brimijoin, Stephen
TI Effects of anti-cocaine vaccine and viral gene transfer of cocaine
hydrolase in mice on cocaine toxicity including motor strength and liver
damage
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article; Proceedings Paper
CT International Meeting on Cholinesterases
CY JUN 04-09, 2012
CL Kazan, RUSSIA
DE Cocaine toxicity; Anti-cocaine vaccine; Mouse; Alanine transaminase;
Histopathology; Grip strength
ID HUMAN BUTYRYLCHOLINESTERASE; INDUCED HEPATOTOXICITY; ABUSE; INTERCEPTION
AB In developing an vivo drug-interception therapy to treat cocaine abuse and hinder relapse into drug seeking provoked by re-encounter with cocaine, two promising agents are: (1) a cocaine hydrolase enzyme (CocH) derived from human butyrylcholinesterase and delivered by gene transfer; (2) an anti-cocaine antibody elicited by vaccination. Recent behavioral experiments showed that antibody and enzyme work in a complementary fashion to reduce cocaine-stimulated locomotor activity in rats and mice. Our present goal was to test protection against liver damage and muscle weakness in mice challenged with massive doses of cocaine at or near the LD50 level (100-120 mg/kg, i.p.). We found that, when the interceptor proteins were combined at doses that were only modestly protective in isolation (enzyme, 1 mg/kg; antibody, 8 mg/kg), they provided complete protection of liver tissue and motor function. When the enzyme levels were similar to 400-fold higher, after in vivo transduction by adeno-associated viral vector, similar protection was observed from CocH alone. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Gao, Yang; Geng, Liyi; Brimijoin, Stephen] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA.
[Orson, Frank; Kinsey, Berma; Shen, Xiaoyun] Dept Med, Houston, TX USA.
[Kosten, Thomas R.] Dept Psychiat & Neurosci, Houston, TX USA.
[Orson, Frank; Kosten, Thomas R.] Dept Pathol & Immunol, Houston, TX USA.
[Orson, Frank; Kinsey, Berma; Kosten, Thomas R.; Shen, Xiaoyun] Dept Vet Affairs Med Ctr, Houston, TX USA.
RP Brimijoin, S (reprint author), Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA.
EM brimijoin@mayo.edu
FU NIDA [DP1 DA031340, R01 DA023979, R01 DA023979 S1]; Mayo Foundation
FX We thank Drs D. Baltimore and S. J. Russell for generously providing
crucial viral vectors for this research. Our work was supported by NIDA
grants DP1 DA031340, R01 DA023979, and R01 DA023979 S1, and by Mayo
Foundation.
NR 21
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U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
EI 1872-7786
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD MAR 25
PY 2013
VL 203
IS 1
SI SI
BP 208
EP 211
DI 10.1016/j.cbi.2012.08.006
PG 4
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 134HU
UT WOS:000318201800042
PM 22935511
ER
PT J
AU Kung, JTY
Lee, JT
AF Kung, Johnny T. Y.
Lee, Jeannie T.
TI RNA in the Loop
SO DEVELOPMENTAL CELL
LA English
DT Editorial Material
ID LONG NONCODING RNAS; CHROMATIN ARCHITECTURE; HUMAN-CELLS; TRANSCRIPTION;
MEDIATOR; ENHANCER
C1 [Kung, Johnny T. Y.; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Kung, Johnny T. Y.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Kung, Johnny T. Y.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu
FU NIGMS NIH HHS [R01 GM090278, R37 GM058839]
NR 10
TC 5
Z9 5
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD MAR 25
PY 2013
VL 24
IS 6
BP 565
EP 567
DI 10.1016/j.devcel.2013.03.009
PG 3
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 126PW
UT WOS:000317634500002
PM 23537627
ER
PT J
AU Beidas, RS
Aarons, G
Barg, F
Evans, A
Hadley, T
Hoagwood, K
Marcus, S
Schoenwald, S
Walsh, L
Mandell, DS
AF Beidas, Rinad S.
Aarons, Gregory
Barg, Frances
Evans, Arthur
Hadley, Trevor
Hoagwood, Kimberly
Marcus, Steven
Schoenwald, Sonja
Walsh, Lucia
Mandell, David S.
TI Policy to implementation: evidence-based practice in community mental
health - study protocol
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Evidence-based practice; Community mental health; Policy;
Implementation; Fidelity; Organizational variables
ID CHILD-WELFARE SYSTEMS; SOCIAL-CONTEXT OSC; ORGANIZATIONAL READINESS;
SERVICES; CLIMATE; LEADERSHIP; THERAPY; INTERVENTIONS; ATTITUDES;
FIDELITY
AB Background: Evidence-based treatments (EBTs) are not widely available in community mental health settings. In response to the call for implementation of evidence-based treatments in the United States, states and counties have mandated behavioral health reform through policies and other initiatives. Evaluations of the impact of these policies on implementation are rare. A systems transformation about to occur in Philadelphia, Pennsylvania, offers an important opportunity to prospectively study implementation in response to a policy mandate.
Methods/design: Using a prospective sequential mixed-methods design, with observations at multiple points in time, we will investigate the responses of staff from 30 community mental health clinics to a policy from the Department of Behavioral Health encouraging and incentivizing providers to implement evidence-based treatments to treat youth with mental health problems. Study participants will be 30 executive directors, 30 clinical directors, and 240 therapists. Data will be collected prior to the policy implementation, and then at two and four years following policy implementation. Quantitative data will include measures of intervention implementation and potential moderators of implementation (i.e., organizational-and leader-level variables) and will be collected from executive directors, clinical directors, and therapists. Measures include self-reported therapist fidelity to evidence-based treatment techniques as measured by the Therapist Procedures Checklist-Revised, organizational variables as measured by the Organizational Social Context Measurement System and the Implementation Climate Assessment, leader variables as measured by the Multifactor Leadership Questionnaire, attitudes towards EBTs as measured by the Evidence-Based Practice Attitude Scale, and knowledge of EBTs as measured by the Knowledge of Evidence-Based Services Questionnaire. Qualitative data will include semi-structured interviews with a subset of the sample to assess the implementation experience of high-, average-, and low-performing agencies. Mixed methods will be integrated through comparing and contrasting results from the two methods for each of the primary hypotheses in this study.
Discussion: Findings from the proposed research will inform both future policy mandates around implementation and the support required for the success of these policies, with the ultimate goal of improving the quality of treatment provided to youth in the public sector.
C1 [Beidas, Rinad S.; Evans, Arthur; Hadley, Trevor; Walsh, Lucia; Mandell, David S.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Aarons, Gregory] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Barg, Frances] Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Evans, Arthur] Dept Behav Hlth & Intellectual DisAbil Serv, Philadelphia, PA USA.
[Hoagwood, Kimberly] NYU, Dept Psychiat, New York, NY 10016 USA.
[Marcus, Steven] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
[Schoenwald, Sonja] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
RP Beidas, RS (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, 3535 Market St,3rd Floor, Philadelphia, PA 19104 USA.
EM rbeidas@upenn.edu
RI Mandell, David/H-2730-2012
OI Mandell, David/0000-0001-8240-820X
FU Department of Behavioral Health and Intellectual DisAbility Services;
Evidence Based Practice and Innovation (EPIC) group; NIMH [K23
MH099179]; National Institute of Mental Health [R25 MH080916]; Quality
Enhancement Research Initiative (QUERI); Department of Veterans Affairs
Contract; Veterans Health Administration; Office of Research &
Development, Health Services Research & Development Service
FX We are especially grateful for the support the Department of Behavioral
Health and Intellectual DisAbility Services has provided for this
project, and for the Evidence Based Practice and Innovation (EPIC)
group. Funding for this research project was supported by the following
grants from NIMH: (K23 MH099179, Beidas). Additionally, the preparation
of this article was supported in part by the Implementation Research
Institute (IRI), at the George Warren Brown School of Social Work,
Washington University in St. Louis; through an award from the National
Institute of Mental Health (R25 MH080916) and Quality Enhancement
Research Initiative (QUERI), Department of Veterans Affairs Contract,
Veterans Health Administration, Office of Research & Development, Health
Services Research & Development Service. Dr. Beidas is an IRI fellow. We
would like to thank the following experts who provided their time and
input on this project: Dr. Marc Atkins, Dr. Ross Brownson, Dr. David
Chambers, Dr. Charles Glisson, Dr. Nicholas Ialongo, Dr. John Landsverk,
and Dr. Enola Proctor. We are also grateful for the time and effort
provided by Steven Lucas and Margaret Mary Downey with this project.
NR 38
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U1 3
U2 38
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD MAR 24
PY 2013
VL 8
AR 38
DI 10.1186/1748-5908-8-38
PG 9
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 137EU
UT WOS:000318419100001
PM 23522556
ER
PT J
AU MacDonald, SM
Jimenez, R
Paetzold, P
Adams, J
Beatty, J
DeLaney, TF
Kooy, H
Taghian, AG
Lu, HM
AF MacDonald, Shannon M.
Jimenez, Rachel
Paetzold, Peter
Adams, Judith
Beatty, Jonathan
DeLaney, Thomas F.
Kooy, Hanne
Taghian, Alphonse G.
Lu, Hsiao-Ming
TI Proton radiotherapy for chest wall and regional lymphatic radiation;
dose comparisons and treatment delivery
SO RADIATION ONCOLOGY
LA English
DT Article
DE Breast cancer; Treatment planning; Proton beam radiation
ID BREAST-CANCER PATIENTS; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIALS;
THERAPY; RISK; PNEUMONITIS; MORTALITY; PHOTONS; SURGERY
AB Purpose: The delivery of post-mastectomy radiation therapy (PMRT) can be challenging for patients with left sided breast cancer that have undergone mastectomy. This study investigates the use of protons for PMRT in selected patients with unfavorable cardiac anatomy. We also report the first clinical application of protons for these patients.
Methods and materials: Eleven patients were planned with protons, partially wide tangent photon fields (PWTF), and photon/electron (P/E) fields. Plans were generated with the goal of achieving 95% coverage of target volumes while maximally sparing cardiac and pulmonary structures. In addition, we report on two patients with unfavorable cardiac anatomy and IMN involvement that were treated with a mix of proton and standard radiation.
Results: PWTF, P/E, and proton plans were generated and compared. Reasonable target volume coverage was achieved with PWTF and P/E fields, but proton therapy achieved superior coverage with a more homogeneous plan. Substantial cardiac and pulmonary sparing was achieved with proton therapy as compared to PWTF and P/E. In the two clinical cases, the delivery of proton radiation with a 7.2 to 9 Gy photon and electron component was feasible and well tolerated. Akimbo positioning was necessary for gantry clearance for one patient; the other was treated on a breast board with standard positioning (arms above her head). LAO field arrangement was used for both patients. Erythema and fatigue were the only noted side effects.
Conclusions: Proton RT enables delivery of radiation to the chest wall and regional lymphatics, including the IMN, without compromise of coverage and with improved sparing of surrounding normal structures. This treatment is feasible, however, optimal patient set up may vary and field size is limited without multiple fields/matching.
C1 [MacDonald, Shannon M.; Jimenez, Rachel; Paetzold, Peter; Adams, Judith; Beatty, Jonathan; DeLaney, Thomas F.; Kooy, Hanne; Taghian, Alphonse G.; Lu, Hsiao-Ming] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
RP MacDonald, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 340,100 Blossom St, Boston, MA 02114 USA.
EM smacdonald@partners.org
NR 19
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U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-717X
J9 RADIAT ONCOL
JI Radiat. Oncol.
PD MAR 24
PY 2013
VL 8
AR 71
DI 10.1186/1748-717X-8-71
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 128RR
UT WOS:000317787000001
PM 23521809
ER
PT J
AU Vollset, SE
Clarke, R
Lewington, S
Ebbing, M
Halsey, J
Lonn, E
Armitage, J
Manson, JE
Hankey, GJ
Spence, JD
Galan, P
Bonaa, KH
Jamison, R
Gaziano, JM
Guarino, P
Baron, JA
Logan, RFA
Giovannucci, EL
den Heijer, M
Ueland, PM
Bennett, D
Collins, R
Peto, R
AF Vollset, Stein Emil
Clarke, Robert
Lewington, Sarah
Ebbing, Marta
Halsey, Jim
Lonn, Eva
Armitage, Jane
Manson, Joann E.
Hankey, Graeme J.
Spence, J. David
Galan, Pilar
Bonaa, Kaare H.
Jamison, Rex
Gaziano, J. Michael
Guarino, Peter
Baron, John A.
Logan, Richard F. A.
Giovannucci, Edward L.
den Heijer, Martin
Ueland, Per M.
Bennett, Derrick
Collins, Rory
Peto, Richard
CA B-Vitamin Treatment Trialists' Co
TI Effects of folic acid supplementation on overall and site-specific
cancer incidence during the randomised trials: meta-analyses of data on
50 000 individuals
SO LANCET
LA English
DT Article
ID NEURAL-TUBE DEFECTS; PERICONCEPTIONAL VITAMIN SUPPLEMENTATION;
PLACEBO-CONTROLLED TRIAL; B-VITAMINS; MYOCARDIAL-INFARCTION;
VASCULAR-DISEASE; RISK-FACTOR; CARDIOVASCULAR-DISEASE; LOWERING
HOMOCYSTEINE; FLOUR FORTIFICATION
AB Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification.
Methods In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49 621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease [n=46 969] and three trials in patients with colorectal adenoma [n=2652]). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR).
Findings During a weighted average scheduled treatment duration of 5.2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57.3 nmol/L for the folic acid groups vs 13.5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1.06, 95% CI 0.99-1.13, p=0.10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0.23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0.13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site.
Interpretation Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials.
C1 [Vollset, Stein Emil] Univ Bergen, Norwegian Inst Publ Hlth, Bergen, Norway.
[Vollset, Stein Emil] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Clarke, Robert; Lewington, Sarah; Halsey, Jim; Armitage, Jane; Bennett, Derrick; Collins, Rory; Peto, Richard] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England.
[Clarke, Robert; Lewington, Sarah; Halsey, Jim; Armitage, Jane; Bennett, Derrick; Collins, Rory; Peto, Richard] Univ Oxford, Epidemiol Studies Unit CTSU, Oxford OX3 7LF, England.
[Ebbing, Marta] Haukeland Hosp, Dept Heart Dis, N-5021 Bergen, Norway.
[Lonn, Eva] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
[Lonn, Eva] McMaster Univ, Dept Med, Div Cardiol, Hamilton, ON, Canada.
[Manson, Joann E.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA.
[Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia.
[Spence, J. David] Univ Western Ontario, Dept Neurol, Robarts Res Inst, London, ON, Canada.
[Bonaa, Kaare H.] Univ Hosp Northern Norway, Dept Heart Dis, Tromso, Norway.
[Jamison, Rex] Vet Affairs Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA.
[Jamison, Rex] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Guarino, Peter] Connecticut VA Healthcare Syst, Dept Vet airs, Cooperat Studies Program, West Haven, CT USA.
[Baron, John A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Logan, Richard F. A.] Univ Nottingham, Div Epidemiol & Publ Hlth, Nottingham NG7 2RD, England.
[Giovannucci, Edward L.] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA.
[den Heijer, Martin] Radboud Univ Nijmegen, Dept Endocrinol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Ueland, Per M.] Haukeland Hosp, Lab Clin Biochem, N-5021 Bergen, Norway.
RP Clarke, R (reprint author), Univ Oxford, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus, Oxford OX3 7LF, England.
EM robert.clarke@ctsu.ox.ac.uk
RI Spence, J. David/K-6396-2013; Ueland, Per/C-7340-2013; Hankey, Graeme
/H-4968-2014;
OI Spence, J. David/0000-0001-7478-1098; Hankey, Graeme
/0000-0002-6044-7328; Blom, Henk/0000-0001-5202-9241
FU British Heart Foundation; Medical Research Council; Cancer Research UK;
Food Standards Agency; UK Medical Research Council; UK Food Standards
Agency [N05072]
FX British Heart Foundation, Medical Research Council, Cancer Research UK,
Food Standards Agency.; Sources of funding for individual trials are
described in their separate publications. The Clinical Trial Service
Unit and Epidemiological Studies Unit (CTSU), where the BVTT secretariat
is located, has a policy of not accepting fees, honoraria, or paid
consultancies directly or indirectly from any industry. It receives its
core funding from the British Heart Foundation, UK Medical Research
Council, and Cancer Research UK. Support for this project was also
provided by a grant from the UK Food Standards Agency (N05072).
NR 43
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U1 2
U2 47
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD MAR 23
PY 2013
VL 381
IS 9871
BP 1029
EP 1036
DI 10.1016/S0140-6736(12)62001-7
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 117EU
UT WOS:000316936800032
PM 23352552
ER
PT J
AU Crabtree, D
Boyer-Guittaut, M
Ouyang, XS
Fineberg, N
Zhang, JH
AF Crabtree, Donna
Boyer-Guittaut, Michael
Ouyang, Xiaosen
Fineberg, Naomi
Zhang, Jianhua
TI Dopamine and its metabolites in cathepsin D heterozygous mice before and
after MPTP administration
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE MPTP; Monoamine; Lysosome; Heterozygotes; Behavioral assessment
ID ALPHA-SYNUCLEIN; RAT-BRAIN;
1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; TRANSFERASE; RESISTANCE;
MECHANISM; TRANSPORT; TOXICITY; OXIDASE; ENZYMES
AB Cathepsin D (CD) is a lysosomal aspartyl protease which plays an important role in alpha-synuclein degradation, and neuronal survival. CD knockout mice die by post-natal day 25 +/- 1 due to intestinal necrosis. We analyzed the young adult male heterozygous mice, and found no behavior abnormalities in the heterozygous mice compared to wildtype littermates. LC3-II, p62, and alpha-synuclein levels are similar, while LAMP1 is higher in the striatum in CD heterozygous compared to wildtype mice. Interestingly, we found that dopamine and metabolites in the striatum and olfactory bulbs are at higher levels than wildtype littermates, while the DOPAC/DA and HVA/DA ratio remain similar between wildtype and CD heterozygous mice. In response to sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, dopamine, DOPAC, and HVA are depleted to similar levels in the striatum in both heterozygous and wildtype mice. Dopamine synthesizing enzyme tyrosine hydroxylase, metabolic enzyme monoamine oxidase, and catechol-O-methyltransferase (COMT) levels are similar in the striatum in wild-type and heterozygous mice. These studies provide valuable information regarding how lysosomal function may contribute to neurochemical homeostasis in animal models. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Crabtree, Donna; Boyer-Guittaut, Michael; Ouyang, Xiaosen; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Boyer-Guittaut, Michael; Ouyang, Xiaosen; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL USA.
[Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA.
[Fineberg, Naomi] UAB Sch Publ Hlth, Dept Biostat, Birmingham, AL USA.
[Boyer-Guittaut, Michael] Univ Franche Comte, Biochim Lab, SFR IBCT,FED 4234, UFR Sci & Tech,EA3922, F-25030 Besancon, France.
RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, BMRII-534,901 19th St S, Birmingham, AL 35294 USA.
EM zhanja@uab.edu
RI di Ronza, Alberto/H-7674-2016;
OI di Ronza, Alberto/0000-0002-9813-5143; Zhang,
Jianhua/0000-0002-2128-9574
FU Michael J Fox Foundation; VA merit award; UAB Behavioral Assessment Core
[P30 NS47466]; [NIHR01-NS064090]
FX We thank members of the Zhang Laboratory for technical help and
discussions. We thank Dr. Paul Saftig for the cathepsin D knockout mice,
Dr. Thomas Van Groen for his help and expertise with the behavioral
assessments. This work was supported by Michael J Fox Foundation,
NIHR01-NS064090 and a VA merit award (to JZ), and in part by P30 NS47466
(UAB Behavioral Assessment Core).
NR 21
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAR 22
PY 2013
VL 538
BP 3
EP 8
DI 10.1016/j.neulet.2013.01.035
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 120FH
UT WOS:000317155700002
PM 23391753
ER
PT J
AU Aguirre, JD
Clark, HM
McIlvin, M
Vazquez, C
Palmere, SL
Grab, DJ
Seshu, J
Hart, PJ
Saito, M
Culotta, VC
AF Aguirre, J. Dafhne
Clark, Hillary M.
McIlvin, Matthew
Vazquez, Christine
Palmere, Shaina L.
Grab, Dennis J.
Seshu, J.
Hart, P. John
Saito, Mak
Culotta, Valeria C.
TI A Manganese-rich Environment Supports Superoxide Dismutase Activity in a
Lyme Disease Pathogen, Borrelia burgdorferi
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI;
LEUCINE AMINOPEPTIDASE; NEISSERIA-GONORRHOEAE; OXIDATIVE STRESS; BINDING
PROTEIN; TYROSINE 34; IRON; RESISTANCE
AB The Lyme disease pathogen Borrelia burgdorferi represents a novel organism in which to study metalloprotein biology in that this spirochete has uniquely evolved with no requirement for iron. Not only is iron low, but we show here that B. burgdorferi has the capacity to accumulate remarkably high levels of manganese. This high manganese is necessary to activate the SodA superoxide dismutase (SOD) essential for virulence. Using a metalloproteomic approach, we demonstrate that a bulk of B. burgdorferi SodA directly associates with manganese, and a smaller pool of inactive enzyme accumulates as apoprotein. Other metalloproteins may have similarly adapted to using manganese as co-factor, including the BB0366 aminopeptidase. Whereas B. burgdorferi SodA has evolved in a manganese-rich, iron-poor environment, the opposite is true for Mn-SODs of organisms such as Escherichia coli and bakers' yeast. These Mn-SODs still capture manganese in an iron-rich cell, and we tested whether the same is true for Borrelia SodA. When expressed in the iron-rich mitochondria of Saccharomyces cerevisiae, B. burgdorferi SodA was inactive. Activity was only possible when cells accumulated extremely high levels of manganese that exceeded cellular iron. Moreover, there was no evidence for iron inactivation of the SOD. B. burgdorferi SodA shows strong overall homology with other members of the Mn-SOD family, but computer-assisted modeling revealed some unusual features of the hydrogen bonding network near the enzyme's active site. The unique properties of B. burgdorferi SodA may represent adaptation to expression in the manganese-rich and iron-poor environment of the spirochete.
C1 [Aguirre, J. Dafhne; Clark, Hillary M.; Vazquez, Christine; Palmere, Shaina L.; Culotta, Valeria C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA.
[McIlvin, Matthew; Saito, Mak] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
[Grab, Dennis J.] Johns Hopkins Univ, Sch Med, Div Med Microbiol, Dept Pathol, Baltimore, MD 21205 USA.
[Seshu, J.] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA.
[Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
RP Culotta, VC (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA.
EM vculotta@jhsph.edu
FU National Institutes of Health [R01 ES08996, GM50016, SC1 AI078559, T32
GM080189]; Johns Hopkins University NIEHS, National Institutes of
Health, center; Robert A. Welch Foundation [AQ-1399]; Veterans Affairs
Department Grant, South Texas Veterans Health Care System [I01BX000506];
Gordon and Betty Moore Foundation Marine Microbiology Program; National
Science Foundation Chemical Oceanography Grant [OCE-1031271]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 ES08996 and GM50016 (to V. C. C.) and SC1 AI078559 (to
J. S.). This work was also supported in part by the Johns Hopkins
University NIEHS, National Institutes of Health, center, by Robert A.
Welch Foundation Grant AQ-1399, and in part by Veterans Affairs
Department Grant I01BX000506, South Texas Veterans Health Care System
(to P. J. H.). Metalloproteomic studies were funded by the Gordon and
Betty Moore Foundation Marine Microbiology Program and National Science
Foundation Chemical Oceanography Grant OCE-1031271 (to M. A. S.).;
Supported by National Institutes of Health Grant T32 GM080189.
NR 57
TC 29
Z9 29
U1 2
U2 49
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 MAR 22
PY 2013
VL 288
IS 12
BP 8468
EP 8478
DI 10.1074/jbc.M112.433540
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 112AS
UT WOS:000316564500044
PM 23376276
ER
PT J
AU Buffen, K
Oosting, M
Mennens, S
Anand, PK
Plantinga, TS
Sturm, P
van de Veerdonk, FL
van der Meer, JWM
Xavier, RJ
Kanneganti, TD
Netea, MG
Joosten, LAB
AF Buffen, Kathrin
Oosting, Marije
Mennens, Svenja
Anand, Paras K.
Plantinga, Theo S.
Sturm, Patrick
van de Veerdonk, Frank L.
van der Meer, Jos W. M.
Xavier, Ramnik J.
Kanneganti, Thirumala-Devi
Netea, Mihai G.
Joosten, Leo A. B.
TI Autophagy Modulates Borrelia burgdorferi-induced Production of
Interleukin-1 beta (IL-1 beta)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INNATE IMMUNE ACTIVATION; NF-KAPPA-B; LYME BORRELIOSIS;
TREPONEMA-PALLIDUM; HUMAN MONOCYTES; DISEASE; INFLAMMASOME; CELLS;
LIPOPROTEINS; ARTHRITIS
AB Borrelia burgdorferi sensu lato is the causative agent of Lyme disease. Recent studies have shown that recognition of the spirochete is mediated by TLR2 and NOD2. The latter receptor has been associated with the induction of the intracellular degradation process called autophagy. The present study demonstrated for the first time the induction of autophagy by exposure to B. burgdorferi and that autophagy modulates the B. burgdorferi-dependent cytokine production. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increased IL-1 beta and IL-6 production in response to the exposure of the spirochete, whereas TNF alpha production was unchanged. Autophagy induction against B. burgdorferi was dependent on reactive oxygen species (ROS) because cells from patients with chronic granulomatous disease, which are defective in ROS production, also produced elevated IL-1 beta. Further, the enhanced production of the proinflammatory cytokines was because of the elevated mRNA expression in the absence of autophagy. Our results thus demonstrate the induction of autophagy, which, in turn, modulates cytokine production by B. burgdorferi for the first time.
C1 [Buffen, Kathrin; Oosting, Marije; Mennens, Svenja; Plantinga, Theo S.; van de Veerdonk, Frank L.; van der Meer, Jos W. M.; Netea, Mihai G.; Joosten, Leo A. B.] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6525 GA Nijmegen, Netherlands.
[Buffen, Kathrin; Oosting, Marije; Plantinga, Theo S.; van de Veerdonk, Frank L.; van der Meer, Jos W. M.; Netea, Mihai G.; Joosten, Leo A. B.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Inst Infect Inflammat & Immun N4i, NL-6525 GA Nijmegen, Netherlands.
[Mennens, Svenja; Anand, Paras K.; Kanneganti, Thirumala-Devi] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
[Sturm, Patrick] Radboud Univ Nijmegen, Dept Microbiol, Med Ctr, NL-6525 GA Nijmegen, Netherlands.
[Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
RP Joosten, LAB (reprint author), Radboud Univ Nijmegen, Dept Med 463, Med Ctr, Geert Grootepl Zuid 8, NL-6525 GA Nijmegen, Netherlands.
EM l.joosten@aig.umcn.nl
RI van de Veerdonk, Frank/C-7256-2008; Plantinga, Theo/A-6895-2015;
Joosten, Leo/H-3138-2015; Netea, Mihai/N-5155-2014; van der Meer,
Jos/C-8521-2013; Mennens, Svenja/F-3106-2016; Oosting,
Marije/H-7437-2015
OI van de Veerdonk, Frank/0000-0002-1121-4894; van der Meer,
Jos/0000-0001-5120-3690;
FU Dutch Arthritis Association [NR 10-1-303]; Veni Grant from the
Netherlands Organization for Scientific Research; National Institute of
Health [R01AR056296]; Vici grant from The Netherlands Organization for
Scientific Research
FX This work was supported in part by Dutch Arthritis Association Grant NR
10-1-303.; Supported by a Veni Grant from the Netherlands Organization
for Scientific Research.; Supported by National Institute of Health
Grant R01AR056296.; Supported by a Vici grant from The Netherlands
Organization for Scientific Research.
NR 46
TC 11
Z9 11
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 22
PY 2013
VL 288
IS 12
BP 8658
EP 8666
DI 10.1074/jbc.M112.412841
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 112AS
UT WOS:000316564500066
PM 23386602
ER
PT J
AU Nag, A
Bochukova, EG
Kremeyer, B
Campbell, DD
Muller, H
Valencia-Duarte, AV
Cardona, J
Rivas, IC
Mesa, SC
Cuartas, M
Garcia, J
Bedoya, G
Cornejo, W
Herrera, LD
Romero, R
Fournier, E
Reus, VI
Lowe, TL
Farooqi, IS
Mathews, CA
McGrath, LM
Yu, DM
Cook, E
Wang, K
Scharf, JM
Pauls, DL
Freimer, NB
Plagnol, V
Ruiz-Linares, A
AF Nag, Abhishek
Bochukova, Elena G.
Kremeyer, Barbara
Campbell, Desmond D.
Muller, Heike
Valencia-Duarte, Ana V.
Cardona, Julio
Rivas, Isabel C.
Mesa, Sandra C.
Cuartas, Mauricio
Garcia, Jharley
Bedoya, Gabriel
Cornejo, William
Herrera, Luis D.
Romero, Roxana
Fournier, Eduardo
Reus, Victor I.
Lowe, Thomas L.
Farooqi, I. Sadaf
Mathews, Carol A.
McGrath, Lauren M.
Yu, Dongmei
Cook, Ed
Wang, Kai
Scharf, Jeremiah M.
Pauls, David L.
Freimer, Nelson B.
Plagnol, Vincent
Ruiz-Linares, Andres
CA Tourette Syndrome Assoc Int
TI CNV Analysis in Tourette Syndrome Implicates Large Genomic
Rearrangements in COL8A1 and NRXN1
SO PLOS ONE
LA English
DT Article
ID COPY NUMBER VARIATION; NERVOUS-SYSTEM; VARIANTS; GENES; SCHIZOPHRENIA;
ASSOCIATION; DISORDER; FAMILY; AUTISM; SUSCEPTIBILITY
AB Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (. 500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with similar to 400kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.
C1 [Nag, Abhishek; Kremeyer, Barbara; Campbell, Desmond D.; Muller, Heike; Plagnol, Vincent; Ruiz-Linares, Andres] UCL, UCL Genet Inst, Dept Genet Evolut & Environm, London, England.
[Bochukova, Elena G.; Farooqi, I. Sadaf] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England.
[Valencia-Duarte, Ana V.; Cuartas, Mauricio; Garcia, Jharley; Bedoya, Gabriel] Univ Antioquia, Genet Mol Lab, SIU, Medellin, Colombia.
[Valencia-Duarte, Ana V.; Cornejo, William] Univ Pontificia Bolivariana, Escuela Ciencias Salud, Medellin, Colombia.
[Cardona, Julio; Rivas, Isabel C.; Mesa, Sandra C.; Cornejo, William] Univ Antioquia, Dept Pediat, Fac Med, Medellin, Colombia.
[Herrera, Luis D.; Romero, Roxana; Fournier, Eduardo] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica.
[Reus, Victor I.; Lowe, Thomas L.; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[McGrath, Lauren M.; Scharf, Jeremiah M.; Pauls, David L.] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA.
[McGrath, Lauren M.; Yu, Dongmei; Scharf, Jeremiah M.; Pauls, David L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Cook, Ed] Univ Illinois, Chicago, IL USA.
[Wang, Kai] Univ So Calif, Los Angeles, CA USA.
[Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA.
RP Ruiz-Linares, A (reprint author), UCL, UCL Genet Inst, Dept Genet Evolut & Environm, London, England.
EM a.ruizlin@ucl.ac.uk
RI reus, victor/I-7923-2015;
OI reus, victor/0000-0002-8193-5697; Campbell, Desmond/0000-0003-1085-714X;
McGrath, Lauren/0000-0001-6928-9656; Plagnol,
Vincent/0000-0002-5597-9215; Farooqi, Sadaf/0000-0001-7609-3504;
Bochukova, Elena/0000-0003-0275-1548
FU National Institutes of Health [NS043538, NS037484, MH085057, NS40024,
NS16648]; CODI; Judah Foundation; Tourette Syndrome Association; United
Kingdom Medical Research Council [G1001158]; NIHR Moorfields Biomedical
Research Council
FX This work was funded by National Institutes of Health
(http://www.nih.gov/) grants NS043538 (to ARL), NS037484 (to NBF),
MH085057 (to JMS), NS40024 (to DLP and JMS) and NS16648 (the Tourette
Syndrome Association International Consortium for Genetics), a CODI
grant
(http://www.udea.edu.co/portal/page/portal/Programas/GruposInvestigacion
/h.Convocatorias/CODI/estrategiaSostenibilidad) (Sostenibilidad,
Universidad de Antioquia), a grant from the Judah Foundation
(http://www.judahfoundation.org/), and the Tourette Syndrome Association
(http://tsa-usa.org/) (fellowship to BK and a grant to DLP). VP is
supported by a grant from the United Kingdom Medical Research Council
(http://www.mrc.ac.uk) (G1001158) and by the NIHR Moorfields Biomedical
Research Council (http://www.brcophthalmology.org/). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 32
TC 24
Z9 24
U1 0
U2 9
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 MAR 22
PY 2013
VL 8
IS 3
AR e59061
DI 10.1371/journal.pone.0059061
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111VQ
UT WOS:000316549400037
PM 23533600
ER
PT J
AU Cattaneo, Z
Vecchi, T
Monegato, M
Pece, A
Merabet, LB
Carbon, CC
AF Cattaneo, Zaira
Vecchi, Tomaso
Monegato, Maura
Pece, Alfredo
Merabet, Lotfi B.
Carbon, Claus-Christian
TI Strabismic amblyopia affects relational but not featural and Gestalt
processing of faces
SO VISION RESEARCH
LA English
DT Article
DE Face processing; Amblyopia; Relational; Featural; Holistic; Face
detection; Hemisphere; Laterality; Recognition; Strabismus; Dissociation
ID EARLY VISUAL DEPRIVATION; FACIAL IDENTITY; RECOGNITION; PERCEPTION;
DEFICIT; IDENTIFICATION; INFORMATION; SENSITIVITY; PROSOPAGNOSIA;
PATTERN
AB The ability to identify faces is of critical importance for normal social interactions. Previous evidence suggests that early visual deprivation may impair certain aspects of face recognition. The effects of strabismic amblyopia on face processing have not been investigated previously. In this study, a group of individuals with amblyopia were administered two tasks known to selectively measure face detection based on a Gestalt representation of a face (Mooney faces task) and featural and relational processing of faces (Jane faces task). Our data show that - when relying on their amblyopic eye only - strabismic amblyopes perform as well as normally sighted individuals in face detection and recognition on the basis of their single features. However, they are significantly impaired in discriminating among different faces on the basis of the spacing of their single features (i.e., configural processing of relational information). Our findings are the first to demonstrate that strabismic amblyopia may cause specific deficits in face recognition, and add to previous reports characterizing visual perceptual deficits associated in amblyopia as high-level and not only as low-level processing. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Cattaneo, Zaira] Univ Milano Bicocca, Dept Psychol, Milan, Italy.
[Cattaneo, Zaira; Vecchi, Tomaso] IRCCS Mondino, Brain Connect Ctr, Pavia, Italy.
[Vecchi, Tomaso; Monegato, Maura] Univ Pavia, Dept Brain & Behav Sci, I-27100 Pavia, Italy.
[Monegato, Maura; Pece, Alfredo] Melegnano Hosp, Ophthalmol Unit, Melegnano, Italy.
[Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Carbon, Claus-Christian] Univ Bamberg, Dept Gen Psychol & Methodol, Bamberg, Germany.
RP Cattaneo, Z (reprint author), Univ Milano Bicocca, Dept Psychol, Milan, Italy.
EM zaira.cattaneo@unimib.it
RI Carbon, Claus-Christian/A-7494-2008
OI Carbon, Claus-Christian/0000-0002-3446-9347
FU Vigoni/DAAD; FIRB grant [RBFR12F0BD_003]
FX The authors thank Cathy Mondloch and her colleagues for providing the
original stimuli of Mondloch, Le Grand, and Maurer (2002) as stimuli for
the "Jane Face task". This work was supported by Vigoni/DAAD grants
(years 2012-2013) to Z.C. and C.C.C. and by a FIRB grant
(RBFR12F0BD_003) to Z.C.
NR 73
TC 2
Z9 2
U1 1
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
EI 1878-5646
J9 VISION RES
JI Vision Res.
PD MAR 22
PY 2013
VL 80
BP 19
EP 30
DI 10.1016/j.visres.2013.01.007
PG 12
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 108OA
UT WOS:000316304000003
PM 23376210
ER
PT J
AU Mattila, PK
Feest, C
Depoil, D
Treanor, B
Montaner, B
Otipoby, KL
Carter, R
Justement, LB
Bruckbauer, A
Batista, FD
AF Mattila, Pieta K.
Feest, Christoph
Depoil, David
Treanor, Bebhinn
Montaner, Beatriz
Otipoby, Kevin L.
Carter, Robert
Justement, Louis B.
Bruckbauer, Andreas
Batista, Facundo D.
TI The Actin and Tetraspanin Networks Organize Receptor Nanoclusters to
Regulate B Cell Receptor-Mediated Signaling
SO IMMUNITY
LA English
DT Article
ID IMMUNE-SYNAPSE FORMATION; ANTIGEN RECEPTOR; MICROCLUSTER FORMATION;
LYMPHOCYTE DEVELOPMENT; MEMBRANE; MICE; ACTIVATION; RESPONSES;
TRANSDUCTION; EXPRESSION
AB A key role is emerging for the cytoskeleton in coordinating receptor signaling, although the underlying molecular requirements remain unclear. Here we show that cytoskeleton disruption triggered signaling requiring not only the B cell receptor (BCR), but also the coreceptor CD19 and tetraspanin CD81, thus providing a mechanism for signal amplification upon surface-bound antigen stimulation. By using superresolution microscopy, we demonstrated that endogenous IgM, IgD, and CD19 exhibited distinct nanoscale organization within the plasma membrane of primary B cells. Upon stimulation, we detect a local convergence of receptors, although their global organization was not dramatically altered. Thus, we postulate that cytoskeleton reorganization releases BCR nanoclusters, which can interact with CD19 held in place by the tetraspanin network. These results not only suggest that receptor compartmentalization regulates antigen-induced activation but also imply a potential role for CD19 in mediating ligand-independent "tonic'' BCR signaling necessary for B cell survival.
C1 [Mattila, Pieta K.; Feest, Christoph; Depoil, David; Treanor, Bebhinn; Montaner, Beatriz; Bruckbauer, Andreas; Batista, Facundo D.] Canc Res UK, London Res Inst, Lymphocyte Interact Lab, London WC2A 3LY, England.
[Otipoby, Kevin L.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Otipoby, Kevin L.] Immune Dis Inst, Boston, MA 02115 USA.
[Carter, Robert] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Justement, Louis B.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
RP Batista, FD (reprint author), Canc Res UK, London Res Inst, Lymphocyte Interact Lab, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM facundo.batista@cancer.org.uk
RI Mattila, Pieta/G-6815-2013; Feest, Christoph/C-7874-2013;
OI Mattila, Pieta/0000-0003-2805-0686; Feest,
Christoph/0000-0002-0772-7267; Justement, Louis/0000-0001-7058-867X
FU Cancer Research UK; Royal Society Wolfson Research Merit Award; Human
Frontier Science Program
FX We are extremely thankful to K. Rajewsky, K. Okkenhaug, and S. Levy for
providing B1-8f Igh, Cd21-cre, E mu-Bcl2 transgenic, PI3K delta-mutant,
and CD81-deficient mice, respectively. We would also like to thank D.
Bray and members of the Lymphocyte Interaction Laboratory for critically
reading the manuscript and for helpful discussions and comments. This
work was supported by Cancer Research UK, Royal Society Wolfson Research
Merit Award (F. D. B.), and Human Frontier Science Program (P.K.M.).
NR 43
TC 97
Z9 99
U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD MAR 21
PY 2013
VL 38
IS 3
BP 461
EP 474
DI 10.1016/j.immuni.2012.11.019
PG 14
WC Immunology
SC Immunology
GA AA2RJ
UT WOS:000330941500012
PM 23499492
ER
PT J
AU Ferguson, AL
Mann, JK
Omarjee, S
Ndung'u, T
Walker, BD
Chakraborty, AK
AF Ferguson, Andrew L.
Mann, Jaclyn K.
Omarjee, Saleha
Ndung'u, Thumbi
Walker, Bruce D.
Chakraborty, Arup K.
TI Translating HIV Sequences into Quantitative Fitness Landscapes Predicts
Viral Vulnerabilities for Rational Immunogen Design
SO IMMUNITY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; REPLICATION CAPACITY;
CLASS-I; ELITE CONTROLLERS; LYMPHOCYTE ESCAPE; VACCINE DESIGN; HLA
ALLELES; P24 GAG; INFECTION
AB A prophylactic or therapeutic vaccine offers the best hope to curb the HIV-AIDS epidemic gripping sub-Saharan Africa, but it remains elusive. A major challenge is the extreme viral sequence variability among strains. Systematic means to guide immunogen design for highly variable pathogens like HIV are not available. Using computational models, we have developed an approach to translate available viral sequence data into quantitative landscapes of viral fitness as a function of the amino acid sequences of its constituent proteins. Predictions emerging from our computationally defined landscapes for the proteins of HIV-1 clade B Gag were positively tested against new in vitro fitness measurements and were consistent with previously defined in vitro measurements and clinical observations. These landscapes chart the peaks and valleys of viral fitness as protein sequences change and inform the design of immunogens and therapies that can target regions of the virus most vulnerable to selection pressure.
C1 [Ferguson, Andrew L.; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Ferguson, Andrew L.; Ndung'u, Thumbi; Walker, Bruce D.; Chakraborty, Arup K.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02129 USA.
[Ferguson, Andrew L.; Ndung'u, Thumbi; Walker, Bruce D.; Chakraborty, Arup K.] Harvard Univ, Boston, MA 02129 USA.
[Mann, Jaclyn K.; Omarjee, Saleha; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, ZA-4013 Durban, South Africa.
[Mann, Jaclyn K.; Omarjee, Saleha; Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV K RITH, ZA-4013 Durban, South Africa.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] MIT, Dept Phys, Cambridge, MA 02139 USA.
[Chakraborty, Arup K.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
RP Chakraborty, AK (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
EM arupc@mit.edu
OI Ndung'u, Thumbi/0000-0003-2962-3992; Ferguson,
Andrew/0000-0002-8829-9726
FU Ragon Institute; National Institutes of Health Director's Pioneers
Award; NIH [AI30914]; Howard Hughes Medical Institute; South African
Department of Science and Technology/National Research Foundation
Research Chair Initiative; Ragon Postdoctoral Fellowship
FX We thank Todd Allen, Herman Eisen, and John Barton for fruitful
discussions. Financial support was provided by the Ragon Institute (B.
D. W., A. K. C., J.K.M., S.O., T.N.), a National Institutes of Health
Director's Pioneers Award (A. K. C.), NIH Award AI30914 (B. D. W.), the
Howard Hughes Medical Institute (B. D. W., T.N.), the South African
Department of Science and Technology/National Research Foundation
Research Chair Initiative (J.K.M., S.O., T.N.), and a Ragon Postdoctoral
Fellowship (A.L.F.).
NR 52
TC 56
Z9 59
U1 3
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD MAR 21
PY 2013
VL 38
IS 3
BP 606
EP 617
DI 10.1016/j.immuni.2012.11.022
PG 12
WC Immunology
SC Immunology
GA AA2RJ
UT WOS:000330941500023
PM 23521886
ER
PT J
AU Musallam, KM
Taher, AT
Cappellini, MD
Sankaran, VG
AF Musallam, Khaled M.
Taher, Ali T.
Cappellini, Maria Domenica
Sankaran, Vijay G.
TI Clinical experience with fetal hemoglobin induction therapy in patients
with beta-thalassemia
SO BLOOD
LA English
DT Review
ID SICKLE-CELL-ANEMIA; RECOMBINANT-HUMAN-ERYTHROPOIETIN; SODIUM
PHENYLBUTYRATE THERAPY; GLOBIN GENE-EXPRESSION; RED-BLOOD-CELLS;
HYDROXYUREA THERAPY; TRANSFUSION REQUIREMENTS; INTERMEDIA PATIENTS; DNA
METHYLATION; EXTRAMEDULLARY HEMATOPOIESIS
AB Recent molecular studies of fetal hemoglobin (HbF) regulation have reinvigorated the field and shown promise for the development of clinical HbF inducers to be used in patients with beta-thalassemia and sickle cell disease. However, while numerous promising inducers of HbF have been studied in the past in beta-thalassemia patient populations, with limited success in some cases, no universally effective agents have been found. Here we examine the clinical studies of such inducers in an attempt to systematically review the field. We examine trials of agents, including 5-azacytidine, hydroxyurea, and short-chain fatty acids. This review highlights the heterogeneity of clinical studies done on these agents, including both the patient populations examined and the study end points. By examining the published studies of these agents, we hope to provide a resource that will be valuable for the design of future studies of HbF inducers in beta-thalassemia patient populations.
C1 [Musallam, Khaled M.; Cappellini, Maria Domenica] Univ Milan, Dept Med & Med Specialties, Fdn IRCCS Ca Granda, Osped Maggiore Policlin, Milan, Italy.
[Musallam, Khaled M.; Taher, Ali T.] Amer Univ Beirut, Med Ctr, Dept Internal Med, Beirut, Lebanon.
[Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA.
[Sankaran, Vijay G.] Broad Inst, Cambridge, MA USA.
[Sankaran, Vijay G.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
RP Sankaran, VG (reprint author), Boston Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA.
EM sankaran@broadinstitute.org
NR 146
TC 41
Z9 44
U1 3
U2 18
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 21
PY 2013
VL 121
IS 12
BP 2199
EP 2212
DI 10.1182/blood-2012-10-408021
PG 14
WC Hematology
SC Hematology
GA 182RI
UT WOS:000321761100010
PM 23315167
ER
PT J
AU Hoggatt, J
Mohammad, KS
Singh, P
Hoggatt, AF
Chitteti, BR
Speth, JM
Hu, PR
Poteat, BA
Stilger, KN
Ferraro, F
Silberstein, L
Wong, FK
Farag, SS
Czader, M
Milne, GL
Breyer, RM
Serezani, CH
Scadden, DT
Guise, TA
Srour, EF
Pelus, LM
AF Hoggatt, Jonathan
Mohammad, Khalid S.
Singh, Pratibha
Hoggatt, Amber F.
Chitteti, Brahmananda R.
Speth, Jennifer M.
Hu, Peirong
Poteat, Bradley A.
Stilger, Kayla N.
Ferraro, Francesca
Silberstein, Lev
Wong, Frankie K.
Farag, Sherif S.
Czader, Magdalena
Milne, Ginger L.
Breyer, Richard M.
Serezani, Carlos H.
Scadden, David T.
Guise, Theresa A.
Srour, Edward F.
Pelus, Louis M.
TI Differential stem- and progenitor-cell trafficking by prostaglandin E-2
SO NATURE
LA English
DT Article
ID BONE-MARROW NICHE; HEMATOPOIETIC STEM; RECEPTOR; MICROENVIRONMENT;
OSTEOPONTIN; IMPACT; SIZE
AB To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury(1-5). Despite considerable advances in the specific cellular or molecular mechanisms governing HSC-niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E-2 (PGE(2)) on HSC function ex vivo(6,7). Here we show that inhibition of endogenous PGE(2) by nonsteroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1-CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE(2) receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.
C1 [Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Speth, Jennifer M.; Hu, Peirong; Stilger, Kayla N.; Czader, Magdalena; Serezani, Carlos H.; Guise, Theresa A.; Srour, Edward F.; Pelus, Louis M.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Hoggatt, Jonathan; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Harvard Med Sch, Ctr Regenerat Med,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hoggatt, Amber F.] Univ Illinois, Biol Resources Lab, Chicago, IL 60612 USA.
[Chitteti, Brahmananda R.; Poteat, Bradley A.; Farag, Sherif S.; Srour, Edward F.] Indiana Univ Sch Med, Div Hematol & Oncol, Indianapolis, IN 46202 USA.
[Milne, Ginger L.] Vanderbilt Univ, Div Clin Pharmacol, Eicosanoid Core Lab, Nashville, TN 37232 USA.
[Breyer, Richard M.] Vanderbilt Univ, Div Nephrol & Hypertens, Nashville, TN 37232 USA.
RP Pelus, LM (reprint author), Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
EM lpelus@iupui.edu
RI Milne, Ginger/D-7648-2014;
OI Milne, Ginger/0000-0003-3890-151X; serezani, carlos/0000-0002-5363-415X
FU National Institutes of Health (NIH) [HL096305, CA143057, CA069158,
HL100402, DK37097]; NIH [DK07519, HL07910, HL087735]; Center of
Excellence in Hematology [P01 DK090948]
FX These studies were supported by National Institutes of Health (NIH)
grants HL096305 (L.M.P.), CA143057, CA069158 (T.A.G., K.S.M.), HL100402
(D.T.S.) and DK37097 (R.M.B.). J.H. was supported by NIH training grants
DK07519, HL07910 and HL087735. Flow cytometry was performed in the Flow
Cytometry Resource Facility of the Indiana University Simon Cancer
Center (NCI P30 CA082709). Additional core support was provided by a
Center of Excellence in Hematology grant P01 DK090948. The authors would
like to thank H. E. Broxmeyer and B. Saez for critically reading the
manuscript.
NR 26
TC 50
Z9 51
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 21
PY 2013
VL 495
IS 7441
BP 365
EP 369
DI 10.1038/nature11929
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500042
PM 23485965
ER
PT J
AU Schulz, TJ
Huang, P
Huang, TL
Xue, RD
McDougall, LE
Townsend, KL
Cypess, AM
Mishina, Y
Gussoni, E
Tseng, YH
AF Schulz, Tim J.
Huang, Ping
Huang, Tian Lian
Xue, Ruidan
McDougall, Lindsay E.
Townsend, Kristy L.
Cypess, Aaron M.
Mishina, Yuji
Gussoni, Emanuela
Tseng, Yu-Hua
TI Brown-fat paucity due to impaired BMP signalling induces compensatory
browning of white fat
SO NATURE
LA English
DT Article
ID ADIPOSE-TISSUE; TRANSCRIPTIONAL CONTROL; ADULT HUMANS; ADIPOCYTES;
THERMOGENESIS; MICE; DISTINCT; REVEALS; MUSCLE; MOUSE
AB Maintenance of body temperature is essential for the survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation(1). Owing to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans(2-5), BAT holds great promise for the treatment of obesity and metabolic syndrome(1). Rodent data suggest the existence of two types of brown fat cells: constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the imterscapular region of mice; and recruitable BAT (rBAT), which resides within white adipose tissue (WAT)(6) and skeletal muscle(7), and has alternatively been called beige(8), brite(9) or inducible BAT(10). Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT(10-12). Here we use mouse models to provide evidence for a systemically active regulatory mechanism that controls whole-body BAT activity for thermoregulation and energy homeostasis. Genetic ablation of the type 1A BMP receptor (Bmpr1a) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown-fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease.
C1 [Schulz, Tim J.; Huang, Tian Lian; Xue, Ruidan; McDougall, Lindsay E.; Townsend, Kristy L.; Cypess, Aaron M.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
[Huang, Ping; Gussoni, Emanuela] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Huang, Ping; Gussoni, Emanuela] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Xue, Ruidan] Fudan Univ, Shanghai Med Coll, Huashan Hosp, Div Endocrinol & Metab, Shanghai 200032, Peoples R China.
[Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[Tseng, Yu-Hua] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Tseng, YH (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
EM yu-hua.tseng@joslin.harvard.edu
RI Schulz, Tim/F-4842-2013
OI Schulz, Tim/0000-0002-8413-3972
FU National Institutes of Health (NIH) [R01 DK077097]; Joslin Diabetes
Center's Diabetes Research Center (DRC from the NIDDK) [P30 DK036836];
Eli Lilly Research Foundation; Harvard Stem Cell Institute; Mary K.
Iacocca Foundation; German Research Foundation (DFG) [SCHU2445/1-1];
American Heart Association [0730285N]; NIH [T32 DK007260, F32 DK091996];
National Natural Science Foundation of China [985III-YFX0302,
NSFC81070680]
FX This work was supported in part by National Institutes of Health (NIH)
grants R01 DK077097 (Y.-H.T.), and Joslin Diabetes Center's Diabetes
Research Center (DRC; P30 DK036836 from the NIDDK), a research grant
from the Eli Lilly Research Foundation, and by funding from the Harvard
Stem Cell Institute (to Y.-H.T.), T.J.S. was supported by the Mary K.
Iacocca Foundation and the German Research Foundation (DFG;
SCHU2445/1-1). P.H. was supported by a Scientist Development Grant from
the American Heart Association (0730285N). K.L.T. was supported by NIH
fellowships (T32 DK007260 and F32 DK091996). R.X. was supported by
Project 985III-YFX0302 and NSFC81070680 from the National Natural
Science Foundation of China. The authors thank Stryker Regenerative
Medicine for the gift of recombinant BMP7. We acknowledge V. Kaartinen,
B. Kahn, K. Lyons and P. Soriano for providing floxed Acvr1 mice,
FABP4-Cre mice, Bmpr1b heterozygous mice and Myf5-Cre mice,
respectively. The authors thank C. R. Kahn, L.J. Goodyear, E. Kokkotou
and D. Breault for comments on the manuscript The authors wish to thank
J. LaVecchio, G. Buruzula, A. Wakabayashi, A. Pinkhasov, A. Clermont, M.
Mulvey, C. Cahill and G. Sankaranarayanan for technical assistance, and
E. Caniano for editorial contributions.
NR 30
TC 123
Z9 126
U1 5
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 21
PY 2013
VL 495
IS 7441
BP 379
EP 383
DI 10.1038/nature11943
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500045
PM 23485971
ER
PT J
AU Fracchia, MS
El Saleeby, CM
Murali, MR
Sagar, P
Mino-Kenudson, M
AF Fracchia, Mary Shannon
El Saleeby, Chadi M.
Murali, Mandakolathur R.
Sagar, Pallavi
Mino-Kenudson, Mari
TI Case 9-2013: A 9-Year-Old Boy with Fever, Cough, Respiratory Distress,
and Chest Pain
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HYPERSENSITIVITY PNEUMONITIS; DISEASE; EPIDEMIOLOGY; DIAGNOSIS;
EVOLUTION; CHILDREN
C1 [Fracchia, Mary Shannon; El Saleeby, Chadi M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Murali, Mandakolathur R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Sagar, Pallavi] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Fracchia, Mary Shannon; El Saleeby, Chadi M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Murali, Mandakolathur R.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Sagar, Pallavi] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Fracchia, MS (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
FU Department of Continuing Education, Harvard Medical School
FX This case was discussed at the postgraduate course, Primary Care
Pediatrics; course directors: Ronni L. Goldsmith, M. D., Peter T.
Greenspan, M. D., Ronald E. Kleinman, M. D., Janice A. Lowe, M. D., and
John Patrick T. Co, M. D., M. P. H., sponsored by the Department of
Continuing Education, Harvard Medical School.
NR 19
TC 3
Z9 3
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 21
PY 2013
VL 368
IS 12
BP 1141
EP 1150
DI 10.1056/NEJMcpc1208144
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 108TH
UT WOS:000316318600009
PM 23514292
ER
PT J
AU Nejad, SH
Bajwa, EK
AF Nejad, Shamim H.
Bajwa, Ednan K.
TI Case 39-2012: A Man with Alcoholism, Recurrent Seizures, and Agitation
Reply
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Nejad, Shamim H.; Bajwa, Ednan K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Nejad, SH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 21
PY 2013
VL 368
IS 12
BP 1164
EP 1165
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 108TH
UT WOS:000316318600028
PM 23514305
ER
PT J
AU Yigit, MV
Ghosh, SK
Kumar, M
Petkova, V
Kavishwar, A
Moore, A
Medarova, Z
AF Yigit, M. V.
Ghosh, S. K.
Kumar, M.
Petkova, V.
Kavishwar, A.
Moore, A.
Medarova, Z.
TI Context-dependent differences in miR-10b breast oncogenesis can be
targeted for the prevention and arrest of lymph node metastasis
SO ONCOGENE
LA English
DT Article
DE imaging; miRNA; metastasis; miR-10b; nanoparticle; therapy
ID SUPERPARAMAGNETIC IRON-OXIDE; CANCER; MICRORNA; THERAPEUTICS; LNA
AB Metastases, and not the primary tumor from which they originate, are the main reason for mortality from carcinoma. Although the molecular mechanisms behind metastasis are poorly understood, it is clear that epigenetic dysregulation at the level of microRNA expression is a key characteristic of the metastatic process that can be exploited for therapy. Here, we describe an miRNA-targeted therapeutic approach for the prevention and arrest of lymph node metastasis. Therapy relies on the inhibition of the pro-metastatic microRNA-10b. It is delivered to primary and lymph node metastatic tumor cells using an imaging-capable nanodrug that is designed to specifically home to these tissues. Treatment of invasive human breast tumor cells (MDA-MB-231) with the nanodrug in vitro downregulates miR-10b and abolishes the invasion and migration of the tumor cells. After intravenous delivery to mice bearing orthotopic MDA-MB-231-luc-D3H2LN tumors, the nanodrug accumulates in the primary tumor and lymph nodes. When treatment is initiated before metastasis to lymph nodes, metastasis is prevented. Treatment after the formation of lymph node metastases arrests the metastatic process without a concomitant effect on primary tumor growth raising the possibility of a context-dependent variation in miR-10b breast oncogenesis. Oncogene (2013) 32, 1530-1538; doi:10.1038/onc.2012.173; published online 14 May 2012
C1 [Yigit, M. V.; Ghosh, S. K.; Kumar, M.; Kavishwar, A.; Moore, A.; Medarova, Z.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Mol Imaging Lab, Dept Radiol, Charlestown, MA USA.
[Yigit, M. V.; Ghosh, S. K.; Kumar, M.; Kavishwar, A.; Moore, A.; Medarova, Z.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Petkova, V.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Mol Imaging Lab,MGH MIT HMS Athinoula, Bldg 75,13th St, Charlestown, MA 02129 USA.
EM amoore@helix.mgh.harvard.edu; zmedarova@partners.org
OI Kavishwar, Amol/0000-0001-8214-6625
FU National Cancer Institute [R00CA129070]; Breast Cancer Alliance
FX We thank Pamela Pantazopoulos and Alana Ross for help with the in-vitro,
in-vivo and ex-vivo studies and Marytheresa Ifediba for proofreading the
manuscript. Confocal microscopy was performed at the Confocal Microscopy
Core at MGH with technical assistance from Igor A Bagayev, MS Work at
the Martinos Center for Biomedical Imaging was supported in part under
Grant R00CA129070 from the National Cancer Institute and a Research
Grant from the Breast Cancer Alliance.
NR 26
TC 34
Z9 34
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 21
PY 2013
VL 32
IS 12
BP 1530
EP 1538
DI 10.1038/onc.2012.173
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 110PC
UT WOS:000316456000006
PM 22580603
ER
PT J
AU Nunes, FP
Merker, VL
Jennings, D
Caruso, PA
di Tomaso, E
Muzikansky, A
Barker, FG
Stemmer-Rachamimov, A
Plotkin, SR
AF Nunes, Fabio P.
Merker, Vanessa L.
Jennings, Dominique
Caruso, Paul A.
di Tomaso, Emmanuelle
Muzikansky, Alona
Barker, Fred G., II
Stemmer-Rachamimov, Anat
Plotkin, Scott R.
TI Bevacizumab Treatment for Meningiomas in NF2: A Retrospective Analysis
of 15 Patients
SO PLOS ONE
LA English
DT Article
ID PHASE-II; NEUROFIBROMATOSIS TYPE-2; RECURRENT MENINGIOMAS; HYDROXYUREA;
REGRESSION; THERAPY; ADULTS
AB Bevacizumab treatment can result in tumor shrinkage of progressive vestibular schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on meningiomas has not been defined. To determine the clinical activity of bevacizumab against NF2-related meningiomas, we measured changes in volume of meningiomas in NF2 patients who received bevacizumab for treatment of progressive vestibular schwannomas. A radiographic response was defined as a 20% decrease in tumor size by volumetric MRI analysis. In addition, we determined the expression pattern of growth factors associated with tumor angiogenesis in paraffin-embedded tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2 patients were included in this study with a median follow up time of 18 months. A volumetric radiographic response was seen in 29% of the meningiomas (14/48). Tumor shrinkage was not durable: the median duration of response was 3.7 months and the median time to progression was 15 months. There was no significant correlation between pre-treatment growth rate and meningioma response in regression models. Tissue analysis showed no correlation between tumor microvascular density and expression of VEGF pathway components. This data suggests that, in contrast to schwannomas, activation of VEGF pathway is not the primary driver of angiogenesis in meningiomas. Our results suggest that a minority of NF2-associated meningiomas shrink during bevacizumab therapy and that these responses were of short duration. These results are comparable to previous studies of bevacizumab in sporadic meningiomas.
C1 [Nunes, Fabio P.; Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Nunes, Fabio P.] Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA.
[Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Jennings, Dominique] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Caruso, Paul A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[di Tomaso, Emmanuelle; Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Muzikansky, Alona] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA.
[Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM splotkin@partners.org
OI Merker, Vanessa/0000-0002-4542-5227
FU United States National Institutes of Heath [5-T32-GM007748-32]
FX This work was supported by a United States National Institutes of Heath
grant (5-T32-GM007748-32) to FPN. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 28
TC 31
Z9 33
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 MAR 21
PY 2013
VL 8
IS 3
AR e59941
DI 10.1371/journal.pone.0059941
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 111UM
UT WOS:000316546400070
PM 23555840
ER
PT J
AU Li, R
Sharp, G
AF Li, Rui
Sharp, Gregory
TI Robust fluoroscopic tracking of fiducial markers: exploiting the spatial
constraints
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID REAL-TIME TUMOR; GATED RADIATION-THERAPY; LUNG-TUMORS; RADIOTHERAPY;
MOTION; SYSTEM; RADIOSURGERY; FEASIBILITY; PROJECTIONS; MANAGEMENT
AB Two new fluoroscopic fiducial tracking methods that exploit the spatial relationship among the multiple implanted fiducial to achieve fast, accurate and robust tracking are proposed in this paper. The spatial relationship between multiple implanted markers are modeled as Gaussian distributions of their pairwise distances over time. The means and standard deviations of these distances are learned from training sequences, and pairwise distances that deviate from these learned distributions are assigned a low spatial matching score. The spatial constraints are incorporated in two different algorithms: a stochastic tracking method and a detection based method. In the stochastic method, hypotheses of the 'true' fiducial position are sampled from a pretrained respiration motion model. Each hypothesis is assigned an importance value based on image matching score and spatial matching score. Learning the parameters of the motion model is needed in addition to learning the distribution parameters of the pairwise distances in the proposed stochastic tracking approach. In the detection based method, a set of possible marker locations are identified by using a template matching based fiducial detector. The best location is obtained by optimizing the image matching score and spatial matching score through non-serial dynamic programming. In this detection based approach, there is no need to learn the respiration motion model. The two proposed algorithms are compared with a recent work using a multiple hypothesis tracking (MHT) algorithm which is denoted by MHT, Tang et al (2007 Phys. Med. Biol. 52 4081-98). Phantom experiments were performed using fluoroscopic videos captured with known motion relative to an anthropomorphic phantom. The patient experiments were performed using a retrospective study of 16 fluoroscopic videos of liver cancer patients with implanted fiducials. For the motion phantom data sets, the detection based approach has the smallest tracking error (mu(err): 0.78-1.74 mm, sigma(err): 0.39-1.16 mm) for the images taken at low exposure (50 mAs). At higher exposure (500 mAs), the stochastic method gave the best performance (mu(err) :similar to 0.39 sigma(err) :similar to 0.27 mm). In contrast, the tracker (MHT) that does not model the spatial constraints only performs well when there is no occluded fiducial. With the RANDO phantom data, both of our proposed methods performed well and have the mean tracking errors around similar to 1.8 mm with the standard deviations similar to 0.93 mm at 100 mAs and similar to 0.91 mm with 0.88 mm standard deviation at 500 mAs. The MHT tracker has the largest tracking errors with mean similar to 4.8 mm) and standard deviation similar to 2.4mmin both sessions with the Rondo phantom data. On the patient data sets, the detection based method gave the smallest error (mu(err): 0.39 mm, sigma(err): similar to 0.19 mm). The stochastic method performed well (mu(err): similar to 0.58 mm, sigma(err): similar to 0.39 mm) when the patient breathed consistently, the accuracy dropped to (mu(err): similar to 1.55 mm) when the patient breathed differently across sessions.
C1 [Li, Rui] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Li, R (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM bucslirui@gmail.com
FU NIH/NCI [P01-CA21239]
FX This research was supported by NIH/NCI grant P01-CA21239.
NR 39
TC 4
Z9 4
U1 0
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 21
PY 2013
VL 58
IS 6
BP 1789
EP 1808
DI 10.1088/0031-9155/58/6/1789
PG 20
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 100WL
UT WOS:000315735400008
PM 23442336
ER
PT J
AU Bahl, S
Chiang, C
Beauchamp, RL
Neale, BM
Daly, MJ
Gusella, JF
Talkowski, ME
Ramesh, V
AF Bahl, Samira
Chiang, Colby
Beauchamp, Roberta L.
Neale, Benjamin M.
Daly, Mark J.
Gusella, James F.
Talkowski, Michael E.
Ramesh, Vijaya
TI Lack of association of rare functional variants in TSC1/TSC2 genes with
autism spectrum disorder
SO MOLECULAR AUTISM
LA English
DT Article
DE Autism spectrum disorder; Tuberous sclerosis complex; Mammalian target
of rapamycin; Next-generation sequencing; Rare variants
ID TUBEROUS SCLEROSIS COMPLEX; DE-NOVO MUTATIONS; DNA-SEQUENCING DATA;
PROTEIN; LIGASE; INDIVIDUALS; GROWTH; TSC1; RHEB; PAM
AB Background: Autism spectrum disorder (ASD) is reported in 30 to 60% of patients with tuberous sclerosis complex (TSC) but shared genetic mechanisms that exist between TSC-associated ASD and idiopathic ASD have yet to be determined. Through the small G-protein Rheb, the TSC proteins, hamartin and tuberin, negatively regulate mammalian target of rapamycin complex 1 (mTORC1) signaling. It is well established that mTORC1 plays a pivotal role in neuronal translation and connectivity, so dysregulation of mTORC1 signaling could be a common feature in many ASDs. Pam, an E3 ubiquitin ligase, binds to TSC proteins and regulates mTORC1 signaling in the CNS, and the FBXO45-Pam ubiquitin ligase complex plays an essential role in neurodevelopment by regulating synapse formation and growth. Since mounting evidence has established autism as a disorder of the synapses, we tested whether rare genetic variants in TSC1, TSC2, MYCBP2, RHEB and FBXO45, genes that regulate mTORC1 signaling and/ or play a role in synapse development and function, contribute to the pathogenesis of idiopathic ASD.
Methods: Exons and splice junctions of TSC1, TSC2, MYCBP2, RHEB and FBXO45 were resequenced for 300 ASD trios from the Simons Simplex Collection (SSC) using a pooled PCR amplification and next-generation sequencing strategy, targeted to the discovery of deleterious coding variation. These detected, potentially functional, variants were confirmed by Sanger sequencing of the individual samples comprising the pools in which they were identified.
Results: We identified a total of 23 missense variants in MYCBP2, TSC1 and TSC2. These variants exhibited a near equal distribution between the proband and parental pools, with no statistical excess in ASD cases (P > 0.05). All proband variants were inherited. No putative deleterious variants were confirmed in RHEB and FBXO45. Three intronic variants, identified as potential splice defects in MYCBP2 did not show aberrant splicing upon RNA assay. Overall, we did not find an over-representation of ASD causal variants in the genes studied to support them as contributors to autism susceptibility.
Conclusions: We did not observe an enrichment of rare functional variants in TSC1 and TSC2 genes in our sample set of 300 trios.
C1 [Bahl, Samira; Chiang, Colby; Beauchamp, Roberta L.; Neale, Benjamin M.; Daly, Mark J.; Gusella, James F.; Talkowski, Michael E.; Ramesh, Vijaya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Neale, Benjamin M.; Daly, Mark J.; Gusella, James F.; Talkowski, Michael E.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02143 USA.
[Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM ramesh@helix.mgh.harvard.edu
OI Chiang, Colby/0000-0002-4113-6065
FU Simons Foundation for Autism Research Initiative [SFARI 95345]; National
Institute of Health [NS024279, MH095867]; TS Alliance
FX We sincerely thank all the families who have participated in the Simons
Simplex study. We are grateful to Tammy Gillis and Mary Anne Anderson in
the Center for Human Genetic Research Genomics Resource and Tissue
Culture Facility for technical assistance. This work was supported by a
grant from Simons Foundation for Autism Research Initiative (SFARI 95345
to VR), National Institute of Health Grants NS024279 (to VR and JFG),
MH095867 (to MET) and a fellowship from TS Alliance (to SB).
NR 47
TC 4
Z9 6
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2040-2392
J9 MOL AUTISM
JI Mol. Autism
PD MAR 20
PY 2013
VL 4
AR 5
DI 10.1186/2040-2392-4-5
PG 11
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA 254UI
UT WOS:000327192900001
PM 23514105
ER
PT J
AU Braverman, ER
Blum, K
Damle, UJ
Kerner, M
Dushaj, K
Oscar-Berman, M
AF Braverman, Eric R.
Blum, Kenneth
Damle, Uma J.
Kerner, Mallory
Dushaj, Kristina
Oscar-Berman, Marlene
TI Evoked Potentials and Neuropsychological Tests Validate Positron
Emission Topography (PET) Brain Metabolism in Cognitively Impaired
Patients
SO PLOS ONE
LA English
DT Article
ID MINI-MENTAL-STATE; FAMILIAL ALZHEIMER-DISEASE; CORTICAL THICKNESS;
AMYLOID PATHOLOGY; MEMORY IMPAIRMENT; FDG-PET; DECLINE; DEMENTIA; MCI;
CSF
AB Fluorodeoxyglucose (FDG) Positron Emission Topography (PET) brain hypometabolism (HM) correlates with diminished cognitive capacity and risk of developing dementia. However, because clinical utility of PET is limited by cost, we sought to determine whether a less costly electrophysiological measure, the P300 evoked potential, in combination with neuropsychological test performance, would validate PET HM in neuropsychiatric patients. We found that patients with amnestic and non-amnestic cognitive impairment and HM (n = 43) evidenced significantly reduced P300 amplitudes, delayed latencies, and neuropsychological deficits, compared to patients with normal brain metabolism (NM; n = 187). Data from patients with missing cognitive test scores (n = 57) were removed from the final sample, and logistic regression modeling was performed on the modified sample (n = 173, p = .000004). The logistic regression modeling, based on P300 and neuropsychological measures, was used to validate membership in the HM vs. NM groups. It showed classification validation in 13/25 HM subjects (52.0%) and in 125/148 NM subjects (84.5%), correlating with total classification accuracy of 79.8%. In this paper, abnormal P300 evoked potentials coupled with cognitive test impairment validates brain metabolism and mild/moderate cognitive impairment (MCI). To this end, we cautiously propose incorporating electrophysiological and neuropsychological assessments as cost-effective brain metabolism and MCI indicators in primary care. Final interpretation of these results must await required additional studies confirming these interesting results.
C1 [Braverman, Eric R.; Blum, Kenneth; Damle, Uma J.; Kerner, Mallory; Dushaj, Kristina] PATH Fdn NY, Dept Clin Neurol, New York, NY 10010 USA.
[Braverman, Eric R.; Blum, Kenneth] Univ Florida, Dept Psychiat, Coll Med, Gainesville, FL 32611 USA.
[Braverman, Eric R.; Blum, Kenneth] Univ Florida, Coll Med, McKnight Brain Inst, Gainesville, FL USA.
[Blum, Kenneth] Univ Vermont, Coll Med, Ctr Clin & Translat Sci, Global Integrated Serv Unit, Burlington, VT USA.
[Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Oscar-Berman, Marlene] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA.
[Oscar-Berman, Marlene] Boston VA Healthcare Syst, Boston, MA USA.
RP Braverman, ER (reprint author), PATH Fdn NY, Dept Clin Neurol, New York, NY 10010 USA.
EM info@pathfoundationny.org
FU Life Extension Foundation; National Institute on Alcohol Abuse and
Alcoholism (NIAAA) [R01 AA07112, K05 AA 00219]; Medical Research Service
of the US Department of Veterans Affairs
FX The authors are grateful to the Life Extension Foundation for their
generous financial support to KB and the PATH Foundation NY. MOB is the
recipient of grants from National Institute on Alcohol Abuse and
Alcoholism (NIAAA) (R01 AA07112, K05 AA 00219) and from the Medical
Research Service of the US Department of Veterans Affairs. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 56
TC 5
Z9 6
U1 0
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 MAR 20
PY 2013
VL 8
IS 3
AR e55398
DI 10.1371/journal.pone.0055398
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SW
UT WOS:000317562600003
PM 23526928
ER
PT J
AU Buys, ES
Ko, YC
Alt, C
Hayton, SR
Jones, A
Tainsh, LT
Ren, RY
Giani, A
Clerte, M
Abernathy, E
Tainsh, RET
Oh, DJ
Malhotra, R
Arora, P
de Waard, N
Yu, BL
Turcotte, R
Nathan, D
Scherrer-Crosbie, M
Loomis, SJ
Kang, JH
Lin, CP
Gong, HY
Rhee, DJ
Brouckaert, P
Wiggs, JL
Gregory, MS
Pasquale, LR
Bloch, KD
Ksander, BR
AF Buys, Emmanuel S.
Ko, Yu-Chieh
Alt, Clemens
Hayton, Sarah R.
Jones, Alexander
Tainsh, Laurel T.
Ren, Ruiyi
Giani, Andrea
Clerte, Maeva
Abernathy, Emma
Tainsh, Robert E. T.
Oh, Dong-Jin
Malhotra, Rajeev
Arora, Pankaj
de Waard, Nadine
Yu, Binglan
Turcotte, Raphael
Nathan, Daniel
Scherrer-Crosbie, Marielle
Loomis, Stephanie J.
Kang, Jae H.
Lin, Charles P.
Gong, Haiyan
Rhee, Douglas J.
Brouckaert, Peter
Wiggs, Janey L.
Gregory, Meredith S.
Pasquale, Louis R.
Bloch, Kenneth D.
Ksander, Bruce R.
TI Soluble Guanylate Cyclase alpha(1)-Deficient Mice: A Novel Murine Model
for Primary Open Angle Glaucoma
SO PLOS ONE
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; I COLLAGEN MUTATION; OCULAR PERFUSION-PRESSURE;
HUMOR OUTFLOW FACILITY; OPTIC-NERVE HEAD; TRABECULAR MESHWORK;
BLOOD-FLOW; ENDOTHELIAL DYSFUNCTION; INTRAOCULAR-PRESSURE;
CLINICAL-TRIAL
AB Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the alpha(1) subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase alpha(1)-deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the alpha(1) and beta(1) subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG.
C1 [Buys, Emmanuel S.; Hayton, Sarah R.; Tainsh, Laurel T.; Tainsh, Robert E. T.; Yu, Binglan; Nathan, Daniel; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med,Med Sch, Boston, MA 02215 USA.
[Ko, Yu-Chieh; Jones, Alexander; Abernathy, Emma; de Waard, Nadine; Gregory, Meredith S.; Pasquale, Louis R.; Ksander, Bruce R.] Harvard Univ, Schepens Eye Res Inst, Dept Ophthalmol, Sch Med, Boston, MA USA.
[Ko, Yu-Chieh] Natl Yang Ming Univ, Sch Med, Dept Ophthalmol, Taipei 112, Taiwan.
[Alt, Clemens; Turcotte, Raphael; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.
[Alt, Clemens; Turcotte, Raphael; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
[Ren, Ruiyi; Gong, Haiyan] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Giani, Andrea; Oh, Dong-Jin; Loomis, Stephanie J.; Rhee, Douglas J.; Wiggs, Janey L.; Gregory, Meredith S.; Pasquale, Louis R.; Ksander, Bruce R.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Clerte, Maeva; Malhotra, Rajeev; Arora, Pankaj; Scherrer-Crosbie, Marielle; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA.
[Turcotte, Raphael] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Kang, Jae H.; Pasquale, Louis R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Brouckaert, Peter] Univ Ghent VIB, Dept Mol Biomed Res, Ghent, Belgium.
RP Buys, ES (reprint author), Harvard Univ, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med,Med Sch, Boston, MA 02215 USA.
EM Ebuys@partners.org
FU Harvard Catalyst-the Harvard Clinical and Translational Science Center
(NIH) [UL1 RR 025758]; Harvard University; Shaffer Fund Grant from the
Glaucoma Research Foundation; NEI [R21 EY020987, R01 EY022746-01, R01
EY015872, R01 EY015473]; American Heart Association Fellow-to-Faculty
Transition Award [11FTF7290032]; NCRR [1S10RR022586]; NIH [CA87969,
CA49449, EY09611, CA055075]; Massachusetts Lions Eye Research Fund;
FWO-Flanders fund; UGent-GOA fund; Harvard Glaucoma Center of
Excellence; Harvard Ophthalmology Scholar award; Physician-Scientist
award from Research to Prevent Blindness in NYC; Allergan Horizon grant;
NHGRI [5U01HG004728]
FX This work was conducted with support from Harvard Catalyst-the Harvard
Clinical and Translational Science Center (NIH Award #UL1 RR 025758, and
financial contributions from Harvard University and its affiliated
academic health care centers) (ESB, BRK); a Shaffer Fund Grant from the
Glaucoma Research Foundation (ESB); NEI R21 EY020987 (ESB, BRK); NEI R01
EY022746-01 (ESB); an American Heart Association Fellow-to-Faculty
Transition Award #11FTF7290032 (RM); NCRR 1S10RR022586 (MSC); NIH
CA87969, CA49449, EY09611, CA055075 (JHK); the Massachusetts Lions Eye
Research Fund (HG, RR); the FWO-Flanders and UGent-GOA funds (PB); NEI
R01 EY015872 (JLW); the Harvard Glaucoma Center of Excellence (LRP and
JLW); a Harvard Ophthalmology Scholar award (LRP); a Physician-Scientist
award from Research to Prevent Blindness in NYC (LRP); an Allergan
Horizon grant (LRP); NEI R01 EY015473 (LRP); and NHGRI 5U01HG004728
(LRP). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 82
TC 21
Z9 21
U1 0
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 MAR 20
PY 2013
VL 8
IS 3
AR e60156
DI 10.1371/journal.pone.0060156
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SW
UT WOS:000317562600124
PM 23527308
ER
PT J
AU Contreras-Shannon, V
Heart, DL
Paredes, RM
Navaira, E
Catano, G
Maffi, SK
Walss-Bass, C
AF Contreras-Shannon, Veronica
Heart, Dylan L.
Paredes, R. Madelaine
Navaira, Erica
Catano, Gabriel
Maffi, Shivani Kaushal
Walss-Bass, Consuelo
TI Clozapine-Induced Mitochondria Alterations and Inflammation in Brain and
Insulin-Responsive Cells
SO PLOS ONE
LA English
DT Article
ID INDUCED METABOLIC ALTERATIONS; OXIDATIVE STRESS; RAT-BRAIN;
ANTIPSYCHOTIC MEDICATIONS; POSSIBLE MECHANISM; ENERGY-METABOLISM;
OBESITY; DYSFUNCTION; RESISTANCE; SCHIZOPHRENIA
AB Background: Metabolic syndrome (MetS) is a constellation of factors including abdominal obesity, hyperglycemia, dyslipidemias, and hypertension that increase morbidity and mortality from diabetes and cardiovascular diseases and affects more than a third of the population in the US. Clozapine, an atypical antipsychotic used for the treatment of schizophrenia, has been found to cause drug-induced metabolic syndrome (DIMS) and may be a useful tool for studying cellular and molecular changes associated with MetS and DIMS. Mitochondria dysfunction, oxidative stress and inflammation are mechanisms proposed for the development of clozapine-related DIMS. In this study, the effects of clozapine on mitochondrial function and inflammation in insulin responsive and obesity-associated cultured cell lines were examined.
Methodology/Principal Findings: Cultured mouse myoblasts (C2C12), adipocytes (3T3-L1), hepatocytes (FL-83B), and monocytes (RAW 264.7) were treated with 0, 25, 50 and 75 mu M clozapine for 24 hours. The mitochondrial selective probe TMRM was used to assess membrane potential and morphology. ATP levels from cell lysates were determined by bioluminescence assay. Cytokine levels in cell supernatants were assessed using a multiplex array. Clozapine was found to alter mitochondria morphology, membrane potential, and volume, and reduce ATP levels in all cell lines. Clozapine also significantly induced the production of proinflammatory cytokines IL-6, GM-CSF and IL12-p70, and this response was particularly robust in the monocyte cell line.
Conclusions/ Significance: Clozapine damages mitochondria and promotes inflammation in insulin responsive cells and obesity-associated cell types. These phenomena are closely associated with changes observed in human and animal studies of MetS, obesity, insulin resistance, and diabetes. Therefore, the use of clozapine in DIMS may be an important and relevant tool for investigating cellular and molecular changes associated with the development of these diseases in the general population.
C1 [Contreras-Shannon, Veronica; Heart, Dylan L.] St Marys Univ, Dept Biol Sci, San Antonio, TX USA.
[Paredes, R. Madelaine; Navaira, Erica; Walss-Bass, Consuelo] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Catano, Gabriel] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Catano, Gabriel] Univ Texas Hlth Sci Ctr San Antonio, Vet Adm Ctr Personalized Med, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Maffi, Shivani Kaushal] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA.
[Maffi, Shivani Kaushal] Reg Acad Hlth Ctr Edinburg, Div Med Res, Edinburg, TX USA.
RP Walss-Bass, C (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
EM walss@uthscsa.edu
FU St. Mary's University Undergraduate Research Office, Biaggini
Undergraduate Research Scholarships, St. Mary's University; Department
of Psychiatry, University of Texas Health Science Center at San Antonio
FX Summer Undergraduate Research Fellowship from the St. Mary's University
Undergraduate Research Office, Biaggini Undergraduate Research
Scholarships, St. Mary's University. Friends for Psychiatric Research
Grant from the Department of Psychiatry, University of Texas Health
Science Center at San Antonio. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 54
TC 23
Z9 23
U1 1
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 MAR 20
PY 2013
VL 8
IS 3
AR e59012
DI 10.1371/journal.pone.0059012
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SW
UT WOS:000317562600051
PM 23527073
ER
PT J
AU Lee, JE
Gohda, T
Walker, WH
Skupien, J
Smiles, AM
Holak, RR
Jeong, J
McDonnell, KP
Krolewski, AS
Niewczas, MA
AF Lee, Jung Eun
Gohda, Tomohito
Walker, William H.
Skupien, Jan
Smiles, Adam M.
Holak, Rita R.
Jeong, Jackson
McDonnell, Kevin P.
Krolewski, Andrzej S.
Niewczas, Monika A.
TI Risk of ESRD and All Cause Mortality in Type 2 Diabetes According to
Circulating Levels of FGF-23 and TNFR1
SO PLOS ONE
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; GROWTH-FACTOR 23; STAGE RENAL-DISEASE; RECEPTORS
1; KLOTHO; INFLAMMATION; FACTOR-23; FGF23; FIBROBLAST-GROWTH-FACTOR-23;
MICROALBUMINURIA
AB Introduction: Recent studies demonstrated that circulating fibroblast growth factor (FGF)-23 was associated with risk of end stage renal disease (ESRD) and mortality. This study aims to examine whether the predictive effect of FGF-23 is independent from circulating levels of tumor necrosis factor receptor 1 (TNFR1), a strong predictor of ESRD in Type 2 diabetes (T2D).
Methods: We studied 380 patients with T2D who were followed for 8-12 years and were used previously to examine the effect of TNFR1. Baseline plasma FGF-23 was measured by immunoassay.
Results: During follow-up, 48 patients (13%) developed ESRD and 83 patients (22%) died without ESRD. In a univariate analysis, baseline circulating levels of FGF-23 and TNFR1 were significantly higher in subjects who subsequently developed ESRD or died without ESRD than in those who remained alive. In a Cox proportional hazard model, baseline concentration of FGF-23 was associated with increased risk of ESRD, however its effect was no longer significant after controlling for TNFR1 and other clinical characteristics (HR 1.3, p = 0.15). The strong effect of circulating level of TNFR1 on risk of ESRD was not changed by including circulating levels of FGF-23 (HR 8.7, p<0.001). In the Cox multivariate model, circulating levels of FGF-23 remained a significant independent predictor of all-cause mortality unrelated to ESRD (HR 1.5, p<0.001).
Conclusions: We demonstrated that the effect of circulating levels of FGF-23 on the risk of ESRD is accounted for by circulating levels of TNFR1. We confirmed that circulating levels of FGF-23 have an independent effect on all-cause mortality in T2D.
C1 [Lee, Jung Eun; Gohda, Tomohito; Walker, William H.; Skupien, Jan; Smiles, Adam M.; Holak, Rita R.; Jeong, Jackson; McDonnell, Kevin P.; Krolewski, Andrzej S.; Niewczas, Monika A.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Lee, Jung Eun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Nephrol, Seoul, South Korea.
[Lee, Jung Eun; Gohda, Tomohito; Skupien, Jan; Krolewski, Andrzej S.; Niewczas, Monika A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Gohda, Tomohito] Juntendo Univ, Sch Med, Dept Internal Med, Div Nephrol, Tokyo 113, Japan.
[Skupien, Jan] Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland.
RP Niewczas, MA (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM Monika.Niewczas@joslin.harvard.edu
RI lee, je/O-6247-2014
FU National Institutes of Health [DK041526, DK067638]; DERC Joslin Diabetes
Center Pilot and Feasibility grant; JDRF [3-2009-397]
FX This study was supported by grants from the National Institutes of
Health DK041526 and DK067638 (ASK), DERC Joslin Diabetes Center Pilot
and Feasibility grant (MAN) and a JDRF fellowship grant 3-2009-397 (JS).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 38
TC 7
Z9 7
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 20
PY 2013
VL 8
IS 3
AR e58007
DI 10.1371/journal.pone.0058007
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SW
UT WOS:000317562600012
PM 23526964
ER
PT J
AU Vrooman, LM
Stevenson, KE
Supko, JG
O'Brien, J
Dahlberg, SE
Asselin, BL
Athale, UH
Clavell, LA
Kelly, KM
Kutok, JL
Laverdiere, C
Lipshultz, SE
Michon, B
Schorin, M
Relling, MV
Cohen, HJ
Neuberg, DS
Sallan, SE
Silverman, LB
AF Vrooman, Lynda M.
Stevenson, Kristen E.
Supko, Jeffrey G.
O'Brien, Jane
Dahlberg, Suzanne E.
Asselin, Barbara L.
Athale, Uma H.
Clavell, Luis A.
Kelly, Kara M.
Kutok, Jeffery L.
Laverdiere, Caroline
Lipshultz, Steven E.
Michon, Bruno
Schorin, Marshall
Relling, Mary V.
Cohen, Harvey J.
Neuberg, Donna S.
Sallan, Stephen E.
Silverman, Lewis B.
TI Postinduction Dexamethasone and Individualized Dosing of Escherichia
Coli L-Asparaginase Each Improve Outcome of Children and Adolescents
With Newly Diagnosed Acute Lymphoblastic Leukemia: Results From a
Randomized Study-Dana-Farber Cancer Institute ALL Consortium Protocol
00-01
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID STANDARD-RISK; CEREBROSPINAL-FLUID; CHILDHOOD; INDUCTION; OSTEONECROSIS;
CHEMOTHERAPY; PREDNISONE; THERAPY; TRIAL; PHARMACOKINETICS
AB Purpose
We assessed the toxicity and efficacy of dexamethasone and a novel dosing method of Escherichia coli L-asparaginase (EC-Asnase) in children and adolescents with newly diagnosed acute lymphoblastic leukemia (ALL).
Patients and Methods
Patients achieving complete remission (CR) on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 were eligible for random assignment to 1) dexamethasone or prednisone, administered as 5-day pulses, every 3 weeks, and 2) weekly EC-Asnase, administered as a 25,000 IU/m(2) fixed dose (FD) or individualized dose (ID) starting at 12,500-IU/m(2), adjusted every 3 weeks based on nadir serum asparaginase activity (NSAA) determinations.
Results
Between 2000 and 2004, 492 evaluable patients (ages 1 to 18 years) enrolled; 473 patients (96%) achieved CR. Four hundred eight patients (86%) participated in the corticosteroid randomization and 384 patients (81%) in the EC-Asnase randomization. With 4.9 years of median follow-up, dexamethasone was associated with superior 5-year event-free survival (EFS; 90% v 81% for prednisone; P = .01) but higher rates of infection (P = .03) and, in older children, higher cumulative incidence of osteonecrosis (P = .02) and fracture (P = .06). ID EC-Asnase had superior 5-year EFS (90% v 82% for FD; P = .04), but did not reduce the frequency of asparaginase-related toxicity. Multivariable analysis identified both dexamethasone and ID EC-Asnase as independent predictors of favorable EFS.
Conclusion
There was no overall difference in skeletal toxicity by corticosteroid type; dexamethasone was associated with more infections and, in older children, increased incidence of osteonecrosis and fracture. There was no difference in asparaginase-related toxicity by EC-Asnase dosing method. Dexamethasone and ID EC-Asnase were each associated with superior EFS. Monitoring NSAA during treatment with EC-Asnase may be an effective strategy to improve outcome in pediatric ALL. J Clin Oncol 31:1202-1210. (C) 2013 by American Society of Clinical Oncology
C1 [Vrooman, Lynda M.; Stevenson, Kristen E.; O'Brien, Jane; Dahlberg, Suzanne E.; Neuberg, Donna S.; Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Vrooman, Lynda M.; Sallan, Stephen E.; Silverman, Lewis B.] Boston Childrens Hosp, Boston, MA USA.
[Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kutok, Jeffery L.] Infin Pharmaceut, Cambridge, MA USA.
[Asselin, Barbara L.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA.
[Kelly, Kara M.] Columbia Univ, Morgan Stanley Childrens Hosp New York Presbyteri, Med Ctr, New York, NY USA.
[Clavell, Luis A.] San Jorge Childrens Hosp, San Juan, PR USA.
[Lipshultz, Steven E.] Univ Miami, Leonard M Miller Sch Med, Miami, FL USA.
[Schorin, Marshall] Inova Fairfax Hosp Children, Falls Church, VA USA.
[Relling, Mary V.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Cohen, Harvey J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Athale, Uma H.] McMaster Univ, Hamilton, ON, Canada.
[Laverdiere, Caroline] Univ Montreal, Hop St Justine, Montreal, PQ H3T 1C5, Canada.
[Michon, Bruno] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada.
RP Vrooman, LM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM lynda_vrooman@dfci.harvard.edu
FU EUSA Pharma; Sigma-Tau Pharmaceuticals; Enzon Pharmaceuticals; National
Cancer Institute [5 P01CA068484, P30 21765]; American Lebanese Syrian
Associated Charities; Linde Family Foundation
FX Although all authors completed the disclosure declaration, the following
author(s) and/or an author's immediate family member(s) indicated a
financial or other interest that is relevant to the subject matter under
consideration in this article. Certain relationships marked with a "U"
are those for which no compensation was received; those relationships
marked with a "C" were compensated. For a detailed description of the
disclosure categories, or for more information about ASCO's conflict of
interest policy, please refer to the Author Disclosure Declaration and
the Disclosures of Potential Conflicts of Interest section in
Information for Contributors. Employment or Leadership Position: None
Consultant or Advisory Role: Lewis B. Silverman, Enzon Pharmaceuticals
(C), EUSA Pharma (C) Stock Ownership: None Honoraria: None Research
Funding: Jeffrey G. Supko, EUSA Pharma; Mary V. Relling, Sigma-Tau
Pharmaceuticals, Enzon Pharmaceuticals; Stephen E. Sallan, Enzon
Pharmaceuticals, EUSA Pharma Expert Testimony: None Other Remuneration:
None; Supported in part by Grants No. 5 P01CA068484 and P30 21765 from
the National Cancer Institute, by the American Lebanese Syrian
Associated Charities, and by the Linde Family Foundation.
NR 33
TC 85
Z9 93
U1 2
U2 11
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 20
PY 2013
VL 31
IS 9
BP 1202
EP 1210
DI 10.1200/JCO.2012.43.2070
PG 9
WC Oncology
SC Oncology
GA 107AS
UT WOS:000316187600021
PM 23358966
ER
PT J
AU Metzger, ML
Meacham, LR
Patterson, B
Casillas, JS
Constine, LS
Hijiya, N
Kenney, LB
Leonard, M
Lockart, BA
Likes, W
Green, DM
AF Metzger, Monika L.
Meacham, Lillian R.
Patterson, Briana
Casillas, Jacqueline S.
Constine, Louis S.
Hijiya, Nobuko
Kenney, Lisa B.
Leonard, Marcia
Lockart, Barbara A.
Likes, Wendy
Green, Daniel M.
TI Female Reproductive Health After Childhood, Adolescent, and Young Adult
Cancers: Guidelines for the Assessment and Management of Female
Reproductive Complications
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ANTI-MULLERIAN HORMONE; CENTRAL PRECOCIOUS PUBERTY; TERM-FOLLOW-UP;
ACUTE LYMPHOBLASTIC-LEUKEMIA; CRYOPRESERVED OVARIAN TISSUE;
VERSUS-HOST-DISEASE; FERTILITY PRESERVATION; HODGKINS-DISEASE;
BREAST-CANCER; REPLACEMENT THERAPY
AB Purpose
As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life.
Methods
The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus.
Results
This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed.
Conclusion
Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life. J Clin Oncol 31:1239-1247. (C) 2013 by American Society of Clinical Oncology
C1 [Metzger, Monika L.; Green, Daniel M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Metzger, Monika L.; Likes, Wendy] Univ Tennessee, Memphis, TN USA.
[Meacham, Lillian R.; Patterson, Briana] Emory Univ, Atlanta, GA 30322 USA.
[Casillas, Jacqueline S.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Constine, Louis S.] Univ Rochester, Rochester, NY USA.
[Hijiya, Nobuko] Northwestern Univ, Evanston, IL 60208 USA.
[Lockart, Barbara A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Kenney, Lisa B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kenney, Lisa B.] Childrens Hosp, Boston, MA 02115 USA.
[Leonard, Marcia] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Metzger, ML (reprint author), 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM monika.metzger@stjude.org
FU NCI NIH HHS [U10 CA095861, U10 CA098543]
NR 147
TC 43
Z9 44
U1 1
U2 20
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 MAR 20
PY 2013
VL 31
IS 9
BP 1239
EP 1247
DI 10.1200/JCO.2012.43.5511
PG 9
WC Oncology
SC Oncology
GA 107AS
UT WOS:000316187600025
PM 23382474
ER
PT J
AU Cosker, KE
Pazyra-Murphy, MF
Fenstermacher, SJ
Segal, RA
AF Cosker, Katharina E.
Pazyra-Murphy, Maria F.
Fenstermacher, Sara J.
Segal, Rosalind A.
TI Target-Derived Neurotrophins Coordinate Transcription and Transport of
Bclw to Prevent Axonal Degeneration
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ACTIN MESSENGER-RNA; ROOT GANGLION NEURONS; NERVE GROWTH-FACTOR;
SYMPATHETIC NEURONS; RETROGRADE TRANSPORT; LOCAL TRANSLATION; SURVIVAL
RESPONSE; PROTEIN-SYNTHESIS; MAMMALIAN-CELLS; DEFICIENT MICE
AB Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transpire in the axon. Here we report that target-derived neurotrophins coordinate transcription of the antiapoptotic gene bclw with transport of bclw mRNA to the axon, and thereby prevent axonal degeneration in rat and mouse sensory neurons. We show that neurotrophin stimulation of nerve terminals elicits new bclw transcripts that are immediately transported to the axons and translated into protein. Bclw interacts with Bax and suppresses the caspase6 apoptotic cascade that fosters axonal degeneration. The scope of bclw regulation at the levels of transcription, transport, and translation provides a mechanism whereby sustained neurotrophin stimulation can be integrated over time, so that axonal survival is restricted to neurons connected within a stable circuit.
C1 [Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.; Segal, Rosalind A.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02215 USA.
EM Rosalind_segal@dfci.harvard.edu
FU National Institutes of Health [R01 NS050674, F31NS077620]; Massachusetts
General Hospital Neurology Clinical Trials Unit; Harvard NeuroDiscovery
Center
FX This work was supported by National Institutes of Health Grant R01
NS050674 to R. A. S. and Grant F31NS077620 to S.J.F., K. E. C. is a
David Mahoney Fellow at Harvard Medical School and a recipient of a
Neurodegenerative Disease Pilot Study grant from Massachusetts General
Hospital Neurology Clinical Trials Unit and Harvard NeuroDiscovery
Center. S.J.F. is a Victoria Quan Fellow at Harvard Medical School.
Confocal microscopy imaging was performed at the Harvard NeuroDiscovery
Center Optical Imaging Program. We thank Stephanie Courchesne for help
in generating in vivo samples, Jose Alfaro and Emily Chadwick for
assistance with bclw-/- mice, Eugene Vaios for assistance
with designing probes for ISH, and the members of the R. A. A.
laboratory and the Qiufu Ma laboratory for helpful advice.
NR 56
TC 16
Z9 16
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 20
PY 2013
VL 33
IS 12
BP 5195
EP +
DI 10.1523/JNEUROSCI.3862-12.2013
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 111XB
UT WOS:000316553800013
PM 23516285
ER
PT J
AU Scimemi, A
Meabon, JS
Woltjer, RL
Sullivan, JM
Diamond, JS
Cook, DG
AF Scimemi, Annalisa
Meabon, James S.
Woltjer, Randall L.
Sullivan, Jane M.
Diamond, Jeffrey S.
Cook, David G.
TI Amyloid-beta(1-42) Slows Clearance of Synaptically Released Glutamate by
Mislocalizing Astrocytic GLT-1
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ALZHEIMERS-DISEASE; TRANSPORTER GLT-1; BRAIN; BETA; NEURODEGENERATION;
EXPRESSION; MECHANISM; NEURONS; PATHWAY; PROTECT
AB GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-beta peptide A beta(1-42) markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimer's disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease.
C1 [Scimemi, Annalisa; Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Meabon, James S.] Univ Washington, Dept Psychiat, Seattle, WA 98108 USA.
[Cook, David G.] Univ Washington, Dept Med, Seattle, WA 98108 USA.
[Cook, David G.] Univ Washington, Dept Pharmacol, Seattle, WA 98108 USA.
[Sullivan, Jane M.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
[Meabon, James S.; Cook, David G.] VA Puget Sound Hlth Care Syst, Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Woltjer, Randall L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA.
RP Cook, DG (reprint author), VA Med Ctr, GRECC, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM dgcook@u.washington.edu
RI Scimemi, Annalisa/O-5396-2014; Diamond, Jeffrey/C-1835-2015
OI Scimemi, Annalisa/0000-0003-4975-093X; Diamond,
Jeffrey/0000-0002-1770-2629
FU Veteran's Affairs Office of Research and Development Medical Research
Service; NIH [T32 AG000258, RO1 NS055804]; NINDS [NS002986]
FX This work was supported by the Veteran's Affairs Office of Research and
Development Medical Research Service (D. G. C.), NIH (Grants T32
AG000258, J.S.M.; and RO1 NS055804, J.M.S.), and NINDS Intramural
Research Program (Grant NS002986, J.S.D.). We thank Mike Ahlquist, Ping
Zhu, and Ning Li for excellent technical assistance.
NR 28
TC 29
Z9 30
U1 1
U2 10
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 MAR 20
PY 2013
VL 33
IS 12
BP 5312
EP 5318
DI 10.1523/JNEUROSCI.5274-12.2013
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 111XB
UT WOS:000316553800023
PM 23516295
ER
PT J
AU Arsenault, JT
Nelissen, K
Jarraya, B
Vanduffel, W
AF Arsenault, John T.
Nelissen, Koen
Jarraya, Bechir
Vanduffel, Wim
TI Dopaminergic Reward Signals Selectively Decrease fMRI Activity in
Primate Visual Cortex
SO NEURON
LA English
DT Article
ID NEURONAL-ACTIVITY; CONTRAST AGENT; HUMAN BRAIN; ATTENTION; RESPONSES;
DORSAL; REPRESENTATIONS; REINFORCERS; PREDICTION; MOTIVATION
AB Stimulus-reward coupling without attention can induce highly specific perceptual learning effects, suggesting that reward triggers selective plasticity within visual cortex. Additionally, dopamine-releasing events temporally surrounding stimulus-reward associations selectively enhance memory. These forms of plasticity may be evoked by selective modulation of stimulus representations during dopamine-inducing events. However, it remains to be shown whether dopaminergic signals can selectively modulate visual cortical activity. We measured fMRI activity in monkey visual cortex during reward-only trials apart from intermixed cue-reward trials. Reward without visual stimulation selectively decreased fMRI activity within the cue representations that had been paired with reward during other trials. Behavioral tests indicated that these same uncued reward trials strengthened cue-reward associations. Furthermore, such spatially-specific activity modulations depended on prediction error, as shown by manipulations of reward magnitude, cue-reward probability, cue-reward familiarity, and dopamine signaling. This cue-selective negative reward signal offers a mechanism for selectively gating sensory cortical plasticity.
C1 [Arsenault, John T.; Nelissen, Koen; Jarraya, Bechir; Vanduffel, Wim] KU Leuven Med Sch, Lab Neuro & Psychophysiol, B-3000 Louvain, Belgium.
[Arsenault, John T.; Jarraya, Bechir; Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Charlestown, MA 02129 USA.
RP Vanduffel, W (reprint author), KU Leuven Med Sch, Lab Neuro & Psychophysiol, Campus Gasthuisberg, B-3000 Louvain, Belgium.
EM wim@nmr.mgh.harvard.edu
OI Jarraya, Bechir/0000-0003-0878-763X
FU Inter-University Attraction Pole [PFV10/008]; Geconcerteerde Onderzoeks
Actie 10/19; Impulsfinanciering Zware Apparatuur; Katholieke
Universiteit Leuven; Fonds Wetenschappelijk Onderzoek-Vlaanderen
[G062208.10, G083111.10, G.0719.12, G0888.13]; National Center for
Research Resources [P41RR14075]
FX We thank C. Fransen, C. Van Eupen, and A. Coeman for animal training and
care; D. Mantini, O. Joly, H. Kolster, W. Depuydt, G. Meulemans, P.
Kayenbergh, M. De Paep, M. Docx, and I. Puttemans for technical
assistance; and P. Roelfsema, T Knapen, T, Donner, and S. Raiguel for
their comments on the manuscript. This work received support from
Inter-University Attraction Pole 7/11, Programme Financing PFV10/008,
Geconcerteerde Onderzoeks Actie 10/19, Impulsfinanciering Zware
Apparatuur and Hercules funding of the Katholieke Universiteit Leuven,
Fonds Wetenschappelijk Onderzoek-Vlaanderen G062208.10, G083111.10 and
G.0719.12, and G0888.13. K.N. is postdoctoral fellow of the Fonds
Wetenschappelijk Onderzoek-Vlaanderen. The Martinos Center for
Biomedical Imaging is supported by National Center for Research
Resources grant P41RR14075.
NR 59
TC 37
Z9 37
U1 4
U2 39
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD MAR 20
PY 2013
VL 77
IS 6
BP 1174
EP 1186
DI 10.1016/j.neuron.2013.01.008
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 113CX
UT WOS:000316645000017
PM 23522051
ER
PT J
AU Miller, CJ
Abraham, KM
Bajor, LA
Lai, ZS
Kim, HM
Nord, KM
Goodrich, DE
Bauer, MS
Kilbourne, AM
AF Miller, Christopher J.
Abraham, Kristen M.
Bajor, Laura A.
Lai, Zongshan
Kim, Hyungjin Myra
Nord, Kristina M.
Goodrich, David E.
Bauer, Mark S.
Kilbourne, Amy M.
TI Quality of life among patients with bipolar disorder in primary care
versus community mental health settings
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Bipolar disorder; Quality of life; Primary care; Community mental health
ID ALCOHOL-USE DISORDERS; GENERAL-POPULATION; AUDIT-C;
PSYCHIATRIC-DISORDERS; SUBSTANCE-ABUSE; RISK DRINKING; I DISORDER;
SCALE; STATES; RELIABILITY
AB Introduction: Bipolar disorder is associated with functional impairment across a number of domains, including health-related quality of life (HRQOL). Many patients are treated exclusively in primary care (PC) settings, yet little is known how HRQOL outcomes compare between PC and community mental health (CMH) settings. This study aimed to explore the correlates of HRQOL across treatment settings using baseline data from a multisite, randomized controlled trial for adults with bipolar disorder.
Methods: HRQOL was measured using the SF-12 physical (PCS) and mental (MCS) composite scale scores. Independent sample t-tests were calculated to compare differences in HRQOL between settings. Multivariate regression models then examined the effect of treatment setting on HRQOL, adjusting for covariate demographic factors, mood symptoms (Internal State Scale), hazardous drinking (AUDIT-C), and substance abuse.
Results: A total of 384 enrolled participants completed baseline surveys. MCS and PCS scores reflected similar impairment in HRQOL across PC and CMH settings (p=0.98 and p=0.49, respectively). Depressive symptoms were associated with lower MCS scores (B=0.68, p < 0.001) while arthritis/chronic pain was strongly related to lower PCS scores (B=5.23, p < 0.001).
Limitations: This study lacked a formal diagnostic interview, relied on cross-sectional self-report, and sampled from a small number of sites in two states.
Discussion: Participants reported similar impairments in both mental and physical HRQOL in PC and CMH treatment settings, emphasizing the need for integrated care for patients with bipolar disorder regardless of where they present for treatment. Published by Elsevier B.V.
C1 [Miller, Christopher J.; Bajor, Laura A.; Lai, Zongshan; Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA.
[Miller, Christopher J.; Bajor, Laura A.; Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Abraham, Kristen M.; Lai, Zongshan; Kim, Hyungjin Myra; Nord, Kristina M.; Goodrich, David E.; Kilbourne, Amy M.] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA.
[Abraham, Kristen M.; Nord, Kristina M.; Goodrich, David E.; Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA.
[Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA.
RP Miller, CJ (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA.
EM Christopher.Miller8@va.gov
OI Goodrich, David/0000-0003-3232-2189
FU National Institute of Mental Health [R01 MH79994]
FX This work was supported by the National Institute of Mental Health (R01
MH79994). The views expressed in this article are those of the authors
and do not necessarily represent the views of the VA.
NR 46
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Z9 11
U1 2
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD MAR 20
PY 2013
VL 146
IS 1
BP 100
EP 105
DI 10.1016/j.jad.2012.08.045
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 098WE
UT WOS:000315579000013
PM 22981021
ER
PT J
AU Zhang, RY
Zhao, Y
Chu, MJ
Mehta, A
Wei, YY
Liu, Y
Xun, PC
Bai, JL
Yu, H
Su, L
Zhang, HX
Hu, ZB
Shen, HB
Chen, F
Christiani, DC
AF Zhang, Ruyang
Zhao, Yang
Chu, Minjie
Mehta, Amar
Wei, Yongyue
Liu, Yao
Xun, Pengcheng
Bai, Jianling
Yu, Hao
Su, Li
Zhang, Hongxi
Hu, Zhibin
Shen, Hongbing
Chen, Feng
Christiani, David C.
TI A Large Scale Gene-Centric Association Study of Lung Function in
Newly-Hired Female Cotton Textile Workers with Endotoxin Exposure
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; AIRWAY EPITHELIUM;
FUNCTION DECLINE; CANCER; DUST; SUSCEPTIBILITY; POLYMORPHISMS;
POPULATION; DISEASE
AB Background: Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood.
Objective: We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.
Methods: DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.
Results: Two SNPs were found to be significant (P<6.29x10(-5)), including rs1910047 (P = 3.07x10(-5), FDR = 0.0778) and rs9469089 (P = 6.19x10(-5), FDR = 0.0967), as well as other eight suggestive (P<5x10(-4)) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (P-trend = 3.01x10(-18)). However, the association was different among age subgroups (P = 7.11x10(-6)) and endotoxin subgroups (P = 1.08x10(-2)). Functional network analysis illustrates potential biological connections of all interacted genes.
Conclusions: Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers.
C1 [Zhang, Ruyang; Zhao, Yang; Chu, Minjie; Wei, Yongyue; Liu, Yao; Bai, Jianling; Yu, Hao; Hu, Zhibin; Shen, Hongbing; Chen, Feng] Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China.
[Zhang, Ruyang; Zhao, Yang; Chu, Minjie; Wei, Yongyue; Liu, Yao; Bai, Jianling; Yu, Hao; Hu, Zhibin; Shen, Hongbing; Chen, Feng] Nanjing Med Univ, Minist Educ MOE, Key Lab Modern Toxicol, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China.
[Zhang, Ruyang; Chu, Minjie; Liu, Yao; Hu, Zhibin; Shen, Hongbing] Nanjing Med Univ, Clin Epidemiol Sect, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Ctr Canc, Nanjing, Jiangsu, Peoples R China.
[Zhao, Yang; Mehta, Amar; Wei, Yongyue; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Mehta, Amar] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Mehta, Amar] Univ Basel, Basel, Switzerland.
[Xun, Pengcheng] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN USA.
[Zhang, Hongxi] Shanghai Med Univ 2, Putuo Dist Peoples Hosp, Shanghai, Peoples R China.
[Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA.
RP Chen, F (reprint author), Nanjing Med Univ, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China.
EM fengchen@njmu.edu.cn; dchris@hsph.harvard.edu
RI Xun, Pengcheng/D-3411-2013
FU USA: The National Institute for Occupational Safety and Health
[RO104241]; USA: National Institute of Environmental Health Sciences
[ES00002]; China: National Natural Science Foundation of China
[81072389, 30901232]; China: Natural Science Foundation of the Jiangsu
Higher Education Institutions of China [10KJA33034]; China: Research
Fund for the Doctoral Program of Higher Education of China
[20113234110002]; China: Research and Innovation Project for College
Graduates of Jiangsu Province [CXZZ11_0733]; China: Priority Academic
Program Development of Jiangsu Higher Education Institutions (PAPD)
FX This study was supported by grants from USA: The National Institute for
Occupational Safety and Health (RO104241), National Institute of
Environmental Health Sciences (ES00002) and China: National Natural
Science Foundation of China (81072389, 30901232), Natural Science
Foundation of the Jiangsu Higher Education Institutions of China
(10KJA33034), the Research Fund for the Doctoral Program of Higher
Education of China (20113234110002), the Research and Innovation Project
for College Graduates of Jiangsu Province (CXZZ11_0733), and the grant
from the Priority Academic Program Development of Jiangsu Higher
Education Institutions (PAPD). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 56
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U1 1
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 MAR 19
PY 2013
VL 8
IS 3
AR e59035
DI 10.1371/journal.pone.0059035
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SR
UT WOS:000317562100068
PM 23527081
ER
PT J
AU Hu, D
Weiner, HL
Ritz, J
AF Hu, Dan
Weiner, Howard L.
Ritz, Jerome
TI Identification of Cytolytic CD161(-)CD56(+) Regulatory CD8 T Cells in
Human Peripheral Blood
SO PLOS ONE
LA English
DT Article
ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NATURAL-KILLER-CELLS; DENDRITIC
CELLS; SELF-TOLERANCE; EXPRESSION; SUBSET; CD27; STIMULATION;
LYMPHOCYTES; BIOLOGY
AB We previously developed methods for establishing CD8 regulatory T cell (Treg) clones from normal human peripheral blood and demonstrated that these clones were capable of killing T cell receptor (TCR)-activated autologous CD4 T cells. Based on phenotypic and functional characterization of the CD8 Treg clones, we have identified a corresponding population of endogenous CD8 Treg in normal human peripheral blood. These cells appear morphologically as large lymphocytes with abundant cytoplasm and have the following unique phenotype: CD3(+)CD8(+)CD161(-)CD56(+). The majority of CD8 Treg express CD45RA and CD62L with low or negative expression of CD45RO, CD25, CD27, CD28 and CCR7. The expression of CD94 and NKG2a on CD8 Treg was elevated compared to conventional CD8 T cells. Following in vitro activation, this T cell subset is capable of killing TCR-activated CD4 T cells. These studies identify an endogenous CD8 Treg population in humans and it will now be possible to characterize these cells in a variety of clinical conditions.
C1 [Hu, Dan; Weiner, Howard L.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Hu, Dan; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Hu, Dan; Weiner, Howard L.; Ritz, Jerome] Harvard Univ, Sch Med, Boston, MA USA.
RP Ritz, J (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Canc Vaccine Ctr, Boston, MA 02115 USA.
EM Jerome_Ritz@dfci.harvard.edu
RI Hu, Dan/D-9642-2015
FU National Institutes of Health [AI29530, CA142106]; National Multiple
Sclerosis Society
FX The research was supported by National Institutes of Health (AI29530 and
CA142106 to J.R.) and the National Multiple Sclerosis Society (to H. L.
W.). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 42
TC 5
Z9 5
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 19
PY 2013
VL 8
IS 3
AR e59545
DI 10.1371/journal.pone.0059545
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SR
UT WOS:000317562100146
PM 23527216
ER
PT J
AU Wang, Z
Ocampo, MA
Pang, RD
Bota, M
Bradesi, S
Mayer, EA
Holschneider, DP
AF Wang, Zhuo
Ocampo, Marco A.
Pang, Raina D.
Bota, Mihail
Bradesi, Sylvie
Mayer, Emeran A.
Holschneider, Daniel P.
TI Alterations in Prefrontal-Limbic Functional Activation and Connectivity
in Chronic Stress-Induced Visceral Hyperalgesia
SO PLOS ONE
LA English
DT Article
ID BRAIN-GUT AXIS; IRRITABLE-BOWEL-SYNDROME; CHRONIC RESTRAINT STRESS;
CENTRAL-NERVOUS-SYSTEM; DENDRITIC REORGANIZATION; VOLUNTARY SUPPRESSION;
PERIAQUEDUCTAL GRAY; CEREBRAL ACTIVATION; PYRAMIDAL NEURONS; FOS
EXPRESSION
AB Repeated water avoidance stress (WAS) induces sustained visceral hyperalgesia (VH) in rats measured as enhanced visceromotor response to colorectal distension (CRD). This model incorporates two characteristic features of human irritable bowel syndrome (IBS), VH and a prominent role of stress in the onset and exacerbation of IBS symptoms. Little is known regarding central mechanisms underlying the stress-induced VH. Here, we applied an autoradiographic perfusion method to map regional and network-level neural correlates of VH. Adult male rats were exposed to WAS or sham treatment for 1 hour/day for 10 days. The visceromotor response was measured before and after the treatment. Cerebral blood flow (CBF) mapping was performed by intravenous injection of radiotracer ([C-14]-iodoantipyrine) while the rat was receiving a 60-mmHg CRD or no distension. Regional CBF-related tissue radioactivity was quantified in autoradiographic images of brain slices and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. Compared to sham rats, stressed rats showed VH in association with greater CRD-evoked activation in the insular cortex, amygdala, and hypothalamus, but reduced activation in the prelimbic area (PrL) of prefrontal cortex. We constrained results of seed correlation analysis by known structural connectivity of the PrL to generate structurally linked functional connectivity (SLFC) of the PrL. Dramatic differences in the SLFC of PrL were noted between stressed and sham rats under distension. In particular, sham rats showed negative correlation between the PrL and amygdala, which was absent in stressed rats. The altered pattern of functional brain activation is in general agreement with that observed in IBS patients in human brain imaging studies, providing further support for the face and construct validity of the WAS model for IBS. The absence of prefrontal cortex-amygdala anticorrelation in stressed rats is consistent with the notion that impaired corticolimbic modulation acts as a central mechanism underlying stress-induced VH.
C1 [Wang, Zhuo; Ocampo, Marco A.; Holschneider, Daniel P.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 93385 USA.
[Pang, Raina D.; Holschneider, Daniel P.] Univ So Calif, Program Neurosci, Los Angeles, CA USA.
[Bota, Mihail] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Holschneider, Daniel P.] Univ So Calif, Dept Neurol, Los Angeles, CA USA.
[Bradesi, Sylvie; Mayer, Emeran A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Bradesi, Sylvie; Mayer, Emeran A.; Holschneider, Daniel P.] Univ Calif Los Angeles, Dept Med, Ctr Neurobiol Stress, Los Angeles, CA 90024 USA.
[Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA.
[Mayer, Emeran A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Mayer, Emeran A.] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA USA.
RP Holschneider, DP (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 93385 USA.
EM holschne@usc.edu
FU United States National Institutes of Health [P50DK064539, R24AT002681]
FX The research was supported by United States National Institutes of
Health grants P50DK064539 (Mayer) and R24AT002681 (Mayer). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 81
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Z9 13
U1 2
U2 9
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 MAR 19
PY 2013
VL 8
IS 3
AR e59138
DI 10.1371/journal.pone.0059138
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SR
UT WOS:000317562100082
PM 23527114
ER
PT J
AU Xiao, WC
Peng, YY
Liu, Y
Li, Z
Li, SL
Zheng, XF
AF Xiao, Weichun
Peng, Yanyan
Liu, Yong
Li, Zhi
Li, Senlin
Zheng, Xiaofeng
TI HSCARG Inhibits NADPH Oxidase Activity through Regulation of the
Expression of p47phox
SO PLOS ONE
LA English
DT Article
ID NF-KAPPA-B; SENSOR PROTEIN; TUMOR-CELLS; ACTIVATION;
DIPHENYLENEIODONIUM; MODULATION; INDUCTION; APOPTOSIS; INCREASE; ASSAY
AB Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase catalyzes the transfer of electrons from NADPH to O-2, which is the main source of reactive oxygen species (ROS) in nonphagocytic cells. Excess ROS are toxic; therefore, keeping ROS in homeostasis in cells can protect cells from oxidative damage. It is meaningful to further understand the molecular mechanism by which ROS homeostasis is mediated. Human protein HSCARG is a newly identified oxidative sensor and a negative regulator of NF-kappa B. Here, we find that HSCARG represses the cellular ROS generation through inhibiting mRNA and protein expression of p47phox, a subunit of NADPH oxidase. In contrast, shRNA-mediated HSCARG knockdown increases endogenous p47phox expression level. And HSCARG has no obvious effect on ROS production in p47phox-depleted cells. Furthermore, HSCARG regulates p47phox through inhibition of NF-kappa B activity. Our findings identify HSCARG as a novel regulator in regulation of the activity of NADPH oxidase and ROS homeostasis.
C1 [Xiao, Weichun; Peng, Yanyan; Liu, Yong; Li, Zhi; Zheng, Xiaofeng] State Key Lab Prot & Plant Gene Res, Beijing, Peoples R China.
[Xiao, Weichun; Peng, Yanyan; Liu, Yong; Li, Zhi; Zheng, Xiaofeng] Peking Univ, Sch Life Sci, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China.
[Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Li, Senlin] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA.
RP Zheng, XF (reprint author), State Key Lab Prot & Plant Gene Res, Beijing, Peoples R China.
EM xiaofengz@pku.edu.cn
FU National Science Foundation of China [30930020, 31170709]; National High
Technology and Development Program of China 973 programs [2010CB911800];
International Centre for Genetic Engineering and Biotechnology
[CRP/CHN09-01]
FX This work was supported by grants from the National Science Foundation
of China (30930020 and 31170709) the National High Technology and
Development Program of China 973 programs (No. 2010CB911800), and the
International Centre for Genetic Engineering and Biotechnology (Project
No. CRP/CHN09-01). The funders had no roles in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 33
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Z9 3
U1 0
U2 13
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 MAR 19
PY 2013
VL 8
IS 3
AR e59301
DI 10.1371/journal.pone.0059301
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125SR
UT WOS:000317562100101
PM 23527155
ER
PT J
AU Li, Y
Meloni, EG
Carlezon, WA
Milad, MR
Pitman, RK
Nader, K
Bolshakov, VY
AF Li, Yan
Meloni, Edward G.
Carlezon, William A., Jr.
Milad, Mohammed R.
Pitman, Roger K.
Nader, Karim
Bolshakov, Vadim Y.
TI Learning and reconsolidation implicate different synaptic mechanisms
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID LONG-TERM-MEMORY; FEAR MEMORY; PROTEIN-SYNTHESIS; MAMMALIAN TARGET;
LATERAL AMYGDALA; CONTEXTUAL FEAR; RNA-SYNTHESIS; CONSOLIDATION;
PLASTICITY; HIPPOCAMPUS
AB Synaptic mechanisms underlying memory reconsolidation after retrieval are largely unknown. Here we report that synapses in projections to the lateral nucleus of the amygdala implicated in auditory fear conditioning, which are potentiated by learning, enter a labile state after memory reactivation, and must be restabilized through a postsynaptic mechanism implicating the mammalian target of rapamycin kinase-dependent signaling. Fear-conditioning-induced synaptic enhancements were primarily presynaptic in origin. Reconsolidation blockade with rapamycin, inhibiting mammalian target of rapamycin kinase activity, suppressed synaptic potentiation in slices from fear-conditioned rats. Surprisingly, this reduction of synaptic efficacy was mediated by post-but not presynaptic mechanisms. These findings suggest that different plasticity rules may apply to the processes underlying the acquisition of original fear memory and postreactivational stabilization of fear-conditioning-induced synaptic enhancements mediating fear memory reconsolidation.
C1 [Li, Yan; Meloni, Edward G.; Carlezon, William A., Jr.; Bolshakov, Vadim Y.] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA.
[Milad, Mohammed R.; Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA.
[Milad, Mohammed R.; Pitman, Roger K.] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Nader, Karim] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada.
RP Nader, K (reprint author), McGill Univ, Dept Psychol, 1205 Dr Penfield Ave, Montreal, PQ H3A 1B1, Canada.
EM karim.nader@mcgill.ca; vadimb@mclean.harvard.edu
FU National Institutes of Health [MH083011, MH090464]; US Army Medical
Research Acquisition Activity Grant [W81XWH-08-2-0126]
FX This study was supported by National Institutes of Health Grants
MH083011 (to V.Y.B) and MH090464 (to V.Y.B.), and US Army Medical
Research Acquisition Activity Grant W81XWH-08-2-0126 (to R.K.P.).
NR 39
TC 25
Z9 26
U1 0
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 19
PY 2013
VL 110
IS 12
BP 4798
EP 4803
DI 10.1073/pnas.1217878110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125EK
UT WOS:000317521600080
PM 23487762
ER
PT J
AU Purdon, PL
Pierce, ET
Mukamel, EA
Prerau, MJ
Walsh, JL
Wong, KFK
Salazar-Gomez, AF
Harrell, PG
Sampson, AL
Cimenser, A
Ching, SN
Kopell, NJ
Tavares-Stoeckel, C
Habeeb, K
Merhar, R
Brown, EN
AF Purdon, Patrick L.
Pierce, Eric T.
Mukamel, Eran A.
Prerau, Michael J.
Walsh, John L.
Wong, Kin Foon K.
Salazar-Gomez, Andres F.
Harrell, Priscilla G.
Sampson, Aaron L.
Cimenser, Aylin
Ching, ShiNung
Kopell, Nancy J.
Tavares-Stoeckel, Casie
Habeeb, Kathleen
Merhar, Rebecca
Brown, Emery N.
TI Electroencephalogram signatures of loss and recovery of consciousness
from propofol
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID SPECTRAL EDGE FREQUENCY; INDUCED ALPHA-RHYTHM; GENERAL-ANESTHESIA;
BISPECTRAL ANALYSIS; STATE INDEX; EEG CHANGES; SLEEP; MECHANISMS;
OSCILLATIONS; SEVOFLURANE
AB Unconsciousness is a fundamental component of general anesthesia (GA), but anesthesiologists have no reliable ways to be certain that a patient is unconscious. To develop EEG signatures that track loss and recovery of consciousness under GA, we recorded high-density EEGs in humans during gradual induction of and emergence from unconsciousness with propofol. The subjects executed an auditory task at 4-s intervals consisting of interleaved verbal and click stimuli to identify loss and recovery of consciousness. During induction, subjects lost responsiveness to the less salient clicks before losing responsiveness to the more salient verbal stimuli; during emergence they recovered responsiveness to the verbal stimuli before recovering responsiveness to the clicks. The median frequency and bandwidth of the frontal EEG power tracked the probability of response to the verbal stimuli during the transitions in consciousness. Loss of consciousness was marked simultaneously by an increase in low-frequency EEG power (<1 Hz), the loss of spatially coherent occipital alpha oscillations (8-12 Hz), and the appearance of spatially coherent frontal alpha oscillations. These dynamics reversed with recovery of consciousness. The low-frequency phase modulated alpha amplitude in two distinct patterns. During profound unconsciousness, alpha amplitudes were maximal at low-frequency peaks, whereas during the transition into and out of unconsciousness, alpha amplitudes were maximal at low-frequency nadirs. This latter phase-amplitude relationship predicted recovery of consciousness. Our results provide insights into the mechanisms of propofol-induced unconsciousness, establish EEG signatures of this brain state that track transitions in consciousness precisely, and suggest strategies for monitoring the brain activity of patients receiving GA.
C1 [Purdon, Patrick L.; Pierce, Eric T.; Prerau, Michael J.; Walsh, John L.; Wong, Kin Foon K.; Salazar-Gomez, Andres F.; Harrell, Priscilla G.; Sampson, Aaron L.; Cimenser, Aylin; Ching, ShiNung; Tavares-Stoeckel, Casie; Merhar, Rebecca; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Habeeb, Kathleen] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA.
[Purdon, Patrick L.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
[Mukamel, Eran A.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02139 USA.
[Mukamel, Eran A.] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA.
[Kopell, Nancy J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
RP Purdon, PL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM patrickp@nmr.mgh.harvard.edu; nk@bu.edu; enb@neurostat.mit.edu
RI Wong, Kin Foon Kevin/C-7896-2014
FU National Institutes of Health (NIH) Director's Pioneer Award
[DP1-OD003646]; NIH Grant [R01-MH071847]; NIH New Innovator Award
[DP2-OD006454]; NIH K-Award [K25-NS057580]; Massachusetts General
Hospital Department of Anesthesia, Critical Care, and Pain Medicine;
Harvard Catalyst; Harvard Clinical and Translational Science Center (NIH
Award) [UL1 RR 025758]; [R01-EB006385]
FX This work was supported by National Institutes of Health (NIH)
Director's Pioneer Award DP1-OD003646 and NIH Grant R01-MH071847 (to
E.N.B.), by NIH New Innovator Award DP2-OD006454 and K-Award
K25-NS057580 (to P.L.P.), and by R01-EB006385 (to E.N.B., P.L.P., and
K.F.K.W.) This work was also supported by the Massachusetts General
Hospital Department of Anesthesia, Critical Care, and Pain Medicine, as
well as the Harvard Catalyst and The Harvard Clinical and Translational
Science Center (NIH Award UL1 RR 025758).
NR 78
TC 89
Z9 90
U1 1
U2 34
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 19
PY 2013
VL 110
IS 12
BP E1142
EP E1151
DI 10.1073/pnas.1221180110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 125EK
UT WOS:000317521600010
PM 23487781
ER
PT J
AU Barton, JP
Sontag, ED
AF Barton, John P.
Sontag, Eduardo D.
TI The Energy Costs of Insulators in Biochemical Networks
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION NETWORKS; NEGATIVE
FEEDBACK-AMPLIFIER; MATHEMATICAL-MODELS; TRADE-OFFS; RETROACTIVITY;
DYNAMICS; BIOLOGY; SYSTEMS; COMPLEXITY
AB Complex networks of biochemical reactions, such as intracellular protein signaling pathways and genetic networks, are often conceptualized in terms of modules-semiindependent collections of components that perform a well-defined function and which may be incorporated in multiple pathways. However, due to sequestration of molecular messengers during interactions and other effects, collectively referred to as retroactivity, real biochemical systems do not exhibit perfect modularity. Biochemical signaling pathways can be insulated from impedance and competition effects, which inhibit modularity, through enzymatic futile cycles that consume energy, typically in the form of ATP. We hypothesize that better insulation necessarily requires higher energy consumption. We test this hypothesis through a combined theoretical and computational analysis of a simplified physical model of covalent cycles, using two innovative measures of insulation, as well as a possible new way to characterize optimal insulation through the balancing of these two measures in a Pareto sense. Our results indicate that indeed better insulation requires more energy. While insulation may facilitate evolution by enabling a modular plug-and-play interconnection architecture, allowing for the creation of new behaviors by adding targets to existing pathways, our work suggests that this potential benefit must be balanced against the metabolic costs of insulation necessarily incurred in not affecting the behavior of existing processes.
C1 [Barton, John P.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Barton, John P.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Barton, John P.] Harvard Univ, Boston, MA 02115 USA.
[Sontag, Eduardo D.] Rutgers State Univ, Dept Math, Piscataway, NJ 08855 USA.
RP Sontag, ED (reprint author), Rutgers State Univ, Dept Math, Piscataway, NJ 08855 USA.
EM sontag@math.rutgers.edu
OI Barton, John/0000-0003-1467-421X; Sontag, Eduardo/0000-0001-8020-5783
FU National Institutes of Health [NIH 1R01GM086881, 1R01GM100473, AFOSR
FA9550-11-1-0247]
FX Work was supported in part by National Institutes of Health grants No.
NIH 1R01GM086881, No. 1R01GM100473, and No. AFOSR FA9550-11-1-0247.
NR 53
TC 10
Z9 10
U1 0
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD MAR 19
PY 2013
VL 104
IS 6
BP 1380
EP 1390
DI 10.1016/j.bpj.2013.01.056
PG 11
WC Biophysics
SC Biophysics
GA 111MO
UT WOS:000316525600022
PM 23528097
ER
PT J
AU Meyer, MJ
Bateman, BT
Kurth, T
Eikermann, M
AF Meyer, Matthew J.
Bateman, Brian T.
Kurth, Tobias
Eikermann, Matthias
TI INTERMEDIATE ACTING NEUROMUSCULAR BLOCKING AGENTS AND POSTOPERATIVE
RESPIRATORY COMPLICATIONS Neostigmine reversal doesn't improve
postoperative respiratory safety
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Letter
C1 [Meyer, Matthew J.; Bateman, Brian T.; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02163 USA.
[Bateman, Brian T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA.
[Kurth, Tobias] INSERM, Neuroepidemiol U708, Bordeaux, France.
[Kurth, Tobias] Univ Bordeaux, Bordeaux, France.
[Kurth, Tobias] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA.
[Eikermann, Matthias] Univ Klinikum Essen, Klin Anaesthesie & Intens Med, Essen, Germany.
RP Meyer, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02163 USA.
EM meikermann@partners.org
RI Kurth, Tobias/A-9243-2012
OI Kurth, Tobias/0000-0001-7169-2620
NR 4
TC 10
Z9 10
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD MAR 19
PY 2013
VL 346
AR f1460
DI 10.1136/bmj.f1460
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 113LX
UT WOS:000316670500017
PM 23512446
ER
PT J
AU Iezzoni, LI
AF Iezzoni, Lisa I.
TI Ups and Downs of Improving Physical Examination Access for Patients and
Physicians
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA.
EM liezzoni@partners.org
NR 6
TC 1
Z9 1
U1 0
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 19
PY 2013
VL 158
IS 6
BP 491
EP 492
DI 10.7326/0003-4819-158-6-201303190-00010
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 112AY
UT WOS:000316565100019
PM 23552461
ER
PT J
AU Cryer, PE
Axelrod, L
Grossman, AB
Heller, SR
Seaquist, ER
Service, FJ
AF Cryer, Philip E.
Axelrod, Lloyd
Grossman, Ashley B.
Heller, Simon R.
Seaquist, Elizabeth R.
Service, F. John
CA Endocrine Soc Task Force
TI Diagnostic Accuracy of an "Amended" Insulin-Glucose Ratio for the
Biochemical Diagnosis of Insulinomas
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID BASAL INSULIN; HYPOGLYCEMIA; MANAGEMENT
C1 [Cryer, Philip E.] Washington Univ, St Louis, MO 63130 USA.
[Axelrod, Lloyd] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Axelrod, Lloyd] Harvard Univ, Sch Med, Boston, MA USA.
[Grossman, Ashley B.] Oxford Ctr Diabet Endocrinol & Metab, Headington, Oxon, England.
[Heller, Simon R.] Sheffield Teaching Hosp, Sheffield, S Yorkshire, England.
[Seaquist, Elizabeth R.] Univ Minnesota, Minneapolis, MN USA.
[Service, F. John] Mayo Clin, Rochester, MN USA.
RP Cryer, PE (reprint author), Washington Univ, St Louis, MO 63130 USA.
OI Heller, Simon/0000-0002-2425-9565
FU NCRR NIH HHS [MO1-RR00036]; NIDDK NIH HHS [P60-DK20579, R37-DK27085,
T32-DK07120]
NR 7
TC 1
Z9 1
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 19
PY 2013
VL 158
IS 6
BP 500
EP 501
DI 10.7326/0003-4819-158-6-201303190-00020
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 112AY
UT WOS:000316565100026
PM 23552360
ER
PT J
AU Adams, SG
Peters, JI
AF Adams, Sandra G.
Peters, Jay I.
TI Amoxicillin/clavulanate vs placebo: more exacerbation cures, fewer
recurrences in mild-to-moderate COPD
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Adams, Sandra G.] Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX 78249 USA.
South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Adams, SG (reprint author), Univ Texas San Antonio, Hlth Sci Ctr, San Antonio, TX 78249 USA.
OI Miravitlles, Marc/0000-0002-9850-9520
NR 2
TC 0
Z9 0
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 19
PY 2013
VL 158
IS 6
AR JC3
DI 10.7326/0003-4819-158-6-201303190-02003
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 112AY
UT WOS:000316565100002
PM 23552686
ER
PT J
AU Kinlay, S
AF Kinlay, Scott
TI Outcomes for Clinical Studies Assessing Drug and Revascularization
Therapies for Claudication and Critical Limb Ischemia in Peripheral
Artery Disease
SO CIRCULATION
LA English
DT Article
ID SUPERFICIAL FEMORAL-ARTERY; QUALITY-OF-LIFE; RANDOMIZED
CONTROLLED-TRIAL; NITINOL STENT IMPLANTATION; PERCUTANEOUS TRANSLUMINAL
ANGIOPLASTY; PACLITAXEL-ELUTING STENTS; ANKLE-BRACHIAL INDEX;
INTERMITTENT CLAUDICATION; BALLOON ANGIOPLASTY; LOWER-EXTREMITY
C1 [Kinlay, Scott] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Kinlay, Scott] Harvard Univ, Sch Med, Boston, MA USA.
RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
EM scott.kinlay@va.gov
FU Clinical Science Research and Development Service of the VA Office of
Research and Development [I01CX000440]
FX This work was supported by Award Number I01CX000440 from the Clinical
Science Research and Development Service of the VA Office of Research
and Development.
NR 86
TC 16
Z9 17
U1 1
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 MAR 19
PY 2013
VL 127
IS 11
BP 1241
EP 1250
DI 10.1161/CIRCULATIONAHA.112.001232
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 108DN
UT WOS:000316271800018
PM 23509032
ER
PT J
AU Aneja, A
Esquitin, R
Shah, K
Iyengar, R
Nisenbaum, R
Melo, M
Matthewkutty, S
Sethi, SS
Mamdani, M
Farkouh, ME
AF Aneja, Ashish
Esquitin, Ricardo
Shah, Kshitij
Iyengar, Rupa
Nisenbaum, Rosane
Melo, Magda
Matthewkutty, Shiny
Sethi, Sanjum S.
Mamdani, Muhammad
Farkouh, Michael E.
TI Authors' Self-Declared Financial Conflicts of Interest Do Not Impact the
Results of Major Cardiovascular Trials
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiovascular; clinical trial; conflicts of interest; financial;
industry; randomized controlled trials
ID CLINICAL-TRIALS; PHARMACEUTICAL-INDUSTRY; INTEREST DISCLOSURE; DRUG
TRIALS; ASSOCIATION; OUTCOMES; TIES
AB Objectives This study assessed whether the results of major, potentially practice-altering cardiovascular trials were influenced by the authors' self-declared financial conflicts of interest (FCOI). Secondary objectives included assessment of trial outcomes by source of funding, by FCOI subtype, and by trial endpoints.
Background Financial conflicts of interest, ubiquitous in cardiovascular medicine because of significant investigator-industry collaborations, potentially can influence trial outcomes.
Methods A MEDLINE search was performed using the MeSH term cardiovascular disease limited to randomized controlled trials and clinical trials published from January 1, 2000, through April 15, 2008, in 3 high-impact journals. Two reviewers independently abstracted data from the published article. Chi-square tests, Fisher exact tests, and multivariate logistic regression were used to assess the associations between FCOI and study characteristics and between FCOI and trial outcomes.
Results Of the 550 articles reviewed, 51.1% satisfied FCOI criteria, including at least one of the following: stock ownership, employee, speaker's bureau, and consultant). Of the 538 articles providing sponsorship information, 34.6% reported funding solely by nonprofit organizations, 48.3% reported funding solely by industry, and 17.1% reported funding by a combination. Prevalence of FCOI significantly increased with level of industry funding: 21.5% (none), 50.0% (shared), 75.0% (industry solely, n = 281, p < 0.0001). However, no differences in reporting of favorable results were detected when articles were analyzed by self-declared FCOI (60.5% vs. 59.5% in those with and without, odds ratio: 1.04, p = 0.81). This result was upheld in multivariate analysis.
Conclusions Authors' self-declared FCOI and source of funding do not seem to impact outcomes in major cardiovascular clinical trials. (J Am Coll Cardiol 2013;61:1137-43) (C) 2013 by the American College of Cardiology Foundation
C1 [Aneja, Ashish] Case Western Reserve Univ, Heart & Vasc Ctr, Cleveland, OH 44106 USA.
[Esquitin, Ricardo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA.
[Shah, Kshitij] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA.
[Iyengar, Rupa; Matthewkutty, Shiny; Sethi, Sanjum S.; Farkouh, Michael E.] Mt Sinai Sch Med, Zena & Michael A Weiner Cardiovasc Inst, New York, NY 10029 USA.
[Nisenbaum, Rosane] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Ctr Res Inner City Hlth,Keenan Res Ctr, Toronto, ON M5B 1W8, Canada.
[Nisenbaum, Rosane] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Nisenbaum, Rosane; Melo, Magda; Mamdani, Muhammad; Farkouh, Michael E.] Univ Toronto, Li Ka Shing Knowledge Inst, Appl Hlth Res Ctr, Toronto, ON, Canada.
[Farkouh, Michael E.] Univ Toronto, Peter Munk Cardiac Ctr, Toronto, ON, Canada.
RP Farkouh, ME (reprint author), Mt Sinai Sch Med, Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1074, New York, NY 10029 USA.
EM Michael.Farkouh@mssm.edu
OI Esquitin, Ricardo/0000-0002-3475-3671
NR 30
TC 9
Z9 10
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 19
PY 2013
VL 61
IS 11
BP 1137
EP 1143
DI 10.1016/j.jacc.2012.10.056
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 103UO
UT WOS:000315945200003
PM 23395075
ER
PT J
AU Mandawat, A
Mandawat, A
Mandawat, MK
AF Mandawat, Aditya
Mandawat, Anant
Mandawat, Mahendra K.
TI Percutaneous Coronary Intervention After ST-Segment Elevation Myocardial
Infarction in Nonagenarians Use Rates and In-Hospital Mortality
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Letter
C1 [Mandawat, Aditya] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Mandawat, Aditya; Mandawat, Anant] Harvard Univ, Sch Med, Boston, MA USA.
[Mandawat, Anant] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mandawat, Mahendra K.] Georgia Hlth Sci Univ, Augusta, GA USA.
[Mandawat, Mahendra K.] Charlie Norwood VA Med Ctr, Augusta, GA 30904 USA.
RP Mandawat, MK (reprint author), Charlie Norwood VA Med Ctr, 1 Freedom Way, Augusta, GA 30904 USA.
EM mahendra.mandawat@va.gov
NR 5
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 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 19
PY 2013
VL 61
IS 11
BP 1207
EP 1208
DI 10.1016/j.jacc.2012.12.019
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 103UO
UT WOS:000315945200015
PM 23375924
ER
PT J
AU Vazquez, F
Lim, JH
Chim, H
Bhalla, K
Girnun, G
Pierce, K
Clish, CB
Granter, SR
Widlund, HR
Spiegelman, BM
Puigserver, P
AF Vazquez, Francisca
Lim, Ji-Hong
Chim, Helen
Bhalla, Kavita
Girnun, Geoff
Pierce, Kerry
Clish, Clary B.
Granter, Scott R.
Widlund, Hans R.
Spiegelman, Bruce M.
Puigserver, Pere
TI PGC1 alpha Expression Defines a Subset of Human Melanoma Tumors with
Increased Mitochondrial Capacity and Resistance to Oxidative Stress
SO CANCER CELL
LA English
DT Article
ID PROMOTES CELL-SURVIVAL; ERR-ALPHA; TRANSCRIPTIONAL COACTIVATOR;
METABOLIC REGULATOR; MALIGNANT-MELANOMA; GLUCOSE-METABOLISM;
CANCER-CELLS; LUNG-CANCER; PGC-1-ALPHA; MITF
AB Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte lineage-specification transcription factor MITF drives PGC1 alpha (PPARGC1A) overexpression in a subset of human melanomas and derived cell lines. Functionally, PGC1 alpha positive melanoma cells exhibit increased mitochondrial energy metabolism and reactive oxygen species (ROS) detoxification capacities that enable survival under oxidative stress conditions. Conversely, PGC1 alpha negative melanoma cells are more glycolytic and sensitive to ROS-inducing drugs. These results demonstrate that differences in PGC1 alpha levels in melanoma tumors have a profound impact in their metabolism, biology, and drug sensitivity.
C1 [Vazquez, Francisca; Lim, Ji-Hong; Chim, Helen; Spiegelman, Bruce M.; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Vazquez, Francisca; Lim, Ji-Hong; Chim, Helen; Spiegelman, Bruce M.; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Bhalla, Kavita; Girnun, Geoff] Univ Maryland, Sch Med, Dept Pathol, Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Pierce, Kerry; Clish, Clary B.] Broad Inst MIT & Harvard, Metabolite Profiling Initiat, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Granter, Scott R.] Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Dept Pathol, Boston, MA 02115 USA.
[Widlund, Hans R.] Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Dept Dermatol, Boston, MA 02115 USA.
RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM pere_puigserver@dfci.harvard.edu
FU Claudia Adams Barr Program in Cancer Research; Dana-Farber Cancer
Institute; [P50CA093683]
FX We thank the Dana-Farber Cancer Institute Microarray Core Facility for
performing the gene-expression arrays and the Dana-Farber RNAi facility
for the shRNA constructs. These studies were funded by the Claudia Adams
Barr Program in Cancer Research and Dana-Farber Cancer Institute funds.
H.R.W. acknowledges support from P50CA093683.
NR 45
TC 135
Z9 139
U1 5
U2 45
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 MAR 18
PY 2013
VL 23
IS 3
BP 287
EP 301
DI 10.1016/j.ccr.2012.11.020
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 110JS
UT WOS:000316439000008
PM 23416000
ER
PT J
AU Haq, R
Shoag, J
Andreu-Perez, P
Yokoyama, S
Edelman, H
Rowe, GC
Frederick, DT
Hurley, AD
Nellore, A
Kung, AL
Wargo, JA
Song, JS
Fisher, DE
Arany, Z
Widlund, HR
AF Haq, Rizwan
Shoag, Jonathan
Andreu-Perez, Pedro
Yokoyama, Satoru
Edelman, Hannah
Rowe, Glenn C.
Frederick, Dennie T.
Hurley, Aeron D.
Nellore, Abhinav
Kung, Andrew L.
Wargo, Jennifer A.
Song, Jun S.
Fisher, David E.
Arany, Zolt
Widlund, Hans R.
TI Oncogenic BRAF Regulates Oxidative Metabolism via PGC1 alpha and MITF
SO CANCER CELL
LA English
DT Article
ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; CONTROLLING MITOCHONDRIAL
BIOGENESIS; B-RAF; METASTATIC MELANOMA; HEPATIC GLUCONEOGENESIS; CELL
PROLIFERATION; PGC-1 COACTIVATORS; MALIGNANT-MELANOMA; SKELETAL-MUSCLE;
CANCER CELLS
AB Activating mutations in BRAF are the most common genetic alterations in melanoma. Inhibition of BRAF by small molecules leads to cell-cycle arrest and apoptosis. We show here that BRAF inhibition also induces an oxidative phosphorylation gene program, mitochondrial biogenesis, and the increased expression of the mitochondrial master regulator, PGC1 alpha. We further show that a target of BRAF, the melanocyte lineage factor MITF, directly regulates the expression of PGC1 alpha. Melanomas with activation of the BRAF/MAPK pathway have suppressed levels of MITF and PGC1 alpha and decreased oxidative metabolism. Conversely, treatment of BRAF-mutated melanomas with BRAF inhibitors renders them addicted to oxidative phosphorylation. Our data thus identify an adaptive metabolic program that limits the efficacy of BRAF inhibitors.
C1 [Haq, Rizwan; Fisher, David E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Haq, Rizwan; Andreu-Perez, Pedro; Yokoyama, Satoru; Edelman, Hannah; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Boston, MA 02114 USA.
[Frederick, Dennie T.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Shoag, Jonathan; Rowe, Glenn C.; Arany, Zolt] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02116 USA.
[Yokoyama, Satoru] Toyama Univ, Inst Nat Med, Div Pathogen Biochem, Toyama 9300194, Japan.
[Hurley, Aeron D.; Widlund, Hans R.] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
[Nellore, Abhinav; Song, Jun S.] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Kung, Andrew L.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10032 USA.
RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA.
EM dfisher3@partners.org; zarany@bidmc.harvard.edu;
hwidlund@bics.bwh.harvard.edu
FU American Skin Association; NIAMS/NIH [R01 AR043369-16]; Melanoma
Research Alliance; Dr. Miriam and Sheldon G. Adelson Medical Research
Foundation; National Cancer Institute [R01CA163336, P50CA093683]
FX We thank A. Winant for assistance with manuscript writing, M. McKee for
electron microscopy, and A. Saur at the Luria Family Imaging Center
(Dana-Farber Cancer Institute) for assistance with mouse xenograft
experiments. This work was supported by the American Skin Association
(to R.H.), NIAMS/NIH (R01 AR043369-16), Melanoma Research Alliance, Dr.
Miriam and Sheldon G. Adelson Medical Research Foundation (to D.E.F.),
and The National Cancer Institute (R01CA163336 to J.S.S. and P50CA093683
to H.R.W.).
NR 76
TC 172
Z9 175
U1 8
U2 45
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 MAR 18
PY 2013
VL 23
IS 3
BP 302
EP 315
DI 10.1016/j.ccr.2013.02.003
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 110JS
UT WOS:000316439000009
PM 23477830
ER
PT J
AU Roti, G
Carlton, A
Ross, KN
Markstein, M
Pajcini, K
Su, AH
Perrimon, N
Pear, WS
Kung, AL
Blacklow, SC
Aster, JC
Stegmaier, K
AF Roti, Giovanni
Carlton, Anne
Ross, Kenneth N.
Markstein, Michele
Pajcini, Kostandin
Su, Angela H.
Perrimon, Norbert
Pear, Warren S.
Kung, Andrew L.
Blacklow, Stephen C.
Aster, Jon C.
Stegmaier, Kimberly
TI Complementary Genomic Screens Identify SERCA as a Therapeutic Target in
NOTCH1 Mutated Cancer
SO CANCER CELL
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GAMMA-SECRETASE
INHIBITORS; T-ALL; MYELOID-LEUKEMIA; CA2+ PUMP; C-MYC; MUTATIONS; GENE;
DROSOPHILA
AB Notch1 is a rational therapeutic target in several human cancers, but as a transcriptional regulator, it poses a drug discovery challenge. To identify Notch1 modulators, we performed two cell-based, high-throughput screens for small-molecule inhibitors and cDNA enhancers of a NOTCH1 allele bearing a leukemia-associated mutation. Sarco/endoplasmic reticulum calcium ATPase (SERCA) channels emerged at the intersection of these complementary screens. SERCA inhibition preferentially impairs the maturation and activity of mutated Notch1 receptors and induces a G(0)/G(1) arrest in NOTCH1-mutated human leukemia cells. A small-molecule SERCA inhibitor has on-target activity in two mouse models of human leukemia and interferes with Notch signaling in Drosophila. These studies "credential" SERCA as a therapeutic target in cancers associated with NOTCH1 mutations.
C1 [Roti, Giovanni; Carlton, Anne; Su, Angela H.; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Blacklow, Stephen C.] Dana Farber Canc Inst, Canc Biol Program, Boston, MA 02215 USA.
[Roti, Giovanni; Carlton, Anne; Su, Angela H.; Stegmaier, Kimberly] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Ross, Kenneth N.; Stegmaier, Kimberly] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA.
[Markstein, Michele] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
[Pajcini, Kostandin; Pear, Warren S.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Pajcini, Kostandin; Pear, Warren S.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Perrimon, Norbert] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Blacklow, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Aster, Jon C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Kung, Andrew L.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
RP Stegmaier, K (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
EM kimberly_stegmaier@dfci.harvard.edu
OI Markstein, Michele/0000-0003-2635-8118; Kung,
Andrew/0000-0002-9091-488X; Carlton, Anne/0000-0002-5921-6004
FU Leukemia and Lymphoma Society (LLS); William Lawrence and Blanche Hughes
Foundation; SynCure Cancer Research Foundation; National Cancer
Institute [P01 CA 068484-11A1]; European Hematology Association-American
Society of Hematology International Fellowship Award; American-Italian
Cancer Foundation; Lady Tata International Award for Research in
Leukaemia; LLS; Fondazione Umberto Veronesi; National Institutes of
Health (NIH)/National Center for Research Resources [5 UL1 RR025758];
NIH [R01 CA 092433]; AULL (Associazione Umbra per lo studio e la terapia
delle Leucemie e Linfomi)
FX This work was supported by the Leukemia and Lymphoma Society (LLS) and
the William Lawrence and Blanche Hughes Foundation (to K.S., J.C.A., and
S.C.B.); the SynCure Cancer Research Foundation and the National Cancer
Institute grant P01 CA 068484-11A1 (to K.S.); the European Hematology
Association-American Society of Hematology International Fellowship
Award, the American-Italian Cancer Foundation Post-Doctoral Research
Fellowship, the Lady Tata International Award for Research in Leukaemia,
and the LLS Special Fellow award and Fondazione Umberto Veronesi (to
G.R.); the LLS Fellow (to K.P.); National Institutes of Health
(NIH)/National Center for Research Resources grants 5 UL1 RR025758 (to
N.P. and M.M.); and NIH grant R01 CA 092433 (to S.C.B.). We thank Zi
Peng Fan and Amanda L. Christie for their technical support, Nicola
Tolliday for stewardship of the chemical screen, the TRiP at Harvard
Medical School for providing transgenic RNAi fly stocks used in this
study, and Maria Pia Briziarelli, AULL (Associazione Umbra per lo studio
e la terapia delle Leucemie e Linfomi), for grant management (G.R.).
NR 64
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U1 1
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD MAR 18
PY 2013
VL 23
IS 3
BP 390
EP 405
DI 10.1016/j.ccr.2013.01.015
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 110JS
UT WOS:000316439000015
PM 23434461
ER
PT J
AU Bested, AC
Logan, AC
Selhub, EM
AF Bested, Alison C.
Logan, Alan C.
Selhub, Eva M.
TI Intestinal microbiota, probiotics and mental health: from Metchnikoff to
modern advances: Part I - autointoxication revisited
SO GUT PATHOGENS
LA English
DT Review
DE Intestinal microbiota; Autointoxication; Depression; Anxiety;
Probiotics; Microbial ecology; Lipopolysaccharide endotoxin; Diet;
Intestinal permeability
ID HELICOBACTER-PYLORI INFECTION; IRRITABLE-BOWEL-SYNDROME; BACILLUS
ACIDOPHILUS; TOOTH LOSS; CHRONIC CONSTIPATION; BACTERIAL-FLORA;
DEPRESSION; THERAPY; DISEASE; SKIN
AB Mental health disorders, depression in particular, have been described as a global epidemic. Research suggests that a variety of lifestyle and environmental changes may be driving at least some portion of the increased prevalence. One area of flourishing research involves the relationship between the intestinal microbiota (as well as the related functional integrity of the gastrointestinal tract) and mental health. In order to appreciate the recent scientific gains in this area, and its potential future directions, it is critical to review the history of the topic. Probiotic administration (e.g. Lactobacillus) and fecal microbiota transfer for conditions associated with depression and anxiety is not a new concept. Here, in the first of a 3-part series, we begin by reviewing the origins of the contemporary research, providing a critical appraisal of what has become a revisionist history of the controversial term 'autointoxication'. We argue that legitimate interests in the gut-brain-microbiota connection were obscured for decades by its association with a narrow historical legacy. Historical perspectives provide a very meaningful context to the current state of the contemporary research as outlined in parts II and III.
C1 [Bested, Alison C.] BC Womens Hosp, Complex Chron Dis Program, Vancouver, BC V6H 3N1, Canada.
[Bested, Alison C.] Ctr Hlth, Vancouver, BC V6H 3N1, Canada.
[Logan, Alan C.] CAMNR, Mill Valley, CA 94941 USA.
[Selhub, Eva M.] Harvard Univ, Sch Med, Waltham, MA 02453 USA.
[Selhub, Eva M.] Massachusetts Gen Hosp, Waltham, MA 02453 USA.
RP Logan, AC (reprint author), CAMNR, 775 Blithedale Ave,Suite 364, Mill Valley, CA 94941 USA.
EM aclnd@cfs-fm.org
FU Genuine Health, Toronto, Canada
FX ACB and EMS have no competing interests. ACL has received consulting
fees from Genuine Health, Toronto, Canada.
NR 155
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U1 2
U2 65
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-4749
J9 GUT PATHOG
JI Gut Pathogens
PD MAR 18
PY 2013
VL 5
AR 5
DI 10.1186/1757-4749-5-5
PG 16
WC Gastroenterology & Hepatology; Microbiology
SC Gastroenterology & Hepatology; Microbiology
GA 118GS
UT WOS:000317013700001
PM 23506618
ER
PT J
AU Caceres, IA
Arcaya, M
Declercq, E
Belanoff, CM
Janakiraman, V
Cohen, B
Ecker, J
Smith, LA
Subramanian, SV
AF Caceres, Isabel A.
Arcaya, Mariana
Declercq, Eugene
Belanoff, Candice M.
Janakiraman, Vanitha
Cohen, Bruce
Ecker, Jeffrey
Smith, Lauren A.
Subramanian, S. V.
TI Hospital Differences in Cesarean Deliveries in Massachusetts (US)
2004-2006: The Case against Case-Mix Artifact
SO PLOS ONE
LA English
DT Article
ID BIRTH-RATES; PHYSICIAN FACTOR; VAGINAL BIRTHS; UNITED-STATES; RISK;
SECTION; ADJUSTMENT; OUTCOMES; WOMEN; TERM
AB Objective: We examined the extent to which differences in hospital-level cesarean delivery rates in Massachusetts were attributable to hospital-level, rather than maternal, characteristics.
Methods: Birth certificate and maternal in-patient hospital discharge records for 2004-06 in Massachusetts were linked. The study population was nulliparous, term, singleton, and vertex births (NTSV) (n = 80,371) in 49 hospitals. Covariates included mother's age, race/ethnicity, education, infant birth weight, gestational age, labor induction (yes/no), hospital shift at time of birth, and preexisting health conditions. We estimated multilevel logistic regression models to assess the likelihood of a cesarean delivery
Results: Overall, among women with NTSV births, 26.5% births were cesarean, with a range of 14% to 38.3% across hospitals. In unadjusted models, the between-hospital variance was 0.103 (SE 0.022); adjusting for demographic, socioeconomic and preexisting medical conditions did not reduce any hospital-level variation 0.108 (SE 0.023).
Conclusion: Even after adjusting for both socio-demographic and clinical factors, the chance of a cesarean delivery for NTSV pregnancies varied according to hospital, suggesting the importance of hospital practices and culture in determining a hospital's cesarean rate.
C1 [Caceres, Isabel A.; Cohen, Bruce] Massachusetts Dept Publ Hlth, Bur Hlth Informat Stat Res & Evaluat, Boston, MA USA.
[Arcaya, Mariana; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Declercq, Eugene; Belanoff, Candice M.] Boston Univ, Dept Community Hlth Sci, Boston, MA 02215 USA.
[Janakiraman, Vanitha; Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Smith, Lauren A.] Massachusetts Dept Hlth, Boston, MA USA.
RP Subramanian, SV (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA.
EM svsubram@hsph.harvard.edu
OI Declercq, Eugene/0000-0001-5411-3033; Belanoff,
Candice/0000-0002-2491-7548
FU Centers for Disease Control and Prevention [200-2009-31671CDC]; National
Cancer Institute's joint Harvard School of Public Health-Dana-Farber
Cancer Institute Educational Program in Cancer Prevention Research;
National Institutes of Health (NIH) [3R25CA057711-18S1]; NIH [NHLBI K25
HL081275]; Robert Wood Johnson Investigator Award in Healthy Policy
Research
FX No direct funding was available for this study. The data for this study
was provided by the Pregnancy to Early Life Longitudinal (PELL) data
system which is supported by the Centers for Disease Control and
Prevention Contract 200-2009-31671CDC. MA is supported as a predoctoral
fellow by the National Cancer Institute's joint Harvard School of Public
Health-Dana-Farber Cancer Institute Educational Program in Cancer
Prevention Research, supported by National Institutes of Health (NIH)
grant number 3R25CA057711-18S1. S.V. Subramanian is supported by the NIH
Career Development Award (NHLBI K25 HL081275) and the Robert Wood
Johnson Investigator Award in Healthy Policy Research. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 35
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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 MAR 18
PY 2013
VL 8
IS 3
AR e57817
DI 10.1371/journal.pone.0057817
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600006
PM 23526952
ER
PT J
AU Desai, BM
Villanueva, J
Nguyen, TTK
Lioni, M
Xiao, M
Kong, J
Krepler, C
Vultur, A
Flaherty, KT
Nathanson, KL
Smalley, KSM
Herlyn, M
AF Desai, Brijal M.
Villanueva, Jessie
Nguyen, Thierry-Thien K.
Lioni, Mercedes
Xiao, Min
Kong, Jun
Krepler, Clemens
Vultur, Adina
Flaherty, Keith T.
Nathanson, Katherine L.
Smalley, Keiran S. M.
Herlyn, Meenhard
TI The Anti-Melanoma Activity of Dinaciclib, a Cyclin-Dependent Kinase
Inhibitor, Is Dependent on p53 Signaling
SO PLOS ONE
LA English
DT Article
ID MEK INHIBITION; MELANOMA-CELLS; MALIGNANT-MELANOMA; LINEAGE SURVIVAL;
RAF KINASE; BRAF; RESISTANCE; GROWTH; EXPRESSION; MUTATIONS
AB Although cyclin dependent kinase (CDK)-2 is known to be dispensable for the growth of most tumors, it is thought to be important for the proliferation of melanoma cells, where its expression is controlled by the melanocyte-lineage specific transcription factor MITF. Treatment of a panel of melanoma cells with the CDK inhibitor dinaciclib led to a concentration-dependent inhibition of growth under both 2D adherent and 3D organotypic cell culture conditions. Dinaciclib targeted melanoma cell lines regardless of cdk2 or MITF levels. Inhibition of growth was associated with a rapid induction of G2/M cell arrest and apoptosis. Treatment of human melanoma mouse xenografts with dinaciclib led to tumor regression associated with reduced retinoblastoma protein phosphorylation and Bcl-2 expression. Further mechanistic studies revealed that dinaciclib induces p53 expression whilst simultaneously downregulating the expression of the anti-apoptotic factors Mcl-1 and XIAP. To clarify the role of p53 activation in the dinaciclib-induced cell death, we generated melanoma cell lines in which p53 expression was knocked down using a shRNA lentiviral vector. Knockdown of p53 completely abolished the induction of apoptosis seen following dinaciclib treatment as shown by a lack of annexin-V staining and caspase-3 cleavage. Altogether, these data show that dinaciclib induces apoptosis in a large panel of melanoma cell lines through a mechanism requiring p53 expression.
C1 [Desai, Brijal M.; Villanueva, Jessie; Nguyen, Thierry-Thien K.; Lioni, Mercedes; Xiao, Min; Kong, Jun; Krepler, Clemens; Vultur, Adina; Herlyn, Meenhard] Wistar Inst Anat & Biol, Philadelphia, PA USA.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Smalley, Keiran S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL USA.
RP Herlyn, M (reprint author), Wistar Inst Anat & Biol, Philadelphia, PA USA.
EM herlynm@wistar.org
OI Nathanson, Katherine/0000-0002-6740-0901
FU National Institutes of Health [CA 76674, CA 25874,, CA 10815,, CA 93372,
CA 47159, CA 80999, CA 098101, CA117881, GM071695]; Commonwealth
Universal Research Enhancement Program; Pennsylvania Department of
Health; American Skin Association; Schering-Plough, Kenilworth, New
Jersey; Adelson Medical Research Foundation
FX This work was supported by grants from the National Institutes of Health
(CA 76674, CA 25874, CA 10815, CA 93372, CA 47159, CA 80999, CA 098101,
CA117881, GM071695); funds from the Commonwealth Universal Research
Enhancement Program; Pennsylvania Department of Health; the American
Skin Association; Schering-Plough, Kenilworth, New Jersey; and the
Adelson Medical Research Foundation. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 51
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U1 2
U2 18
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 MAR 18
PY 2013
VL 8
IS 3
AR e59588
DI 10.1371/journal.pone.0059588
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600067
PM 23527225
ER
PT J
AU Madsen, J
Gaiha, GD
Palaniyar, N
Dong, T
Mitchell, DA
Clark, HW
AF Madsen, Jens
Gaiha, Gaurav D.
Palaniyar, Nades
Dong, Tao
Mitchell, Daniel A.
Clark, Howard W.
TI Surfactant Protein D Modulates HIV Infection of Both T-Cells and
Dendritic Cells
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MANNOSE-BINDING LECTIN; HELICAL
COILED-COIL; INFLUENZA-A VIRUS; CARBOHYDRATE-RECOGNITION; ENVELOPE
GLYCOPROTEIN; PULMONARY COLLECTINS; ALVEOLAR MACROPHAGES; TYPE-1
INFECTIVITY; LIGAND-BINDING
AB Surfactant Protein D (SP-D) is an oligomerized C-type lectin molecule with immunomodulatory properties and involvement in lung surfactant homeostasis in the respiratory tract. SP-D binds to the enveloped viruses, influenza A virus and respiratory syncytial virus and inhibits their replication in vitro and in vivo. SP-D has been shown to bind to HIV via the HIV envelope protein gp120 and inhibit infectivity in vitro. Here we show that SP-D binds to different strains of HIV (BaL and IIIB) and the binding occurs at both pH 7.4 and 5.0 resembling physiological relevant pH values found in the body and the female urogenital tract, respectively. The binding of SP-D to HIV particles and gp120 was inhibited by the presence of several hexoses with mannose found to be the strongest inhibitor. Competition studies showed that soluble CD4 and CVN did not interfere with the interaction between SP-D and gp120. However, soluble recombinant DC-SIGN was shown to inhibit the binding between SP-D and gp120. SP-D agglutinated HIV and gp120 in a calcium dependent manner. SP-D inhibited the infectivity of HIV strains at both pH values of 7.4 and 5.0 in a concentration dependent manner. The inhibition of the infectivity was abolished by the presence of mannose. SP-D enhanced the binding of HIV to immature monocyte derived dendritic cells (iMDDCs) and was also found to enhance HIV capture and transfer to the T-cell like line PM1. These results suggest that SP-D can bind to and inhibit direct infection of T-cells by HIV but also enhance the transfer of infectious HIV particles from DCs to T-cells in vivo.
C1 [Madsen, Jens; Clark, Howard W.] Univ Southampton, Southampton Gen Hosp, Dept Child Hlth, Sir Henry Wellcome Labs,Fac Med, Southampton, Hants, England.
[Madsen, Jens; Clark, Howard W.] Univ Southampton, Inst Life Sci, Southampton, Hants, England.
[Gaiha, Gaurav D.] Massachusetts Gen Hosp, Massachusetts Inst Technol & Harvard, Ragon Inst, Charlestown, MA USA.
[Palaniyar, Nades] Univ Toronto, SickKids Res Inst, Toronto, ON, Canada.
[Dong, Tao] Univ Oxford, Weatherall Inst Mol Med, Human Immunol Unit, MRC, Oxford, England.
[Mitchell, Daniel A.] Univ Warwick, Warwick Med Sch, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England.
RP Madsen, J (reprint author), Univ Southampton, Southampton Gen Hosp, Dept Child Hlth, Sir Henry Wellcome Labs,Fac Med, Southampton, Hants, England.
EM j.madsen@soton.ac.uk
RI Mitchell, Daniel/A-6580-2009; Madsen, Jens/N-8082-2013;
OI Mitchell, Daniel/0000-0003-0936-6212; Madsen, Jens/0000-0003-1664-7645;
Clark, Howard/0000-0001-7354-2028; Palaniyar, Nades/0000-0002-2170-8548
FU Medical Research Council (UK)
FX This work was supported by the Medical Research Council (UK). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 64
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Z9 7
U1 0
U2 13
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 MAR 18
PY 2013
VL 8
IS 3
AR e59047
DI 10.1371/journal.pone.0059047
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600031
PM 23527085
ER
PT J
AU Sun, Y
Hu, ZT
Goeb, Y
Dreier, L
AF Sun, Yu
Hu, Zhitao
Goeb, Yannick
Dreier, Lars
TI The F-Box Protein MEC-15 (FBXW9) Promotes Synaptic Transmission in
GABAergic Motor Neurons in C. elegans
SO PLOS ONE
LA English
DT Article
ID GLR-1 GLUTAMATE RECEPTORS; UBIQUITIN LIGASE COMPLEX;
CAENORHABDITIS-ELEGANS; NEUROMUSCULAR-JUNCTION; SYSTEMATIC ANALYSIS;
TOUCH SENSITIVITY; ABUNDANCE; MUTANTS; BETA; DIFFERENTIATION
AB Ubiquitination controls the activity of many proteins and has been implicated in almost every aspect of neuronal cell biology. Characterizing the precise function of ubiquitin ligases, the enzymes that catalyze ubiquitination of target proteins, is key to understanding distinct functions of ubiquitination. F-box proteins are the variable subunits of the large family of SCF ubiquitin ligases and are responsible for binding and recognizing specific ubiquitination targets. Here, we investigated the function of the F-box protein MEC-15 (FBXW9), one of a small number of F-box proteins evolutionarily conserved from C. elegans to mammals. mec-15 is widely expressed in the nervous system including GABAergic and cholinergic motor neurons. Electrophysiological and behavioral analyses indicate that GABAergic synaptic transmission is reduced in mec-15 mutants while cholinergic transmission appears normal. In the absence of MEC-15, the abundance of the synaptic vesicle protein SNB-1 (synaptobrevin) is reduced at synapses and increased in cell bodies of GABAergic motor neurons, suggesting that MEC-15 affects the trafficking of SNB-1 between cell bodies and synapses and may promote GABA release by regulating the abundance of SNB-1 at synapses.
C1 [Sun, Yu; Goeb, Yannick; Dreier, Lars] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Hu, Zhitao] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
RP Dreier, L (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
EM larsdreier@ucla.edu
FU University of California Los Angeles
FX This work received start-up funds from University of California Los
Angeles. 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 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 MAR 18
PY 2013
VL 8
IS 3
AR e59132
DI 10.1371/journal.pone.0059132
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600042
ER
PT J
AU Vandenwijngaert, S
Pokreisz, P
Hermans, H
Gillijns, H
Pellens, M
Bax, NAM
Coppiello, G
Oosterlinck, W
Balogh, A
Papp, Z
Bouten, CVC
Bartunek, J
D'hooge, J
Luttun, A
Verbeken, E
Herregods, MC
Herijgers, P
Bloch, KD
Janssens, S
AF Vandenwijngaert, Sara
Pokreisz, Peter
Hermans, Hadewich
Gillijns, Hilde
Pellens, Marijke
Bax, Noortje A. M.
Coppiello, Giulia
Oosterlinck, Wouter
Balogh, Agnes
Papp, Zoltan
Bouten, Carlijn V. C.
Bartunek, Jozef
D'hooge, Jan
Luttun, Aernout
Verbeken, Erik
Herregods, Marie Christine
Herijgers, Paul
Bloch, Kenneth D.
Janssens, Stefan
TI Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure
Overload Hypertrophy Contribute to Adverse LV Remodeling
SO PLOS ONE
LA English
DT Article
ID PHOSPHODIESTERASE TYPE 5; ADVANCED HEART-FAILURE;
PULMONARY-HYPERTENSION; INHIBITION; SILDENAFIL; EXPRESSION;
CONTRACTILITY; MYOCARDIUM; STIFFNESS; 1-YEAR
AB Background: The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC).
Methodology/Principal Findings: In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dt(max) and dP/dt(min) with prolonged tau (P, 0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro.
Conclusions/Significance: Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target.
C1 [Vandenwijngaert, Sara; Pokreisz, Peter; Hermans, Hadewich; Gillijns, Hilde; Pellens, Marijke; Coppiello, Giulia; Oosterlinck, Wouter; Bartunek, Jozef; D'hooge, Jan; Luttun, Aernout; Herregods, Marie Christine; Herijgers, Paul; Janssens, Stefan] Katholieke Univ Leuven, Dept Cardiovasc Sci, Louvain, Belgium.
[Bax, Noortje A. M.; Bouten, Carlijn V. C.] Eindhoven Univ Technol, Dept Biomed Engn, NL-5600 MB Eindhoven, Netherlands.
[Balogh, Agnes; Papp, Zoltan] Univ Debrecen, Med & Hlth Sci Ctr, Res Ctr Mol Med, Div Clin Physiol,Inst Cardiol, H-4012 Debrecen, Hungary.
[Bartunek, Jozef] Onze Lieve Vrouw Hosp, Ctr Cardiovasc, Aalst, Belgium.
[Verbeken, Erik] Katholieke Univ Leuven, Dept Imaging & Pathol, Louvain, Belgium.
[Bloch, Kenneth D.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA USA.
RP Janssens, S (reprint author), Katholieke Univ Leuven, Dept Cardiovasc Sci, Louvain, Belgium.
EM stefan.janssens@med.kuleuven.be
OI Luttun, Aernout/0000-0001-7902-9524
FU Fund for Scientific Research Flanders; Departmental Research Grant of KU
Leuven [PF10/014]; European Research Council [FP-7-StG-IMAGINED 203291];
[TAMOP-4.2.2.A-11/1/KONV-2012-0045]
FX This work was supported by the Fund for Scientific Research Flanders (to
SV, PP, and SJ), and a Departmental Research Grant of KU Leuven
(PF10/014). The work was also supported by the
TAMOP-4.2.2.A-11/1/KONV-2012-0045 project (to AB and ZP), and a European
Research Council Starting Grant FP-7-StG-IMAGINED 203291 (to AL). 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 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 18
PY 2013
VL 8
IS 3
AR e58841
DI 10.1371/journal.pone.0058841
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZS
UT WOS:000316411600013
PM 23527037
ER
PT J
AU Bested, AC
Logan, AC
Selhub, EM
AF Bested, Alison C.
Logan, Alan C.
Selhub, Eva M.
TI Intestinal microbiota, probiotics and mental health: from Metchnikoff to
modern advances: part III - convergence toward clinical trials
SO GUT PATHOGENS
LA English
DT Review
DE Intestinal microbiota; Autointoxication; Depression; Anxiety;
Probiotics; Microbial ecology; Lipopolysaccharide endotoxin; Diet;
Intestinal permeability; MMP-9; Microbial ecosystems
ID IRRITABLE-BOWEL-SYNDROME; BIFIDOBACTERIUM-INFANTIS 35624; FERMENTED
DAIRY PRODUCT; ANXIETY-LIKE BEHAVIOR; QUALITY-OF-LIFE; GUT-BRAIN AXIS;
CAMPYLOBACTER-JEJUNI; VISCERAL HYPERSENSITIVITY;
LACTOBACILLUS-HELVETICUS; COLORECTAL DISTENSION
AB Rapid scientific and technological advances have allowed for a more detailed understanding of the relevance of intestinal microbiota, and the entire body-wide microbiome, to human health and well-being. Rodent studies have provided suggestive evidence that probiotics (e.g. lactobacillus and bifidobacteria) can influence behavior. More importantly, emerging clinical studies indicate that the administration of beneficial microbes, via supplementation and/or fecal microbial transplant (FMT), can influence end-points related to mood state (glycemic control, oxidative status, uremic toxins), brain function (functional magnetic resonance imaging fMRI), and mental outlook (depression, anxiety). However, despite the advances in the area of gastro-biological psychiatry, it becomes clear that there remains an urgent need to explore the value of beneficial microbes in controlled clinical investigations. With the history explored in this series, it is fair to ask if we are now on the cusp of major clinical breakthroughs, or are we merely in the quicksand of Autointoxication II?
C1 [Bested, Alison C.] BC Womens Hosp & Hlth Ctr, Complex Chron Dis Program, Vancouver, BC V6H 3N1, Canada.
[Logan, Alan C.] CAMNR, Mill Valley, CA 94941 USA.
[Selhub, Eva M.] Harvard Univ, Sch Med, Waltham, MA 02453 USA.
[Selhub, Eva M.] Massachusetts Gen Hosp, Waltham, MA 02453 USA.
RP Logan, AC (reprint author), CAMNR, 775 Blithedale Ave Suite 364, Mill Valley, CA 94941 USA.
EM aclnd@cfs-fm.org
FU Genuine Health, Toronto, Canada
FX ACB and EMS have no competing interests. ACL has received consulting
fees from Genuine Health, Toronto, Canada.
NR 132
TC 25
Z9 29
U1 9
U2 107
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-4749
J9 GUT PATHOG
JI Gut Pathogens
PD MAR 16
PY 2013
VL 5
AR 4
DI 10.1186/1757-4749-5-4
PG 13
WC Gastroenterology & Hepatology; Microbiology
SC Gastroenterology & Hepatology; Microbiology
GA 118GQ
UT WOS:000317013300001
PM 23497650
ER
PT J
AU Wang, X
Yu, QM
Wu, Q
Bu, Y
Chang, NN
Yan, SY
Zhou, XH
Zhu, XJ
Xiong, JW
AF Wang, Xu
Yu, Qingming
Wu, Qing
Bu, Ye
Chang, Nan-Nan
Yan, Shouyu
Zhou, Xiao-Hai
Zhu, Xiaojun
Xiong, Jing-Wei
TI Genetic interaction between pku300 and fbn2b controls endocardial cell
proliferation and valve development in zebrafish
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Scotch tape; Cardiac valve development; Endocardial cell proliferation;
Zebrafish
ID ATRIOVENTRICULAR-CANAL FORMATION; CARDIOVASCULAR DEVELOPMENT; CUSHION
DEVELOPMENT; MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR; CARDIAC
DEVELOPMENT; DEVELOPING HEART; NF-ATC; MORPHOGENESIS; PROGENITORS
AB Abnormal cardiac valve morphogenesis is a common cause of human congenital heart disease. The molecular mechanisms regulating endocardial cell proliferation and differentiation into cardiac valves remain largely unknown, although great progress has been made on the endocardial contribution to the atrioventricular cushion and valve formation. We found that scotch tape(te382) (sco(te382)) encodes a novel transmembrane protein that is crucial for endocardial cell proliferation and heart valve development. The zebrafish sco(te382) mutant showed diminished endocardial cell proliferation, lack of heart valve leaflets and abnormal common cardinal and caudal veins. Positional cloning revealed a C946T nonsense mutation of a novel gene pku300 in the sco(te382) locus, which encoded a 540-amino-acid protein on cell membranes with one putative transmembrane domain and three IgG domains. A known G3935T missense mutation of fbn2b was also found similar to 570 kb away from pku300 in sco(te382) mutants. The genetic mutant sco(pku300), derived from sco(te382), only had the C946T mutation of pku300 and showed reduced numbers of atrial endocardial cells and an abnormal common cardinal vein. Morpholino knockdown of fbn2b led to fewer atrial endocardial cells and an abnormal caudal vein. Knockdown of both pku300 and fbn2b phenocopied these phenotypes in sco(te382) genetic mutants. pku300 transgenic expression in endocardial and endothelial cells, but not myocardial cells, partially rescued the atrial endocardial defects in sco(te382)mutants. Mechanistically, pku300 and fbn2b were required for endocardial cell proliferation, endocardial Notch signaling and the proper formation of endocardial cell adhesion and tight junctions, all of which are crucial for cardiac valve development. We conclude that pku300 and fbn2b represent the few genes capable of regulating endocardial cell proliferation and signaling in zebrafish cardiac valve development.
C1 [Wang, Xu; Wu, Qing; Bu, Ye; Chang, Nan-Nan; Yan, Shouyu; Zhou, Xiao-Hai; Zhu, Xiaojun; Xiong, Jing-Wei] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China.
[Yu, Qingming] Massachusetts Gen Hosp, Dept Med Nephrol, Boston, MA 02129 USA.
[Yu, Qingming] Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Xiong, JW (reprint author), Peking Univ, Inst Mol Med, Yi He Yuan Lu 5, Beijing 100871, Peoples R China.
EM jingwei_xiong@pku.edu.cn
RI Xiong, Jing-Wei/A-7113-2011
FU National Key Basic Research Program of China [2010CB529503,
2012CB944501]; National Natural Science Foundation of China [30971662,
31271549]; National Institutes of Health (NIH) [T32-DK07540-22]; March
of Dimes Birth Defects Foundation [1-FY2007-471]; Harvard University
FX This research was funded by the National Key Basic Research Program of
China [grant numbers 2010CB529503 and 2012CB944501]; the National
Natural Science Foundation of China [grant numbers 30971662 and
31271549]; a National Institutes of Health (NIH) training grant [grant
number T32-DK07540-22]; the March of Dimes Birth Defects Foundation
[grant number 1-FY2007-471]; and the Milton Fund from Harvard
University. Deposited in PMC for release after 12 months.
NR 58
TC 6
Z9 6
U1 0
U2 2
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAR 15
PY 2013
VL 126
IS 6
BP 1381
EP 1391
DI 10.1242/jcs.116996
PG 11
WC Cell Biology
SC Cell Biology
GA 139CQ
UT WOS:000318559500010
PM 23418350
ER
PT J
AU Frenkel, D
Huang, ZH
Maron, R
Koldzic, DN
Moskowitz, MA
Weiner, HL
AF Frenkel, Dan
Huang, Zhihong
Maron, Ruth
Koldzic, Djordje N.
Moskowitz, Michael A.
Weiner, Howard L.
TI Neuroprotection by IL-10 producing MOG CD4+ T-cells following ischemic
stroke (vol 233, pg 125, 2005)
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Correction
C1 [Frenkel, Dan; Maron, Ruth; Koldzic, Djordje N.; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
[Huang, Zhihong; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA USA.
[Huang, Zhihong; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Unit, Boston, MA USA.
[Huang, Zhihong; Moskowitz, Michael A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
RP Weiner, HL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
EM hweiner@rics.bwh.harvard.edu
NR 1
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD MAR 15
PY 2013
VL 326
IS 1-2
BP 123
EP 123
DI 10.1016/j.jns.2013.01.027
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 128WA
UT WOS:000317799200024
ER
PT J
AU Li, YX
Wang, XY
Zheng, HY
Wang, CY
Minvielle, S
Magrangeas, F
Avet-Loiseau, H
Shah, PK
Zhang, Y
Munshi, NC
Li, C
AF Li, Yingxiang
Wang, Xujun
Zheng, Haiyang
Wang, Chengyang
Minvielle, Stephane
Magrangeas, Florence
Avet-Loiseau, Herve
Shah, Parantu K.
Zhang, Yong
Munshi, Nikhil C.
Li, Cheng
TI Classify Hyperdiploidy Status of Multiple Myeloma Patients Using Gene
Expression Profiles
SO PLOS ONE
LA English
DT Article
ID PROBE LEVEL; ABNORMALITIES; PATHOGENESIS; PREDICTION; ANEUPLOIDY;
PROGNOSIS
AB Multiple myeloma (MM) is a cancer of antibody-making plasma cells. It frequently harbors alterations in DNA and chromosome copy numbers, and can be divided into two major subtypes, hyperdiploid (HMM) and non-hyperdiploid multiple myeloma (NHMM). The two subtypes have different survival prognosis, possibly due to different but converging paths to oncogenesis. Existing methods for identifying the two subtypes are fluorescence in situ hybridization (FISH) and copy number microarrays, with increased cost and sample requirements. We hypothesize that chromosome alterations have their imprint in gene expression through dosage effect. Using five MM expression datasets that have HMM status measured by FISH and copy number microarrays, we have developed and validated a K-nearest-neighbor method to classify MM into HMM and NHMM based on gene expression profiles. Classification accuracy for test datasets ranges from 0.83 to 0.88. This classification will enable researchers to study differences and commonalities of the two MM subtypes in disease biology and prognosis using expression datasets without need for additional subtype measurements. Our study also supports the advantages of using cancer specific characteristics in feature design and pooling multiple rounds of classification results to improve accuracy. We provide R source code and processed datasets at www.ChengLiLab.org/software.
C1 [Li, Yingxiang; Wang, Xujun; Zheng, Haiyang; Wang, Chengyang; Zhang, Yong; Li, Cheng] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China.
[Minvielle, Stephane; Magrangeas, Florence; Avet-Loiseau, Herve] Univ Nantes, Unite Mixte Genom Canc, Ctr Hosp Univ Nantes, Inserm UMR892,CNRS 6299, Nantes, France.
[Shah, Parantu K.; Li, Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Shah, Parantu K.; Li, Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA.
[Munshi, Nikhil C.] Boston VA Healthcare Syst, Boston, MA USA.
RP Li, C (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China.
EM lch3000@gmail.com
RI Zhang, Yong/B-4838-2011; Magrangeas, Florence/L-3080-2015; Minvielle,
Stephane/K-8251-2015
OI Zhang, Yong/0000-0001-6316-2734;
FU National Basic Research Program of China (973 Program) [2010CB944904];
National Institutes of Health (NIH) [R01 GM077122]; NIH [RO1-124929,
PO1-155258, P50-100007, PO1-78378]; Dept. of Veterans Affairs Merit
Review Awards; Claudia Adams Barr Program in Innovative Basic Cancer
Research; Multiple Myeloma Career Development Award; French National
Research Agency [R08079NS]
FX This work was supported by National Basic Research Program of China (973
Program; No. 2010CB944904) (YL, XW, HZ, CW, YZ) and National Institutes
of Health (NIH) R01 GM077122 (CL). This work was also supported in part
by NIH grants RO1-124929, PO1-155258, P50-100007 and PO1-78378 to NCM
and CL and from the Dept. of Veterans Affairs Merit Review Awards to
NCM. PKS was supported by Claudia Adams Barr Program in Innovative Basic
Cancer Research and the Multiple Myeloma Career Development Award. SM
and FM were supported by French National Research Agency, Grant
R08079NS. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 22
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Z9 2
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 15
PY 2013
VL 8
IS 3
AR e58809
DI 10.1371/journal.pone.0058809
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZC
UT WOS:000316409800032
PM 23554930
ER
PT J
AU Qiu, HB
Zhang, LY
Ren, C
Zeng, ZL
Wu, WJ
Luo, HY
Zhou, ZW
Xu, RH
AF Qiu, Hai-bo
Zhang, Li-yi
Ren, Chao
Zeng, Zhao-lei
Wu, Wen-jing
Luo, Hui-yan
Zhou, Zhi-wei
Xu, Rui-hua
TI Targeting CDH17 Suppresses Tumor Progression in Gastric Cancer by
Downregulating Wnt/beta-Catenin Signaling
SO PLOS ONE
LA English
DT Article
ID LIVER-INTESTINE-CADHERIN; CELL-ADHESION; CARCINOMA; EXPRESSION;
METAPLASIA; CDX2; ACTIVATION; STOMACH; PEPTIDE; RISK
AB Purpose: Gastric cancer remains one of the leading causes of cancer death worldwide. Patients usually present late with local invasion or metastasis, for which there are no effective therapies available. Following previous studies that identified the adhesion molecule Cadherin-17(CDH17) as a potential marker for gastric carcinoma, we performed proof-of-principle studies to develop rational therapeutic approaches targeting CDH17 for treating this disease.
Methods: Immunohistochemistry was used to study the expression of CDH17 in 156 gastric carcinomas, and the relationship between survival and CDH17 expression was studied by multivariate analyses. The effect of RNA interference-mediated knockdown of CDH17 on proliferation of gastric carcinoma cell lines was examined in vitro and in vivo, as well as the effects on downstream signaling by immunoblotting.
Results: CDH17 was consistently up-regulated in human gastric cancers, and overall survival in patients with CDH17 upregulation was poorer than in those without expression of this gene (5 yrs overall survival rate 29.0% vs. 45.0%, P < 0.01). Functional assays demonstrated that CDH17 knockdown inhibited cell proliferation, adhesion, migration, invasion, clonogenicity and induce G0/G1 arrest. In mice, shRNA-mediated CDH17 knockdown markedly inhibits tumor growth; intratumoral injection of CDH17 shRNAs results in significant antitumor effects on transplanted tumor models. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt/beta-catenin signaling.
Conclusion: Our results identify CDH17 as a biomarker of gastric carcinoma and attractive therapeutic target for this aggressive malignancy.
C1 [Qiu, Hai-bo; Ren, Chao; Zeng, Zhao-lei; Wu, Wen-jing; Luo, Hui-yan; Zhou, Zhi-wei; Xu, Rui-hua] State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China.
[Qiu, Hai-bo; Ren, Chao; Zeng, Zhao-lei; Wu, Wen-jing; Luo, Hui-yan; Xu, Rui-hua] Sun Yat Sen Univ, Dept Med Oncol, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China.
[Qiu, Hai-bo; Zhou, Zhi-wei] Sun Yat Sen Univ, Dept Gastr & Pancreat Surg, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China.
[Zhang, Li-yi] Univ Hong Kong, Dept Clin Oncol, Pokfulam, Hong Kong, Peoples R China.
[Qiu, Hai-bo] Dana Farber Canc Inst, Div Surg Oncol, Boston, MA 02115 USA.
[Qiu, Hai-bo] Harvard Univ, Sch Med, Boston, MA USA.
RP Xu, RH (reprint author), State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China.
EM xurh@sysucc.org.cn
FU National Natural Science Foundation [30672408]
FX This work was supported by National Natural Science Foundation (30672408
to RHX). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 29
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U1 1
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 MAR 15
PY 2013
VL 8
IS 3
AR e56959
DI 10.1371/journal.pone.0056959
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109ZC
UT WOS:000316409800005
PM 23554857
ER
PT J
AU McDaid, J
Farkash, EA
Steele, DJR
Martins, PN
Kotton, CN
Elias, N
Ko, DSC
Colvin, RB
Hertl, M
AF McDaid, James
Farkash, Evan A.
Steele, David J. R.
Martins, Paulo N.
Kotton, Camille N.
Elias, Nahel
Ko, Dicken S. C.
Colvin, Robert B.
Hertl, Martin
TI Transitional Cell Carcinoma Arising Within a Pediatric Donor Renal
Transplant in Association With BK Nephropathy
SO TRANSPLANTATION
LA English
DT Letter
ID POLYOMAVIRUS; RECIPIENTS
C1 [McDaid, James; Martins, Paulo N.; Elias, Nahel; Ko, Dicken S. C.; Hertl, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Transplant Surg, Boston, MA 02114 USA.
[Farkash, Evan A.; Colvin, Robert B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Steele, David J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA 02114 USA.
[Kotton, Camille N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA.
[Ko, Dicken S. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA.
RP McDaid, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Transplant Surg, White 5, Boston, MA 02114 USA.
EM jmcdaid@doctors.net.uk
NR 7
TC 6
Z9 6
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 MAR 15
PY 2013
VL 95
IS 5
BP E28
EP E30
DI 10.1097/TP.0b013e31828235ec
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 102UX
UT WOS:000315870900003
PM 23503509
ER
PT J
AU Andrews, JR
Morrow, C
Wood, R
AF Andrews, Jason R.
Morrow, Carl
Wood, Robin
TI Modeling the Role of Public Transportation in Sustaining Tuberculosis
Transmission in South Africa
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE HIV; indoor air quality; mathematical model; transmission; tuberculosis
ID HIGH-INCIDENCE AREA; MYCOBACTERIUM-TUBERCULOSIS; AIRBORNE INFECTION;
MIXING PATTERNS; HIGH HIV; COMMUNITY; RISK; PREVALENCE; AIR; ADOLESCENTS
AB Current tuberculosis notification rates in South Africa are among the highest ever recorded. Although the human immunodeficiency virus epidemic has been a critical factor, the density of respiratory contacts in high-risk environments may be an important and underappreciated driver. Using a modified Wells-Riley model for airborne disease transmission, we estimated the risk of tuberculosis transmission on 3 modes of public transit (minibus taxis, buses, and trains) in Cape Town, South Africa, using exhaled carbon dioxide as a natural tracer gas to evaluate air exchange. Carbon dioxide measurements were performed between October and December of 2011. Environmental risk, reflected in the rebreathed fraction of air, was highest in minibus taxis and lowest in trains; however, the average number of passengers sharing an indoor space was highest in trains and lowest in minibus taxis. Among daily commuters, the annual risk of tuberculosis infection was projected to be 3.5%-5.0% and was highest among minibus taxi commuters. Assuming a duration of infectiousness of 1 year, the basic reproductive number attributable to transportation was more than 1 in all 3 modes of transportation. Given its poor ventilation and high respiratory contact rates, public transportation may play a critical role in sustaining tuberculosis transmission in South African cities.
C1 [Andrews, Jason R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA.
[Morrow, Carl; Wood, Robin] Univ Cape Town, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
RP Andrews, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM Jandrews6@partners.org
OI Andrews, Jason/0000-0002-5967-251X
FU National Institute of Allergy and Infectious Diseases [R01 AI058736,
T32AI007433]; Harvard Global Health Institute
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (grants R01 AI058736 and T32AI007433) and the
Harvard Global Health Institute.
NR 27
TC 20
Z9 20
U1 3
U2 19
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 15
PY 2013
VL 177
IS 6
BP 556
EP 561
DI 10.1093/aje/kws331
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 109NE
UT WOS:000316374500009
PM 23423215
ER
PT J
AU Naeije, R
Vanderpool, R
Dhakal, BP
Saggar, R
Saggar, R
Vachiery, JL
Lewis, GD
AF Naeije, Robert
Vanderpool, Rebecca
Dhakal, Bishnu P.
Saggar, Rajeev
Saggar, Rajan
Vachiery, Jean-Luc
Lewis, Gregory D.
TI Exercise-induced Pulmonary Hypertension Physiological Basis and
Methodological Concerns
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Review
DE pulmonary circulation; pulmonary vascular resistance; pulmonary arterial
compliance; cardiac output; exercise capacity
ID STRESS DOPPLER-ECHOCARDIOGRAPHY; PRESSURE-FLOW RELATIONSHIPS; ARTERY
SYSTOLIC PRESSURE; HEALTHY OLD MEN; SYSTEMIC-SCLEROSIS; CARDIAC-OUTPUT;
HEART-FAILURE; ASYMPTOMATIC CARRIERS; VASCULAR-DISEASE; CIRCULATION
AB Exercise stresses the pulmonary circulation through increases in cardiac output ((Q) over dot) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)-flow relationships ranges from 0.5 to 3 mm Hg.min.L-1. The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a (Q) over dot of less than 10 L.min(-1) or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multi-point PAP-flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase (Q) over dot at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology.
C1 [Naeije, Robert; Vanderpool, Rebecca; Vachiery, Jean-Luc] Erasme Acad Hosp, Dept Cardiol, Pulm Hypertens Clin, Brussels, Belgium.
[Dhakal, Bishnu P.; Lewis, Gregory D.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Saggar, Rajeev; Saggar, Rajan] St Joseph Hosp & Med Ctr, Heart Lung Inst, Phoenix, AZ USA.
RP Naeije, R (reprint author), Univ Libre Brussels, Dept Pathophysiol, Erasme Campus,808 Lennik Rd, B-1070 Brussels, Belgium.
EM rnaeije@ulb.ac.be
FU National Institutes of Health [NIH-K23HL091106]; Fonds de la Recherche
Scientifique Medicale [3.4637.09]; Actelion Chair; Pfizer Aspire Award;
Marie Curie postdoctoral grant, European Respiratory Society
FX Supported by National Institutes of Health grant NIH-K23HL091106
(G.D.L.) Fonds de la Recherche Scientifique Medicale-3.4637.09 (R.N.),
Actelion Chair (R.N.), Pfizer Aspire Award (G.D.L.), Marie Curie
postdoctoral grant, European Respiratory Society (R.V.).
NR 65
TC 74
Z9 76
U1 0
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 15
PY 2013
VL 187
IS 6
BP 576
EP 583
DI 10.1164/rccm.201211-2090CI
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 110DW
UT WOS:000316423800006
PM 23348976
ER
PT J
AU Ganz, PA
Bower, JE
Kwan, L
Castellon, SA
Silverman, DHS
Geist, C
Breen, EC
Irwin, MR
Cole, SW
AF Ganz, Patricia A.
Bower, J. E.
Kwan, L.
Castellon, S. A.
Silverman, D. H. S.
Geist, C.
Breen, E. C.
Irwin, M. R.
Cole, S. W.
TI Does tumor necrosis factor-alpha (TNF-alpha) play a role in
post-chemotherapy cerebral dysfunction?
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Breast cancer; Cognitive complaints; Chemotherapy; Proinflammatory
cytokines; TNF-alpha; Neuropsychological testing; Brain imaging
ID BREAST-CANCER SURVIVORS; FATIGUE SYMPTOM INVENTORY; QUALITY-OF-LIFE;
ADJUVANT CHEMOTHERAPY; COGNITIVE FUNCTION; INFLAMMATORY BIOMARKERS;
LONGITUDINAL ASSESSMENT; CHEMORADIATION THERAPY; SYSTEMIC CHEMOTHERAPY;
POSTMENOPAUSAL WOMEN
AB Post-chemotherapy treated cancer patients frequently report cognitive difficulties. The biology of this phenomenon is poorly understood, with uncertainty about possible direct toxic effects on the brain, secondary effects from systemic inflammation, host factors/genetic predisposition to cognitive complaints, or hormonal changes influencing cognitive function. To elucidate possible mechanisms associated with post-treatment cognitive dysfunction among breast cancer survivors, in 2007 we established a prospective, longitudinal, observational cohort study of early stage breast cancer patients, recruited at the end of initial treatments (primary treatment exposure included surgery, +/- radiation, +/- chemotherapy), and prior to the initiation of adjuvant endocrine therapy. We assessed cognitive complaints, neuropsychological (NP) test performance, markers of inflammation, and brain imaging at baseline, 6 months and 12 months after enrollment. In this analysis of data from the first 93 patients enrolled in the cohort study, we focus on the relationship of circulating levels of proinflammatory cytokines to cerebral functioning and chemotherapy exposure. Among the proinflammatory cytokines tested (IL-1ra, sTNE-RII, CRP, and IL-6) at baseline, only sTNE-RII was increased among chemotherapy exposed patients, with a significant decline in the year after treatment (p = 0.003). Higher baseline sTNE-RII in chemotherapy patients was significantly associated with increased memory complaints. In chemotherapy exposed patients, the longitudinal decline in sTNE-RII was significantly correlated with fewer memory complaints over 12 months (r = -0.34, p = 0.04). Higher baseline sTNE-RII was also associated with relatively diminished brain metabolism in the inferior frontal cortex (r = -0.55, p = 0.02), as well as relatively increased inferior frontal metabolism after 1 year, in chemotherapy-exposed subjects. These preliminary findings suggest that post-chemotherapy increases in TNF-alpha, may be playing an important role in the manifestations of cognitive complaints in breast cancer survivors. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Ganz, Patricia A.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Sangeles, CA USA.
[Ganz, Patricia A.; Cole, S. W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Ganz, Patricia A.; Bower, J. E.; Kwan, L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA.
[Bower, J. E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Bower, J. E.; Breen, E. C.; Irwin, M. R.; Cole, S. W.] Semel Inst Neurosci, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA.
[Castellon, S. A.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
[Silverman, D. H. S.; Geist, C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med & Mol Pharmacol, Los Angeles, CA 90095 USA.
[Breen, E. C.; Irwin, M. R.; Cole, S. W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
RP Ganz, PA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, A2-125 CHS,650 Charles Young Dr South,Box 956900, Los Angeles, CA 90095 USA.
EM pganz@mednet.ucla.edu
RI Irwin, Michael/H-4870-2013
OI Irwin, Michael/0000-0002-1502-8431
FU Breast Cancer Research Foundation (BCRF) [NIH/NCI R01 CA 109650]; an
American Society Clinical Research Professorship; UCLA Older Americans
Independence Center (OAIC); OAIC Inflammatory Biology Core [NIH/NIA
P30-AG028748]; Norman Cousins Center [PNI. R01-AG034588, R01-AG026364,
R01-CA119159, R01-HL079955, R01-HL095799, P30-AG028748, UL RR 033176]
FX NIH/NCI R01 CA 109650; the Breast Cancer Research Foundation (BCRF); an
American Society Clinical Research Professorship to Dr. Ganz; the UCLA
Older Americans Independence Center (OAIC) and the OAIC Inflammatory
Biology Core (NIH/NIA P30-AG028748); the Norman Cousins Center for PNI.
R01-AG034588; R01-AG026364; R01-CA119159; R01-HL079955; R01-HL095799;
P30-AG028748; UL RR 033176 to Dr. Irwin.
NR 60
TC 50
Z9 51
U1 3
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD MAR 15
PY 2013
VL 30
SI SI
BP S99
EP S108
DI 10.1016/j.bbi.2012.07.015
PG 10
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 111GW
UT WOS:000316510800012
PM 22884417
ER
PT J
AU Deutsch, MA
Sturzu, A
Wu, SM
AF Deutsch, Marcus-Andre
Sturzu, Anthony
Wu, Sean M.
TI At a Crossroad Cell Therapy for Cardiac Repair
SO CIRCULATION RESEARCH
LA English
DT Article
DE cardiomyocytes; cardiovascular disease; stem cells; regeneration
ID ACUTE MYOCARDIAL-INFARCTION; MESENCHYMAL STEM-CELLS; LEFT-VENTRICULAR
FUNCTION; CARDIOSPHERE-DERIVED CELLS; RANDOMIZED PHASE-1 TRIAL; MARROW
MONONUCLEAR-CELLS; BONE-MARROW; ISCHEMIC CARDIOMYOPATHY; HUMAN
FIBROBLASTS; PROGENITOR CELLS
C1 [Deutsch, Marcus-Andre; Sturzu, Anthony] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Deutsch, Marcus-Andre] Tech Univ Munich, Dept Cardiovasc Surg, German Heart Ctr Munich, D-80290 Munich, Germany.
[Wu, Sean M.] Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
[Wu, Sean M.] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
RP Wu, SM (reprint author), G1120A Lokey Stem Cell Bldg,265 Campus Dr, Stanford, CA 94305 USA.
EM smwu@stanford.edu
FU NHLBI NIH HHS [U01 HL099776]; NIH HHS [DP2 OD004411]
NR 70
TC 14
Z9 14
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD MAR 15
PY 2013
VL 112
IS 6
BP 884
EP 890
DI 10.1161/CIRCRESAHA.112.275974
PG 7
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 107BO
UT WOS:000316189900005
PM 23493304
ER
PT J
AU Jung, K
Kim, P
Leuschner, F
Gorbatov, R
Kim, JK
Ueno, T
Nahrendorf, M
Yun, SH
AF Jung, Keehoon
Kim, Pilhan
Leuschner, Florian
Gorbatov, Rostic
Kim, Jun Ki
Ueno, Takuya
Nahrendorf, Matthias
Yun, Seok Hyun
TI Endoscopic Time-Lapse Imaging of Immune Cells in Infarcted Mouse Hearts
SO CIRCULATION RESEARCH
LA English
DT Article
DE circulation; imaging; leukocytes; monocyte; myocardial infarction
ID FRACTALKINE RECEPTOR CX(3)CR1; GREEN FLUORESCENT PROTEIN;
MYOCARDIAL-INFARCTION; VIVO; MONOCYTES; ATHEROSCLEROSIS; MICROSCOPY;
RESOLUTION; IDENTIFICATION; INFLAMMATION
AB Rationale: High-resolution imaging of the heart in vivo is challenging owing to the difficulty in accessing the heart and the tissue motion caused by the heartbeat.
Objective: Here, we describe a suction-assisted endoscope for visualizing fluorescently labeled cells and vessels in the beating heart tissue through a small incision made in the intercostal space.
Methods and Results: A suction tube with a diameter of 2 to 3 mm stabilizes the local tissue motion safely and effectively at a suction pressure of 50 mm Hg. Using a minimally invasive endoscope integrated into a confocal microscope, we performed fluorescence cellular imaging in both normal and diseased hearts in live mice for an hour per session repeatedly over a few weeks. Real-time imaging revealed the surprisingly rapid infiltration of CX(3)CR1(+) monocytes into the injured site within several minutes after acute myocardial infarction.
Conclusions: The time-lapse analysis of flowing and rolling (patrolling) monocytes in the heart and the peripheral circulation provides evidence that the massively recruited monocytes come first from the vascular reservoir and later from the spleen. The imaging method requires minimal surgical preparation and can be implemented into standard intravital microscopes. Our results demonstrate the applicability of our imaging method for a wide range of cardiovascular research. (Circ Res. 2013;112:891-899.)
C1 [Jung, Keehoon; Kim, Pilhan; Kim, Jun Ki; Yun, Seok Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Ctr Photomed, Cambridge, MA 02139 USA.
[Leuschner, Florian; Gorbatov, Rostic; Ueno, Takuya; Nahrendorf, Matthias] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02139 USA.
[Kim, Pilhan; Kim, Jun Ki; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol WCU, Taejon 305701, South Korea.
[Yun, Seok Hyun] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA.
[Leuschner, Florian] Heidelberg Univ, Dept Internal Med 3, Heidelberg, Germany.
[Leuschner, Florian] DZHK German Ctr Cardiovasc Res, Heidelberg, Germany.
RP Yun, SH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 65 Landsdowne St Rm 525, Cambridge, MA 02139 USA.
EM syun@hms.harvard.edu
RI Kim, Pilhan/C-1836-2011
OI Kim, Pilhan/0000-0001-8388-1840
FU Massachusetts General Hospital The Executive Committee on Research
Postdoctoral Fellowship; National Institutes of Health [U54CA143837,
R01AI 081734, P41EB015903]; Ministry of Education, Science, and
Technology of Korea [R31-2008-000-10071-0, 2011-0009503, WCI 2011-001]
FX This work was supported by grants from Massachusetts General Hospital
The Executive Committee on Research Postdoctoral Fellowship, National
Institutes of Health (U54CA143837, R01AI 081734, P41EB015903), and the
Ministry of Education, Science, and Technology of Korea (World Class
University R31-2008-000-10071-0, 2011-0009503, and WCI 2011-001).
NR 33
TC 42
Z9 45
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD MAR 15
PY 2013
VL 112
IS 6
BP 891
EP U75
DI 10.1161/CIRCRESAHA.111.300484
PG 29
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 107BO
UT WOS:000316189900006
PM 23392842
ER
PT J
AU Gregoire, S
Karra, R
Passer, D
Deutsch, MA
Krane, M
Feistritzer, R
Sturzu, A
Domian, I
Saga, Y
Wu, SM
AF Gregoire, Serge
Karra, Ravi
Passer, Derek
Deutsch, Marcus-Andre
Krane, Markus
Feistritzer, Rebecca
Sturzu, Anthony
Domian, Ibrahim
Saga, Yumiko
Wu, Sean M.
TI Essential and Unexpected Role of Yin Yang 1 to Promote Mesodermal
Cardiac Differentiation
SO CIRCULATION RESEARCH
LA English
DT Article
DE cardiac development; congenital heart disease; progenitor cell; stem
cell
ID CARDIOVASCULAR PROGENITOR CELLS; ENHANCER-BINDING-PROTEIN; SERUM
RESPONSE FACTOR; HEART TUBE FORMATION; TRANSCRIPTION FACTOR;
GENE-EXPRESSION; OUTFLOW TRACT; SMOOTH-MUSCLE; VENTRAL MORPHOGENESIS;
YY1
AB Rationale: Cardiogenesis is regulated by a complex interplay between transcription factors. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs).
Objective: To identify novel regulators of mesodermal cardiac lineage commitment.
Methods and Results: We performed a bioinformatic-based transcription factor binding site analysis on upstream promoter regions of genes that are enriched in embryonic stem cell-derived CPCs. From 32 candidate transcription factors screened, we found that Yin Yang 1 (YY1), a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1-kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays, in vivo chromatin immunoprecipitation, and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with Gata4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by embryonic stem cell-based assays in which we showed that the overexpression of YY1 enhanced the cardiogenic differentiation of embryonic stem cells into CPCs.
Conclusions: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes. (Circ Res. 2013;112:900-910.)
C1 [Gregoire, Serge; Passer, Derek; Deutsch, Marcus-Andre; Krane, Markus; Feistritzer, Rebecca; Sturzu, Anthony; Domian, Ibrahim; Wu, Sean M.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Karra, Ravi] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA.
[Deutsch, Marcus-Andre; Krane, Markus] Clin Tech Univ Muenchen, German Heart Ctr, Dept Cardiovasc Surg, Munich, Germany.
[Saga, Yumiko] Natl Inst Genet, Div Mammalian Dev, Mishima, Shizuoka 411, Japan.
[Domian, Ibrahim; Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Wu, SM (reprint author), G1120A Lokey Stem Cell Bldg,265 Campus Dr, Stanford, CA 94305 USA.
EM smwu@stanford.edu
FU Massachusetts General Hospital Fund for Medical Discovery; American
Heart Association; German Research Foundation; German Heart Foundation;
National Institute of Health; National Heart, Lung, and Blood Institute;
Harvard Stem Cell Institute
FX Financial support was provided by the Massachusetts General Hospital
Fund for Medical Discovery and the American Heart Association (S. G.),
by the German Research Foundation (M. K.) and the German Heart
Foundation (M-A. D.), and by National Institute of Health Director's New
Innovator Award, the National Heart, Lung, and Blood Institute, and the
Harvard Stem Cell Institute (S.M.W.)
NR 66
TC 18
Z9 19
U1 0
U2 6
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 MAR 15
PY 2013
VL 112
IS 6
BP 900
EP U104
DI 10.1161/CIRCRESAHA.113.259259
PG 28
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 107BO
UT WOS:000316189900007
PM 23307821
ER
PT J
AU Schott, AF
Landis, MD
Dontu, G
Griffith, KA
Layman, RM
Krop, I
Paskett, LA
Wong, H
Dobrolecki, LE
Lewis, MT
Froehlich, AM
Paranilam, J
Hayes, DF
Wicha, MS
Chang, JC
AF Schott, Anne F.
Landis, Melissa D.
Dontu, Gabriela
Griffith, Kent A.
Layman, Rachel M.
Krop, Ian
Paskett, Lacey A.
Wong, Helen
Dobrolecki, Lacey E.
Lewis, Michael T.
Froehlich, Amber M.
Paranilam, Jaya
Hayes, Daniel F.
Wicha, Max S.
Chang, Jenny C.
TI Preclinical and Clinical Studies of Gamma Secretase Inhibitors with
Docetaxel on Human Breast Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MAMMARY STEM-CELLS; CANCER CELLS; NOTCH; CHEMOTHERAPY; EXPRESSION;
RESISTANCE; RECEPTOR; MK-0752; CULTURE; GROWTH
AB Purpose: Accumulating evidence supports the existence of breast cancer stem cells (BCSC), which are characterized by their capacity to self-renew and divide indefinitely and resistance to conventional therapies. The Notch pathway is important for stem cell renewal and is a potential target for BCSC-directed therapy.
Experimental Design: Using human breast tumorgraft studies, we evaluated the impact of gamma secretase inhibitors (GSI) on the BCSC population and the efficacy of combining GSI with docetaxel treatment. The mouse experimental therapy paralleled a concurrent clinical trial in patients with advanced breast cancer, designed to determine the maximum-tolerated dose of the GSI, MK-0752, administered sequentially with docetaxel, and to evaluate BCSC markers in serial tumor biopsies.
Results: Treatment with GSI reduced BCSCs in MC1 and BCM-2147 tumorgrafts by inhibition of the Notch pathway. GSI enhanced the efficacy of docetaxel in preclinical studies. In the clinical trial, 30 patients with advanced breast cancer were treated with escalating doses of MK-0752 plus docetaxel. Clinically, meaningful doses of both drugs were possible with manageable toxicity and preliminary evidence of efficacy. A decrease in CD44(+)/CD24(-), ALDH(+), and mammosphere-forming efficiency were observed in tumors of patients undergoing serial biopsies.
Conclusions: These preclinical data show that pharmacologic inhibition of the Notch pathway can reduce BCSCs in breast tumorgraft models. The clinical trial shows feasibility of combination GSI and chemotherapy, and together these results encourage further study of Notch pathway inhibitors in combination with chemotherapy in breast cancer. Clin Cancer Res; 19(6); 1512-24. (C) 2012 AACR.
C1 [Schott, Anne F.; Griffith, Kent A.; Hayes, Daniel F.; Wicha, Max S.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Landis, Melissa D.; Paskett, Lacey A.; Wong, Helen; Dobrolecki, Lacey E.; Froehlich, Amber M.; Paranilam, Jaya; Chang, Jenny C.] Methodist Hosp, Res Inst, Houston, TX 77030 USA.
[Lewis, Michael T.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Dontu, Gabriela] Kings Coll London, Sch Med, London, England.
[Layman, Rachel M.] Ohio State Univ, Columbus, OH 43210 USA.
[Krop, Ian] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chang, Jenny C.] Weill Cornell Med Sch, New York, NY USA.
RP Schott, AF (reprint author), Univ Michigan, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM aschott@umich.edu
RI Layman, Rachel/E-3475-2011
FU Merck; Sharpe; Dohme [IISP 31841]; NIH [1R01CA138197, U54 1
U54CA149196-01]
FX This work was supported by Merck, Sharpe, and Dohme [grant: IISP #31841
(A.F. Schott, Principal Investigator)]. Preclinical work was also
supported by the NIH (1R01CA138197 and U54 1 U54CA149196-01).
NR 29
TC 71
Z9 75
U1 1
U2 20
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2013
VL 19
IS 6
BP 1512
EP 1524
DI 10.1158/1078-0432.CCR-11-3326
PG 13
WC Oncology
SC Oncology
GA 107BE
UT WOS:000316188900023
PM 23340294
ER
PT J
AU Zhu, AX
Ancukiewicz, M
Supko, JG
Sahani, DV
Blaszkowsky, LS
Meyerhardt, JA
Abrams, TA
McCleary, NJ
Bhargava, P
Muzikansky, A
Sheehan, S
Regan, E
Vasudev, E
Knowles, M
Fuchs, CS
Ryan, DP
Jain, RK
Duda, DG
AF Zhu, Andrew X.
Ancukiewicz, Marek
Supko, Jeffrey G.
Sahani, Dushyant V.
Blaszkowsky, Lawrence S.
Meyerhardt, Jeffrey A.
Abrams, Thomas A.
McCleary, Nadine Jackson
Bhargava, Pankaj
Muzikansky, Alona
Sheehan, Susan
Regan, Eileen
Vasudev, Eamala
Knowles, Michelle
Fuchs, Charles S.
Ryan, David P.
Jain, Rakesh K.
Duda, Dan G.
TI Efficacy, Safety, Pharmacokinetics, and Biomarkers of Cediranib
Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; MYELOID CELLS; SOLID
TUMORS; CANCER; INHIBITOR; AZD2171; RECEPTOR; THERAPY; TARGETS
AB Purpose: We conducted a single-arm phase II study of cediranib, a pan-VEGFR tyrosine kinase inhibitor, in patients with advanced hepatocellular carcinoma (HCC).
Experimental Design: Patients with histologically confirmed measurable advanced HCC and adequate hematologic, hepatic, and renal functions received cediranib 30-mg orally once daily (4 weeks/cycle). The primary endpoint was progression-free survival (PFS) rate at 3 months. Other endpoints included response rates, overall survival (OS), pharmacokinetics (PK), and biomarkers for cediranib.
Results: Cediranib treatment resulted in an estimated 3-month PFS rate of 77% (60%, 99%). Median PFS was 5.3 (3.5,9.7) months, stable disease was seen in 5/17 patients (29%), and median OS was 11.7 (7.5-13.6) months. Grade 3 toxicities included hypertension (29%), hyponatremia (29%), and hyperbilirubinemia (18%). Cediranib PK were comparable to those seen in cancer patients with normal hepatic function. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2, and Ang-2 decreased after cediranib treatment. PFS was inversely correlated with baseline levels of VEGF, sVEGFR2, and bFGF and with on-treatment levels of bFGF and IGF-1, and directly associated with on-treatment levels of IFN-gamma. OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-alpha, CAIX, and CD34(+)CD133(+)CD45(dim) circulating progenitor cells and on-treatment levels of sVEGFR2.
Conclusions: Despite the limitations of primary endpoint selection, cediranib at 30-mg daily showed a high incidence of toxicity and preliminary evidence of antitumor activity in advanced HCC. Hepatic dysfunction did not seem to affect the steady-state PK of cediranib. Exploratory studies suggested proangiogenic and inflammatory factors as potential biomarkers of anti-VEGF therapy in HCC. Clin Cancer Res; 19(6); 1557-66. (C)2013 AACR.
C1 [Zhu, Andrew X.; Ancukiewicz, Marek; Supko, Jeffrey G.; Sahani, Dushyant V.; Blaszkowsky, Lawrence S.; Muzikansky, Alona; Sheehan, Susan; Vasudev, Eamala; Knowles, Michelle; Ryan, David P.; Jain, Rakesh K.; Duda, Dan G.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Meyerhardt, Jeffrey A.; Abrams, Thomas A.; McCleary, Nadine Jackson; Bhargava, Pankaj; Regan, Eileen; Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Zhu, Andrew X.; Ancukiewicz, Marek; Supko, Jeffrey G.; Sahani, Dushyant V.; Blaszkowsky, Lawrence S.; Meyerhardt, Jeffrey A.; Abrams, Thomas A.; McCleary, Nadine Jackson; Bhargava, Pankaj; Vasudev, Eamala; Fuchs, Charles S.; Ryan, David P.; Jain, Rakesh K.; Duda, Dan G.] Harvard Univ, Sch Med, Boston, MA USA.
RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH POB 232, Boston, MA 02114 USA.
EM azhu@partners.org; duda@steele.mgh.harvard.edu
FU Dyax; MedImmune; Roche; US National Cancer Center (NCI) Cancer Therapy
Evaluation Program (CTEP); AstraZeneca; NCI [P01-CA80124, R01-CA115767,
R01-CA126642, R21-CA139168, R01-CA159258]; Department of Defense
[W81XWH-10-1-0016]; American Cancer Society [RSG-11-073-01TBG]
FX A.X. Zhu is a consultant/advisory board member of Sanofi-Aventis,
Bristol-Myers-Squibb, Eisai, Daiichi Sankyo, and Ecelixis. P. Bhargava
is employed by Sanofi Oncology. D. P. Ryan is a consultant/advisory
board member of Genomic Health and Boerhinger Ingelheim. R. K. Jain has
commercial research grants from Dyax, MedImmune, and Roche; ownership
interest (including patents) in XTuit, Enlight, and SynDevRx; and is a
consultant/advisory board member of Dyax, Noxxon, Enlight, XTuit, H&Q
Healthcare Investors, H&Q Life Sciences Investors, and SynDevRx. The
other authors disclosed no potential conflicts of interest.; This study
was supported by US National Cancer Center (NCI) Cancer Therapy
Evaluation Program (CTEP) and AstraZeneca. The research of R. K. Jain is
supported by NCI grants P01-CA80124, R01-CA115767, and R01-CA126642 and
Department of Defense Innovator Award W81XWH-10-1-0016. D. G. Duda is
supported by NCI grants R21-CA139168 and R01-CA159258 and American
Cancer Society grant RSG-11-073-01TBG.
NR 29
TC 29
Z9 33
U1 1
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2013
VL 19
IS 6
BP 1557
EP 1566
DI 10.1158/1078-0432.CCR-12-3041
PG 10
WC Oncology
SC Oncology
GA 107BE
UT WOS:000316188900027
PM 23362324
ER
PT J
AU Drappatz, J
Brenner, A
Wong, ET
Eichler, A
Schiff, D
Groves, MD
Mikkelsen, T
Rosenfeld, S
Sarantopoulos, J
Meyers, CA
Fielding, RM
Elian, K
Wang, XL
Lawrence, B
Shing, MN
Kelsey, S
Castaigne, JP
Wen, PY
AF Drappatz, Jan
Brenner, Andrew
Wong, Eric T.
Eichler, April
Schiff, David
Groves, Morris D.
Mikkelsen, Tom
Rosenfeld, Steve
Sarantopoulos, John
Meyers, Christina A.
Fielding, Robert M.
Elian, Kelly
Wang, Xiaolin
Lawrence, Betty
Shing, Mona
Kelsey, Stephen
Castaigne, Jean Paul
Wen, Patrick Y.
TI Phase I Study of GRN1005 in Recurrent Malignant Glioma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; RECEPTOR-RELATED PROTEIN; DENSITY-LIPOPROTEIN
RECEPTOR; DELIVERY VECTOR ANGIOPEP-2; MEDIATED TRANSCYTOSIS; PACLITAXEL;
TUMORS; GLIOBLASTOMA; TISSUE; VITRO
AB Purpose: GRN1005 is a peptide-drug conjugate with the ability to penetrate the blood-brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor-related protein-1. We conducted a first-in-human phase I trial of GRN1005 in patients with recurrent glioma.
Methods: Patients received GRN1005 by intravenous infusion every 3 weeks. Doses were escalated using a modified Fibonacci scheme. Study objectives included safety, tolerability, identification of the maximum tolerated dose (MTD), pharmacokinetics, and preliminary evidence of efficacy. Tumor extracted from patients undergoing surgery following administration of GRN1005 was analyzed to determine whether therapeutic concentrations of GRN1005 were achieved.
Results: Sixty-three patients received GRN1005 at doses of 30 to 700 mg/m(2) every 3 weeks. Therapy was well tolerated with neutropenia, leucopenia, and fatigue as the most frequent drug-associated grade 3/4 or higher toxicities. The MTD was 650 mg/m(2) every 3 weeks. Dose-limiting toxicities were grade 3 mucositis and grade 4 neutropenia. There was no evidence of central nervous system toxicity or antibody production. Pharmacokinetic analysis showed that exposure to GRN1005 was dose proportional. We observed one complete and two partial responses. Eight of 27 patients dosed >= 420 mg/m(2) had stable disease, which lasted a median of 51 days. Therapeutic concentrations of GRN1005 and free paclitaxel were shown in tumor tissue of surgical patients dosed with >= 200 mg/m(2).
Conclusion: GRN1005 delivers paclitaxel across the BBB and achieves therapeutic concentrations in tumor tissue. It has similar toxicity to paclitaxel and appears to have activity in recurrent glioma. The recommended phase II dose is 650 mg/m(2) every 3 weeks. Clin Cancer Res; 19(6); 1567-76. (C)2013 AACR.
C1 [Drappatz, Jan; Wen, Patrick Y.] Dana Farber Canc Inst, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA.
[Drappatz, Jan; Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurol, Div Canc Neurol, Boston, MA 02115 USA.
[Wong, Eric T.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Eichler, April] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Drappatz, Jan; Wong, Eric T.; Eichler, April; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Drappatz, Jan] UPMC Canc Ctr, Dept Neurol, Div Hematol & Oncol, Pittsburgh, PA USA.
[Drappatz, Jan] UPMC Canc Ctr, Dept Med, Div Hematol & Oncol, Pittsburgh, PA USA.
[Brenner, Andrew; Sarantopoulos, John] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Groves, Morris D.; Meyers, Christina A.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Schiff, David] Univ Virginia, Hlth Sci Ctr, Dept Neurol, Div Neurooncol, Charlottesville, VA 22908 USA.
[Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA.
[Rosenfeld, Steve] Columbia Univ, Neurol Inst, New York, NY USA.
[Fielding, Robert M.] Biol Serv, Boulder, CO USA.
[Elian, Kelly; Lawrence, Betty; Castaigne, Jean Paul] Angiochem Inc, Montreal, PQ, Canada.
[Wang, Xiaolin; Shing, Mona; Kelsey, Stephen] Geron Corp, Menlo Pk, CA USA.
RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM pwen@partners.org
FU Genentech; Angiochem; Geron Corporation; Angiochem, Inc.
FX J. Drappatz is a consultant/advisory board member of Angiochem. M. D.
Groves has received a commercial research grant from Genentech and
honoraria from speakers bureau of Merck, and is a consultant/advisory
board member of Genentech. R. M. Fielding is a consultant/advisory board
member of Angiochem. Immediate family members of K. Elian have ownership
interest (including patents) in Angiochem. S. Kelsey has ownership
interest (including patents) in Geron Corporation. P.Y. Wen has other
commercial research support from Angiochem and Geron Corporation. No
potential conflicts of interest were disclosed by the other authors.;
The study was supported by Angiochem, Inc.
NR 47
TC 33
Z9 34
U1 1
U2 23
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2013
VL 19
IS 6
BP 1567
EP 1576
DI 10.1158/1078-0432.CCR-12-2481
PG 10
WC Oncology
SC Oncology
GA 107BE
UT WOS:000316188900028
PM 23349317
ER
PT J
AU Schoenfeld, JD
Margalit, DN
Kasperzyk, JL
Shui, IM
Rider, JR
Epstein, MM
Meisner, A
Kenfield, SA
Martin, NE
Nguyen, PL
Kantoff, PW
Giovannucci, EL
Stampfer, MJ
Mucci, LA
AF Schoenfeld, Jonathan D.
Margalit, Danielle N.
Kasperzyk, Julie L.
Shui, Irene M.
Rider, Jennifer R.
Epstein, Mara M.
Meisner, Allison
Kenfield, Stacey A.
Martin, Neil E.
Nguyen, Paul L.
Kantoff, Philip W.
Giovannucci, Edward L.
Stampfer, Meir J.
Mucci, Lorelei A.
TI A Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts
Outcome after Radiation Therapy for Localized Prostate Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RIBONUCLEASE-L GENE; RISK; VARIANTS; ASSOCIATION; RADIOTHERAPY; CELLS;
HPC1; PHARMACOGENETICS; HEREDITARY; APOPTOSIS
AB Purpose: To study associations between single nucleotide polymorphisms (SNP) in Ribonuclease L (RNASEL), a gene implicated in inflammation and prostate cancer risk, and outcomes after radiation therapy.
Experimental Design: We followed participants in the prospective US Health Professionals Follow-Up Study treated with radiation therapy for early-stage prostate cancer. Three SNPs were genotyped based on previously determined functional and biological significance. We used multivariable Cox proportional hazards models to assess per-allele associations with the primary outcome defined as time to a composite endpoint including development of lethal prostate cancer or biochemical recurrence.
Results: We followed 434 patients treated with radiation therapy for a median of 9 years. On multivariate analysis, the rs12757998 variant allele was associated with significantly decreased risk of the composite endpoint [HR: 0.65; 95% confidence interval (CI), 0.45-0.94%; P = 0.02] driven by decreased biochemical recurrence (HR: 0.60; 95% CI, 0.40-0.89%; P = 0.01) and men treated with external beam (HR: 0.58; 95% CI, 0.36-0.93%; P = 0.02). In contrast, in 516 men from the same cohort treated with radical prostatectomy, we found no significant impact of this variant on outcome. Furthermore, the rs12757998 variant allele significantly modified the association between androgen deprivation therapy and outcomes after radiation therapy (p-interaction 0.02).
Conclusion: We show an association between RNASEL SNP rs12757998 and outcome after radiation therapy for prostate cancer. This SNP is associated with increased circulating C-reactive protein and interleukin-6, suggesting a potential role for inflammation in the response to radiation. If validated, genetic predictors of outcome may help inform prostate cancer management. Clin Cancer Res; 19(6); 1612-9. (C)2013 AACR.
C1 [Schoenfeld, Jonathan D.] Harvard Radiat Oncol Program, Boston, MA USA.
[Margalit, Danielle N.; Kasperzyk, Julie L.; Rider, Jennifer R.; Martin, Neil E.; Nguyen, Paul L.; Kantoff, Philip W.; Stampfer, Meir J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Margalit, Danielle N.; Martin, Neil E.; Nguyen, Paul L.; Kantoff, Philip W.; Stampfer, Meir J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kasperzyk, Julie L.; Shui, Irene M.; Rider, Jennifer R.; Epstein, Mara M.; Meisner, Allison; Kenfield, Stacey A.; Giovannucci, Edward L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Schoenfeld, JD (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA.
EM jdschoenfeld@partners.org
RI Martin, Neil/E-2193-2014;
OI Martin, Neil/0000-0002-8164-8516; Rider, Jennifer/0000-0002-2637-6036
FU NIH [5 T32 CA09001-36, R25 CA098566]; US Army Prostate Cancer
Post-doctoral Fellowship; anonymous family foundation; Prostate Cancer
Foundation; National Institutes of Health/National Cancer Institute [R01
CA133891, R01CA141298-02, P01 CA055075]
FX J. D. Schoenfeld, J. L. Kasperzyk, and I. M. Shui were supported by NIH
Training Grant 5 T32 CA09001-36 and I. M. Shui was additionally
supported by US Army Prostate Cancer Post-doctoral Fellowship; M. M.
Epstein is supported by National Institutes of Health research training
grant R25 CA098566; P. L. Nguyen was supported by a grant from an
anonymous family foundation; and L. A. Mucci, P. L. Nguyen, and N. E.
Martin are supported by the Prostate Cancer Foundation. The project was
supported by grants from the National Institutes of Health/National
Cancer Institute (grant numbers R01 CA133891, R01CA141298-02, and P01
CA055075).
NR 45
TC 10
Z9 11
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2013
VL 19
IS 6
BP 1612
EP 1619
DI 10.1158/1078-0432.CCR-12-2718
PG 8
WC Oncology
SC Oncology
GA 107BE
UT WOS:000316188900033
PM 23382116
ER
PT J
AU Wang, QQ
Moore, MJ
Adelmant, G
Marto, JA
Silver, PA
AF Wang, Qingqing
Moore, Michael J.
Adelmant, Guillaume
Marto, Jarrod A.
Silver, Pamela A.
TI PQBP1, a factor linked to intellectual disability, affects alternative
splicing associated with neurite outgrowth
SO GENES & DEVELOPMENT
LA English
DT Article
DE PQBP1; alternative splicing; neurite outgrowth; neurological disorders
ID PRE-MESSENGER-RNA; DOMINANT RETINITIS-PIGMENTOSA; POLYGLUTAMINE TRACT;
NERVOUS-SYSTEM; PROTEIN PQBP1; AXON GROWTH; WW DOMAIN; VASE EXON; GENE;
EXPRESSION
AB Polyglutamine-binding protein 1 (PQBP1) is a highly conserved protein associated with neurodegenerative disorders. Here, we identify PQBP1 as an alternative messenger RNA (mRNA) splicing (AS) effector capable of influencing splicing of multiple mRNA targets. PQBP1 is associated with many splicing factors, including the key U2 small nuclear ribonucleoprotein (snRNP) component SF3B1 (subunit 1 of the splicing factor 3B [SF3B] protein complex). Loss of functional PQBP1 reduced SF3B1 substrate mRNA association and led to significant changes in AS patterns. Depletion of PQBP1 in primary mouse neurons reduced dendritic outgrowth and altered AS of mRNAs enriched for functions in neuron projection development. Disease-linked PQBP1 mutants were deficient in splicing factor associations and could not complement neurite outgrowth defects. Our results indicate that PQBP1 can affect the AS of multiple mRNAs and indicate specific affected targets whose splice site determination may contribute to the disease phenotype in PQBP1-linked neurological disorders.
C1 [Wang, Qingqing; Silver, Pamela A.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Moore, Michael J.] Rockefeller Univ, Mol Neurooncol Lab, New York, NY 10065 USA.
[Adelmant, Guillaume; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA.
[Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Silver, Pamela A.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM pamela_silver@hms.harvard.edu
FU National Institutes of Health [GM057476, GM36373]
FX We thank Hsi-Wen Liao, Athar Malik, David Lipton, and Seth Margolis for
help with neuron culture and RNAi; Alan Mardinly for help with Sholl
analysis; Jennifer Waters for help with imaging; and Daniel Ducat and
Yvonne Chen for thoughtful critiques. We are indebted to Michael
Greenberg's laboratory for the generous sharing of mouse embryonic
cortical neurons. Microscope imaging was done in the Nikon Imaging
Center at Harvard Medical School. Sequencing was performed by the
biopolymer facility at Harvard Medical School. This work was supported
by grants GM36373 and GM057476 to P.A.S. from the National Institutes of
Health.
NR 49
TC 20
Z9 23
U1 0
U2 15
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD MAR 15
PY 2013
VL 27
IS 6
BP 615
EP 626
DI 10.1101/gad.212308.112
PG 12
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 108VB
UT WOS:000316323200005
PM 23512658
ER
PT J
AU Baena, E
Shao, Z
Linn, DE
Glass, K
Hamblen, MJ
Fujiwara, Y
Kim, J
Nguyen, M
Zhang, X
Godinho, FJ
Bronson, RT
Mucci, LA
Loda, M
Yuan, GC
Orkin, SH
Li, Z
AF Baena, Esther
Shao, Zhen
Linn, Douglas E.
Glass, Kimberly
Hamblen, Melanie J.
Fujiwara, Yuko
Kim, Jonghwan
Minh Nguyen
Zhang, Xin
Godinho, Frank J.
Bronson, Roderick T.
Mucci, Lorelei A.
Loda, Massimo
Yuan, Guo-Cheng
Orkin, Stuart H.
Li, Zhe
TI ETV1 directs androgen metabolism and confers aggressive prostate cancer
in targeted mice and patients
SO GENES & DEVELOPMENT
LA English
DT Article
DE ERG; ETS transcription factor; ETV1; Pten; androgen receptor; metabolism
ID ETS TRANSCRIPTION FACTORS; EMBRYONIC STEM-CELLS; IN-VIVO; ERG
IMMUNOHISTOCHEMISTRY; RADICAL PROSTATECTOMY; TUMOR-SUPPRESSOR; PSA
RECURRENCE; GENE FUSIONS; EXPRESSION; RECEPTOR
AB Distinguishing aggressive from indolent disease and developing effective therapy for advanced disease are the major challenges in prostate cancer research. Chromosomal rearrangements involving ETS transcription factors, such as ERG and ETV1, occur frequently in prostate cancer. How they contribute to tumorigenesis and whether they play similar or distinct in vivo roles remain elusive. Here we show that in mice with ERG or ETV1 targeted to the endogenous Tmprss2 locus, either factor cooperated with loss of a single copy of Pten, leading to localized cancer, but only ETV1 appeared to support development of invasive adenocarcinoma under the background of full Pten loss. Mechanistic studies demonstrated that ERG and ETV1 control a common transcriptional network but largely in an opposing fashion. In particular, while ERG negatively regulates the androgen receptor (AR) transcriptional program, ETV1 cooperates with AR signaling by favoring activation of the AR transcriptional program. Furthermore, we found that ETV1 expression, but not that of ERG, promotes autonomous testosterone production. Last, we confirmed the association of an ETV1 expression signature with aggressive disease and poorer outcome in patient data. The distinct biology of ETV1-associated prostate cancer suggests that this disease class may require new therapies directed to underlying programs controlled by ETV1.
C1 [Baena, Esther; Shao, Zhen; Hamblen, Melanie J.; Fujiwara, Yuko; Kim, Jonghwan; Minh Nguyen; Godinho, Frank J.; Orkin, Stuart H.; Li, Zhe] Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA.
[Baena, Esther; Shao, Zhen; Hamblen, Melanie J.; Fujiwara, Yuko; Kim, Jonghwan; Minh Nguyen; Godinho, Frank J.; Orkin, Stuart H.; Li, Zhe] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Shao, Zhen; Glass, Kimberly; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Linn, Douglas E.; Zhang, Xin; Li, Zhe] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Hamblen, Melanie J.; Fujiwara, Yuko; Godinho, Frank J.; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Bronson, Roderick T.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Dept Epidemiol, Boston, MA 02115 USA.
[Loda, Massimo] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
RP Orkin, SH (reprint author), Boston Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA.
EM stuart_orkin@dfci.harvard.edu; zli4@rics.bwh.harvard.edu
FU Career Development Award from Dana-Farber/Harvard Cancer Center Prostate
Cancer SPORE; Spanish Ministry of Science [EX2006-0958]; Department of
Defense [PC060492, PC100704, PC080097]; NIH [U01CA105423]
FX We thank Drs. Larisa Litovchick, Carmen Priolo, and Fatima Al-Shahrour
for reagents, mouse surgical techniques, analysis support, and helpful
discussions, and Dr. Maaike van Bragt for FACS analysis of knock-in
mammary glands. This work was supported by a Career Development Award
from Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (to Z.L.),
a post-doctoral award from the Spanish Ministry of Science (EX2006-0958
to E.B.), and grants from the Department of Defense (PC060492 to S.H.O.,
PC100704 to Z.L., and PC080097 to E.B.) and NIH (U01CA105423 to S.H.O.).
S.H.O. is an Investigator of Howard Hughes Medical Institute.
NR 72
TC 52
Z9 52
U1 0
U2 10
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD MAR 15
PY 2013
VL 27
IS 6
BP 683
EP 698
DI 10.1101/gad.211011.112
PG 16
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 108VB
UT WOS:000316323200010
PM 23512661
ER
PT J
AU Valencia, A
Sapp, E
Kimm, JS
McClory, H
Reeves, PB
Alexander, J
Ansong, KA
Masso, N
Frosch, MP
Kegel, KB
Li, XY
DiFiglia, M
AF Valencia, Antonio
Sapp, Ellen
Kimm, Jeffrey S.
McClory, Hollis
Reeves, Patrick B.
Alexander, Jonathan
Ansong, Kwadwo A.
Masso, Nicholas
Frosch, Matthew P.
Kegel, Kimberly B.
Li, Xueyi
DiFiglia, Marian
TI Elevated NADPH oxidase activity contributes to oxidative stress and cell
death in Huntington's disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID TRANSGENIC MOUSE MODEL; LIPID RAFTS; INTRANUCLEAR INCLUSIONS; NEURITE
OUTGROWTH; MUTANT HUNTINGTIN; CYTOCHROME-C; EARLY MOTOR; ACTIVATION;
NEURONS; BRAIN
AB A mutation in the huntingtin (Htt) gene produces mutant Htt and Huntington's disease (HD), a neurodegenerative disorder. HD patients have oxidative damage in the brain, but the causes are unclear. Compared with controls, we found brain levels of NADPH oxidase (NOX) activity, which produces reactive oxygen species (ROS), elevated in human HD postmortem cortex and striatum and highest in striatum of presymptomatic individuals. Synaptosome fractions from cortex and striatum of HD140Q/140Q mice had elevated NOX activity at 3 months of age and a further rise at 6 and 12 months compared with synaptosomes of age-matched wild-type (WT) mice. High NOX activity in primary cortical and striatal neurons of HD140Q/140Q mice correlated with more ROS and neurite swellings. These features and neuronal cell death were markedly reduced by treatment with NOX inhibitors such as diphenyleneiodonium (DPI), apocynin (APO) and VAS2870. The rise in ROS levels in mitochondria of HD140Q/140Q neurons followed the rise in NOX activity and inhibiting only mitochondrial ROS was not neuroprotective. Mutant Htt colocalized at plasma membrane lipid rafts with gp91-phox, a catalytic subunit for the NOX2 isoform. Assembly of NOX2 components at lipid rafts requires activation of Rac1 which was also elevated in HD140Q/140Q neurons. HD140Q/140Q mice bred to gp91-phox knock-out mice had lower NOX activity in the brain and in primary neurons, and neurons had normal ROS levels and significantly improved survival. These findings suggest that increased NOX2 activity at lipid rafts is an early and major source of oxidative stress and cell death in HD140Q/140Q neurons.
C1 [Valencia, Antonio; Sapp, Ellen; Kimm, Jeffrey S.; McClory, Hollis; Reeves, Patrick B.; Alexander, Jonathan; Ansong, Kwadwo A.; Masso, Nicholas; Kegel, Kimberly B.; Li, Xueyi; DiFiglia, Marian] Massachusetts Gen Hosp East, Dept Neurol, Charlestown, MA 02129 USA.
[Valencia, Antonio; Sapp, Ellen; Kimm, Jeffrey S.; McClory, Hollis; Reeves, Patrick B.; Alexander, Jonathan; Ansong, Kwadwo A.; Masso, Nicholas; Kegel, Kimberly B.; Li, Xueyi; DiFiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Pathol Serv, Boston, MA 02114 USA.
[Frosch, Matthew P.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP DiFiglia, M (reprint author), Massachusetts Gen Hosp East, Dept Neurol, 114,16th St,Room 2002, Charlestown, MA 02129 USA.
EM difiglia@helix.mgh.harvard.edu
FU Hereditary Disease Foundation; Fundacion Mexico en Harvard A.C.; CHDI
Foundation; HDSA Foundation; NIH-NINDS [NS74381]
FX This study was supported by fellowships from the Hereditary Disease
Foundation to A.V. and X.L., Fundacion Mexico en Harvard A.C. to A.V.,
and CHDI and HDSA Foundations and NIH-NINDS NS74381 to M.D.
NR 86
TC 50
Z9 53
U1 2
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 MAR 15
PY 2013
VL 22
IS 6
BP 1112
EP 1131
DI 10.1093/hmg/dds516
PG 20
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 108MD
UT WOS:000316296600005
PM 23223017
ER
PT J
AU Das, F
Ghosh-Choudhury, N
Bera, A
Dey, N
Abboud, HE
Kasinath, BS
Choudhury, GG
AF Das, Falguni
Ghosh-Choudhury, Nandini
Bera, Amit
Dey, Nirmalya
Abboud, Hanna E.
Kasinath, Balakuntalam S.
Choudhury, Goutam Ghosh
TI Transforming Growth Factor beta Integrates Smad 3 to Mechanistic Target
of Rapamycin Complexes to Arrest Deptor Abundance for Glomerular
Mesangial Cell Hypertrophy
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MESSENGER-RNA TRANSLATION; PLASMINOGEN-ACTIVATOR INHIBITOR-1;
SMOOTH-MUSCLE-CELLS; RICTOR-MTOR COMPLEX; HIGH GLUCOSE;
DIABETIC-NEPHROPATHY; SIGNAL-TRANSDUCTION; MAMMALIAN TARGET; FIBRONECTIN
EXPRESSION; MESENCHYMAL TRANSITION
AB In many renal diseases, transforming growth factor beta (TGF beta)-stimulated canonical Smad 3 and noncanonical mechanistic target of rapamycin (mTOR) promote increased protein synthesis and mesangial cell hypertrophy. The cellular underpinnings involving these signaling molecules to regulate mesangial cell hypertrophy are not fully understood. Deptor has recently been identified as an mTOR interacting protein and functions as an endogenous inhibitor of the kinase activity for both TORC1 and TORC2. Prolonged incubation of mesangial cells with TGF beta reduced the levels of deptor concomitant with an increase in TORC1 and TORC2 activity. Sustained TGF beta activation was required to inhibit association of deptor with mTOR, whereas rapid activation had no effect. Using the mTOR inhibitor PP242, we found that TGF beta-induced both early and sustained activation of TORC1 and TORC2 was necessary for deptor suppression. PP242-induced reversal of deptor suppression by TGF beta was associated with a significant inhibition of TGF beta-stimulated protein synthesis and hypertrophy. Interestingly, expression of siRNA against Smad 3 or Smad 7, which blocks TGF beta receptor-specific Smad 3 signaling, prevented TGF beta-induced suppression of deptor abundance and TORC1/2 activities. Furthermore, overexpression of Smad 3 decreased deptor expression similar to TGF beta stimulation concomitant with increased TORC1 and TORC2 activities. Finally, knockdown of deptor reversed Smad 7-mediated inhibition of protein synthesis and mesangial cell hypertrophy induced by TGF beta. These data reveal the requirement of both early and late activation of mTOR for TGF beta-induced protein synthesis. Our results support that TGF beta-stimulated Smad 3 acts as a key node to instill a feedback loop between deptor down-regulation and TORC1/2 activation in driving mesangial cell hypertrophy.
C1 [Ghosh-Choudhury, Nandini; Abboud, Hanna E.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Vet Affairs Res, San Antonio, TX 78229 USA.
[Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Das, Falguni; Bera, Amit; Dey, Nirmalya; Abboud, Hanna E.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
EM choudhuryg@uthscsa.edu
FU National Institutes of Health [RO1 DK50190, RO1 AR 52425, RO1 DK 78971,
RO1 DK 077295, RC2A 036613]; Veterans Affairs Merit Review grants;
Ronald P. Williams Orthopedic Oncology Developmental Research Award from
the Cancer Therapy and Research Center, San Antonio; Juvenile Diabetes
Research Foundation; Veterans Affairs Research Service; Veterans Affairs
Senior Research Career Scientist Award; Juvenile Diabetes Research
Foundation [1-2008-185]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant RO1 DK50190 and Veterans Affairs Merit Review grants (to G.
G. C.).; Supported by National Institutes of Health Grant RO1 AR 52425,
Veterans Affairs Merit Review grants, and a Ronald P. Williams
Orthopedic Oncology Developmental Research Award from the Cancer Therapy
and Research Center, San Antonio.; Supported by National Institutes of
Health Grant RO1 DK 78971 and Veterans Affairs Merit Review and Juvenile
Diabetes Research Foundation grants.; Supported by National Institutes
of Health Grants RO1 DK 077295 and RC2A 036613 and the Veterans Affairs
Research Service.; Recipient of Veterans Affairs Senior Research Career
Scientist Award and supported by Juvenile Diabetes Research Foundation
Grant 1-2008-185.
NR 65
TC 10
Z9 12
U1 2
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 15
PY 2013
VL 288
IS 11
BP 7756
EP 7768
DI 10.1074/jbc.M113.455782
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 110OW
UT WOS:000316455300031
PM 23362262
ER
PT J
AU Villiger, M
Zhang, EZ
Nadkarni, S
Oh, WY
Bouma, BE
Vakoc, BJ
AF Villiger, Martin
Zhang, Ellen Ziyi
Nadkarni, Seemantini
Oh, Wang-Yuhl
Bouma, Brett E.
Vakoc, Benjamin J.
TI Artifacts in polarization-sensitive optical coherence tomography caused
by polarization mode dispersion
SO OPTICS LETTERS
LA English
DT Article
ID FIBERS; NOISE
AB Polarization mode dispersion (PMD) severely degrades images of biological tissue measured with polarization-sensitive optical coherence tomography. It adds a bias to the local retardation value that can be spatially confined, resulting in regions of seemingly high sample birefringence that are purely artificial. Here, we demonstrate and analyze this effect, both experimentally and with numerical simulations, and show that artifacts can be avoided by limiting the system PMD to less than the system axial resolution. Even then, spatial averaging over a dimension larger than that characteristic of speckle is required to remove a PMD-induced bias of the local retardation values. (C) 2013 Optical Society of America
C1 [Villiger, Martin; Zhang, Ellen Ziyi; Nadkarni, Seemantini; Bouma, Brett E.; Vakoc, Benjamin J.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Villiger, Martin; Zhang, Ellen Ziyi; Nadkarni, Seemantini; Bouma, Brett E.; Vakoc, Benjamin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Oh, Wang-Yuhl] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea.
[Bouma, Brett E.; Vakoc, Benjamin J.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02142 USA.
RP Villiger, M (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM mvilliger@partners.org
FU NIH [P41EB015903, ROI CA163528]; NRF of Korea [2012-0005633]; Swiss
National Science Foundation
FX Research in this publication was supported in part by the NIH grants
P41EB015903 and ROI CA163528, and by the NRF of Korea, grant
2012-0005633. M. V. was supported by a fellowship from the Swiss
National Science Foundation.
NR 10
TC 13
Z9 13
U1 1
U2 8
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 0146-9592
J9 OPT LETT
JI Opt. Lett.
PD MAR 15
PY 2013
VL 38
IS 6
BP 923
EP 925
PG 3
WC Optics
SC Optics
GA 111SK
UT WOS:000316540800039
PM 23503261
ER
PT J
AU Rhee, HW
Zou, P
Udeshi, ND
Martell, JD
Mootha, VK
Carr, SA
Ting, AY
AF Rhee, Hyun-Woo
Zou, Peng
Udeshi, Namrata D.
Martell, Jeffrey D.
Mootha, Vamsi K.
Carr, Steven A.
Ting, Alice Y.
TI Proteomic Mapping of Mitochondria in Living Cells via Spatially
Restricted Enzymatic Tagging
SO SCIENCE
LA English
DT Article
ID PROTOPORPHYRINOGEN OXIDASE; CROSS-LINK; HEME; PEROXIDASE; BIOTINYLATION;
BIOSYNTHESIS; MICROSCOPY; TYRAMIDE; DISEASE; COMPLEX
AB Microscopy and mass spectrometry (MS) are complementary techniques: The former provides spatiotemporal information in living cells, but only for a handful of recombinant proteins at a time, whereas the latter can detect thousands of endogenous proteins simultaneously, but only in lysed samples. Here, we introduce technology that combines these strengths by offering spatially and temporally resolved proteomic maps of endogenous proteins within living cells. Our method relies on a genetically targetable peroxidase enzyme that biotinylates nearby proteins, which are subsequently purified and identified by MS. We used this approach to identify 495 proteins within the human mitochondrial matrix, including 31 not previously linked to mitochondria. The labeling was exceptionally specific and distinguished between inner membrane proteins facing the matrix versus the intermembrane space (IMS). Several proteins previously thought to reside in the IMS or outer membrane, including protoporphyrinogen oxidase, were reassigned to the matrix by our proteomic data and confirmed by electron microscopy. The specificity of peroxidase-mediated proteomic mapping in live cells, combined with its ease of use, offers biologists a powerful tool for understanding the molecular composition of living cells.
C1 [Rhee, Hyun-Woo; Zou, Peng; Martell, Jeffrey D.; Ting, Alice Y.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Udeshi, Namrata D.; Mootha, Vamsi K.; Carr, Steven A.; Ting, Alice Y.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA.
[Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
RP Ting, AY (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM ating@mit.edu
FU NIH [DP1 OD003961, R01 GM077465]; Dreyfus Foundation; American Chemical
Society; Broad Institute of MIT and Harvard
FX We thank N. Watson (Whitehead Institute Keck Microscopy Facility) and E.
Vasile (Koch Institute Microscopy Core Facility) for performing EM
imaging, H. B. Fraser for assistance with data analysis and manuscript
editing, C. Uttamapinant for picoyl azide-AF647, X. Zhuang and her lab
for advice on STORM, H. A. Dailey for advice on CPOX and PPOX, and S.
Calvo for assistance with data analysis. Funding was provided by the NIH
(grants DP1 OD003961 to A.Y.T. and R01 GM077465 to V. K. M.), the
Dreyfus Foundation (A.Y.T.), the American Chemical Society (A.Y.T.), and
the Broad Institute of MIT and Harvard (S. A. C.). The authors have no
conflicting financial interests. A patent application relating to the
use of enzymes for proteomic mapping in live cells has been filed by
MIT. Proteomic data can be found in supplementary tables S1 to S9. The
authors will make the genetic constructs used in this work widely
available to the academic community through Addgene (www.addgene.org/).
NR 26
TC 150
Z9 153
U1 11
U2 163
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 MAR 15
PY 2013
VL 339
IS 6125
BP 1328
EP 1331
DI 10.1126/science.1230593
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105GC
UT WOS:000316053400040
PM 23371551
ER
PT J
AU Tevaarwerk, AJ
Gray, RJ
Schneider, BP
Smith, ML
Wagner, LI
Fetting, JH
Davidson, N
Goldstein, LJ
Miller, KD
Sparano, JA
AF Tevaarwerk, Amye J.
Gray, Robert J.
Schneider, Bryan P.
Smith, Mary Lou
Wagner, Lynne I.
Fetting, John H.
Davidson, Nancy
Goldstein, Lori J.
Miller, Kathy D.
Sparano, Joseph A.
TI Survival in patients with metastatic recurrent breast cancer after
adjuvant chemotherapy Little Evidence of Improvement Over the Past 30
Years
SO CANCER
LA English
DT Article
DE breast cancer; distant disease recurrence; survival; distant
recurrence-free interval; metastatic disease
ID COOPERATIVE-ONCOLOGY-GROUP; PROGNOSTIC-FACTORS; RANDOMIZED-TRIALS; PLUS
DOCETAXEL; PHASE-III; STAGE IV; THERAPY; WOMEN; INTERGROUP;
POSTMENOPAUSAL
AB BACKGROUND: Population-based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy. METHODS: Adjuvant chemotherapy trials coordinated by the Eastern Cooperative Oncology Group that accrued patients between 1978 and 2002 were reviewed. Survival after distant disease recurrence was estimated for progressive time periods, and adjusted for baseline covariates in a Cox proportional hazards model. RESULTS: Of the 13,785 patients who received adjuvant chemotherapy in 11 trials, 3447 (25%) developed distant disease recurrence; the median survival after recurrence was 20 months (95% confidence interval, 19 months-21 months). Factors associated with inferior survival included a shorter distant recurrence-free interval (DRFI), estrogen receptor-negative and progesterone receptor-negative disease, the number of positive axillary lymph nodes present at the time of diagnosis, and black race (P < .0001 for all). When the time period of recurrence was added to the model, it was not found to be significantly associated with survival for the general population with disease recurrence. Survival improved over time only in those patients with hormone receptor-negative disease with a DRFI 3 years, both among the 5 most recent and the entire trial data sets (P = .01 and P = .05, respectively). CONCLUSIONS: In contrast to reports from population-based studies, no general improvement in survival was observed over the last 30 years for patients who developed distant disease recurrence after adjuvant chemotherapy after adjusting for DRFI. Improved survival for patients with hormone receptor-negative disease with a short DRFI suggests a benefit from trastuzumab. Cancer 2013. (c) 2012 American Cancer Society.
C1 [Tevaarwerk, Amye J.] Univ Wisconsin, Med Oncol Clin, Carbone Comprehens Canc Ctr, Madison, WI 53705 USA.
[Gray, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Schneider, Bryan P.; Miller, Kathy D.] Indiana Univ, Dept Med, Div Hematol Oncol, Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA.
[Smith, Mary Lou] Res Advocacy Network, Plano, TX USA.
[Wagner, Lynne I.] Northwestern Univ, Dept Psychiat & Behav Sci, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
[Fetting, John H.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA.
[Davidson, Nancy] Univ Pittsburgh, Dept Med, Inst Canc, Pittsburgh, PA USA.
[Goldstein, Lori J.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Sparano, Joseph A.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
RP Tevaarwerk, AJ (reprint author), Univ Wisconsin, Med Oncol Clin, Carbone Comprehens Canc Ctr, 1111 Highland Ave,Room 6037, Madison, WI 53705 USA.
EM at4@medicine.wisc.edu
FU Public Health Service grants [CA23318, CA66636, CA21115, CA21076,
CA49883, CA17145, CA16116, CA39229, CA27525, CA14958]; Department of
Health and Human Services; National Cancer Institute, National
Institutes of Health
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, CA21076, CA49883, CA17145,
CA16116, CA39229, CA27525, and CA14958 and from the National Cancer
Institute, 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 31
TC 35
Z9 35
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2013
VL 119
IS 6
BP 1140
EP 1148
DI 10.1002/cncr.27819
PG 9
WC Oncology
SC Oncology
GA 100JW
UT WOS:000315696600007
PM 23065954
ER
PT J
AU Hur, C
Miller, M
Kong, CY
Dowling, EC
Nattinger, KJ
Dunn, M
Feuer, EJ
AF Hur, Chin
Miller, Melecia
Kong, Chung Yin
Dowling, Emily C.
Nattinger, Kevin J.
Dunn, Michelle
Feuer, Eric J.
TI Trends in esophageal adenocarcinoma incidence and mortality
SO CANCER
LA English
DT Article
DE esophageal neoplasms; adenocarcinoma; incidence; mortality;
epidemiology; SEER program
ID BARRETTS-ESOPHAGUS; UNITED-STATES; RISING INCIDENCE; GASTRIC CARDIA;
CANCER; SURVEILLANCE; SURVIVAL; EPIDEMIOLOGY; DIAGNOSIS; RATES
AB BACKGROUND: Over the past several decades, the incidence of esophageal adenocarcinoma (EAC) has rapidly increased. The purpose of this analysis was to examine temporal trends in EAC incidence and mortality within the US population and, in addition, to explore these trends within subgroups of the population. METHODS: The National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER 9) data were used to examine incidence and incidence-based (IB) mortality in EAC from 1975 to 2009. Secular trends in incidence and IB mortality by cancer stage, sex, and race were further characterized using the NCI's Joinpoint Regression program. RESULTS: Based on SEER 9 data, EAC incidence and IB mortality continues to increase in the United States. However, since the mid-1990s, the overall rate of increase in both EAC incidence and IB mortality appears to be slowing. In addition, in early-stage cancers, there is a noticeable leveling off of IB mortality rates and divergence from incidence starting in the late 1990s. Over the study period, the average annual percentage increase in incidence was 6.1% in men and 5.9% in women. CONCLUSIONS: EAC incidence and IB mortality rates continue to rise in the United States, although at a slower rate in more recent years. In early-stage cancers, IB mortality and incidence rates have diverged primarily because IB mortality rates have plateaued beginning in the late 1990s. Although EAC continues to be less common in women, the rate of increase in EAC incidence is similar in both sexes. Cancer 2013. (c) 2012 American Cancer Society.
C1 [Hur, Chin; Miller, Melecia; Kong, Chung Yin; Dowling, Emily C.; Nattinger, Kevin J.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Hur, Chin; Nattinger, Kevin J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Hur, Chin; Kong, Chung Yin] Harvard Univ, Sch Med, Boston, MA USA.
[Dunn, Michelle; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Hur, C (reprint author), ITA, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM chur@partners.org
OI Hur, Chin/0000-0002-2819-7576
FU National Institutes of Health [R01CA140574, U01CA152926, K25CA133141]
FX This work was supported by the National Institutes of Health (grants
R01CA140574 and U01CA152926 to Dr. Hur and grant K25CA133141 to Dr.
Kong).
NR 22
TC 102
Z9 103
U1 2
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2013
VL 119
IS 6
BP 1149
EP 1158
DI 10.1002/cncr.27834
PG 10
WC Oncology
SC Oncology
GA 100JW
UT WOS:000315696600008
PM 23303625
ER
PT J
AU Brawarsky, P
Neville, BA
Fitzmaurice, GM
Earle, C
Haas, JS
AF Brawarsky, Phyllis
Neville, Bridget A.
Fitzmaurice, Garrett M.
Earle, Craig
Haas, Jennifer S.
TI Surveillance after resection for colorectal cancer
SO CANCER
LA English
DT Article
DE colorectal cancer; survivorship; disparities; race; ethnicity;
surveillance
ID FOLLOW-UP; RACIAL-DIFFERENCES; CLINICAL-ONCOLOGY; AMERICAN-SOCIETY;
UNITED-STATES; POPULATION; COLONOSCOPY; GUIDELINES; DIAGNOSIS; SURVIVORS
AB BACKGROUND: Professional societies recommend posttreatment surveillance for colorectal cancer (CRC) survivors. This study describes the use of surveillance over time, with a particular focus on racial/ethnic disparities, and also examines the role of area characteristics, such as capacity for CRC screening, on surveillance. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify individuals aged 66 to 85 years who were diagnosed with CRC from 1993 to 2005 and treated with surgery. The study examined factors associated with subsequent receipt of a colonoscopy, carcinoembryonic antigen (CEA) testing, primary care (PC) visits, and a composite measure of overall surveillance. RESULTS: Of eligible subjects, 61.0% had a colonoscopy, 68.0% had CEA testing, 77.1% had PC visits, and 43.0% received overall surveillance. After adjustment, blacks were less likely than whites to undergo colonoscopy (odds ratio [OR] 0.76, 95% confidence interval [CI] = 0.69-0.83) and to receive CEA testing and overall surveillance, whereas white/Hispanic rates did not differ. Rates for all outcomes increased from 1993 to 2005, but black/white disparities remained. Individuals in areas with greatest capacity for CRC screening were more likely (OR = 1.09, 95% CI = 1.02-1.18) to receive colonoscopy, and those in areas with the greatest percentage of blacks were less likely (OR = 0.89, 95% CI = 0.83-0.95) to receive colonoscopy. Those living in areas with shortage of PC were less likely to receive PC visits (OR = 0.55, 95% CI = 0.48-0.64) and overall surveillance (OR = 0.83, 95% CI = 0.71-0.98). CONCLUSIONS: Many CRC survivors do not get recommended surveillance, and black/white disparities in rates of surveillance have not improved. Characteristics of the area where an individual lives contribute to the use of surveillance. Cancer 2013. (c) 2012 American Cancer Society.
C1 [Brawarsky, Phyllis; Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02120 USA.
[Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Fitzmaurice, Garrett M.] McLean Hosp, Lab Psychiat Biostat, Belmont, MA 02178 USA.
[Fitzmaurice, Garrett M.; Haas, Jennifer S.] Harvard Univ, Sch Med, Boston, MA 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, 1620 Tremont St, Boston, MA 02120 USA.
EM jhaas@partners.org
FU American Cancer Society [RSGT CPHPS-114979]
FX This study was supported by a grant from the American Cancer Society
(RSGT CPHPS-114979).
NR 28
TC 6
Z9 7
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2013
VL 119
IS 6
BP 1235
EP 1242
DI 10.1002/cncr.27852
PG 8
WC Oncology
SC Oncology
GA 100JW
UT WOS:000315696600018
PM 23184361
ER
PT J
AU Chubiz, JEC
Lee, JM
Gilmore, ME
Kong, CY
Lowry, KP
Halpern, EF
McMahon, PM
Ryan, PD
Gazelle, GS
AF Chubiz, Jessica E. Cott
Lee, Janie M.
Gilmore, Michael E.
Kong, Chung Y.
Lowry, Kathryn P.
Halpern, Elkan F.
McMahon, Pamela M.
Ryan, Paula D.
Gazelle, G. Scott
TI Cost-effectiveness of alternating magnetic resonance imaging and digital
mammography screening in BRCA1 and BRCA2 gene mutation carriers
SO CANCER
LA English
DT Article
DE BRCA1 gene; BRCA2 gene; breast neoplasms; cancer screening; cost
effectiveness
ID REDUCING SALPINGO-OOPHORECTOMY; HIGH FAMILIAL RISK; BREAST-CANCER; FILM
MAMMOGRAPHY; PERFORMANCE BENCHMARKS; AMERICAN-COLLEGE; WOMEN; CARE; MRI;
SURVEILLANCE
AB BACKGROUND: Current clinical guidelines recommend earlier, more intensive breast cancer screening with both magnetic resonance imaging (MRI) and mammography for women with breast cancer susceptibility gene (BRCA) mutations. Unspecified details of screening schedules are a challenge for implementing guidelines. METHODS: A Markov Monte Carlo computer model was used to simulate screening in asymptomatic women who were BRCA1 and BRCA2 mutation carriers. Three dual-modality strategies were compared with digital mammography (DM) alone: 1) DM and MRI alternating at 6-month intervals beginning at age 25 years (Alt25), 2) annual MRI beginning at age 25 years with alternating DM added at age 30 years (MRI25/Alt30), and 3) DM and MRI alternating at 6-month intervals beginning at age 30 years (Alt30). Primary outcomes were quality-adjusted life years (QALYs), lifetime costs (in 2010 US dollars), and incremental cost-effectiveness (dollars per QALY gained). Additional outcomes included potential harms of screening, and lifetime costs stratified into component categories (screening and diagnosis, treatment, mortality, and patient time costs). RESULTS: All 3 dual-modality screening strategies increased QALYs and costs. Alt30 screening had the lowest incremental costs per additional QALY gained (BRCA1, $74,200 per QALY; BRCA2, $215,700 per QALY). False-positive test results increased substantially with dual-modality screening and occurred more frequently in BRCA2 carriers. Downstream savings in both breast cancer treatment and mortality costs were outweighed by increases in up-front screening and diagnosis costs. The results were influenced most by estimates of breast cancer risk and MRI costs. CONCLUSIONS: Alternating MRI and DM screening at 6-month intervals beginning at age 30 years was identified as a clinically effective approach to applying current guidelines, and was more cost-effective in BRCA1 gene mutation carriers compared with BRCA2 gene mutation carriers. Cancer 2013. (c) 2012 American Cancer Society.
C1 [Chubiz, Jessica E. Cott; Lee, Janie M.; Gilmore, Michael E.; Kong, Chung Y.; Lowry, Kathryn P.; Halpern, Elkan F.; McMahon, Pamela M.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Lee, Janie M.; Kong, Chung Y.; Lowry, Kathryn P.; Halpern, Elkan F.; McMahon, Pamela M.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA.
[Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Ryan, Paula D.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
RP Lee, JM (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM janie@mgh-ita.org
FU National Institutes of Health (NIH) [NIH K07-CA128816, NIH K25-CA133141,
NIH R00-CA126147]; Harvard Medical School Office for Enrichment
Programming; National Cancer Institute [U01CA63740, U01CA86076,
U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040,
HHSN261201100031C]
FX This work was supported by National Institutes of Health (NIH) grants
NIH K07-CA128816 (Dr. Lee), NIH K25-CA133141 (Dr. Kong), and NIH
R00-CA126147 (Dr. McMahon) and by the Harvard Medical School Office for
Enrichment Programming (Dr. Lowry). Provision of selected model input
parameter values by the Breast Cancer Surveillance Consortium (BCSC) was
supported by the National Cancer Institute (U01CA63740, U01CA86076,
U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040,
and HHSN261201100031C).
NR 56
TC 12
Z9 12
U1 1
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2013
VL 119
IS 6
BP 1266
EP 1276
DI 10.1002/cncr.27864
PG 11
WC Oncology
SC Oncology
GA 100JW
UT WOS:000315696600022
ER
PT J
AU Winkfield, KM
Gabeau, D
AF Winkfield, Karen M.
Gabeau, Darlene
TI Why Workforce Diversity in Oncology Matters
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID DISPARITIES; IMPACT
C1 [Winkfield, Karen M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Gabeau, Darlene] Roger Williams Radiat Therapy, 21st Century Oncol, Providence, RI USA.
RP Winkfield, KM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA.
EM kwinkfield@partners.org
NR 10
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2013
VL 85
IS 4
BP 900
EP 901
DI 10.1016/j.ijrobp.2012.11.004
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 101YC
UT WOS:000315809300017
PM 23452453
ER
PT J
AU Childs, SK
Chen, YH
Duggan, MM
Golshan, M
Pochebit, S
Punglia, RS
Wong, JS
Bellon, JR
AF Childs, Stephanie K.
Chen, Yu-Hui
Duggan, Margaret M.
Golshan, Mehra
Pochebit, Stephen
Punglia, Rinaa S.
Wong, Julia S.
Bellon, Jennifer R.
TI Impact of Margin Status on Local Recurrence After Mastectomy for Ductal
Carcinoma In Situ
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID SKIN-SPARING MASTECTOMY; BREAST-CONSERVATION; RADIATION-THERAPY;
RADIOTHERAPY; CANCER; DCIS
AB Purpose: To examine the rate of local recurrence according to the margin status for patients with pure ductal carcinoma in situ (DCIS) treated by mastectomy.
Methods and Materials: One hundred forty-five consecutive women who underwent mastectomy with or without radiation therapy for DCIS from 1998 to 2005 were included in this retrospective analysis. Only patients with pure DCIS were eligible; patients with microinvasion were excluded. The primary endpoint was local recurrence, defined as recurrence on the chest wall; regional and distant recurrences were secondary endpoints. Outcomes were analyzed according to margin status (positive, close (<= 2 mm), or negative), location of the closest margin (superficial, deep, or both), nuclear grade, necrosis, receptor status, type of mastectomy, and receipt of hormonal therapy.
Results: The primary cohort consisted of 142 patients who did not receive postmastectomy radiation therapy (PMRT). For those patients, the median follow-up time was 7.6 years (range, 0.6-13.0 years). Twenty-one patients (15%) had a positive margin, and 23 patients (16%) had a close (<= 2 mm) margin. The deep margin was close in 14 patients and positive in 6 patients. The superficial margin was close in 13 patients and positive in 19 patients. One patient experienced an isolated invasive chest wall recurrence, and 1 patient had simultaneous chest wall, regional nodal, and distant metastases. The crude rates of chest wall recurrence were 2/142 (1.4%) for all patients, 1/21 (4.8%) for those with positive margins, 1/23 (4.3%) for those with close margins, and 0/98 for patients with negative margins. PMRT was given as part of the initial treatment to 3 patients, 1 of whom had an isolated chest wall recurrence.
Conclusions: Mastectomy for pure DCIS resulted in a low rate of local or distant recurrences. Even with positive or close mastectomy margins, the rates of chest wall recurrences were so low that PMRT is likely not warranted. (C) 2013 Elsevier Inc.
C1 [Childs, Stephanie K.] Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
[Chen, Yu-Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Chen, Yu-Hui] Faulkner Hosp, Dept Surg, Boston, MA USA.
[Pochebit, Stephen] Faulkner Hosp, Dept Pathol, Boston, MA USA.
[Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Punglia, Rinaa S.; Wong, Julia S.; Bellon, Jennifer R.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Duggan, Margaret M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Bellon, JR (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM jbellon@lroc.harvard.edu
NR 15
TC 8
Z9 8
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2013
VL 85
IS 4
BP 948
EP 952
DI 10.1016/j.ijrobp.2012.07.2377
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 101YC
UT WOS:000315809300026
PM 22975615
ER
PT J
AU Elnahal, SM
Kerstiens, J
Helsper, RS
Zietman, AL
Johnstone, PAS
AF Elnahal, Shereef M.
Kerstiens, John
Helsper, Richard S.
Zietman, Anthony L.
Johnstone, Peter A. S.
TI Proton Beam Therapy and Accountable Care: The Challenges Ahead
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID COST-EFFECTIVENESS; MEDICARE; ORGANIZATIONS
AB Purpose: Proton beam therapy (PBT) centers have drawn increasing public scrutiny for their high cost. The behavior of such facilities is likely to change under the Affordable Care Act. We modeled how accountable care reform may affect the financial standing of PBT centers and their incentives to treat complex patient cases.
Methods and Materials: We used operational data and publicly listed Medicare rates to model the relationship between financial metrics for PBT center performance and case mix (defined as the percentage of complex cases, such as pediatric central nervous system tumors). Financial metrics included total daily revenues and debt coverage (daily revenues - daily debt payments). Fee-for-service (FFS) and accountable care (ACO) reimbursement scenarios were modeled. Sensitivity analyses were performed around the room time required to treat noncomplex cases: simple (30 minutes), prostate (24 minutes), and short prostate (15 minutes). Sensitivity analyses were also performed for total machine operating time (14, 16, and 18 h/d).
Results: Reimbursement under ACOs could reduce daily revenues in PBT centers by up to 32%. The incremental revenue gained by replacing 1 complex case with noncomplex cases was lowest for simple cases and highest for short prostate cases. ACO rates reduced this incremental incentive by 53.2% for simple cases and 41.7% for short prostate cases. To cover daily debt payments after ACO rates were imposed, 26% fewer complex patients were allowable at varying capital costs and interest rates. Only facilities with total machine operating times of 18 hours per day would cover debt payments in all scenarios.
Conclusions: Debt-financed PBT centers will face steep challenges to remain financially viable after ACO implementation. Paradoxically, reduced reimbursement for noncomplex cases will require PBT centers to treat more such cases over cases for which PBT has demonstrated superior outcomes. Relative losses will be highest for those facilities focused primarily on treating noncomplex cases. (C) 2013 Elsevier Inc.
C1 [Elnahal, Shereef M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kerstiens, John; Johnstone, Peter A. S.] Indiana Univ, Proton Therapy Ctr, Bloomington, IN USA.
[Helsper, Richard S.] Genesis HealthCare Syst, Zanesville, OH USA.
[Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Johnstone, Peter A. S.] Indiana Univ Sch Med, Dept Radiat Oncol, Indianapolis, IN USA.
RP Elnahal, SM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM selnahal@partners.org
NR 16
TC 10
Z9 10
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2013
VL 85
IS 4
BP E165
EP E172
DI 10.1016/j.ijrobp.2012.10.038
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 101YC
UT WOS:000315809300001
PM 23265572
ER
PT J
AU Shah, A
Paly, JJ
Efstathiou, JA
Bekelman, JE
AF Shah, Anand
Paly, Jonathan J.
Efstathiou, Jason A.
Bekelman, Justin E.
TI Physician Evaluation of Internet Health Information on Proton Therapy
for Prostate Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article; Proceedings Paper
CT 54th Annual Meeting of the American-Society-of-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
ID QUALITY
AB Purpose: Many patients considering prostate cancer (PCa) treatment options report seeking proton beam therapy (PBT) based in part on information readily available on the Internet. There is, however, potential for considerable variation in Internet health information (IHI). We thus evaluated the characteristics, quality, and accuracy of IHI on PBT for PCa.
Methods and Materials: We undertook a qualitative research study using snowball-purposive sampling in which we evaluated the top 50 Google search results for "proton prostate cancer." Quality was evaluated on a 5-point scale using the validated 15-question DISCERN instrument. Accuracy was evaluated by comparing IHI with the best available evidence.
Results: Thirty-seven IHI websites were included in the final sample. These websites most frequently were patient information/support resources (46%), were focused exclusively on PBT (51%), and had a commercial affiliation (38%). There was a significant difference in quality according to the type of IHI. Substantial inaccuracies were noted in the study sample compared with best available or contextual evidence.
Conclusions: There are shortcomings in quality and accuracy in consumer-oriented IHI on PBT for PCa. Providers must be prepared to educate patients how to critically evaluate IHI related to PBT for PCa to best inform their treatment decisions. (C) 2013 Elsevier Inc.
C1 [Shah, Anand; Bekelman, Justin E.] Univ Penn, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Bekelman, Justin E.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Bekelman, Justin E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Shah, Anand] Columbia Univ, Med Ctr, Dept Radiat Oncol, New York, NY 10032 USA.
[Paly, Jonathan J.; Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA.
RP Shah, A (reprint author), Columbia Univ, Med Ctr, Dept Radiat Oncol, 622 W 168th St, New York, NY 10032 USA.
EM as4351@columbia.edu
FU NCI NIH HHS [L30 CA142482]
NR 17
TC 8
Z9 8
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2013
VL 85
IS 4
BP E173
EP E177
DI 10.1016/j.ijrobp.2012.10.039
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 101YC
UT WOS:000315809300002
PM 23245278
ER
PT J
AU Sandoval, GJ
Graham, DB
Bhattacharya, D
Sleckman, BP
Xavier, RJ
Swat, W
AF Sandoval, Gabriel J.
Graham, Daniel B.
Bhattacharya, Deepta
Sleckman, Barry P.
Xavier, Ramnik J.
Swat, Wojciech
TI Cutting Edge: Cell-Autonomous Control of IL-7 Response Revealed in a
Novel Stage of Precursor B Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LIGHT-CHAIN RECOMBINATION; LYMPHOCYTE DEVELOPMENT; REGULATORY FACTOR-4;
MYC; GENE; EXPRESSION; LEUKEMIA; RECEPTOR; SLP-65; ACTIVATION
AB During early stages of B-lineage differentiation in bone marrow, signals emanating from IL-7R and pre-BCR are thought to synergistically induce proliferative expansion of progenitor cells. Paradoxically, loss of pre-BCR-signaling components is associated with leukemia in both mice and humans. Exactly how progenitor B cells perform the task of balancing proliferative burst dependent on IL-7 with the termination of IL-7 signals and the initiation of L chain gene rearrangement remains to be elucidated. In this article, we provide genetic and functional evidence that the cessation of the IL-7 response of pre-B cells is controlled via a cell-autonomous mechanism that operates at a discrete developmental transition inside Fraction C' (large pre-BII) marked by transient expression of c-Myc. Our data indicate that pre-BCR cooperates with IL-7R in expanding the pre-B cell pool, but it is also critical to control the differentiation program shutting off the c-Myc gene in large pre-B cells. The Journal of Immunology, 2013, 190: 2485-2489.
C1 [Sandoval, Gabriel J.; Graham, Daniel B.; Bhattacharya, Deepta; Sleckman, Barry P.; Swat, Wojciech] Washington Univ, Sch Med, Dept Pathol & Immunol, Div Immunobiol, St Louis, MO 63110 USA.
[Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Broad Inst, Cambridge, MA 02138 USA.
RP Swat, W (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 South Euclid Ave, St Louis, MO 63110 USA.
EM swat@wustl.edu
FU National Institutes of Health [R01AI061077, R01AI073718, DK083756,
DK043351, AI047829, K01 DK078318]; Leukemia and Lymphoma Society
FX This work was supported by National Institutes of Health Grants
R01AI061077 and R01AI073718 (to W.S.), DK083756 and DK043351 (to
R.J.X.), AI047829 (to B.P.S.), and K01 DK078318 (to D.B.) as well as a
Leukemia and Lymphoma Society Scholar Award (to W.S.) and Special
Fellowship Award (to D.B.G.).
NR 27
TC 5
Z9 5
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2013
VL 190
IS 6
BP 2485
EP 2489
DI 10.4049/jimmunol.1203208
PG 5
WC Immunology
SC Immunology
GA 099XG
UT WOS:000315657200004
PM 23420891
ER
PT J
AU Balkaya, M
Krober, J
Gertz, K
Peruzzaro, S
Endres, M
AF Balkaya, Mustafa
Kroeber, Jan
Gertz, Karen
Peruzzaro, Sarah
Endres, Matthias
TI Characterization of long-term functional outcome in a murine model of
mild brain ischemia
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Mild brain ischemia; Middle cerebral artery occlusion; Long-term
functional outcome; Behavioral characterization
ID MIDDLE CEREBRAL-ARTERY; ADHESIVE REMOVAL TEST; ENVIRONMENTAL ENRICHMENT;
STROKE RESEARCH; AGED RATS; MOUSE; MICE; DEFICITS; NEUROPROTECTION;
SENSORIMOTOR
AB Evaluation of functional outcome over the course of several weeks after ischemia is a key component in improving the clinical relevance of experimental stroke studies. Using a battery of behavioral tests, we characterized functional outcome in mice over 4 weeks following 30 min of proximal middle cerebral artery occlusion (MCAo). We evaluated rotarod, chimney, pole and cylinder tests to assess short term functional deficits in a transient stroke model which induces infarcts mainly in the striatum. The corner test, adhesive removal test, cylinder test, catwalk, paw preference test and novel tests of rotation were evaluated for long-term functional outcome. Rotarod detected deficits within the first week and pole test was reliable up to intermediate time points after MCAo. Corner test, adhesive removal test, catwalk and paw preference test detected deficits for up to 4 weeks, as did the novel corner rotation and bowl tests. Chimney and cylinder test did not prove useful in our model of mild stroke. In summary, we established the pole test and rotarod as useful tools to evaluate sensory motor deficits early after mild stroke, and corner test and adhesive removal test at later time-points. Alternatively, corner rotation may be a suitable test of long-term function. Test batteries may be further complemented by catwalk and paw preference test for clinically relevant deficits. There was no correlation of behavioral outcome with lesion size at 28 days, and determining whether these tests are useful for detecting a potential benefit of neuroprotective or regenerative therapies requires further testing. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Balkaya, Mustafa; Kroeber, Jan; Gertz, Karen; Peruzzaro, Sarah; Endres, Matthias] Charite, Klin Hsch Ambulanz Neurol, D-10117 Berlin, Germany.
[Kroeber, Jan; Gertz, Karen; Endres, Matthias] Charite, Ctr Stroke Res Berlin, D-10117 Berlin, Germany.
[Endres, Matthias] Charite, Ctr Excellence Neurocure, D-10117 Berlin, Germany.
RP Balkaya, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, 149 13th St, Charlestown, MA 02129 USA.
EM mgokalpbalkaya@partners.org
RI Gertz, Karen/J-1603-2015
FU Deutsche Forschungsgemeinschaft [SFB TRR43, Exc257]; Volkswagen Stiftung
(Lichtenberg Program); Bundesministerium fur Bildung und Forschung
(Center for Stroke Research Berlin); European Union's Seventh Framework
Programme (FP7) [201024, 202213]
FX This work was supported by the Deutsche Forschungsgemeinschaft (SFB
TRR43 and Exc257 to M.E.), the Volkswagen Stiftung (Lichtenberg Program
to M.E.), the Bundesministerium fur Bildung und Forschung (Center for
Stroke Research Berlin), the European Union's Seventh Framework
Programme (FP7/2008-2013) under grant agreements No 201024 and No 202213
(European Stroke Network, WP7 'stroke model platform').
NR 28
TC 28
Z9 29
U1 0
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD MAR 15
PY 2013
VL 213
IS 2
BP 179
EP 187
DI 10.1016/j.jneumeth.2012.12.021
PG 9
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 098NY
UT WOS:000315557200003
PM 23291083
ER
PT J
AU van Scheltinga, AFT
Bakker, SC
van Haren, NEM
Derks, EM
Buizer-Voskamp, JE
Boos, HBM
Cahn, W
Pol, HEH
Ripke, S
Ophoff, RA
Kahn, RS
AF van Scheltinga, Afke F. Terwisscha
Bakker, Steven C.
van Haren, Neeltje E. M.
Derks, Eske M.
Buizer-Voskamp, Jacobine E.
Boos, Heleen B. M.
Cahn, Wiepke
Pol, Hilleke E. Hulshoff
Ripke, Stephan
Ophoff, Roel A.
Kahn, Rene S.
CA Psychiat Genome-wide Assoc Study
TI Genetic Schizophrenia Risk Variants Jointly Modulate Total Brain and
White Matter Volume
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Endophenotype; genome-wide; imaging; psychiatric; SNPs; structural MRI
ID COMMON SNPS; IN-VIVO; ASSOCIATION; SUSCEPTIBILITY; ABNORMALITIES;
HERITABILITY; METAANALYSIS; MORPHOLOGY; DISORDERS; PSYCHOSIS
AB Background: Thousands of common single nucleotide polymorphisms (SNPs) are weakly associated with schizophrenia. It is likely that subsets of disease-associated SNPs are associated with distinct heritable disease-associated phenotypes. Therefore, we examined the shared genetic susceptibility modulating schizophrenia and brain volume.
Methods: Odds ratios for genome-wide SNP data were calculated in the sample collected by the Psychiatric Genome-wide Association Study Consortium (8690 schizophrenia patients and 11,831 control subjects, excluding subjects from the present study). These were used to calculate individual polygenic schizophrenia (risk) scores in an independent sample of 152 schizophrenia patients and 142 healthy control subjects with available structural magnetic resonance imaging scans.
Results: In the entire group, the polygenic schizophrenia score was significantly associated with total brain volume (R-2 = 048, p = 1.6 x 10(-4)) and white matter volume (R-2 = .051, p = 8.6 x 10(-5)) equally in patients and control subjects. The number of (independent) SNPs that substantially influenced both disease risk and white matter (n = 2020) was much smaller than the entire set of SNPs that modulated disease status (n = 14,751). From the set of 2020 SNPs, a group of 186 SNPs showed most evidence for association with white matter volume and an explorative functional analysis showed that these SNPs were located in genes with neuronal functions.
Conclusions: These results indicate that a relatively small subset of schizophrenia genetic risk variants is related to the (normal) development of white matter. This, in turn, suggests that disruptions in white matter growth increase the susceptibility to develop schizophrenia.
C1 [van Scheltinga, Afke F. Terwisscha; Bakker, Steven C.; van Haren, Neeltje E. M.; Buizer-Voskamp, Jacobine E.; Boos, Heleen B. M.; Cahn, Wiepke; Pol, Hilleke E. Hulshoff; Ophoff, Roel A.; Kahn, Rene S.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, NL-3584 CX Utrecht, Netherlands.
[Derks, Eske M.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands.
[Ripke, Stephan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA.
RP van Scheltinga, AFT (reprint author), Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Huispost A00-241,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.
EM aterwiss@umcutrecht.nl
RI Cichon, Sven/H-8803-2013; Hulshoff Pol, Hilleke/B-4795-2014; Hansen,
Thomas/O-5965-2014; Melle, Ingrid /B-4858-2011; McQuillin,
Andrew/C-1623-2008; Derks, Eske/A-1652-2017;
OI Thygesen, Johan H/0000-0002-7479-3459; Mattheisen,
Manuel/0000-0002-8442-493X; Suvisaari, Jaana/0000-0001-7167-0990;
Bruggeman, Richard/0000-0002-3238-8471; Stefansson,
Hreinn/0000-0002-9331-6666; Agartz, Ingrid/0000-0002-9839-5391; Nothen,
Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426;
Andreassen, Ole A./0000-0002-4461-3568; Visscher,
Peter/0000-0002-2143-8760; Cichon, Sven/0000-0002-9475-086X; Hulshoff
Pol, Hilleke/0000-0002-2038-5281; Myin-Germeys,
Inez/0000-0002-3731-4930; lichtenstein, paul/0000-0003-3037-5287;
Hansen, Thomas/0000-0001-6703-7762; Melle, Ingrid /0000-0002-9783-548X;
McQuillin, Andrew/0000-0003-1567-2240; Derks, Eske/0000-0002-6292-6883;
Rethelyi, Janos/0000-0002-3641-012X; Bergen, Sarah/0000-0002-5888-0034;
KELLER, MATTHEW/0000-0002-6075-9882; Zammit, Stanley/0000-0002-2647-9211
FU Zorg Onderzoek Nederland; Medische Wetenschappen [91686137]; Dutch Brain
Foundation [14F06(2)-34]; Top Institute Pharma [T5-203]; Medische
Wetenschappen, within the Mental Health program [10.000.1001]; National
Institute of Mental Health [RO1 MG078075]; Psychiatric Genomics
Consortium; Eli Lilly; Janssen Pharmaceutica; GlaxoSmithKline;
Bristol-Myers Squibb; AstraZeneca Pharmaceuticals; Pfizer; Forest
Pharmaceuticals; Novartis; Solvay; Generation Scotland; Genetics Health
Initiative; Organon; Foundation for the National Institutes of Health;
Shire; Forest; Merck; PGxHealth (a division of Clinical Data, Inc.);
Roche Diagnostics; Vanda Pharmaceuticals; Eli Lilly Company; Golden
Helix, Inc.; InforMed Insights; Janssen; EGIS; H. Lundbeck A/S; Richter;
Schering-Plough; Johnson Johnson; Janssen-Cilag; Hospira (Mayne);
Hospira; Janssen Cilag; Denmark-Aarhus group
FX This work was supported by a Veni grant from Zorg Onderzoek Nederland,
Medische Wetenschappen to SCB (the Dutch organization for health
research and development, project number: 91686137), by a grant from the
Dutch Brain Foundation to SCB [Grant 14F06(2)-34], and by Top Institute
Pharma (project T5-203). The Genetic Risk and Outcome of Psychosis
project was supported by a Grant from Zorg Onderzoek Nederland, Medische
Wetenschappen, within the Mental Health program (project number:
10.000.1001). Genome-wide association study of this sample was funded by
the National Institute of Mental Health (Grant RO1 MG078075 to RAO).;
All individual authors on this paper declare no biomedical financial
interests or potential conflicts of interest. The following are
financial disclosures for the Psychiatric Genomics Consortium: Eli Lilly
funded portions of the genotyping for the Clinical Antipsychotic Trials
of Intervention Effectiveness Study and TOP. PFS received research
funding from Eli Lilly in connection with the Clinical Antipsychotic
Trials of Intervention Effectiveness Study. TSS received research
funding from Eli Lilly and consulting fees from Janssen Pharmaceutica,
GlaxoSmithKline, and Bristol-Myers Squibb. JAL received research funding
from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, GlaxoSmithKline,
Janssen Pharmaceutica, and Pfizer and consulting and educational fees
from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly,
Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica,
Novartis, Pfizer, and Solvay. DStC received research funding from
GlaxoSmithKline and Generation Scotland, Genetics Health Initiative. FA
received funds from Pfizer, Organon, and the Foundation for the National
Institutes of Health. DWB has received research support from Shire and
Forest, has been on the speakers' bureau for Pfizer, and has received
consulting honoraria from Forest and Jazz. TW has received consulting
and lecture fees from H. Lundbeck A/S. OAA has received Speaker's
honorarium from AstraZeneca, Janssen, Bristol-Myers Squibb, and
GlaxoSmithKline. IM has received a Speaker's honorarium from Janssen and
AstraZeneca. AKM has received consulting fees or honoraria from Eli
Lilly & Company, Janssen Pharmaceutica, Merck, Bristol-Meyers Squibb,
Pfizer, PGxHealth (a division of Clinical Data, Inc.), Roche
Diagnostics, and Vanda Pharmaceuticals and has received research support
from Eli Lilly & Company. TL has received consulting fees or honoraria
from Merck, Eli Lilly & Company, Golden Helix, Inc., InforMed Insights,
and PGxHealth (a division of Clinical Data, Inc.). IB has been an
advisory board member, consultant, and lecturer for AstraZeneca,
Bristol-Myers Squibb, Eli Lilly, EGIS, Janssen, H. Lundbeck A/S,
Novartis, Pfizer, Richter, and Schering-Plough and received a grant for
an investigator-initiated study from H. Lundbeck A/S. JJM has received
consulting and speaker's fees from Johnson & Johnson, Schering-Plough
and Eli Lilly. CP has received grant support from Janssen-Cilag, Eli
Lilly, Hospira (Mayne), and AstraZeneca; provided consultancy to
Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, Pfizer, and
Schering-Plough; and has undertaken investigator-initiated studies
supported by Eli Lilly, Hospira, Janssen Cilag, and AstraZeneca. The
Denmark-Aarhus group (The GEMSStud [Genetic and Phenotypic Architecture
of Metabolic Syndrome-Associated Components in Dyslipidemic and
Normolipidemic Subjects Study] with principal investigators ADB, OM, and
PBM) received research funding from H. Lundbeck A/S. EGJ has served as
an unpaid consultant for Eli Lilly.
NR 32
TC 22
Z9 22
U1 1
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 15
PY 2013
VL 73
IS 6
BP 525
EP 531
DI 10.1016/j.biopsych.2012.08.017
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 093JA
UT WOS:000315186700007
ER
PT J
AU Johnson, JR
Tchesnokova, V
Johnston, B
Clabots, C
Roberts, PL
Billig, M
Riddell, K
Rogers, P
Qin, X
Butler-Wu, S
Price, LB
Aziz, M
Nicolas-Chanoine, MH
DebRoy, C
Robicsek, A
Hansen, G
Urban, C
Platell, J
Trott, DJ
Zhanel, G
Weissman, SJ
Cookson, BT
Fang, FC
Limaye, AP
Scholes, D
Chattopadhyay, S
Hooper, DC
Sokurenko, EV
AF Johnson, James R.
Tchesnokova, Veronika
Johnston, Brian
Clabots, Connie
Roberts, Pacita L.
Billig, Mariya
Riddell, Kim
Rogers, Peggy
Qin, Xuan
Butler-Wu, Susan
Price, Lance B.
Aziz, Maliha
Nicolas-Chanoine, Marie-Helene
DebRoy, Chitrita
Robicsek, Ari
Hansen, Glen
Urban, Carl
Platell, Joanne
Trott, Darren J.
Zhanel, George
Weissman, Scott J.
Cookson, Brad T.
Fang, Ferric C.
Limaye, Ajit P.
Scholes, Delia
Chattopadhyay, Sujay
Hooper, David C.
Sokurenko, Evgeni V.
TI Abrupt Emergence of a Single Dominant Multidrug-Resistant Strain of
Escherichia coli
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Escherichia coli infections; antimicrobial resistance; extended-spectrum
beta-lactamase; CTX-M-15; fluoroquinolone resistance; multidrug
resistance; sequence type ST131; multilocus sequence typing; molecular
epidemiology; FimH
ID SEQUENCE TYPE ST131; EXTRAINTESTINAL INFECTIONS; UNITED-STATES;
MECHANISMS; ANIMALS; CLONE
AB Background. Fluoroquinolone-resistant Escherichia coli are increasingly prevalent. Their clonal origins-potentially critical for control efforts-remain undefined.
Methods. Antimicrobial resistance profiles and fine clonal structure were determined for 236 diverse-source historical (1967-2009) E. coli isolates representing sequence type ST131 and 853 recent (2010-2011) consecutive E. coli isolates from 5 clinical laboratories in Seattle, Washington, and Minneapolis, Minnesota. Clonal structure was resolved based on fimH sequence (fimbrial adhesin gene: H subclone assignments), multilocus sequence typing, gyrA and parC sequence (fluoroquinolone resistance-determining loci), and pulsed-field gel electrophoresis.
Results. Of the recent fluoroquinolone-resistant clinical isolates, 52% represented a single ST131 subclonal lineage, H30, which expanded abruptly after 2000. This subclone had a unique and conserved gyrA/parC allele combination, supporting its tight clonality. Unlike other ST131 subclones, H30 was significantly associated with fluoroquinolone resistance and was the most prevalent subclone among current E. coli clinical isolates, overall (10.4%) and within every resistance category (11%-52%).
Conclusions. Most current fluoroquinolone-resistant E. coli clinical isolates, and the largest share of multidrug-resistant isolates, represent a highly clonal subgroup that likely originated from a single rapidly expanded and disseminated ST131 strain. Focused attention to this strain will be required to control the fluoroquinolone and multidrug-resistant E. coli epidemic.
C1 [Johnson, James R.; Johnston, Brian; Clabots, Connie] VA Med Ctr, Minneapolis, MN 55417 USA.
[Johnson, James R.; Johnston, Brian; Clabots, Connie] Univ Minnesota, Minneapolis, MN USA.
[Tchesnokova, Veronika; Billig, Mariya; Cookson, Brad T.; Fang, Ferric C.; Chattopadhyay, Sujay; Sokurenko, Evgeni V.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA.
[Roberts, Pacita L.; Limaye, Ajit P.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Riddell, Kim; Rogers, Peggy] Grp Hlth Cooperat Puget Sound, Grp Hlth Clin Lab, Seattle, WA USA.
[Qin, Xuan] Seattle Childrens Hosp, Dept Lab Med, Seattle, WA USA.
[Butler-Wu, Susan; Cookson, Brad T.; Fang, Ferric C.] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA.
[Price, Lance B.; Aziz, Maliha] Translat Genom Res Inst TGen, Flagstaff, AZ USA.
[Nicolas-Chanoine, Marie-Helene] Hop Beaujon, Clichy, France.
[DebRoy, Chitrita] Penn State Univ, University Pk, PA 16802 USA.
[Robicsek, Ari] NorthShore Univ HealthSyst, Evanston, IL USA.
[Hansen, Glen] Hennepin Cty Med Ctr, Mineapolis, MN USA.
[Urban, Carl] New York Hosp Queens, Flushing, NY USA.
[Urban, Carl] NYU, Sch Med, New York, NY USA.
[Platell, Joanne] Biosecur Queensland, Anim Dis Surveillance Lab, Toowoomba, Qld, Australia.
[Trott, Darren J.] Univ Adelaide, Roseworthy, Australia.
[Zhanel, George] Univ Manitoba, Winnipeg, MB, Canada.
[Weissman, Scott J.] Seattle Childrens Res Inst, Seattle, WA USA.
[Scholes, Delia] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Hooper, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hooper, David C.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA.
RP Johnson, JR (reprint author), VA Med Ctr, 1 Vet Dr, Minneapolis, MN 55417 USA.
EM johns007@umn.edu
OI Fang, Ferric/0000-0002-3243-110X
FU Office of Research and Development, Medical Research Service, Department
of Veterans Affairs, Merit Review grant [1 I01 CX000192 01]; NIH ARRA
[1RC4AI092828]; Cepheid; Rib-X Pharmaceuticals; Merck; Rochester
Medical; Syntiron; Direction de la Recherche Clinique AP-HP; Group
Health; ARC Linkage; Achaogen; Cubist; Affinium; Sunovion; Pfizer
FX This material is based upon work supported by Office of Research and
Development, Medical Research Service, Department of Veterans Affairs,
Merit Review grant 1 I01 CX000192 01 (J. R. J.), and NIH ARRA award
1RC4AI092828 (E. V. S.).; The following authors report these conflicts
of interest: F. C. F.: Consultancy, research grants, and educational
presentations with Cepheid. D. C. H.: Research grant from Rib-X
Pharmaceuticals, consultancies with Fab Pharma and Pfizer, speakers
bureau with Pfizer. J. R. J.: Research grants and contracts from Merck,
Rochester Medical, and Syntiron; patent pending for detection of the H30
ST131 subclone. L. B. P.: Patent pending for detection of the H30 ST131
subclone. M.-H. N.-C.: Expert testimony for Region Wallon; research
grant from Direction de la Recherche Clinique AP-HP; lectures for
Novartis; travel reimbursement for 2012 ICAAC speaker. E. V. S.:
Research grant from Group Health; patent pending for detection of the
H30 ST131 subclone. D. T.: Research grant from ARC Linkage; consultancy
from Pfizer and Bayer; speaker for Bayer Animal Health. C. U.:
Consultancy with Pfizer, lecture/speaker for Forest Pharmaceuticals,
Cubist, and Pfizer. G. Z.: Research grants from Achaogen, Merck, Pfizer,
Cubist, Affinium, and Sunovion. All other authors report no potential
conflicts.
NR 26
TC 96
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U1 1
U2 31
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2013
VL 207
IS 6
BP 919
EP 928
DI 10.1093/infdis/jis933
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 092XO
UT WOS:000315156500008
PM 23288927
ER
PT J
AU Kim, AY
Onofrey, S
Church, DR
AF Kim, Arthur Y.
Onofrey, Shauna
Church, Daniel R.
TI An Epidemiologic Update on Hepatitis C Infection in Persons Living With
or at Risk of HIV Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE sexual transmission; epidemiology; viral infection; incidence;
prevalence; perinatal transmission; men who have sex with men
ID VIRUS-INFECTION; UNITED-STATES; VIRAL-HEPATITIS; NATURAL-HISTORY; LIVER
FIBROSIS; YOUNG-ADULTS; INDIVIDUALS; OUTBREAK; COHORT; MEN
AB Due to shared routes of transmission, coinfection with both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) is relatively common and results in accelerated liver disease, driving morbidity and mortality. Deaths related to HCV now exceed deaths related to HIV in the United States, and co-infected patients bear a significant proportion of that mortality. This burden may be addressed by novel antiviral therapies that promise increased rates of cure or by enhanced access to liver transplantation, but these are costly interventions. Ultimately, the future burden of coinfection is addressed by greater understanding of who is at risk for development of each infection, thus guiding preventive efforts. Key recent reports regarding the US burden of morbidity and mortality due to HCV and groups at risk for coinfection are reviewed, with a focus on recently described HCV occurring among young injection drug users and men who have sex with men. Given the lack of available vaccine against HCV, enhanced detection and surveillance is a vital component of our public health strategy to combat HCV.
C1 [Kim, Arthur Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA.
[Onofrey, Shauna; Church, Daniel R.] Massachusetts Dept Publ Hlth, Jamaica Plain, MA USA.
RP Kim, AY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA.
EM akim1@partners.org
FU National Institutes of Health [U19 AI066345, R01 DA 033541, R01 DA
031056, R01 DA 031059]
FX A. Y. K. is supported by the National Institutes of Health, grants U19
AI066345, R01 DA 033541, R01 DA 031056, R01 DA 031059. The sponsors had
no role in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; and preparation, review, or
approval of the manuscript.
NR 26
TC 35
Z9 35
U1 0
U2 23
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2013
VL 207
SU 1
BP S1
EP S6
DI 10.1093/infdis/jis927
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 089FG
UT WOS:000314895000001
PM 23390299
ER
PT J
AU Lauer, GM
AF Lauer, Georg M.
TI Immune Responses to Hepatitis C Virus (HCV) Infection and the Prospects
for an Effective HCV Vaccine or Immunotherapies
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE hepatitis C virus; acute infection; T cells; protective immunity;
vaccine
ID VIRAL PERSISTENCE; CELL RESPONSES; DRUG-USERS; B-VIRUS; CLEARANCE;
RESOLUTION; DETERMINANTS; REINFECTION; CHALLENGE
AB Infection with hepatitis C virus (HCV) typically leads to persistent infection, with > 170 million people estimated to be affected worldwide, putting them at risk for chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Importantly, 20%-30% of individuals are able to control the virus spontaneously, usually within 6 months of exposure. This suggests that HCV vaccines and immunotherapies are a distinct possibility. We discuss here the role of T cells in controlling HCV, the gaps in our understanding of protective HCV immunity, and the recent introduction of a HCV T-cell vaccine into clinical trials.
C1 [Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Lauer, Georg M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Lauer, GM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM glauer@helix.mgh.harvard.edu
RI Cheng, Yushao/E-6256-2011
FU National Institutes of Health [U19 AI082630, U19 AI066345]
FX This work was supported by the National Institutes of Health (grants U19
AI082630 and U19 AI066345).
NR 27
TC 21
Z9 23
U1 0
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2013
VL 207
SU 1
BP S7
EP S12
DI 10.1093/infdis/jis762
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 089FG
UT WOS:000314895000002
PM 23390305
ER
PT J
AU Lin, WY
Weinberg, EM
Chung, RT
AF Lin, Wenyu
Weinberg, Ethan M.
Chung, Raymond T.
TI Pathogenesis of Accelerated Fibrosis in HIV/HCV Co-infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Hepatitis C Virus (HCV); Human Immunodeficiency Virus (HIV); Hepatic
Fibrogenesis
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; LIVER FIBROSIS;
STELLATE CELLS; MICROBIAL TRANSLOCATION; OXIDATIVE STRESS;
HIV-INFECTION; PROGRESSION; FIBROGENESIS; ACTIVATION
AB Human immunodeficiency virus (HIV) infection is a major cause of acceleration of hepatitis C virus-related liver disease, cirrhosis, and death. However, studies of liver disease pathogenesis in HIV/HCV coinfection have thus far been limited. Emerging data support multiple derangements attending HIV coinfection, including increases in profibrogenic cytokine expression and secretion, generation of enhanced oxidative stress, and increases in hepaotcyte apoptosis. These derangements may be further augmented in the presence of increased microbial translocation in the setting of HIV disease. New insight into the mechanisms of HIV/HCV pathogenesis causing accelerated liver fibrosis could lead to new therapeutic strategies designed to retard ths process.
C1 [Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA USA.
[Weinberg, Ethan M.] Weill Cornell Med Ctr, Div Gastroenterol & Hepatol, New York, NY USA.
RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 1007, Boston, MA 02114 USA.
EM rtchung@partners.org
FU National Institutes of Health [AI069939, DK098079]
FX This work was supported by the National Institutes of Health (grants
AI069939 and DK098079).
NR 28
TC 37
Z9 40
U1 1
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2013
VL 207
SU 1
BP S13
EP S18
DI 10.1093/infdis/jis926
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 089FG
UT WOS:000314895000003
PM 23390300
ER
PT J
AU Stock, S
DeGruttola, V
AF Stock, Shannon
DeGruttola, Victor
TI Recursive partitioning for monotone missing at random longitudinal
markers
SO STATISTICS IN MEDICINE
LA English
DT Article
DE inverse probability weighting; recursive partitioning; U-statistics
ID REGRESSION TREES; CLASSIFICATION; INFECTION; RESPONSES
AB The development of HIV resistance mutations reduces the efficacy of specific antiretroviral drugs used to treat HIV infection and cross-resistance within classes of drugs is common. Recursive partitioning has been extensively used to identify resistance mutations associated with a reduced virologic response measured at a single time point; here we describe a statistical method that accommodates a large set of genetic or other covariates and a longitudinal response. This recursive partitioning approach for continuous longitudinal data uses the kernel of a U-statistic as the splitting criterion and avoids the need for parametric assumptions regarding the relationship between observed response trajectories and covariates. We propose an extension of this approach that allows longitudinal measurements to be monotone missing at random by making use of inverse probability weights. We assess the performance of our method using extensive simulation studies and apply them to data collected by the Forum for Collaborative HIV Research as part of an investigation of the viral genetic mutations associated with reduced clinical efficacy of the drug abacavir. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Stock, Shannon] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Stock, Shannon; DeGruttola, Victor] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Stock, S (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, CLS11007,450 Brookline Ave, Boston, MA 02215 USA.
EM sstock@jimmy.harvard.edu
FU NIH [AI R01 51164, AI T32 007358]
FX The authors would like to thank Eric Tchetgen Tchetgen for his help with
methods to accommodate missing data, as well as the reviewer and
associate editor for their helpful suggestions and comments. This work
was supported by NIH grants AI R01 51164 and AI T32 007358.
NR 14
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD MAR 15
PY 2013
VL 32
IS 6
BP 978
EP 994
DI 10.1002/sim.5574
PG 17
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 092BT
UT WOS:000315094500007
PM 22941582
ER
PT J
AU Rego, EM
Kim, HT
Ruiz-Arguelles, GJ
Undurraga, MS
Uriarte, MD
Jacomo, RH
Gutierrez-Aguirre, H
Melo, RAM
Bittencourt, R
Pasquini, R
Pagnano, K
Fagundes, EM
Chauffaille, MD
Chiattone, CS
Martinez, L
Meillon, LA
Gomez-Almaguer, D
Kwaan, HC
Garces-Eisele, J
Gallagher, R
Niemeyer, CM
Schrier, SL
Tallman, M
Grimwade, D
Ganser, A
Berliner, N
Ribeiro, RC
Lo-Coco, F
Lowenberg, B
Sanz, MA
AF Rego, Eduardo M.
Kim, Haesook T.
Ruiz-Argueelles, Guillermo J.
Undurraga, Maria Soledad
Uriarte, Maria del Rosario
Jacomo, Rafael H.
Gutierrez-Aguirre, Homero
Melo, Raul A. M.
Bittencourt, Rosane
Pasquini, Ricardo
Pagnano, Katia
Fagundes, Evandro M.
Chauffaille, Maria de Lourdes
Chiattone, Carlos S.
Martinez, Lem
Meillon, Luis A.
Gomez-Almaguer, David
Kwaan, Hau C.
Garces-Eisele, Javier
Gallagher, Robert
Niemeyer, Charlotte M.
Schrier, Stanley L.
Tallman, Martin
Grimwade, David
Ganser, Arnold
Berliner, Nancy
Ribeiro, Raul C.
Lo-Coco, Francesco
Loewenberg, Bob
Sanz, Miguel A.
TI Improving acute promyelocytic leukemia (APL) outcome in developing
countries through networking, results of the International Consortium on
APL
SO BLOOD
LA English
DT Article
ID TRANS-RETINOIC ACID; AGENT ARSENIC TRIOXIDE; MINIMAL-RESIDUAL-DISEASE;
RISK-ADAPTED TREATMENT; ALPHA FUSION GENE; EARLY DEATH RATE; RT-PCR
ANALYSIS; ANTHRACYCLINE MONOCHEMOTHERAPY; REMISSION INDUCTION;
CLINICAL-FEATURES
AB Thanks to modern treatment with all-trans retinoic acid and chemotherapy, acute promyelocytic leukemia (APL) is now the most curable type of leukemia. However, this progress has not yielded equivalent benefit in developing countries. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) was established to create a network of institutions in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. The IC-APL formulated expeditious diagnostic, treatment, and supportive guidelines that were adapted to local circumstances. APL was chosen as a model disease because of the potential impact on improved diagnosis and treatment. The project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, and laboratory and data management training programs. In addition, participating institutions held regular virtual and face-to-face meetings. Complete hematological remission was achieved in 153/180 (85%) patients and 27 (15%) died during induction. After a median follow-up of 28 months, the 2-year cumulative incidence of relapse, overall survival (OS), and disease-free survival (DFS) were 4.5%, 80%, and 91%, respectively. The establishment of the IC-APL network resulted in a decrease of almost 50% in early mortality and an improvement in OS of almost 30% compared with historical controls, resulting in OS and DFS similar to those reported in developed countries.
C1 [Rego, Eduardo M.; Jacomo, Rafael H.] Univ Sao Paulo, Hematol Oncol Div, Dept Internal Med, Med Sch Ribeirao Preto, BR-14048900 Ribeirao Preto, Brazil.
[Rego, Eduardo M.; Jacomo, Rafael H.] Univ Sao Paulo, Ctr Cell Based Therapy, BR-14048900 Ribeirao Preto, Brazil.
[Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Ruiz-Argueelles, Guillermo J.; Garces-Eisele, Javier] Clin Ruiz Puebla, Puebla, Mexico.
[Undurraga, Maria Soledad] Hosp Salvador, Dept Hematol, Santiago, Chile.
[Uriarte, Maria del Rosario; Martinez, Lem] Asociac Espanola Primera Socorros Mutuos, Montevideo, Uruguay.
[Gutierrez-Aguirre, Homero; Gomez-Almaguer, David] Hosp Univ Dr Jose E Gonzalez, Div Hematol, Monterrey, Mexico.
[Melo, Raul A. M.] Fundacao HEMOPE, Recife, PE, Brazil.
[Bittencourt, Rosane] Univ Fed Rio Grande do Sul, Div Hematol, Porto Alegre, RS, Brazil.
[Pasquini, Ricardo] Univ Fed Parana, Div Hematol, BR-80060000 Curitiba, Parana, Brazil.
[Pagnano, Katia] Univ Campinas UNICAMP, Hematol & Hemotherapy Ctr, Campinas, Brazil.
[Fagundes, Evandro M.] Univ Fed Minas Gerais, Div Hematol, Belo Horizonte, MG, Brazil.
[Chauffaille, Maria de Lourdes] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Chiattone, Carlos S.] Santa Casa Med Sch, Div Hematol, Sao Paulo, Brazil.
[Meillon, Luis A.] Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico.
[Kwaan, Hau C.] Northwestern Univ, Feinberg Sch Med, Hematol Oncol Div, Chicago, IL 60611 USA.
[Gallagher, Robert] Albert Einstein Canc Ctr, New York, NY USA.
[Niemeyer, Charlotte M.] Univ Med Ctr, Dept Pediat & Adolescent Med, Freiburg, Germany.
[Schrier, Stanley L.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Tallman, Martin] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, Weill Cornell Med Coll, New York, NY 10021 USA.
[Grimwade, David] Kings Coll London Sch Med, Dept Med & Mol Genet, London, England.
[Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany.
[Berliner, Nancy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Ribeiro, Raul C.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Lo-Coco, Francesco] Univ Roma Tor Vergata, Dept Biopathol, Rome, Italy.
[Lo-Coco, Francesco] Santa Lucia Fdn, Rome, Italy.
[Loewenberg, Bob] Erasmus MC, Dept Hematol, Rotterdam, Netherlands.
[Sanz, Miguel A.] Valencia Univ Med Sch, Hosp Univ La Fe, Dept Hematol, Valencia, Spain.
RP Rego, EM (reprint author), Univ Sao Paulo, Hematol Oncol Div, Dept Internal Med, Med Sch Ribeirao Preto, Av Bandeirantes 3900, BR-14048900 Ribeirao Preto, Brazil.
EM emrego@hcrp.fmrp.usp.br
RI UNICAMP, CCES - /J-7787-2015; Rego, Eduardo/A-1058-2012
OI Rego, Eduardo/0000-0003-1567-4086
FU American Society of Hematology; Fondazione Umberto Veronesi; Roche Saudi
Arabia; Fundacao de Apoio a Pesquisa do Estado de Sao Paulo
[1998/14247-6]; Fundacion Mexicana para la Salud; St. Jude Children's
Research Hospital; Cephalon Europe
FX This study was supported by the American Society of Hematology,
Fondazione Umberto Veronesi, Roche Saudi Arabia, Fundacao de Apoio a
Pesquisa do Estado de Sao Paulo (grant 1998/14247-6), Fundacion Mexicana
para la Salud, St. Jude Children's Research Hospital, and Cephalon
Europe.
NR 44
TC 21
Z9 28
U1 2
U2 10
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 14
PY 2013
VL 121
IS 11
BP 1935
EP 1943
DI 10.1182/blood-2012-08-449918
PG 9
WC Hematology
SC Hematology
GA 182PR
UT WOS:000321756700009
PM 23319575
ER
PT J
AU Richardson, PG
Siegel, D
Baz, R
Kelley, SL
Munshi, NC
Laubach, J
Sullivan, D
Alsina, M
Schlossman, R
Ghobrial, IM
Doss, D
Loughney, N
McBride, L
Bilotti, E
Anand, P
Nardelli, L
Wear, S
Larkins, G
Chen, M
Zaki, MH
Jacques, C
Anderson, KC
AF Richardson, Paul G.
Siegel, David
Baz, Rachid
Kelley, Susan L.
Munshi, Nikhil C.
Laubach, Jacob
Sullivan, Daniel
Alsina, Melissa
Schlossman, Robert
Ghobrial, Irene M.
Doss, Deborah
Loughney, Nora
McBride, Laura
Bilotti, Elizabeth
Anand, Palka
Nardelli, Lisa
Wear, Sandra
Larkins, Gail
Chen, Min
Zaki, Mohamad H.
Jacques, Christian
Anderson, Kenneth C.
TI Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with
refractory multiple myeloma who have received lenalidomide and
bortezomib
SO BLOOD
LA English
DT Article
ID PERIPHERAL NEUROPATHY; THALIDOMIDE ANALOGS; THERAPY; CELLS;
IMMUNOMODULATION; REVERSIBILITY; SURVIVAL; INHIBIT; CC-4047; IMPACT
AB This phase 1 dose-escalation study determined the maximum tolerated dose (MTD) of oral pomalidomide (4 dose levels) administered on days 1 to 21 of each 28-day cycle in patients with relapsed and refractory multiple myeloma (RRMM). After four cycles, patients who progressed or had not achieved minimal response (serum and urine M-protein reduction of >= 25% and >= 50%) could receive dexamethasone 40 mg per week. Safety and efficacy were evaluated. Thirty-eight patients who had received both bortezomib and lenalidomide (median 6 prior therapies) were enrolled; 63% were refractory to both lenalidomide and bortezomib. There were four dose-limiting toxicities (grade 4 neutropenia) at 5 mg per day and so the MTD was 4 mg per day. Rates of peripheral neuropathy and venous thromboembolism were low (<= 5%). Among the 38 patients enrolled (including 22 with added dexamethasone), 42% achieved minimal response or better, 21% achieved partial response or better, and 3% achieved complete response. Median duration of response, progression-free survival, and overall survival were 4.6, 4.6, and 18.3 months, respectively. Pomalidomide 4 mg per day on days 1 to 21 of each 28-day cycle, with or without dexamethasone (40 mg/week), has encouraging activity with manageable toxicity in RRMM, including those refractory to both lenalidomide and bortezomib.
C1 [Richardson, Paul G.; Munshi, Nikhil C.; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene M.; Doss, Deborah; Loughney, Nora; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Siegel, David; McBride, Laura; Bilotti, Elizabeth; Anand, Palka] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Baz, Rachid; Sullivan, Daniel; Alsina, Melissa; Nardelli, Lisa] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Kelley, Susan L.; Wear, Sandra] Multiple Myeloma Res Consortium, Norwalk, CT USA.
[Larkins, Gail; Chen, Min; Zaki, Mohamad H.; Jacques, Christian] Celgene Corp, Summit, NJ USA.
RP Richardson, PG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, 450 Brookline Ave, Boston, MA 02215 USA.
EM Paul_Richardson@dfci.harvard.edu
FU Celgene Corporation; Dana-Farber Cancer Institute; John Theuer Cancer
Center-Hackensack University Medical Center; H. Lee Moffitt Cancer and
Research Institute; Massachusetts General Hospital; Mayo Clinic Arizona;
Mayo Clinic Minnesota; Roswell Park Cancer Institute; Ohio State
University-James Cancer Hospital; University of Michigan Comprehensive
Cancer Center; Washington University-Siteman Cancer Center; St Vincent's
Comprehensive Cancer Center; University of Pittsburgh Cancer Institute;
Emory University; Princess Margaret Hospital-UHN; Cross Cancer Center;
University of Calgary-Tom Baker Cancer Center; Vancouver General
Hospital; Diamond Health Care Centre; Royal Victoria Hospital McGill
University; Multiple Myeloma Research Consortium
FX The authors received editorial support from Adriana Stan, PhD (Excerpta
Medica) in the preparation of this manuscript, funded by Celgene
Corporation.; We thank the following institutions, which collaborated
and supported this study: Dana-Farber Cancer Institute, John Theuer
Cancer Center-Hackensack University Medical Center, H. Lee Moffitt
Cancer and Research Institute, Massachusetts General Hospital, Mayo
Clinic Arizona, Mayo Clinic Minnesota, Roswell Park Cancer Institute,
The Ohio State University-James Cancer Hospital, University of Michigan
Comprehensive Cancer Center, Washington University-Siteman Cancer
Center, St Vincent's Comprehensive Cancer Center, University of
Pittsburgh Cancer Institute, Emory University, Princess Margaret
Hospital-UHN, Cross Cancer Center, University of Calgary-Tom Baker
Cancer Center, Vancouver General Hospital, Diamond Health Care Centre,
Royal Victoria Hospital McGill University, Multiple Myeloma Research
Consortium, Clinical Research Staff, Celgene Corporation. We also thank
our patients and their families.
NR 29
TC 85
Z9 89
U1 0
U2 15
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 14
PY 2013
VL 121
IS 11
BP 1961
EP 1967
DI 10.1182/blood-2012-08-450742
PG 7
WC Hematology
SC Hematology
GA 182PR
UT WOS:000321756700012
PM 23243282
ER
PT J
AU Xu, L
Hunter, ZR
Yang, G
Zhou, YS
Cao, Y
Liu, X
Morra, E
Trojani, A
Greco, A
Arcaini, L
Varettoni, M
Brown, JR
Tai, YT
Anderson, KC
Munshi, NC
Patterson, CJ
Manning, RJ
Tripsas, CK
Lindeman, NI
Treon, SP
AF Xu, Lian
Hunter, Zachary R.
Yang, Guang
Zhou, Yangsheng
Cao, Yang
Liu, Xia
Morra, Enrica
Trojani, Alessandra
Greco, Antonino
Arcaini, Luca
Varettoni, Marzia
Brown, Jennifer R.
Tai, Yu-Tzu
Anderson, Kenneth C.
Munshi, Nikhil C.
Patterson, Christopher J.
Manning, Robert J.
Tripsas, Christina K.
Lindeman, Neal I.
Treon, Steven P.
TI MYD88 L265P in Waldenstrom macroglobulinemia, immunoglobulin M
monoclonal gammopathy, and other B-cell lymphoproliferative disorders
using conventional and quantitative allele-specific polymerase chain
reaction
SO BLOOD
LA English
DT Article
ID UNDETERMINED SIGNIFICANCE; FOLLICULAR LYMPHOMA; KAPPA-B; MUTATION;
ESTABLISHMENT; EVOLUTION; COMPLEX; GENOME; IRAK1; LINE
AB By whole-genome and/or Sanger sequencing, we recently identified a somatic mutation (MYD88 L265P) that stimulates nuclear factor kappa B activity and is present in >90% of Waldenstrom macroglobulinemia (WM) patients. MYD88 L265P was absent in 90% of immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS) patients. We therefore developed conventional and real-time allele-specific polymerase chain reaction (AS-PCR) assays for more sensitive detection and quantification of MYD88 L265P. Using either assay, MYD88 L265P was detected in 97 of 104 (93%) WM and 13 of 24 (54%) IgM MGUS patients and was either absent or rarely expressed in samples from splenic marginal zone lymphoma (2/20; 10%), CLL (1/26; 4%), multiple myeloma (including IgM cases, 0/14), and immunoglobulin G MGUS (0/9) patients as well as healthy donors (0/40; P < 1.5 x 10(-5) for WM vs other cohorts). Real-time AS-PCR identified IgM MGUS patients progressing to WM and showed a high rate of concordance between MYD88 L265P Delta C-T and BM disease involvement (r = 0.89, P = .008) in WM patients undergoing treatment. These studies identify MYD88 L265P as a widely present mutation in WM and IgM MGUS patients using highly sensitive and specific AS-PCR assays with potential use in diagnostic discrimination and/or response assessment. The finding of this mutation in many IgM MGUS patients suggests that MYD88 L265P may be an early oncogenic event in WM pathogenesis.
C1 [Xu, Lian; Hunter, Zachary R.; Yang, Guang; Zhou, Yangsheng; Cao, Yang; Liu, Xia; Patterson, Christopher J.; Manning, Robert J.; Tripsas, Christina K.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02215 USA.
[Xu, Lian; Hunter, Zachary R.; Yang, Guang; Zhou, Yangsheng; Cao, Yang; Liu, Xia; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.; Lindeman, Neal I.; Treon, Steven P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Morra, Enrica; Trojani, Alessandra; Greco, Antonino] Osped Niguarda Ca Granda, Div Hematol, Milan, Italy.
[Arcaini, Luca; Varettoni, Marzia] Univ Pavia, Sch Med, Dept Hematol Oncol, I-27100 Pavia, Italy.
[Arcaini, Luca; Varettoni, Marzia] Policlin San Matteo, Fdn Ist Ricovero & Cura Carattere Sci, I-27100 Pavia, Italy.
[Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA.
[Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,45 Brookline Ave, Boston, MA 02215 USA.
EM steven_treon@dfci.harvard.edu
RI Arcaini, Luca/P-8913-2015;
OI Arcaini, Luca/0000-0002-9504-991X; Hunter, Zachary/0000-0002-1689-1691
FU Peter and Helen Bing Foundation; Coyote Fund for WM; International
Waldenstrom's Macroglobulinemia Foundation; Waldenstrom's Cancer Fund;
Bailey Family Fund for WM; D'Amato Family Fund for Genomic Discovery;
Edward and Linda Nelson Fund for WM Research; Bauman Family Trust;
Tannenhauser Family Foundation
FX This study was supported by the Peter and Helen Bing Foundation, the
Coyote Fund for WM, the International Waldenstrom's Macroglobulinemia
Foundation, the Waldenstrom's Cancer Fund, the Bailey Family Fund for
WM, the D'Amato Family Fund for Genomic Discovery, the Edward and Linda
Nelson Fund for WM Research, the Bauman Family Trust, and the
Tannenhauser Family Foundation.
NR 30
TC 106
Z9 110
U1 1
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 14
PY 2013
VL 121
IS 11
BP 2051
EP 2058
DI 10.1182/blood-2012-09-454355
PG 8
WC Hematology
SC Hematology
GA 182PR
UT WOS:000321756700022
PM 23321251
ER
PT J
AU Qin, LL
Zhao, DZ
Xu, JF
Ren, XH
Terwilliger, EF
Parangi, S
Lawler, J
Dvorak, HF
Zeng, HY
AF Qin, Liuliang
Zhao, Dezheng
Xu, Jianfeng
Ren, Xianghui
Terwilliger, Ernest F.
Parangi, Sareh
Lawler, Jack
Dvorak, Harold F.
Zeng, Huiyan
TI The vascular permeabilizing factors histamine and serotonin induce
angiogenesis through TR3/Nur77 and subsequently truncate it through
thrombospondin-1
SO BLOOD
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; MAST-CELL HISTAMINE;
TUMOR-GROWTH; VEGF-A; RECEPTOR; CANCER; INFLAMMATION; EXPRESSION; TISSUE
AB Angiogenesis plays an important role in cancer and in many other human diseases. Vascular endothelial growth factor-A (VEGF-A), the best known angiogenic factor, was originally discovered as a potent vascular permeability factor (VPF), suggesting that other vascular permeabilizing agents, such as histamine and serotonin, might also have angiogenic activity. We recently demonstrated that, like VEGF-A, histamine and serotonin up-regulate the orphan nuclear receptor and transcription factor TR3 (mouse homolog Nur77) and that TR3/Nur77 is essential for their vascular permeabilizing activities. We now report that histamine and serotonin are also angiogenic factors that, at low micromolar concentrations, induce endothelial cell proliferation, migration and tube formation in vitro, and angiogenesis in vivo. All of these responses are mediated through specific histamine and serotonin receptors, are independent of VEGF-A, and are directly dependent on TR3/Nur77. Initially, the angiogenic response closely resembled that induced by VEGF-A, with generation of "mother" vessels. However, after similar to 10 days, mother vessels began to regress as histamine and serotonin, unlike VEGF-A, up-regulated the potent angiogenesis inhibitor thrombospondin-1, thereby triggering a negative feedback loop. Thus, histamine and serotonin induce an angiogenic response that fits the time scale of acute inflammation.
C1 [Qin, Liuliang; Lawler, Jack; Dvorak, Harold F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Zhao, Dezheng] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol,Dept Med, Boston, MA 02215 USA.
[Zhao, Dezheng; Lawler, Jack; Dvorak, Harold F.; Zeng, Huiyan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Vasc Biol Res Ctr, Boston, MA 02215 USA.
[Xu, Jianfeng; Ren, Xianghui; Terwilliger, Ernest F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Expt Med,Dept Med, Boston, MA 02215 USA.
[Parangi, Sareh] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Zeng, Huiyan] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Mol & Vasc Biol,Dept Med, Boston, MA 02215 USA.
RP Zeng, HY (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Mol & Vasc Biol, 99 Brookline Ave RN 270F, Boston, MA 02215 USA.
EM hzeng@caregroup.harvard.edu
FU National Institutes of Health [K01 CA098581, R01CA133235, CA-142262, P01
CA-92644]; National Foundation for Cancer Research; [CA-130895];
[NS071197]
FX This study was supported in part by research funding from National
Institutes of Health grants K01 CA098581 and R01CA133235 (H.Z.);
CA-142262, P01 CA-92644, and a contract from the National Foundation for
Cancer Research (H. F. D.); and CA-130895 and NS071197 (J.L.).
NR 42
TC 20
Z9 20
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 14
PY 2013
VL 121
IS 11
BP 2154
EP 2164
DI 10.1182/blood-2012-07-443903
PG 11
WC Hematology
SC Hematology
GA 182PR
UT WOS:000321756700035
PM 23315169
ER
PT J
AU Bested, AC
Logan, AC
Selhub, EM
AF Bested, Alison C.
Logan, Alan C.
Selhub, Eva M.
TI Intestinal microbiota, probiotics and mental health: from Metchnikoff to
modern advances: Part II - contemporary contextual research
SO GUT PATHOGENS
LA English
DT Review
DE Intestinal microbiota; Autointoxication; Depression; Anxiety;
Probiotics; Microbial ecology; Lipopolysaccharide endotoxin; Diet;
Intestinal permeability; Microbial ecosystems
ID IRRITABLE-BOWEL-SYNDROME; CHRONIC-FATIGUE-SYNDROME; HIGH-FAT-DIET;
LACTOBACILLUS-PLANTARUM 299V; JUNCTION PROTEIN EXPRESSION; AUTISM
SPECTRUM DISORDERS; HUMAN FECAL MICROBIOTA; GUT MICROBIOTA; BACTERIAL
OVERGROWTH; MAJOR DEPRESSION
AB In recent years there has been a renewed interest concerning the ways in which the gastrointestinal tract - its functional integrity and microbial residents - might influence human mood (e.g. depression) and behavioral disorders. Once a hotbed of scientific interest in the early 20th century, this area lay dormant for decades, in part due to its association with the controversial term 'autointoxication'. Here we review contemporary findings related to intestinal permeability, small intestinal bacterial overgrowth, lipopolysaccharide endotoxin (LPS) exposure, D-lactic acid, propionic acid, and discuss their relevance to microbiota and mental health. In addition, we include the context of modern dietary habits as they relate to depression, anxiety and their potential interaction with intestinal microbiota.
C1 [Bested, Alison C.] BC Womens Hosp & Hlth Ctr, Complex Chron Dis Program, Vancouver, BC V6H 3N1, Canada.
[Logan, Alan C.] CAMNR, Mill Valley, CA 94941 USA.
[Selhub, Eva M.] Harvard Univ, Sch Med, Waltham, MA 02453 USA.
[Selhub, Eva M.] Massachusetts Gen Hosp, Waltham, MA 02453 USA.
RP Logan, AC (reprint author), CAMNR, 775 Blithedale Ave,Suite 364, Mill Valley, CA 94941 USA.
EM aclnd@cfs-fm.org
FU Genuine Health, Toronto, Canada
FX ACB and EMS have no competing interests. ACL has received consulting
fees from Genuine Health, Toronto, Canada.
NR 202
TC 21
Z9 22
U1 1
U2 75
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-4749
J9 GUT PATHOG
JI Gut Pathogens
PD MAR 14
PY 2013
VL 5
AR 3
DI 10.1186/1757-4749-5-3
PG 14
WC Gastroenterology & Hepatology; Microbiology
SC Gastroenterology & Hepatology; Microbiology
GA 118GP
UT WOS:000317013100001
PM 23497633
ER
PT J
AU Morancho, B
Parra-Palau, JL
Ibrahim, YH
Morales, CB
Peg, V
Bech-Serra, JJ
Pandiella, A
Canals, F
Baselga, J
Rubio, I
Arribas, J
AF Morancho, B.
Parra-Palau, J. L.
Ibrahim, Y. H.
Bernado Morales, C.
Peg, V.
Bech-Serra, J. J.
Pandiella, A.
Canals, F.
Baselga, J.
Rubio, I.
Arribas, J.
TI A dominant-negative N-terminal fragment of HER2 frequently expressed in
breast cancers
SO ONCOGENE
LA English
DT Article
DE HER2; ErbB2; breast cancer
ID RECEPTOR; CLEAVAGE; ERBB-2; GELDANAMYCIN; IDENTIFICATION; TRASTUZUMAB;
DEGRADATION; EFFECTOR; P95HER2; GROWTH
AB The transmembrane tyrosine kinase HER2 (ErbB2, neu) is a prototypical biomarker for breast cancers and a therapeutic target. Although anti-HER2 therapies are remarkably effective, HER2-positive tumors are heterogeneous and some subtypes do not respond or develop resistance to these therapies. Here we show that H2NTF, a novel N-terminal fragment of HER2, is expressed at variable levels in 60% of the breast cancer samples analyzed. Characterization of H2NTF shows that it is devoid of the tyrosine kinase domain but it readily interacts with full-length HER2 and other HER receptors. As a consequence, H2NTF acts as a dominant-negative, attenuating the signaling triggered by full-length HER receptors. Expression of H2NTF results in resistance to the treatment with low concentrations of trastuzumab in vitro. However, cells expressing H2NTF and non-expressing cells have similar sensitivity to trastuzumab in vivo, indicating that H2NTF/trastuzumab complexes trigger antibody-dependent cell-mediated cytotoxicity. Oncogene (2013) 32, 1452-1459; doi:10.1038/onc.2012.152; published online 28 May 2012
C1 [Morancho, B.; Parra-Palau, J. L.; Ibrahim, Y. H.; Bernado Morales, C.; Bech-Serra, J. J.; Canals, F.; Baselga, J.; Arribas, J.] Vall dHebron Inst Oncol VHIO, Preclin Res Program, Barcelona 08035, Spain.
[Peg, V.] Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Dept Pathol, Bellaterra, Spain.
[Peg, V.] Univ Autonoma Barcelona, Dept Morphol Sci, Bellaterra, Spain.
[Pandiella, A.] Univ Salamanca, CSIC, Inst Biol Mol Celular & Celular Canc, E-37008 Salamanca, Spain.
[Baselga, J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Rubio, I.] Vall dHebron Univ Hosp, Breast Canc Ctr, Barcelona, Spain.
[Arribas, J.] Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Bellaterra, Spain.
[Arribas, J.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain.
RP Arribas, J (reprint author), Vall dHebron Inst Oncol VHIO, Preclin Res Program, Psg Vall dHebron 119-129, Barcelona 08035, Spain.
EM jarribas@vhio.net
RI Arribas, Joaquin/M-4482-2014; Pandiella, Atanasio/O-5180-2014;
OI Arribas, Joaquin/0000-0002-0504-0664; Pandiella,
Atanasio/0000-0002-4704-8971; Peg, Vicente/0000-0002-5203-6166
FU Instituto de Salud Carlos III (Intrasalud) [PI081154, PI11/02496];
Instituto de Salud Carlos III (network of cooperative cancer research)
[RTICC-RD06/0020/0022, RTICC-RD06/0020/0041]; GlaxoSmithKline; Breast
Cancer Research Foundation (BCRF)
FX This work was supported by Instituto de Salud Carlos III (Intrasalud
PI081154, PI11/02496 and the network of cooperative cancer research
(RTICC-RD06/0020/0022 and RTICC-RD06/0020/0041)), GlaxoSmithKline and
the Breast Cancer Research Foundation (BCRF).
NR 23
TC 4
Z9 4
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR 14
PY 2013
VL 32
IS 11
BP 1452
EP 1459
DI 10.1038/onc.2012.152
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 110OZ
UT WOS:000316455600011
PM 22641219
ER
PT J
AU Suidan, GL
Duerschmied, D
Dillon, GM
Vanderhorst, V
Hampton, TG
Wong, SL
Voorhees, JR
Wagner, DD
AF Suidan, Georgette L.
Duerschmied, Daniel
Dillon, Gregory M.
Vanderhorst, Veronique
Hampton, Thomas G.
Wong, Siu Ling
Voorhees, Jaymie R.
Wagner, Denisa D.
TI Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities
SO PLOS ONE
LA English
DT Article
ID SEROTONIN(1A) RECEPTOR; DEFICIENT MICE; NEONATAL-RAT; ANXIETY; DYNAMICS;
BEHAVIOR; ATTENTION; DISORDER; MODEL; BRAIN
AB The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (-/-) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system.
C1 [Suidan, Georgette L.; Duerschmied, Daniel; Wong, Siu Ling; Voorhees, Jaymie R.; Wagner, Denisa D.] Immune Dis Inst, Boston, MA USA.
[Suidan, Georgette L.; Duerschmied, Daniel; Wong, Siu Ling; Voorhees, Jaymie R.; Wagner, Denisa D.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
[Wagner, Denisa D.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA.
[Suidan, Georgette L.; Duerschmied, Daniel; Wong, Siu Ling; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Duerschmied, Daniel] Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol 1, Freiburg, Germany.
[Dillon, Gregory M.] Harvard NeuroDiscovery Ctr, Neurobehav Lab, Boston, MA USA.
[Dillon, Gregory M.; Vanderhorst, Veronique] Harvard Univ, Sch Med, Boston, MA USA.
[Vanderhorst, Veronique] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Hampton, Thomas G.] Neurosci Discovery Core, Framingham, MA USA.
RP Wagner, DD (reprint author), Immune Dis Inst, Boston, MA USA.
EM Denisa.Wagner@childrens.harvard.edu
FU National Heart, Lung and Blood Institute of the National Institutes of
Health [R01 HL041002]; National Research Service Award from the National
Institutes of Neurological Disease and Stroke of the National Institutes
of Health [1F32NS073245]
FX This work was generously supported by National Heart, Lung and Blood
Institute of the National Institutes of Health grant R01 HL041002 (to
DDW) and a National Research Service Award from the National Institutes
of Neurological Disease and Stroke of the National Institutes of Health
grant 1F32NS073245 (to GLS). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 45
TC 4
Z9 4
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 MAR 14
PY 2013
VL 8
IS 3
AR e59032
DI 10.1371/journal.pone.0059032
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 109YM
UT WOS:000316407400088
PM 23516593
ER
PT J
AU Lee, JT
Bartolomei, MS
AF Lee, Jeannie T.
Bartolomei, Marisa S.
TI X-Inactivation, Imprinting, and Long Noncoding RNAs in Health and
Disease
SO CELL
LA English
DT Review
ID PLURIPOTENT STEM-CELLS; EARLY MOUSE EMBRYOS; FACULTATIVE HETEROCHROMATIN
FORMATION; ASSISTED REPRODUCTIVE TECHNOLOGY;
BECKWITH-WIEDEMANN-SYNDROME; CHROMOSOME INACTIVATION; XIST RNA; DOSAGE
COMPENSATION; PREIMPLANTATION DEVELOPMENT; CHROMATIN-STRUCTURE
AB X chromosome inactivation and genomic imprinting are classic epigenetic processes that cause disease when not appropriately regulated in mammals. Whereas X chromosome inactivation evolved to solve the problem of gene dosage, the purpose of genomic imprinting remains controversial. Nevertheless, the two phenomena are united by allelic control of large gene clusters, such that only one copy of a gene is expressed in every cell. Allelic regulation poses significant challenges because it requires coordinated long-range control in cis and stable propagation over time. Long noncoding RNAs have emerged as a common theme, and their contributions to diseases of imprinting and the X chromosome have become apparent. Here, we review recent advances in basic biology, the connections to disease, and preview potential therapeutic strategies for future development.
C1 [Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Bartolomei, Marisa S.] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu; bartolom@mail.med.upenn.edu
FU National Institutes of Health; Howard Hughes Medical Institute
FX We thank the Lee and Bartolomei labs for many inspirational discussions,
and the National Institutes of Health and the Howard Hughes Medical
Institute for supporting their research.
NR 152
TC 232
Z9 243
U1 14
U2 117
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 14
PY 2013
VL 152
IS 6
BP 1308
EP 1323
DI 10.1016/j.cell.2013.02.016
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 107CO
UT WOS:000316192500012
PM 23498939
ER
PT J
AU Price, BD
D'Andrea, AD
AF Price, Brendan D.
D'Andrea, Alan D.
TI Chromatin Remodeling at DNA Double-Strand Breaks
SO CELL
LA English
DT Review
ID HISTONE H2AX PHOSPHORYLATION; DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION;
KAP-1 PHOSPHORYLATION; H4-K16 ACETYLATION; GENOME INTEGRITY; REPAIR
PROTEINS; END RESECTION; FACTOR CHD4; NUCLEOSOME
AB DNA double-strand breaks (DSBs) can arise from multiple sources, including exposure to ionizing radiation. The repair of DSBs involves both posttranslational modification of nucleosomes and concentration of DNA-repair proteins at the site of damage. Consequently, nucleosome packing and chromatin architecture surrounding the DSB may limit the ability of the DNA-damage response to access and repair the break. Here, we review early chromatin-based events that promote the formation of open, relaxed chromatin structures at DSBs and that allow the DNA-repair machinery to access the spatially confined region surrounding the DSB, thereby facilitating mammalian DSB repair.
C1 [Price, Brendan D.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02215 USA.
RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, 450 Brookline Ave, Boston, MA 02215 USA.
EM alan_dandrea@dfci.harvard.edu
FU NIH [CA64585, CA93602, RO1-DK43889]
FX This work was supported by NIH grants CA64585 and CA93602 to B.D.P. and
grant RO1-DK43889 to A.D.D.
NR 100
TC 146
Z9 149
U1 6
U2 97
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 14
PY 2013
VL 152
IS 6
BP 1344
EP 1354
DI 10.1016/j.cell.2013.02.011
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 107CO
UT WOS:000316192500014
PM 23498941
ER
PT J
AU Morrow, M
Winograd, JM
Freer, PE
Eichhorn, JH
AF Morrow, Monica
Winograd, Jonathan M.
Freer, Phoebe E.
Eichhorn, John H.
TI Case 8-2013: A 48-Year-Old Woman with Carcinoma In Situ of the Breast
Ductal carcinoma in situ of the breast
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ACELLULAR DERMAL MATRIX; SKIN-SPARING MASTECTOMY; CONTRALATERAL
PROPHYLACTIC MASTECTOMY; RANDOMIZED CONTROLLED-TRIAL; LOCAL RECURRENCE;
CANCER; RECONSTRUCTION; TOMOSYNTHESIS; RADIOTHERAPY; WOMEN
C1 [Morrow, Monica] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
[Morrow, Monica] Weill Cornell Med Coll, Dept Surg, New York, NY USA.
[Winograd, Jonathan M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Freer, Phoebe E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Eichhorn, John H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Winograd, Jonathan M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Freer, Phoebe E.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Eichhorn, John H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Morrow, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA.
NR 40
TC 2
Z9 2
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 14
PY 2013
VL 368
IS 11
BP 1046
EP 1053
DI 10.1056/NEJMcpc1214221
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 104HF
UT WOS:000315982100012
PM 23484832
ER
PT J
AU Moslehi, J
AF Moslehi, Javid
TI The Cardiovascular Perils of Cancer Survivorship
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID EARLY BREAST-CANCER; THERAPY
C1 [Moslehi, Javid] Brigham & Womens Hosp, Watkins Clin, Dana Farber Canc Inst, Cardiooncol Program, Boston, MA 02115 USA.
[Moslehi, Javid] Harvard Univ, Sch Med, Boston, MA USA.
RP Moslehi, J (reprint author), Brigham & Womens Hosp, Watkins Clin, Dana Farber Canc Inst, Cardiooncol Program, 75 Francis St, Boston, MA 02115 USA.
NR 10
TC 13
Z9 13
U1 0
U2 9
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 14
PY 2013
VL 368
IS 11
BP 1055
EP 1056
DI 10.1056/NEJMe1215300
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 104HF
UT WOS:000315982100013
PM 23484833
ER
PT J
AU Mitnick, CD
Franke, MF
Rich, ML
Viru, FAA
Appleton, SC
Atwood, SS
Bayona, JN
Bonilla, CA
Chalco, K
Fraser, HSF
Furin, JJ
Guerra, D
Hurtado, RM
Joseph, K
Llaro, K
Mestanza, L
Mukherjee, JS
Munoz, M
Palacios, E
Sanchez, E
Seung, KJ
Shin, SS
Sloutsky, A
Tolman, AW
Becerra, MC
AF Mitnick, Carole D.
Franke, Molly F.
Rich, Michael L.
Alcantara Viru, Felix A.
Appleton, Sasha C.
Atwood, Sidney S.
Bayona, Jaime N.
Bonilla, Cesar A.
Chalco, Katiuska
Fraser, Hamish S. F.
Furin, Jennifer J.
Guerra, Dalia
Hurtado, Rocio M.
Joseph, Keith
Llaro, Karim
Mestanza, Lorena
Mukherjee, Joia S.
Munoz, Maribel
Palacios, Eda
Sanchez, Epifanio
Seung, Kwonjune J.
Shin, Sonya S.
Sloutsky, Alexander
Tolman, Arielle W.
Becerra, Mercedes C.
TI Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease
All-Cause Mortality
SO PLOS ONE
LA English
DT Article
ID MDR-TB; MYCOBACTERIUM-TUBERCULOSIS; TREATMENT OUTCOMES; STANDARDIZED
TREATMENT; THERAPY; PERU; TIME; LIMA; FLUOROQUINOLONES; METAANALYSIS
AB Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.
Objectives: This study assessed the impact of an aggressive regimen-one containing at least five likely effective drugs, including a fluoroquinolone and injectable-on treatment outcomes in a large MDR-TB patient cohort.
Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.
Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93).
Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.
C1 [Mitnick, Carole D.; Franke, Molly F.; Mukherjee, Joia S.; Tolman, Arielle W.; Becerra, Mercedes C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA.
[Mitnick, Carole D.; Franke, Molly F.; Rich, Michael L.; Appleton, Sasha C.; Bayona, Jaime N.; Fraser, Hamish S. F.; Joseph, Keith; Mukherjee, Joia S.; Seung, Kwonjune J.; Shin, Sonya S.; Becerra, Mercedes C.] Partners Hlth, Boston, MA USA.
[Mitnick, Carole D.; Rich, Michael L.; Atwood, Sidney S.; Fraser, Hamish S. F.; Joseph, Keith; Mukherjee, Joia S.; Seung, Kwonjune J.; Shin, Sonya S.; Becerra, Mercedes C.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
[Alcantara Viru, Felix A.; Bayona, Jaime N.; Chalco, Katiuska; Guerra, Dalia; Llaro, Karim; Mestanza, Lorena; Munoz, Maribel; Palacios, Eda] Socios Salud Sucursal Peru, Lima, Peru.
[Bonilla, Cesar A.] Minist Hlth, Lima, Peru.
[Furin, Jennifer J.] Case Western Reserve Univ, TB Res Unit, Cleveland, OH 44106 USA.
[Hurtado, Rocio M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hurtado, Rocio M.] Global Hlth Comm, Boston, MA USA.
[Sanchez, Epifanio] Hosp Nacl Sergio E Bernales, Lima, Peru.
[Sloutsky, Alexander] Ctr Hlth Policy & Res, Massachusetts Supranat TB Reference Lab, Boston, MA USA.
RP Mitnick, CD (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02215 USA.
EM carole_mitnick@hms.harvard.edu
RI Fraser, Hamish/E-3773-2013
FU National Institute of Allergy and Infectious Diseases [1 K01
AI065836-01]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (http://www.niaid.nih.gov/Pages/default.aspx) (1 K01
AI065836-01 to CDM). The funder had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 59
TC 30
Z9 30
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 13
PY 2013
VL 8
IS 3
AR e58664
DI 10.1371/journal.pone.0058664
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 115YY
UT WOS:000316849200103
PM 23516529
ER
PT J
AU Wong, ES
Liu, CF
AF Wong, Edwin S.
Liu, Chuan-Fen
TI The relationship between local area labor market conditions and the use
of Veterans Affairs health services
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
DE Health services; Utilization; Veterans; Socioeconomic factors
ID QUALITY-OF-CARE; BEHAVIORAL-MODEL; MEDICAL-CARE; SYSTEM; ACCESS; VA;
ALCOHOL; TRENDS
AB Background: In the U.S., economic conditions are intertwined with labor market decisions, access to health care, health care utilization and health outcomes. The Veterans Affairs (VA) health care system has served as a safety net provider by supplying free or reduced cost care to qualifying veterans. This study examines whether local area labor market conditions, measured using county-level unemployment rates, influence whether veterans obtain health care from the VA.
Methods: We used survey data from the Behavioral Risk Factor Surveillance System in years 2000, 2003 and 2004 to construct a random sample of 73,964 respondents self-identified as veterans. VA health service utilization was defined as whether veterans received all, some or no care from the VA. Hierarchical ordered logistic regression was used to address unobserved state and county random effects while adjusting for individual characteristics. Local area labor market conditions were defined as the average 12-month unemployment rate in veterans' county of residence.
Results: The mean unemployment rate for veterans receiving all, some and no care was 5.56%, 5.37% and 5.24%, respectively. After covariate adjustment, a one percentage point increase in the unemployment rate in a veteran's county of residence was associated with an increase in the probability of receiving all care (0.34%, p-value = 0.056) or some care (0.29%, p-value = 0.023) from the VA.
Conclusions: Our findings suggest that the important role of the VA in providing health care services to veterans is magnified in locations with high unemployment.
C1 [Wong, Edwin S.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA.
[Wong, Edwin S.; Liu, Chuan-Fen] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA.
RP Wong, ES (reprint author), VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM edwin.wong@va.gov
FU VA Health Services Research and Development Postdoctoral Fellowship [TPP
61-024]
FX Dr. Wong is supported by VA Health Services Research and Development
Postdoctoral Fellowship TPP 61-024. 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 and the University of
Washington.
NR 41
TC 0
Z9 0
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD MAR 13
PY 2013
VL 13
AR 96
DI 10.1186/1472-6963-13-96
PG 10
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 119QI
UT WOS:000317112000001
ER
PT J
AU Cassol, E
Cassetta, L
Rizzi, C
Gabuzda, D
Alfano, M
Poli, G
AF Cassol, Edana
Cassetta, Luca
Rizzi, Chiara
Gabuzda, Dana
Alfano, Massimo
Poli, Guido
TI Dendritic cell-specific intercellular adhesion molecule-3 grabbing
nonintegrin mediates HIV-1 infection of and transmission by
M2a-polarized macrophages in vitro
SO AIDS
LA English
DT Article
DE dendritic cell-specific intercellular adhesion molecule-3 grabbing
nonintegrin; HIV transmission; HIV-1; macrophage polarization; T cells
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; DC-SIGN;
VERTICAL TRANSMISSION; INDUCED EXPRESSION; GENE-EXPRESSION; TYPE-1
HIV-1; T-CELLS; POLARIZATION; TROPISM
AB Objective: To assess in-vitro effects of monocyte-derived macrophage (MDM) polarization into M1 and M2a cells on HIV-1 replication and transmission and obtain new insights into the potential importance of macrophage polarization in vivo.
Design: Human peripheral blood monocytes were differentiated into MDM for 7 days. Control and MDM polarized into M1 or M2a cells were exposed to different strains of HIV-1 and assessed for their ability to bind and transmit virus to CD4(+) T lymphocytes.
Methods: MDM were incubated with either tumour necrosis factor-alpha (TNF-alpha) along with interferon-gamma (IFN-gamma) or with interleukin-4 (IL-4) for 18 h to obtain M1 or M2a cells, respectively. Expression of cell surface antigens, including CD4 and dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN), was evaluated by flow cytometry. C-C chemokine receptor type 5 (CCR5)-dependent (R5) HIV-1 binding, DNA synthesis and viral replication were assessed in the presence or absence of anti-DC-SIGN blocking mAbs. Transmission of C-X-C chemokine receptor type 4 (CXCR4)-dependent (X4) and R5 HIV-1 from MDM to IL-2 activated CD4(+) T cells was also investigated.
Results: DC-SIGN was strongly upregulated on M2a-MDM and downregulated on M1-MDM compared with control MDM. DC-SIGN facilitated HIV-1 entry and DNA synthesis in M2a-MDM, compensating for their low levels of CD4 cell expression. M2a-MDM efficiently transmitted both R5 and X4 HIV-1 to CD4(+) T cells in a DC-SIGN-dependent manner.
Conclusion: DC-SIGN facilitates HIV-1 infection of M2a-MDM, and HIV-1 transfer from M2a-MDM to CD4(+) T cells. M2a-polarized tissue macrophages may play an important role in the capture and spread of HIV-1 in mucosal tissues and placenta. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:707-716
C1 [Cassol, Edana; Cassetta, Luca; Rizzi, Chiara; Alfano, Massimo; Poli, Guido] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, AIDS Immunopathogenesis Unit, I-20132 Milan, Italy.
[Cassol, Edana; Cassetta, Luca; Poli, Guido] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy.
[Cassol, Edana; Gabuzda, Dana] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
RP Cassol, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
EM edana_cassol@dfci.harvard.edu
FU Fondation Dormeur; Europrise [LSHP CT-2006-037611]; Italian Ministry of
Health Grant Program of AIDS Research; CIHR fellowship; NIH [R01
MH83588]
FX This study was supported in part by the Fondation Dormeur, by Europrise
(grant no. LSHP CT-2006-037611 to G.P.) and by the Italian Ministry of
Health Grant Program of AIDS Research 2009-2010 (to M.A. and G.P.). E.C.
was supported in part by a CIHR fellowship. D.G. was supported by NIH
R01 MH83588.
NR 42
TC 5
Z9 6
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2013
VL 27
IS 5
BP 707
EP 716
DI 10.1097/QAD.0b013e32835cfc82
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 098CY
UT WOS:000315524700004
PM 23211775
ER
PT J
AU Perederiy, JV
Luikart, BW
Washburn, EK
Schnell, E
Westbrook, GL
AF Perederiy, Julia V.
Luikart, Bryan W.
Washburn, Eric K.
Schnell, Eric
Westbrook, Gary L.
TI Neural Injury Alters Proliferation and Integration of Adult-Generated
Neurons in the Dentate Gyrus
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ENTORHINAL CORTEX LESION; ELECTRON-MICROSCOPIC ANALYSIS; TRAUMATIC
BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; RAT FASCIA-DENTATA; GRANULE CELLS;
HIPPOCAMPAL NEUROGENESIS; INDUCED SYNAPTOGENESIS; VESICULAR GLUTAMATE;
RECEPTOR ACTIVATION
AB Neural plasticity following brain injury illustrates the potential for regeneration in the central nervous system. Lesioning of the perforant path, which innervates the outer two-thirds of the molecular layer of the dentate gyrus, was one of the first models to demonstrate structural plasticity of mature granule cells (Parnavelas et al., 1974; Caceres and Steward, 1983; Diekmann et al., 1996). The dentate gyrus also harbors a continuously proliferating population of neuronal precursors that can integrate into functional circuits and show enhanced short-term plasticity (Schmidt-Hieber et al., 2004; Abrous et al., 2005). To examine the response of adult-generated granule cells to unilateral complete transection of the perforant path in vivo, we tracked these cells using transgenic POMC-EGFP mice or by retroviral expression of GFP. Lesioning triggered a marked proliferation of newborn neurons. Subsequently, the dendrites of newborn neurons showed reduced complexity within the denervated zone, but dendritic spines still formed in the absence of glutamatergic nerve terminals. Electron micrographs confirmed the lack of intact presynaptic terminals apposing spines on mature cells and on newborn neurons. Newborn neurons, but not mature granule cells, had a higher density of dendritic spines in the inner molecular layer postlesion accompanied by an increase in miniature EPSC amplitudes and rise times. Our results indicate that injury causes an increase in newborn neurons and lamina-specific synaptic reorganization indicative of enhanced plasticity. The presence of de novo dendritic spines in the denervated zone suggests that the postlesion environment provides the necessary signals for spine formation.
C1 [Perederiy, Julia V.; Luikart, Bryan W.; Washburn, Eric K.; Westbrook, Gary L.] OHSU, Vollum Inst, Portland, OR 97239 USA.
[Schnell, Eric] Portland VA Med Ctr, Portland, OR 97239 USA.
[Schnell, Eric] OHSU Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA.
RP Perederiy, JV (reprint author), OHSU, Vollum Inst, L474,3181 Southwest Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM perederi@ohsu.edu
OI Schnell, Eric/0000-0002-5623-5015
FU NIH [MH46613, P30 NS06180]; Oregon Partnership for Alzheimer's Research
Tax Check-Off Grant
FX This work was supported by NIH Grant MH46613 and by Oregon Partnership
for Alzheimer's Research Tax Check-Off Grant. We thank Oswald Steward
for training in the perforant path lesion procedure. We thank Stephanie
Kaech-Petrie with the Jungers Center Microscopy Core for assistance with
imaging parameters and Sue Aicher, Melissa Williams, Lisa Dirling, and
Robert Kayton with the Electron Microscopy Core for tissue preparation
and assistance with imaging equipment (supported by NIH Grant P30
NS06180).
NR 82
TC 15
Z9 15
U1 0
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 13
PY 2013
VL 33
IS 11
BP 4754
EP 4767
DI 10.1523/JNEUROSCI.4785-12.2013
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 106CO
UT WOS:000316119200011
PM 23486947
ER
PT J
AU Clair, C
Rigotti, NA
Porneala, B
Fox, CS
D'Agostino, RB
Pencina, MJ
Meigs, JB
AF Clair, Carole
Rigotti, Nancy A.
Porneala, Bianca
Fox, Caroline S.
D'Agostino, Ralph B., Sr.
Pencina, Michael J.
Meigs, James B.
TI Association of Smoking Cessation and Weight Change With Cardiovascular
Disease Among Adults With and Without Diabetes
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; CORONARY-HEART-DISEASE; CIGARETTE-SMOKING;
UNITED-STATES; RISK-FACTORS; MORTALITY; MELLITUS; WOMEN; POPULATION;
OUTCOMES
AB Importance Smoking cessation reduces the risks of cardiovascular disease (CVD), but weight gain that follows quitting smoking may weaken the CVD benefit of quitting.
Objective To test the hypothesis that weight gain following smoking cessation does not attenuate the benefits of smoking cessation among adults with and without diabetes.
Design, Setting, and Participants Prospective community-based cohort study using data from the Framingham Offspring Study collected from 1984 through 2011. At each 4-year examination, self-reported smoking status was assessed and categorized as smoker, recent quitter (-4 years), long-term quitter (-4 years), and nonsmoker. Pooled Cox proportional hazards models were used to estimate the association between quitting smoking and 6-year CVD events and to test whether 4-year change in weight following smoking cessation modified the association between smoking cessation and CVD events.
Main Outcome Measure Incidence over 6 years of total CVD events, comprising coronary heart disease, cerebrovascular events, peripheral artery disease, and congestive heart failure.
Results After a mean follow-up of 25 (SD, 9.6) years, 631 CVD events occurred among 3251 participants. Median 4-year weight gain was greater for recent quitters without diabetes (2.7 kg [interquartile range {IQR}, -0.5 to 6.4]) and with diabetes (3.6 kg [IQR, -1.4 to 8.2]) than for long-term quitters (0.9 kg [IQR, -1.4 to 3.2] and 0.0 kg [IQR, -3.2 to 3.2], respectively, P < .001). Among participants without diabetes, age-and sex-adjusted incidence rate of CVD was 5.9 per 100 person-examinations (95% CI, 4.9-7.1) in smokers, 3.2 per 100 person-examinations (95% CI, 2.1-4.5) in recent quitters, 3.1 per 100 person-examinations (95% CI, 2.6-3.7) in long-term quitters, and 2.4 per 100 person-examinations (95% CI, 2.0-3.0) in nonsmokers. After adjustment for CVD risk factors, compared with smokers, recent quitters had a hazard ratio (HR) for CVD of 0.47 (95% CI, 0.23-0.94) and long-term quitters had an HR of 0.46 (95% CI, 0.34-0.63); these associations had only a minimal change after further adjustment for weight change. Among participants with diabetes, there were similar point estimates that did not reach statistical significance.
Conclusions and Relevance In this community-based cohort, smoking cessation was associated with a lower risk of CVD events among participants without diabetes, and weight gain that occurred following smoking cessation did not modify this association. This supports a net cardiovascular benefit of smoking cessation, despite subsequent weight gain. JAMA. 2013;309(10):1014-1021 www.jama.com
C1 [Clair, Carole; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Clair, Carole; Rigotti, Nancy A.; Porneala, Bianca; Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA.
[Fox, Caroline S.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Pencina, Michael J.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Pencina, Michael J.] Harvard Clin Res Inst, Boston, MA USA.
RP Clair, C (reprint author), Univ Lausanne, Dept Ambulatory Care & Community Med, 44 Bugnon Ave, CH-1011 Lausanne, Switzerland.
EM carole.willi@gmail.com
RI Clair, Carole/D-9786-2014
OI Clair, Carole/0000-0001-5281-0943
FU UpToDate Inc; Swiss National Science Foundation [PBLAP3-127728/1]; SICPA
Foundation; National Heart, Lung, and Blood Institute (NHLBI)
[5K24HL4440-10]; National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) [K24 DK080140]; Swiss National Science Foundation;
NHLBI Framingham Heart Study [N01-HC-25195]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Rigotti reported serving as an
unpaid consultant to Pfizer and Allere Wellbeing Inc; conducting
research projects sponsored by Pfizer and Nabi Biopharmaceuticals; and
receiving royalties from UpToDate Inc for chapters related to smoking
cessation. Dr Pencina reported serving as a data and safety monitoring
board member for Thoracos. No other authors reported disclosures.; Dr
Clair was supported by a grant from the Swiss National Science
Foundation (PBLAP3-127728/1) and by a grant from the SICPA Foundation.
Dr Rigotti was supported by National Heart, Lung, and Blood Institute
(NHLBI) grant 5K24HL4440-10. Dr Meigs was supported by National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant
K24 DK080140.; The Swiss National Science Foundation, SICPA Foundation,
and NIDDK had no role in the design and conduct of the study; the
collection, management, analysis, and interpretation of the data; or the
preparation, review, or approval of the manuscript. The Framingham Heart
Study is supported by the NHLBI Framingham Heart Study (contract
N01-HC-25195 [Drs D'Agostino and Pencina]). The NHLBI approved the
manuscript.
NR 26
TC 71
Z9 73
U1 3
U2 26
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 13
PY 2013
VL 309
IS 10
BP 1014
EP 1021
DI 10.1001/jama.2013.1644
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 103SH
UT WOS:000315938700030
PM 23483176
ER
PT J
AU Chhatriwalla, AK
Amin, AP
Kennedy, KF
House, JA
Cohen, DJ
Rao, SV
Messenger, JC
Marso, SP
AF Chhatriwalla, Adnan K.
Amin, Amit P.
Kennedy, Kevin F.
House, John A.
Cohen, David J.
Rao, Sunil V.
Messenger, John C.
Marso, Steven P.
CA Natl Cardiovasc Data Registry
TI Association Between Bleeding Events and In-hospital Mortality After
Percutaneous Coronary Intervention
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID GLYCOPROTEIN IIB/IIIA INHIBITION; CARDIOVASCULAR DATA REGISTRY;
MYOCARDIAL-INFARCTION; CLINICAL-OUTCOMES; ACUITY TRIAL; ANTITHROMBOTIC
THERAPY; ECONOMIC-EVALUATION; PROGNOSTIC IMPACT; PROPENSITY SCORE;
ISCHEMIC EVENTS
AB Importance Bleeding is the most common complication after percutaneous coronary intervention (PCI) and is associated with increased morbidity and health care costs. The incidence of bleeding-related mortality after PCI has not been described in a nationally representative population. Furthermore, the relationships among bleeding risk, bleeding site, and mortality are unclear.
Objectives To describe the association between bleeding events and in-hospital mortality after PCI and to estimate the adjusted population attributable risk (estimated as the proportion of mortality risk associated with bleeding events), risk difference, and number needed to harm (NNH) for bleeding-related in-hospital mortality after PCI.
Design, Setting, and Patients Data from 3 386 688 procedures in the CathPCI Registry performed in the United States between 2004 and 2011 were analyzed. The population attributable risk was calculated after adjustment for baseline demographic, clinical, and procedural variables. To calculate the NNH for bleeding-related mortality, a propensity-matched analysis was performed.
Main Outcome Measures In-hospital mortality.
Results There were 57 246 bleeding events (1.7%) and 22 165 in-hospital deaths (0.65%) in 3 386 688 PCI procedures. The adjusted population attributable risk for mortality related to major bleeding was 12.1% (95% CI, 11.4%-12.7%) in the entire CathPCI cohort. The propensity-matched population consisted of 56 078 procedures with a major bleeding event and 224 312 controls. In this matched cohort, major bleeding was associated with increased in-hospital mortality (5.26% vs 1.87%; risk difference, 3.39% [95% CI, 3.20%-3.59%]; NNH=29 [95% CI, 28-31]; P < .001). The association between major bleeding and in-hospital mortality was observed in all strata of preprocedural bleeding risk (low: 1.62% vs 0.17%; risk difference, 1.45% [95% CI, 1.13%-1.77%], NNH=69 [95% CI, 57-88], P < .001; intermediate: 3.27% vs 0.71%; risk difference, 2.56% [95% CI, 2.33%-2.79%], NNH=39 [95% CI, 36-43], P < .001; and high: 8.16% vs 3.45%; risk difference, 4.71% [95% CI, 4.35%-5.07%], NNH=21 [95% CI, 20-23], P < .001). Although both access-site and non-access-site bleeding were associated with increased in-hospital mortality (2.73% vs 1.87%; risk difference, 0.86% [95% CI, 0.66%-1.05%], NNH=117 [95% CI, 95-151], P < .001; and 8.25% vs 1.87%; risk difference, 6.39% [95% CI, 6.04%-6.73%], NNH=16 [95% CI, 15-17], P < .001, respectively), the NNH was lower for nonaccess bleeding.
Conclusions and Relevance In a large registry of patients undergoing PCI, post-procedural bleeding events were associated with increased risk of in-hospital mortality, with an estimated 12.1% of deaths related to bleeding complications. JAMA. 2013;309(10):1022-1029 www.jama.com
C1 [Kennedy, Kevin F.; House, John A.] St Lukes Mid Amer Heart Inst, Dept Biostat, Kansas City, MO 64111 USA.
[Chhatriwalla, Adnan K.; Cohen, David J.; Marso, Steven P.] St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Chhatriwalla, Adnan K.; Cohen, David J.; Marso, Steven P.] Univ Missouri Kansas City, Sch Med, Dept Internal Med, Div Cardiol, Kansas City, MO USA.
[Amin, Amit P.] Washington Univ, Sch Med, Dept Internal Med, Div Cardiol, St Louis, MO 63110 USA.
[Rao, Sunil V.] Duke Clin Res Inst, Dept Internal Med, Div Cardiol, Durham, NC USA.
[Messenger, John C.] Univ Colorado Denver, Dept Internal Med, Div Cardiol, Denver, CO USA.
[Messenger, John C.] Denver VA Med Ctr, Denver, CO USA.
RP Chhatriwalla, AK (reprint author), St Lukes Mid Amer Heart Inst, 4300 Wornall Rd,Ste 2000, Kansas City, MO 64111 USA.
EM achhatri-walla@saint-lukes.org
FU Medtronic; Edwards Lifesciences; Abbott Vascular; Boston Scientific; Eli
Lilly; AstraZeneca; Biomet Inc; Daiichii Sankyo; Medicines Company; Novo
Nordisk; Amylin Pharmaceuticals; Volcano Corporation; Terumo Medical;
American College of Cardiology Foundation's National Cardiovascular Data
Registry (NCDR)
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Chhatriwalla reports that he will
be receiving speaking honoraria from Edwards Lifesciences to be paid
directly to Saint Luke's Hospital Foundation of Kansas City. Mr House
reports receiving consulting honoraria from Vita Solutions and KU
Medical Center. Dr Cohen reports medical board membership for Medtronic
and Abbott Vascular and reports receiving research support from
Medtronic, Edwards Lifesciences, Abbott Vascular, Boston Scientific, Eli
Lilly, AstraZeneca, Biomet Inc, and Daiichii Sankyo; consultant
honoraria from AstraZeneca, Eli Lilly, Merck, and Janssen
Pharmaceuticals; and speaking honoraria from St Jude Medical and Eli
Lilly. Dr Rao reports receiving research support and consultant
honoraria from The Medicines Company. Dr Marso reports that all
compensation for research activities, including research grants and
consulting fees from The Medicines Company, Novo Nordisk, Abbott
Vascular, Amylin Pharmaceuticals, Boston Scientific, Volcano
Corporation, and Terumo Medical, was paid directly to the Saint Luke's
Hospital Foundation of Kansas City. No other disclosures were reported.;
This research was supported by the American College of Cardiology
Foundation's National Cardiovascular Data Registry (NCDR).
NR 33
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U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 13
PY 2013
VL 309
IS 10
BP 1022
EP 1029
DI 10.1001/jama.2013.1556
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 103SH
UT WOS:000315938700031
PM 23483177
ER
PT J
AU Stamatakis, KA
Norton, WE
Stirman, SW
Melvin, C
Brownson, RC
AF Stamatakis, Katherine A.
Norton, Wynne E.
Stirman, Shannon W.
Melvin, Cathy
Brownson, Ross C.
TI Developing the next generation of dissemination and implementation
researchers: insights from initial trainees
SO IMPLEMENTATION SCIENCE
LA English
DT Article
DE Dissemination and implementation research; Career development;
Early-stage investigators
ID KNOWLEDGE TRANSLATION; ACADEMIC MEDICINE; MENTORS; COMPETENCES;
STRATEGIES; SCHOLARS; SCIENCE
AB Background: Dissemination and implementation (D&I) research is a relatively young discipline, underscoring the importance of training and career development in building and sustaining the field. As such, D&I research faces several challenges in designing formal training programs and guidance for career development. A cohort of early-stage investigators (ESI) recently involved in an implementation research training program provided a resource for formative data in identifying needs and solutions around career development.
Results: Responses outlined fellows' perspectives on the perceived usefulness and importance of, as well as barriers to, developing practice linkages, acquiring additional methods training, academic advancement, and identifying institutional supports. Mentorship was a cross-cutting issue and was further discussed in terms of ways it could foster career advancement in the context of D&I research.
Conclusions: Advancing an emerging field while simultaneously developing an academic career offers a unique challenge to ESIs in D&I research. This article summarizes findings from the formative data that outlines some directions for ESIs and provides linkages to the literature and other resources on key points.
C1 [Stamatakis, Katherine A.; Brownson, Ross C.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO 63130 USA.
[Stamatakis, Katherine A.; Brownson, Ross C.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA.
[Norton, Wynne E.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL 35294 USA.
[Stirman, Shannon W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA.
[Stirman, Shannon W.] Boston Univ, Boston, MA 02215 USA.
[Melvin, Cathy] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Melvin, Cathy] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Brownson, Ross C.] Washington Univ, Brown Sch, Prevent Res Ctr St Louis, St Louis, MO USA.
RP Stamatakis, KA (reprint author), Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO 63130 USA.
EM stamatakisk@wustl.edu
FU Washington University Institute of Clinical and Translational Sciences
from the National Center for Advancing Translational Sciences [UL1
TR000448, KL2 TR000450]; Implementation Research Institute (IRI), at the
George Warren Brown School of Social Work, Washington University in St.
Louis; National Institute of Mental Health [R25 MH080916-01A2];
Department of Veterans Affairs, Health Services Research & Development
Service, Quality Enhancement Research Initiative (QUERI) [R00 MH
080100]; Centers for Disease Control and Prevention (the Prevention
Research Centers Program) [U48/DP001903]
FX This publication was supported by the Washington University Institute of
Clinical and Translational Sciences grant UL1 TR000448 and KL2 TR000450
from the National Center for Advancing Translational Sciences. The
preparation of this article was also supported in part by the
Implementation Research Institute (IRI), at the George Warren Brown
School of Social Work, Washington University in St. Louis; through an
award from the National Institute of Mental Health (R25 MH080916-01A2)
and the Department of Veterans Affairs, Health Services Research &
Development Service, Quality Enhancement Research Initiative (QUERI), in
part by R00 MH 080100, and in part by Cooperative Agreement Number
U48/DP001903 from the Centers for Disease Control and Prevention (the
Prevention Research Centers Program). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH, VA, or CDC.
NR 22
TC 8
Z9 8
U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD MAR 12
PY 2013
VL 8
AR 29
DI 10.1186/1748-5908-8-29
PG 6
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 137EM
UT WOS:000318418300001
PM 23497462
ER
PT J
AU Leshchiner, ES
Braun, CR
Bird, GH
Walensky, LD
AF Leshchiner, Elizaveta S.
Braun, Craig R.
Bird, Gregory H.
Walensky, Loren D.
TI Direct activation of full-length proapoptotic BAK
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE apoptosis; BCL-2 family; SAHB; stapled peptide; photocrosslinking
ID STABILIZED ALPHA-HELICES; BCL-2 HOMOLOG BAK; MITOCHONDRIAL APOPTOSIS;
CYTOCHROME-C; BH3 DOMAIN; CELL-DEATH; MEMBRANE PERMEABILIZATION; X-RAY;
PROTEIN; INHIBITOR
AB Proapoptotic B-cell lymphoma 2 (BCL-2) antagonist/killer (BAK) and BCL-2-associated X (BAX) form toxic mitochondrial pores in response to cellular stress. Whereas BAX resides predominantly in the cytosol, BAK is constitutively localized to the outer mitochondrial membrane. Select BCL-2 homology domain 3 (BH3) helices activate BAX directly by engaging an alpha 1/alpha 6 trigger site. The inability to express full-length BAK has hampered full dissection of its activation mechanism. Here, we report the production of full-length, monomeric BAK by mutagenesis-based solubilization of its C-terminal alpha-helical surface. Recombinant BAK autotranslocates to mitochondria but only releases cytochrome c upon BH3 triggering. A direct activation mechanism was explicitly demonstrated using a liposomal system that recapitulates BAK-mediated release upon addition of BH3 ligands. Photoreactive BH3 helices mapped both triggering and autointeractions to the canonical BH3-binding pocket of BAK, whereas the same ligands crosslinked to the alpha 1/alpha 6 site of BAX. Thus, activation of both BAK and BAX is initiated by direct BH3-interaction but at distinct trigger sites. These structural and biochemical insights provide opportunities for developing proapoptotic agents that activate the death pathway through direct but differential engagement of BAK and BAX.
C1 [Leshchiner, Elizaveta S.; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Leshchiner, Elizaveta S.; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02215 USA.
[Leshchiner, Elizaveta S.; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Leshchiner, Elizaveta S.; Braun, Craig R.; Bird, Gregory H.; Walensky, Loren D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Leshchiner, Elizaveta S.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
EM Loren_Walensky@dfci.harvard.edu
OI Bird, Geoffrey/0000-0002-2310-0202
FU National Institutes of Health [5R01CA050239, 5R01GM090299]; Stand Up to
Cancer Innovative Research Grant; Lander Fellowship in Cancer Chemical
Biology; American Association of University Women International
Fellowship
FX We thank Eric D. Smith for graphical support, Marina Godes for technical
assistance with mitochondrial isolation and purification, David
Whitehead for protein production support, Eileen White for providing
wild-type and Bax-/-Bak-/- iBMK cells, David
Andrews for guidance on the liposomal assay system, and Steven Gygi and
Wilhelm Haas for their advice and input on the MS analyses. This work
was supported by National Institutes of Health Grants 5R01CA050239 and
5R01GM090299 and a Stand Up to Cancer Innovative Research Grant (to
L.D.W.) and a Lander Fellowship in Cancer Chemical Biology and an
American Association of University Women International Fellowship (to
E.S.L.).
NR 57
TC 59
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U1 1
U2 20
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 12
PY 2013
VL 110
IS 11
BP E986
EP E995
DI 10.1073/pnas.1214313110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107RK
UT WOS:000316238300069
PM 23404709
ER
PT J
AU Baik, A
Olenchock, B
Moslehi, J
Kaelin, WG
AF Baik, Alan
Olenchock, Ben
Moslehi, Javid
Kaelin, William G., Jr.
TI ACUTE HYPOXIA-INDUCIBLE FACTOR EGLN1 INACTIVATION PROTECTS AGAINST
ISCHEMIA-REPERFUSION INJURY BY REGULATION OF GLUCOSE OXIDATION AND
REACTIVE OXYGEN SPECIES GENERATION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E28
EP E28
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200029
ER
PT J
AU Bhatia, RS
Picard, M
Weiner, R
Milford, C
AF Bhatia, Rajan Sacha
Picard, Michael
Weiner, Rory
Milford, Creagh
TI AN EDUCATIONAL INTERVENTION REDUCES THE RATE OF INAPPROPRIATE
TRANSTHORACIC ECHOCARDIOGRAMS ON AN INPATIENT MEDICAL SERVICE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Bhatia, Rajan Sacha; Picard, Michael; Weiner, Rory; Milford, Creagh] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E2122
EP E2122
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202326
ER
PT J
AU Chandrashekhar, R
Akers, S
Vakilipour, A
Shiva-Kumar, P
Haines, P
Jain, S
Saif, H
Witschey, W
Ferrari, VA
Chirinos, JA
AF Chandrashekhar, Rahul
Akers, Scott
Vakilipour, Amin
Shiva-Kumar, Prithvi
Haines, Philip
Jain, Snigdha
Saif, Hassam
Witschey, Walter
Ferrari, Victor A.
Chirinos, Julio A.
TI TIME-RESOLVED LEFT VENTRICULAR MYOCARDIAL STRESS IN HEART FAILURE WITH
REDUCED EJECTION FRACTION REVEALS A MARKED INCREASE IN LATE SYSTOLIC
MYOCARDIAL LOAD
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Philadelphia VA Med Ctr, Philadelphia, PA USA.
Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E613
EP E613
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200613
ER
PT J
AU Chirinos, JA
Shiva-Kumar, P
Chandrashekhar, R
Haines, P
Vakilipour, A
Saif, H
Witschey, W
Pandya, N
Segers, P
Ferrari, V
Akers, S
AF Chirinos, Julio A.
Shiva-Kumar, Prithvi
Chandrashekhar, Rahul
Haines, Philip
Vakilipour, Amin
Saif, Hassam
Witschey, Walter
Pandya, Nirzari
Segers, Patrick
Ferrari, Victor
Akers, Scott
TI RELATIONSHIP BETWEEN ARTERIAL LOAD AND LV CONCENTRIC HYPERTROPHY
ASSESSED WITH MRI
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Philadelphia VA Med Ctr, Philadelphia, PA USA.
Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1473
EP E1473
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201578
ER
PT J
AU Chou, ET
Zakroysky, P
Hayden, D
Woodard, P
Wiviott, S
Nagurney, J
Fleg, J
Lee, H
Schoenfeld, D
Hoffmann, U
Truong, Q
AF Chou, Eric T.
Zakroysky, Pearl
Hayden, Doug
Woodard, Pamela
Wiviott, Stephen
Nagurney, John
Fleg, Jerome
Lee, Hang
Schoenfeld, David
Hoffmann, Udo
Quynh Truong
TI UTILITY OF CORONARY ARTERY CALCIUM SCANNING IN EMERGENCY DEPARTMENT
EVALUATION FOR ACUTE CHEST PAIN: THE ROMICAT II TRIAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Kaiser Permanente Fontana Med Ctr, Fontana, CA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1109
EP E1109
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201214
ER
PT J
AU Daniels, K
Arena, R
Zavin, A
Allsup, K
Lazzari, A
Schulze, PC
Forman, DE
AF Daniels, Karla
Arena, Ross
Zavin, Alexandra
Allsup, Kelly
Lazzari, Antonio
Schulze, P. Christian
Forman, Daniel E.
TI ADIPONECTIN RESISTANCE IN NON-CACHECTIC HEART FAILURE PATIENTS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 VA Boston Healthcare Syst, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
RI Arena, Ross/A-3141-2008
OI Arena, Ross/0000-0002-6675-1996
NR 0
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 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E600
EP E600
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200600
ER
PT J
AU De Berardinis, B
Magrini, L
Gaggin, HK
Belcker, A
Zancla, B
Femia, A
Simon, M
Motiwala, S
Bhardwaj, A
Parry, B
Nagurney, TJ
Di Somma, S
Januzzi, JL
AF De Berardinis, Benedetta
Magrini, Laura
Gaggin, Hanna K.
Belcker, Arianna
Zancla, Benedetta
Femia, Alexandra
Simon, Mandy
Motiwala, Shweta
Bhardwaj, Anju
Parry, Blair
Nagurney, Toby J.
Di Somma, Salvatore
Januzzi, James L.
TI A PROSPECTIVE, BLINDED STUDY OF BIOIMPEDANCE VECTOR ANALYSIS AND
BIOMARKER TESTING FOR THE PREDICTION OF WORSENING RENAL FUNCTION IN
CONSECUTIVE PATIENTS WITH ACUTELY DECOMPENSATED HEART FAILURE: PRIMARY
RESULTS OF THE BIOMONITORING AND CARDIORENAL SYNDROME IN HEART FAILURE
(BIONICS-HF) TRIAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Univ Roma La Sapienza, Dep Med Surg Sci & Traslat Med, Rome, Italy.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E639
EP E639
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200639
ER
PT J
AU Elmariah, S
Furlan, A
Reisman, M
Burke, D
Vardi, M
Ling, SQ
Chen, XH
Mauri, L
AF Elmariah, Sammy
Furlan, Anthony
Reisman, Mark
Burke, David
Vardi, Moshe
Ling, Shuqiong
Chen, Xiaohua
Mauri, Laura
CA CLOSURE I Investigators
TI PREDICTORS OF RECURRENT NEUROLOGIC EVENTS IN PATIENTS WITH PATENT
FORAMEN OVALE: INSIGHTS FROM THE CLOSURE I TRIAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Clin Res Inst, Boston, MA USA.
NR 0
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 MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1749
EP E1749
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201854
ER
PT J
AU Emami, H
Subramanian, S
Vucic, E
Vijayakumar, J
Fifer, K
Brady, TJ
Rudd, JHF
Fayad, ZA
Van Dyke, TE
Tawakol, A
AF Emami, Hamed
Subramanian, Sharath
Vucic, Esad
Vijayakumar, Jayanthi
Fifer, Kenneth
Brady, Thomas J.
Rudd, James H. F.
Fayad, Zahi A.
Van Dyke, Thomas E.
Tawakol, Ahmed
TI HIGH DOSE ATORVASTATIN REDUCES PERIODONTAL ACTIVITY IN PROPORTION TO
ATHEROSCLEROTIC INFLAMMATION: A POTENTIALLY NOVEL PLEIOTROPIC EFFECT OF
STATINS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Harvard Univ, Sch Med, Forsyth Inst, Boston, MA USA.
FU Academy of Medical Sciences (AMS) [AMS-SGCL1-Rudd]
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1055
EP E1055
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201160
ER
PT J
AU Falk, RH
Laubach, JP
Kruger, J
Quarta, CC
AF Falk, Rodney H.
Laubach, Jacob P.
Kruger, Jenna
Quarta, Candida Cristina
TI BORTEZOMIB/DEXAMETHASONE-BASED TREATMENT FOR LIGHT-CHAIN CARDIAC
AMYLOIDOSIS RESULTS IN MARKEDLY PROLONGED SURVIVAL COMPARED TO
PREVIOUSLY USED REGIMENS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 MAR 12
PY 2013
VL 61
IS 10
SU S
BP E712
EP E712
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200712
ER
PT J
AU Gaggin, HK
Motiwala, S
Bhardwaj, A
Szymonifka, J
Parks, K
Januzzi, J
AF Gaggin, Hanna Kim
Motiwala, Shweta
Bhardwaj, Anju
Szymonifka, Jackie
Parks, Kimberly
Januzzi, James
TI CIRCULATING CONCENTRATIONS OF SOLUBLE ST2 IDENTIFY BENEFIT OF HIGH DOSE
BETA BLOCKER IN CHRONIC HEART FAILURE: RESULTS FROM THE PROBNP
OUTPATIENT TAILORED CHRONIC HEART FAILURE THERAPY (PROTECT) STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Gaggin, Hanna Kim; Motiwala, Shweta; Bhardwaj, Anju; Szymonifka, Jackie; Parks, Kimberly; Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E746
EP E746
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200746
ER
PT J
AU Grinstein, J
Bonaca, M
Sabatine, M
Jarolim, P
Conrad, M
Braunwald, E
Giugliano, R
Newby, LK
Morrow, D
AF Grinstein, Jonathan
Bonaca, Marc
Sabatine, Marc
Jarolim, Petr
Conrad, Michael
Braunwald, Eugene
Giugliano, Robert
Newby, L. Kristin
Morrow, David
TI PROGNOSTIC IMPLICATIONS OF LOW-LEVEL CARDIAC TROPONIN ELEVATION USING
THE HIGH-SENSITIVITY ASSAY FOR CARDIAC TROPONIN T: RESULTS FROM EARLY
ACS & SEPIA-TIMI 42
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 TIMI Study Grp, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E110
EP E110
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200111
ER
PT J
AU Hu, SN
Jia, HB
Hou, JB
Lei, X
Tian, JW
Kato, K
Yonetsu, T
Vergallo, R
Abtahian, F
Han, ZG
Meng, LB
Yu, H
Zhang, SS
Yu, B
Jang, IK
AF Hu, Sining
Jia, Haibo
Hou, Jingbo
Lei, Xing
Tian, JinWei
Kato, Koji
Yonetsu, Taishi
Vergallo, Rocco
Abtahian, Farhad
Han, Zhigang
Meng, Lingbo
Yu, Huai
Zhang, Shaosong
Yu, Bo
Jang, Ik-Kyung
TI ATTENUATED RESPONSE OF LIPID PLAQUE TO CHOLESTEROL LOWERING THERAPY IN
DIABETIC PATIENT: AN OPTICAL COHERENCE TOMOGRAPHY STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E219
EP E219
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200220
ER
PT J
AU Hulten, E
Bittencourt, M
Singh, A
O'Leary, D
Patil, M
Osmani, W
Abbara, S
Steigner, M
Nasir, K
Truong, Q
Klein, J
Hainer, J
Rybicki, F
Hoffmann, U
Di Carli, M
Ghoshhajra, B
Blankstein, R
AF Hulten, Edward
Bittencourt, Marcio
Singh, Avinainder
O'Leary, Daniel
Patil, Mitalee
Osmani, Wafa
Abbara, Suhny
Steigner, Michael
Nasir, Khurram
Quynh Truong
Klein, Josh
Hainer, Jon
Rybicki, Frank
Hoffmann, Udo
Di Carli, Marcelo
Ghoshhajra, Brian
Blankstein, Ron
TI CHANGE IN STATIN THERAPY AFTER CCTA IS ASSOCIATED WITH LOWER
LDL-CHOLESTEROL WITHOUT CHANGE IN THREE-YEAR PROGNOSIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1106
EP E1106
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201211
ER
PT J
AU Januzzi, JL
Zakroysky, P
Truong, Q
Woodard, P
Pope, JH
Hauser, T
Nagurney, J
Schoenfeld, D
Peacock, WF
Wiviott, S
Pang, P
Udelson, J
Hoffmann, U
AF Januzzi, James L.
Zakroysky, Pearl
Quynh Truong
Woodard, Pamela
Pope, James Hector
Hauser, Thomas
Nagurney, John
Schoenfeld, David
Peacock, W. Frank
Wiviott, Stephen
Pang, Peter
Udelson, James
Hoffmann, Udo
TI PERFORMANCE OF TWO SENSITIVE TROPONIN I ASSAYS FOR THE EVALUATION OF
SUSPECTED ACS : RESULTS FROM THE MULTICENTER RULE OUT MYOCARDIAL
INFARCTION USING COMPUTER ASSISTED TOMOGRAPHY (ROMICAT) II BIOMARKER
SUB-STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Januzzi, James L.; Zakroysky, Pearl; Quynh Truong; Woodard, Pamela; Pope, James Hector; Hauser, Thomas; Nagurney, John; Schoenfeld, David; Peacock, W. Frank; Wiviott, Stephen; Pang, Peter; Udelson, James; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E229
EP E229
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200230
ER
PT J
AU Jia, HB
Yonetsu, T
Jang, YS
Walters, D
Prasad, A
Chia, S
Kato, K
Abtahian, F
Vergallo, R
Tian, JW
Hu, SN
Lee, H
Zhang, SS
Yu, B
Jang, IK
AF Jia, Haibo
Yonetsu, Taishi
Jang, Yang-Soo
Walters, Darren
Prasad, Abhiram
Chia, Stanley
Kato, Koji
Abtahian, Farhad
Vergallo, Rocco
Tian, JinWei
Hu, Sining
Lee, Hang
Zhang, Shaosong
Yu, Bo
Jang, Ik-Kyung
TI NEW INSIGHTS INTO DISTRIBUTION OF VARIOUS PLAQUE TYPES AROUND CORONARY
ARTERY BIFURCATIONS: AN IN VIVO OPTICAL COHERENCE TOMOGRAPHY STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1709
EP E1709
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201814
ER
PT J
AU Jia, HB
Li, N
Wang, XD
Kato, K
Yonetsu, T
Hu, SN
Tian, JW
Zhang, SS
Hou, JB
Yu, B
Jang, IK
AF Jia, Haibo
Li, Ning
Wang, Xuedong
Kato, Koji
Yonetsu, Taishi
Hu, Sining
Tian, Jinwei
Zhang, Shaosong
Hou, Jingbo
Yu, Bo
Jang, Ik-Kyung
TI CHRONIC TOTAL OCCLUSION: OPTICAL COHERENCE TOMOGRAPHY FINDINGS AT SIX
MONTHS FOLLOWING TREATMENT WITH SIROLIMUS ELUTING STENTS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1688
EP E1688
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201793
ER
PT J
AU Kato, K
Yonetsu, T
Jia, HB
Abtahian, F
Vergallo, R
Kim, SJ
Lee, H
McNulty, I
Lee, S
Uemura, S
Jang, YS
Park, SJ
Mizuno, K
Yu, B
Jang, IK
AF Kato, Koji
Yonetsu, Taishi
Jia, Haibo
Abtahian, Farhad
Vergallo, Rocco
Kim, Soo-Joong
Lee, Hang
McNulty, Iris
Lee, Stephen
Uemura, Shiro
Jang, Yang Soo
Park, Seung-Jung
Mizuno, Kyoichi
Yu, Bo
Jang, Ik-Kyung
TI NON-CULPRIT CORONARY PLAQUE CHARACTERISTICS OF CHRONIC KIDNEY DISEASE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Kato, Koji; Yonetsu, Taishi; Jia, Haibo; Abtahian, Farhad; Vergallo, Rocco; Kim, Soo-Joong; Lee, Hang; McNulty, Iris; Lee, Stephen; Uemura, Shiro; Jang, Yang Soo; Park, Seung-Jung; Mizuno, Kyoichi; Yu, Bo; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1730
EP E1730
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201835
ER
PT J
AU Le Elizabeth, DT
Pascotto, M
Leong-Poi, H
Sari, I
Micari, A
Kaul, S
AF Le Elizabeth, Dai-Trang
Pascotto, Marco
Leong-Poi, Howard
Sari, Ibrahim
Micari, Antonio
Kaul, Sanjiv
TI ANTI-INFLAMMATORY AND PRO-ANGIOGENIC EFFECTS OF BETA-BLOCKERS IN A
CANINE MODEL OF CHRONIC ISCHEMIC CARDIOMYOPATHY: COMPARISON BETWEEN
CARVEDILOL AND METOPROLOL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Portland VA Med Ctr, Portland, OR USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1175
EP E1175
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201280
ER
PT J
AU Lin, EY
Cohen, HW
Johnson, J
Stefanescu, A
Bhatt, AB
Lui, GK
AF Lin, Elaine Y.
Cohen, Hillel W.
Johnson, Jacob
Stefanescu, Ada
Bhatt, Ami B.
Lui, George K.
TI PREDICTING OUTCOMES USING THE HEART FAILURE SURVIVAL SCORE IN ADULTS
WITH CONGENITAL HEART DISEASE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E507
EP E507
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200507
ER
PT J
AU MacNabb, MH
Abdelbaky, A
Lavender, ZR
Kaplan, RS
di Carli, M
Taqueti, V
Foster, C
Mann, J
Comley, R
Weber, CIK
Tawakol, A
AF MacNabb, Megan H.
Abdelbaky, Amr
Lavender, Zachary R.
Kaplan, Rebecca S.
di Carli, Marcelo
Taqueti, Viviany
Foster, Courtney
Mann, Jessica
Comley, Robert
Weber, Chek Ing Kiu
Tawakol, Ahmed
TI ARTERIAL INFLAMMATION IS HIGHER IN INDIVIDUALS WITH CHRONIC KIDNEY
DISEASE AND LOW FRAMINGHAM RISK SCORES
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
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 ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E838
EP E838
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200838
ER
PT J
AU May, EB
Scirica, B
Bonaca, M
Murphy, S
Braunwald, E
Morrow, D
AF May, Erin Bohula
Scirica, Benjamin
Bonaca, Marc
Murphy, Sabina
Braunwald, Eugene
Morrow, David
TI PROGNOSTIC VALUE OF HIGH-SENSITIVITY CRP FOR CARDIOVASCULAR OUTCOMES IN
TRA 2 degrees P-TIMI 50
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
TIMI Study Grp, Boston, MA USA.
NR 0
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 MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1162
EP E1162
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201267
ER
PT J
AU Mehrotra, P
Jansen, K
Tan, T
Flynn, A
Elmariah, S
Picard, M
Hung, J
AF Mehrotra, Praveen
Jansen, Katrijn
Tan, Timothy
Flynn, Aidan
Elmariah, Sammy
Picard, Michael
Hung, Judy
TI PROGNOSIS OF PATIENTS WITH ISOLATED SEVERE AORTIC STENOSIS: ARE OUTCOMES
SIMILAR FOR ALL PATIENTS WITH AN AORTIC VALVE AREA LESS THAN 1.0 CM2?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1937
EP E1937
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202141
ER
PT J
AU Motiwala, S
Szymonifka, J
Belcher, A
Weiner, R
Baggish, A
Sluss, P
Gaggin, H
Bhardwaj, A
Januzzi, J
AF Motiwala, Shweta
Szymonifka, Jackie
Belcher, Arianna
Weiner, Rory
Baggish, Aaron
Sluss, Patrick
Gaggin, Hanna
Bhardwaj, Anju
Januzzi, James
TI SERIAL MEASUREMENT OF GALECTIN-3 PREDICTS CHRONIC HEART FAILURE OUTCOMES
AND VENTRICULAR REMODELING: RESULTS FROM THE PROBNP OUTPATIENT TAILORED
CHRONIC HEART FAILURE THERAPY (PROTECT) STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Motiwala, Shweta; Szymonifka, Jackie; Belcher, Arianna; Weiner, Rory; Baggish, Aaron; Sluss, Patrick; Gaggin, Hanna; Bhardwaj, Anju; Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E745
EP E745
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200745
ER
PT J
AU Motiwala, S
Bhardwaj, A
Szymonifka, J
Belcher, A
Weiner, R
Baggish, A
Gaggin, H
Januzzi, J
AF Motiwala, Shweta
Bhardwaj, Anju
Szymonifka, Jackie
Belcher, Arianna
Weiner, Rory
Baggish, Aaron
Gaggin, Hanna
Januzzi, James
TI SERIAL MEASUREMENT OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 7
PREDICTS CHRONIC HEART FAILURE OUTCOMES AND VENTRICULAR REMODELING:
RESULTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE
THERAPY (PROTECT) STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Motiwala, Shweta; Bhardwaj, Anju; Szymonifka, Jackie; Belcher, Arianna; Weiner, Rory; Baggish, Aaron; Gaggin, Hanna; Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E565
EP E565
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200565
ER
PT J
AU Niesor, EJ
Schwartz, G
Suchankova, G
Benghozi, R
Abt, M
Kallend, D
AF Niesor, Eric J.
Schwartz, Gregory
Suchankova, Gabriela
Benghozi, Renee
Abt, Markus
Kallend, David
TI STATIN-INDUCED DECREASE IN ABCA1 EXPRESSION VIA MIR33 INDUCTION MAY
COUNTERACT CHOLESTEROL EFFLUX BY HIGH-DENSITY LIPOPROTEINS RAISED WITH
THE CHOLESTERYL ESTER TRANSFER PROTEIN MODULATOR DALCETRAPIB
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 F Hoffmann La Roche Ltd, Basel, Switzerland.
Denver VA Med Ctr, Denver, CO USA.
NR 0
TC 2
Z9 2
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 MAR 12
PY 2013
VL 61
IS 10
SU S
BP E2032
EP E2032
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202236
ER
PT J
AU Nunes, MCP
Tan, T
Elmariah, S
do Lago, R
Inglessis, I
Palacios, I
Hung, J
Levine, R
AF Pereira Nunes, Maria Carmo
Tan, Timothy
Elmariah, Sammy
do Lago, Rodrigo
Inglessis, Ignacio
Palacios, Igor
Hung, Judy
Levine, Robert
TI NET ATRIOVENTRICULAR COMPLIANCE IS AN INDEPENDENT PREDICTOR OF MORTALITY
IN MITRAL STENOSIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA.
Univ Fed Minas Gerais, Sch Med, Belo Horizonte, MG, Brazil.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1931
EP E1931
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202135
ER
PT J
AU Rajabali, A
Asrani, P
Bhatt, A
He, W
Benavidez, O
AF Rajabali, Alefiyah
Asrani, Priyanka
Bhatt, Ami
He, Wei
Benavidez, Oscar
TI HIGH RESOURCE USE AMONG ADULT CONGENITAL HEART SURGERY ADMISSIONS IN
ADULT HOSPITALS: RISK FACTORS AND ASSOCIATION WITH DEATH AND
COMPLICATIONS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Rajabali, Alefiyah; Asrani, Priyanka; Bhatt, Ami; He, Wei; Benavidez, Oscar] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E534
EP E534
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200534
ER
PT J
AU Saha, S
Beatty, A
Mishra, R
Whooley, M
Schiller, N
AF Saha, Sandeep
Beatty, Alexis
Mishra, Rakesh
Whooley, Mary
Schiller, Nelson
TI AN ECHOCARDIOGRAPHIC COMPOSITE CARDIAC CALCIFICATION SCORE PREDICTS
MAJOR CARDIOVASCULAR EVENTS IN PATIENTS WITH STABLE CORONARY ARTERY
DISEASE: THE HEART AND SOUL STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1024
EP E1024
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201129
ER
PT J
AU Singh, P
Tawakol, A
Mojena, M
Pimentel-Santillana, M
Fayad, ZA
Rudd, J
Traves, PG
Fernandez, M
Tejedor, A
Bosca, L
AF Singh, Parmanand
Tawakol, Ahmed
Mojena, Marina
Pimentel-Santillana, Maria
Fayad, Zahi A.
Rudd, James
Traves, Paqui G.
Fernandez, Maria
Tejedor, Alberto
Bosca, Lisardo
TI GM-CSF ENHANCES GLYCOLYTIC ACTIVITY IN MACROPHAGES IN VITRO AND IMPROVES
DETECTION OF ATHEROSCLEROTIC INFLAMMATION IN VIVO
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Inst Invest Biomed Alberto Sols, Madrid, Spain.
RI G. Traves, Paqui/L-5693-2014; Pimentel-Santillana, Maria/L-9437-2014
OI G. Traves, Paqui/0000-0001-5749-8426; Pimentel-Santillana,
Maria/0000-0003-1179-4259
NR 0
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1153
EP E1153
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201258
ER
PT J
AU Tian, JW
Hu, SN
Jia, HB
Abtahian, F
Kato, K
Yonetsu, T
Vergallo, R
McNulty, I
Zhang, SS
Yu, B
Jang, IK
AF Tian, JinWei
Hu, Sining
Jia, Haibo
Abtahian, Farhad
Kato, Koji
Yonetsu, Taishi
Vergallo, Rocco
McNulty, Iris
Zhang, Shaosong
Yu, Bo
Jang, Ik-Kyung
TI GENDER DIFFERENCE IN CULPRIT LESION CHARACTERISTICS IN PATIENTS WITH
ACS: AN OPTICAL COHERENCE TOMOGRAPHY STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E79
EP E79
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200080
ER
PT J
AU Truong, QA
Thai, WE
Wai, B
Zhou, Q
Brown, H
Bennett, R
Beaudoin, J
Singh, J
Barrett, C
Danik, S
AF Truong, Quynh A.
Thai, Wai-ee
Wai, Bryan
Zhou, Qing
Brown, Heather
Bennett, Richard
Beaudoin, Jonathan
Singh, Jagmeet
Barrett, Conor
Danik, Stephan
TI A NEW METHOD USING CARDIAC CT KINEMATICS TO REFLECT THE ACTIVATION
PATTERN VISUALIZED WITH ELECTROANATOMICAL MAP: CARDIAC CT PHASE TIME
VELOCITY ACTIVATION-ENCODED MAP (ACTIVATE)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
QI Imaging LLC, Redwood City, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E913
EP E913
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201018
ER
PT J
AU Truong, QA
Thai, WE
Szymonifka, J
Basnet, S
Wai, B
Grunau, Z
Beaudoin, J
Smith, CL
Babatunde, A
Ajijola, O
Singh, J
Januzzi, J
AF Truong, Quynh A.
Thai, Wai-ee
Szymonifka, Jackie
Basnet, Sandeep
Wai, Bryan
Grunau, Zachary
Beaudoin, Jonathan
Smith, Chelsea L.
Babatunde, Adefolakemi
Ajijola, Olujimi
Singh, Jagmeet
Januzzi, James
TI CORONARY SINUS LEVEL OF GALECTIN-3 IS A BETTER PREDICTOR THAN PERIPHERAL
VENOUS LEVEL OF MAJOR ADVERSE CARDIAC EVENTS IN PATIENTS WITH CARDIAC
RESYNCHRONIZATION THERAPY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Truong, Quynh A.; Thai, Wai-ee; Szymonifka, Jackie; Basnet, Sandeep; Wai, Bryan; Grunau, Zachary; Beaudoin, Jonathan; Smith, Chelsea L.; Babatunde, Adefolakemi; Ajijola, Olujimi; Singh, Jagmeet; Januzzi, James] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E248
EP E248
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200248
ER
PT J
AU Vergallo, R
Yonetsu, T
Lee, S
Uemura, S
Kato, K
Jia, HB
Abtahian, F
Tian, JW
Hu, SN
Aguirre, A
McNulty, I
Lee, H
Zhang, SS
Yu, B
Porto, I
Biasucci, L
Crea, F
Jang, IK
AF Vergallo, Rocco
Yonetsu, Taishi
Lee, Stephen
Uemura, Shiro
Kato, Koji
Jia, Haibo
Abtahian, Farhad
Tian, Jinwei
Hu, Sining
Aguirre, Aaron
McNulty, Iris
Lee, Hang
Zhang, Shaosong
Yu, Bo
Porto, Italo
Biasucci, Luigi
Crea, Filippo
Jang, Ik-Kyung
TI CORRELATION BETWEEN DEGREE OF NEOINTIMAL HYPERPLASIA AND INCIDENCE AND
CHARACTERISTICS OF NEOATHEROSCLEROSIS AFTER STENT IMPLANTATION: AN
OPTICAL COHERENCE TOMOGRAPHY STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Vergallo, Rocco; Yonetsu, Taishi; Lee, Stephen; Uemura, Shiro; Kato, Koji; Jia, Haibo; Abtahian, Farhad; Tian, Jinwei; Hu, Sining; Aguirre, Aaron; McNulty, Iris; Lee, Hang; Zhang, Shaosong; Yu, Bo; Porto, Italo; Biasucci, Luigi; Crea, Filippo; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
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 MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1800
EP E1800
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202005
ER
PT J
AU Weinberg, I
Rogers, K
Halpern, E
Jaff, M
AF Weinberg, Ido
Rogers, Kevin
Halpern, Elkan
Jaff, Michael
TI PREDICTORS OF CLINICAL BENEFIT OF RENAL ARTERY STENTING IN 1,003
PATIENTS IN SIX PROSPECTIVE MULTICENTER TRIALS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Weinberg, Ido; Rogers, Kevin; Halpern, Elkan; Jaff, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E2058
EP E2058
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202262
ER
PT J
AU Weiner, RB
Isaacs, SK
Wang, F
Berkstresser, B
Wang, T
Hutter, A
Lewis, G
Picard, M
Baggish, A
AF Weiner, Rory B.
Isaacs, Stephanie K.
Wang, Francis
Berkstresser, Brant
Wang, Thomas
Hutter, Adolph
Lewis, Gregory
Picard, Michael
Baggish, Aaron
TI FUNCTIONAL IMPLICATIONS OF THE ATHLETE'S HEART: MYOCARDIAL STRAIN AND
TWIST PROVIDE A MECHANISM FOR THE ADAPTIVE RESPONSE TO INTRAVASCULAR
VOLUME CHALLENGE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Weiner, Rory B.; Isaacs, Stephanie K.; Wang, Francis; Berkstresser, Brant; Wang, Thomas; Hutter, Adolph; Lewis, Gregory; Picard, Michael; Baggish, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1624
EP E1624
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201729
ER
PT J
AU Yonetsu, T
Kato, K
Yu, B
Uemura, S
Jia, HB
Vergallo, R
Abtahian, F
Tian, JW
Hu, SN
Aguirre, A
McNulty, I
Zhang, SS
Lee, H
Jang, IK
AF Yonetsu, Taishi
Kato, Koji
Yu, Bo
Uemura, Shiro
Jia, Haibo
Vergallo, Rocco
Abtahian, Farhad
Tian, Jinwei
Hu, Sining
Aguirre, Aaron
McNulty, Iris
Zhang, Shaosong
Lee, Hang
Jang, Ik-Kyung
TI COMPREHENSIVE THREE-VESSEL PLAQUE MAPPING BY OPTICAL COHERENCE
TOMOGRAPHY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Yonetsu, Taishi; Kato, Koji; Yu, Bo; Uemura, Shiro; Jia, Haibo; Vergallo, Rocco; Abtahian, Farhad; Tian, Jinwei; Hu, Sining; Aguirre, Aaron; McNulty, Iris; Zhang, Shaosong; Lee, Hang; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1783
EP E1783
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555201888
ER
PT J
AU Yonetsu, T
Suh, W
Abtahian, F
Kato, K
Vergallo, R
Jia, HB
Kim, SJ
McNulty, I
Lee, H
Jang, IK
AF Yonetsu, Taishi
Suh, William
Abtahian, Farhad
Kato, Koji
Vergallo, Rocco
Jia, Haibo
Kim, Soo-Joong
McNulty, Iris
Lee, Hang
Jang, Ik-Kyung
TI COMPARISON OF NEAR-INFRARED SPECTROSCOPY AND OPTICAL COHERENCE
TOMOGRAPHY FOR DETECTION OF LIPID
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Yonetsu, Taishi; Suh, William; Abtahian, Farhad; Kato, Koji; Vergallo, Rocco; Jia, Haibo; Kim, Soo-Joong; McNulty, Iris; Lee, Hang; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E1796
EP E1796
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555202001
ER
PT J
AU Zakroysky, P
Basnet, S
Thai, WE
Onandia, ZG
Gandhi, S
Truong, Q
AF Zakroysky, Pearl
Basnet, Sandeep
Thai, Wai-ee
Onandia, Zurine Galvan
Gandhi, Sachin
Quynh Truong
TI DRAMATIC REDUCTION IN ACUTE CORONARY SYNDROME WITH STEROID EXPOSURE IN
PATIENTS WITH INFLAMMATORY BOWEL DISEASE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Zakroysky, Pearl; Basnet, Sandeep; Thai, Wai-ee; Onandia, Zurine Galvan; Gandhi, Sachin; Quynh Truong] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E180
EP E180
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200181
ER
PT J
AU Zeng, X
Nunes, M
Hung, J
AF Zeng, Xin
Nunes, Maria
Hung, Judy
TI ASYMMETRIC OR SYMMETRIC MITRAL LEAFLET TETHERING: PATTERN OF TETHERING
AN IMPORTANT DETERMINANT OF ISCHEMIC MITRAL REGURGITATION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Session of the American-College-of-Cardiology
CY MAR 09-11, 2013
CL San Francisco, CA
SP Amer Coll Cardiol
C1 [Zeng, Xin; Nunes, Maria; Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 12
PY 2013
VL 61
IS 10
SU S
BP E884
EP E884
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 111XO
UT WOS:000316555200884
ER
PT J
AU Ghaffari, R
Page, SL
Farrahi, S
Sellon, JB
Freeman, DM
AF Ghaffari, Roozbeh
Page, Scott L.
Farrahi, Shirin
Sellon, Jonathan B.
Freeman, Dennis M.
TI Electrokinetic properties of the mammalian tectorial membrane
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cochlear amplification; cochlear mechanics; mechanoelectrical
transduction; motility
ID POLYELECTROLYTE GEL MODEL; HAIR CELL BUNDLES; INNER-EAR; EQUILIBRIUM
BEHAVIOR; TRAVELING-WAVES; HEARING-LOSS; TRANSDUCTION; COCHLEA; ORGAN;
CORTI
AB The tectorial membrane (TM) clearly plays a mechanical role in stimulating cochlear sensory receptors, but the presence of fixed charge in TM constituents suggests that electromechanical properties also may be important. Here, we measure the fixed charge density of the TM and show that this density of fixed charge is sufficient to affect mechanical properties and to generate electrokinetic motions. In particular, alternating currents applied to the middle and marginal zones of isolated TM segments evoke motions at audio frequencies (1-1,000 Hz). Electrically evoked motions are nanometer scaled (similar to 5-900 nm), decrease with increasing stimulus frequency, and scale linearly over a broad range of electric field amplitudes (0.05-20 kV/m). These findings show that the mammalian TM is highly charged and suggest the importance of a unique TM electrokinetic mechanism.
C1 [Ghaffari, Roozbeh; Page, Scott L.; Farrahi, Shirin; Sellon, Jonathan B.; Freeman, Dennis M.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
[Ghaffari, Roozbeh; Sellon, Jonathan B.; Freeman, Dennis M.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Page, Scott L.; Farrahi, Shirin; Freeman, Dennis M.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Freeman, Dennis M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA.
RP Freeman, DM (reprint author), MIT, Elect Res Lab, Cambridge, MA 02139 USA.
EM freeman@mit.edu
FU National Institutes of Health [R01-DC00238]; Harvard-MIT Division of
Health Sciences and Technology
FX We thank A. Grodzinsky and J. Guinan for helpful discussions about the
manuscript. This research was supported by National Institutes of Health
Grant R01-DC00238. R.G. was supported in part by a training grant from
the National Institutes of Health to the Speech and Hearing Bioscience
and Technology Program of the Harvard-MIT Division of Health Sciences
and Technology.
NR 61
TC 4
Z9 4
U1 0
U2 11
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 12
PY 2013
VL 110
IS 11
BP 4279
EP 4284
DI 10.1073/pnas.1214744110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107RK
UT WOS:000316238300033
PM 23440188
ER
PT J
AU Haq, R
Yokoyama, S
Hawryluk, EB
Jonssond, GB
Frederick, DT
McHenry, K
Porter, D
Tran, TN
Love, KT
Langer, R
Anderson, DG
Garraway, LA
Duncan, LM
Morton, DL
Hoon, DSB
Wargo, JA
Song, JS
Fisher, DE
AF Haq, Rizwan
Yokoyama, Satoru
Hawryluk, Elena B.
Jonssond, Goran B.
Frederick, Dennie Tampers
McHenry, Kevin
Porter, Dale
Tran, Thanh-Nga
Love, Kevin T.
Langer, Robert
Anderson, Daniel G.
Garraway, Levi A.
Duncan, Lyn McDivitt
Morton, Donald L.
Hoon, Dave S. B.
Wargo, Jennifer A.
Song, Jun S.
Fisher, David E.
TI BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that
confers resistance to BRAF inhibition
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID MALIGNANT-MELANOMA; METASTATIC MELANOMA; SURVIVAL ONCOGENE; CELL-LINES;
IN-VIVO; B-RAF; CANCER; MUTATION; MITF; SENSITIVITY
AB Although targeting oncogenic mutations in the BRAF serine/threonine kinase with small molecule inhibitors can lead to significant clinical responses in melanoma, it fails to eradicate tumors in nearly all patients. Successful therapy will be aided by identification of intrinsic mechanisms that protect tumor cells from death. Here, we used a bioinformatics approach to identify drug-able, "driver" oncogenes restricted to tumor versus normal tissues. Applying this method to 88 short-term melanoma cell cultures, we show that the antiapoptotic BCL2 family member BCL2A1 is recurrently amplified in similar to 30% of melanomas and is necessary for melanoma growth. BCL2A1 overexpression also promotes melanomagenesis of BRAF-immortalized melanocytes. We find that high-level expression of BCL2A1 is restricted to melanoma due to direct transcriptional control by the melanoma oncogene MITF. Although BRAF inhibitors lead to cell cycle arrest and modest apoptosis, we find that apoptosis is significantly enhanced by suppression of BCL2A1 in melanomas with BCL2A1 or MITF amplification. Moreover, we find that BCL2A1 expression is associated with poorer clinical responses to BRAF pathway inhibitors in melanoma patients. Cotreatment of melanomas with BRAF inhibitors and obatoclax, an inhibitor of BCL2A1 and other BCL2 family members, overcomes intrinsic resistance to BRAF inhibitors in BCL2A1-amplified cells in vitro and in vivo. These studies identify MITF-BCL2A1 as a lineage-specific oncogenic pathway in melanoma and underscore its role for improved response to BRAF-directed therapy.
C1 [Haq, Rizwan; Fisher, David E.] Massachusetts Gen Hosp, Dept Med, Div Med Oncol, Boston, MA 02115 USA.
[Haq, Rizwan; Yokoyama, Satoru; Hawryluk, Elena B.; Tran, Thanh-Nga; Fisher, David E.] Massachusetts Gen Hosp, Dermatol & Cutaneous Biol Res Ctr, Boston, MA 02115 USA.
[Frederick, Dennie Tampers; Wargo, Jennifer A.] Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Duncan, Lyn McDivitt] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02115 USA.
[Yokoyama, Satoru] Toyama Univ, Inst Nat Med, Div Pathogen Biochem, Toyama 9300194, Japan.
[Jonssond, Goran B.] Lund Univ, Dept Oncol, SE-22100 Lund, Sweden.
[Love, Kevin T.; Langer, Robert] Oncol Drug Discovery, Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
[Love, Kevin T.; Langer, Robert; Anderson, Daniel G.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Langer, Robert; Anderson, Daniel G.] MIT, Harvard MIT Div Hlth Sci & Technol, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Garraway, Levi A.] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Garraway, Levi A.] MIT, Cambridge, MA 02142 USA.
[Morton, Donald L.] John Wayne Canc Inst, Dept Mol Oncol, Santa Monica, CA 90404 USA.
[Hoon, Dave S. B.; Song, Jun S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94107 USA.
[Song, Jun S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA.
RP Song, JS (reprint author), Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94107 USA.
EM Songj@humgen.ucsf.edu; dfisher3@partners.org
RI Jonsson, Goran/D-1212-2014;
OI Hoon, Dave/0000-0003-1915-3683
FU American Skin Association; National Institute of Arthritis and
Musculoskeletal and Skin Diseases/National Institutes of Health (NIH);
Melanoma Research Alliance; Dr. Miriam and Sheldon G. Adelson Medical
Research Foundation; Ministry of Education, Culture, Sports, Science,
and Technology, Japan [24700971]; NIH [eb00244]; PhRMA Foundation;
University of California at San Francisco (UCSF); Committee on Research;
UCSF Research Allocation Program; National Cancer Institute
[R01CA163336]
FX We thank Meenhard Herlyn (Wistar Institute) for cell lines, Gideon
Bollag and Plexxikon for PLX4720-containing chow, Hans Widlund (Brigham
and Women's Hospital), and members of the Fisher laboratory for
discussions and suggestions. We thank Juying Li for advice, Su-Jean Seo
(Beth-Israel Deaconess Hospital) for help with microscopy, and
Myung-Shin Sims (John Wayne Cancer Institute) for statistical help. This
work was supported by the American Skin Association (R.H.); National
Institute of Arthritis and Musculoskeletal and Skin Diseases/National
Institutes of Health (NIH); the Melanoma Research Alliance; the Dr.
Miriam and Sheldon G. Adelson Medical Research Foundation (D.L.M.,
D.S.B.H., and D.E.F.); and Grant-in-Aid 24700971 for Young Scientists
(B) (to S.Y.) from the Ministry of Education, Culture, Sports, Science,
and Technology, Japan. D.G.A. is supported by NIH Grant eb00244. J.S.S.
acknowledges support from the PhRMA Foundation, University of California
at San Francisco (UCSF), Committee on Research, UCSF Research Allocation
Program, and National Cancer Institute Grant R01CA163336. D.E.F. is a
Distinguished Clinical Scholar of the Doris Duke Medical Foundation.
NR 43
TC 75
Z9 76
U1 0
U2 19
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 12
PY 2013
VL 110
IS 11
BP 4321
EP 4326
DI 10.1073/pnas.1205575110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107RK
UT WOS:000316238300040
PM 23447565
ER
PT J
AU Chiyomaru, T
Yamamura, S
Fukuhara, S
Hidaka, H
Majid, S
Saini, S
Arora, S
Deng, GR
Shahryari, V
Chang, I
Tanaka, Y
Tabatabai, ZL
Enokida, H
Seki, N
Nakagawa, M
Dahiya, R
AF Chiyomaru, Takeshi
Yamamura, Soichiro
Fukuhara, Shinichiro
Hidaka, Hideo
Majid, Shahana
Saini, Sharanjot
Arora, Sumit
Deng, Guoren
Shahryari, Varahram
Chang, Inik
Tanaka, Yuichiro
Tabatabai, Z. Laura
Enokida, Hideki
Seki, Naohiko
Nakagawa, Masayuki
Dahiya, Rajvir
TI Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate
Cancer
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; MATRIX-METALLOPROTEINASE TYPE-2; INHIBITS
CELL-PROLIFERATION; ANDROGEN-INDEPENDENCE; ENRICHMENT ANALYSIS;
SIGNALING PATHWAY; INDUCED APOPTOSIS; GENE-EXPRESSION; BLADDER-CANCER;
TARGETING EGFR
AB Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs). In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa) and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1) and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as 'Pathways in cancer', 'Jak-STAT signaling pathway', and 'Wnt signaling pathway'. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 39 UTR of several target genes (such as RAC1, EGFR and EP300) that are components of 'Pathways in cancer'. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.
C1 [Chiyomaru, Takeshi; Yamamura, Soichiro; Fukuhara, Shinichiro; Majid, Shahana; Saini, Sharanjot; Arora, Sumit; Deng, Guoren; Shahryari, Varahram; Chang, Inik; Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA.
[Chiyomaru, Takeshi; Yamamura, Soichiro; Fukuhara, Shinichiro; Majid, Shahana; Saini, Sharanjot; Arora, Sumit; Deng, Guoren; Shahryari, Varahram; Chang, Inik; Tanaka, Yuichiro; Tabatabai, Z. Laura; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hidaka, Hideo; Enokida, Hideki; Nakagawa, Masayuki] Kagoshima Univ, Dept Urol, Grad Sch Med & Dent Sci, Kagoshima 890, Japan.
[Tabatabai, Z. Laura] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA USA.
[Seki, Naohiko] Chiba Univ, Grad Sch Med, Dept Funct Genom, Chiba, Japan.
RP Dahiya, R (reprint author), San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA.
EM rdahiya@urology.ucsf.edu
FU National Center for Research Resources of the National Institutes of
Health [R01CA160079, R01CA138642, T32DK007790]; VA Merit Review; VA
Program Project
FX This research was supported by the National Center for Research
Resources of the National Institutes of Health through Grant Numbers
R01CA160079, R01CA138642, T32DK007790 and VA Merit Review and VA Program
Project. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 55
TC 49
Z9 52
U1 0
U2 12
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 MAR 12
PY 2013
VL 8
IS 3
AR e58929
DI 10.1371/journal.pone.0058929
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WV
UT WOS:000316252500058
PM 23554959
ER
PT J
AU Kamlet, AS
Neumann, CN
Lee, E
Carlin, SM
Moseley, CK
Stephenson, N
Hooker, JM
Ritter, T
AF Kamlet, Adam S.
Neumann, Constanze N.
Lee, Eunsung
Carlin, Stephen M.
Moseley, Christian K.
Stephenson, Nickeisha
Hooker, Jacob M.
Ritter, Tobias
TI Application of Palladium-Mediated F-18-Fluorination to PET Radiotracer
Development: Overcoming Hurdles to Translation
SO PLOS ONE
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; RECEPTOR MESSENGER-RNA; REDUCTIVE
ELIMINATION; CELLULAR-LOCALIZATION; TRANSPORTER BINDING; DRUG
DEVELOPMENT; HUMAN BRAIN; FLUORINE; CHEMISTRY; LIGANDS
AB New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging-an important milestone on the path to human PET imaging. The method, which transforms [F-18]fluoride into an electrophilic fluorination reagent, provides access to aryl-F-18 bonds that would be challenging to synthesize via conventional radiochemistry methods.
C1 [Kamlet, Adam S.; Neumann, Constanze N.; Lee, Eunsung; Stephenson, Nickeisha; Ritter, Tobias] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Carlin, Stephen M.; Moseley, Christian K.; Hooker, Jacob M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Carlin, Stephen M.; Moseley, Christian K.; Hooker, Jacob M.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Hooker, Jacob M.; Ritter, Tobias] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
RP Hooker, JM (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM hooker@nmr.mgh.harvard.edu; ritter@chemistry.harvard.edu
RI Lee, Eunsung/F-5308-2013;
OI Hooker, Jacob/0000-0002-9394-7708
FU National Institutes of Health (NIH) [GM088237, MH093874, EB013042,
S10RR017208, S10RR022976]
FX This work was supported by the National Institutes of Health (NIH)
(GM088237, MH093874, EB013042, S10RR017208, and S10RR022976). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 49
TC 27
Z9 27
U1 3
U2 64
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 MAR 12
PY 2013
VL 8
IS 3
AR e59187
DI 10.1371/journal.pone.0059187
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WV
UT WOS:000316252500072
PM 23554994
ER
PT J
AU Stipp, RN
Boisvert, H
Smith, DJ
Hofling, JF
Duncan, MJ
Mattos-Graner, RO
AF Stipp, Rafael N.
Boisvert, Heike
Smith, Daniel J.
Hoefling, Jose F.
Duncan, Margaret J.
Mattos-Graner, Renata O.
TI CovR and VicRK Regulate Cell Surface Biogenesis Genes Required for
Biofilm Formation in Streptococcus mutans
SO PLOS ONE
LA English
DT Article
ID GLUCAN-BINDING-PROTEIN; GLUCOSYLTRANSFERASE GTFBC OPERON;
SIGNAL-TRANSDUCTION PATHWAY; YYCF RESPONSE REGULATOR; GRAM-POSITIVE
BACTERIA; STAPHYLOCOCCUS-AUREUS; ORAL STREPTOCOCCI; MUREIN HYDROLASE;
PNEUMONIAE R6; IN-VIVO
AB The two-component system VicRK and the orphan regulator CovR of Streptococcus mutans co-regulate a group of virulence genes associated with the synthesis of and interaction with extracellular polysaccharides of the biofilm matrix. Knockout mutants of vicK and covR display abnormal cell division and morphology phenotypes, although the gene function defects involved are as yet unknown. Using transcriptomic comparisons between parent strain UA159 with vicK (UAvic) or covR (UAcov) deletion mutants together with electrophoretic motility shift assays (EMSA), we identified genes directly regulated by both VicR and CovR with putative functions in cell wall/surface biogenesis, including gbpB, wapE, smaA, SMU.2146c, and lysM. Deletion mutants of genes regulated by VicR and CovR (wapE, lysM, smaA), or regulated only by VicR (SMU.2146c) or CovR (epsC) promoted significant alterations in biofilm initiation, including increased fragility, defects in microcolony formation, and atypical cell morphology and/or chaining. Significant reductions in mureinolytic activity and/or increases in DNA release during growth were observed in knockout mutants of smaA, wapE, lysM, SMU.2146c and epsC, implying roles in cell wall biogenesis. WapE and lysM mutations also affected cell hydrophobicity and sensitivity to osmotic or oxidative stress. Finally, vicR, covR and VicRK/CovR-targets (gbpB, wapE, smaA, SMU.2146c, lysM, epsC) are up-regulated in UA159 during biofilm initiation, in a sucrose-dependent manner. These data support a model in which VicRK and CovR coordinate cell division and surface biogenesis with the extracellular synthesis of polysaccharides, a process apparently required for formation of structurally stable biofilms in the presence of sucrose.
C1 [Stipp, Rafael N.; Hoefling, Jose F.; Mattos-Graner, Renata O.] Univ Campinas UNICAMP, Dept Oral Diag, Piracicaba Dent Sch, Sao Paulo, Brazil.
[Boisvert, Heike; Duncan, Margaret J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA.
[Smith, Daniel J.] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA.
RP Mattos-Graner, RO (reprint author), Univ Campinas UNICAMP, Dept Oral Diag, Piracicaba Dent Sch, Sao Paulo, Brazil.
EM rmgraner@fop.unicamp.br
RI Mattos-Graner, Renata/C-9410-2012
OI Mattos-Graner, Renata/0000-0001-8309-8135
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [proc.
07/56100-2, 09/54182-7, proc. 06/55933-8]; National Institutes of Health
(NIH) Fogarty award [R03-TW-06324]; CAPES (PNPD); [R01 DE15931]; [R37
DE06153]
FX This study was supported by Fundacao de Amparo a Pesquisa do Estado de
Sao Paulo (FAPESP, proc. 07/56100-2 and 09/54182-7) and the National
Institutes of Health (NIH) Fogarty award R03-TW-06324. RNS was supported
by FAPESP (proc. 06/55933-8) and CAPES (PNPD, 2010). MJD was supported
by R01 DE15931 and R37 DE06153. DJS was supported by R37 DE06153. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 57
TC 15
Z9 16
U1 1
U2 23
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 MAR 12
PY 2013
VL 8
IS 3
AR e58271
DI 10.1371/journal.pone.0058271
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WV
UT WOS:000316252500019
PM 23554881
ER
PT J
AU Iskandrian, AE
Hage, FG
AF Iskandrian, Ami E.
Hage, Fadi G.
TI Declining Frequency of Ischemia Detection Using Stress Myocardial
Perfusion Imaging
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE coronary artery disease risk factors; myocardial ischemia; perfusion;
prognosis
ID AMERICAN-HEART-ASSOCIATION; CORONARY-ARTERY-DISEASE; OPTIMAL MEDICAL
THERAPY; COMPUTED-TOMOGRAPHY; NUCLEAR CARDIOLOGY; TRIAL; OUTCOMES; RISK
C1 [Iskandrian, Ami E.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA.
RP Iskandrian, AE (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, 318 LHRB,1900 Univ Blvd, Birmingham, AL 35294 USA.
EM aiskand@uab.edu
OI Hage, Fadi/0000-0002-1397-4942
NR 17
TC 10
Z9 11
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 MAR 12
PY 2013
VL 61
IS 10
BP 1066
EP 1068
DI 10.1016/j.jacc.2012.12.009
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 100HA
UT WOS:000315687300006
PM 23473412
ER
PT J
AU Knight, SJ
AF Knight, Sara J.
TI Bridging the Gap at the Center of Patient Centeredness Individual
Patient Preferences in Health Care Decision Making
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID MEN
C1 [Knight, Sara J.] US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Off Res & Dev, Vet Hlth Adm, Washington, DC 20420 USA.
[Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
RP Knight, SJ (reprint author), US Dept Vet Affairs, Hlth Serv Res & Dev Serv, Off Res & Dev, Vet Hlth Adm, 180 Vermont Ave NW, Washington, DC 20420 USA.
EM sara.knight@va.gov
NR 9
TC 1
Z9 1
U1 2
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 11
PY 2013
VL 173
IS 5
BP 369
EP 370
DI 10.1001/jamainternmed.2013.3370
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153OY
UT WOS:000319613100009
PM 23400376
ER
PT J
AU Prochazka, AV
Caverly, T
AF Prochazka, Allan V.
Caverly, Tanner
TI General Health Checks in Adults for Reducing Morbidity and Mortality
From Disease Summary Review of Primary Findings and Conclusions
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Prochazka, Allan V.] Denver VA Med Ctr, Dept Ambulatory Care, Denver, CO 80220 USA.
Univ Colorado, Sch Med, Div Gen Internal Med, Denver, CO USA.
RP Prochazka, AV (reprint author), Denver VA Med Ctr, Dept Ambulatory Care, 11B,1055 Clermont, Denver, CO 80220 USA.
EM allan.prochazka@va.gov
NR 8
TC 5
Z9 6
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 11
PY 2013
VL 173
IS 5
BP 371
EP 372
DI 10.1001/jamainternmed.2013.3187
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153OY
UT WOS:000319613100010
PM 23318544
ER
PT J
AU Dodson, JA
Fried, TR
Van Ness, PH
Goldstein, NE
Lampert, R
AF Dodson, John A.
Fried, Terri R.
Van Ness, Peter H.
Goldstein, Nathan E.
Lampert, Rachel
TI Patient Preferences for Deactivation of Implantable
Cardioverter-Defibrillators
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
ID LIFE; END; MANAGEMENT
C1 [Dodson, John A.; Lampert, Rachel] Yale Univ, Sch Med, Cardiol Sect, Dept Internal Med, New Haven, CT 06520 USA.
[Dodson, John A.; Fried, Terri R.; Van Ness, Peter H.] Yale Univ, Sch Med, Sect Geriatr, Dept Internal Med, New Haven, CT 06520 USA.
Mt Sinai Sch Med, Dept Geriatr & Palliat Care, New York, NY USA.
[Goldstein, Nathan E.] James J Peters VA Med Ctr, Bronx, NY USA.
RP Lampert, R (reprint author), Yale Univ, Sch Med, Cardiol Sect, 789 Howard Ave,Dana 3,Room 319, New Haven, CT 06520 USA.
EM rachel.lampert@yale.edu
FU NIA NIH HHS [T32 AG019134, P30 AG021342, P30AG021342, K24AG028443, K24
AG028443]
NR 9
TC 18
Z9 18
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 11
PY 2013
VL 173
IS 5
BP 377
EP 379
DI 10.1001/jamainternmed.2013.1883
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153OY
UT WOS:000319613100013
PM 23358714
ER
PT J
AU Steinman, MA
AF Steinman, Michael A.
TI Reaching Out to Patients to Identify Adverse Drug Reactions and
Nonadherence: Necessary but Not Sufficient
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID MEDICATION; CARE
C1 [Steinman, Michael A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Steinman, MA (reprint author), San Francisco VA Med Ctr, POB 181G,4150 Clement St, San Francisco, CA 94121 USA.
EM mike.steinman@ucsf.edu
FU NIA NIH HHS [K23 AG030999, 1K23-AG030999.]
NR 8
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 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 11
PY 2013
VL 173
IS 5
BP 384
EP 385
DI 10.1001/jamainternmed.2013.2965
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153OY
UT WOS:000319613100017
PM 23381677
ER
PT J
AU Chatterjee, P
Joynt, KE
Jha, AK
AF Chatterjee, Paula
Joynt, Karen E.
Jha, Ashish K.
TI Safety-Net Hospitals: Other Hospitals Score Similarly on Patient
Experience reply
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
C1 [Chatterjee, Paula; Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy, Boston, MA 02115 USA.
[Chatterjee, Paula; Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Management, Boston, MA 02115 USA.
[Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
[Joynt, Karen E.; Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA.
[Joynt, Karen E.] Harvard Univ, Div Cardiovasc Med, Sch Med, Boston, MA 02115 USA.
[Jha, Ashish K.] Harvard Univ, Div Gen Internal Med, Sch Med, Boston, MA 02115 USA.
[Chatterjee, Paula] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
EM ajha@hsph.harvard.edu
NR 3
TC 0
Z9 0
U1 2
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAR 11
PY 2013
VL 173
IS 5
BP 390
EP 391
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 153OY
UT WOS:000319613100022
ER
PT J
AU Naik, AD
Martin, LA
Karel, M
Wachen, JS
Mulligan, E
Gosian, JS
Herman, LI
Moye, J
AF Naik, Aanand D.
Martin, Lindsey A.
Karel, Michele
Wachen, Jennifer Schuster
Mulligan, Elizabeth
Gosian, Jeffrey S.
Herman, Levi Ian
Moye, Jennifer
TI Cancer survivor rehabilitation and recovery: Protocol for the Veterans
Cancer Rehabilitation Study (Vet-CaRes)
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
DE Cancer care; Cancer survivorship; Veterans; Aging; Psychosocial;
Functional assessment; Quality of life
ID QUALITY-OF-LIFE; BREAST-CANCER; QUESTIONNAIRE; HEALTH; OLDER;
COMORBIDITY; RELIABILITY; PERSPECTIVE; DISTRESS; VALIDITY
AB Background: Cancer survivors are a rapidly growing and aging population in the U. S., but there are many challenges associated with the survivorship experience such as functional disabilities and psychosocial distress. When viewed next to the general population, Veterans are especially at risk for these challenges as they are older and have a high incidence of co-morbid conditions. While the Institute of Medicine (IOM) has called for further cancer survivorship research to address these challenges, we still know little about this experience from the perspective of aging Veterans.
Methods/design: We conducted a longitudinal, mixed-methods study over the course of three and a half years at the Boston and Houston VA Medical Centers. We recruited 170 Veterans diagnosed with head and neck, colorectal and esophageal/gastric cancers that were identified from the VA tumor registry. Veterans completed three in-depth interviews, conducted at 6, 12 and 18 months after pathology confirmation, measuring the physical, social and psychological factors related to cancer survivorship. The longitudinal design allowed us to assess any changes in cancer related disability and distress over time.
Discussion: Weekly teleconference study team meetings were a key aspect to the research process. Issues related to recruitment, data management and analysis, and the dissemination of research results was discussed. Interviewers presented detailed case reports of completed interviews that allowed us to refine our interview protocols. We also discussed issues relevant to the Veteran population of which we were previously unaware and some of the challenges of the research process itself. This novel study produced a robust data set that documents the functional and psychosocial cancer survivorship experiences of aging Veterans. The longitudinal design will help us more fully understand the recovery patterns for this specific population, and identify the unique needs and gaps in health services.
C1 [Naik, Aanand D.; Martin, Lindsey A.; Herman, Levi Ian] Michael E DeBakey VA Med Ctr, Houston VA Hlth Serv, Res & Dev Ctr Excellence, Houston, TX USA.
[Naik, Aanand D.; Martin, Lindsey A.; Herman, Levi Ian] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Karel, Michele; Wachen, Jennifer Schuster; Mulligan, Elizabeth; Gosian, Jeffrey S.; Moye, Jennifer] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Karel, Michele; Mulligan, Elizabeth; Gosian, Jeffrey S.; Moye, Jennifer] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Wachen, Jennifer Schuster] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Martin, LA (reprint author), Michael E DeBakey VA Med Ctr, Houston VA Hlth Serv, Res & Dev Ctr Excellence, Houston, TX USA.
EM Lindsey.Martin3@va.gov
RI Moye, Jennifer/F-2240-2017
OI Moye, Jennifer/0000-0002-3434-347X
FU Department of Veterans Affairs Rehabilitation Research and Development
Service [5I01RX000104-02]
FX Funding for this study was provided by the Department of Veterans
Affairs Rehabilitation Research and Development Service
(5I01RX000104-02).
NR 45
TC 7
Z9 7
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD MAR 11
PY 2013
VL 13
AR 93
DI 10.1186/1472-6963-13-93
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 124KI
UT WOS:000317461800001
PM 23497430
ER
PT J
AU Cleary, RT
Sun, HY
Huynh, T
Manning, SM
Li, YJ
Rotenberg, A
Talos, DM
Kahle, KT
Jackson, M
Rakhade, SN
Berry, G
Jensen, FE
AF Cleary, Ryan T.
Sun, Hongyu
Thanhthao Huynh
Manning, Simon M.
Li, Yijun
Rotenberg, Alexander
Talos, Delia M.
Kahle, Kristopher T.
Jackson, Michele
Rakhade, Sanjay N.
Berry, Gerard
Jensen, Frances E.
TI Bumetanide Enhances Phenobarbital Efficacy in a Rat Model of Hypoxic
Neonatal Seizures
SO PLOS ONE
LA English
DT Article
ID NA-K-2CL COTRANSPORTER NKCC1; CRITICALLY ILL INFANTS; DEVELOPING BRAIN;
ANTIEPILEPTIC DRUGS; APOPTOTIC NEURODEGENERATION; STATUS EPILEPTICUS;
IMMATURE BRAIN; HIPPOCAMPUS; GABA; PHARMACOKINETICS
AB Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na+-K+-2 Cl- cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABA(A) receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in E-GABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.
C1 [Cleary, Ryan T.; Sun, Hongyu; Thanhthao Huynh; Manning, Simon M.; Rotenberg, Alexander; Talos, Delia M.; Jackson, Michele; Rakhade, Sanjay N.; Jensen, Frances E.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Li, Yijun; Berry, Gerard] Childrens Hosp, Div Genet & Metab, Boston, MA 02115 USA.
[Manning, Simon M.] Brigham & Womens Hosp, Div Newborn Med, Boston, MA 02115 USA.
[Jensen, Frances E.] Harvard Univ, Sch Med, Program Neurobiol, Boston, MA USA.
[Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA USA.
RP Jensen, FE (reprint author), Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
EM frances.jensen@uphs.upenn.edu
OI Berry, Gerard/0000-0001-5299-3313
FU National Institutes of Health (NIH) [NS 31718, 1R21NS080268]; National
Institutes of Health (NIH) (Office of the Director) [DPI OD003347];
Intellectual Developmental Disabilities Center [P30 HD18655]
FX This work was supported by National Institutes of Health (NIH) Grants:
NS 31718 (NINDS) (FEJ), DPI OD003347 (from the Office of the Director)
(FEJ), 1R21NS080268 (FEJ), and Intellectual Developmental Disabilities
Center Grant P30 HD18655 (NICHD). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
TC 39
Z9 40
U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 11
PY 2013
VL 8
IS 3
AR e57148
DI 10.1371/journal.pone.0057148
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WI
UT WOS:000316251100007
PM 23536761
ER
PT J
AU Guo, YY
Yuan, HS
Cho, HS
Kuruppu, D
Jokivarsi, K
Agarwal, A
Shah, K
Josephson, L
AF Guo, Yanyan
Yuan, Hushan
Cho, Hoonsung
Kuruppu, Darshini
Jokivarsi, Kimmo
Agarwal, Aayush
Shah, Khalid
Josephson, Lee
TI High Efficiency Diffusion Molecular Retention Tumor Targeting
SO PLOS ONE
LA English
DT Article
ID BENIGN PROSTATIC HYPERPLASIA; RGD PEPTIDES; NEUROENDOCRINE TUMORS;
THERAPY; DESIGN; CANCER; NANOPARTICLE; THERAPEUTICS; PROTEINS; ANALOGS
AB Here we introduce diffusion molecular retention (DMR) tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT) injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding) and RAD (control) probes were synthesized bearing DOTA (for (111) In3+), a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or IV methods was assessed by surface fluorescence, biodistribution of [In-111] RGD and [In-111] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [In-111] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352% ID/g tumor obtained by DMR (vs 4.14% ID/g by IV). The high efficiency molecular targeting of DMR employed low probe doses (e. g. 25 ng as RGD peptide), which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e. g. toxic, short range alpha emitters) for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.
C1 [Guo, Yanyan; Yuan, Hushan; Cho, Hoonsung; Kuruppu, Darshini; Josephson, Lee] Massachusetts Gen Hosp, Dept Radiol, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA.
[Jokivarsi, Kimmo; Josephson, Lee] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Jokivarsi, Kimmo] Univ Eastern Finland, AI Virtanen Inst, Dept Neurobiol, Kuopio, Finland.
[Agarwal, Aayush; Shah, Khalid] Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Dept Radiol, Charlestown, MA USA.
RP Josephson, L (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Translat Nucl Med & Mol Imaging, Charlestown, MA 02129 USA.
EM ljosephson@mgh.harvard.edu
FU National Institutes of Health [R01 EB 011996, R01 EB 009691]
FX National Institutes of Health Grants to Josephson # R01 EB 011996 and #
R01 EB 009691. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 52
TC 7
Z9 7
U1 1
U2 23
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 MAR 11
PY 2013
VL 8
IS 3
AR e58290
DI 10.1371/journal.pone.0058290
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WI
UT WOS:000316251100041
PM 23505478
ER
PT J
AU Schwede, M
Spentzos, D
Bentink, S
Hofmann, O
Haibe-Kains, B
Harrington, D
Quackenbush, J
Culhane, AC
AF Schwede, Matthew
Spentzos, Dimitrios
Bentink, Stefan
Hofmann, Oliver
Haibe-Kains, Benjamin
Harrington, David
Quackenbush, John
Culhane, Aedin C.
TI Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II
Subtype and Prognosis
SO PLOS ONE
LA English
DT Article
ID NEGATIVE BREAST-CANCER; TO-MESENCHYMAL TRANSITION; GRADE SEROUS
CARCINOMA; BRCA MUTATION CARRIERS; POLY(ADP-RIBOSE) POLYMERASE;
MOLECULAR SUBTYPES; SET ENRICHMENT; P53 STATUS; TUMORS; METASTASIS
AB Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable in the clinical management or treatment of ovarian cancer.
C1 [Schwede, Matthew; Bentink, Stefan; Haibe-Kains, Benjamin; Harrington, David; Quackenbush, John; Culhane, Aedin C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hofmann, Oliver; Harrington, David; Quackenbush, John; Culhane, Aedin C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Spentzos, Dimitrios] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA.
[Bentink, Stefan] Exosome Diagnost GmbH, Martinsried, Germany.
[Haibe-Kains, Benjamin] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada.
RP Culhane, AC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM aedin@jimmy.harvard.edu
RI Haibe-Kains, Benjamin/D-3702-2011;
OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Hofmann,
Oliver/0000-0002-7738-1513; Coppola, Vincenzo/0000-0001-6163-1779
FU National Institutes of Health [1U19CA148065]; Dana-Farber Cancer
Institute Women's Cancers Program; Claudia Adams Barr foundation
FX Funding for this work was provided by the National Institutes of Health
1U19CA148065 (J.Q., B.H.K.), Dana-Farber Cancer Institute Women's
Cancers Program (awarded to A.C.C; M.S, A.C.C.) and the Claudia Adams
Barr foundation (J.Q. and A.C.C.). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 68
TC 17
Z9 17
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 11
PY 2013
VL 8
IS 3
AR e57799
DI 10.1371/journal.pone.0057799
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WI
UT WOS:000316251100016
PM 23536770
ER
PT J
AU Wright, AA
Stieglitz, H
Kupersztoch, YM
Paulk, ME
Kim, Y
Katz, IT
Munoz, F
Jimenez, RB
Mutchler, J
Rivera, L
Back, AL
Prigerson, HG
AF Wright, Alexi A.
Stieglitz, Heather
Kupersztoch, Yankel M.
Paulk, M. Elizabeth
Kim, Yookyung
Katz, Ingrid T.
Munoz, Francisco
Jimenez, Rachel B.
Mutchler, Jan
Rivera, Lorna
Back, Anthony L.
Prigerson, Holly G.
TI United States Acculturation and Cancer Patients' End-of-Life Care
SO PLOS ONE
LA English
DT Article
ID STAGE LUNG-CANCER; ETHNIC-DIFFERENCES; SOCIOECONOMIC-STATUS;
RACIAL-DIFFERENCES; MEXICAN-AMERICANS; AFRICAN-AMERICAN;
CLINICAL-TRIALS; CULTURAL ISSUES; PALLIATIVE CARE; THE-LITERATURE
AB Background: Culture shapes how people understand illness and death, but few studies examine whether acculturation influences patients' end-of-life treatment preferences and medical care.
Methods and Findings: In this multi-site, prospective, longitudinal cohort study of terminally-ill cancer patients and their caregivers (n = 171 dyads), trained interviewers administered the United States Acculturation Scale (USAS). The USAS is a 19-item scale developed to assess the degree of "Americanization" in first generation or non-US born caregivers of terminally-ill cancer patients. We evaluated the internal consistency, concurrent, criterion, and content validity of the USAS. We also examined whether caregivers' USAS scores predicted patients' communication, treatment preferences, and end-of-life medical care in multivariable models that corrected for significant confounding influences (e.g. education, country of origin, English proficiency). The USAS measure was internally consistent (Cronbach alpha = 0.98); and significantly associated with US birthplace (r = 0.66, P < 0.0001). USAS scores were predictive of patients' preferences for prognostic information (AOR = 1.31, 95% CI: 1.00-1.72), but not comfort asking physicians' questions about care (AOR 1.23, 95% CI: 0.87-1.73). They predicted patients' preferences for feeding tubes (AOR = 0.68, 95% CI: 0.49-0.99) and wish to avoid dying in an intensive care unit (AOR = 1.36, 95% CI: 1.05-1.76). Scores indicating greater acculturation were also associated with increased odds of patient participation in clinical trials (AOR = 2.20, 95% CI: 1.28-3.78), compared with lower USAS scores, and greater odds of patients receiving chemotherapy (AOR = 1.59, 95% CI: 1.20-2.12).
Conclusion: The USAS is a reliable and valid measure of "Americanization" associated with advanced cancer patients' end-of-life preferences and care. USAS scores indicating greater caregiver acculturation were associated with increased odds of patient participation in cancer treatment (chemotherapy, clinical trials) compared with lower scores. Future studies should examine the effects of acculturation on end-of-life care to identify patient and provider factors that explain these effects and targets for future interventions to improve care (e.g., by designing more culturally-competent health education materials).
C1 [Wright, Alexi A.; Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wright, Alexi A.; Jimenez, Rachel B.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA.
[Wright, Alexi A.; Katz, Ingrid T.; Jimenez, Rachel B.; Prigerson, Holly G.] Harvard Univ, Sch Med, Boston, MA USA.
[Wright, Alexi A.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Stieglitz, Heather] Parkland Ctr Clin Innovat, Dallas, TX USA.
[Kupersztoch, Yankel M.; Paulk, M. Elizabeth] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kim, Yookyung] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Katz, Ingrid T.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Munoz, Francisco] Pomona Valley Hosp Med Ctr, Pomona, CA USA.
[Jimenez, Rachel B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Mutchler, Jan; Rivera, Lorna] Univ Massachusetts, Boston, MA 02125 USA.
[Back, Anthony L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM Holly_Prigerson@dfci.harvard.edu
FU National Institute of Mental Health [MH63892]; National Cancer Institute
[CA 106370, CA 156732]; Conquer Cancer Foundation of the American
Society of Clinical Oncology; National Palliative Care Research Center;
American Cancer Society; Center for Psychosocial Epidemiology and
Outcomes Research, Dana-Farber Cancer Institute
FX This research was supported in part by the following grants to Dr.
Prigerson: MH63892 from the National Institute of Mental Health and CA
106370 and CA 156732 from the National Cancer Institute; by Career
Development Awards sponsored by the Conquer Cancer Foundation of the
American Society of Clinical Oncology, the National Palliative Care
Research Center, and the American Cancer Society to Dr. Wright; and by
the Center for Psychosocial Epidemiology and Outcomes Research,
Dana-Farber Cancer Institute. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 61
TC 4
Z9 4
U1 4
U2 20
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 MAR 11
PY 2013
VL 8
IS 3
AR e58663
DI 10.1371/journal.pone.0058663
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 107WI
UT WOS:000316251100076
PM 23536809
ER
PT J
AU Ohashi, K
Maruvka, YE
Michor, F
Pao, W
AF Ohashi, Kadoaki
Maruvka, Yosef E.
Michor, Franziska
Pao, William
TI Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-Resistant
Disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID CELL LUNG-CANCER; CHRONIC MYELOID-LEUKEMIA; PREVIOUSLY TREATED PATIENTS;
CISPLATIN PLUS GEMCITABINE; NERVOUS-SYSTEM METASTASES; DOSE WEEKLY
ERLOTINIB; RANDOMIZED PHASE-III; ACQUIRED-RESISTANCE; EGFR MUTATIONS;
NEVER-SMOKERS
AB Purpose
EGFR-mutant lung cancer was first described as a new clinical entity in 2004. Here, we present an update on new controversies and conclusions regarding the disease.
Methods
This article reviews the clinical implications of EGFR mutations in lung cancer with a focus on epidermal growth factor receptor tyrosine kinase inhibitor resistance.
Results
The discovery of EGFR mutations has altered the ways in which we consider and treat non-small-cell lung cancer (NSCLC). Patients whose metastatic tumors harbor EGFR mutations are expected to live longer than 2 years, more than double the previous survival rates for lung cancer.
Conclusion
The information presented in this review can guide practitioners and help them inform their patients about EGFR mutations and their impact on the treatment of NSCLC. Efforts should now concentrate on making EGFR-mutant lung cancer a chronic rather than fatal disease. J Clin Oncol 31:1070-1080. (C) 2013 by American Society of Clinical Oncology
C1 [Ohashi, Kadoaki; Pao, William] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Maruvka, Yosef E.; Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Maruvka, Yosef E.; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Pao, W (reprint author), Vanderbilt Ingram Canc Ctr, 2220 Pierce Ave,777 PRB, Nashville, TN 37232 USA.
EM william.pao@vanderbilt.edu
RI Mendez, Pedro /J-8955-2016
OI Mendez, Pedro /0000-0001-6713-7907
FU National Cancer Institute, National Institutes of Health [R01-CA121210,
P01-CA129243, U54-CA143798, P30-CA68485]; AstraZeneca; Clovis;
Bristol-Myers Squibb
FX Supported by Grants No. R01-CA121210, P01-CA129243, U54-CA143798, and
P30-CA68485 from the National Cancer Institute, National Institutes of
Health.; William Pao, AstraZeneca, Clovis, Bristol-Myers Squibb
NR 114
TC 161
Z9 168
U1 0
U2 41
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 MAR 10
PY 2013
VL 31
IS 8
BP 1070
EP 1080
DI 10.1200/JCO.2012.43.3912
PG 11
WC Oncology
SC Oncology
GA 104LL
UT WOS:000315994300011
PM 23401451
ER
PT J
AU Oxnard, GR
Binder, A
Janne, PA
AF Oxnard, Geoffrey R.
Binder, Adam
Jaenne, Pasi A.
TI New Targetable Oncogenes in Non-Small-Cell Lung Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID GROWTH-FACTOR RECEPTOR; ANAPLASTIC LYMPHOMA KINASE; HARBORING BRAF
MUTATIONS; PHASE-III TRIAL; THYROID-CANCER; SIGNALING PATHWAY;
BREAST-CANCER; PIK3CA GENE; ADENOCARCINOMA; INHIBITOR
AB The identification of oncogenic driver mutations underlying sensitivity to epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non-small-cell lung cancer. A number of new potentially oncogenic gene alterations have been characterized in recent years, including BRAF mutations, HER2 insertions, PIK3CA mutations, FGFR1 amplifications, DDR2 mutations, ROS1 rearrangements, and RET rearrangements. In this review, we will discuss the techniques used to discover each of these candidate oncogenes, the prevalence of each in non-small-cell lung cancer, the preclinical data supporting their role in lung cancer, and data on small molecular inhibitors in development. J Clin Oncol 31:1097-1104. (C) 2013 by American Society of Clinical Oncology
C1 [Oxnard, Geoffrey R.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Oxnard, Geoffrey R.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA.
[Binder, Adam] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,HIM223, Boston, MA 02215 USA.
EM pasi_janne@dfci.harvard.edu
FU National Cancer Institute, National Institutes of Health [P50-CA090578]
FX Supported in part by Grant No. P50-CA090578 from the National Cancer
Institute, National Institutes of Health.
NR 81
TC 132
Z9 135
U1 4
U2 42
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 MAR 10
PY 2013
VL 31
IS 8
BP 1097
EP 1104
DI 10.1200/JCO.2012.42.9829
PG 8
WC Oncology
SC Oncology
GA 104LL
UT WOS:000315994300014
PM 23401445
ER
PT J
AU Shaw, AT
Engelman, JA
AF Shaw, Alice T.
Engelman, Jeffrey A.
TI ALK in Lung Cancer: Past, Present, and Future
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID ANAPLASTIC LYMPHOMA KINASE; EML4-ALK FUSION GENE; EGFR MUTATION;
1ST-LINE TREATMENT; OPEN-LABEL; RESISTANCE; CHEMOTHERAPY; GEFITINIB;
CRIZOTINIB; INHIBITORS
AB In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers. J Clin Oncol 31:1105-1111. (C) 2013 by American Society of Clinical Oncology
C1 [Shaw, Alice T.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Shaw, Alice T.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7B,32 Fruit St, Boston, MA 02114 USA.
EM ashaw1@partners.org
FU Novartis; AstraZeneca; sanofi-aventis
FX Alice T. Shaw, Novartis, AstraZeneca; Jeffrey A. Engelman, Novartis,
AstraZeneca, sanofi-aventis
NR 45
TC 130
Z9 136
U1 2
U2 33
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2013
VL 31
IS 8
BP 1105
EP 1111
DI 10.1200/JCO.2012.44.5353
PG 7
WC Oncology
SC Oncology
GA 104LL
UT WOS:000315994300015
PM 23401436
ER
PT J
AU Barthelemy, O
Limbourg, T
Collet, JP
Beygui, F
Silvain, J
Bellemain-Appaix, A
Cayla, G
Chastre, T
Baumgartner, I
Rother, J
Zeymer, U
Bhatt, DL
Steg, G
Montalescot, G
AF Barthelemy, Olivier
Limbourg, Tobias
Collet, Jean Philippe
Beygui, Farzin
Silvain, Johanne
Bellemain-Appaix, Anne
Cayla, Guillaume
Chastre, Thomas
Baumgartner, Iris
Roether, Joachim
Zeymer, Uwe
Bhatt, Deepak L.
Steg, Gabriel
Montalescot, Gilles
CA REACH Registry Investigators
TI Impact of non-steroidal anti-inflammatory drugs (NSAIDs) on
cardiovascular outcomes in patients with stable atherothrombosis or
multiple risk factors
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE NSAIDs; Cardiovascular outcomes; Myocardial infarction; Stroke;
Bleeding; Atherothrombosis
ID RANDOMIZED CONTROLLED-TRIAL; RHEUMATOID-ARTHRITIS; CYCLOOXYGENASE-2
INHIBITORS; GASTROINTESTINAL TOXICITY; MYOCARDIAL-INFARCTION;
BLOOD-PRESSURE; STROKE; ROFECOXIB; CELECOXIB; NAPROXEN
AB Background: We aimed to assess whether the use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of cardiovascular (CV) events in stable patients with established atherothrombosis or multiple risk factors.
Methods: We analysed the 23,728 European patients of the REACH Registry; 20,588 (86.8%) had established atherothrombotic disease and 3140 (13.2%) had multiple risk factors only. Aspirin (ASA) and/or NSAIDs use was determined at enrolment and ischemic events were recorded over two years of follow-up. cMACCE was defined as the composite of CV death, MI or stroke. Bleeding was defined as any bleeding leading to both hospitalisation and transfusion.
Results: The mean age of population was 67.2 +/- 9.8 years. At baseline, 1573 patients (6.6%) received NSAIDs and 15,395 (64.9%) received ASA. Four groups were defined: 1) no ASA/no NSAIDs, 2) ASA only, 3) NSAIDs only, 4) NSAIDs + ASA, with 7722 (32.5%), 14,433 (60.8%), 611 (2.6%) and 962 (4.1%) patients in these groups, respectively. Among the 22,028 (92.8%) with complete 2-year follow-up, 683 (3.2%) died from CV causes, while 395 (1.9%) had MI, 665 (3.1%) stroke, 1651 (7.6%) cMACCE and 199 (1.0%) bleeding. After adjustment, NSAID use was independently associated with an increased risk of stroke (OR 1.635; 95% CI 1.239-2.159, p<0.001), and a trend towards an increased bleeding rate (OR 1.554; CI 95% 0.960-2.51, p=0.07). No association was found between NSAID use and MI or MACCE.
Conclusions: In stable atherothrombosis patients, the use of NSAIDs appears to be independently associated with an increased cerebrovascular event risk. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Barthelemy, Olivier; Collet, Jean Philippe; Beygui, Farzin; Silvain, Johanne; Bellemain-Appaix, Anne; Cayla, Guillaume; Chastre, Thomas; Montalescot, Gilles] APHP, Inst Cardiol, INSERM, CMR937, Paris, France.
[Barthelemy, Olivier; Collet, Jean Philippe; Beygui, Farzin; Silvain, Johanne; Bellemain-Appaix, Anne; Cayla, Guillaume; Chastre, Thomas; Montalescot, Gilles] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France.
[Limbourg, Tobias; Zeymer, Uwe] Heidelberg Univ, Inst Herzinfarktforsch Ludwigshafen, Ludwigshafen, Germany.
[Baumgartner, Iris] Univ Hosp Bern, Swiss Cardiovasc Ctr, Div Clin & Intervent Angiol, Inselspital, CH-3010 Bern, Switzerland.
[Roether, Joachim] Hamburg Med Sch, Dept Neurol, Asklepios Klin Altona, Hamburg, Germany.
[Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
[Steg, Gabriel] Univ Paris 07, INSERM, U698, Paris, France.
[Steg, Gabriel] AP HP, Paris, France.
RP Montalescot, G (reprint author), Ctr Hosp Univ Pitie Salpetriere, AP HP, Inst Cardiol, Bur 236, 47-83 Blvd Hop, F-75013 Paris, France.
EM gilles.montalescot@psl.aphp.fr
FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan)
FX The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb,
and the Waksman Foundation (Tokyo, Japan). The REACH Registry is
endorsed by the World Heart Federation. A complete list of REACH
investigators is accessible online at www.reachregistry.org. The REACH
Registry enforces a no ghost-writing policy. The first draught was
written by Olivier Barthelemy. We thank Deborah Burrage, PhD, for her
assistance with coordinating revisions and providing editorial help in
preparing this manuscript including editing, checking content and
language, formatting, referencing and preparing tables and figures, and
Tobias Limbourg for his support with statistical analyses.
NR 30
TC 8
Z9 8
U1 7
U2 27
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD MAR 10
PY 2013
VL 163
IS 3
BP 266
EP 271
DI 10.1016/j.ijcard.2011.06.015
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 092XJ
UT WOS:000315156000013
PM 21719126
ER
PT J
AU Pride, YB
Cutlip, DE
AF Pride, Yuri B.
Cutlip, Donald E.
TI Disappearing stents-DREAMS of a sorcerer's apprentice?
SO LANCET
LA English
DT Editorial Material
ID PACLITAXEL-ELUTING STENTS; VASCULAR SCAFFOLD; CORONARY-ARTERIES;
EVEROLIMUS; THROMBOSIS; OUTCOMES; 2ND-GENERATION; METAANALYSIS; HUMANS;
TRIAL
C1 [Pride, Yuri B.; Cutlip, Donald E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,Dept Med, Boston, MA 02215 USA.
RP Cutlip, DE (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,Dept Med, Boston, MA 02215 USA.
EM dcutlip@bidmc.harvard.edu
NR 16
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 0140-6736
J9 LANCET
JI Lancet
PD MAR 9
PY 2013
VL 381
IS 9869
BP 787
EP 789
DI 10.1016/S0140-6736(12)62036-4
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105IL
UT WOS:000316060600009
PM 23332166
ER
PT J
AU He, YQ
Cao, ZW
De Groot, AS
Brusic, V
Schonbach, C
Petrovsky, N
AF He, Yongqun
Cao, Zhiwei
De Groot, Anne S.
Brusic, Vladimir
Schoenbach, Christian
Petrovsky, Nikolai
TI Computational vaccinology and the ICoVax 2012 workshop
SO BMC BIOINFORMATICS
LA English
DT Editorial Material
ID YELLOW-FEVER VACCINE; IMMUNOTHERAPY VACCINES; REVERSE VACCINOLOGY;
EPITOPE PREDICTION; SYSTEMS BIOLOGY; UNITED-STATES; ASSOCIATION;
DETERMINANTS; INFORMATICS; RESPONSES
AB Computational vaccinology or vaccine informatics is an interdisciplinary field that addresses scientific and clinical questions in vaccinology using computational and informatics approaches. Computational vaccinology overlaps with many other fields such as immunoinformatics, reverse vaccinology, postlicensure vaccine research, vaccinomics, literature mining, and systems vaccinology. The second ISV Pre-conference Computational Vaccinology Workshop (ICoVax 2012) was held on October 13, 2013 in Shanghai, China. A number of topics were presented in the workshop, including allergen predictions, prediction of linear T cell epitopes and functional conformational epitopes, prediction of protein-ligand binding regions, vaccine design using reverse vaccinology, and case studies in computational vaccinology. Although a significant progress has been made to date, a number of challenges still exist in the field. This Editorial provides a list of major challenges for the future of computational vaccinology and identifies developing themes that will expand and evolve over the next few years.
C1 [He, Yongqun] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Unit Lab Anim Med, Ann Arbor, MI 48109 USA.
[He, Yongqun] Univ Michigan, Sch Med, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Cao, Zhiwei] Tongji Univ, Dept Biomed Engn, Coll Life Sci & Technol, Shanghai 200092, Peoples R China.
[De Groot, Anne S.] EpiVax Inc, Providence, RI 02903 USA.
[De Groot, Anne S.] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02903 USA.
[Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Schoenbach, Christian] Kyushu Inst Technol, Dept Biosci & Bioinformat, Fukuoka 8208502, Japan.
[Schoenbach, Christian] Kyushu Inst Technol, Biomed Informat Res & Dev Ctr BMIRC, Fukuoka 8208502, Japan.
[Petrovsky, Nikolai] Flinders Med Ctr, Bedford Pk, SA 5042, Australia.
RP He, YQ (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Unit Lab Anim Med, Ann Arbor, MI 48109 USA.
EM yongqunh@umich.edu
RI De Groot, Anne/B-6221-2013; Schonbach, Christian/B-1998-2009;
OI De Groot, Anne/0000-0001-5911-1459; Schonbach,
Christian/0000-0002-0693-7617; He, Yongqun/0000-0001-9189-9661;
Petrovsky, Nikolai/0000-0002-1580-5245
FU NIAID NIH HHS [1R01AI081062, U19AI082642]
NR 48
TC 12
Z9 12
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAR 8
PY 2013
VL 14
SU 4
AR I1
DI 10.1186/1471-2105-14-S4-I1
PG 6
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 142RR
UT WOS:000318815300001
PM 23514034
ER
PT J
AU Bergwitz, C
Wee, MJ
Sinha, S
Huang, JN
DeRobertis, C
Mensah, LB
Cohen, J
Friedman, A
Kulkarni, M
Hu, YH
Vinayagam, A
Schnall-Levin, M
Berger, B
Perkins, LA
Mohr, SE
Perrimon, N
AF Bergwitz, Clemens
Wee, Mark J.
Sinha, Sumi
Huang, Joanne
DeRobertis, Charles
Mensah, Lawrence B.
Cohen, Jonathan
Friedman, Adam
Kulkarni, Meghana
Hu, Yanhui
Vinayagam, Arunachalam
Schnall-Levin, Michael
Berger, Bonnie
Perkins, Lizabeth A.
Mohr, Stephanie E.
Perrimon, Norbert
TI Genetic Determinants of Phosphate Response in Drosophila
SO PLOS ONE
LA English
DT Article
ID RECEPTOR TYROSINE KINASE; CHRONIC KIDNEY-DISEASE; VASCULAR
CALCIFICATION; INORGANIC-PHOSPHATE; MINERAL METABOLISM; IN-VITRO;
PROTEIN; EXPRESSION; MICE; BONE
AB Phosphate is required for many important cellular processes and having too little phosphate or too much can cause disease and reduce life span in humans. However, the mechanisms underlying homeostatic control of extracellular phosphate levels and cellular effects of phosphate are poorly understood. Here, we establish Drosophila melanogaster as a model system for the study of phosphate effects. We found that Drosophila larval development depends on the availability of phosphate in the medium. Conversely, life span is reduced when adult flies are cultured on high phosphate medium or when hemolymph phosphate is increased in flies with impaired Malpighian tubules. In addition, RNAi-mediated inhibition of MAPK-signaling by knockdown of Ras85D, phl/D-Raf or Dsor1/MEK affects larval development, adult life span and hemolymph phosphate, suggesting that some in vivo effects involve activation of this signaling pathway by phosphate. To identify novel genetic determinants of phosphate responses, we used Drosophila hemocyte-like cultured cells (S2R+) to perform a genome-wide RNAi screen using MAPK activation as the readout. We identified a number of candidate genes potentially important for the cellular response to phosphate. Evaluation of 51 genes in live flies revealed some that affect larval development, adult life span and hemolymph phosphate levels.
C1 [Bergwitz, Clemens; Wee, Mark J.; Sinha, Sumi; Huang, Joanne; DeRobertis, Charles; Mensah, Lawrence B.; Cohen, Jonathan] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Friedman, Adam; Kulkarni, Meghana; Hu, Yanhui; Vinayagam, Arunachalam; Perkins, Lizabeth A.; Mohr, Stephanie E.; Perrimon, Norbert] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA USA.
[Schnall-Levin, Michael; Berger, Bonnie] MIT, Dept Math & Comp Sci, Cambridge, MA 02139 USA.
[Schnall-Levin, Michael; Berger, Bonnie] MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA.
RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
EM cwhb2002@yahoo.com
OI arunachalam, vinayagam/0000-0003-0091-4497; Mohr,
Stephanie/0000-0001-9639-7708
FU Harvard Catalyst; NIDDK [1K08 DK08361]
FX CB received funding for this project by the Harvard Catalyst and NIDDK
1K08 DK08361. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 73
TC 3
Z9 3
U1 0
U2 27
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 MAR 8
PY 2013
VL 8
IS 3
AR e56753
DI 10.1371/journal.pone.0056753
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 140TZ
UT WOS:000318679900014
PM 23520455
ER
PT J
AU Dams, J
Klotsche, J
Bornschein, B
Reese, JP
Balzer-Geldsetzer, M
Winter, Y
Schrag, A
Siderowf, A
Oertel, WH
Deuschl, G
Siebert, U
Dodel, R
AF Dams, Judith
Klotsche, Jens
Bornschein, Bernhard
Reese, Jens P.
Balzer-Geldsetzer, Monika
Winter, Yaroslav
Schrag, Anette
Siderowf, Andrew
Oertel, Wolfgang H.
Deuschl, Guenther
Siebert, Uwe
Dodel, Richard
TI Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson's
disease
SO HEALTH AND QUALITY OF LIFE OUTCOMES
LA English
DT Article
DE Parkinson's disease; Quality of life; EuroQoL/EQ-5D; UPDRS; PDQ-8;
Prediction
ID QUALITY-OF-LIFE
AB Background: Clinical studies employ the Unified Parkinson's Disease Rating Scale (UPDRS) to measure the severity of Parkinson's disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates.
Methods: Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson's disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson's disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R-2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon's link test. Three independent data sets validated the models.
Results: The regression analyses resulted in a single best prediction model (R-2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R-2 of 0.60 and 0.67. The independent data confirmed the prediction models.
Conclusion: The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.
C1 [Dams, Judith; Reese, Jens P.; Balzer-Geldsetzer, Monika; Winter, Yaroslav; Oertel, Wolfgang H.; Dodel, Richard] Philipps Univ, Dept Neurol, Marburg, Germany.
[Klotsche, Jens] German Rheumatism Res Ctr, Leibniz Inst, Epidemiol Unit, Berlin, Germany.
[Bornschein, Bernhard; Siebert, Uwe] UMIT Univ Hlth Sci, Dept Publ Hlth & Hlth Technol Assessment, Inst Publ Hlth, Hall It, Australia.
[Schrag, Anette] Royal Free & Univ Coll Med Sch, Dept Clin Neurosci, London WC1E 6BT, England.
[Siderowf, Andrew] Avid Radiopharmaceut, Philadelphia, PA USA.
[Deuschl, Guenther] Univ Kiel, Dept Neurol, Kiel, Germany.
[Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Publ Hlth Decis Modelling, Innsbruck, Austria.
[Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA 02115 USA.
[Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA.
[Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Dodel, R (reprint author), Philipps Univ, Dept Neurol, Marburg, Germany.
EM dodel@med.uni-marburg.de
RI Deuschl, Gunther/A-7986-2010
FU German Federal Ministry of Education and Research/Parkinson Competence
Network [01GI9901/1]; German Parkinson Association; COMET Center
ONCOTYROL; Austrian Federal Ministries BMVIT/BMWFJ (via FFG); Tiroler
Zukunftsstiftung/Standortagentur Tirol (SAT)
FX This study was supported by a research grant from the German Federal
Ministry of Education and Research/Parkinson Competence Network,
01GI9901/1 and the German Parkinson Association. Prof. Siebert's work
was in part supported by the COMET Center ONCOTYROL, which is funded by
the Austrian Federal Ministries BMVIT/BMWFJ (via FFG) and the Tiroler
Zukunftsstiftung/Standortagentur Tirol (SAT). Andrew Siderowf is an
employee of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli
Lilly and Co. No competing financial and non-financial interests exist
which adversely affected the preparation of this manuscript.
NR 16
TC 10
Z9 10
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7525
J9 HEALTH QUAL LIFE OUT
JI Health Qual. Life Outcomes
PD MAR 8
PY 2013
VL 11
AR 35
DI 10.1186/1477-7525-11-35
PG 7
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 126WE
UT WOS:000317651900001
PM 23497005
ER
PT J
AU Arystarkhova, E
Liu, YB
Salazar, C
Stanojevic, V
Clifford, RJ
Kaplan, JH
Kidder, GM
Sweadner, KJ
AF Arystarkhova, Elena
Liu, Yi B.
Salazar, Cynthia
Stanojevic, Violeta
Clifford, Rebecca J.
Kaplan, Jack H.
Kidder, Gerald M.
Sweadner, Kathleen J.
TI Hyperplasia of Pancreatic Beta Cells and Improved Glucose Tolerance in
Mice Deficient in the FXYD2 Subunit of Na, K-ATPase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SODIUM-POTASSIUM PUMP; GAMMA-SUBUNIT; RENAL NA,K-ATPASE;
IMMUNOCYTOCHEMICAL LOCALIZATION; CRYSTAL-STRUCTURE; MAMMALIAN-CELLS;
FUNCTIONAL-ROLE; CULTURED-CELLS; EXPRESSION; MASS
AB Restoration of the functional potency of pancreatic islets either through enhanced proliferation (hyperplasia) or increase in size (hypertrophy) of beta cells is a major objective for intervention in diabetes. We have obtained experimental evidence that global knock-out of a small, single-span regulatory subunit of Na,K-ATPase, FXYD2, alters glucose control. Adult Fxyd2(-/-) mice showed significantly lower blood glucose levels, no signs of peripheral insulin resistance, and improved glucose tolerance compared with their littermate controls. Strikingly, there was a substantial hyperplasia in pancreatic beta cells from the Fxyd2(-/-) mice compared with the wild type littermates, compatible with an observed increase in the level of circulating insulin. No changes were seen in the exocrine compartment of the pancreas, and the mice had only a mild, well-adapted renal phenotype. Morphometric analysis revealed an increase in beta cell mass in KO compared with WT mice. This appears to explain a phenotype of hyperinsulinemia. By RT-PCR, Western blot, and immunocytochemistry we showed the FXYD2b splice variant in pancreatic beta cells from wild type mice. Phosphorylation of Akt kinase was significantly higher under basal conditions in freshly isolated islets from Fxyd2(-/-) mice compared with their WT littermates. Inducible expression of FXYD2 in INS 832/13 cells produced a reduction in the phosphorylation level of Akt, and phosphorylation was restored in parallel with degradation of FXYD2. Thus we suggest that in pancreatic beta cells FXYD2 plays a role in Akt signaling pathways associated with cell growth and proliferation.
C1 [Arystarkhova, Elena; Liu, Yi B.; Salazar, Cynthia; Sweadner, Kathleen J.] Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA.
[Stanojevic, Violeta] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA.
[Clifford, Rebecca J.; Kaplan, Jack H.] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
[Kidder, Gerald M.] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6C 2V5, Canada.
[Kidder, Gerald M.] Childrens Hlth Res Inst, Div Genet & Dev, London, ON N6C 2V5, Canada.
RP Arystarkhova, E (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Edwards 410,55 Fruit St, Boston, MA 02114 USA.
EM aristarkhova@helix.mgh.harvard.edu
OI Kaplan, Jack/0000-0002-7048-6574
FU National Institutes of Health [HL036271, NS045083, NS050696]; Pilot
Feasibility Grant [5P30DK057521-12]; American Recovery and Reinvestment
Act supplement [NS050696]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants HL036271, NS045083, and NS050696. This work was also
supported by Pilot Feasibility Grant 5P30DK057521-12 (Boston Area
Diabetes Endocrinology Research Center) and American Recovery and
Reinvestment Act supplement to Grant NS050696.
NR 37
TC 4
Z9 4
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
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 8
PY 2013
VL 288
IS 10
BP 7077
EP 7085
DI 10.1074/jbc.M112.401190
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 104NY
UT WOS:000316002400029
PM 23344951
ER
PT J
AU Rass, E
Chandramouly, G
Zha, S
Alt, FW
Xie, AY
AF Rass, Emilie
Chandramouly, Gurushankar
Zha, Shan
Alt, Frederick W.
Xie, Anyong
TI Ataxia Telangiectasia Mutated (ATM) Is Dispensable for Endonuclease
I-Scel-induced Homologous Recombination in Mouse Embryonic Stem Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; HISTONE H2AX; GENOMIC
INSTABILITY; IONIZING-RADIATION; FUNCTIONAL SYNERGY; KINASE-ACTIVITY;
REPAIR PATHWAY; MDC1; PHOSPHORYLATION
AB Ataxia telangiectasia mutated (ATM) is activated upon DNA double strand breaks (DSBs) and phosphorylates numerous DSB response proteins, including histone H2AX on serine 139 (Ser-139) to form gamma-H2AX. Through interaction with MDC1, gamma-H2AX promotes DSB repair by homologous recombination (HR). H2AX Ser-139 can also be phosphorylated by DNA-dependent protein kinase catalytic subunit and ataxia telangiectasia- and Rad3-related kinase. Thus, we tested whether ATM functions in HR, particularly that controlled by gamma-H2AX, by comparing HR occurring at the euchromatic ROSA26 locus between mouse embryonic stem cells lacking either ATM, H2AX, or both. We show here that loss of ATM does not impair HR, including H2AX-dependent HR, but confers sensitivity to inhibition of poly(ADP-ribose) polymerases. Loss of ATM or H2AX has independent contributions to cellular sensitivity to ionizing radiation. The ATM-independent HR function of H2AX requires both Ser-139 phosphorylation and gamma-H2AX/MDC1 interaction. Our data suggest that ATM is dispensable for HR, including that controlled by H2AX, in the context of euchromatin, excluding the implication of such an HR function in genomic instability, hypersensitivity to DNA damage, and poly(ADP-ribose) polymerase inhibition associated with ATM deficiency.
C1 [Rass, Emilie; Chandramouly, Gurushankar; Xie, Anyong] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Rass, Emilie; Chandramouly, Gurushankar; Xie, Anyong] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Zha, Shan; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Immune Dis Inst, Boston, MA 02115 USA.
[Zha, Shan; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Xie, AY (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol & Oncol, 330 Brookline Ave, Boston, MA 02215 USA.
EM axie@bidmc.harvard.edu
FU National Institutes of Health [R01GM073894]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01GM073894.
NR 54
TC 9
Z9 9
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 8
PY 2013
VL 288
IS 10
BP 7086
EP 7095
DI 10.1074/jbc.M112.445825
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 104NY
UT WOS:000316002400030
PM 23355489
ER
PT J
AU Lim, JH
Gerhart-Hines, Z
Dominy, JE
Lee, Y
Kim, S
Tabata, M
Xiang, YK
Puigserver, P
AF Lim, Ji-Hong
Gerhart-Hines, Zachary
Dominy, John E.
Lee, Yoonjin
Kim, Sungjin
Tabata, Mitsuhisa
Xiang, Yang K.
Puigserver, Pere
TI Oleic Acid Stimulates Complete Oxidation of Fatty Acids through Protein
Kinase A-dependent Activation of SIRT1-PGC1 alpha Complex
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INDUCED INSULIN-RESISTANCE; MITOCHONDRIAL BIOGENESIS; SKELETAL-MUSCLE;
TRANSCRIPTIONAL COACTIVATOR; PGC-1-ALPHA EXPRESSION; METABOLIC
REGULATOR; ENERGY-EXPENDITURE; LIPID-METABOLISM; SIRT1; AMPK
AB Fatty acids are essential components of the dynamic lipid metabolism in cells. Fatty acids can also signal to intracellular pathways to trigger a broad range of cellular responses. Oleic acid is an abundant monounsaturated omega-9 fatty acid that impinges on different biological processes, but the mechanisms of action are not completely understood. Here, we report that oleic acid stimulates the cAMP/protein kinase A pathway and activates the SIRT1-PGC1 alpha transcriptional complex to modulate rates of fatty acid oxidation. In skeletal muscle cells, oleic acid treatment increased intracellular levels of cyclic adenosine monophosphate (cAMP) that turned on protein kinase A activity. This resulted in SIRT1 phosphorylation at Ser-434 and elevation of its catalytic deacetylase activity. A direct SIRT1 substrate is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha), which became deacetylated and hyperactive after oleic acid treatment. Importantly, oleic acid, but not other long chain fatty acids such as palmitate, increased the expression of genes linked to fatty acid oxidation pathway in a SIRT1-PGC1 alpha-dependent mechanism. As a result, oleic acid potently accelerated rates of complete fatty acid oxidation in skeletal muscle cells. These results illustrate how a single long chain fatty acid specifically controls lipid oxidation through a signaling/transcriptional pathway. Pharmacological manipulation of this lipid signaling pathway might provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.
C1 [Lim, Ji-Hong; Gerhart-Hines, Zachary; Dominy, John E.; Lee, Yoonjin; Tabata, Mitsuhisa; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Lim, Ji-Hong; Gerhart-Hines, Zachary; Dominy, John E.; Lee, Yoonjin; Tabata, Mitsuhisa; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kim, Sungjin; Xiang, Yang K.] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA.
RP Puigserver, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,CLSB-11144, Boston, MA 02215 USA.
EM pere_puigserver@dfci.harvard.edu
FU Dana-Farber Cancer Institute; American Diabetes Association; Department
of Defense; National Institutes of Health/NIDDK [RO1 069966]; National
Institutes of Health [RO1-HL82846]; American Heart Association
[12EIA841007]
FX This work was supported by the Dana-Farber Cancer Institute, the
American Diabetes Association, the Department of Defense, National
Institutes of Health/NIDDK Grant RO1 069966 (to P. P.) as well as
National Institutes of Health Grant RO1-HL82846 and American Heart
Association Grant 12EIA841007 (to Y. K. X.).; Supported by an American
Diabetes Association mentor supported post-doctoral fellowship.;
Supported in part by a fellowship from the American Heart Association.;
Supported in part by an National Research Service Award Kirschstein
fellowship from the National Institutes of Health.
NR 40
TC 24
Z9 29
U1 0
U2 13
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 8
PY 2013
VL 288
IS 10
BP 7117
EP 7126
DI 10.1074/jbc.M112.415729
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 104NY
UT WOS:000316002400033
PM 23329830
ER
PT J
AU Bass, AJ
Wang, TC
AF Bass, Adam J.
Wang, Timothy C.
TI An Inflammatory Situation: SOX2 and STAT3 Cooperate in Squamous Cell
Carcinoma Initiation
SO CELL STEM CELL
LA English
DT Editorial Material
ID SURVIVAL; ROLES; MICE; STEM
AB Although SOX2 has been identified as a squamous cell carcinoma oncogene, mechanisms of SOX2-induce oncogenesis have remained elusive. In this issue of Cell Stem Cell, Li et al. (2013) show that SOX2 synergizes with inflammation-induced STAT3 activation to transform basal progenitors and initiate squamous cell carcinoma.
C1 [Bass, Adam J.] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Boston, MA 02215 USA.
[Bass, Adam J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bass, Adam J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Bass, Adam J.] Broad Inst, Cambridge, MA 02142 USA.
[Wang, Timothy C.] Columbia Univ Coll Phys & Surg, Div Digest & Liver Dis, New York, NY 10032 USA.
[Wang, Timothy C.] Columbia Univ Coll Phys & Surg, Herbert Irving Canc Res Ctr, New York, NY 10032 USA.
RP Wang, TC (reprint author), Columbia Univ Coll Phys & Surg, Div Digest & Liver Dis, New York, NY 10032 USA.
EM tcw21@columbia.edu
NR 9
TC 4
Z9 6
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAR 7
PY 2013
VL 12
IS 3
BP 266
EP 268
DI 10.1016/j.stem.2013.02.004
PG 4
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 287VC
UT WOS:000329569400002
PM 23472866
ER
PT J
AU Hogdal, LJ
Letai, A
AF Hogdal, Leah J.
Letai, Anthony
TI BCL-2 Inhibition: Stemming the Tide of Myeloid Malignancies
SO CELL STEM CELL
LA English
DT Editorial Material
ID BH3 MIMETIC ABT-737; LEUKEMIA; SENSITIVITY; APOPTOSIS
AB Leukemia stem cells (LSCs) are likely to be the source for both therapeutic resistance and relapse in myeloid malignancies. As reported in this issue of Cell Stem Cell, Lagadinou et al. (2013) and Goff et al. (2013) support selective targeting of LSCs by small molecule antagonists of anti-apoptotic BCL-2 family proteins.
C1 [Hogdal, Leah J.; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM anthony_letai@dfci.harvard.edu
FU NCI NIH HHS [R01 CA129974]
NR 10
TC 3
Z9 4
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAR 7
PY 2013
VL 12
IS 3
BP 269
EP 270
DI 10.1016/j.stem.2013.02.006
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 287VC
UT WOS:000329569400003
PM 23472867
ER
PT J
AU McMurry, AJ
Murphy, SN
MacFadden, D
Weber, G
Simons, WW
Orechia, J
Bickel, J
Wattanasin, N
Gilbert, C
Trevvett, P
Churchill, S
Kohane, IS
AF McMurry, Andrew J.
Murphy, Shawn N.
MacFadden, Douglas
Weber, Griffin
Simons, William W.
Orechia, John
Bickel, Jonathan
Wattanasin, Nich
Gilbert, Clint
Trevvett, Philip
Churchill, Susanne
Kohane, Isaac S.
TI SHRINE: Enabling Nationally Scalable Multi-Site Disease Studies
SO PLOS ONE
LA English
DT Article
ID ELECTRONIC MEDICAL-RECORDS; INTEGRATING BIOLOGY; CLINICAL-RESEARCH;
MYOCARDIAL-INFARCTION; DISCOVERY RESEARCH; DIABETES-MELLITUS;
PUBLIC-HEALTH; CARE; INFORMATICS; SYSTEM
AB Results of medical research studies are often contradictory or cannot be reproduced. One reason is that there may not be enough patient subjects available for observation for a long enough time period. Another reason is that patient populations may vary considerably with respect to geographic and demographic boundaries thus limiting how broadly the results apply. Even when similar patient populations are pooled together from multiple locations, differences in medical treatment and record systems can limit which outcome measures can be commonly analyzed. In total, these differences in medical research settings can lead to differing conclusions or can even prevent some studies from starting. We thus sought to create a patient research system that could aggregate as many patient observations as possible from a large number of hospitals in a uniform way. We call this system the 'Shared Health Research Information Network', with the following properties: (1) reuse electronic health data from everyday clinical care for research purposes, (2) respect patient privacy and hospital autonomy, (3) aggregate patient populations across many hospitals to achieve statistically significant sample sizes that can be validated independently of a single research setting, (4) harmonize the observation facts recorded at each institution such that queries can be made across many hospitals in parallel, (5) scale to regional and national collaborations. The purpose of this report is to provide open source software for multi-site clinical studies and to report on early uses of this application. At this time SHRINE implementations have been used for multi-site studies of autism co-morbidity, juvenile idiopathic arthritis, peripartum cardiomyopathy, colorectal cancer, diabetes, and others. The wide range of study objectives and growing adoption suggest that SHRINE may be applicable beyond the research uses and participating hospitals named in this report.
C1 [McMurry, Andrew J.; MacFadden, Douglas; Simons, William W.; Gilbert, Clint; Trevvett, Philip; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[McMurry, Andrew J.; Bickel, Jonathan; Kohane, Isaac S.] Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA.
[McMurry, Andrew J.; Murphy, Shawn N.; Weber, Griffin; Churchill, Susanne; Kohane, Isaac S.] Brigham & Womens Hosp, Natl Ctr Biomed Comp I2b2, Boston, MA 02115 USA.
[McMurry, Andrew J.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
[Murphy, Shawn N.; Wattanasin, Nich; Churchill, Susanne] Res Comp, Partners Healthcare Syst, Boston, MA 02215 USA.
[Murphy, Shawn N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Weber, Griffin] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Weber, Griffin] Harvard Univ, Med Sch Informat Technol, Boston, MA 02115 USA.
[Orechia, John] Dana Farber Canc Inst, Clin Res Informat Technol, Boston, MA 02115 USA.
[Bickel, Jonathan] Childrens Hosp, Dept Informat Syst, Boston, MA 02115 USA.
RP McMurry, AJ (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
EM Andrew_McMurry@hms.harvard.edu
OI Weber, Griffin/0000-0002-2597-881X
FU CTSA award (National Institutes of Health/National Center for Research
Resources NIH/NCRR) [1UL1RR025758-01]; i2b2 National Center for
Biomedical Computing [NIH/NLM U54 LM008748]
FX This work was funded in part by the CTSA award (National Institutes of
Health/National Center for Research Resources NIH/NCRR 1UL1RR025758-01)
and the i2b2 National Center for Biomedical Computing (NIH/NLM U54
LM008748). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 68
TC 35
Z9 35
U1 2
U2 17
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 MAR 7
PY 2013
VL 8
IS 3
AR e55811
DI 10.1371/journal.pone.0055811
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500004
PM 23533569
ER
PT J
AU Rice, WL
Van Hoek, AN
Paunescu, TG
Huynh, C
Goetze, B
Singh, B
Scipioni, L
Stern, LA
Brown, D
AF Rice, William L.
Van Hoek, Alfred N.
Paunescu, Teodor G.
Huynh, Chuong
Goetze, Bernhard
Singh, Bipin
Scipioni, Larry
Stern, Lewis A.
Brown, Dennis
TI High Resolution Helium Ion Scanning Microscopy of the Rat Kidney
SO PLOS ONE
LA English
DT Article
ID ACUTE RESPIRATORY-ACIDOSIS; ELECTRON-MICROSCOPY; INTERCALATED CELLS;
HEYMANN NEPHRITIS; COLLECTING DUCT; EPITHELIAL-CELLS; BRUSH-BORDER;
COATED PITS; ULTRASTRUCTURE; IDENTIFICATION
AB Helium ion scanning microscopy is a novel imaging technology with the potential to provide sub-nanometer resolution images of uncoated biological tissues. So far, however, it has been used mainly in materials science applications. Here, we took advantage of helium ion microscopy to explore the epithelium of the rat kidney with unsurpassed image quality and detail. In addition, we evaluated different tissue preparation methods for their ability to preserve tissue architecture. We found that high contrast, high resolution imaging of the renal tubule surface is possible with a relatively simple processing procedure that consists of transcardial perfusion with aldehyde fixatives, vibratome tissue sectioning, tissue dehydration with graded methanol solutions and careful critical point drying. Coupled with the helium ion system, fine details such as membrane texture and membranous nanoprojections on the glomerular podocytes were visualized, and pores within the filtration slit diaphragm could be seen in much greater detail than in previous scanning EM studies. In the collecting duct, the extensive and striking apical microplicae of the intercalated cells were imaged without the shrunken or distorted appearance that is typical with conventional sample processing and scanning electron microscopy. Membrane depressions visible on principal cells suggest possible endo- or exocytotic events, and central cilia on these cells were imaged with remarkable preservation and clarity. We also demonstrate the use of colloidal gold probes for highlighting specific cell-surface proteins and find that 15 nm gold labels are practical and easily distinguishable, indicating that external labels of various sizes can be used to detect multiple targets in the same tissue. We conclude that this technology represents a technical breakthrough in imaging the topographical ultrastructure of animal tissues. Its use in future studies should allow the study of fine cellular details and provide significant advances in our understanding of cell surface structures and membrane organization.
C1 [Rice, William L.; Van Hoek, Alfred N.; Paunescu, Teodor G.; Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
[Rice, William L.; Van Hoek, Alfred N.; Paunescu, Teodor G.; Brown, Dennis] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Rice, William L.; Van Hoek, Alfred N.; Paunescu, Teodor G.; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA.
[Huynh, Chuong; Goetze, Bernhard; Singh, Bipin; Scipioni, Larry; Stern, Lewis A.] Carl Zeiss Microscopy, Peabody, MA USA.
RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
EM brown.dennis@mgh.harvard.edu
FU NIH [DK42956]; Zeiss Corporation; Massachusetts General Hospital
FX Funding was in part from an NIH grant to D. Brown to examine the role of
renal intercalated cell cells in kidney function (DK42956). Additional
funding was provided by a sponsored research agreement to Dr. Brown from
the Zeiss Corporation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.; The authors have read the journal's policy and have the
following conflicts. The work was performed partially with a sponsored
research agreement between the Massachusetts General Hospital and the
Zeiss Corporation. Four of the authors are employed by the Zeiss
Corporation in the Helium Ion Microscopy Facility in Peabody, MA. The
corresponding author D. Brown is the PI of the sponsored research
agreement from the Zeiss Corporation. This does not alter the authors'
adherence to all the PLOS ONE policies on sharing data and materials.
NR 37
TC 17
Z9 17
U1 1
U2 21
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 MAR 7
PY 2013
VL 8
IS 3
AR e57051
DI 10.1371/journal.pone.0057051
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500010
PM 23505418
ER
PT J
AU Wanic, K
Krolewski, B
Ju, WJ
Placha, G
Niewczas, MA
Walker, W
Warram, JH
Kretzler, M
Krolewski, AS
AF Wanic, Krzysztof
Krolewski, Bozena
Ju, Wenjun
Placha, Grzegorz
Niewczas, Monika A.
Walker, William
Warram, James H.
Kretzler, Matthias
Krolewski, Andrzej S.
TI Transcriptome Analysis of Proximal Tubular Cells (HK-2) Exposed to
Urines of Type 1 Diabetes Patients at Risk of Early Progressive Renal
Function Decline
SO PLOS ONE
LA English
DT Article
ID TNF RECEPTORS 1; NEPHROTIC SYNDROME; URINARY PROTEINS; EPITHELIAL-CELLS;
NECROSIS-FACTOR; NEPHROPATHY; MICROALBUMINURIA; EXPRESSION; DISEASE;
VEGF
AB Background: In patients with Type 1 Diabetes (T1D) who develop microalbuminuria, progressive decline in glomerular filtration rate (GFR) may be initiated by leakage into the urine of toxic proteins (txUPs). This study tested this hypothesis.
Methods: After archiving baseline urine, we followed T1D patients with microalbuminuria for 8-12 years to distinguish those in whom GFR declined (Decliners) and those in whom it remained stable (Non-decliners). Human proximal tubular cells (HK-2 cells) were grown in serum-free medium enriched with pooled urines from Decliners or Non-decliners. We determined genome-wide expression profiles in extracted mRNA.
Results: The two pooled urines induced differential expression of 312 genes. In terms of gene ontology, molecular functions of the 119 up-regulated genes were enriched for protein binding and peptidase inhibitor activities. Their biologic processes were enriched for defense response, responses to other organisms, regulation of cellular processes, or response to stress or stimulus, and programmed cell death. The 195 down-regulated genes were disproportionately represented in molecular functions of cation binding, hydrolase activity, and DNA binding. They were disproportionately represented in biological processes for regulation of metabolic processes, nucleic acid metabolic processes, cellular response to stress and macromolecule biosynthesis. The set of up-regulated genes in HK-2 cells overlaps significantly with sets of over-expressed genes in tubular and interstitial compartments of kidney biopsies from patients with advanced DN (33 genes in one study and 25 in the other compared with 10.3 expected by chance, p<10(-9) and p<10(-4), respectively). The overlap included genes encoding chemokines and cytokines. Overlap of down-regulated genes was no more than expected by chance.
Conclusions: Molecular processes in tubules and interstitium seen in advanced diabetic nephropathy can be induced in vitro by exposure to urine from patients with minimal microalbuminuria who subsequently developed progressive renal function decline, presumably due to putative txUPs.
C1 [Wanic, Krzysztof; Krolewski, Bozena; Placha, Grzegorz; Niewczas, Monika A.; Walker, William; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA.
[Wanic, Krzysztof; Krolewski, Bozena; Placha, Grzegorz; Niewczas, Monika A.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Wanic, Krzysztof] Jagiellonian Univ, Dept Metab Dis, Krakow, Poland.
[Ju, Wenjun; Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA.
[Placha, Grzegorz] Warsaw Med Univ, Dept Hypertens, Warsaw, Poland.
RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA.
EM Andrzej.Krolewski@joslin.harvard.edu
FU NIH [DK41526, DK67638]; JDRF [JDRF 3-2005-908, JDRF 3-2004-631]
FX This research was supported by NIH grants DK41526 & DK67638 (to ASK); KW
and GP were supported by the JDRF fellowships (JDRF 3-2005-908, & JDRF
3-2004-631). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 26
TC 2
Z9 2
U1 0
U2 2
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 MAR 7
PY 2013
VL 8
IS 3
AR e57751
DI 10.1371/journal.pone.0057751
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 136BN
UT WOS:000318334500030
PM 23505438
ER
PT J
AU Kampa-Schittenhelm, KM
Heinrich, MC
Akmut, F
Dohner, H
Dohner, K
Schittenhelm, MM
AF Kampa-Schittenhelm, Kerstin Maria
Heinrich, Michael Charles
Akmut, Figen
Doehner, Hartmut
Doehner, Konstanze
Schittenhelm, Marcus Matthias
TI Quizartinib (AC220) is a potent second generation class III tyrosine
kinase inhibitor that displays a distinct inhibition profile against
mutant-FLT3, -PDGFRA and -KIT isoforms
SO MOLECULAR CANCER
LA English
DT Article
DE AC220; Quizartinib; Leukemia; KIT; FLT3; PDGFR
ID ACUTE MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMOR; INTERNAL TANDEM
DUPLICATIONS; LIGAND-INDEPENDENT ACTIVATION; MAST-CELL LEUKEMIA; C-KIT;
MYELODYSPLASTIC SYNDROME; FLT3 GENE; WILD-TYPE; SYSTEMIC MASTOCYTOSIS
AB Background: Activating mutations of class III receptor tyrosine kinases (RTK) FLT3, PDGFR and KIT are associated with multiple human neoplasms including hematologic malignancies, for example: systemic mast cell disorders (KIT), non-CML myeloproliferative neoplasms (PDGFR) and subsets of acute leukemias (FLT3 and KIT). First generation tyrosine kinase inhibitors (TKI) are rapidly being integrated into routine cancer care. However, the expanding spectrum of TK-mutations, bioavailability issues and the emerging problem of primary or secondary TKI-therapy resistance have lead to the search for novel second generation TKIs to improve target potency and to overcome resistant clones.
Quizartinib was recently demonstrated to be a selective FLT3 inhibitor with excellent pharmacokinetics and promising in vivo activity in a phase II study for FLT3 ITD + AML patients. In vitro kinase assays have suggested that in addition to FLT3, quizartinib also targets related class III RTK isoforms.
Methods: Various FLT3 or KIT leukemia cell lines and native blasts were used to determine the antiproliferative and proapoptotic efficacy of quizartinib. To better compare differences between the mutant kinase isoforms, we generated an isogenic BaF3 cell line expressing different FLT3, KIT or BCR/ABL isoforms. Using immunoblotting, we examined the effects of quizartinib on activation of mutant KIT or FLT3 isoforms.
Results: Kinase inhibition of (mutant) KIT, PDGFR and FLT3 isoforms by quizartinib leads to potent inhibition of cellular proliferation and induction of apoptosis in in vitro leukemia models as well as in native leukemia blasts treated ex vivo. However, the sensitivity patterns vary widely depending on the underlying (mutant)-kinase isoform, with some isoforms being relatively insensitive to this agent (e. g. FLT3 D835V and KIT codon D816 mutations). Evaluation of sensitivities in an isogenic cellular background confirms a direct association with the underlying mutant-TK isoform - which is further validated by immunoblotting experiments demonstrating kinase inhibition consistent with the cellular sensitivity/resistance to quizartinib.
Conclusion: Quizartinib is a potent second-generation class III receptor TK-inhibitor - but specific, mutation restricted spectrum of activity may require mutation screening prior to therapy.
C1 [Kampa-Schittenhelm, Kerstin Maria; Akmut, Figen; Schittenhelm, Marcus Matthias] Univ Tubingen Hosp, Dept Hematol Oncol Rheumatol Immunol & Pulmol, Tubingen, Germany.
[Heinrich, Michael Charles] Portland VA Med Ctr, Dept Med, Div Hematol & Med Oncol, Portland, OR USA.
[Heinrich, Michael Charles] OHSU Knight Canc Inst, Portland, OR USA.
[Doehner, Hartmut; Doehner, Konstanze] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany.
RP Kampa-Schittenhelm, KM (reprint author), Univ Tubingen Hosp, Dept Hematol Oncol Rheumatol Immunol & Pulmol, Tubingen, Germany.
EM kerstin.kampa-schittenhelm@med.uni-tuebingen.de
FU Deutsche Krebshilfe Foundation; IZKF Program of the Medical Faculty
Tubingen; Carreras Scholarship Program; Leukemia and Lymphoma Society;
Department of Veterans Affairs; Deutsche Forschungsgemeinschaft; Open
Access Publishing Fund of Tubingen University
FX Grant support in part by the Deutsche Krebshilfe Foundation (MMS, KKS),
the IZKF Program of the Medical Faculty Tubingen (MMS) and the Carreras
Scholarship Program (KKS), a grant from the Leukemia and Lymphoma
Society (MCH) and a Merit Review Grant from the Department of Veterans
Affairs (MCH). We acknowledge support by Deutsche Forschungsgemeinschaft
and Open Access Publishing Fund of Tubingen University.
NR 52
TC 26
Z9 27
U1 0
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD MAR 7
PY 2013
VL 12
AR 19
DI 10.1186/1476-4598-12-19
PG 15
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 133BS
UT WOS:000318113000001
PM 23497317
ER
PT J
AU Chen, XL
Shen, YP
Zhang, F
Chiang, C
Pillalamarri, V
Blumenthal, I
Talkowski, M
Wu, BL
Gusella, JF
AF Chen, Xiaoli
Shen, Yiping
Zhang, Feng
Chiang, Colby
Pillalamarri, Vamsee
Blumenthal, Ian
Talkowski, Michael
Wu, Bai-Lin
Gusella, James F.
TI Molecular Analysis of a Deletion Hotspot in the NRXN1 Region Reveals the
Involvement of Short Inverted Repeats in Deletion CNVs
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID COPY-NUMBER VARIATION; AUTISM SPECTRUM DISORDERS; HUMAN GENOME;
STRUCTURAL VARIANTS; SEGMENTAL DUPLICATIONS; COMPLEX REARRANGEMENTS;
GENETIC INSTABILITY; SCHIZOPHRENIA; PALINDROME; RISK
AB NRXN1 microdeletions occur at a relatively high frequency and confer increased risk for neurodevelopmental and neurobehavioral abnormalities. The mechanism that makes NRXN1 a deletion hotspot is unknown. Here, we identified deletions of the NRXN1 region in affected cohorts, confirming a strong association with the autism spectrum and other neurodevelopmental disorders. Interestingly, deletions in both affected and control individuals were clustered in the 5' portion of NRXN1 and its immediate upstream region. To explore the mechanism of deletion, we mapped and analyzed the breakpoints of 32 deletions. At the deletion breakpoints, frequent microhomology (68.8%, 2-19 bp) suggested predominant mechanisms of DNA replication error and/or microhomology-mediated end-joining. Long terminal repeat (LTR) elements, unique non-B-DNA structures, and MEME-defined sequence motifs were significantly enriched, but Alu and LINE sequences were not. Importantly, small-size inverted repeats (minus self chains, minus sequence motifs, and partial complementary sequences) were significantly overrepresented in the vicinity of NRXN1 region deletion breakpoints, suggesting that, although they are not interrupted by the deletion process, such inverted repeats can predispose a region to genomic instability by mediating single-strand DNA looping via the annealing of partially reverse complementary strands and the promoting of DNA replication fork stalling and DNA replication error. Our observations highlight the potential importance of inverted repeats of variable sizes in generating a rearrangement hotspot in which individual breakpoints are not recurrent. Mechanisms that involve short inverted repeats in initiating deletion may also apply to other deletion hotspots in the human genome.
C1 [Chen, Xiaoli] Capital Inst Pediat, Beijing 100020, Peoples R China.
[Chen, Xiaoli; Shen, Yiping; Chiang, Colby; Pillalamarri, Vamsee; Blumenthal, Ian; Talkowski, Michael; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Chen, Xiaoli; Shen, Yiping; Wu, Bai-Lin] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
[Shen, Yiping] Shanghai Jiao Tong Univ, Shanghai Childrens Med Ctr, Sch Med, Shanghai 200127, Peoples R China.
[Shen, Yiping; Wu, Bai-Lin] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Zhang, Feng] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Zhang, Feng] Fudan Univ, Sch Life Sci, Minist Educ, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China.
[Talkowski, Michael] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Talkowski, Michael; Gusella, James F.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Wu, Bai-Lin] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China.
[Wu, Bai-Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China.
[Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Wu, BL (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA.
EM bai-lin.wu@childrens.harvard.edu; gusella@helix.mgh.harvard.edu
RI Zhang, Feng/C-7735-2009;
OI Chiang, Colby/0000-0002-4113-6065
FU Natural Science Foundation of China [81100841]; Beijing Science and
Technology Fund for Chinese Returned Oversea Scientist; Shanghai Science
and Technology Commission [11dz1950300]; National Basic Research Program
of China [2011CBA00401, 2012CB944600]; Ministry-of Science and
Technology of China for the National 973 Program on Population and
Health [2010CB529601]; Nature Science Fund of Shanghai [09JC1402400,
09ZR1404500]; NIH [GM061354, HD065286]; Autism Speaks grant [2042];
National Institute of Mental Health (NIMH) National Research Service
Award [MH087123]; Mass General Hospital Executive Committee on Research
Fund for Medical Discovery award
FX This work was supported by the Natural Science Foundation of China
(grant 81100841) and the Beijing Science and Technology Fund for Chinese
Returned Oversea Scientist (to X.L.C.); a Shanghai Science and
Technology Commission major issue grant (11dz1950300) to Y.S.; the
National Basic Research Program of China (grants 2011CBA00401 and
2012CB944600 to F.Z.); the Ministry-of Science and Technology of China
for the National 973 Program on Population and Health (grant
2010CB529601 to B.L.W.) and the Nature Science Fund of Shanghai
(09JC1402400 and 09ZR1404500 to B.L.W.), and NIH grants GM061354 and
HD065286 and Autism Speaks grant 2042 to J.F.G. M.T. was supported by a
National Institute of Mental Health (NIMH) National Research Service
Award (grant MH087123) and a Mass General Hospital Executive Committee
on Research Fund for Medical Discovery award.
NR 78
TC 20
Z9 23
U1 0
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 7
PY 2013
VL 92
IS 3
BP 375
EP 386
DI 10.1016/j.ajhg.2013.02.006
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 106RF
UT WOS:000316161700010
PM 23472757
ER
PT J
AU Simon, JA
Kingston, RE
AF Simon, Jeffrey A.
Kingston, Robert E.
TI Occupying Chromatin: Polycomb Mechanisms for Getting to Genomic Targets,
Stopping Transcriptional Traffic, and Staying Put
SO MOLECULAR CELL
LA English
DT Review
ID RNA-POLYMERASE-II; H3 LYSINE 27; HISTONE METHYLTRANSFERASE ACTIVITY;
EMBRYONIC STEM-CELLS; REPRESSIVE COMPLEX 1; GROUP PROTEIN COMPLEXES;
REPLICATION IN-VITRO; LONG NONCODING RNA; GROUP CBX FAMILY;
GENE-EXPRESSION
AB Chromatin modification by Polycomb proteins provides an essential strategy for gene silencing in higher eukaryotes. Polycomb repressive complexes (PRCs) silence key developmental regulators and are centrally integrated in the transcriptional circuitry of stem cells. PRC2 trimethylates histone H3 on lysine 27 (H3K27me3), and PRC1-type complexes ubiquitylate histone H2A and compact polynucleosomes. How PRCs are deployed to select and silence genomic targets is the subject of intense investigation. We review advances on targeting, modulation, and functions of PRC1 and PRC2 and progress on defining the transcriptional steps they impact. Recent findings emphasize PRC1 targeting independent of H3K27me3, nonenzymatic PRC1-mediated compaction, and connections between PRCs and noncoding RNAs. Systematic analyses of Polycomb complexes and associated histone modifications during DNA replication and mitosis have also emerged. The stage is now set to reveal fundamental epigenetic mechanisms that determine how Polycomb target genes are silenced and how Polycomb silence is preserved through cell-cycle progression.
C1 [Simon, Jeffrey A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
[Kingston, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA.
[Kingston, Robert E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Simon, JA (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
EM simon004@umn.edu; kingston@molbio.mgh.harvard.edu
FU NIGMS NIH HHS [R01 GM043901, R01 GM049850]
NR 157
TC 266
Z9 272
U1 11
U2 97
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD MAR 7
PY 2013
VL 49
IS 5
BP 808
EP 824
DI 10.1016/j.molcel.2013.02.013
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 106TQ
UT WOS:000316168000004
PM 23473600
ER
PT J
AU Staber, PB
Zhang, P
Ye, M
Welner, RS
Nombela-Arrieta, C
Bach, C
Kerenyi, M
Bartholdy, BA
Zhang, H
Alberich-Jorda, M
Lee, S
Yang, H
Ng, F
Zhang, JY
Leddin, M
Silberstein, LE
Hoefler, G
Orkin, SH
Gottgens, B
Rosenbauer, F
Huang, G
Tenen, DG
AF Staber, Philipp B.
Zhang, Pu
Ye, Min
Welner, Robert S.
Nombela-Arrieta, Cesar
Bach, Christian
Kerenyi, Marc
Bartholdy, Boris A.
Zhang, Hong
Alberich-Jorda, Meritxell
Lee, Sanghoon
Yang, Henry
Ng, Felicia
Zhang, Junyan
Leddin, Mathias
Silberstein, Leslie E.
Hoefler, Gerald
Orkin, Stuart H.
Goettgens, Berthold
Rosenbauer, Frank
Huang, Gang
Tenen, Daniel G.
TI Sustained PU.1 Levels Balance Cell-Cycle Regulators to Prevent
Exhaustion of Adult Hematopoietic Stem Cells
SO MOLECULAR CELL
LA English
DT Article
ID TRANSCRIPTION FACTOR PU.1; SELF-RENEWAL; PROGENITOR CELLS; GENE;
ELEMENTS; DIFFERENTIATION; PROLIFERATION; MAINTENANCE; ACTIVATION;
MACROPHAGE
AB To provide a lifelong supply of blood cells, hematopoietic stem cells (HSCs) need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU.1 acts upstream of these regulators. So far, attempts to uncover PU.1's role in HSC biology have failed because of the technical limitations of complete loss-of-function models. With the use of hypomorphic mice with decreased PU.1 levels specifically in phenotypic HSCs, we found reduced HSC long-term repopulation potential that could be rescued completely by restoring PU.1 levels. PU.1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell-cycle regulators. Levels of PU.1 were sustained through autoregulatory PU.1 binding to an upstream enhancer that formed an active looped chromosome architecture in HSCs. These results establish that PU.1 mediates chromosome looping and functions as a master regulator of HSC proliferation.
C1 [Staber, Philipp B.; Zhang, Pu; Ye, Min; Welner, Robert S.; Bach, Christian; Kerenyi, Marc; Bartholdy, Boris A.; Zhang, Hong; Alberich-Jorda, Meritxell; Zhang, Junyan; Silberstein, Leslie E.; Orkin, Stuart H.; Tenen, Daniel G.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Nombela-Arrieta, Cesar; Silberstein, Leslie E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA.
[Kerenyi, Marc; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Kerenyi, Marc; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Staber, Philipp B.] Med Univ Graz, Div Hematol, A-8036 Graz, Austria.
[Hoefler, Gerald] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria.
[Staber, Philipp B.] Med Univ Vienna, Comprehens Canc Ctr Vienna, Div Hematol & Hemostaseol, A-1090 Vienna, Austria.
[Lee, Sanghoon; Yang, Henry; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 119615, Singapore.
[Ng, Felicia; Goettgens, Berthold] Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[Ng, Felicia; Goettgens, Berthold] Wellcome Trust Res Labs, Cambridge CB2 0XY, England.
[Ng, Felicia; Goettgens, Berthold] MRC Stem Cell Inst, Cambridge CB2 0XY, England.
[Leddin, Mathias; Rosenbauer, Frank] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Rosenbauer, Frank] Univ Munster, Inst Mol Tumor Biol, D-48149 Munster, Germany.
[Huang, Gang] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
RP Staber, PB (reprint author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA.
EM pstaber@bidmc.harvard.edu; csidgt@nus.edu.sg
RI Alberich Jorda, Meritxell/G-3137-2014; Hoefler, Gerald/H-1796-2016;
OI Bach, Christian/0000-0003-4675-7896; Nombela-Arrieta,
Cesar/0000-0003-0415-259X; Gottgens, Berthold/0000-0001-6302-5705;
Hoefler, Gerald/0000-0002-9056-3063; Rosenbauer,
Frank/0000-0001-7977-9421; Tenen, Daniel/0000-0002-6423-3888
FU NIH [R01HL112719]; Austrian Research Foundation [J2876-B12]; Austrian
Academy of Science [11379]; European Union [P10E-254486]; German
Research Foundation (DFG fellowship) [BA 4186/1-1]; Yousef Jameel
scholarship
FX We thank Christopher Hetherington and Alexander Ebralidze for expert
assistance with quantitative 3C analysis, the Dartmouth Transgenic
Facility directed by Steven Fiering, and the BIDMC Flow Cytometry
Facility. We thank Dr. Wenyi Wei and Dr. Peter Sicinski for providing
reagents (the anti-Cdc25a antibody and the Cdk1 expression construct,
respectively). We are grateful to the members of the Tenen laboratory
for helpful discussions, especially Annalisa Di Ruscio, Elena Levantini,
and Deepak Bararia. This work was supported by NIH grant R01HL112719 to
D.G.T. and by fellowships from the Austrian Research Foundation (Erwin
Schrodinger Stipendium: J2876-B12) and the Austrian Academy of Science
(APART Stipendium: 11379) to P.B.S. Starting in January, 2012, P.B.S.
has received a Marie Curie International Outgoing Fellowship from the
European Union (P10E-254486). C.B. was supported by the German Research
Foundation (DFG fellowship BA 4186/1-1). F.N. is the recipient of a
Yousef Jameel scholarship administered by the Cambridge Commonwealth and
Overseas Trust.
NR 44
TC 34
Z9 35
U1 2
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD MAR 7
PY 2013
VL 49
IS 5
BP 934
EP 946
DI 10.1016/j.molcel.2013.01.007
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 106TQ
UT WOS:000316168000015
PM 23395001
ER
PT J
AU Chatzaki, E
Anton, PA
Million, M
Lambropoulou, M
Constantinidis, T
Kolios, G
Tache, Y
Grigoriadis, DE
AF Chatzaki, Ekaterini
Anton, Peter A.
Million, Mulugeta
Lambropoulou, Maria
Constantinidis, Theodoros
Kolios, George
Tache, Yvette
Grigoriadis, Dimitri E.
TI Corticotropin-releasing factor receptor subtype 2 in human colonic
mucosa: Down-regulation in ulcerative colitis
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Colonic mucosa; Corticotropin-releasing factor; Corticotropin-releasing
factor receptor; Human immunodeficiency virus; Ulcerative colitis;
Urocortin
ID INFLAMMATORY-BOWEL-DISEASE; STRESS-RELATED ALTERATIONS; ENTERIC
NERVOUS-SYSTEM; FACTOR CRF RECEPTOR; GUT MOTOR FUNCTION;
GASTROINTESTINAL-TRACT; RHEUMATOID-ARTHRITIS; PSYCHOLOGICAL STRESS;
RAT-BRAIN; UROCORTIN
AB AIM: To assess corticotropin-releasing factor receptor 2 (CRF2) expression in the colon of healthy subjects and patients with ulcerative colitis (UC).
METHODS: We examined CRF2 gene and protein expression in the distal/sigmoid colonic mucosal biopsies from healthy subjects and patients with UC (active or disease in remission), human immunodeficiency virus (HIV) and functional bowel disease (FBD) by reverse transcription-polymerase chain reaction and immunofluorescence.
RESULTS: Gene expression of CRF2 was demonstrated in the normal human colonic biopsies, but not in the human colorectal adenocarcinoma cell line Caco2. Receptor protein localization showed immunoreactive CRF2 receptors in the lamina propria and in the epithelial cells of the distal/sigmoid biopsy samples. Interestingly, CRF2 immunoreactivity was no longer observed in epithelial cells of patients with mild-moderately active UC and disease in remission, while receptor protein expression did not change in the lamina propria. No differences in CRF2 expression profile were observed in distal/sigmoid intestinal biopsies from HIV infection and FBD patients, showing no signs of inflammation.
CONCLUSION: The down-regulation of the CRF2 receptor in the distal/sigmoid biopsies of UC patients is indicative of change in CRF2 signalling associated with the process of inflammation. (C) 2013 Baishideng. All rights reserved.
C1 [Chatzaki, Ekaterini; Grigoriadis, Dimitri E.] Neurocrine Biosci Inc, San Diego, CA 92121 USA.
[Chatzaki, Ekaterini; Kolios, George] Democritus Univ Thrace, Pharmacol Lab, Fac Med, Dragana 68100, Alexandroupolis, Greece.
[Anton, Peter A.] Univ Calif Los Angeles, Ctr HIV Prevent Res, Div Digest Dis, Los Angeles, CA 90073 USA.
[Anton, Peter A.; Million, Mulugeta; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Anton, Peter A.; Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, Digest Dis Res Ctr, Los Angeles, CA 90073 USA.
[Anton, Peter A.; Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90073 USA.
[Lambropoulou, Maria] Democritus Univ Thrace, Lab Histol Embryol, Fac Med, Dragana 68100, Alexandroupolis, Greece.
[Constantinidis, Theodoros] Democritus Univ Thrace, Lab Hyg & Environm Protect, Fac Med, Dragana 68100, Alexandroupolis, Greece.
RP Chatzaki, E (reprint author), Democritus Univ Thrace, Pharmacol Lab, Fac Med, Dragana 68100, Alexandroupolis, Greece.
EM achatzak@med.duth.gr
RI Kolios, George/N-6641-2013;
OI Kolios, George/0000-0002-2066-4782
FU National Institute of Diabetes and Digestive and Kidney Diseases R01
grant [DK-57238]; Veteran Administration Research Career Scientist
Award; NIH [DK-78676]; [DK-41301]
FX Supported by The National Institute of Diabetes and Digestive and Kidney
Diseases R01 grant DK-57238; Center Grant DK-41301 (Clinical core);
Veteran Administration Research Career Scientist Award (YT); and NIH
DK-78676 (MM)
NR 55
TC 9
Z9 9
U1 0
U2 1
PU BAISHIDENG PUBL GRP CO LTD
PI WANCHAI
PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG
100025, PEOPLES R CHINA
SN 1007-9327
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD MAR 7
PY 2013
VL 19
IS 9
BP 1416
EP 1423
DI 10.3748/wjg.v19.i9.1416
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 104NT
UT WOS:000316001700012
PM 23539366
ER
PT J
AU Kidwell, CS
Jahan, R
Gornbein, J
Alger, JR
Nenov, V
Ajani, Z
Feng, L
Meyer, BC
Olson, S
Schwamm, LH
Yoo, AJ
Marshall, RS
Meyers, PM
Yavagal, DR
Wintermark, M
Guzy, J
Starkman, S
Saver, JL
AF Kidwell, Chelsea S.
Jahan, Reza
Gornbein, Jeffrey
Alger, Jeffry R.
Nenov, Val
Ajani, Zahra
Feng, Lei
Meyer, Brett C.
Olson, Scott
Schwamm, Lee H.
Yoo, Albert J.
Marshall, Randolph S.
Meyers, Philip M.
Yavagal, Dileep R.
Wintermark, Max
Guzy, Judy
Starkman, Sidney
Saver, Jeffrey L.
CA MR RESCUE Investigators
TI A Trial of Imaging Selection and Endovascular Treatment for Ischemic
Stroke
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID RANDOMIZED-TRIAL; MERCI TRIAL; THROMBECTOMY; ALTEPLASE; SAFETY; MRI;
REVASCULARIZATION; REPERFUSION; MANAGEMENT; DIFFUSION
AB BACKGROUND
Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear.
METHODS
In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead).
RESULTS
Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P = 0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P = 0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P = 0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P = 0.14).
CONCLUSIONS
A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.)
C1 [Kidwell, Chelsea S.] Georgetown Univ, Dept Neurol, Washington, DC 20007 USA.
[Kidwell, Chelsea S.] Georgetown Univ, Stroke Ctr, Washington, DC 20007 USA.
[Jahan, Reza] Univ Calif Los Angeles, Dept Radiol & Neurosurg, Los Angeles, CA USA.
[Gornbein, Jeffrey] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA.
[Alger, Jeffry R.; Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Nenov, Val] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA.
[Guzy, Judy; Starkman, Sidney] Univ Calif Los Angeles, Dept Emergency Med & Neurol, Los Angeles, CA USA.
[Jahan, Reza; Alger, Jeffry R.; Guzy, Judy; Starkman, Sidney; Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA.
[Ajani, Zahra] Kaiser Permanente, Dept Neurol, Los Angeles, CA USA.
[Feng, Lei] Kaiser Permanente, Dept Radiol, Los Angeles, CA USA.
[Meyer, Brett C.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Olson, Scott] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.
[Meyer, Brett C.] Univ Calif San Diego, Stroke Ctr, San Diego, CA 92103 USA.
[Olson, Scott] Scripps Clin, Div Neurosurg, La Jolla, CA 92037 USA.
[Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Yoo, Albert J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Marshall, Randolph S.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA.
[Meyers, Philip M.] Columbia Univ Coll Phys & Surg, Dept Neurol Surg & Radiol, New York, NY 10032 USA.
[Yavagal, Dileep R.] Univ Miami, Jackson Mem Hosp, Dept Neurol, Miami, FL 33136 USA.
[Yavagal, Dileep R.] Univ Miami, Jackson Mem Hosp, Dept Neurosurg, Miami, FL 33136 USA.
[Wintermark, Max] Univ Virginia, Dept Radiol, Neuroradiol Div, Charlottesville, VA USA.
RP Kidwell, CS (reprint author), Georgetown Univ, Bldg D,Suite 150,4000 Reservoir Rd NW, Washington, DC 20007 USA.
EM ck256@georgetown.edu
RI Buck, Brian/B-8482-2009; Demchuk, Andrew/E-1103-2012;
OI Buck, Brian/0000-0002-7984-6062; Demchuk, Andrew/0000-0002-4930-7789;
Kummer, Terrance/0000-0001-8938-8280; Ajani, Zahra/0000-0001-6187-5204;
Molyneaux, Bradley/0000-0002-3377-1229; Gonzalez,
Nestor/0000-0002-8277-6317; Saver, Jeffrey/0000-0001-9141-2251;
Wintermark, Max/0000-0002-6726-3951; Schwamm, Lee/0000-0003-0592-9145
FU National Institute of Neurological Disorders and Stroke; NINDS [P50
NS044378]
FX Funded by the National Institute of Neurological Disorders and Stroke;
MR RESCUE ClinicalTrials.gov number, NCT00389467.); Supported by a grant
(P50 NS044378) from NINDS. Concentric Medical provided study catheters
and devices from the initiation of the study until August 2007;
thereafter, costs for all study catheters and devices were covered by
study funds or third-party payers.
NR 22
TC 602
Z9 622
U1 3
U2 73
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 7
PY 2013
VL 368
IS 10
BP 914
EP 923
DI 10.1056/NEJMoa1212793
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 100BG
UT WOS:000315669100007
PM 23394476
ER
PT J
AU Tarter, L
Yazdany, J
Moyers, B
Barnett, C
Dhaliwal, G
AF Tarter, Laura
Yazdany, Jinoos
Moyers, Brian
Barnett, Christopher
Dhaliwal, Gurpreet
TI The Heart of the Matter
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; LIBMAN-SACKS ENDOCARDITIS;
ANTIPHOSPHOLIPID ANTIBODIES; VALVE REPLACEMENT; DISEASE; INVOLVEMENT
C1 [Tarter, Laura] Stanford Univ, Med Ctr, Dept Med, Div Rheumatol & Immunol, Palo Alto, CA 94304 USA.
[Yazdany, Jinoos] Univ Calif San Francisco, Div Rheumatol, San Francisco, CA USA.
[Moyers, Brian; Barnett, Christopher] Univ Calif San Francisco, Div Cardiol, San Francisco, CA USA.
[Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Barnett, Christopher] San Francisco Gen Hosp, San Francisco, CA 94110 USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Tarter, L (reprint author), Stanford Univ, Med Ctr, Dept Med, Div Rheumatol & Immunol, 1000 Welch Rd,Suite 203, Palo Alto, CA 94304 USA.
EM tarter@gmail.com
NR 15
TC 1
Z9 2
U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 7
PY 2013
VL 368
IS 10
BP 944
EP 950
DI 10.1056/NEJMcps1114207
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 100BG
UT WOS:000315669100012
PM 23465105
ER
PT J
AU Rosenbaum, L
AF Rosenbaum, Lisa
TI The Whole Ball Game - Overcoming the Blind Spots in Health Care Reform
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID LOW-BACK-PAIN; TRIAL
C1 [Rosenbaum, Lisa] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Rosenbaum, Lisa] Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA.
RP Rosenbaum, L (reprint author), Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
NR 11
TC 10
Z9 10
U1 0
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 7
PY 2013
VL 368
IS 10
BP 959
EP 962
DI 10.1056/NEJMms1301576
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 100BG
UT WOS:000315669100015
PM 23465107
ER
PT J
AU Schaefferkoetter, J
Casey, M
Townsend, D
El Fakhri, G
AF Schaefferkoetter, Joshua
Casey, Michael
Townsend, David
El Fakhri, Georges
TI Clinical impact of time-of-flight and point response modeling in PET
reconstructions: a lesion detection study
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID HUMAN-OBSERVER; IMAGE-RECONSTRUCTION; NOISE; PERFORMANCE; LROC
AB Time-of-flight (TOF) and point spread function (PSF) modeling have been shown to improve PET reconstructions, but the impact on physicians in the clinical setting has not been thoroughly investigated. A lesion detection and localization study was performed using simulated lesions in real patient images. Four reconstruction schemes were considered: ordinary Poisson OSEM (OP) alone and combined with TOF, PSF, and TOF + PSF. The images were presented to physicians experienced in reading PET images, and the performance of each was quantified using localization receiver operating characteristic. Numerical observers (non-prewhitening and Hotelling) were used to identify optimal reconstruction parameters, and observer SNR was compared to the performance of the physicians. The numerical models showed good agreement with human performance, and best performance was achieved by both when using TOF + PSF. These findings suggest a large potential benefit of TOF + PSF for oncology PET studies, especially in the detection of small, low-intensity, focal disease in larger patients.
C1 [Schaefferkoetter, Joshua] Univ Tennessee, Med Ctr, Knoxville, TN 37920 USA.
[Casey, Michael] Siemens Med Solut, Knoxville, TN 37919 USA.
[Townsend, David] A STAR NUS Clin Imaging Res Ctr, Singapore 117599, Singapore.
[El Fakhri, Georges] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol Dept,Ctr Adv Med Imaging Sci, Boston, MA 02114 USA.
RP Schaefferkoetter, J (reprint author), Univ Tennessee, Med Ctr, Knoxville, TN 37920 USA.
EM jschaefferkoetter@utmck.edu; elfakhri@pet.mgh.harvard.edu
FU National Institutes of Health [R01HL110241, R01CA165221]
FX The authors wish to thank the three physicians who assisted with this
study, Drs Yitong Fu, Karen Wells and Yong Bradley, of the University of
Tennessee Medical Center, Knoxville, TN, and also Harold Rothfuss, Jim
Hamill, and Judson Jones of Siemens Medical Solutions, Knoxville, TN for
many helpful discussions. The assistance of Nathalie AbiHatem and
Jinsong Oyang in selecting possible lesion locations is also
acknowledged. One of the authors (GEF) acknowledges support, in part,
from the National Institutes of Health grant R01HL110241 and
R01CA165221.
NR 28
TC 29
Z9 29
U1 0
U2 16
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2013
VL 58
IS 5
BP 1465
EP 1478
DI 10.1088/0031-9155/58/5/1465
PG 14
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 093KS
UT WOS:000315191400019
PM 23403399
ER
PT J
AU Singh, JA
Lewallen, DG
AF Singh, Jasvinder A.
Lewallen, David G.
TI Income and patient-reported outcomes (PROs) after primary total knee
arthroplasty
SO BMC MEDICINE
LA English
DT Article
DE arthroplasty; income; joint replacement; patient-reported outcomes; risk
factor; total knee replacement
ID TOTAL HIP-ARTHROPLASTY; SEVERE FUNCTIONAL LIMITATION; TOTAL JOINT
ARTHROPLASTY; CLINICAL RATING SYSTEM; SOCIOECONOMIC-STATUS; REPLACEMENT
SURGERY; HEALTH-CARE; PAIN; PREDICTORS; EXPECTATIONS
AB Background: To assess whether income is associated with patient-reported outcomes (PROs) after primary total knee arthroplasty (TKA).
Methods: We used prospectively collected data from the Mayo Clinic Total Joint Registry to assess the association of income with index knee functional improvement, moderate to severe pain and moderate to severe activity limitation at 2-year and 5-year follow-up after primary TKA using multivariable-adjusted logistic regression analyses.
Results: There were 7, 139 primary TKAs at 2 years and 4, 234 at 5 years. In multivariable-adjusted analyses, at 2-year follow-up, compared to income > US$45, 000, lower incomes of <= US$35, 000 and > US$35, 000 to 45, 000 were associated (1) significantly with moderate to severe pain with an odds ratio (OR) 0.61 (95% CI 0.40 to 0.94) (P = 0.02) and 0.68 (95% CI 0.49 to 0.94) (P = 0.02); and (2) trended towards significance for moderate to severe activity limitation with OR 0.78 (95% CI 0.60 to 1.02) (P = 0.07) and no significant association with OR 0.96 (95% CI 0.78 to 1.20) (P = 0.75), respectively. At 5 years, odds were not statistically significantly different by income, although numerically they favored lower income. In multivariable-adjusted analyses, overall improvement in knee function was rated as 'better' slightly more often at 2 years by patients with income in the <= US$35, 000 range compared to patients with income > US$45, 000, with an OR 1.9 (95% CI 1.0 to 3.6) (P = 0.06).
Conclusions: We found that patients with lower income had better pain outcomes compared to patients with higher income. There was more improvement in knee function, and a trend towards less overall activity limitation after primary TKA in lower income patients compared to those with higher incomes. Insights into mediators of these relationships need to be investigated to understand how income influences outcomes after TKA.
C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA.
[Singh, Jasvinder A.] Birmingham VA Med Ctr, C SMART, Birmingham, AL 35233 USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA.
[Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA.
RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, 700 19th St S, Birmingham, AL 35233 USA.
EM jasvinder.md@gmail.com
OI singh, jasvinder/0000-0003-3485-0006
FU Takeda; Savient; URL pharmaceuticals; Regeneron; Allergan; Ardea;
Novartis; Zimmer; Orthosonic; Osteotech; Pipeline Biomedical; DePuy;
Stryker; Biomet; Mayo Clinic Orthopedic Surgery research funds; Agency
for Health Quality and Research Center for Education and Research on
Therapeutics (CERTs); National Institute of Arthritis, Musculoskeletal
and Skin Diseases (NIAMS); National Institute of Aging (NIA); National
Cancer Institute (NCI)
FX The authors report no financial conflicts related directly to this
study. JAS has received research grants from Takeda and Savient; and
consultant fees from URL pharmaceuticals, Savient, Takeda, Regeneron,
Allergan, Ardea and Novartis. DGL has received royalties/speaker fees
from Zimmer, Orthosonic and Osteotech, has been a paid consultant to and
owns stock in Pipeline Biomedical and has received institutional
research funds from DePuy, Stryker, Biomet and Zimmer.; This material is
the result of work supported by Mayo Clinic Orthopedic Surgery research
funds and the resources and use of facilities at the Birmingham VA
Medical Center, Alabama, USA. JAS is also supported by grants from the
Agency for Health Quality and Research Center for Education and Research
on Therapeutics (CERTs), National Institute of Arthritis,
Musculoskeletal and Skin Diseases (NIAMS), National Institute of Aging
(NIA) and National Cancer Institute (NCI).
NR 53
TC 4
Z9 4
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD MAR 6
PY 2013
VL 11
AR 62
DI 10.1186/1741-7015-11-62
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 137LE
UT WOS:000318436600001
PM 23497272
ER
PT J
AU Warner, ET
Glasgow, RE
Emmons, KM
Bennett, GG
Askew, S
Rosner, B
Colditz, GA
AF Warner, Erica T.
Glasgow, Russell E.
Emmons, Karen M.
Bennett, Gary G.
Askew, Sandy
Rosner, Bernard
Colditz, Graham A.
TI Recruitment and retention of participants in a pragmatic randomized
intervention trial at three community health clinics: Results and
lessons learned
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Health disparities; Weight-loss; Obesity; Hypertension; Pragmatic trial;
Recruitment; Retention
ID TERM WEIGHT-LOSS; AFRICAN-AMERICANS; MEDICAL-RESEARCH; FOLLOW-UP;
OBESITY; PROGRAM; COHORT; WOMEN; HYPERTENSION; PREVALENCE
AB Background: Obesity and hypertension and their associated health complications disproportionately affect communities of color and people of lower socioeconomic status. Recruitment and retention of these populations in research trials, and retention in weight loss trials has been an ongoing challenge.
Methods: Be Fit, Be Well was a pragmatic randomized weight loss and hypertension management trial of patients attending one of three community health centers in Boston, Massachusetts. Participants were asked to complete follow-up assessments every 6-months for two years. We describe challenges encountered and strategies implemented to recruit and retain trial participants over the 24-month intervention. We also identify baseline participant characteristics associated with retention status. Retention strategies included financial incentives, contact between assessment visits, building relationships with health center primary care providers (PCPs) and staff, and putting participant convenience first.
Results: Active refusal rates were low with 130 of 2,631 patients refusing participation (4.9%). Of 474 eligible persons completing telephone screening, 365 (77.0%) completed their baseline visit and were randomized into the study. The study population was predominantly non-Hispanic Black (71.2%), female (68.5%) and reported annual household income of less than $35,000 (70.1%). Recruitment strategies included use of passive approval of potential participants by PCPs, use of part-time staff, and outsourcing calls to a call center. A total of 314 (86.0%) people completed the 24-month visit. Retention levels varied across study visits and intervention condition. Most participants completed three or more visits (69.6%), with 205 (56.2%) completing all four. At 24-months, lower retention was observed for males and the intervention condition. Retention strategies included building strong relationships with clinic staff, flexibility in overcoming participant barriers through use of taxi vouchers, night and weekend appointments, and keeping participants engaged via newsletters and social gatherings.
Conclusion: We were able to retain 86.0% of participants at 24-months. Recruitment and retention of high percentages of racial/ethnic minorities and lower income samples is possible with planning, coordination with a trusted community setting and staff (e.g. community health centers and RAs), adaptability and building strong relationships.
C1 [Warner, Erica T.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Warner, Erica T.; Emmons, Karen M.; Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Div Populat Sci, Boston, MA 02115 USA.
[Warner, Erica T.; Rosner, Bernard] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
[Bennett, Gary G.; Askew, Sandy] Duke Univ, Duke Global Hlth Inst, Durham, NC USA.
[Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Rosner, Bernard] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
RP Warner, ET (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM ewarner@hsph.harvard.edu
RI Colditz, Graham/A-3963-2009
OI Colditz, Graham/0000-0002-7307-0291
FU National Heart, Lung, and Blood Institute [U01-HL087071, K22CA126992,
K05CA124415-04, 5T32CA009001-36, 5R25GM055353-14]
FX This work was supported in part by grant U01-HL087071 from the National
Heart, Lung, and Blood Institute and grants K22CA126992 (Dr. Bennett),
K05CA124415-04 (Dr. Emmons), 5T32CA009001-36 (Dr. Warner), and
5R25GM055353-14 (Dr. Warner).
NR 36
TC 13
Z9 13
U1 3
U2 17
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 MAR 6
PY 2013
VL 13
AR 192
DI 10.1186/1471-2458-13-192
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 119UH
UT WOS:000317123500002
PM 23496916
ER
PT J
AU Shao, LJ
Zhou, ZS
Cai, Y
Castro, P
Dakhov, O
Shi, P
Bai, YX
Ji, HX
Shen, WH
Wang, JH
AF Shao, Longjiang
Zhou, Zhansong
Cai, Yi
Castro, Patricia
Dakhov, Olga
Shi, Ping
Bai, Yaoxia
Ji, Huixiang
Shen, Wenhao
Wang, Jianghua
TI Celastrol Suppresses Tumor Cell Growth through Targeting an
AR-ERG-NF-kappa B Pathway in TMPRSS2/ERG Fusion Gene Expressing Prostate
Cancer
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTIONAL ACTIVITY; SIGNALING PATHWAYS; IKK-EPSILON; P65 SUBUNIT;
NUDE-MICE; GOD VINE; PHOSPHORYLATION; PROGRESSION; ACTIVATION; KINASE
AB The TMPRSS2/ERG (T/E) fusion gene is present in the majority of all prostate cancers (PCa). We have shown previously that NF-kappa B signaling is highly activated in these T/E fusion expressing cells via phosphorylation of NF-kB p65 Ser536 (p536). We therefore hypothesize that targeting NF-kB signaling may be an efficacious approach for the subgroup of PCas that carry T/E fusions. Celastrol is a well known NF-kB inhibitor, and thus may inhibit T/E fusion expressing PCa cell growth. We therefore evaluated Celastrol's effects in vitro and in vivo in VCaP cells, which express the T/E fusion gene. VCaP cells were treated with different concentrations of Celastrol and growth inhibition and target expression were evaluated. To test its ability to inhibit growth in vivo, 0.5 mg/kg Celastrol was used to treat mice bearing subcutaneous VCaP xenograft tumors. Our results show Celastrol can significantly inhibit the growth of T/E fusion expressing PCa cells both in vitro and in vivo through targeting three critical signaling pathways: AR, ERG and NF-kB in these cells. When mice received 0.5 mg/kg Celastrol for 4 times/week, significant growth inhibition was seen with no obvious toxicity or significant weight loss. Therefore, Celastrol is a promising candidate drug for T/E fusion expressing PCa. Our findings provide a novel strategy for the targeted therapy which may benefit the more than half of PCa patients who have T/E fusion expressing PCas.
C1 [Shao, Longjiang; Cai, Yi; Castro, Patricia; Dakhov, Olga; Wang, Jianghua] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[Shao, Longjiang; Cai, Yi; Castro, Patricia; Dakhov, Olga; Wang, Jianghua] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA.
[Zhou, Zhansong; Shi, Ping; Bai, Yaoxia; Ji, Huixiang; Shen, Wenhao] South West Hosp, Dept Urol, Chongqing, Peoples R China.
RP Wang, JH (reprint author), Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
EM jwang1@bcm.edu
FU Department of Defense Prostate Cancer Research program [DOD
W81XWH-08-1-0055]; NCI; Duncan Cancer Center Human Tissue and Pathology
Core [NCI: P30CA125123]
FX This work was supported by the Department of Defense Prostate Cancer
Research program (DOD W81XWH-08-1-0055; JW) and the NCI to the Dan L.
Duncan Cancer Center Human Tissue and Pathology Core (NCI: P30CA125123).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 50
TC 18
Z9 19
U1 1
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 MAR 6
PY 2013
VL 8
IS 3
AR e58391
DI 10.1371/journal.pone.0058391
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117EP
UT WOS:000316936100115
PM 23554889
ER
PT J
AU Huang, HW
Chen, ZX
Huang, XD
AF Huang, Hanwen
Chen, Zhongxue
Huang, Xudong
TI Age-adjusted nonparametric detection of differential DNA methylation
with case-control designs
SO BMC BIOINFORMATICS
LA English
DT Article
DE Nonparametric method; One-sided test; Combining p-value
ID GENOME-WIDE ASSOCIATION; EXPRESSED GENES; ARRAY DATA; CANCER; LOCI;
PROBABILITIES; TESTS
AB Background: DNA methylation profiles differ among disease types and, therefore, can be used in disease diagnosis. In addition, large-scale whole genome DNA methylation data offer tremendous potential in understanding the role of DNA methylation in normal development and function. However, due to the unique feature of the methylation data, powerful and robust statistical methods are very limited in this area.
Results: In this paper, we proposed and examined a new statistical method to detect differentially methylated loci for case control designs that is fully nonparametric and does not depend on any assumption for the underlying distribution of the data. Moreover, the proposed method adjusts for the age effect that has been shown to be highly correlated with DNA methylation profiles. Using simulation studies and a real data application, we have demonstrated the advantages of our method over existing commonly used methods.
Conclusions: Compared to existing methods, our method improved the detection power for differentially methylated loci for case control designs and controlled the type I error well. Its applications are not limited to methylation data; it can be extended to many other case-control studies.
C1 [Huang, Hanwen] Univ Georgia, Dept Epidemiol & Biostat, Athens, GA 30605 USA.
[Chen, Zhongxue] Indiana Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Bloomington, IN 47405 USA.
[Huang, Xudong] Massachusetts Gen Hosp, Neurochem Lab, Dept Psychiat, Charlestown, MA 02129 USA.
[Huang, Xudong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Chen, ZX (reprint author), Indiana Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, 1025 E 7th St, Bloomington, IN 47405 USA.
EM zc3@indiana.edu
RI Chen, Zhongxue/K-1372-2013
OI Chen, Zhongxue/0000-0003-2537-7843
FU School of Public Health at the Indiana University Bloomington
FX The authors would like to thank Ms. Kim Lawson for her professional
editorial assistance, which highly improved the presentation of this
paper. ZC also thanks the support from the faculty research funds
awarded by the School of Public Health at the Indiana University
Bloomington.
NR 32
TC 9
Z9 9
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAR 6
PY 2013
VL 14
AR 86
DI 10.1186/1471-2105-14-86
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 106ZV
UT WOS:000316185300001
PM 23497201
ER
PT J
AU Wojno, AP
Pierce, EA
Bennett, J
AF Wojno, Adam P.
Pierce, Eric A.
Bennett, Jean
TI Seeing the Light
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID LEBER CONGENITAL AMAUROSIS; GENE-THERAPY; CHILDHOOD BLINDNESS; RPE65
MUTATIONS; CANINE MODEL; VISION; ROD
AB One-time gene therapy resulted in multiyear visual improvement, and new approaches were used to evaluate effects on retinal structure.
C1 [Wojno, Adam P.; Bennett, Jean] Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
[Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst,Dept Ophthalmol, Boston, MA 02114 USA.
RP Bennett, J (reprint author), Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
EM jebennet@mail.med.upenn.edu
OI Pierce, Eric/0000-0002-2354-4102
NR 7
TC 3
Z9 3
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 MAR 6
PY 2013
VL 5
IS 175
AR 175fs8
DI 10.1126/scitranslmed.3005798
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 103MY
UT WOS:000315922500002
PM 23467559
ER
PT J
AU Ruchelsman, DE
Christoforou, D
Jupiter, JB
AF Ruchelsman, David E.
Christoforou, Dimitrios
Jupiter, Jesse B.
TI Fractures of the Radial Head and Neck
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Review
ID PARTIAL ARTICULAR FRACTURES; MEDIAL COLLATERAL LIGAMENT; ESSEX-LOPRESTI
INJURY; TERM-FOLLOW-UP; MASON TYPE-III; INTERNAL-FIXATION; OPEN
REDUCTION; INTEROSSEOUS MEMBRANE; ELBOW DISLOCATION; MORPHOMETRIC
PARAMETERS
C1 [Ruchelsman, David E.; Christoforou, Dimitrios; Jupiter, Jesse B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, Boston, MA 02114 USA.
Tufts Univ, Sch Med, Newton Wellesley Hosp, Boston, MA 02111 USA.
RP Ruchelsman, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Hand & Upper Extrem Serv, 55 Fruit St,Yawkey Ctr,Suite 2100, Boston, MA 02114 USA.
EM druchelsman@partners.org; jjupiter1@partners.org
NR 93
TC 13
Z9 16
U1 0
U2 6
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD MAR 6
PY 2013
VL 95A
IS 5
BP 469
EP 478
DI 10.2106/JBJS.J.01989
PG 10
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AF8MV
UT WOS:000334971200012
PM 23467871
ER
PT J
AU Berg, AH
Drechsler, C
Wenger, J
Buccafusca, R
Hod, T
Kalim, S
Ramma, W
Parikh, SM
Steen, H
Friedman, DJ
Danziger, J
Wanner, C
Thadhani, R
Karumanchi, SA
AF Berg, Anders H.
Drechsler, Christiane
Wenger, Julia
Buccafusca, Roberto
Hod, Tammy
Kalim, Sahir
Ramma, Wenda
Parikh, Samir M.
Steen, Hanno
Friedman, David J.
Danziger, John
Wanner, Christoph
Thadhani, Ravi
Karumanchi, S. Ananth
TI Carbamylation of Serum Albumin as a Risk Factor for Mortality in
Patients with Kidney Failure
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID HEMODIALYSIS-PATIENTS; AMINO-ACIDS; FUNCTIONAL GROUPS; RENAL-FAILURE;
MAINTENANCE HEMODIALYSIS; PERITONEAL-DIALYSIS; ENDOTHELIAL-CELLS;
PROTEIN; CYANATE; UREA
AB Urea, the toxic end product of protein catabolism, is elevated in end-stage renal disease (ESRD), although it is unclear whether or how it contributes to disease. Urea can promote the carbamylation of proteins on multiple lysine side chains, including human albumin, which has a predominant carbamylation site on Lys(549). The proportion of serum albumin carbamylated on Lys(549) (% C-Alb) correlated with time-averaged blood urea concentrations and was twice as high in ESRD patients than in non-uremic subjects (0.90% versus 0.42%). Baseline %C-Alb was higher in ESRD subjects who died within 1 year than in those who survived longer than 1 year (1.01% versus 0.77%) and was associated with an increased risk of death within 1 year (hazard ratio, 3.76). These findings were validated in an independent cohort of diabetic ESRD subjects (hazard ratio, 3.73). Decreased concentrations of serum amino acids correlated with higher %C-Alb in ESRD patients, and mice with diet-induced amino acid deficiencies exhibited greater susceptibility to albumin carbamylation than did chow-fed mice. In vitro studies showed that amino acids such as cysteine, histidine, arginine, and lysine, as well as other nucleophiles such as taurine, inhibited cyanate-induced C-Alb formation at physiologic pH and temperature. Together, these results suggest that chronically elevated urea promotes carbamylation of proteins in ESRD and that serum amino acid concentrations may modulate this protein modification. In summary, we have identified serum % C-Alb as a risk factor for mortality in patients with ESRD and propose that this risk factor may be modifiable with supplemental amino acid therapy.
C1 [Berg, Anders H.; Ramma, Wenda] Beth Israel Deaconess Med Ctr, Dept Pathol, Div Clin Chem, Boston, MA 02215 USA.
[Drechsler, Christiane; Wanner, Christoph] Univ Wurzburg, Dept Internal Med, Div Nephrol, D-97074 Wurzburg, Germany.
[Wenger, Julia; Kalim, Sahir; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Wenger, Julia; Kalim, Sahir; Thadhani, Ravi] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Buccafusca, Roberto; Hod, Tammy; Parikh, Samir M.; Friedman, David J.; Danziger, John; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA.
[Buccafusca, Roberto; Hod, Tammy; Parikh, Samir M.; Friedman, David J.; Danziger, John; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Dept Med, Boston, MA 02215 USA.
[Buccafusca, Roberto; Hod, Tammy; Parikh, Samir M.; Friedman, David J.; Danziger, John; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Buccafusca, Roberto; Steen, Hanno] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Buccafusca, Roberto; Steen, Hanno] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02215 USA.
RP Berg, AH (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, Div Clin Chem, 330 Brookline Ave, Boston, MA 02215 USA.
EM ahberg@bidmc.harvard.edu
FU Beth Israel Deaconess Medical Center Department of Pathology; Howard
Hughes Medical Institute; University Hospital Wuerzberg
"Gundausstattung" grant program; [K24 DK094872]
FX Supported by the Beth Israel Deaconess Medical Center Department of
Pathology (to A.H.B.); the Howard Hughes Medical Institute (to S.A.K.);
K24 DK094872 (to R.T.); and the University Hospital Wuerzberg
"Gundausstattung" grant program (to C.D. and C.W.).
NR 54
TC 23
Z9 24
U1 2
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 6
PY 2013
VL 5
IS 175
AR 175ra29
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 103MY
UT WOS:000315922500004
PM 23467560
ER
PT J
AU Chen, CY
Garcia-Santos, D
Ishikawa, Y
Seguin, A
Li, LT
Fegan, KH
Hildick-Smith, GJ
Shah, DI
Cooney, JD
Chen, W
King, MJ
Yien, YY
Schultz, IJ
Anderson, H
Dalton, AJ
Freedman, ML
Kingsley, PD
Palis, J
Hattangadi, SM
Lodish, HF
Ward, DM
Kaplan, J
Maeda, T
Ponka, P
Paw, BH
AF Chen, Caiyong
Garcia-Santos, Daniel
Ishikawa, Yuichi
Seguin, Alexandra
Li, Liangtao
Fegan, Katherine H.
Hildick-Smith, Gordon J.
Shah, Dhvanit I.
Cooney, Jeffrey D.
Chen, Wen
King, Matthew J.
Yien, Yvette Y.
Schultz, Iman J.
Anderson, Heidi
Dalton, Arthur J.
Freedman, Matthew L.
Kingsley, Paul D.
Palis, James
Hattangadi, Shilpa M.
Lodish, Harvey F.
Ward, Diane M.
Kaplan, Jerry
Maeda, Takahiro
Ponka, Prem
Paw, Barry H.
TI Snx3 Regulates Recycling of the Transferrin Receptor and Iron
Assimilation
SO CELL METABOLISM
LA English
DT Article
ID ERYTHROID-DIFFERENTIATION; PROTEIN TRAFFICKING; RESPONSIVE ELEMENTS;
SORTING NEXINS; HBD MICE; CELLS; METABOLISM; GENE; TRANSPORT; LOCI
AB Sorting of endocytic ligands and receptors is critical for diverse cellular processes. The physiological significance of endosomal sorting proteins in vertebrates, however, remains largely unknown. Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors. Snx3 is highly expressed in vertebrate hematopoietic tissues. Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates due to impaired transferrin (Tf)-mediated iron uptake and its accumulation in early endosomes. This impaired iron assimilation can be complemented with non-Tf iron chelates. We show that Snx3 and Vps35, a component of the retromer, interact with Tfrc to sort it to the recycling endosomes. Our findings uncover a role of Snx3 in regulating Tfrc recycling, iron homeostasis, and erythropoiesis. Thus, the identification of Snx3 provides a genetic tool for exploring erythropoiesis and disorders of iron metabolism.
C1 [Chen, Caiyong; Ishikawa, Yuichi; Hildick-Smith, Gordon J.; Shah, Dhvanit I.; Cooney, Jeffrey D.; Chen, Wen; King, Matthew J.; Yien, Yvette Y.; Schultz, Iman J.; Anderson, Heidi; Dalton, Arthur J.; Hattangadi, Shilpa M.; Maeda, Takahiro; Paw, Barry H.] Harvard Univ, Sch Med, Dept Med, Div Hematol,Brigham & Womens Hosp, Boston, MA 02115 USA.
[Garcia-Santos, Daniel; Ponka, Prem] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3G 1Y6, Canada.
[Garcia-Santos, Daniel; Ponka, Prem] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada.
[Seguin, Alexandra; Li, Liangtao; Ward, Diane M.; Kaplan, Jerry] Univ Utah, Dept Pathol, Sch Med, Salt Lake City, UT 84312 USA.
[Fegan, Katherine H.; Kingsley, Paul D.; Palis, James] Univ Rochester, Sch Med & Dent, Dept Pediat, Ctr Pediat Biomed Res, Rochester, NY 14642 USA.
[Freedman, Matthew L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Hattangadi, Shilpa M.; Paw, Barry H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Hattangadi, Shilpa M.; Paw, Barry H.] Harvard Univ, Sch Med, Dept Med, Div Hematol Oncol,Boston Childrens Hosp, Boston, MA 02115 USA.
[Hattangadi, Shilpa M.; Lodish, Harvey F.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Hattangadi, Shilpa M.; Lodish, Harvey F.] MIT, Cambridge, MA 02142 USA.
RP Paw, BH (reprint author), Harvard Univ, Sch Med, Dept Med, Div Hematol,Brigham & Womens Hosp, Boston, MA 02115 USA.
EM bpaw@rics.bwh.harvard.edu
RI Ponka, Prem/A-4123-2011;
OI Garcia dos Santos, Daniel/0000-0003-3894-427X
FU Cooley's Anemia Foundation; American Heart Association; American Society
of Hematology; Dutch National Science Fund-NWO; Finnish Sigrid Juselius
Foundation; March of Dimes Foundation [6-FY09-289]; Canadian Institutes
of Health Research; National Institutes of Health [T32 HL007574, K01
DK085217, K08 DK076848, R01 DK09361, P01 HL032262, R01 HL026922, R01
DK052380, R01 DK070838]
FX We thank members of our lab (Jacky Chung, Diana Branco, Adrianne Kolpak)
and Dr. Elizabeth Leibold for critical discussion and reading of the
manuscript, Dr. Yan Zhang for help with the enzymatic assays, Dr.
Rebecca Wingert for the zebrafish tfr1a cDNA clone, Dr. Leonard Zon for
the Tg(globin LCR: eGFP) transgenic line, Dr. Karin Hoffmeister for use
of the FACS machine, and Christian Lawrence and his team for the
zebrafish husbandry. This work was supported by grants from the Cooley's
Anemia Foundation (C. C., D. I. S.), the American Heart Association (J.
D. C., M. J. K., A. J. D.), the American Society of Hematology (M. J.
K.), the Dutch National Science Fund-NWO (I. J. S.), the Finnish Sigrid
Juselius Foundation (H. A.), the March of Dimes Foundation (6-FY09-289,
B. H. P.), the Canadian Institutes of Health Research (D. G.-S. and P.
P.), and the National Institutes of Health (T32 HL007574, Y. Y. Y.; K01
DK085217, D. I. S.; K08 DK076848, S. M. H.; R01 DK09361, J. P.; P01
HL032262, H. F. L.; R01 HL026922, D. M. W.; R01 DK052380, J. K.; R01
DK070838 and P01 HL032262, B. H. P.). C. C. and B. H. P. designed
studies, performed experiments, analyzed data, and wrote the manuscript.
D. G.-S. and P. P. measured the uptake of 59 Fe-Tf. Y. I. and T. M.
measured the surface-bound Tfrc level and the recycling of internalized
Tf-Alexa 647. A. S., L. L., D. M. W., and J. K. analyzed the subcellular
localization of Tf-Alexa 488 and performed the enzymatic assays. K. H.
F., P. D. K., and J. P. performed the in situ hybridization studies in
mouse embryos. G. J. H.-S. and J. D. C. performed flow cytometry
experiments on Tg(globin-LCR: eGFP) line. D. I. S. performed the qRT-PCR
analysis. W. C. constructed Tfrc-FLAG and Abcb10-FLAG constructs and
generated the MEL clones stably expressing these constructs. M. J. K.,
Y. Y. Y., I. J. S., H. A., and A. J. D. helped with RNA-seq data
analysis and zebrafish colony maintenance. M. L. F. analyzed the GWAS
database for potential interesting SNPs in Snx3. S. M. H. and H. F. L.
provided gene expression data from the RNA-seq experiment and knocked
down Snx3 in mouse primary fetal liver cells.
NR 53
TC 22
Z9 25
U1 3
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD MAR 5
PY 2013
VL 17
IS 3
BP 343
EP 352
DI 10.1016/j.cmet.2013.01.013
PG 10
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 242TP
UT WOS:000326265400007
PM 23416069
ER
PT J
AU Gameiro, PA
Yang, JJ
Metelo, AM
Perez-Carro, R
Baker, R
Wang, ZW
Arreola, A
Rathmell, WK
Olumi, A
Lopez-Larrubia, P
Stephanopoulos, G
Iliopoulos, O
AF Gameiro, Paulo A.
Yang, Juanjuan
Metelo, Ana M.
Perez-Carro, Rocio
Baker, Rania
Wang, Zongwei
Arreola, Alexandra
Rathmell, W. Kimryn
Olumi, Aria
Lopez-Larrubia, Pilar
Stephanopoulos, Gregory
Iliopoulos, Othon
TI In Vivo HIF-Mediated Reductive Carboxylation Is Regulated by Citrate
Levels and Sensitizes VHL-Deficient Cells to Glutamine Deprivation
SO CELL METABOLISM
LA English
DT Article
ID ADENINE DINUCLEOTIDE PHOSPHATE; HYPOXIA-INDUCIBLE FACTOR-1;
TUMOR-SUPPRESSOR PROTEIN; ISOCITRATE DEHYDROGENASE; OXIDATIVE STRESS;
BINDING SITES; METABOLISM; CANCER; LIPOGENESIS; SUBSTRATE
AB Hypoxic and VHL-deficient cells use glutamine to generate citrate and lipids through reductive carboxylation (RC) of alpha-ketoglutarate. To gain insights into the role of HIF and the molecular mechanisms underlying RC, we took advantage of a panel of disease-associated VHL mutants and showed that HIF expression is necessary and sufficient for the induction of RC in human renal cell carcinoma (RCC) cells. HIF expression drastically reduced intracellular citrate levels. Feeding VHL-deficient RCC cells with acetate or citrate or knocking down PDK-1 and ACLY restored citrate levels and suppressed RC. These data suggest that HIF-induced low intracellular citrate levels promote the reductive flux by mass action to maintain lipogenesis. Using [C1-13] glutamine, we demonstrated in vivo RC activity in VHL-deficient tumors growing as xenografts in mice. Lastly, HIF rendered VHL-deficient cells sensitive to glutamine deprivation in vitro, and systemic administration of glutaminase inhibitors suppressed the growth of RCC cells as mice xenografts.
C1 [Gameiro, Paulo A.; Yang, Juanjuan; Metelo, Ana M.; Baker, Rania; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA.
[Gameiro, Paulo A.; Yang, Juanjuan; Metelo, Ana M.; Baker, Rania; Iliopoulos, Othon] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA.
[Wang, Zongwei; Olumi, Aria] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Gameiro, Paulo A.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Gameiro, Paulo A.] Univ Coimbra, Dept Life Sci, P-3004517 Coimbra, Portugal.
[Arreola, Alexandra; Rathmell, W. Kimryn] Univ N Carolina, Dept Med, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Arreola, Alexandra; Rathmell, W. Kimryn] Univ N Carolina, Dept Genet, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Perez-Carro, Rocio; Lopez-Larrubia, Pilar] CSIC UAM, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain.
RP Iliopoulos, O (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, Charlestown, MA 02129 USA.
EM oiliopoulos@partners.org
RI Lopez-Larrubia, Pilar/B-3902-2013
OI Lopez-Larrubia, Pilar/0000-0002-5141-8736
FU NIH [R01 CA122591]; MGH Proton Beam Federal Share Project; Astra-Zeneca;
Foundation for Science and Technology (FCT), Portugal; MICINN
[CTQ-2010-20960-CO2-02]; [NIHR01 DK075850]
FX The authors declare no conflict of interest. This work was supported by
NIH R01 CA122591, the MGH Proton Beam Federal Share Project, and an
Astra-Zeneca Award (all to O.I.); funding from the Foundation for
Science and Technology (FCT), Portugal (to P. A. G.); MICINN
CTQ-2010-20960-CO2-02 (to P. L-L.); and NIHR01 DK075850 (to G. S.). We
would like to thank Konstantia Angelidou (Harvard School of Public
Health) for advice on statistical methods and Dr. Ralph DeBerardinis for
helpful suggestions on the in vivo labeling experiments.
NR 45
TC 77
Z9 78
U1 2
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD MAR 5
PY 2013
VL 17
IS 3
BP 372
EP 385
DI 10.1016/j.cmet.2013.02.002
PG 14
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 242TP
UT WOS:000326265400009
PM 23473032
ER
PT J
AU Nathan, DM
Russell, S
AF Nathan, David M.
Russell, Steven
TI The future of care for type 1 diabetes
SO CANADIAN MEDICAL ASSOCIATION JOURNAL
LA English
DT Editorial Material
ID INSULIN DELIVERY; COMPLICATIONS; PANCREAS; MELLITUS
C1 [Nathan, David M.; Russell, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Nathan, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
EM dnathan@partners.org
NR 10
TC 0
Z9 0
U1 0
U2 2
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA
SN 0820-3946
J9 CAN MED ASSOC J
JI Can. Med. Assoc. J.
PD MAR 5
PY 2013
VL 185
IS 4
BP 285
EP 286
DI 10.1503/cmaj.130011
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 180VM
UT WOS:000321626900016
PM 23359043
ER
PT J
AU Degeling, MH
Bovenberg, MSS
Lewandrowski, GK
de Gooijer, MC
Vleggeert-Lankamp, CLA
Tannous, M
Maguire, CA
Tannous, BA
AF Degeling, M. Hannah
Bovenberg, M. Sarah S.
Lewandrowski, Grant K.
de Gooijer, Mark C.
Vleggeert-Lankamp, Carmen L. A.
Tannous, Marie
Maguire, Casey A.
Tannous, Bakhos A.
TI Directed Molecular Evolution Reveals Gaussia Luciferase Variants with
Enhanced Light Output Stability
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID REPORTER GENE-EXPRESSION; IN-VIVO; BIOLUMINESCENCE; APOPTOSIS; PRINCEPS;
CELLS
AB Gaussia Luciferase (Gluc) has proven to be a powerful mammalian cell reporter for monitoring numerous biological processes in immunology, virology, oncology, and neuroscience. Current limitations of Gluc as a reporter include its emission of blue light, which is absorbed by mammalian tissues, limiting its use in vivo, and a flash-type bioluminescence reaction, making it unsuited for high-throughput applications. To overcome these limitations, a library of Gluc variants was generated using directed molecular evolution and screened for relative light: output, a shift in emission spectrum, and glow-type light emission kinetics. Several variants with a 10-15 nm shift in their light emission peak were found. Further, a Gluc variant that catalyzes a glow-type bioluminescence reaction, suited for high-throughput applications, was also identified. These results indicate that molecular evolution could be used to modulate Gluc bioluminescence reaction characteristics.
C1 [Degeling, M. Hannah; Bovenberg, M. Sarah S.; Lewandrowski, Grant K.; de Gooijer, Mark C.; Maguire, Casey A.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Neurosci, Expt Therapeut & Mol Imaging Lab, Dept Neurol, Charlestown, MA 02129 USA.
[Degeling, M. Hannah; Bovenberg, M. Sarah S.; Lewandrowski, Grant K.; de Gooijer, Mark C.; Maguire, Casey A.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA.
[Degeling, M. Hannah; Bovenberg, M. Sarah S.; Vleggeert-Lankamp, Carmen L. A.] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands.
[de Gooijer, Mark C.] Canc Ctr Amsterdam, VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, NL-1007 MB Amsterdam, Netherlands.
[Tannous, Marie] Notre Dame Univ, Fac Nat & Appl Sci, Barsa, Lebanon.
RP Tannous, BA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM btannous@hms.harvard.edu
FU NIH/NINDS [P30NS045776, 1R01NS064983]; American Brain Tumor Association;
Fulbright scholarship; Saal van Zwanenberg Foundation; VSB fonds; Dr.
Hendrik Muller Vaderlandschfonds; Dutch Cancer Foundation (KWF
Kankerbestrijding); Hersenstichting brain fund; Huygens Scholarship
Program
FX This work was supported by grants from NIH/NINDS P30NS045776 and
1R01NS064983 (BAT). C.M. is supported by a Fellowship from the American
Brain Tumor Association. M.H.D. is supported by a Fulbright scholarship,
the Saal van Zwanenberg Foundation, VSB fonds, Dr. Hendrik Muller
Vaderlandschfonds, the Dutch Cancer Foundation (KWF Kankerbestrijding),
the Hersenstichting brain fund, and the Jo Keur (Leiden hospital).
M.S.B. was supported by a Fulbright scholarship, the Huygens Scholarship
Program, VSB fonds, and the Saal van Zwanenberg Foundation. M.C.d.G. is
supported by a Fulbright scholarship. We thank John Darga of the Center
for Computational and Integrative Biology, Massachusetts General
Hospital, for performing the bacteria colony picking and growth of the
Gluc plasmid library.tbl1.
NR 23
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U1 0
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD MAR 5
PY 2013
VL 85
IS 5
BP 3006
EP 3012
DI 10.1021/ac4003134
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 118NG
UT WOS:000317031600064
PM 23425213
ER
PT J
AU Chapman, JW
O'Callaghan, CJ
Hu, N
Ding, K
Yothers, GA
Catalano, PJ
Shi, Q
Gray, RG
O'Connell, MJ
Sargent, DJ
AF Chapman, J. W.
O'Callaghan, C. J.
Hu, N.
Ding, K.
Yothers, G. A.
Catalano, P. J.
Shi, Q.
Gray, R. G.
O'Connell, M. J.
Sargent, D. J.
CA ACCENT Collaborative Grp
TI Innovative estimation of survival using log-normal survival modelling on
ACCENT database
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE colon cancer; survival; log-normal; Cox; Kaplan-Meier; ACCENT database
ID INDIVIDUAL PATIENT DATA; 18 RANDOMIZED-TRIALS; COLORECTAL-CANCER;
COLON-CANCER; PROPORTIONAL-HAZARDS; BREAST-CANCER; CETUXIMAB; THERAPY
AB Background: The ACCENT database, with individual patient data for 20 898 patients from 18 colon cancer clinical trials, was used to support Food and Drug Administration (FDA) approval of 3-year disease-free survival as a surrogate for 5-year overall survival. We hypothesised substantive differences in survival estimation with log-normal modelling rather than standard Kaplan-Meier or Cox approaches.
Methods: Time to relapse, disease-free survival, and overall survival were estimated using Kaplan-Meier, Cox, and log-normal approaches for male subjects aged 60-65 years, with stage III colon cancer, treated with 5-fluorouracil-based chemotherapy regimens (with 5FU), or with surgery alone (without 5FU).
Results: Absolute differences between Cox and log-normal estimates with (without) 5FU varied by end point. The log-normal model had 5.8 (6.3)% higher estimated 3-year time to relapse than the Cox model; 4.8 (5.1)% higher 3-year disease-free survival; and 3.2 (2.2)% higher 5-year overall survival. Model checking indicated greater data support for the log-normal than the Cox model, with Cox and Kaplan Meier estimates being more similar. All three model types indicate consistent evidence of treatment benefit on both 3-year disease-free survival and 5-year overall survival; patients allocated to 5FU had 5.0-6.7% higher 3-year disease-free survival and 5.3-6.8% higher 5-year overall survival.
Conclusion: Substantive absolute differences between estimates of 3-year disease-free survival and 5-year overall survival with log-normal and Cox models were large enough to be clinically relevant, and warrant further consideration.
C1 [Chapman, J. W.; O'Callaghan, C. J.; Hu, N.; Ding, K.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
[Yothers, G. A.] Univ Pittsburgh, NSABP Biostat Ctr, Pittsburgh, PA USA.
[Yothers, G. A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Catalano, P. J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Shi, Q.; Sargent, D. J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Gray, R. G.] Univ Birmingham, Birmingham, W Midlands, England.
[Yothers, G. A.; O'Connell, M. J.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
RP Chapman, JW (reprint author), Queens Univ, NCIC Clin Trials Grp, 10 Stuart St, Kingston, ON, Canada.
EM jchapman@ctg.queensu.ca
OI Sargent, Daniel/0000-0002-2684-4741; Yothers, Greg/0000-0002-7965-7333
FU Canadian Cancer Society Research Institute; NCCTG grant from the
National Cancer Institute at the National Institutes of Health
[CA25224]; Canadian National Sciences and Engineering Research Council;
Queen's University Department of Community Health and Epidemiology
FX This work was supported by a Canadian Cancer Society Research Institute
grant to the NCIC Clinical Trials Group (CTG) for NCIC CTG Faculty; the
ACCENT group is supported by the NCCTG grant from the National Cancer
Institute at the National Institutes of Health (Grant CA25224); and N Hu
was supported by a Canadian National Sciences and Engineering Research
Council grant to K Ding and by Queen's University Department of
Community Health and Epidemiology graduate student support.
NR 19
TC 3
Z9 4
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 5
PY 2013
VL 108
IS 4
BP 784
EP 790
DI 10.1038/bjc.2013.34
PG 7
WC Oncology
SC Oncology
GA 114XI
UT WOS:000316775900008
PM 23385733
ER
PT J
AU Shekelle, PG
Pronovost, PJ
Wachter, RM
McDonald, KM
Schoelles, K
Dy, SM
Shojania, K
Reston, JT
Adams, AS
Angood, PB
Bates, DW
Bickman, L
Carayon, P
Donaldson, L
Duan, NH
Farley, DO
Greenhalgh, T
Haughom, JL
Lake, E
Lilford, R
Lohr, KN
Meyer, GS
Miller, MR
Neuhauser, DV
Ryan, G
Saint, S
Shortell, SM
Stevens, DP
Walshe, K
AF Shekelle, Paul G.
Pronovost, Peter J.
Wachter, Robert M.
McDonald, Kathryn M.
Schoelles, Karen
Dy, Sydney M.
Shojania, Kaveh
Reston, James T.
Adams, Alyce S.
Angood, Peter B.
Bates, David W.
Bickman, Leonard
Carayon, Pascale
Donaldson, Liam
Duan, Naihua
Farley, Donna O.
Greenhalgh, Trisha
Haughom, John L.
Lake, Eileen
Lilford, Richard
Lohr, Kathleen N.
Meyer, Gregg S.
Miller, Marlene R.
Neuhauser, Duncan V.
Ryan, Gery
Saint, Sanjay
Shortell, Stephen M.
Stevens, David P.
Walshe, Kieran
TI The Top Patient Safety Strategies That Can Be Encouraged for Adoption
Now
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID SYSTEMATIC REVIEWS
C1 [Shekelle, Paul G.] RAND Corp, Santa Monica, CA 90401 USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Stanford Ctr Hlth Policy, Stanford, CA USA.
Ctr Primary Care & Outcomes Res, Stanford, CA USA.
Kaiser Permanente, Oakland, CA 94612 USA.
Univ Calif Berkeley, Berkeley, CA 94720 USA.
Johns Hopkins Univ, Baltimore, MD 21231 USA.
Johns Hopkins Childrens Ctr, Baltimore, MD 21287 USA.
ECRI Inst, Plymouth Meeting, PA 19462 USA.
RAND Corp, Pittsburgh, PA 15213 USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Toronto, Ottawa, ON, Canada.
Natl Qual Forum, Washington, DC USA.
Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA.
Vanderbilt Univ, Peabody Coll, Nashville, TN 37203 USA.
Univ Wisconsin, Madison, WI 53706 USA.
Univ London Imperial Coll Sci Technol & Med, London W2 1NY, England.
Univ London, London, England.
Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
Univ Manchester, Manchester Business Sch, Manchester M15 6PB, Lancs, England.
New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
PeaceHlth Med Grp, Eugene, OR USA.
Res Triangle Inst Int, Res Triangle Pk, NC 27709 USA.
Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH 03766 USA.
Case Western Reserve Univ, Cleveland, OH 44106 USA.
Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI 48105 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
RP Shekelle, PG (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA.
EM shekelle@rand.org
RI Greenhalgh, Trisha/B-1825-2015;
OI Greenhalgh, Trisha/0000-0003-2369-8088; Bickman,
Leonard/0000-0002-0746-3791
FU PHS HHS [HHSA-290-2007-10062I]
NR 10
TC 97
Z9 98
U1 1
U2 15
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 5
PY 2013
VL 158
IS 5
BP 365
EP +
DI 10.7326/0003-4819-158-5-201303051-00001
PN 2
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105HX
UT WOS:000316058600001
PM 23460091
ER
PT J
AU Miake-Lye, IM
Hempel, S
Ganz, DA
Shekelle, PG
AF Miake-Lye, Isomi M.
Hempel, Susanne
Ganz, David A.
Shekelle, Paul G.
TI Inpatient Fall Prevention Programs as a Patient Safety Strategy A
Systematic Review
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ACUTE-CARE; MULTIFACTORIAL INTERVENTION;
METHODOLOGICAL QUALITY; RISK-ASSESSMENT; ADVERSE EVENTS; HOSPITALS;
INJURIES; MULTIDISCIPLINARY; IMPLEMENTATION
AB Falls are common among inpatients. Several reviews, including 4 meta-analyses involving 19 studies, show that multicomponent programs to prevent falls among inpatients reduce relative risk for falls by as much as 30%. The purpose of this updated review is to reassess the benefits and harms of fall prevention programs in acute care settings and to identify factors associated with successful implementation of these programs. We searched for new evidence using PubMed from 2005 to September 2012. Two new, large, randomized, controlled trials supported the conclusions of the existing meta-analyses. An optimal bundle of components was not identified. Harms were not systematically examined, but potential harms included increased use of restraints and sedating drugs and decreased efforts to mobilize patients. Eleven studies showed that the following themes were associated with successful implementation: leadership support, engagement of front-line staff in program design, guidance of the prevention program by a multidisciplinary committee, pilot-testing interventions, use of information technology systems to provide data about falls, staff education and training, and changes in nihilistic attitudes about fall prevention. Future research would advance knowledge by identifying optimal bundles of component interventions for particular patients and by determining whether effectiveness relies more on the mix of the components or use of certain implementation strategies. Ann Intern Med. 2013;158:390-396. www.annals.org
C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Shekelle, Paul G.] RAND Corp, Santa Monica, CA 90401 USA.
RP Shekelle, PG (reprint author), RAND Corp, Santa Monica, CA 90401 USA.
EM shekelle@rand.org
FU AHRQ, U.S. Department of Health and Human Services
[HHSA-290-2007-10062I, HHSA-290-2010-00017I, HHSA-290-32001T]; Veterans
Affairs Health Services Research & Development Service, Veterans Health
Administration, U.S. Department of Veterans Affairs through the Veterans
Affairs Greater Los Angeles Health Services Research & Development
Center of Excellence [VA CD2 08-012-1]; AHRQ; AHRQ, Veterans Affairs
Health Services Research and Development Service; Veterans Affairs;
Centers for Medicare & Medicaid Services; National Institute of Nursing
Research; Office of the National Coordinator
FX Financial Support: From the AHRQ, U.S. Department of Health and Human
Services (contracts HHSA-290-2007-10062I, HHSA-290-2010-00017I, and
HHSA-290-32001T). Dr. Ganz was supported by a Career Development Award
from the Veterans Affairs Health Services Research & Development
Service, Veterans Health Administration, U.S. Department of Veterans
Affairs through the Veterans Affairs Greater Los Angeles Health Services
Research & Development Center of Excellence (project VA CD2 08-012-1).;
Potential Conflicts of Interest: Dr. Hempel: Grant (money to
institution): AHRQ. Dr. Ganz: Grant (money to institution): AHRQ,
Veterans Affairs Health Services Research and Development Service. Dr.
Shekelle: Consultancy: ECRI Institute; Employment: Veterans Affairs;
Grants/grants pending: AHRQ, Veterans Affairs, Centers for Medicare &
Medicaid Services, National Institute of Nursing Research, Office of the
National Coordinator; Royalties: UpToDate. Ms. Miake-Lye: None
disclosed. Disclosures can also be viewed at
www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum =
M12-2569.
NR 57
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U1 0
U2 26
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 5
PY 2013
VL 158
IS 5
BP 390
EP +
DI 10.7326/0003-4819-158-5-201303051-00005
PN 2
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105HX
UT WOS:000316058600005
PM 23460095
ER
PT J
AU Shekelle, PG
AF Shekelle, Paul G.
TI Nurse-Patient Ratios as a Patient Safety Strategy A Systematic Review
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID INTENSIVE-CARE-UNIT; STAFFING LEVELS; HOSPITAL MORTALITY; JOB
DISSATISFACTION; OUTCOMES EVIDENCE; 30-DAY MORTALITY; HEALTH-CARE;
QUALITY; COST; ASSOCIATION
AB A small percentage of patients die during hospitalization or shortly thereafter, and it is widely believed that more or better nursing care could prevent some of these deaths. The author systematically reviewed the evidence about nurse staffing ratios and in-hospital death through September 2012. From 550 titles, 87 articles were reviewed and 15 new studies that augmented the 2 existing reviews were selected. The strongest evidence supporting a causal relationship between higher nurse staffing levels and decreased inpatient mortality comes from a longitudinal study in a single hospital that carefully accounted for nurse staffing and patient comorbid conditions and a meta-analysis that found a "dose-response relationship" in observational studies of nurse staffing and death. No studies reported any serious harms associated with an increase in nurse staffing. Limiting any stronger conclusions is the lack of an evaluation of an intervention to increase nurse staffing ratios. The formal costs of increasing the nurse-patient ratio cannot be calculated because there has been no evaluation of an intentional change in nurse staffing to improve patient outcomes. Ann Intern Med. 2013;158:404-409. www.annals.org
C1 [Shekelle, Paul G.] RAND Corp, Santa Monica, CA 90401 USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Shekelle, PG (reprint author), RAND Corp, 1776 Main St, Santa Monica, CA 90401 USA.
EM shekelle@rand.org
FU Agency for Healthcare Research and Quality, U.S. Department of Health
and Human Services [HHSA-290-2007-10062I]; Agency for Healthcare
Research and Quality; Veterans Affairs; Centers for Medicare & Medicaid
Services; National Institute of Nursing Research; Office of the National
Coordinator
FX Financial Support: From the Agency for Healthcare Research and Quality,
U.S. Department of Health and Human Services (contract
HHSA-290-2007-10062I).; Potential Conflicts of Interest: Consultancy:
ECRI Institute; Employment: Veterans Affairs; Grants/grants pending:
Agency for Healthcare Research and Quality, Veterans Affairs, Centers
for Medicare & Medicaid Services, National Institute of Nursing
Research, Office of the National Coordinator; Royalties: UpToDate.
Disclosures can also be viewed at
www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-257
4.
NR 46
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U1 4
U2 42
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 5
PY 2013
VL 158
IS 5
BP 404
EP +
DI 10.7326/0003-4819-158-5-201303051-00007
PN 2
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105HX
UT WOS:000316058600007
PM 23460097
ER
PT J
AU Bromley, SK
Larson, RP
Ziegler, SF
Luster, AD
AF Bromley, Shannon K.
Larson, Ryan P.
Ziegler, Steven F.
Luster, Andrew D.
TI IL-23 Induces Atopic Dermatitis-Like Inflammation Instead of
Psoriasis-Like Inflammation in CCR2-Deficient Mice
SO PLOS ONE
LA English
DT Article
ID THYMIC STROMAL LYMPHOPOIETIN; INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY;
HUMAN TH17 CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHEMOKINE
RECEPTOR (CCR)2; CHRONIC PLAQUE PSORIASIS; HUMAN EPITHELIAL-CELLS;
T-CELLS; DENDRITIC CELLS; AIRWAY INFLAMMATION
AB Psoriasis is an immune-mediated chronic inflammatory skin disease, characterized by epidermal hyperplasia and infiltration of leukocytes into the dermis and epidermis. IL-23 is expressed in psoriatic skin, and IL-23 injected into the skin of mice produces IL-22-dependent dermal inflammation and acanthosis. The chemokine receptor CCR2 has been implicated in the pathogenesis of several inflammatory diseases, including psoriasis. CCR2-positive cells and the CCR2 ligand, CCL2 are abundant in psoriatic lesions. To examine the requirement of CCR2 in the development of IL-23-induced cutaneous inflammation, we injected the ears of wild-type (WT) and CCR2-deficient (CCR2(-)/(-)) mice with IL-23. CCR2(-)/(-) mice had increased ear swelling and epidermal thickening, which was correlated with increased cutaneous IL-4 levels and increased numbers of eosinophils within the skin. In addition, TSLP, a cytokine known to promote and amplify T helper cell type 2 (Th2) immune responses, was also increased within the inflamed skin of CCR2(-)/(-) mice. Our data suggest that increased levels of TSLP in CCR2(-)/(-) mice may contribute to the propensity of these mice to develop increased Th2-type immune responses.
C1 [Bromley, Shannon K.; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA.
[Larson, Ryan P.; Ziegler, Steven F.] Univ Washington, Dept Immunol, Sch Med, Seattle, WA 98195 USA.
[Larson, Ryan P.; Ziegler, Steven F.] Virginia Mason, Program Immunol, Benaroya Res Inst, Seattle, WA USA.
RP Bromley, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02115 USA.
EM sbromley@helix.mgh.harvard.edu; aluster@mgh.harvard.edu
FU National Institutes of Health [R37-AI040618, R01-AR056113,
K01-AR053715]; Claflin Distinguished Scholar Award
FX Supported by the National Institutes of Health grant R37-AI040618 to
ADL, R01-AR056113 to SFZ, and K01-AR053715 to SKB and a Claflin
Distinguished Scholar Award to SKB. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 66
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 5
PY 2013
VL 8
IS 3
AR e58196
DI 10.1371/journal.pone.0058196
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099RC
UT WOS:000315637900104
PM 23472158
ER
PT J
AU Matthews, LT
Sibeko, S
Mansoor, LE
Yende-Zuma, N
Bangsberg, DR
Karim, QA
AF Matthews, Lynn T.
Sibeko, Sengeziwe
Mansoor, Leila E.
Yende-Zuma, Nonhlanhla
Bangsberg, David R.
Karim, Quarraisha Abdool
TI Women with Pregnancies Had Lower Adherence to 1% Tenofovir Vaginal Gel
as HIV Preexposure Prophylaxis in CAPRISA 004, a Phase IIB
Randomized-Controlled Trial
SO PLOS ONE
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; SOUTH-AFRICA; ANTIRETROVIRAL THERAPY;
CONTRACEPTIVE USE; MALE CIRCUMCISION; SERODISCORDANT COUPLES; HORMONAL
CONTRACEPTION; DOUBLE-BLIND; PREVENTION; INFECTION
AB Background: Antiretroviral prophylaxis may be a critical strategy to reduce periconception HIV transmission. Maximizing the benefit of periconception pharmacologic HIV risk-reduction requires an understanding of the links between pregnancy and adherence to this prevention strategy.
Methods: We assessed study gel adherence among women with pregnancies compared to women without pregnancies enrolled in the CAPRISA 004 phase IIB trial of 1% vaginal tenofovir gel. Pregnancy was assessed with monthly urine tests. Adherence was measured monthly and defined as proportion of sex acts covered by two returned, used applicators based on pre- and post-coital dosing. High adherence was defined as a median adherence score of >80%, that is, more than 80% of sex acts were covered by two applications of study gel. A multivariate generalized estimating equations (GEE) model with a binomial distribution was used to assess covariates associated with high adherence (>80%) over time. Median adherence before and after pregnancy was compared using Wilcoxon signed rank test.
Results: Among 868 women, 53 had at least 1 pregnancy (4.06 per 100 woman years, 95% CI: 3.04, 5.31). Women with pregnancies had lower median adherence compared to women without pregnancies (50% [IQR: 45-83] vs. 60% [IQR: 50-100], p = 0.02). Women with pregnancies also had a 48% lower odds of high adherence compared to women without pregnancies when adjusting for confounders (aOR 0.52, 95% CI: 0.41-0.66, p<0.0001). Among women with pregnancies, adherence before and after pregnancy was not different (50% [IQR: 46-83] vs. 55% [IQR: 20-100], p = 0.68).
Conclusions: Women with pregnancies were less likely to have high adherence to study gel compared to women without pregnancies. Understanding these differences may inform findings from HIV prevention trials and future implementation of antiretroviral prophylaxis for at-risk women who choose to conceive. The protocol for the parent trial is registered on ClinicalTrials.gov, NCT00441298, http://www.clinicaltrials.gov/ct2/show/NCT00441298.
C1 [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Div Infect Dis, Ctr Global Hlth, Boston, MA 02114 USA.
[Matthews, Lynn T.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Matthews, Lynn T.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA.
[Sibeko, Sengeziwe; Mansoor, Leila E.; Yende-Zuma, Nonhlanhla; Karim, Quarraisha Abdool] Ctr AIDS Program Res South Africa CAPRISA, Durban, Kwazulu Natal, South Africa.
[Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda.
[Karim, Quarraisha Abdool] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Ctr Global Hlth, Boston, MA 02114 USA.
EM ltmatthews@partners.org
FU United States Agency for International Development (USAID) [FHI360,
GPO-A-00-05-00022-00, 132119]; Technology Innovation Agency (LIFElab) of
the South African government's Department of Science Technology;
Burroughs Wellcome Fund; American Society for Tropical Medicine and
Hygiene; [NIMH MH095655]; [NIMH MH087227]
FX The parent trial (CAPRISA 004) was supported by the United States Agency
for International Development (USAID), FHI360 [ USAID co-operative
agreement # GPO-A-00-05-00022-00, contract # 132119], and the Technology
Innovation Agency (LIFElab) of the South African government's Department
of Science & Technology. Tenofovir was provided by Gilead Sciences and
the gel was manufactured and supplied for the CAPRISA 004 trial by
CONRAD. Dr. Matthews is supported by a postdoctoral fellowship in
infectious diseases from the Burroughs Wellcome Fund and the American
Society for Tropical Medicine and Hygiene, and by a K23 award (NIMH
MH095655). Dr. Bangsberg was supported by a K24 award (NIMH MH087227).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 54
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U1 0
U2 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 MAR 5
PY 2013
VL 8
IS 3
AR e56400
DI 10.1371/journal.pone.0056400
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099RC
UT WOS:000315637900009
PM 23472071
ER
PT J
AU Kalantarian, S
Stern, TA
Mansour, M
Ruskin, JN
AF Kalantarian, Shadi
Stern, Theodore A.
Mansour, Moussa
Ruskin, Jeremy N.
TI Cognitive Impairment Associated With Atrial Fibrillation A Meta-analysis
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Review
ID C-REACTIVE PROTEIN; RISK-FACTORS; POSTSTROKE DEMENTIA; CEREBRAL
INFARCTION; ALZHEIMER-DISEASE; ISCHEMIC-STROKE; HEART-FAILURE;
UNITED-STATES; POPULATION; DECLINE
AB Background: Atrial fibrillation (AF) has been linked with an increased risk for cognitive impairment and dementia.
Purpose: To complete a meta-analysis of studies examining the association between AF and cognitive impairment.
Data Sources: Search of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and hand search of article references.
Study Selection: Prospective and nonprospective studies reporting adjusted risk estimates for the association between AF and cognitive impairment.
Data Extraction: Two abstracters independently extracted data on study characteristics, risk estimates, methods of AF and outcome ascertainment, and methodological quality.
Data Synthesis: Twenty-one studies were included in the meta-analysis. Atrial fibrillation was significantly associated with a higher risk for cognitive impairment in patients with first-ever or recurrent stroke (relative risk [RR], 2.70 [95% CI, 1.82 to 4.00]) and in a broader population including patients with or without a history of stroke (RR, 1.40 [CI, 1.19 to 1.64]). The association in the latter group remained significant independent proof of clinical stroke history (RR, 1.34 [CI, 1.13 to 1.58]). However, there was significant heterogeneity among studies of the broader population (I-2 = 69.4%). Limiting the analysis to prospective studies yielded similar results (RR, 1.36 [CI, 1.12 to 1.65]). Restricting the analysis to studies of dementia eliminated the significant heterogeneity (P = 0.137) but did not alter the pooled estimate substantially (RR, 1.38 [CI, 1.22 to 1.56]).
Limitations: There is an inherent bias because of confounding variables in observational studies. There was significant heterogeneity among included studies.
Conclusion: Evidence suggests that AF is associated with a higher risk for cognitive impairment and dementia, with or without a history of clinical stroke. Further studies are required to elucidate the association between AF and subtypes of dementia as well as the cause of cognitive impairment.
C1 [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA.
RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA.
EM jruskin@partners.org
FU Deane Institute for Integrative Research in Atrial Fibrillation and
Stroke at Massachusetts General Hospital; Harvard Catalyst; Harvard
Clinical and Translational Science Center (National Institutes of
Health) [UL1 RR 025758]; Harvard University
FX Grant Support: By the Deane Institute for Integrative Research in Atrial
Fibrillation and Stroke at Massachusetts General Hospital. This work was
conducted with support from Harvard Catalyst and 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).
NR 51
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U2 18
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 5
PY 2013
VL 158
IS 5
BP 338
EP +
DI 10.7326/0003-4819-158-5-201303050-00007
PN 1
PG 20
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105HP
UT WOS:000316057700005
PM 23460057
ER
PT J
AU Wachter, RM
Pronovost, PJ
Shekelle, PG
AF Wachter, Robert M.
Pronovost, Peter J.
Shekelle, Paul G.
TI Strategies to Improve Patient Safety: The Evidence Base Matures
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Wachter, Robert M.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Pronovost, Peter J.] Johns Hopkins Med Patient Safety & Qual, Baltimore, MD USA.
[Shekelle, Paul G.] W Los Angeles Vet Affairs Med Ctr, Santa Monica, CA USA.
[Shekelle, Paul G.] RAND Corp, Santa Monica, CA USA.
RP Wachter, RM (reprint author), Univ Calif San Francisco, Room M-994,505 Parnassus Ave, San Francisco, CA 94143 USA.
EM bobw@medicine.ucsf.edu
NR 25
TC 12
Z9 14
U1 0
U2 13
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 5
PY 2013
VL 158
IS 5
BP 350
EP +
DI 10.7326/0003-4819-158-5-201303050-00010
PN 1
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 105HP
UT WOS:000316057700008
PM 23460060
ER
PT J
AU Chan, HH
Wang, EM
Sun, MS
Hsu, PI
Tsai, WL
Tsai, TJ
Wang, KM
Chen, WC
Wang, HM
Liang, HL
Lai, KH
Brugge, WR
AF Chan, Hoi-Hung
Wang, E-Ming
Sun, Meng-Shun
Hsu, Ping-I
Tsai, Wei-Lun
Tsai, Tzung-Jiun
Wang, Kai-Ming
Chen, Wen-Chi
Wang, Huay-Min
Liang, Huei-Lung
Lai, Kwok-Hung
Brugge, William Robert
TI Linear echoendoscope-guided ERCP for the diagnosis of occult common bile
duct stones
SO BMC GASTROENTEROLOGY
LA English
DT Article
DE Linear echoendoscope; Occult common bile duct stones
ID ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHY; PROSPECTIVE MULTICENTER;
LAPAROSCOPIC CHOLECYSTECTOMY; THERAPEUTIC ERCP; COMPLICATIONS;
CHOLEDOCHOLITHIASIS; MANAGEMENT; ULTRASONOGRAPHY; SPHINCTEROTOMY;
PANCREATITIS
AB Background: Less than 67% of patients with intermediate risk for common bile duct (CBD) stones require therapeutic intervention. It is important to have an accurate, safe, and reliable method for the definitive diagnosis of CBD stones before initiating therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Few publications detail the diagnostic efficacy of linear echoendoscopy (EUS) for CBD stones.
Methods: 30 patients with biliary colic, pancreatitis, unexplained derangement of liver function tests, and/or dilated CBD without an identifiable cause were enrolled in the study. When a CBD stone was disclosed by linear EUS, ERCP with stone extraction was performed. Patients who failed ERCP were referred for surgical intervention. If no stone was found by EUS, ERCP would not be performed and patients were followed-up for possible biliary symptoms for up to three months.
Results: The major reason for enrollment was acute pancreatitis. The mean predicted risk for CBD stones was 47% (28-61). Of the 12 patients who were positive for CBD stones by EUS, nine had successful ERCP, one failed ERCP (later treated successfully by surgical intervention) and two were false-positive cases. No procedure-related adverse events were noted. For those 18 patients without evidence of CBD stones by EUS, no false-negative case was noted during the three-month follow-up period. Linear EUS had sensitivity, specificity, positive and negative predicted values for the detection of CBD stones of 1, 0.9, 0.8 and 1, respectively.
Conclusion: Linear EUS is safe and efficacious for the diagnosis of occult CBD stones in patients with intermediate risk for the disease.
C1 [Chan, Hoi-Hung; Wang, E-Ming; Hsu, Ping-I; Tsai, Wei-Lun; Tsai, Tzung-Jiun; Wang, Kai-Ming; Chen, Wen-Chi; Wang, Huay-Min; Lai, Kwok-Hung] Kaohsiung Vet Gen Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung 81362, Taiwan.
[Chan, Hoi-Hung; Wang, E-Ming] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 80424, Taiwan.
[Chan, Hoi-Hung] Tajen Univ, Coll Pharm & & Hlth Care, Yanpu Township 907, Pingtung County, Taiwan.
[Chan, Hoi-Hung; Hsu, Ping-I; Tsai, Wei-Lun; Chen, Wen-Chi; Liang, Huei-Lung; Lai, Kwok-Hung] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.
[Sun, Meng-Shun] Yuans Gen Hosp, Dept Gastroenterol & Hepatol, Kaohsiung 80249, Taiwan.
[Liang, Huei-Lung] Kaohsiung Vet Gen Hosp, Dept Radiol, Kaohsiung 81362, Taiwan.
[Brugge, William Robert] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
RP Lai, KH (reprint author), Kaohsiung Vet Gen Hosp, Dept Internal Med, Div Gastroenterol, 386 Ta Chung 1st Rd, Kaohsiung 81362, Taiwan.
EM khlai@vghks.gov.tw; wbrugge@partners.org
NR 17
TC 5
Z9 5
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-230X
J9 BMC GASTROENTEROL
JI BMC Gastroenterol.
PD MAR 5
PY 2013
VL 13
AR 44
DI 10.1186/1471-230X-13-44
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 107FA
UT WOS:000316199000001
PM 23497328
ER
PT J
AU Ganda, A
Magnusson, M
Yvan-Charvet, L
Hedblad, B
Engstrom, G
Ai, D
Wang, TJ
Gerszten, RE
Melander, O
Tall, AR
AF Ganda, Anjali
Magnusson, Martin
Yvan-Charvet, Laurent
Hedblad, Bo
Engstrom, Gunnar
Ai, Ding
Wang, Thomas J.
Gerszten, Robert E.
Melander, Olle
Tall, Alan R.
TI Mild Renal Dysfunction and Metabolites Tied to Low HDL Cholesterol Are
Associated With Monocytosis and Atherosclerosis
SO CIRCULATION
LA English
DT Article
DE atherosclerosis; immunology; kidney; metabolomics; risk factors
ID CHRONIC KIDNEY-DISEASE; INTIMA-MEDIA THICKNESS; SERUM CYSTATIN-C;
GLOMERULAR-FILTRATION-RATE; ISCHEMIC-HEART-DISEASE; CARDIOVASCULAR
EVENTS; CAROTID ATHEROSCLEROSIS; FUNCTION DECLINE; ELDERLY PERSONS; CELL
COUNT
AB Background-The number of circulating blood monocytes impacts atherosclerotic lesion size, and in mouse models, elevated levels of high-density lipoprotein cholesterol suppress blood monocyte counts and atherosclerosis. We hypothesized that individuals with mild renal dysfunction at increased cardiovascular risk would have reduced high-density lipoprotein levels, high blood monocyte counts, and accelerated atherosclerosis.
Methods and Results-To test whether mild renal dysfunction is associated with an increase in a leukocyte subpopulation rich in monocytes that has a known association with future coronary events, we divided individuals from the Malmo Diet and Cancer study (MDC) into baseline cystatin C quintiles (n=4757). Lower levels of renal function were accompanied by higher monocyte counts, and monocytes were independently associated with carotid bulb intima-media thickness cross-sectionally (P=0.02). Cystatin C levels were positively and plasma high-density lipoprotein cholesterol levels negatively associated with monocyte counts at baseline, after adjustment for traditional risk factors. Several amino acid metabolites tied to low levels of high-density lipoprotein cholesterol and insulin resistance measured in a subset of individuals (n=752) by use of liquid chromatography-mass spectrometry were independently associated with a 22% to 34% increased risk of being in the top quartile of monocytes (P<0.05).
Conclusions-A low high-density lipoprotein cholesterol, insulin resistance phenotype occurs in subjects with mild renal dysfunction and is associated with elevated monocytes and atherosclerosis. High blood monocyte counts may represent a previously unrecognized mechanism underlying the strong relationship between cystatin C and cardiovascular risk. (Circulation. 2013; 127: 988-996.)
C1 [Ganda, Anjali] Columbia Univ, Coll Phys & Surg, Div Nephrol, New York, NY 10032 USA.
[Ganda, Anjali; Yvan-Charvet, Laurent; Ai, Ding; Tall, Alan R.] Columbia Univ, Coll Phys & Surg, Div Mol Med, New York, NY 10032 USA.
[Magnusson, Martin] Skane Univ Hosp, Dept Cardiol, Malmo, Sweden.
[Hedblad, Bo; Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, Malmo, Sweden.
[Magnusson, Martin; Hedblad, Bo; Engstrom, Gunnar; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Wang, Thomas J.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Wang, Thomas J.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA.
[Gerszten, Robert E.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA.
RP Ganda, A (reprint author), Columbia Univ, Coll Phys & Surg, Div Nephrol, PH4-124,622 W 168th St, New York, NY 10032 USA.
EM ag355@columbia.edu
OI Yvan-Charvet, Laurent/0000-0002-7748-4942; Engstrom,
Gunnar/0000-0002-8618-9152; Magnusson, Martin/0000-0003-1710-5936
FU National Center for Advancing Translational Sciences, National
Institutes of Health [UL1 TR000040, UL1 RR024156]; Leducq Foundation;
Swedish Medical Research Council; Swedish Heart and Lung Foundation;
Medical Faculty of Lund University; Skane University Hospital; Albert
Pahlsson Research Foundation; Crafoord Foundation; Ernhold Lundstroms
Research Foundation; Region Skane; Hulda and Conrad Mossfelt Foundation;
Southwest Skanes Diabetes Foundation; King Gustaf V and Queen Victoria
Foundation; Lennart Hanssons Memorial Fund; Knut and Alice Wallenberg
Foundation; Marianne and Marcus Wallenberg Foundation; National
Institutes of Health [HL 98280, DK 081572]
FX Dr Ganda was supported by the National Center for Advancing
Translational Sciences, National Institutes of Health, through grant
number UL1 TR000040, formerly the National Center for Research
Resources, grant number UL1 RR024156. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. This research was
additionally supported by the Leducq Foundation. Drs Magnusson and
Melander were supported by grants from the Swedish Medical Research
Council, the Swedish Heart and Lung Foundation, the Medical Faculty of
Lund University, Skane University Hospital, the Albert Pahlsson Research
Foundation, the Crafoord Foundation, the Ernhold Lundstroms Research
Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation,
the Southwest Skanes Diabetes Foundation, the King Gustaf V and Queen
Victoria Foundation, the Lennart Hanssons Memorial Fund, Knut and Alice
Wallenberg Foundation, and the Marianne and Marcus Wallenberg
Foundation. Dr Gerszten was supported by National Institutes of Health
R01 grants HL 98280 and DK 081572.
NR 50
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Z9 23
U1 1
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 5
PY 2013
VL 127
IS 9
BP 988
EP +
DI 10.1161/CIRCULATIONAHA.112.000682
PG 14
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 101WJ
UT WOS:000315804800013
PM 23378299
ER
PT J
AU Dec, GW
AF Dec, G. William
TI Steroid Therapy Effectively Delays Duchenne's Cardiomyopathy
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE cardiomyopathy; Duchenne muscular dystrophy; mortality; steroids
ID MUSCULAR-DYSTROPHY
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Dec, GW (reprint author), Massachusetts Gen Hosp, Bigelow 810,55 Fruit St, Boston, MA 02114 USA.
EM gdec@partners.org
NR 9
TC 9
Z9 9
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 5
PY 2013
VL 61
IS 9
BP 955
EP 956
DI 10.1016/j.jacc.2012.12.011
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 094VZ
UT WOS:000315294100011
PM 23352780
ER
PT J
AU Maguen, S
Madden, E
Bosch, J
Galatzer-Levy, I
Knight, SJ
Litz, BT
Marmar, CR
McCaslin, SE
AF Maguen, Shira
Madden, Erin
Bosch, Jeane
Galatzer-Levy, Isaac
Knight, Sara J.
Litz, Brett T.
Marmar, Charles R.
McCaslin, Shannon E.
TI Killing and latent classes of PTSD symptoms in Iraq and Afghanistan
veterans
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Veterans; Killing; Trauma; Posttraumatic stress disorder
ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH SYMPTOMS; WAR VETERANS;
IMPACT; MODEL; HETEROGENEITY; SUBTHRESHOLD; IMPAIRMENT; NUMBER
AB Background: Our goal was to better understand distinct PTSD symptom presentations in Iraq and Afghanistan Veterans (N=227) and to determine whether those who killed in war were at risk for being in the most symptomatic class.
Methods: We used latent class analysis of responses to the PTSD checklist and logistic regression of most symptomatic class.
Results: We found that a four-class solution best fit the data, with the following profiles emerging: High Symptom (34% of participants), Intermediate Symptom (41%), Intermediate Symptom with Low Emotional Numbing (10%), and Low Symptom (15%). The largest group of individuals who reported killing (45%) was in the High Symptom class, and those who killed had twice the odds of being in the most symptomatic PTSD class, compared to those who did not kill. Those who endorsed killing a non-combatant (OR=4.56, 95% CI [1.77, 11.7], p < 0.01) or killing in the context of anger or revenge (OR=4.63, 95% CI=[1.89, 11.4], p < 0.001) were more likely to belong to the most symptomatic PTSD class, compared to those who did not kill.
Limitations: The study was retrospective and cross-sectional. The results may not generalize to veterans of other wars.
Conclusions: Killing in war may be an important indicator of risk for developing frequent and severe PTSD symptoms. This has implications for the mental healthcare of veterans, providing evidence that a comprehensive evaluation of returning veterans should include an assessment of killing experiences and reactions to killing. Published by Elsevier B.V.
C1 [Maguen, Shira; Madden, Erin; Bosch, Jeane; Knight, Sara J.; McCaslin, Shannon E.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Maguen, Shira; Madden, Erin; Bosch, Jeane; Knight, Sara J.; McCaslin, Shannon E.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Galatzer-Levy, Isaac; Marmar, Charles R.] NYU, Langone Med Ctr, New York, NY USA.
[Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program P 116, 4150 Clement St, San Francisco, CA 94121 USA.
EM Shira.Maguen@va.gov
OI Galatzer-Levy, Isaac/0000-0003-1864-064X
FU VA Clinical Science Research and Development Career Development Award
[CDA-2-032-06 F]; VA Health Services Research and Development Career
Development Award [RCD 06-042]
FX This research was supported by VA Clinical Science Research and
Development Career Development Award (CDA-2-032-06 F: McCaslin) and VA
Health Services Research and Development Career Development Award (RCD
06-042: Maguen). The authors would like to thank Gary Tarasovsky, Tom
Metzler, Thomas Neylan and John McQuaid for their contributions to this
manuscript. We would also like to thank the veterans for their time and
participation.
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U2 25
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD MAR 5
PY 2013
VL 145
IS 3
BP 344
EP 348
DI 10.1016/j.jad.2012.08.021
PG 5
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 086LX
UT WOS:000314686600011
PM 22959679
ER
PT J
AU Topor, DR
Swenson, L
Hunt, JI
Birmaher, B
Strober, M
Yen, S
Hoeppner, BB
Case, BG
Hower, H
Weinstock, LM
Ryan, N
Goldstein, B
Goldstein, T
Gill, MK
Axelson, D
Keller, M
AF Topor, David R.
Swenson, Lance
Hunt, Jeffrey I.
Birmaher, Boris
Strober, Michael
Yen, Shirley
Hoeppner, Bettina B.
Case, Brady G.
Hower, Heather
Weinstock, Lauren M.
Ryan, Neal
Goldstein, Benjamin
Goldstein, Tina
Gill, Mary Kay
Axelson, David
Keller, Martin
TI Manic symptoms in youth with bipolar disorder: Factor analysis by age of
symptom onset and current age
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Pediatric bipolar disorder; Course; Onset
ID SPECTRUM DISORDERS; RATING-SCALE; STEP-BD; NUMBER; ADOLESCENTS;
QUESTIONNAIRE; INSTRUMENTS; PREDICTORS; COMPONENTS; CHILDREN
AB Background: Factor analysis has been used to identify potential clinical subtypes of mania in pediatric bipolar disorder. Results vary in the number of factors retained. The present study used a formal diagnostic instrument to examine how symptoms of mania in young people are expressed, depending on age of symptom onset and current age.
Methods: Trained clinicians completed the Schedule of Affective Disorders and Schizophrenia for School-Age Children (K-SADS) Mania Rating Scale (MRS) with parents of 163 children with child-onset of symptoms (before age 12), 94 adolescents with child-onset of symptoms, and 90 adolescents with adolescent-onset of symptoms (after age 12). Factor analysis of symptom ratings during the most severe lifetime manic episode was performed for each age group.
Results: Symptom factor structures were established for each age group. Two factors were evident for children with child-onset of symptoms ("activated/pleasure seeking" and "labile/disorganized"), one factor was present for adolescents with child-onset of symptoms ("activated/pleasure seeking/disorganized") and two factors were evident for adolescents with adolescent-onset of symptoms ("activated/pleasure seeking" and "disorganized/psychotic"). The factor structures for children with child-onset and adolescents with adolescent-onset of symptoms were highly similar, with the latter factor structure including psychotic symptoms.
Limitations: Limitations include reliance on retrospective parent report and potential issues with generalizability.
Conclusions: Findings suggest mania symptomatology is largely similar when examined by both age of onset and current age, with some notable differences. Specifically, psychotic symptoms begin emerging as a distinct factor in adolescents with adolescent-onset of symptoms. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Topor, David R.] VA Boston Healthcare Syst, Boston, MA USA.
[Topor, David R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Swenson, Lance] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA.
[Hunt, Jeffrey I.; Yen, Shirley; Case, Brady G.; Hower, Heather; Weinstock, Lauren M.; Keller, Martin] Brown Univ, Dept Psychiat, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Birmaher, Boris; Ryan, Neal; Goldstein, Tina; Gill, Mary Kay; Axelson, David] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Med Ctr, Pittsburgh, PA 15213 USA.
[Strober, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Goldstein, Benjamin] Univ Toronto, Fac Med, Dept Psychiat, Sunnybrook Hlth Serv Ctr, Toronto, ON M5S 1A1, Canada.
[Hoeppner, Bettina B.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Addict Med, Boston, MA 02114 USA.
RP Hunt, JI (reprint author), Brown Univ, Dept Psychiat, Warren Alpert Med Sch, Providence, RI 02912 USA.
EM Jeffrey_Hunt@Brown.edu
RI Case, Brady/M-1879-2015;
OI Case, Brady/0000-0001-9512-0416; Weinstock, Lauren/0000-0001-9970-235X
FU National Institute of Mental Health [MH59929, MH59977, MH59691]; Leon
Levy Foundation; American Academy of Child and Adolescent Psychiatry Eli
lily Pilot Research Award; American Psychiatric Association AstraZeneca
Young Minds in Psychiatry Award; Pfizer; NIMH; NIDA; NICHD; The
Pittsburgh Foundation Emmerling Fun; Ryan Licht Sang Bipolar Foundation
FX This work was supported by grants MH59929 (Dr. Birmaher), MH59977 (Dr.
Strober) and MH59691 (Dr. Keller) from the National Institute of Mental
Health.; Potential conflicts of interest include being an editor of a
Wiley Publishers newsletter (Dr. Hunt), being a consultant for Schering
Plough (Dr. Birmaher), receiving royalties from publications from Random
House, Inc. and Lippincott, Williams, 82 Wilkins (Dr. Birmaher),
receiving past support from the Leon Levy Foundation, American Academy
of Child and Adolescent Psychiatry Eli lily Pilot Research Award, and
the American Psychiatric Association AstraZeneca Young Minds in
Psychiatry Award (Dr. Case), receiving an investigator-initiated grant
from Pfizer (Dr. Benjamin Goldstein), receiving a speaker's honoraria
from Purdue Pharmaceuticals (Dr. Benjamin Goldstein) receiving travel
support as a Bristol-Myers Squibb consultant (Dr. Benjamin Goldstein),
receiving past grant funding from NIMH, NIDA, NICHD, The Pittsburgh
Foundation Emmerling Fun, and the Ryan Licht Sang Bipolar Foundation
(Dr. Tina Goldstein), receiving royalties from Guilford Press (Dr. Tina
Goldstein), serving as a consultant to Cenerex, Medtronic, and Sierra
Neuropharmaceuticals (Dr. Keller), receiving grant funding from Pfizer
(Dr. Keller), and serving on the Cenerex Advisory Board (Dr. Keller).
NR 22
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Z9 8
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD MAR 5
PY 2013
VL 145
IS 3
BP 409
EP 412
DI 10.1016/j.jad.2012.06.024
PG 4
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 086LX
UT WOS:000314686600021
PM 23021377
ER
PT J
AU Gao, AQ
Kantarci, A
Herrera, BS
Gao, HW
Van Dyke, TE
AF Gao, Anqi
Kantarci, Alpdogan
Herrera, Bruno Schneider
Gao, Hongwei
Van Dyke, Thomas E.
TI A critical role for suppressors of cytokine signaling 3 in regulating
LPS-induced transcriptional activation of matrix metalloproteinase-13 in
osteoblasts
SO PEERJ
LA English
DT Article
DE Inflammation; Periodontitis; Cytokine; Osteoblasts
AB Suppressor of cytokine signaling 3 (SOCS3) is a key regulator of cytokine signaling in macrophages and T cells. Although SOCS3 seems to contribute to the balance between the pro-inflammatory actions of IL-6 family of cytokines and anti-inflammatory signaling of IL-10 by negatively regulating gp130/Jak/Stat3 signal transduction, how and the molecular mechanisms whereby SOCS3 controls the downstream impact of TLR4 are largely unknown and current data are controversial. Furthermore, very little is known regarding SOCS3 function in cells other than myeloid cells and T cells. Our previous study demonstrates that SOCS3 is expressed in osteoblasts and functions as a critical inhibitor of LPS-induced IL-6 expression. However, the function of SOCS3 in osteoblasts remains largely unknown. In the current study, we report for the first time that LPS stimulation of osteoblasts induces the transcriptional activation of matrix metalloproteinase (MMP)-13, a central regulator of bone resorption. Importantly, we demonstrate that SOCS3 overexpression leads to a significant decrease of LPS-induced MMP-13 expression in both primary murine calvariae osteoblasts and a mouse osteoblast-like cell line, MC3T3-E1. Our findings implicate SOCS3 as an important regulatory mediator in bone inflammatory diseases by targetingMMP-13.
C1 [Gao, Anqi; Kantarci, Alpdogan; Herrera, Bruno Schneider; Van Dyke, Thomas E.] Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA.
[Gao, Hongwei] Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med,Med Sch, Boston, MA 02115 USA.
RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Periodontol, Cambridge, MA 02142 USA.
EM tvandyke@forsyth.org
FU National Institutes of Health [DE15566, DE19938]
FX This work was supported in part by National Institutes of Health Grants
DE15566 and DE19938. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 43
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U1 0
U2 3
PU PEERJ INC
PI LONDON
PA 341-345 OLD ST, THIRD FLR, LONDON, EC1V 9LL, ENGLAND
SN 2167-8359
J9 PEERJ
JI PeerJ
PD MAR 5
PY 2013
VL 1
AR UNSP e51
DI 10.7717/peerj.51
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36AK
UT WOS:000209185800005
PM 23638389
ER
PT J
AU Greenberg, CC
Wind, JK
Chang, GJ
Chen, RC
Schrag, D
AF Greenberg, Caprice C.
Wind, Jennifer K.
Chang, George J.
Chen, Ronald C.
Schrag, Deborah
TI Stakeholder engagement for comparative effectiveness research in cancer
care: experience of the DEcIDE Cancer Consortium
SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH
LA English
DT Article
DE cancer; CER; comparative effectiveness research; stakeholder
AB Stakeholder input is a critical component of comparative effectiveness research. To ensure that the research activities of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network, supported by the Agency for Healthcare Research and Quality, translate into the greatest impact for everyday practice and policy-making in cancer, we were tasked with soliciting stakeholder input regarding priority areas in cancer-related comparative effectiveness research for the DEcIDE Cancer Consortium. Given the increasing emphasis on stakeholder engagement in research, many investigators are facing a similar task, yet there is limited literature to guide such efforts, particularly in cancer care. To help fill this gap, we present our approach to operationalizing stakeholder engagement and discuss it in the context of other recent developments in the area. We describe challenges encountered in convening stakeholders from multiple vantage points to prioritize topics and strategies used to mitigate these barriers. We offer several recommendations regarding how to best solicit stakeholder input to inform comparative effectiveness research in cancer care. These recommendations can inform other initiatives currently facing the challenges of engaging stakeholders in priority setting for cancer.
C1 [Greenberg, Caprice C.; Wind, Jennifer K.; Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA.
[Greenberg, Caprice C.] Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program, Madison, WI USA.
[Chang, George J.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Chen, Ronald C.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA.
RP Greenberg, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA.
EM greenberg@surgery.wisc.edu
FU Agency for Healthcare Research and Quality, US Department of Health and
Human Services as part of the Developing Evidence to Inform Decisions
about Effectiveness (DEcIDE) program [HHSA290201000006I]
FX This project was funded under Contract number HHSA290201000006I from the
Agency for Healthcare Research and Quality, US Department of Health and
Human Services as part of the Developing Evidence to Inform Decisions
about Effectiveness (DEcIDE) program. 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 14
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U1 1
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 2042-6305
EI 2042-6313
J9 J COMP EFFECT RES
JI J. Comp. Eff. Res.
PD MAR
PY 2013
VL 2
IS 2
BP 117
EP 125
DI 10.2217/CER.12.80
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 299CN
UT WOS:000330372700010
PM 24236554
ER
PT J
AU Raffetto, JD
AF Raffetto, J. D.
TI Inflammation in chronic venous ulcers
SO PHLEBOLOGY
LA English
DT Review
DE Inflammation; leukocytes; macrophages; venous ulcer; cytokines; growth
factors; matrix metalloproteinases; wound fluid; extracellular matrix;
collagen
ID CHRONIC LEG ULCERS; MATRIX METALLOPROTEINASE INDUCER; ELEVATED
EXPRESSION; CYTOKINE LEVELS; DISEASE; LIPODERMATOSCLEROSIS;
MICROCIRCULATION; INSUFFICIENCY; ULCERATION; ACTIVATION
AB Chronic venous ulcers (CVUs) occur in approximately 1% of the general population. Risk factors for chronic venous disease (CVD) include heredity, age, female sex and obesity. Although not restricted to the elderly, the prevalence of CVD, especially leg ulcers, increases with age. 1 CVD has a considerable impact on health-care resources. It has been estimated that venous ulcers cause the loss of approximately two million working days and incur treatment costs of approximately $3 billion per year in the USA. 2 Overall, CVD has been estimated to account for 1-3% of the total health-care budgets in countries with developed health-care systems. 1 The pathophysiology of dermal abnormalities in CVU is reflective of a complex interplay that involves sustained venous hypertension, inflammation, changes in microcirculation, cytokine and matrix metalloproteinase (MMP) activation, resulting in altered cellular function and delayed wound healing.(3,4)
C1 [Raffetto, J. D.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, West Roxbury, MA 02135 USA.
[Raffetto, J. D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Raffetto, JD (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy,Surg 112, West Roxbury, MA 02135 USA.
EM joseph.raffetto@med.va.gov
NR 21
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Z9 24
U1 1
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0268-3555
EI 1758-1125
J9 PHLEBOLOGY
JI Phlebology
PD MAR
PY 2013
VL 28
SU 1
BP 61
EP 67
DI 10.1177/0268355513476844
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 298CY
UT WOS:000330302800013
PM 23482537
ER
PT J
AU Achildi, O
Leong, SH
Maust, DT
Streim, JE
Oslin, DW
AF Achildi, Olga
Leong, Shirley H.
Maust, Donovan T.
Streim, Joel E.
Oslin, David W.
TI Patterns of Newly-Prescribed Benzodiazepines in Late Life
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Achildi, Olga; Leong, Shirley H.; Maust, Donovan T.; Streim, Joel E.; Oslin, David W.] Univ Penn, Philadelphia, PA 19104 USA.
[Achildi, Olga; Leong, Shirley H.; Maust, Donovan T.; Streim, Joel E.; Oslin, David W.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S90
EP S91
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400089
ER
PT J
AU Asbury, M
Helstrom, A
Benson, A
Leong, SH
Zimmerman, J
Streim, JE
Oslin, DW
AF Asbury, Melanie
Helstrom, Amy
Benson, Amy
Leong, Shirley H.
Zimmerman, Jacob
Streim, Joel E.
Oslin, David W.
TI Experience of Pain in the Elderly in Relation to Mood, Anxiety and
Physical Quality of Life in a PACE/BHL Program
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Asbury, Melanie; Helstrom, Amy; Benson, Amy; Zimmerman, Jacob; Streim, Joel E.; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Helstrom, Amy; Benson, Amy; Leong, Shirley H.; Streim, Joel E.; Oslin, David W.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S109
EP S110
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400118
ER
PT J
AU Beristianos, M
Yaffe, K
Neylan, T
Covinsky, K
Byers, AL
AF Beristianos, Matthew
Yaffe, Kristine
Neylan, Thomas
Covinsky, Kenneth
Byers, Amy L.
TI Late-Life PTSD, Comorbid Psychiatric and Behavioral Disorders and Risk
of Mortality among Veterans
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Beristianos, Matthew; Yaffe, Kristine; Neylan, Thomas; Covinsky, Kenneth; Byers, Amy L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Beristianos, Matthew; Yaffe, Kristine; Neylan, Thomas; Covinsky, Kenneth; Byers, Amy L.] San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S89
EP S90
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400088
ER
PT J
AU Byers, AL
Barry, LC
Okereke, OI
Yaffe, K
AF Byers, Amy L.
Barry, Lisa C.
Okereke, Olivia I.
Yaffe, Kristine
TI NEW EPIDEMIOLOGICAL EVIDENCE FOR MENTAL HEALTH PREDICTING LATE-LIFE
COGNITIVE AND FUNCTIONAL DECLINE
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Byers, Amy L.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Barry, Lisa C.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA.
[Okereke, Olivia I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Okereke, Olivia I.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RI Okereke, Olivia/R-9934-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S25
EP S26
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400032
ER
PT J
AU Cohen, CI
Kasckow, J
Rajji, T
Vahia, I
AF Cohen, Carl I.
Kasckow, John
Rajji, Tarek
Vahia, Ipsit
TI ADVANCES IN LATE LIFE SCHIZOPHRENIA RESEARCH
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Rajji, Tarek] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
[Rajji, Tarek] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Kasckow, John] Suny Downstate Med Ctr, New York, NY USA.
[Cohen, Carl I.] Univ Toronto, Toronto, ON, Canada.
[Vahia, Ipsit] Univ Calif San Diego, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S5
EP S6
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400003
ER
PT J
AU DeWitt, MA
Barnes, DE
Kunik, ME
Gordon, SM
AF DeWitt, Marie A.
Barnes, Deborah E.
Kunik, Mark E.
Gordon, Sharon M.
TI VA SYMPOSIUM: LINKS TO DEMENTIA
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [DeWitt, Marie A.; Kunik, Mark E.] Michael E DeBakey VAMC, Houston, TX USA.
[Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Gordon, Sharon M.] VA Tennessee Valley Hlth Care Syst, Nashville, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S40
EP S41
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400053
ER
PT J
AU Ege, MA
Messias, E
Krain, L
Thapa, PB
AF Ege, Margaret A.
Messias, Erick
Krain, Lewis
Thapa, Puru B.
TI AAGP Annual Meeting 2013
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Ege, Margaret A.; Messias, Erick; Krain, Lewis; Thapa, Puru B.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA.
[Krain, Lewis] US Dept Vet Affairs, Dept Psychiat, North Little Rock, AR USA.
[Thapa, Puru B.] Arkansas Mental Hlth Res & Training Inst, Little Rock, AR USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S63
EP S63
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400054
ER
PT J
AU Fischer, C
Sweet, RA
Ismail, Z
AF Fischer, Corinne
Sweet, Robert A.
Ismail, Zahinoor
TI FITTING A SQUARE PEG INTO A ROUND HOLE: UNDERSTANDING PSYCHOTIC SYMPTOMS
IN ALZHEIMER'S DISEASE
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Fischer, Corinne] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Ismail, Zahinoor] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Fischer, Corinne; Ismail, Zahinoor] Univ Toronto, Toronto, ON, Canada.
[Sweet, Robert A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Sweet, Robert A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA.
OI Fischer, Corinne/0000-0002-1047-0167
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S16
EP S16
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400018
ER
PT J
AU Hochstetler, H
Doraiswamy, PM
Sperling, RA
Johnson, KA
Reiman, E
Sabbagh, MN
Sadowsky, CH
Joshi, AD
Lu, M
Mintun, MA
Pontecorvo, MJ
Skovronsky, DM
AF Hochstetler, Helen
Doraiswamy, P. Murali
Sperling, Reisa A.
Johnson, Keith A.
Reiman, Eric
Sabbagh, Marwan N.
Sadowsky, Carl H.
Joshi, Abhinay D.
Lu, Ming
Mintun, Mark A.
Pontecorvo, Michael J.
Skovronsky, Daniel M.
TI Relationship of Florbetapir F18 PET Amyloid Plaque Neuroimaging with
Future Cognitive Decline over 36 Months
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Hochstetler, Helen] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Doraiswamy, P. Murali] Duke Univ, Med Ctr, Durham, NC USA.
[Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Reiman, Eric] Banner Alzheimers Inst, Phoenix, AZ USA.
[Sabbagh, Marwan N.] Banner Sun Hlth Res Inst, Sun City, AZ USA.
[Sadowsky, Carl H.] Nova SE Univ, Ft Lauderdale, FL 33314 USA.
[Joshi, Abhinay D.; Lu, Ming; Mintun, Mark A.; Pontecorvo, Michael J.; Skovronsky, Daniel M.] Avid Radiopharmaceut, Philadelphia, PA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S136
EP S136
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400150
ER
PT J
AU Lanctot, K
Chau, S
Herrmann, N
Drye, L
Rosenberg, P
Scherer, RW
Vaidya, V
Black, S
Mintzer, J
AF Lanctot, Krista
Chau, Sarah
Herrmann, Nathan
Drye, Lea
Rosenberg, Paul
Scherer, Roberta W.
Vaidya, Vijay
Black, Sandra
Mintzer, Jacobo
TI Effects of Methylphenidate on Attention and Association with Apathy in
AD patients
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Lanctot, Krista; Chau, Sarah; Herrmann, Nathan; Black, Sandra] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Drye, Lea; Rosenberg, Paul; Scherer, Roberta W.; Vaidya, Vijay] Johns Hopkins Univ, Baltimore, MD USA.
[Mintzer, Jacobo] Med Univ S Carolina, Charleston, SC 29425 USA.
[Mintzer, Jacobo] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S158
EP S159
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400179
ER
PT J
AU Maust, DT
Oslin, DW
Marcus, S
AF Maust, Donovan T.
Oslin, David W.
Marcus, Steven
TI The Association of Age and Clinical Factors in Psychotropic Prescribing
Nationwide
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Maust, Donovan T.; Oslin, David W.; Marcus, Steven] Univ Penn, Philadelphia, PA 19104 USA.
[Oslin, David W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S114
EP S116
PG 4
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400124
ER
PT J
AU Sasaki, DA
Takahashi, NY
Feil, D
AF Sasaki, Dean A.
Takahashi, Nancy Y.
Feil, Denise
TI A Qualitative Study of Medical Student Attitudes About Individualizing
Diabetes Care in Vulnerable Elders
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Sasaki, Dean A.] UCSF, San Francisco, CA USA.
[Sasaki, Dean A.; Takahashi, Nancy Y.; Feil, Denise] Univ Calif Los Angeles, Los Angeles, CA USA.
[Takahashi, Nancy Y.; Feil, Denise] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S110
EP S110
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400119
ER
PT J
AU Streim, JE
Oslin, DW
Liptzin, B
Moak, GS
AF Streim, Joel E.
Oslin, David W.
Liptzin, Benjamin
Moak, Gary S.
TI EVOLVING ROLES FOR GERIATRIC MENTAL HEALTH PROVIDERS IN THE 21ST CENTURY
HEALTHCARE SYSTEM
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Streim, Joel E.; Oslin, David W.] Univ Penn, Philadelphia, PA 19104 USA.
[Streim, Joel E.; Oslin, David W.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Liptzin, Benjamin] Baystate Med Ctr, Springfield, MA USA.
[Liptzin, Benjamin] Tufts Univ, Boston, MA 02111 USA.
[Moak, Gary S.] Moak Ctr Hlth Aging, Westborough, MA USA.
[Moak, Gary S.] Univ Massachusetts, Worcester, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S14
EP S15
PG 4
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400016
ER
PT J
AU Streim, JE
Oslin, DW
Maust, DT
Mavandadi, S
AF Streim, Joel E.
Oslin, David W.
Maust, Donovan T.
Mavandadi, Shahrzad
TI A STATE-WIDE PROGRAM OF COLLABORATIVE CARE: WORKING TOWARDS GERIATRIC
MENTAL HEALTHCARE REFORM
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Streim, Joel E.; Oslin, David W.; Maust, Donovan T.; Mavandadi, Shahrzad] Univ Penn, Philadelphia, PA 19104 USA.
[Streim, Joel E.; Oslin, David W.; Maust, Donovan T.; Mavandadi, Shahrzad] Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S5
EP S5
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400002
ER
PT J
AU Sultzer, DL
Leskin, LP
Jacobs, ZM
Melrose, RJ
Harwood, DG
Narvaez, TA
Ando, TK
Mandelkern, MA
AF Sultzer, David L.
Leskin, Lorraine P.
Jacobs, Zachary M.
Melrose, Rebecca J.
Harwood, Dylan G.
Narvaez, Theresa A.
Ando, Timothy K.
Mandelkern, Mark A.
TI Cognitive, behavioral, and emotional domains of apathy in Alzheimer's
disease: clinical and neurobiological features
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Sultzer, David L.; Leskin, Lorraine P.; Jacobs, Zachary M.; Melrose, Rebecca J.; Harwood, Dylan G.; Narvaez, Theresa A.; Ando, Timothy K.] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA.
[Sultzer, David L.; Melrose, Rebecca J.; Harwood, Dylan G.] UCLA Dept Psychiat & Biobehav Sci, Los Angeles, CA USA.
[Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA USA.
[Mandelkern, Mark A.] UC Irvine, Dept Phys, Irvine, CA USA.
NR 0
TC 3
Z9 3
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S144
EP S145
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400160
ER
PT J
AU Yoder, M
Kasckow, J
Thorp, SR
Magruder, KM
AF Yoder, Matthew
Kasckow, John
Thorp, Steven R.
Magruder, Kathryn M.
TI PSYCHOSOCIAL INTERVENTIONS FOR OLDER PATIENTS WITH POST TRAUMATIC STRESS
DISORDER
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
CY MAR 14-17, 2013
CL Los Angeles, CA
SP Amer Assoc Geriatr Psychiat
C1 [Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
[Kasckow, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Yoder, Matthew; Magruder, Kathryn M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Thorp, Steven R.] Univ Calif San Diego, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2013
VL 21
IS 3
SU S
BP S29
EP S30
PG 3
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 298XQ
UT WOS:000330358400038
ER
PT J
AU Tellechea, A
Kafanas, A
Leal, EC
Tecilazich, F
Kuchibhotla, S
Auster, ME
Kontoes, I
Paolino, J
Carvalho, E
Nabzdyk, LP
Veves, A
AF Tellechea, Ana
Kafanas, Antonios
Leal, Ermelindo C.
Tecilazich, Francesco
Kuchibhotla, Sarada
Auster, Michael E.
Kontoes, Iraklis
Paolino, Jacqueline
Carvalho, Eugenia
Nabzdyk, Leena Pradhan
Veves, Aristidis
TI Increased Skin Inflammation and Blood Vessel Density in Human and
Experimental Diabetes
SO INTERNATIONAL JOURNAL OF LOWER EXTREMITY WOUNDS
LA English
DT Article
DE diabetes; wound healing; skin changes; skin inflammation; skin blood
vessels
ID INSULIN-RESISTANCE; METABOLIC SYNDROME; FOOT ULCERATION; DYSFUNCTION;
CYTOKINES; OBESITY; INTERLEUKIN-6; REACTIVITY; NEUROPATHY; MECHANISMS
AB Systemic inflammation is associated with impaired wound healing in diabetes mellitus (DM) patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all DM animal models compared with their non-DM controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around preexisting skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes.
C1 [Tellechea, Ana; Kafanas, Antonios; Leal, Ermelindo C.; Tecilazich, Francesco; Kuchibhotla, Sarada; Auster, Michael E.; Kontoes, Iraklis; Paolino, Jacqueline; Nabzdyk, Leena Pradhan; Veves, Aristidis] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Tellechea, Ana; Leal, Ermelindo C.; Carvalho, Eugenia] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Paolino, Jacqueline] Mt Sinai Sch Med, New York, NY USA.
RP Veves, A (reprint author), Microcirculat Lab, Palmer 321A,BIDMC West,One Deaconess Rd, Boston, MA 02215 USA.
EM aveves@bidmc.harvard.edu
RI Leal, Ermelindo/G-3051-2010;
OI Leal, Ermelindo/0000-0003-1748-9861; Tellechea, Ana/0000-0001-9387-7706;
Carvalho, Eugenia/0000-0001-6264-3632
FU National Institutes of Health [R01-DK076937, R01 NS066205]; National
Center for Research Resources [UL1RR025758]; Portuguese Foundation for
Science and Technology (FCT) [SFRH/BD/48624/2008, SFRH/BPD/46341/2008]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported by National Institutes of Health Grants R01-DK076937 and
R01 NS066205 to AV. The project described was supported by the 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 Institute of Health. AT was
supported by the SFRH/BD/48624/2008 grant and EL by the
SFRH/BPD/46341/2008 grant from the Portuguese Foundation for Science and
Technology (FCT).
NR 21
TC 16
Z9 16
U1 2
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1534-7346
EI 1552-6941
J9 INT J LOW EXTR WOUND
JI Int. J. Low. Extrem. Wounds
PD MAR
PY 2013
VL 12
IS 1
BP 4
EP 11
DI 10.1177/1534734612474303
PG 8
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 298AR
UT WOS:000330296800002
PM 23446362
ER
PT J
AU Garibyan, L
Avashia, N
AF Garibyan, Lilit
Avashia, Nidhi
TI Polymerase Chain Reaction
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID QUANTITATIVE PCR; CELL
C1 [Garibyan, Lilit] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA.
[Garibyan, Lilit] Harvard Med Sch, Boston, MA USA.
[Avashia, Nidhi] Boston Univ, Dept Dermatol, Boston, MA USA.
[Avashia, Nidhi] Boston Med Ctr, Boston, MA USA.
RP Garibyan, L (reprint author), Wellman Ctr Photomed, 50 Blossom St, Tier 2, Boston, MA 02114 USA.
EM lgaribyan@partners.org
FU NIAMS NIH HHS [T32 AR007098]
NR 10
TC 17
Z9 17
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2013
VL 133
IS 3
BP E1
EP E4
DI 10.1038/jid.2013.1
PG 4
WC Dermatology
SC Dermatology
GA 090VQ
UT WOS:000315008500047
PM 23399825
ER
PT J
AU Desikan, RS
McEvoy, LK
Holland, D
Thompson, WK
Brewer, JB
Aisen, PS
Andreassen, OA
Hyman, BT
Sperling, RA
Dale, AM
AF Desikan, R. S.
McEvoy, L. K.
Holland, D.
Thompson, W. K.
Brewer, J. B.
Aisen, P. S.
Andreassen, O. A.
Hyman, B. T.
Sperling, R. A.
Dale, A. M.
CA Alzheimer's Dis Neuroimaging Initi
TI Apolipoprotein E epsilon 4 Does Not Modulate Amyloid-beta-Associated
Neurodegeneration in Preclinical Alzheimer Disease
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID ENTORHINAL CORTEX NEURONS; NORMAL OLDER-ADULTS; MOUSE MODEL;
CEREBRAL-CORTEX; VOLUME LOSS; TAU; DEPOSITION; BRAIN; ATROPHY; OCCURS
AB These authors investigated the relationship between amyloid-, phosphorylated tau, and apolipoprotein E in preclinical Alzheimer disease in 170 patients and controls who had serial imaging up to 3.5 years after the initial study. Global volumes as well as volumes in brain regions known to be involved in the chronic stages of the disease were assessed. Their results led them to propose that atrophy rates are primarily influenced by apolipoprotein E via amyloid- mechanisms and that amyloid- -associated neurodegeneration occurs only in the presence of phosphorylated tau.
BACKGROUND AND PURPOSE: Among cognitively healthy older individuals, the relationship among the 2 hallmark proteins of AD (A and APOE epsilon 4) and neurodegeneration is not well-understood. Here, we investigated the relationship between A, p-, and APOE epsilon 4 on longitudinal brain atrophy in preclinical AD.
MATERIALS AND METHODS: We examined 107 cognitively healthy older adults who underwent longitudinal MR imaging and baseline lumbar puncture. Within the same linear mixed-effects model, we concurrently investigated main and interactive effects between the APOE epsilon 4 genotype and CSF A(1-42), CSF p- and CSF A(1-42), and the APOE epsilon 4 genotype and CSF p- on entorhinal cortex atrophy rate. We also examined the relationship of APOE epsilon 4, CSF p-, and CSF A(1-42) on the atrophy rate of other AD-vulnerable neuroanatomic regions.
RESULTS: The full model with main and interactive effects demonstrated a significant interaction only between CSF p- and CSF A(1-42) on entorhinal cortex atrophy rate, indicating elevated atrophy with time in individuals with increased CSF p- and decreased CSF A(1-42). The APOE epsilon 4 genotype was significantly and specifically associated with CSF A(1-42). However, the interaction between the APOE epsilon 4 genotype and either CSF A(1-42) or CSF p- on entorhinal cortex atrophy rate was not significant. We found similar results in other AD-vulnerable regions.
CONCLUSIONS: On the basis of our findings and building on prior experimental evidence, we propose a model of the pathogenic cascade underlying preclinical AD in which APOE epsilon 4 primarily influences the pathology of Alzheimer disease via A-related mechanisms, and in turn, A-associated neurodegeneration occurs only in the presence of p-.
C1 [Desikan, R. S.; McEvoy, L. K.; Brewer, J. B.; Dale, A. M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92037 USA.
[Holland, D.; Brewer, J. B.; Aisen, P. S.; Dale, A. M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Thompson, W. K.; Andreassen, O. A.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Andreassen, O. A.] Univ Oslo, Inst Clin Med, Oslo, Norway.
[Andreassen, O. A.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway.
[Hyman, B. T.; Sperling, R. A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sperling, R. A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
RP Desikan, RS (reprint author), Univ Calif San Diego, Dept Radiol, 8950 Villa La Jolla Dr,Suite C101, La Jolla, CA 92037 USA.
EM rdesikan@ucsd.edu
RI Saykin, Andrew/A-1318-2007
OI Saykin, Andrew/0000-0002-1376-8532
FU National Institutes of Health [R01AG031224, K01AG029218, K02 NS067427,
T32 EB005970, P30 AG010129, K01 AG030514]; Alzheimer Disease
Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01
AG024904]; National Institute on Aging, the National Institute of
Biomedical Imaging and Bioengineering; Canadian Institutes of Health
Research
FX This research was supported by grants from the National Institutes of
Health (R01AG031224, K01AG029218, K02 NS067427, T32 EB005970). Data
collection and sharing for this project were funded by the Alzheimer
Disease Neuroimaging Initiative (ADNI) (National Institutes of Health
Grant U01 AG024904). ADNI is funded by the National Institute on Aging,
the National Institute of Biomedical Imaging and Bioengineering, and
through generous contributions from the following: Abbott, Alzheimer's
Association, Alzheimer's Drug Discovery Foundation, Amorfix Life
Sciences Ltd, AstraZeneca, Bayer HealthCare, BioClinica Inc, Biogen Idec
Inc, Bristol-Myers Squibb Company, Eisai Inc, Elan Pharmaceuticals Inc,
Eli Lilly and Company, F. Hoffmann-La Roche Ltd and its affiliated
company Genentech Inc, GE Healthcare, Innogenetics, N.V., IXICO Ltd,
Janssen Alzheimer Immunotherapy Research & Development LLC, Johnson &
Johnson Pharmaceutical Research & Development LLC, Medpace Inc, Merck &
Co Inc, Meso Scale Diagnostics LLC, Novartis Pharmaceuticals
Corporation, Pfizer Inc, Servier, Synarc Inc, and Takeda Pharmaceutical
Company. The Canadian Institutes of Health Research is providing funds
to support ADNI clinical sites in Canada. Private sector contributions
are facilitated by the Foundation for the National Institutes of Health
(www.fnih.org). The grantee organization is the Northern California
Institute for Research and Education, and the study is coordinated by
the Alzheimer Disease Cooperative Study at the University of California,
San Diego. ADNI data are disseminated by the Laboratory for Neuro
Imaging at the University of California, Los Angeles. This research was
also supported by National Institutes of Health grants P30 AG010129 and
K01 AG030514.
NR 31
TC 12
Z9 12
U1 0
U2 2
PU AMER SOC NEURORADIOLOGY
PI DENVILLE
PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA
SN 0195-6108
EI 1936-959X
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD MAR
PY 2013
VL 34
IS 3
BP 505
EP 510
DI 10.3174/ajnr.A3267
PG 6
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 291RN
UT WOS:000329846900010
PM 22976236
ER
EF